SUBCHAPTER V—DRUGS AND DEVICES
Part A—Drugs and Devices
§351. Adulterated drugs and devices
A drug or device shall be deemed to be adulterated—
(a) Poisonous, insanitary, etc., ingredients; adequate controls in manufacture
(1) If it consists in whole or in part of any filthy, putrid, or decomposed substance; or (2)(A) if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health; or (B) if it is a drug and the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess; or (C) if it is a compounded positron emission tomography drug and the methods used in, or the facilities and controls used for, its compounding, processing, packing, or holding do not conform to or are not operated or administered in conformity with the positron emission tomography compounding standards and the official monographs of the United States Pharmacopoeia to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, that it purports or is represented to possess; or (3) if its container is composed, in whole or in part, of any poisonous or deleterious substance which may render the contents injurious to health; or (4) if (A) it bears or contains, for purposes of coloring only, a color additive which is unsafe within the meaning of
(b) Strength, quality, or purity differing from official compendium
If it purports to be or is represented as a drug the name of which is recognized in an official compendium, and its strength differs from, or its quality or purity falls below, the standard set forth in such compendium. Such determination as to strength, quality, or purity shall be made in accordance with the tests or methods of assay set forth in such compendium, except that whenever tests or methods of assay have not been prescribed in such compendium, or such tests or methods of assay as are prescribed are, in the judgment of the Secretary, insufficient for the making of such determination, the Secretary shall bring such fact to the attention of the appropriate body charged with the revision of such compendium, and if such body fails within a reasonable time to prescribe tests or methods of assay which, in the judgment of the Secretary, are sufficient for purposes of this paragraph, then the Secretary shall promulgate regulations prescribing appropriate tests or methods of assay in accordance with which such determination as to strength, quality, or purity shall be made. No drug defined in an official compendium shall be deemed to be adulterated under this paragraph because it differs from the standard of strength, quality, or purity therefor set forth in such compendium, if its difference in strength, quality, or purity from such standard is plainly stated on its label. Whenever a drug is recognized in both the United States Pharmacopoeia and the Homoeopathic Pharmacopoeia of the United States it shall be subject to the requirements of the United States Pharmacopoeia unless it is labeled and offered for sale as a homoeopathic drug, in which case it shall be subject to the provisions of the Homoeopathic Pharmacopoeia of the United States and not to those of the United States Pharmacopoeia.
(c) Misrepresentation of strength, etc., where drug is unrecognized in compendium
If it is not subject to the provisions of paragraph (b) of this section and its strength differs from, or its purity or quality falls below, that which it purports or is represented to possess.
(d) Mixture with or substitution of another substance
If it is a drug and any substance has been (1) mixed or packed therewith so as to reduce its quality or strength or (2) substituted wholly or in part therefor.
(e) Devices not in conformity with performance standards
(1) If it is, or purports to be or is represented as, a device which is subject to a performance standard established under
(2) If it is declared to be, purports to be, or is represented as, a device that is in conformity with any standard recognized under
(f) Certain class III devices
(1) If it is a class III device—
(A)(i) which is required by a regulation promulgated under subsection (b) of
(ii)(I) for which an application for premarket approval or a notice of completion of a product development protocol was not filed with the Secretary within the ninety-day period beginning on the date of the promulgation of such regulation, or
(II) for which such an application was filed and approval of the application has been denied, suspended, or withdrawn, or such a notice was filed and has been declared not completed or the approval of the device under the protocol has been withdrawn;
(B)(i) which was classified under
(ii) which has an application which has been suspended or is otherwise not in effect; or
(C) which was classified under
(2)(A) In the case of a device classified under
(B) In the case of a device subject to a regulation promulgated under subsection (b) of
(i) on the last day of the thirtieth calendar month beginning after the month in which the classification of the device in class III became effective under
(ii) on the ninetieth day after the date of the promulgation of such regulation,
whichever occurs later.
(g) Banned devices
If it is a banned device.
(h) Manufacture, packing, storage, or installation of device not in conformity with applicable requirements or conditions
If it is a device and the methods used in, or the facilities or controls used for, its manufacture, packing, storage, or installation are not in conformity with applicable requirements under
(i) Failure to comply with requirements under which device was exempted for investigational use
If it is a device for which an exemption has been granted under
(June 25, 1938, ch. 675, §501,
Amendments
1997—Par. (a)(2)(C).
Par. (e).
1992—Par. (a)(4).
1990—Par. (f)(1).
1976—Par. (a).
Pars. (e) to (i).
1968—Par. (a).
1962—Par. (a).
1960—Par. (a).
Effective and Termination Dates of 1997 Amendment
Section 121(b)(2) of
Amendment by
Effective Date of 1968 Amendment
Amendment by
Effective Date of 1962 Amendment; Exceptions
Amendment by
Effective Date of 1960 Amendment
Amendment by
Effective Date; Postponement
Par. (a)(4) effective Jan. 1, 1940, see act June 23, 1939, ch. 242,
Transfer of Functions
For transfer of functions of Federal Security Administrator to Secretary of Health, Education, and Welfare [now Health and Human Services], and of Food and Drug Administration in the Department of Agriculture to Federal Security Agency, see note set out under
Section Referred to in Other Sections
This section is referred to in
1 So in original. Probably should be "subparagraph".
§352. Misbranded drugs and devices
A drug or device shall be deemed to be misbranded—
(a) False or misleading label
If its labeling is false or misleading in any particular. Health care economic information provided to a formulary committee, or other similar entity, in the course of the committee or the entity carrying out its responsibilities for the selection of drugs for managed care or other similar organizations, shall not be considered to be false or misleading under this paragraph if the health care economic information directly relates to an indication approved under
(b) Package form; contents of label
If in package form unless it bears a label containing (1) the name and place of business of the manufacturer, packer, or distributor; and (2) an accurate statement of the quantity of the contents in terms of weight, measure, or numerical count: Provided, That under clause (2) of this paragraph reasonable variations shall be permitted, and exemptions as to small packages shall be established, by regulations prescribed by the Secretary.
(c) Prominence of information on label
If any word, statement, or other information required by or under authority of this chapter to appear on the label or labeling is not prominently placed thereon with such conspicuousness (as compared with other words, statements, designs, or devices, in the labeling) and in such terms as to render it likely to be read and understood by the ordinary individual under customary conditions of purchase and use.
(d) Repealed. Pub. L. 105–115, title I, §126(b), Nov. 21, 1997, 111 Stat. 2327
(e) Designation of drugs or devices by established names
(1)(A) If it is a drug, unless its label bears, to the exclusion of any other nonproprietary name (except the applicable systematic chemical name or the chemical formula)—
(i) the established name (as defined in subparagraph (3)) of the drug, if there is such a name;
(ii) the established name and quantity or, if determined to be appropriate by the Secretary, the proportion of each active ingredient, including the quantity, kind, and proportion of any alcohol, and also including whether active or not the established name and quantity or if determined to be appropriate by the Secretary, the proportion of any bromides, ether, chloroform, acetanilide, acetophenetidin, amidopyrine, antipyrine, atropine, hyoscine, hyoscyamine, arsenic, digitalis, digitalis glucosides, mercury, ouabain, strophanthin, strychnine, thyroid, or any derivative or preparation of any such substances, contained therein, except that the requirement for stating the quantity of the active ingredients, other than the quantity of those specifically named in this subclause, shall not apply to nonprescription drugs not intended for human use; and
(iii) the established name of each inactive ingredient listed in alphabetical order on the outside container of the retail package and, if determined to be appropriate by the Secretary, on the immediate container, as prescribed in regulation promulgated by the Secretary, except that nothing in this subclause shall be deemed to require that any trade secret be divulged, and except that the requirements of this subclause with respect to alphabetical order shall apply only to nonprescription drugs that are not also cosmetics and that this subclause shall not apply to nonprescription drugs not intended for human use.
(B) For any prescription drug the established name of such drug or ingredient, as the case may be, on such label (and on any labeling on which a name for such drug or ingredient is used) shall be printed prominently and in type at least half as large as that used thereon for any proprietary name or designation for such drug or ingredient, except that to the extent that compliance with the requirements of subclause (ii) or (iii) of clause (A) or this clause is impracticable, exemptions shall be established by regulations promulgated by the Secretary.
(2) If it is a device and it has an established name, unless its label bears, to the exclusion of any other nonproprietary name, its established name (as defined in subparagraph (4)) prominently printed in type at least half as large as that used thereon for any proprietary name or designation for such device, except that to the extent compliance with the requirements of this subparagraph is impracticable, exemptions shall be established by regulations promulgated by the Secretary.
(3) As used in subparagraph (1), the term "established name", with respect to a drug or ingredient thereof, means (A) the applicable official name designated pursuant to
(4) As used in subparagraph (2), the term "established name" with respect to a device means (A) the applicable official name of the device designated pursuant to
(f) Directions for use and warnings on label
Unless its labeling bears (1) adequate directions for use; and (2) such adequate warnings against use in those pathological conditions or by children where its use may be dangerous to health, or against unsafe dosage or methods or duration of administration or application, in such manner and form, as are necessary for the protection of users, except that where any requirement of clause (1) of this paragraph, as applied to any drug or device, is not necessary for the protection of the public health, the Secretary shall promulgate regulations exempting such drug or device from such requirement.
(g) Representations as recognized drug; packing and labeling; inconsistent requirements for designation of drug
If it purports to be a drug the name of which is recognized in an official compendium, unless it is packaged and labeled as prescribed therein. The method of packing may be modified with the consent of the Secretary. Whenever a drug is recognized in both the United States Pharmacopoeia and the Homoeopathic Pharmacopoeia of the United States, it shall be subject to the requirements of the United States Pharmacopoeia with respect to packaging and labeling unless it is labeled and offered for sale as a homoeopathic drug, in which case it shall be subject to the provisions of the Homoeopathic Pharmacopoeia of the United States, and not those of the United States Pharmacopoeia, except that in the event of inconsistency between the requirements of this paragraph and those of paragraph (e) as to the name by which the drug or its ingredients shall be designated, the requirements of paragraph (e) shall prevail.
(h) Deteriorative drugs; packing and labeling
If it has been found by the Secretary to be a drug liable to deterioration, unless it is packaged in such form and manner, and its label bears a statement of such precautions, as the Secretary shall by regulations require as necessary for the protection of the public health. No such regulation shall be established for any drug recognized in an official compendium until the Secretary shall have informed the appropriate body charged with the revision of such compendium of the need for such packaging or labeling requirements and such body shall have failed within a reasonable time to prescribe such requirements.
(i) Drug; misleading container; imitation; offer for sale under another name
(1) If it is a drug and its container is so made, formed, or filled as to be misleading; or (2) if it is an imitation of another drug; or (3) if it is offered for sale under the name of another drug.
(j) Health-endangering when used as prescribed
If it is dangerous to health when used in the dosage or manner, or with the frequency or duration prescribed, recommended, or suggested in the labeling thereof.
(k), (l) Repealed. Pub. L. 105–115, title I, §125(a)(2)(B), (b)(2)(D), Nov. 21, 1997, 111 Stat. 2325
(m) Color additives; packing and labeling
If it is a color additive the intended use of which is for the purpose of coloring only, unless its packaging and labeling are in conformity with such packaging and labeling requirements applicable to such color additive, as may be contained in regulations issued under
(n) Prescription drug advertisements: established name; quantitative formula; side effects, contraindications, and effectiveness; prior approval; false advertising; labeling; construction of the Convention on Psychotropic Substances
In the case of any prescription drug distributed or offered for sale in any State, unless the manufacturer, packer, or distributor thereof includes in all advertisements and other descriptive printed matter issued or caused to be issued by the manufacturer, packer, or distributor with respect to that drug a true statement of (1) the established name as defined in paragraph (e) of this section, printed prominently and in type at least half as large as that used for any trade or brand name thereof, (2) the formula showing quantitatively each ingredient of such drug to the extent required for labels under paragraph (e) of this section, and (3) such other information in brief summary relating to side effects, contraindications, and effectiveness as shall be required in regulations which shall be issued by the Secretary in accordance with the procedure specified in
(o) Drugs or devices from nonregistered establishments
If it was manufactured, prepared, propagated, compounded, or processed in an establishment in any State not duly registered under
(p) Packaging or labeling of drugs in violation of regulations
If it is a drug and its packaging or labeling is in violation of an applicable regulation issued pursuant to
(q) Restricted devices using false or misleading advertising or used in violation of regulations
In the case of any restricted device distributed or offered for sale in any State, if (1) its advertising is false or misleading in any particular, or (2) it is sold, distributed, or used in violation of regulations prescribed under
(r) Restricted devices not carrying requisite accompanying statements in advertisements and other descriptive printed matter
In the case of any restricted device distributed or offered for sale in any State, unless the manufacturer, packer, or distributor thereof includes in all advertisements and other descriptive printed matter issued or caused to be issued by the manufacturer, packer, or distributor with respect to that device (1) a true statement of the device's established name as defined in subsection (e) of this section, printed prominently and in type at least half as large as that used for any trade or brand name thereof, and (2) a brief statement of the intended uses of the device and relevant warnings, precautions, side effects, and contraindications and, in the case of specific devices made subject to a finding by the Secretary after notice and opportunity for comment that such action is necessary to protect the public health, a full description of the components of such device or the formula showing quantitatively each ingredient of such device to the extent required in regulations which shall be issued by the Secretary after an opportunity for a hearing. Except in extraordinary circumstances, no regulation issued under this paragraph shall require prior approval by the Secretary of the content of any advertisement and no advertisement of a restricted device, published after the effective date of this paragraph shall, with respect to the matters specified in this paragraph or covered by regulations issued hereunder, be subject to the provisions of
(s) Devices subject to performance standards not bearing requisite labeling
If it is a device subject to a performance standard established under
(t) Devices for which there has been a failure or refusal to give required notification or to furnish required material or information
If it is a device and there was a failure or refusal (1) to comply with any requirement prescribed under
(June 25, 1938, ch. 675, §502,
Amendments
1997—Par. (a).
Par. (d).
Par. (e)(1).
Par. (k).
Par. (l).
1993—Par. (e)(3).
Par. (f).
Par. (g).
Par. (n).
1992—Par. (m).
Par. (t)(3).
1978—Par. (n).
1976—Par. (e).
Par. (j).
Par. (m).
Par. (o).
Pars. (q) to (t).
1970—Par. (p).
1968—Par. (l).
1962—Par. (e).
Par. (g).
Par. (l).
Par. (n).
Par. (o).
1960—Par. (m).
1953—Par. (l). Act Aug. 5, 1953, substituted "chlortetracycline" for "aureomycin".
1949—Par. (l). Act July 13, 1949, inserted ", aureomycin, chloramphenicol, or bacitracin" after "streptomycin".
1947—Par. (l). Act Mar. 10, 1947, inserted "or streptomycin" after "penicillin".
1945—Par. (l). Act July 6, 1945, added par. (l).
1941—Par. (k). Act Dec. 22, 1941, added par. (k).
1939—Par. (d). Act June 29, 1939, substituted "name, and quality or proportion" for "name, quantity, and percentage".
Effective Date of 1997 Amendment
Amendment by sections 114(a), 126(b), and 412(c) of
Effective Date of 1978 Amendment
Amendment by
Effective Date of 1970 Amendment
Amendment by
Effective Date of 1968 Amendment
Amendment by
Effective Date of 1962 Amendment
Section 112(c) of
Section 131(b) of
Amendment by
Effective Date of 1960 Amendment
Amendment by
Effective Date; Postponement
Pars. (b) and (d) to (h) effective Jan. 1, 1940, and such paragraphs effective July 1, 1940, as provided by regulations for certain lithographed labeling and containers bearing certain labeling, see act June 23, 1939, ch. 242,
Transfer of Functions
For transfer of functions of Federal Security Administrator to Secretary of Health, Education, and Welfare [now Health and Human Services], and of Food and Drug Administration in the Department of Agriculture to Federal Security Agency, see note set out under
Study and Report
Section 114(b) of
Counterfeiting of Drugs; Congressional Findings and Declaration of Policy
Section 9(a) of
Provisions as effective Feb. 1, 1966, see section 11 of
Section Referred to in Other Sections
This section is referred to in
§353. Exemptions and consideration for certain drugs, devices, and biological products
(a) Regulations for goods to be processed, labeled, or repacked elsewhere
The Secretary is directed to promulgate regulations exempting from any labeling or packaging requirement of this chapter drugs and devices which are, in accordance with the practice of the trade, to be processed, labeled, or repacked in substantial quantities at establishments other than those where originally processed or packed, on condition that such drugs and devices are not adulterated or misbranded under the provisions of this chapter upon removal from such processing, labeling, or repacking establishment.
(b) Prescription by physician; exemption from labeling and prescription requirements; misbranded drugs; compliance with narcotic and marihuana laws
(1) A drug intended for use by man which—
(A) because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner licensed by law to administer such drug; or
(B) is limited by an approved application under
shall be dispensed only (i) upon a written prescription of a practitioner licensed by law to administer such drug, or (ii) upon an oral prescription of such practitioner which is reduced promptly to writing and filed by the pharmacist, or (iii) by refilling any such written or oral prescription if such refilling is authorized by the prescriber either in the original prescription or by oral order which is reduced promptly to writing and filed by the pharmacist. The act of dispensing a drug contrary to the provisions of this paragraph shall be deemed to be an act which results in the drug being misbranded while held for sale.
(2) Any drug dispensed by filling or refilling a written or oral prescription of a practitioner licensed by law to administer such drug shall be exempt from the requirements of
(3) The Secretary may by regulation remove drugs subject to
(4)(A) A drug that is subject to paragraph (1) shall be deemed to be misbranded if at any time prior to dispensing the label of the drug fails to bear, at a minimum, the symbol "Rx only".
(B) A drug to which paragraph (1) does not apply shall be deemed to be misbranded if at any time prior to dispensing the label of the drug bears the symbol described in subparagraph (A).
(5) Nothing in this subsection shall be construed to relieve any person from any requirement prescribed by or under authority of law with respect to drugs now included or which may hereafter be included within the classifications stated in
(c) Sales restrictions
(1) No person may sell, purchase, or trade or offer to sell, purchase, or trade any drug sample. For purposes of this paragraph and subsection (d) of this section, the term "drug sample" means a unit of a drug, subject to subsection (b) of this section, which is not intended to be sold and is intended to promote the sale of the drug. Nothing in this paragraph shall subject an officer or executive of a drug manufacturer or distributor to criminal liability solely because of a sale, purchase, trade, or offer to sell, purchase, or trade in violation of this paragraph by other employees of the manufacturer or distributor.
(2) No person may sell, purchase, or trade, offer to sell, purchase, or trade, or counterfeit any coupon. For purposes of this paragraph, the term "coupon" means a form which may be redeemed, at no cost or at a reduced cost, for a drug which is prescribed in accordance with subsection (b) of this section.
(3)(A) No person may sell, purchase, or trade, or offer to sell, purchase, or trade, any drug—
(i) which is subject to subsection (b) of this section, and
(ii)(I) which was purchased by a public or private hospital or other health care entity, or
(II) which was donated or supplied at a reduced price to a charitable organization described in
(B) Subparagraph (A) does not apply to—
(i) the purchase or other acquisition by a hospital or other health care entity which is a member of a group purchasing organization of a drug for its own use from the group purchasing organization or from other hospitals or health care entities which are members of such organization,
(ii) the sale, purchase, or trade of a drug or an offer to sell, purchase, or trade a drug by an organization described in subparagraph (A)(ii)(II) to a nonprofit affiliate of the organization to the extent otherwise permitted by law,
(iii) a sale, purchase, or trade of a drug or an offer to sell, purchase, or trade a drug among hospitals or other health care entities which are under common control,
(iv) a sale, purchase, or trade of a drug or an offer to sell, purchase, or trade a drug for emergency medical reasons, or
(v) a sale, purchase, or trade of a drug, an offer to sell, purchase, or trade a drug, or the dispensing of a drug pursuant to a prescription executed in accordance with subsection (b) of this section.
For purposes of this paragraph, the term "entity" does not include a wholesale distributor of drugs or a retail pharmacy licensed under State law and the term "emergency medical reasons" includes transfers of a drug between health care entities or from a health care entity to a retail pharmacy undertaken to alleviate temporary shortages of the drug arising from delays in or interruptions of regular distribution schedules.
(d) Distribution of drug samples
(1) Except as provided in paragraphs (2) and (3), no person may distribute any drug sample. For purposes of this subsection, the term "distribute" does not include the providing of a drug sample to a patient by a—
(A) practitioner licensed to prescribe such drug,
(B) health care professional acting at the direction and under the supervision of such a practitioner, or
(C) pharmacy of a hospital or of another health care entity that is acting at the direction of such a practitioner and that received such sample pursuant to paragraph (2) or (3).
(2)(A) The manufacturer or authorized distributor of record of a drug subject to subsection (b) of this section may, in accordance with this paragraph, distribute drug samples by mail or common carrier to practitioners licensed to prescribe such drugs or, at the request of a licensed practitioner, to pharmacies of hospitals or other health care entities. Such a distribution of drug samples may only be made—
(i) in response to a written request for drug samples made on a form which meets the requirements of subparagraph (B), and
(ii) under a system which requires the recipient of the drug sample to execute a written receipt for the drug sample upon its delivery and the return of the receipt to the manufacturer or authorized distributor of record.
(B) A written request for a drug sample required by subparagraph (A)(i) shall contain—
(i) the name, address, professional designation, and signature of the practitioner making the request,
(ii) the identity of the drug sample requested and the quantity requested,
(iii) the name of the manufacturer of the drug sample requested, and
(iv) the date of the request.
(C) Each drug manufacturer or authorized distributor of record which makes distributions by mail or common carrier under this paragraph shall maintain, for a period of 3 years, the request forms submitted for such distributions and the receipts submitted for such distributions and shall maintain a record of distributions of drug samples which identifies the drugs distributed and the recipients of the distributions. Forms, receipts, and records required to be maintained under this subparagraph shall be made available by the drug manufacturer or authorized distributor of record to Federal and State officials engaged in the regulation of drugs and in the enforcement of laws applicable to drugs.
(3) The manufacturer or authorized distributor of record of a drug subject to subsection (b) of this section may, by means other than mail or common carrier, distribute drug samples only if the manufacturer or authorized distributor of record makes the distributions in accordance with subparagraph (A) and carries out the activities described in subparagraphs (B) through (F) as follows:
(A) Drug samples may only be distributed—
(i) to practitioners licensed to prescribe such drugs if they make a written request for the drug samples, or
(ii) at the written request of such a licensed practitioner, to pharmacies of hospitals or other health care entities.
A written request for drug samples shall be made on a form which contains the practitioner's name, address, and professional designation, the identity of the drug sample requested, the quantity of drug samples requested, the name of the manufacturer or authorized distributor of record of the drug sample, the date of the request and signature of the practitioner making the request.
(B) Drug manufacturers or authorized distributors of record shall store drug samples under conditions that will maintain their stability, integrity, and effectiveness and will assure that the drug samples will be free of contamination, deterioration, and adulteration.
(C) Drug manufacturers or authorized distributors of record shall conduct, at least annually, a complete and accurate inventory of all drug samples in the possession of representatives of the manufacturer or authorized distributor of record. Drug manufacturers or authorized distributors of record shall maintain lists of the names and address of each of their representatives who distribute drug samples and of the sites where drug samples are stored. Drug manufacturers or authorized distributors of record shall maintain records for at least 3 years of all drug samples distributed, destroyed, or returned to the manufacturer or authorized distributor of record, of all inventories maintained under this subparagraph, of all thefts or significant losses of drug samples, and of all requests made under subparagraph (A) for drug samples. Records and lists maintained under this subparagraph shall be made available by the drug manufacturer or authorized distributor of record to the Secretary upon request.
(D) Drug manufacturers or authorized distributors of record shall notify the Secretary of any significant loss of drug samples and any known theft of drug samples.
(E) Drug manufacturers or authorized distributors of record shall report to the Secretary any conviction of their representatives for violations of subsection (c)(1) of this section or a State law because of the sale, purchase, or trade of a drug sample or the offer to sell, purchase, or trade a drug sample.
(F) Drug manufacturers or authorized distributors of record shall provide to the Secretary the name and telephone number of the individual responsible for responding to a request for information respecting drug samples.
(e) Wholesale distributors; guidelines for licensing; definitions
(1)(A) Each person who is engaged in the wholesale distribution of a drug subject to subsection (b) of this section and who is not the manufacturer or an authorized distributor of record of such drug shall, before each wholesale distribution of such drug (including each distribution to an authorized distributor of record or to a retail pharmacy), provide to the person who receives the drug a statement (in such form and containing such information as the Secretary may require) identifying each prior sale, purchase, or trade of such drug (including the date of the transaction and the names and addresses of all parties to the transaction).
(B) Each manufacturer of a drug subject to subsection (b) of this section shall maintain at its corporate offices a current list of the authorized distributors of record of such drug.
(2)(A) No person may engage in the wholesale distribution in interstate commerce of drugs subject to subsection (b) of this section in a State unless such person is licensed by the State in accordance with the guidelines issued under subparagraph (B).
(B) The Secretary shall by regulation issue guidelines establishing minimum standards, terms, and conditions for the licensing of persons to make wholesale distributions in interstate commerce of drugs subject to subsection (b) of this section. Such guidelines shall prescribe requirements for the storage and handling of such drugs and for the establishment and maintenance of records of the distributions of such drugs.
(3) For the purposes of this subsection and subsection (d) of this section—
(A) the term "authorized distributors of record" means those distributors with whom a manufacturer has established an ongoing relationship to distribute such manufacturer's products, and
(B) the term "wholesale distribution" means distribution of drugs subject to subsection (b) of this section to other than the consumer or patient but does not include intracompany sales and does not include distributions of drugs described in subsection (c)(3)(B) of this section.
(f) Veterinary prescription drugs
(1)(A) A drug intended for use by animals other than man, other than a veterinary feed directive drug intended for use in animal feed or an animal feed bearing or containing a veterinary feed directive drug, which—
(i) because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary for its use, is not safe for animal use except under the professional supervision of a licensed veterinarian, or
(ii) is limited by an approved application under subsection (b) of
shall be dispensed only by or upon the lawful written or oral order of a licensed veterinarian in the course of the veterinarian's professional practice.
(B) For purposes of subparagraph (A), an order is lawful if the order—
(i) is a prescription or other order authorized by law,
(ii) is, if an oral order, promptly reduced to writing by the person lawfully filling the order, and filed by that person, and
(iii) is refilled only if authorized in the original order or in a subsequent oral order promptly reduced to writing by the person lawfully filling the order, and filed by that person.
(C) The act of dispensing a drug contrary to the provisions of this paragraph shall be deemed to be an act which results in the drug being misbranded while held for sale.
(2) Any drug when dispensed in accordance with paragraph (1) of this subsection—
(A) shall be exempt from the requirements of
(B) shall be exempt from the packaging requirements of subsections (g), (h), and (p) of such section, if—
(i) when dispensed by a licensed veterinarian, the drug bears a label containing the name and address of the practitioner and any directions for use and cautionary statements specified by the practitioner, or
(ii) when dispensed by filling the lawful order of a licensed veterinarian, the drug bears a label containing the name and address of the dispenser, the serial number and date of the order or of its filling, the name of the licensed veterinarian, and the directions for use and cautionary statements, if any, contained in such order.
The preceding sentence shall not apply to any drug dispensed in the course of the conduct of a business of dispensing drugs pursuant to diagnosis by mail.
(3) The Secretary may by regulation exempt drugs for animals other than man subject to
(4) A drug which is subject to paragraph (1) shall be deemed to be misbranded if at any time prior to dispensing its label fails to bear the statement "Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.". A drug to which paragraph (1) does not apply shall be deemed to be misbranded if at any time prior to dispensing its label bears the statement specified in the preceding sentence.
(g) Regulation of combination products
(1) The Secretary shall designate a component of the Food and Drug Administration to regulate products that constitute a combination of a drug, device, or biological product. The Secretary shall determine the primary mode of action of the combination product. If the Secretary determines that the primary mode of action is that of—
(A) a drug (other than a biological product), the persons charged with premarket review of drugs shall have primary jurisdiction,
(B) a device, the persons charged with premarket review of devices shall have primary jurisdiction, or
(C) a biological product, the persons charged with premarket review of biological products shall have primary jurisdiction.
(2) Nothing in this subsection shall prevent the Secretary from using any agency resources of the Food and Drug Administration necessary to ensure adequate review of the safety, effectiveness, or substantial equivalence of an article.
(3) The Secretary shall promulgate regulations to implement market clearance procedures in accordance with paragraphs (1) and (2) not later than 1 year after November 28, 1990.
(4) As used in this subsection:
(A) The term "biological product" has the meaning given the term in
(B) The term "market clearance" includes—
(i) approval of an application under section 355, 357,1 360e, or 360j(g) of this title,
(ii) a finding of substantial equivalence under this part, and
(iii) approval of a biologics license application under subsection (a) of
(June 25, 1938, ch. 675, §503,
References in Text
Codification
In subsec. (b)(5), "
Amendments
1997—Subsec. (b)(1)(A) to (C).
Subsec. (b)(3).
Subsec. (b)(4).
Subsec. (g)(4)(A).
Subsec. (g)(4)(B)(iii).
1996—Subsec. (f)(1)(A).
1992—Subsec. (d)(1).
Subsec. (d)(2).
Subsec. (d)(3).
Subsec. (e)(1).
Subsec. (e)(2)(A).
Subsec. (e)(3).
Subsec. (e)(4).
Subsec. (f)(1)(B).
Subsec. (g)(3).
1991—Subsec. (c).
Subsec. (c)(2), (3)(B)(v).
Subsec. (d)(3)(E).
Subsec. (f).
Subsec. (g).
1990—
Subsec. (f).
1988—Subsec. (c).
Subsec. (d).
Subsec. (e).
1970—Subsec. (b)(2).
1962—Subsec. (b)(1)(C).
1951—Subsec. (b). Act Oct. 26, 1951, amended subsec. (b) generally to protect the public from abuses in the sale of potent prescription drugs, and to relieve retail pharmacists and the public from unnecessary restrictions on the dispensation of drugs that are safe to use without supervision of a doctor.
Effective Date of 1997 Amendment
Amendment by
Termination Date of 1992 Amendment
Section 2(d) of
Effective Date of 1988 Amendment
Section 8 of
"(a)
"(b)
"(1) Section 503(d) of the Federal Food, Drug, and Cosmetic Act [
"(2) The Secretary of Health and Human Services shall by regulation issue the guidelines required by section 503(e)(2)(B) of the Federal Food, Drug, and Cosmetic Act [
Effective Date of 1970 Amendment
Amendment by
Effective Date of 1962 Amendment
Amendment by
Effective Date of 1951 Amendment
Amendment by act Oct. 26, 1951, effective six months after Oct. 26, 1951, see section 3 of act Oct. 26, 1951, set out as a note under
Transfer of Functions
For transfer of functions of Federal Security Administrator to Secretary of Health, Education, and Welfare [now Health and Human Services], and of Food and Drug Administration in the Department of Agriculture to Federal Security Agency, see note set out under
Effective Medication Guides
"(a)
"(b)
"(c)
"(1) identify the plan goals;
"(2) assess the effectiveness of the current private-sector approaches used to provide oral and written prescription information to consumers;
"(3) develop guidelines for providing effective oral and written prescription information consistent with the findings of any such assessment;
"(4) contain elements necessary to ensure the transmittal of useful information to the consuming public, including being scientifically accurate, non-promotional in tone and content, sufficiently specific and comprehensive as to adequately inform consumers about the use of the product, and in an understandable, legible format that is readily comprehensible and not confusing to consumers expected to use the product.[;]
"(5) develop a mechanism to assess periodically the quality of the oral and written prescription information and the frequency with which the information is provided to consumers; and
"(6) provide for compliance with relevant State board regulations.
"(d)
"(e)
Congressional Findings
Section 2 of
"(1) American consumers cannot purchase prescription drugs with the certainty that the products are safe and effective.
"(2) The integrity of the distribution system for prescription drugs is insufficient to prevent the introduction and eventual retail sale of substandard, ineffective, or even counterfeit drugs.
"(3) The existence and operation of a wholesale submarket, commonly known as the 'diversion market', prevents effective control over or even routine knowledge of the true sources of prescription drugs in a significant number of cases.
"(4) Large amounts of drugs are being reimported to the United States as American goods returned. These imports are a health and safety risk to American consumers because they may have become subpotent or adulterated during foreign handling and shipping.
"(5) The ready market for prescription drug reimports has been the catalyst for a continuing series of frauds against American manufacturers and has provided the cover for the importation of foreign counterfeit drugs.
"(6) The existing system of providing drug samples to physicians through manufacturer's representatives has been abused for decades and has resulted in the sale to consumers of misbranded, expired, and adulterated pharmaceuticals.
"(7) The bulk resale of below wholesale priced prescription drugs by health care entities, for ultimate sale at retail, helps fuel the diversion market and is an unfair form of competition to wholesalers and retailers that must pay otherwise prevailing market prices.
"(8) The effect of these several practices and conditions is to create an unacceptable risk that counterfeit, adulterated, misbranded, subpotent, or expired drugs will be sold to American consumers."
Section Referred to in Other Sections
This section is referred to in
1 See References in Text note below.
§353a. Pharmacy compounding
(a) In general
(1) is by—
(A) a licensed pharmacist in a State licensed pharmacy or a Federal facility, or
(B) a licensed physician,
on the prescription order for such individual patient made by a licensed physician or other licensed practitioner authorized by State law to prescribe drugs; or
(2)(A) is by a licensed pharmacist or licensed physician in limited quantities before the receipt of a valid prescription order for such individual patient; and
(B) is based on a history of the licensed pharmacist or licensed physician receiving valid prescription orders for the compounding of the drug product, which orders have been generated solely within an established relationship between—
(i) the licensed pharmacist or licensed physician; and
(ii)(I) such individual patient for whom the prescription order will be provided; or
(II) the physician or other licensed practitioner who will write such prescription order.
(b) Compounded drug
(1) Licensed pharmacist and licensed physician
A drug product may be compounded under subsection (a) of this section if the licensed pharmacist or licensed physician—
(A) compounds the drug product using bulk drug substances, as defined in regulations of the Secretary published at section 207.3(a)(4) of title 21 of the Code of Federal Regulations—
(i) that—
(I) comply with the standards of an applicable United States Pharmacopoeia or National Formulary monograph, if a monograph exists, and the United States Pharmacopoeia chapter on pharmacy compounding;
(II) if such a monograph does not exist, are drug substances that are components of drugs approved by the Secretary; or
(III) if such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary, that appear on a list developed by the Secretary through regulations issued by the Secretary under subsection (d) of this section;
(ii) that are manufactured by an establishment that is registered under
(iii) that are accompanied by valid certificates of analysis for each bulk drug substance;
(B) compounds the drug product using ingredients (other than bulk drug substances) that comply with the standards of an applicable United States Pharmacopoeia or National Formulary monograph, if a monograph exists, and the United States Pharmacopoeia chapter on pharmacy compounding;
(C) does not compound a drug product that appears on a list published by the Secretary in the Federal Register of drug products that have been withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective; and
(D) does not compound regularly or in inordinate amounts (as defined by the Secretary) any drug products that are essentially copies of a commercially available drug product.
(2) Definition
For purposes of paragraph (1)(D), the term "essentially a copy of a commercially available drug product" does not include a drug product in which there is a change, made for an identified individual patient, which produces for that patient a significant difference, as determined by the prescribing practitioner, between the compounded drug and the comparable commercially available drug product.
(3) Drug product
A drug product may be compounded under subsection (a) only if—
(A) such drug product is not a drug product identified by the Secretary by regulation as a drug product that presents demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product; and
(B) such drug product is compounded in a State—
(i) that has entered into a memorandum of understanding with the Secretary which addresses the distribution of inordinate amounts of compounded drug products interstate and provides for appropriate investigation by a State agency of complaints relating to compounded drug products distributed outside such State; or
(ii) that has not entered into the memorandum of understanding described in clause (i) and the licensed pharmacist, licensed pharmacy, or licensed physician distributes (or causes to be distributed) compounded drug products out of the State in which they are compounded in quantities that do not exceed 5 percent of the total prescription orders dispensed or distributed by such pharmacy or physician.
The Secretary shall, in consultation with the National Association of Boards of Pharmacy, develop a standard memorandum of understanding for use by the States in complying with subparagraph (B)(i).
(c) Advertising and promotion
A drug may be compounded under subsection (a) of this section only if the pharmacy, licensed pharmacist, or licensed physician does not advertise or promote the compounding of any particular drug, class of drug, or type of drug. The pharmacy, licensed pharmacist, or licensed physician may advertise and promote the compounding service provided by the licensed pharmacist or licensed physician.
(d) Regulations
(1) In general
The Secretary shall issue regulations to implement this section. Before issuing regulations to implement subsections (b)(1)(A)(i)(III), (b)(1)(C), or (b)(3)(A) of this section, the Secretary shall convene and consult an advisory committee on compounding unless the Secretary determines that the issuance of such regulations before consultation is necessary to protect the public health. The advisory committee shall include representatives from the National Association of Boards of Pharmacy, the United States Pharmacopoeia, pharmacy, physician, and consumer organizations, and other experts selected by the Secretary.
(2) Limiting compounding
The Secretary, in consultation with the United States Pharmacopoeia Convention, Incorporated, shall promulgate regulations identifying drug substances that may be used in compounding under subsection (b)(1)(A)(i)(III) of this section for which a monograph does not exist or which are not components of drug products approved by the Secretary. The Secretary shall include in the regulation the criteria for such substances, which shall include historical use, reports in peer reviewed medical literature, or other criteria the Secretary may identify.
(e) Application
This section shall not apply to—
(1) compounded positron emission tomography drugs as defined in
(2) radiopharmaceuticals.
(f) "Compounding" defined
As used in this section, the term "compounding" does not include mixing, reconstituting, or other such acts that are performed in accordance with directions contained in approved labeling provided by the product's manufacturer and other manufacturer directions consistent with that labeling.
(June 25, 1938, ch. 675, §503A, as added
Effective Date
Section 127(b) of
§354. Veterinary feed directive drugs
(a) Lawful veterinary feed directive requirement
(1) A drug intended for use in or on animal feed which is limited by an approved application filed pursuant to
(2) A veterinary feed directive is lawful if it—
(A) contains such information as the Secretary may by general regulation or by order require; and
(B) is in compliance with the conditions and indications for use of the drug set forth in the notice published pursuant to
(3)(A) Any persons involved in the distribution or use of animal feed bearing or containing a veterinary feed directive drug and the licensed veterinarian issuing the veterinary feed directive shall maintain a copy of the veterinary feed directive applicable to each such feed, except in the case of a person distributing such feed to another person for further distribution. Such person distributing the feed shall maintain a written acknowledgment from the person to whom the feed is shipped stating that that person shall not ship or move such feed to an animal production facility without a veterinary feed directive or ship such feed to another person for further distribution unless that person has provided the same written acknowledgment to its immediate supplier.
(B) Every person required under subparagraph (A) to maintain records, and every person in charge or custody thereof, shall, upon request of an officer or employee designated by the Secretary, permit such officer or employee at all reasonable times to have access to and copy and verify such records.
(C) Any person who distributes animal feed bearing or containing a veterinary feed directive drug shall upon first engaging in such distribution notify the Secretary of that person's name and place of business. The failure to provide such notification shall be deemed to be an act which results in the drug being misbranded.
(b) Labeling and advertising
A veterinary feed directive drug and any feed bearing or containing a veterinary feed directive drug shall be deemed to be misbranded if their labeling fails to bear such cautionary statement and such other information as the Secretary may by general regulation or by order prescribe, or their advertising fails to conform to the conditions and indications for use published pursuant to
(c) Nonprescription status
Neither a drug subject to this section, nor animal feed bearing or containing such a drug, shall be deemed to be a prescription article under any Federal or State law.
(June 25, 1938, ch. 675, §504, as added
Prior Provisions
A prior section 354, act June 25, 1938, ch. 675, §504,
Section Referred to in Other Sections
This section is referred to in
§355. New drugs
(a) Necessity of effective approval of application
No person shall introduce or deliver for introduction into interstate commerce any new drug, unless an approval of an application filed pursuant to subsection (b) or (j) of this section is effective with respect to such drug.
(b) Filing application; contents
(1) Any person may file with the Secretary an application with respect to any drug subject to the provisions of subsection (a) of this section. Such person shall submit to the Secretary as a part of the application (A) full reports of investigations which have been made to show whether or not such drug is safe for use and whether such drug is effective in use; (B) a full list of the articles used as components of such drug; (C) a full statement of the composition of such drug; (D) a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such drug; (E) such samples of such drug and of the articles used as components thereof as the Secretary may require; and (F) specimens of the labeling proposed to be used for such drug. The applicant shall file with the application the patent number and the expiration date of any patent which claims the drug for which the applicant submitted the application or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug. If an application is filed under this subsection for a drug and a patent which claims such drug or a method of using such drug is issued after the filing date but before approval of the application, the applicant shall amend the application to include the information required by the preceding sentence. Upon approval of the application, the Secretary shall publish information submitted under the two preceding sentences. The Secretary shall, in consultation with the Director of the National Institutes of Health and with representatives of the drug manufacturing industry, review and develop guidance, as appropriate, on the inclusion of women and minorities in clinical trials required by clause (A).
(2) An application submitted under paragraph (1) for a drug for which the investigations described in clause (A) of such paragraph and relied upon by the applicant for approval of the application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted shall also include—
(A) a certification, in the opinion of the applicant and to the best of his knowledge, with respect to each patent which claims the drug for which such investigations were conducted or which claims a use for such drug for which the applicant is seeking approval under this subsection and for which information is required to be filed under paragraph (1) or subsection (c) of this section—
(i) that such patent information has not been filed,
(ii) that such patent has expired,
(iii) of the date on which such patent will expire, or
(iv) that such patent is invalid or will not be infringed by the manufacture, use, or sale of the new drug for which the application is submitted; and
(B) if with respect to the drug for which investigations described in paragraph (1)(A) were conducted information was filed under paragraph (1) or subsection (c) of this section for a method of use patent which does not claim a use for which the applicant is seeking approval under this subsection, a statement that the method of use patent does not claim such a use.
(3)(A) An applicant who makes a certification described in paragraph (2)(A)(iv) shall include in the application a statement that the applicant will give the notice required by subparagraph (B) to—
(i) each owner of the patent which is the subject of the certification or the representative of such owner designated to receive such notice, and
(ii) the holder of the approved application under subsection (b) of this section for the drug which is claimed by the patent or a use of which is claimed by the patent or the representative of such holder designated to receive such notice.
(B) The notice referred to in subparagraph (A) shall state that an application has been submitted under this subsection for the drug with respect to which the certification is made to obtain approval to engage in the commercial manufacture, use, or sale of the drug before the expiration of the patent referred to in the certification. Such notice shall include a detailed statement of the factual and legal basis of the applicant's opinion that the patent is not valid or will not be infringed.
(C) If an application is amended to include a certification described in paragraph (2)(A)(iv), the notice required by subparagraph (B) shall be given when the amended application is submitted.
(4)(A) The Secretary shall issue guidance for the individuals who review applications submitted under paragraph (1) or under
(B) The Secretary shall meet with a sponsor of an investigation or an applicant for approval for a drug under this subsection or
(C) Any agreement regarding the parameters of the design and size of clinical trials of a new drug under this paragraph that is reached between the Secretary and a sponsor or applicant shall be reduced to writing and made part of the administrative record by the Secretary. Such agreement shall not be changed after the testing begins, except—
(i) with the written agreement of the sponsor or applicant; or
(ii) pursuant to a decision, made in accordance with subparagraph (D) by the director of the reviewing division, that a substantial scientific issue essential to determining the safety or effectiveness of the drug has been identified after the testing has begun.
(D) A decision under subparagraph (C)(ii) by the director shall be in writing and the Secretary shall provide to the sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant will be present and at which the director will document the scientific issue involved.
(E) The written decisions of the reviewing division shall be binding upon, and may not directly or indirectly be changed by, the field or compliance division personnel unless such field or compliance division personnel demonstrate to the reviewing division why such decision should be modified.
(F) No action by the reviewing division may be delayed because of the unavailability of information from or action by field personnel unless the reviewing division determines that a delay is necessary to assure the marketing of a safe and effective drug.
(G) For purposes of this paragraph, the reviewing division is the division responsible for the review of an application for approval of a drug under this subsection or
(c) Period for approval of application; period for, notice, and expedition of hearing; period for issuance of order
(1) Within one hundred and eighty days after the filing of an application under subsection (b) of this section, or such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall either—
(A) approve the application if he then finds that none of the grounds for denying approval specified in subsection (d) of this section applies, or
(B) give the applicant notice of an opportunity for a hearing before the Secretary under subsection (d) of this section on the question whether such application is approvable. If the applicant elects to accept the opportunity for hearing by written request within thirty days after such notice, such hearing shall commence not more than ninety days after the expiration of such thirty days unless the Secretary and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the Secretary's order thereon shall be issued within ninety days after the date fixed by the Secretary for filing final briefs.
(2) If the patent information described in subsection (b) of this section could not be filed with the submission of an application under subsection (b) of this section because the application was filed before the patent information was required under subsection (b) of this section or a patent was issued after the application was approved under such subsection, the holder of an approved application shall file with the Secretary the patent number and the expiration date of any patent which claims the drug for which the application was submitted or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug. If the holder of an approved application could not file patent information under subsection (b) of this section because it was not required at the time the application was approved, the holder shall file such information under this subsection not later than thirty days after September 24, 1984, and if the holder of an approved application could not file patent information under subsection (b) of this section because no patent had been issued when an application was filed or approved, the holder shall file such information under this subsection not later than thirty days after the date the patent involved is issued. Upon the submission of patent information under this subsection, the Secretary shall publish it.
(3) The approval of an application filed under subsection (b) of this section which contains a certification required by paragraph (2) of such subsection shall be made effective on the last applicable date determined under the following:
(A) If the applicant only made a certification described in clause (i) or (ii) of subsection (b)(2)(A) of this section or in both such clauses, the approval may be made effective immediately.
(B) If the applicant made a certification described in clause (iii) of subsection (b)(2)(A) of this section, the approval may be made effective on the date certified under clause (iii).
(C) If the applicant made a certification described in clause (iv) of subsection (b)(2)(A) of this section, the approval shall be made effective immediately unless an action is brought for infringement of a patent which is the subject of the certification before the expiration of forty-five days from the date the notice provided under paragraph (3)(B) is received. If such an action is brought before the expiration of such days, the approval may be made effective upon the expiration of the thirty-month period beginning on the date of the receipt of the notice provided under paragraph (3)(B) or such shorter or longer period as the court may order because either party to the action failed to reasonably cooperate in expediting the action, except that—
(i) if before the expiration of such period the court decides that such patent is invalid or not infringed, the approval may be made effective on the date of the court decision,
(ii) if before the expiration of such period the court decides that such patent has been infringed, the approval may be made effective on such date as the court orders under
(iii) if before the expiration of such period the court grants a preliminary injunction prohibiting the applicant from engaging in the commercial manufacture or sale of the drug until the court decides the issues of patent validity and infringement and if the court decides that such patent is invalid or not infringed, the approval shall be made effective on the date of such court decision.
In such an action, each of the parties shall reasonably cooperate in expediting the action. Until the expiration of forty-five days from the date the notice made under paragraph (3)(B) is received, no action may be brought under
(D)(i) If an application (other than an abbreviated new drug application) submitted under subsection (b) of this section for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under subsection (b) of this section, was approved during the period beginning January 1, 1982, and ending on September 24, 1984, the Secretary may not make the approval of another application for a drug for which the investigations described in clause (A) of subsection (b)(1) of this section and relied upon by the applicant for approval of the application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted effective before the expiration of ten years from the date of the approval of the application previously approved under subsection (b) of this section.
(ii) If an application submitted under subsection (b) of this section for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under subsection (b) of this section, is approved after September 24, 1984, no application which refers to the drug for which the subsection (b) application was submitted and for which the investigations described in clause (A) of subsection (b)(1) of this section and relied upon by the applicant for approval of the application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted may be submitted under subsection (b) of this section before the expiration of five years from the date of the approval of the application under subsection (b) of this section, except that such an application may be submitted under subsection (b) of this section after the expiration of four years from the date of the approval of the subsection (b) application if it contains a certification of patent invalidity or noninfringement described in clause (iv) of subsection (b)(2)(A) of this section. The approval of such an application shall be made effective in accordance with this paragraph except that, if an action for patent infringement is commenced during the one-year period beginning forty-eight months after the date of the approval of the subsection (b) application, the thirty-month period referred to in subparagraph (C) shall be extended by such amount of time (if any) which is required for seven and one-half years to have elapsed from the date of approval of the subsection (b) application.
(iii) If an application submitted under subsection (b) of this section for a drug, which includes an active ingredient (including any ester or salt of the active ingredient) that has been approved in another application approved under subsection (b) of this section, is approved after September 24, 1984, and if such application contains reports of new clinical investigations (other than bioavailability studies) essential to the approval of the application and conducted or sponsored by the applicant, the Secretary may not make the approval of an application submitted under subsection (b) of this section for the conditions of approval of such drug in the approved subsection (b) application effective before the expiration of three years from the date of the approval of the application under subsection (b) of this section if the investigations described in clause (A) of subsection (b)(1) of this section and relied upon by the applicant for approval of the application were not conducted by or for the applicant and if the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.
(iv) If a supplement to an application approved under subsection (b) of this section is approved after September 24, 1984, and the supplement contains reports of new clinical investigations (other than bioavailabilty 1 studies) essential to the approval of the supplement and conducted or sponsored by the person submitting the supplement, the Secretary may not make the approval of an application submitted under subsection (b) of this section for a change approved in the supplement effective before the expiration of three years from the date of the approval of the supplement under subsection (b) of this section if the investigations described in clause (A) of subsection (b)(1) of this section and relied upon by the applicant for approval of the application were not conducted by or for the applicant and if the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.
(v) If an application (or supplement to an application) submitted under subsection (b) of this section for a drug, which includes an active ingredient (including any ester or salt of the active ingredient) that has been approved in another application under subsection (b) of this section, was approved during the period beginning January 1, 1982, and ending on September 24, 1984, the Secretary may not make the approval of an application submitted under this subsection and for which the investigations described in clause (A) of subsection (b)(1) of this section and relied upon by the applicant for approval of the application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted and which refers to the drug for which the subsection (b) application was submitted effective before the expiration of two years from September 24, 1984.
(4) A drug manufactured in a pilot or other small facility may be used to demonstrate the safety and effectiveness of the drug and to obtain approval for the drug prior to manufacture of the drug in a larger facility, unless the Secretary makes a determination that a full scale production facility is necessary to ensure the safety or effectiveness of the drug.
(d) Grounds for refusing application; approval of application; "substantial evidence" defined
If the Secretary finds, after due notice to the applicant in accordance with subsection (c) of this section and giving him an opportunity for a hearing, in accordance with said subsection, that (1) the investigations, reports of which are required to be submitted to the Secretary pursuant to subsection (b) of this section, do not include adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof; (2) the results of such tests show that such drug is unsafe for use under such conditions or do not show that such drug is safe for use under such conditions; (3) the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such drug are inadequate to preserve its identity, strength, quality, and purity; (4) upon the basis of the information submitted to him as part of the application, or upon the basis of any other information before him with respect to such drug, he has insufficient information to determine whether such drug is safe for use under such conditions; or (5) evaluated on the basis of the information submitted to him as part of the application and any other information before him with respect to such drug, there is a lack of substantial evidence that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof; or (6) the application failed to contain the patent information prescribed by subsection (b) of this section; or (7) based on a fair evaluation of all material facts, such labeling is false or misleading in any particular; he shall issue an order refusing to approve the application. If, after such notice and opportunity for hearing, the Secretary finds that clauses (1) through (6) do not apply, he shall issue an order approving the application. As used in this subsection and subsection (e) of this section, the term "substantial evidence" means evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof. If the Secretary determines, based on relevant science, that data from one adequate and well-controlled clinical investigation and confirmatory evidence (obtained prior to or after such investigation) are sufficient to establish effectiveness, the Secretary may consider such data and evidence to constitute substantial evidence for purposes of the preceding sentence.
(e) Withdrawal of approval; grounds; immediate suspension upon finding imminent hazard to public health
The Secretary shall, after due notice and opportunity for hearing to the applicant, withdraw approval of an application with respect to any drug under this section if the Secretary finds (1) that clinical or other experience, tests, or other scientific data show that such drug is unsafe for use under the conditions of use upon the basis of which the application was approved; (2) that new evidence of clinical experience, not contained in such application or not available to the Secretary until after such application was approved, or tests by new methods, or tests by methods not deemed reasonably applicable when such application was approved, evaluated together with the evidence available to the Secretary when the application was approved, shows that such drug is not shown to be safe for use under the conditions of use upon the basis of which the application was approved; or (3) on the basis of new information before him with respect to such drug, evaluated together with the evidence available to him when the application was approved, that there is a lack of substantial evidence that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling thereof; or (4) the patent information prescribed by subsection (c) of this section was not filed within thirty days after the receipt of written notice from the Secretary specifying the failure to file such information; or (5) that the application contains any untrue statement of a material fact: Provided, That if the Secretary (or in his absence the officer acting as Secretary) finds that there is an imminent hazard to the public health, he may suspend the approval of such application immediately, and give the applicant prompt notice of his action and afford the applicant the opportunity for an expedited hearing under this subsection; but the authority conferred by this proviso to suspend the approval of an application shall not be delegated. The Secretary may also, after due notice and opportunity for hearing to the applicant, withdraw the approval of an application submitted under subsection (b) or (j) of this section with respect to any drug under this section if the Secretary finds (1) that the applicant has failed to establish a system for maintaining required records, or has repeatedly or deliberately failed to maintain such records or to make required reports, in accordance with a regulation or order under subsection (k) of this section or to comply with the notice requirements of
(f) Revocation of order refusing, withdrawing or suspending approval of application
Whenever the Secretary finds that the facts so require, he shall revoke any previous order under subsection (d) or (e) of this section refusing, withdrawing, or suspending approval of an application and shall approve such application or reinstate such approval, as may be appropriate.
(g) Service of orders
Orders of the Secretary issued under this section shall be served (1) in person by any officer or employee of the department designated by the Secretary or (2) by mailing the order by registered mail or by certified mail addressed to the applicant or respondent at his last-known address in the records of the Secretary.
(h) Appeal from order
An appeal may be taken by the applicant from an order of the Secretary refusing or withdrawing approval of an application under this section. Such appeal shall be taken by filing in the United States court of appeals or the circuit wherein such applicant resides or has his principal place of business, or in the United States Court of Appeals for the District of Columbia Circuit, within sixty days after the entry of such order, a written petition praying that the order of the Secretary be set aside. A copy of such petition shall be forthwith transmitted by the clerk of the court to the Secretary, or any officer designated by him for that purpose, and thereupon the Secretary shall certify and file in the court the record upon which the order complained of was entered, as provided in
(i) Exemptions of drugs for research; discretionary and mandatory conditions; direct reports to Secretary
(1) The Secretary shall promulgate regulations for exempting from the operation of the foregoing subsections of this section drugs intended solely for investigational use by experts qualified by scientific training and experience to investigate the safety and effectiveness of drugs. Such regulations may, within the discretion of the Secretary, among other conditions relating to the protection of the public health, provide for conditioning such exemption upon—
(A) the submission to the Secretary, before any clinical testing of a new drug is undertaken, of reports, by the manufacturer or the sponsor of the investigation of such drug, of preclinical tests (including tests on animals) of such drug adequate to justify the proposed clinical testing;
(B) the manufacturer or the sponsor of the investigation of a new drug proposed to be distributed to investigators for clinical testing obtaining a signed agreement from each of such investigators that patients to whom the drug is administered will be under his personal supervision, or under the supervision of investigators responsible to him, and that he will not supply such drug to any other investigator, or to clinics, for administration to human beings; and
(C) the establishment and maintenance of such records, and the making of such reports to the Secretary, by the manufacturer or the sponsor of the investigation of such drug, of data (including but not limited to analytical reports by investigators) obtained as the result of such investigational use of such drug, as the Secretary finds will enable him to evaluate the safety and effectiveness of such drug in the event of the filing of an application pursuant to subsection (b) of this section.
(2) Subject to paragraph (3), a clinical investigation of a new drug may begin 30 days after the Secretary has received from the manufacturer or sponsor of the investigation a submission containing such information about the drug and the clinical investigation, including—
(A) information on design of the investigation and adequate reports of basic information, certified by the applicant to be accurate reports, necessary to assess the safety of the drug for use in clinical investigation; and
(B) adequate information on the chemistry and manufacturing of the drug, controls available for the drug, and primary data tabulations from animal or human studies.
(3)(A) At any time, the Secretary may prohibit the sponsor of an investigation from conducting the investigation (referred to in this paragraph as a "clinical hold") if the Secretary makes a determination described in subparagraph (B). The Secretary shall specify the basis for the clinical hold, including the specific information available to the Secretary which served as the basis for such clinical hold, and confirm such determination in writing.
(B) For purposes of subparagraph (A), a determination described in this subparagraph with respect to a clinical hold is that—
(i) the drug involved represents an unreasonable risk to the safety of the persons who are the subjects of the clinical investigation, taking into account the qualifications of the clinical investigators, information about the drug, the design of the clinical investigation, the condition for which the drug is to be investigated, and the health status of the subjects involved; or
(ii) the clinical hold should be issued for such other reasons as the Secretary may by regulation establish (including reasons established by regulation before November 21, 1997).
(C) Any written request to the Secretary from the sponsor of an investigation that a clinical hold be removed shall receive a decision, in writing and specifying the reasons therefor, within 30 days after receipt of such request. Any such request shall include sufficient information to support the removal of such clinical hold.
(4) Regulations under paragraph (1) shall provide that such exemption shall be conditioned upon the manufacturer, or the sponsor of the investigation, requiring that experts using such drugs for investigational purposes certify to such manufacturer or sponsor that they will inform any human beings to whom such drugs, or any controls used in connection therewith, are being administered, or their representatives, that such drugs are being used for investigational purposes and will obtain the consent of such human beings or their representatives, except where it is not feasible or it is contrary to the best interests of such human beings. Nothing in this subsection shall be construed to require any clinical investigator to submit directly to the Secretary reports on the investigational use of drugs.
(j) Abbreviated new drug applications
(1) Any person may file with the Secretary an abbreviated application for the approval of a new drug.
(2)(A) An abbreviated application for a new drug shall contain—
(i) information to show that the conditions of use prescribed, recommended, or suggested in the labeling proposed for the new drug have been previously approved for a drug listed under paragraph (7) (hereinafter in this subsection referred to as a "listed drug");
(ii)(I) if the listed drug referred to in clause (i) has only one active ingredient, information to show that the active ingredient of the new drug is the same as that of the listed drug;
(II) if the listed drug referred to in clause (i) has more than one active ingredient, information to show that the active ingredients of the new drug are the same as those of the listed drug, or
(III) if the listed drug referred to in clause (i) has more than one active ingredient and if one of the active ingredients of the new drug is different and the application is filed pursuant to the approval of a petition filed under subparagraph (C), information to show that the other active ingredients of the new drug are the same as the active ingredients of the listed drug, information to show that the different active ingredient is an active ingredient of a listed drug or of a drug which does not meet the requirements of
(iii) information to show that the route of administration, the dosage form, and the strength of the new drug are the same as those of the listed drug referred to in clause (i) or, if the route of administration, the dosage form, or the strength of the new drug is different and the application is filed pursuant to the approval of a petition filed under subparagraph (C), such information respecting the route of administration, dosage form, or strength with respect to which the petition was filed as the Secretary may require;
(iv) information to show that the new drug is bioequivalent to the listed drug referred to in clause (i), except that if the application is filed pursuant to the approval of a petition filed under subparagraph (C), information to show that the active ingredients of the new drug are of the same pharmacological or therapeutic class as those of the listed drug referred to in clause (i) and the new drug can be expected to have the same therapeutic effect as the listed drug when administered to patients for a condition of use referred to in clause (i);
(v) information to show that the labeling proposed for the new drug is the same as the labeling approved for the listed drug referred to in clause (i) except for changes required because of differences approved under a petition filed under subparagraph (C) or because the new drug and the listed drug are produced or distributed by different manufacturers;
(vi) the items specified in clauses (B) through (F) of subsection (b)(1) of this section;
(vii) a certification, in the opinion of the applicant and to the best of his knowledge, with respect to each patent which claims the listed drug referred to in clause (i) or which claims a use for such listed drug for which the applicant is seeking approval under this subsection and for which information is required to be filed under subsection (b) or (c) of this section—
(I) that such patent information has not been filed,
(II) that such patent has expired,
(III) of the date on which such patent will expire, or
(IV) that such patent is invalid or will not be infringed by the manufacture, use, or sale of the new drug for which the application is submitted; and
(viii) if with respect to the listed drug referred to in clause (i) information was filed under subsection (b) or (c) of this section for a method of use patent which does not claim a use for which the applicant is seeking approval under this subsection, a statement that the method of use patent does not claim such a use.
The Secretary may not require that an abbreviated application contain information in addition to that required by clauses (i) through (viii).
(B)(i) An applicant who makes a certification described in subparagraph (A)(vii)(IV) shall include in the application a statement that the applicant will give the notice required by clause (ii) to—
(I) each owner of the patent which is the subject of the certification or the representative of such owner designated to receive such notice, and
(II) the holder of the approved application under subsection (b) of this section for the drug which is claimed by the patent or a use of which is claimed by the patent or the representative of such holder designated to receive such notice.
(ii) The notice referred to in clause (i) shall state that an application, which contains data from bioavailability or bioequivalence studies, has been submitted under this subsection for the drug with respect to which the certification is made to obtain approval to engage in the commercial manufacture, use, or sale of such drug before the expiration of the patent referred to in the certification. Such notice shall include a detailed statement of the factual and legal basis of the applicant's opinion that the patent is not valid or will not be infringed.
(iii) If an application is amended to include a certification described in subparagraph (A)(vii)(IV), the notice required by clause (ii) shall be given when the amended application is submitted.
(C) If a person wants to submit an abbreviated application for a new drug which has a different active ingredient or whose route of administration, dosage form, or strength differ from that of a listed drug, such person shall submit a petition to the Secretary seeking permission to file such an application. The Secretary shall approve or disapprove a petition submitted under this subparagraph within ninety days of the date the petition is submitted. The Secretary shall approve such a petition unless the Secretary finds—
(i) that investigations must be conducted to show the safety and effectiveness of the drug or of any of its active ingredients, the route of administration, the dosage form, or strength which differ from the listed drug; or
(ii) that any drug with a different active ingredient may not be adequately evaluated for approval as safe and effective on the basis of the information required to be submitted in an abbreviated application.
(3)(A) The Secretary shall issue guidance for the individuals who review applications submitted under paragraph (1), which shall relate to promptness in conducting the review, technical excellence, lack of bias and conflict of interest, and knowledge of regulatory and scientific standards, and which shall apply equally to all individuals who review such applications.
(B) The Secretary shall meet with a sponsor of an investigation or an applicant for approval for a drug under this subsection if the sponsor or applicant makes a reasonable written request for a meeting for the purpose of reaching agreement on the design and size of bioavailability and bioequivalence studies needed for approval of such application. The sponsor or applicant shall provide information necessary for discussion and agreement on the design and size of such studies. Minutes of any such meeting shall be prepared by the Secretary and made available to the sponsor or applicant.
(C) Any agreement regarding the parameters of design and size of bioavailability and bioequivalence studies of a drug under this paragraph that is reached between the Secretary and a sponsor or applicant shall be reduced to writing and made part of the administrative record by the Secretary. Such agreement shall not be changed after the testing begins, except—
(i) with the written agreement of the sponsor or applicant; or
(ii) pursuant to a decision, made in accordance with subparagraph (D) by the director of the reviewing division, that a substantial scientific issue essential to determining the safety or effectiveness of the drug has been identified after the testing has begun.
(D) A decision under subparagraph (C)(ii) by the director shall be in writing and the Secretary shall provide to the sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant will be present and at which the director will document the scientific issue involved.
(E) The written decisions of the reviewing division shall be binding upon, and may not directly or indirectly be changed by, the field or compliance office personnel unless such field or compliance office personnel demonstrate to the reviewing division why such decision should be modified.
(F) No action by the reviewing division may be delayed because of the unavailability of information from or action by field personnel unless the reviewing division determines that a delay is necessary to assure the marketing of a safe and effective drug.
(G) For purposes of this paragraph, the reviewing division is the division responsible for the review of an application for approval of a drug under this subsection (including scientific matters, chemistry, manufacturing, and controls).
(4) Subject to paragraph (5), the Secretary shall approve an application for a drug unless the Secretary finds—
(A) the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of the drug are inadequate to assure and preserve its identity, strength, quality, and purity;
(B) information submitted with the application is insufficient to show that each of the proposed conditions of use have been previously approved for the listed drug referred to in the application;
(C)(i) if the listed drug has only one active ingredient, information submitted with the application is insufficient to show that the active ingredient is the same as that of the listed drug;
(ii) if the listed drug has more than one active ingredient, information submitted with the application is insufficient to show that the active ingredients are the same as the active ingredients of the listed drug, or
(iii) if the listed drug has more than one active ingredient and if the application is for a drug which has an active ingredient different from the listed drug, information submitted with the application is insufficient to show—
(I) that the other active ingredients are the same as the active ingredients of the listed drug, or
(II) that the different active ingredient is an active ingredient of a listed drug or a drug which does not meet the requirements of
or no petition to file an application for the drug with the different ingredient was approved under paragraph (2)(C);
(D)(i) if the application is for a drug whose route of administration, dosage form, or strength of the drug is the same as the route of administration, dosage form, or strength of the listed drug referred to in the application, information submitted in the application is insufficient to show that the route of administration, dosage form, or strength is the same as that of the listed drug, or
(ii) if the application is for a drug whose route of administration, dosage form, or strength of the drug is different from that of the listed drug referred to in the application, no petition to file an application for the drug with the different route of administration, dosage form, or strength was approved under paragraph (2)(C);
(E) if the application was filed pursuant to the approval of a petition under paragraph (2)(C), the application did not contain the information required by the Secretary respecting the active ingredient, route of administration, dosage form, or strength which is not the same;
(F) information submitted in the application is insufficient to show that the drug is bioequivalent to the listed drug referred to in the application or, if the application was filed pursuant to a petition approved under paragraph (2)(C), information submitted in the application is insufficient to show that the active ingredients of the new drug are of the same pharmacological or therapeutic class as those of the listed drug referred to in paragraph (2)(A)(i) and that the new drug can be expected to have the same therapeutic effect as the listed drug when administered to patients for a condition of use referred to in such paragraph;
(G) information submitted in the application is insufficient to show that the labeling proposed for the drug is the same as the labeling approved for the listed drug referred to in the application except for changes required because of differences approved under a petition filed under paragraph (2)(C) or because the drug and the listed drug are produced or distributed by different manufacturers;
(H) information submitted in the application or any other information available to the Secretary shows that (i) the inactive ingredients of the drug are unsafe for use under the conditions prescribed, recommended, or suggested in the labeling proposed for the drug, or (ii) the composition of the drug is unsafe under such conditions because of the type or quantity of inactive ingredients included or the manner in which the inactive ingredients are included;
(I) the approval under subsection (c) of this section of the listed drug referred to in the application under this subsection has been withdrawn or suspended for grounds described in the first sentence of subsection (e) of this section, the Secretary has published a notice of opportunity for hearing to withdraw approval of the listed drug under subsection (c) of this section for grounds described in the first sentence of subsection (e) of this section, the approval under this subsection of the listed drug referred to in the application under this subsection has been withdrawn or suspended under paragraph (6), or the Secretary has determined that the listed drug has been withdrawn from sale for safety or effectiveness reasons;
(J) the application does not meet any other requirement of paragraph (2)(A); or
(K) the application contains an untrue statement of material fact.
(5)(A) Within one hundred and eighty days of the initial receipt of an application under paragraph (2) or within such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall approve or disapprove the application.
(B) The approval of an application submitted under paragraph (2) shall be made effective on the last applicable date determined under the following:
(i) If the applicant only made a certification described in subclause (I) or (II) of paragraph (2)(A)(vii) or in both such subclauses, the approval may be made effective immediately.
(ii) If the applicant made a certification described in subclause (III) of paragraph (2)(A)(vii), the approval may be made effective on the date certified under subclause (III).
(iii) If the applicant made a certification described in subclause (IV) of paragraph (2)(A)(vii), the approval shall be made effective immediately unless an action is brought for infringement of a patent which is the subject of the certification before the expiration of forty-five days from the date the notice provided under paragraph (2)(B)(i) is received. If such an action is brought before the expiration of such days, the approval shall be made effective upon the expiration of the thirty-month period beginning on the date of the receipt of the notice provided under paragraph (2)(B)(i) or such shorter or longer period as the court may order because either party to the action failed to reasonably cooperate in expediting the action, except that—
(I) if before the expiration of such period the court decides that such patent is invalid or not infringed, the approval shall be made effective on the date of the court decision,
(II) if before the expiration of such period the court decides that such patent has been infringed, the approval shall be made effective on such date as the court orders under
(III) if before the expiration of such period the court grants a preliminary injunction prohibiting the applicant from engaging in the commercial manufacture or sale of the drug until the court decides the issues of patent validity and infringement and if the court decides that such patent is invalid or not infringed, the approval shall be made effective on the date of such court decision.
In such an action, each of the parties shall reasonably cooperate in expediting the action. Until the expiration of forty-five days from the date the notice made under paragraph (2)(B)(i) is received, no action may be brought under
(iv) If the application contains a certification described in subclause (IV) of paragraph (2)(A)(vii) and is for a drug for which a previous application has been submitted under this subsection continuing such a certification, the application shall be made effective not earlier than one hundred and eighty days after—
(I) the date the Secretary receives notice from the applicant under the previous application of the first commercial marketing of the drug under the previous application, or
(II) the date of a decision of a court in an action described in clause (iii) holding the patent which is the subject of the certification to be invalid or not infringed,
whichever is earlier.
(C) If the Secretary decides to disapprove an application, the Secretary shall give the applicant notice of an opportunity for a hearing before the Secretary on the question of whether such application is approvable. If the applicant elects to accept the opportunity for hearing by written request within thirty days after such notice, such hearing shall commence not more than ninety days after the expiration of such thirty days unless the Secretary and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the Secretary's order thereon shall be issued within ninety days after the date fixed by the Secretary for filing final briefs.
(D)(i) If an application (other than an abbreviated new drug application) submitted under subsection (b) of this section for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under subsection (b) of this section, was approved during the period beginning January 1, 1982, and ending on September 24, 1984, the Secretary may not make the approval of an application submitted under this subsection which refers to the drug for which the subsection (b) application was submitted effective before the expiration of ten years from the date of the approval of the application under subsection (b) of this section.
(ii) If an application submitted under subsection (b) of this section for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under subsection (b) of this section, is approved after September 24, 1984, no application may be submitted under this subsection which refers to the drug for which the subsection (b) application was submitted before the expiration of five years from the date of the approval of the application under subsection (b) of this section, except that such an application may be submitted under this subsection after the expiration of four years from the date of the approval of the subsection (b) application if it contains a certification of patent invalidity or noninfringement described in subclause (IV) of paragraph (2)(A)(vii). The approval of such an application shall be made effective in accordance with subparagraph (B) except that, if an action for patent infringement is commenced during the one-year period beginning forty-eight months after the date of the approval of the subsection (b) application, the thirty-month period referred to in subparagraph (B)(iii) shall be extended by such amount of time (if any) which is required for seven and one-half years to have elapsed from the date of approval of the subsection (b) application.
(iii) If an application submitted under subsection (b) of this section for a drug, which includes an active ingredient (including any ester or salt of the active ingredient) that has been approved in another application approved under subsection (b) of this section, is approved after September 24, 1984, and if such application contains reports of new clinical investigations (other than bioavailability studies) essential to the approval of the application and conducted or sponsored by the applicant, the Secretary may not make the approval of an application submitted under this subsection for the conditions of approval of such drug in the subsection (b) application effective before the expiration of three years from the date of the approval of the application under subsection (b) of this section for such drug.
(iv) If a supplement to an application approved under subsection (b) of this section is approved after September 24, 1984, and the supplement contains reports of new clinical investigations (other than bioavailability studies) essential to the approval of the supplement and conducted or sponsored by the person submitting the supplement, the Secretary may not make the approval of an application submitted under this subsection for a change approved in the supplement effective before the expiration of three years from the date of the approval of the supplement under subsection (b) of this section.
(v) If an application (or supplement to an application) submitted under subsection (b) of this section for a drug, which includes an active ingredient (including any ester or salt of the active ingredient) that has been approved in another application under subsection (b) of this section, was approved during the period beginning January 1, 1982, and ending on September 24, 1984, the Secretary may not make the approval of an application submitted under this subsection which refers to the drug for which the subsection (b) application was submitted or which refers to a change approved in a supplement to the subsection (b) application effective before the expiration of two years from September 24, 1984.
(6) If a drug approved under this subsection refers in its approved application to a drug the approval of which was withdrawn or suspended for grounds described in the first sentence of subsection (e) of this section or was withdrawn or suspended under this paragraph or which, as determined by the Secretary, has been withdrawn from sale for safety or effectiveness reasons, the approval of the drug under this subsection shall be withdrawn or suspended—
(A) for the same period as the withdrawal or suspension under subsection (e) of this section or this paragraph, or
(B) if the listed drug has been withdrawn from sale, for the period of withdrawal from sale or, if earlier, the period ending on the date the Secretary determines that the withdrawal from sale is not for safety or effectiveness reasons.
(7)(A)(i) Within sixty days of September 24, 1984, the Secretary shall publish and make available to the public—
(I) a list in alphabetical order of the official and proprietary name of each drug which has been approved for safety and effectiveness under subsection (c) of this section before September 24, 1984;
(II) the date of approval if the drug is approved after 1981 and the number of the application which was approved; and
(III) whether in vitro or in vivo bioequivalence studies, or both such studies, are required for applications filed under this subsection which will refer to the drug published.
(ii) Every thirty days after the publication of the first list under clause (i) the Secretary shall revise the list to include each drug which has been approved for safety and effectiveness under subsection (c) of this section or approved under this subsection during the thirty-day period.
(iii) When patent information submitted under subsection (b) or (c) of this section respecting a drug included on the list is to be published by the Secretary, the Secretary shall, in revisions made under clause (ii), include such information for such drug.
(B) A drug approved for safety and effectiveness under subsection (c) of this section or approved under this subsection shall, for purposes of this subsection, be considered to have been published under subparagraph (A) on the date of its approval or September 24, 1984, whichever is later.
(C) If the approval of a drug was withdrawn or suspended for grounds described in the first sentence of subsection (e) of this section or was withdrawn or suspended under paragraph (6) or if the Secretary determines that a drug has been withdrawn from sale for safety or effectiveness reasons, it may not be published in the list under subparagraph (A) or, if the withdrawal or suspension occurred after its publication in such list, it shall be immediately removed from such list—
(i) for the same period as the withdrawal or suspension under subsection (e) of this section or paragraph (6), or
(ii) if the listed drug has been withdrawn from sale, for the period of withdrawal from sale or, if earlier, the period ending on the date the Secretary determines that the withdrawal from sale is not for safety or effectiveness reasons.
A notice of the removal shall be published in the Federal Register.
(8) For purposes of this subsection:
(A) The term "bioavailability" means the rate and extent to which the active ingredient or therapeutic ingredient is absorbed from a drug and becomes available at the site of drug action.
(B) A drug shall be considered to be bioequivalent to a listed drug if—
(i) the rate and extent of absorption of the drug do not show a significant difference from the rate and extent of absorption of the listed drug when administered at the same molar dose of the therapeutic ingredient under similar experimental conditions in either a single dose or multiple doses; or
(ii) the extent of absorption of the drug does not show a significant difference from the extent of absorption of the listed drug when administered at the same molar dose of the therapeutic ingredient under similar experimental conditions in either a single dose or multiple doses and the difference from the listed drug in the rate of absorption of the drug is intentional, is reflected in its proposed labeling, is not essential to the attainment of effective body drug concentrations on chronic use, and is considered medically insignificant for the drug.
(9) The Secretary shall, with respect to each application submitted under this subsection, maintain a record of—
(A) the name of the applicant,
(B) the name of the drug covered by the application,
(C) the name of each person to whom the review of the chemistry of the application was assigned and the date of such assignment, and
(D) the name of each person to whom the bioequivalence review for such application was assigned and the date of such assignment.
The information the Secretary is required to maintain under this paragraph with respect to an application submitted under this subsection shall be made available to the public after the approval of such application.
(k) Records and reports; required information; regulations and orders; access to records
(1) In the case of any drug for which an approval of an application filed under subsection (b) or (j) of this section is in effect, the applicant shall establish and maintain such records, and make such reports to the Secretary, of data relating to clinical experience and other data or information, received or otherwise obtained by such applicant with respect to such drug, as the Secretary may by general regulation, or by order with respect to such application, prescribe on the basis of a finding that such records and reports are necessary in order to enable the Secretary to determine, or facilitate a determination, whether there is or may be ground for invoking subsection (e) of this section. Regulations and orders issued under this subsection and under subsection (i) of this section shall have due regard for the professional ethics of the medical profession and the interests of patients and shall provide, where the Secretary deems it to be appropriate, for the examination, upon request, by the persons to whom such regulations or orders are applicable, of similar information received or otherwise obtained by the Secretary.
(2) Every person required under this section to maintain records, and every person in charge or custody thereof, shall, upon request of an officer or employee designated by the Secretary, permit such officer or employee at all reasonable times to have access to and copy and verify such records.
(l) Public disclosure of safety and effectiveness data
Safety and effectiveness data and information which has been submitted in an application under subsection (b) of this section for a drug and which has not previously been disclosed to the public shall be made available to the public, upon request, unless extraordinary circumstances are shown—
(1) if no work is being or will be undertaken to have the application approved,
(2) if the Secretary has determined that the application is not approvable and all legal appeals have been exhausted,
(3) if approval of the application under subsection (c) of this section is withdrawn and all legal appeals have been exhausted,
(4) if the Secretary has determined that such drug is not a new drug, or
(5) upon the effective date of the approval of the first application under subsection (j) of this section which refers to such drug or upon the date upon which the approval of an application under subsection (j) of this section which refers to such drug could be made effective if such an application had been submitted.
(m) "Patent" defined
For purposes of this section, the term "patent" means a patent issued by the United States Patent and Trademark Office.
(n) Scientific advisory panels
(1) For the purpose of providing expert scientific advice and recommendations to the Secretary regarding a clinical investigation of a drug or the approval for marketing of a drug under this section or
(2) The Secretary may delegate the appointment and oversight authority granted under
(3) The Secretary shall make appointments to each panel established under paragraph (1) so that each panel shall consist of—
(A) members who are qualified by training and experience to evaluate the safety and effectiveness of the drugs to be referred to the panel and who, to the extent feasible, possess skill and experience in the development, manufacture, or utilization of such drugs;
(B) members with diverse expertise in such fields as clinical and administrative medicine, pharmacy, pharmacology, pharmacoeconomics, biological and physical sciences, and other related professions;
(C) a representative of consumer interests, and a representative of interests of the drug manufacturing industry not directly affected by the matter to be brought before the panel; and
(D) two or more members who are specialists or have other expertise in the particular disease or condition for which the drug under review is proposed to be indicated.
Scientific, trade, and consumer organizations shall be afforded an opportunity to nominate individuals for appointment to the panels. No individual who is in the regular full-time employ of the United States and engaged in the administration of this chapter may be a voting member of any panel. The Secretary shall designate one of the members of each panel to serve as chairman thereof.
(4) Each member of a panel shall publicly disclose all conflicts of interest that member may have with the work to be undertaken by the panel. No member of a panel may vote on any matter where the member or the immediate family of such member could gain financially from the advice given to the Secretary. The Secretary may grant a waiver of any conflict of interest requirement upon public disclosure of such conflict of interest if such waiver is necessary to afford the panel essential expertise, except that the Secretary may not grant a waiver for a member of a panel when the member's own scientific work is involved.
(5) The Secretary shall, as appropriate, provide education and training to each new panel member before such member participates in a panel's activities, including education regarding requirements under this chapter and related regulations of the Secretary, and the administrative processes and procedures related to panel meetings.
(6) Panel members (other than officers or employees of the United States), while attending meetings or conferences of a panel or otherwise engaged in its business, shall be entitled to receive compensation for each day so engaged, including traveltime, at rates to be fixed by the Secretary, but not to exceed the daily equivalent of the rate in effect for positions classified above grade GS–15 of the General Schedule. While serving away from their homes or regular places of business, panel members may be allowed travel expenses (including per diem in lieu of subsistence) as authorized by
(7) The Secretary shall ensure that scientific advisory panels meet regularly and at appropriate intervals so that any matter to be reviewed by such a panel can be presented to the panel not more than 60 days after the matter is ready for such review. Meetings of the panel may be held using electronic communication to convene the meetings.
(8) Within 90 days after a scientific advisory panel makes recommendations on any matter under its review, the Food and Drug Administration official responsible for the matter shall review the conclusions and recommendations of the panel, and notify the affected persons of the final decision on the matter, or of the reasons that no such decision has been reached. Each such final decision shall be documented including the rationale for the decision.
(June 25, 1938, ch. 675, §505,
References in Text
The General Schedule, referred to in subsec. (n)(6), is set out under
Amendments
1999—Subsec. (m).
1997—Subsec. (b)(1).
Subsec. (b)(4).
Subsec. (c)(4).
Subsec. (d).
Subsec. (i).
Subsec. (j)(2)(A)(i).
Subsec. (j)(3).
Subsec. (j)(4).
Subsec. (j)(4)(I).
Subsec. (j)(5), (6).
Subsec. (j)(7).
Subsec. (j)(8), (9).
Subsec. (n).
1993—Subsec. (j)(6)(A)(ii).
Subsec. (j)(6)(A)(iii).
Subsec. (k)(1).
1992—Subsec. (j)(8).
1984—Subsec. (a).
Subsec. (b).
Subsec. (c).
Subsec. (d)(6), (7).
Subsec. (e).
Subsecs. (j), (k).
Subsec. (k)(1).
Subsecs. (l), (m).
1972—Subsec. (e).
1962—Subsec. (a).
Subsec. (b).
Subsec. (c).
Subsec. (d).
Subsec. (e).
Subsec. (f).
Subsec. (h).
Subsec. (i).
Subsec. (j).
1960—Subsec. (g).
Effective Date of 1999 Amendment
Amendment by
Effective Date of 1997 Amendment
Amendment by
Effective Date of 1984 Amendment
Section 105 of
"(a) The Secretary of Health and Human Services shall promulgate, in accordance with the notice and comment requirements of
"(b) During the period beginning sixty days after the date of the enactment of this Act [Sept. 24, 1984], and ending on the date regulations promulgated under subsection (a) take effect, abbreviated new drug applications may be submitted in accordance with the provisions of section 314.2 of title 21 of the Code of Federal Regulations and shall be considered as suitable for any drug which has been approved for safety and effectiveness under section 505(c) of the Federal Food, Drug, and Cosmetic Act [subsec. (c) of this section] before the date of the enactment of this Act. If any such provision is inconsistent with the requirements of section 505(j) of the Federal Food, Drug, and Cosmetic Act, the Secretary shall consider the application under the applicable requirements of such section. The Secretary of Health and Human Services may not approve such an abbreviated new drug application which is filed for a drug which is described in sections 505(c)(3)(D) and 505(j)(4)(D) of the Federal Food, Drug, and Cosmetic Act, except in accordance with such section."
Effective Date of 1972 Amendment
Amendment by
Effective Date of 1962 Amendment
Amendment by
Construction of Amendments by Pub. L. 102–282
Amendment by
Transfer of Functions
For transfer of functions of Federal Security Administrator to Secretary of Health, Education, and Welfare [now Health and Human Services], and of Food and Drug Administration in the Department of Agriculture to Federal Security Agency, see note set out under
Data Requirements for Drugs and Biologics
Section 118 of
Requirements for Review of Approval Procedures and Current Good Manufacturing Practices for Positron Emission Technology
Section 121(c) of
"(1)
"(A)
"(i) appropriate procedures for the approval of positron emission tomography drugs pursuant to section 505 of the Federal Food, Drug, and Cosmetic Act (
"(ii) appropriate current good manufacturing practice requirements for such drugs.
"(B)
"(2)
"(A)
"(B)
"Compounded Positron Emission Topography Drug" Defined
Section 121(e) of
Requirements for Radiopharmaceuticals
Section 122 of
"(a)
"(1)
"(A)
"(B)
"(2)
"(b)
"(1) an article—
"(A) that is intended for use in the diagnosis or monitoring of a disease or a manifestation of a disease in humans; and
"(B) that exhibits spontaneous disintegration of unstable nuclei with the emission of nuclear particles or photons; or
"(2) any nonradioactive reagent kit or nuclide generator that is intended to be used in the preparation of any such article."
Special Rule
Section 123(f) of
Transition
Section 125(d) of
"(1)
"(2)
"(A)(i) Subsections (c)(2), (d)(6), (e)(4), (j)(2)(A)(vii), (j)(2)(A)(viii), (j)(2)(B), (j)(4)(B), and (j)(4)(D); and
"(ii) The third and fourth sentences of subsection (b)(1) (regarding the filing and publication of patent information); and
"(B) Subsections (b)(2)(A), (b)(2)(B), (b)(3), and (c)(3) if the investigations relied upon by the applicant for approval of the application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.
"(3)
Termination of Advisory Panels
Advisory panels established after Jan. 5, 1973, to terminate not later than the expiration of the 2-year period beginning on the date of their establishment, unless, in the case of a panel established by the President or an officer of the Federal Government, such panel is renewed by appropriate action prior to the expiration of such 2-year period, or in the case of a panel established by Congress, its duration is otherwise provided for by law. See sections 3(2) and 14 of
Appeals Taken Prior to October 10, 1962
Section 104(d)(3) of
Section Referred to in Other Sections
This section is referred to in
1 So in original. Probably should be "bioavailability".
§355a. Pediatric studies of drugs
(a) Market exclusivity for new drugs
If, prior to approval of an application that is submitted under
(1)(A)(i) the period referred to in subsection (c)(3)(D)(ii) of
(ii) the period referred to in clauses (iii) and (iv) of subsection (c)(3)(D) of such section, and in clauses (iii) and (iv) of subsection (j)(4)(D) of such section, is deemed to be three years and six months rather than three years; and
(B) if the drug is designated under
(2)(A) if the drug is the subject of—
(i) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II) of
(ii) a listed patent for which a certification has been submitted under subsections (b)(2)(A)(iii) or (j)(2)(A)(vii)(III) of
the period during which an application may not be approved under
(B) if the drug is the subject of a listed patent for which a certification has been submitted under subsection (b)(2)(A)(iv) or (j)(2)(A)(vii)(IV) of
(b) Secretary to develop list of drugs for which additional pediatric information may be beneficial
Not later than 180 days after November 21, 1997, the Secretary, after consultation with experts in pediatric research shall develop, prioritize, and publish an initial list of approved drugs for which additional pediatric information may produce health benefits in the pediatric population. The Secretary shall annually update the list.
(c) Market exclusivity for already-marketed drugs
If the Secretary makes a written request to the holder of an approved application under
(1)(A)(i) the period referred to in subsection (c)(3)(D)(ii) of
(ii) the period referred to in clauses (iii) and (iv) of subsection (c)(3)(D) of such section, and in clauses (iii) and (iv) of subsection (j)(4)(D) of such section, is deemed to be three years and six months rather than three years; and
(B) if the drug is designated under
(2)(A) if the drug is the subject of—
(i) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II) of
(ii) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(iii) or (j)(2)(A)(vii)(III) of
the period during which an application may not be approved under
(B) if the drug is the subject of a listed patent for which a certification has been submitted under subsection (b)(2)(A)(iv) or (j)(2)(A)(vii)(IV) of
(d) Conduct of pediatric studies
(1) Agreement for studies
The Secretary may, pursuant to a written request from the Secretary under subsection (a) or (c) of this section, after consultation with—
(A) the sponsor of an application for an investigational new drug under
(B) the sponsor of an application for a new drug under
(C) the holder of an approved application for a drug under
agree with the sponsor or holder for the conduct of pediatric studies for such drug. Such agreement shall be in writing and shall include a timeframe for such studies.
(2) Written protocols to meet the studies requirement
If the sponsor or holder and the Secretary agree upon written protocols for the studies, the studies requirement of subsection (a) or (c) of this section is satisfied upon the completion of the studies and submission of the reports thereof in accordance with the original written request and the written agreement referred to in paragraph (1). Not later than 60 days after the submission of the report of the studies, the Secretary shall determine if such studies were or were not conducted in accordance with the original written request and the written agreement and reported in accordance with the requirements of the Secretary for filing and so notify the sponsor or holder.
(3) Other methods to meet the studies requirement
If the sponsor or holder and the Secretary have not agreed in writing on the protocols for the studies, the studies requirement of subsection (a) or (c) of this section is satisfied when such studies have been completed and the reports accepted by the Secretary. Not later than 90 days after the submission of the reports of the studies, the Secretary shall accept or reject such reports and so notify the sponsor or holder. The Secretary's only responsibility in accepting or rejecting the reports shall be to determine, within the 90 days, whether the studies fairly respond to the written request, have been conducted in accordance with commonly accepted scientific principles and protocols, and have been reported in accordance with the requirements of the Secretary for filing.
(e) Delay of effective date for certain application
If the Secretary determines that the acceptance or approval of an application under
(f) Notice of determinations on studies requirement
The Secretary shall publish a notice of any determination that the requirements of subsection (d) of this section have been met and that submissions and approvals under subsection (b)(2) or (j) of
(g) Definitions
As used in this section, the term "pediatric studies" or "studies" means at least one clinical investigation (that, at the Secretary's discretion, may include pharmacokinetic studies) in pediatric age groups in which a drug is anticipated to be used.
(h) Limitations
A drug to which the six-month period under subsection (a) or (b) of this section has already been applied—
(1) may receive an additional six-month period under subsection (c)(1)(A)(ii) of this section for a supplemental application if all other requirements under this section are satisfied, except that such a drug may not receive any additional such period under subsection (c)(2) of this section; and
(2) may not receive any additional such period under subsection (c)(1)(B) of this section.
(i) Relationship to regulations
Notwithstanding any other provision of law, if any pediatric study is required pursuant to regulations promulgated by the Secretary and such study meets the completeness, timeliness, and other requirements of this section, such study shall be deemed to satisfy the requirement for market exclusivity pursuant to this section.
(j) Sunset
A drug may not receive any six-month period under subsection (a) or (c) of this section unless the application for the drug under
(1) the drug was in commercial distribution as of November 21, 1997;
(2) the drug was included by the Secretary on the list under subsection (b) of this section as of January 1, 2002;
(3) the Secretary determines that there is a continuing need for information relating to the use of the drug in the pediatric population and that the drug may provide health benefits in that population; and
(4) all requirements of this section are met.
(k) Report
The Secretary shall conduct a study and report to Congress not later than January 1, 2001, based on the experience under the program established under this section. The study and report shall examine all relevant issues, including—
(1) the effectiveness of the program in improving information about important pediatric uses for approved drugs;
(2) the adequacy of the incentive provided under this section;
(3) the economic impact of the program on taxpayers and consumers, including the impact of the lack of lower cost generic drugs on patients, including on lower income patients; and
(4) any suggestions for modification that the Secretary determines to be appropriate.
(June 25, 1938, ch. 675, §505A, as added
§356. Fast track products
(a) Designation of drug as fast track product
(1) In general
The Secretary shall, at the request of the sponsor of a new drug, facilitate the development and expedite the review of such drug if it is intended for the treatment of a serious or life-threatening condition and it demonstrates the potential to address unmet medical needs for such a condition. (In this section, such a drug is referred to as a "fast track product".)
(2) Request for designation
The sponsor of a new drug may request the Secretary to designate the drug as a fast track product. A request for the designation may be made concurrently with, or at any time after, submission of an application for the investigation of the drug under
(3) Designation
Within 60 calendar days after the receipt of a request under paragraph (2), the Secretary shall determine whether the drug that is the subject of the request meets the criteria described in paragraph (1). If the Secretary finds that the drug meets the criteria, the Secretary shall designate the drug as a fast track product and shall take such actions as are appropriate to expedite the development and review of the application for approval of such product.
(b) Approval of application for fast track product
(1) In general
The Secretary may approve an application for approval of a fast track product under
(2) Limitation
Approval of a fast track product under this subsection may be subject to the requirements—
(A) that the sponsor conduct appropriate post-approval studies to validate the surrogate endpoint or otherwise confirm the effect on the clinical endpoint; and
(B) that the sponsor submit copies of all promotional materials related to the fast track product during the preapproval review period and, following approval and for such period thereafter as the Secretary determines to be appropriate, at least 30 days prior to dissemination of the materials.
(3) Expedited withdrawal of approval
The Secretary may withdraw approval of a fast track product using expedited procedures (as prescribed by the Secretary in regulations which shall include an opportunity for an informal hearing) if—
(A) the sponsor fails to conduct any required post-approval study of the fast track drug with due diligence;
(B) a post-approval study of the fast track product fails to verify clinical benefit of the product;
(C) other evidence demonstrates that the fast track product is not safe or effective under the conditions of use; or
(D) the sponsor disseminates false or misleading promotional materials with respect to the product.
(c) Review of incomplete applications for approval of fast track product
(1) In general
If the Secretary determines, after preliminary evaluation of clinical data submitted by the sponsor, that a fast track product may be effective, the Secretary shall evaluate for filing, and may commence review of portions of, an application for the approval of the product before the sponsor submits a complete application. The Secretary shall commence such review only if the applicant—
(A) provides a schedule for submission of information necessary to make the application complete; and
(B) pays any fee that may be required under
(2) Exception
Any time period for review of human drug applications that has been agreed to by the Secretary and that has been set forth in goals identified in letters of the Secretary (relating to the use of fees collected under
(d) Awareness efforts
The Secretary shall—
(1) develop and disseminate to physicians, patient organizations, pharmaceutical and biotechnology companies, and other appropriate persons a description of the provisions of this section applicable to fast track products; and
(2) establish a program to encourage the development of surrogate endpoints that are reasonably likely to predict clinical benefit for serious or life-threatening conditions for which there exist significant unmet medical needs.
(June 25, 1938, ch. 675, §506, as added
Prior Provisions
A prior section 356, act June 25, 1938, ch. 675, §506, as added Dec. 22, 1941, ch. 613, §3,
Effective Date
Section effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of
Guidance
Section 112(b) of
Section Referred to in Other Sections
This section is referred to in title 15 section 1459; title 42 section 1396r–8.
§356a. Manufacturing changes
(a) In general
With respect to a drug for which there is in effect an approved application under
(1) the holder of the approved application or license (referred to in this section as a "holder") has validated the effects of the change in accordance with subsection (b) of this section; and
(2)(A) in the case of a major manufacturing change, the holder has complied with the requirements of subsection (c) of this section; or
(B) in the case of a change that is not a major manufacturing change, the holder complies with the applicable requirements of subsection (d) of this section.
(b) Validation of effects of changes
For purposes of subsection (a)(1) of this section, a drug made with a manufacturing change (whether a major manufacturing change or otherwise) may be distributed only if, before distribution of the drug as so made, the holder involved validates the effects of the change on the identity, strength, quality, purity, and potency of the drug as the identity, strength, quality, purity, and potency may relate to the safety or effectiveness of the drug.
(c) Major manufacturing changes
(1) Requirement of supplemental application
For purposes of subsection (a)(2)(A) of this section, a drug made with a major manufacturing change may be distributed only if, before the distribution of the drug as so made, the holder involved submits to the Secretary a supplemental application for such change and the Secretary approves the application. The application shall contain such information as the Secretary determines to be appropriate, and shall include the information developed under subsection (b) of this section by the holder in validating the effects of the change.
(2) Changes qualifying as major changes
For purposes of subsection (a)(2)(A) of this section, a major manufacturing change is a manufacturing change that is determined by the Secretary to have substantial potential to adversely affect the identity, strength, quality, purity, or potency of the drug as they may relate to the safety or effectiveness of a drug. Such a change includes a change that—
(A) is made in the qualitative or quantitative formulation of the drug involved or in the specifications in the approved application or license referred to in subsection (a) of this section for the drug (unless exempted by the Secretary by regulation or guidance from the requirements of this subsection);
(B) is determined by the Secretary by regulation or guidance to require completion of an appropriate clinical study demonstrating equivalence of the drug to the drug as manufactured without the change; or
(C) is another type of change determined by the Secretary by regulation or guidance to have a substantial potential to adversely affect the safety or effectiveness of the drug.
(d) Other manufacturing changes
(1) In general
For purposes of subsection (a)(2)(B) of this section, the Secretary may regulate drugs made with manufacturing changes that are not major manufacturing changes as follows:
(A) The Secretary may in accordance with paragraph (2) authorize holders to distribute such drugs without submitting a supplemental application for such changes.
(B) The Secretary may in accordance with paragraph (3) require that, prior to the distribution of such drugs, holders submit to the Secretary supplemental applications for such changes.
(C) The Secretary may establish categories of such changes and designate categories to which subparagraph (A) applies and categories to which subparagraph (B) applies.
(2) Changes not requiring supplemental application
(A) Submission of report
A holder making a manufacturing change to which paragraph (1)(A) applies shall submit to the Secretary a report on the change, which shall contain such information as the Secretary determines to be appropriate, and which shall include the information developed under subsection (b) of this section by the holder in validating the effects of the change. The report shall be submitted by such date as the Secretary may specify.
(B) Authority regarding annual reports
In the case of a holder that during a single year makes more than one manufacturing change to which paragraph (1)(A) applies, the Secretary may in carrying out subparagraph (A) authorize the holder to comply with such subparagraph by submitting a single report for the year that provides the information required in such subparagraph for all the changes made by the holder during the year.
(3) Changes requiring supplemental application
(A) Submission of supplemental application
The supplemental application required under paragraph (1)(B) for a manufacturing change shall contain such information as the Secretary determines to be appropriate, which shall include the information developed under subsection (b) of this section by the holder in validating the effects of the change.
(B) Authority for distribution
In the case of a manufacturing change to which paragraph (1)(B) applies:
(i) The holder involved may commence distribution of the drug involved 30 days after the Secretary receives the supplemental application under such paragraph, unless the Secretary notifies the holder within such 30-day period that prior approval of the application is required before distribution may be commenced.
(ii) The Secretary may designate a category of such changes for the purpose of providing that, in the case of a change that is in such category, the holder involved may commence distribution of the drug involved upon the receipt by the Secretary of a supplemental application for the change.
(iii) If the Secretary disapproves the supplemental application, the Secretary may order the manufacturer to cease the distribution of the drugs that have been made with the manufacturing change.
(June 25, 1938, ch. 675, §506A, as added
Effective Date
Section 116(b) of
§356b. Reports of postmarketing studies
(a) Submission
(1) In general
A sponsor of a drug that has entered into an agreement with the Secretary to conduct a postmarketing study of a drug shall submit to the Secretary, within 1 year after the approval of such drug and annually thereafter until the study is completed or terminated, a report of the progress of the study or the reasons for the failure of the sponsor to conduct the study. The report shall be submitted in such form as is prescribed by the Secretary in regulations issued by the Secretary.
(2) Agreements prior to effective date
Any agreement entered into between the Secretary and a sponsor of a drug, prior to November 21, 1997, to conduct a postmarketing study of a drug shall be subject to the requirements of paragraph (1). An initial report for such an agreement shall be submitted within 6 months after the date of the issuance of the regulations under paragraph (1).
(b) Consideration of information as public information
Any information pertaining to a report described in subsection (a) of this section shall be considered to be public information to the extent that the information is necessary—
(1) to identify the sponsor; and
(2) to establish the status of a study described in subsection (a) of this section and the reasons, if any, for any failure to carry out the study.
(c) Status of studies and reports
The Secretary shall annually develop and publish in the Federal Register a report that provides information on the status of the postmarketing studies—
(1) that sponsors have entered into agreements to conduct; and
(2) for which reports have been submitted under subsection (a)(1) of this section.
(June 25, 1938, ch. 675, §506B, as added
Effective Date
Section effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of
Report to Congressional Committees
Section 130(b) of
"(1) a summary of the reports submitted under section 506B of the Federal Food, Drug, and Cosmetic Act [
"(2) an evaluation of—
"(A) the performance of the sponsors referred to in such section in fulfilling the agreements with respect to the conduct of postmarketing studies described in such section of such Act; and
"(B) the timeliness of the Secretary's review of the postmarketing studies; and
"(3) any legislative recommendations respecting the postmarketing studies."
§356c. Discontinuance of life saving product
(a) In general
A manufacturer that is the sole manufacturer of a drug—
(1) that is—
(A) life-supporting;
(B) life-sustaining; or
(C) intended for use in the prevention of a debilitating disease or condition;
(2) for which an application has been approved under
(3) that is not a product that was originally derived from human tissue and was replaced by a recombinant product,
shall notify the Secretary of a discontinuance of the manufacture of the drug at least 6 months prior to the date of the discontinuance.
(b) Reduction in notification period
The notification period required under subsection (a) of this section for a manufacturer may be reduced if the manufacturer certifies to the Secretary that good cause exists for the reduction, such as a situation in which—
(1) a public health problem may result from continuation of the manufacturing for the 6-month period;
(2) a biomaterials shortage prevents the continuation of the manufacturing for the 6-month period;
(3) a liability problem may exist for the manufacturer if the manufacturing is continued for the 6-month period;
(4) continuation of the manufacturing for the 6-month period may cause substantial economic hardship for the manufacturer;
(5) the manufacturer has filed for bankruptcy under
(6) the manufacturer can continue the distribution of the drug involved for 6 months.
(c) Distribution
To the maximum extent practicable, the Secretary shall distribute information on the discontinuation of the drugs described in subsection (a) of this section to appropriate physician and patient organizations.
(June 25, 1938, ch. 675, §506C, as added
Effective Date
Section effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of
§357. Repealed. Pub. L. 105–115, title I, §125(b)(1), Nov. 21, 1997, 111 Stat. 2325
Section, act June 25, 1938, ch. 675, §507, as added July 6, 1945, ch. 281, §3,
§358. Authority to designate official names
(a) Necessity or desirability; use in official compendiums; infringement of trademarks
The Secretary may designate an official name for any drug or device if he determines that such action is necessary or desirable in the interest of usefulness and simplicity. Any official name designated under this section for any drug or device shall be the only official name of that drug or device used in any official compendium published after such name has been prescribed or for any other purpose of this chapter. In no event, however, shall the Secretary establish an official name so as to infringe a valid trademark.
(b) Review of names in official compendiums
Within a reasonable time after October 10, 1962, and at such other times as he may deem necessary, the Secretary shall cause a review to be made of the official names by which drugs are identified in the official United States Pharmacopoeia, the official Homoeopathic Pharmacopoeia of the United States, and the official National Formulary, and all supplements thereto, and at such times as he may deem necessary shall cause a review to be made of the official names by which devices are identified in any official compendium (and all supplements thereto) to determine whether revision of any of those names is necessary or desirable in the interest of usefulness and simplicity.
(c) Determinations of complexity, usefulness, multiplicity, or lack of name; designation by Secretary
Whenever he determines after any such review that (1) any such official name is unduly complex or is not useful for any other reason, (2) two or more official names have been applied to a single drug or device, or to two or more drugs which are identical in chemical structure and pharmacological action and which are substantially identical in strength, quality, and purity, or to two or more devices which are substantially equivalent in design and purpose or (3) no official name has been applied to a medically useful drug or device, he shall transmit in writing to the compiler of each official compendium in which that drug or drugs or device are identified and recognized his request for the recommendation of a single official name for such drug or drugs or device which will have usefulness and simplicity. Whenever such a single official name has not been recommended within one hundred and eighty days after such request, or the Secretary determines that any name so recommended is not useful for any reason, he shall designate a single official name for such drug or drugs or device. Whenever he determines that the name so recommended is useful, he shall designate that name as the official name of such drug or drugs or device. Such designation shall be made as a regulation upon public notice and in accordance with the procedure set forth in
(d) Revised official names; compilation, publication, and public distribution of listings
After each such review, and at such other times as the Secretary may determine to be necessary or desirable, the Secretary shall cause to be compiled, published, and publicly distributed a list which shall list all revised official names of drugs or devices designated under this section and shall contain such descriptive and explanatory matter as the Secretary may determine to be required for the effective use of those names.
(e) Request by compiler of official compendium for designation of name
Upon a request in writing by any compiler of an official compendium that the Secretary exercise the authority granted to him under subsection (a) of this section, he shall upon public notice and in accordance with the procedure set forth in
(June 25, 1938, ch. 675, §508, as added
Amendments
1993—Subsecs. (c), (e).
1976—Subsec. (a).
Subsec. (b).
Subsec. (c)(2).
Subsec. (c)(3).
Subsec. (d).
Subsec. (e).
Effective Date
Section 111(b) of
Section Referred to in Other Sections
This section is referred to in
§359. Nonapplicability of subchapter to cosmetics
This subchapter, as amended by the Drug Amendments of 1962, shall not apply to any cosmetic unless such cosmetic is also a drug or device or component thereof.
(June 25, 1938, ch. 675, §509, as added
References in Text
This subchapter, as amended by the Drug Amendments of 1962, referred to in text, means the amendment of this subchapter by
The Drug Amendments of 1962, referred to in text, is
§360. Registration of producers of drugs or devices
(a) Definitions
As used in this section—
(1) the term "manufacture, preparation, propagation, compounding, or processing" shall include repackaging or otherwise changing the container, wrapper, or labeling of any drug package or device package in furtherance of the distribution of the drug or device from the original place of manufacture to the person who makes final delivery or sale to the ultimate consumer or user; and
(2) the term "name" shall include in the case of a partnership the name of each partner and, in the case of a corporation, the name of each corporate officer and director, and the State of incorporation.
(b) Annual registration
On or before December 31 of each year every person who owns or operates any establishment in any State engaged in the manufacture, preparation, propagation, compounding, or processing of a drug or drugs or a device or devices shall register with the Secretary his name, places of business, and all such establishments.
(c) New producers
Every person upon first engaging in the manufacture, preparation, propagation, compounding, or processing of a drug or drugs or a device or devices in any establishment which he owns or operates in any State shall immediately register with the Secretary his name, place of business, and such establishment.
(d) Additional establishments
Every person duly registered in accordance with the foregoing subsections of this section shall immediately register with the Secretary any additional establishment which he owns or operates in any State and in which he begins the manufacture, preparation, propagation, compounding, or processing of a drug or drugs or a device or devices.
(e) Registration number; uniform system for identification of devices intended for human use
The Secretary may assign a registration number to any person or any establishment registered in accordance with this section. The Secretary may also assign a listing number to each drug or class of drugs listed under subsection (j) of this section. Any number assigned pursuant to the preceding sentence shall be the same as that assigned pursuant to the National Drug Code. The Secretary may by regulation prescribe a uniform system for the identification of devices intended for human use and may require that persons who are required to list such devices pursuant to subsection (j) of this section shall list such devices in accordance with such system.
(f) Availability of registrations for inspection
The Secretary shall make available for inspection, to any person so requesting, any registration filed pursuant to this section; except that any list submitted pursuant to paragraph (3) of subsection (j) of this section and the information accompanying any list or notice filed under paragraph (1) or (2) of that subsection shall be exempt from such inspection unless the Secretary finds that such an exemption would be inconsistent with protection of the public health.
(g) Exclusions from application of section
The foregoing subsections of this section shall not apply to—
(1) pharmacies which maintain establishments in conformance with any applicable local laws regulating the practice of pharmacy and medicine and which are regularly engaged in dispensing prescription drugs or devices, upon prescriptions of practitioners licensed to administer such drugs or devices to patients under the care of such practitioners in the course of their professional practice, and which do not manufacture, prepare, propagate, compound, or process drugs or devices for sale other than in the regular course of their business of dispensing or selling drugs or devices at retail;
(2) practitioners licensed by law to prescribe or administer drugs or devices and who manufacture, prepare, propagate, compound, or process drugs or devices solely for use in the course of their professional practice;
(3) persons who manufacture, prepare, propagate, compound, or process drugs or devices solely for use in research, teaching, or chemical analysis and not for sale;
(4) any distributor who acts as a wholesale distributor of devices, and who does not manufacture, repackage, process, or relabel a device; or
(5) such other classes of persons as the Secretary may by regulation exempt from the application of this section upon a finding that registration by such classes of persons in accordance with this section is not necessary for the protection of the public health.
In this subsection, the term "wholesale distributor" means any person (other than the manufacturer or the initial importer) who distributes a device from the original place of manufacture to the person who makes the final delivery or sale of the device to the ultimate consumer or user.
(h) Inspection of premises
Every establishment in any State registered with the Secretary pursuant to this section shall be subject to inspection pursuant to
(i) Registration of foreign establishments
(1) Any establishment within any foreign country engaged in the manufacture, preparation, propagation, compounding, or processing of a drug or a device that is imported or offered for import into the United States shall register with the Secretary the name and place of business of the establishment and the name of the United States agent for the establishment.
(2) The establishment shall also provide the information required by subsection (j) of this section.
(3) The Secretary is authorized to enter into cooperative arrangements with officials of foreign countries to ensure that adequate and effective means are available for purposes of determining, from time to time, whether drugs or devices manufactured, prepared, propagated, compounded, or processed by an establishment described in paragraph (1), if imported or offered for import into the United States, shall be refused admission on any of the grounds set forth in
(j) Filing of lists of drugs and devices manufactured, prepared, propagated and compounded by registrants; statements; accompanying disclosures
(1) Every person who registers with the Secretary under subsection (b), (c), or (d) of this section shall, at the time of registration under any such subsection, file with the Secretary a list of all drugs and a list of all devices and a brief statement of the basis for believing that each device included in the list is a device rather than a drug (with each drug and device in each list listed by its established name (as defined in
(A) in the case of a drug contained in the applicable list and subject to
(B) in the case of any other drug or device contained in an applicable list—
(i) which drug is subject to
(ii) which drug is not subject to
(C) in the case of any drug contained in an applicable list which is described in subparagraph (B), a quantitative listing of its active ingredient or ingredients, except that with respect to a particular drug product the Secretary may require the submission of a quantitative listing of all ingredients if he finds that such submission is necessary to carry out the purposes of this chapter; and
(D) if the registrant filing a list has determined that a particular drug product or device contained in such list is not subject to
(2) Each person who registers with the Secretary under this section shall report to the Secretary once during the month of June of each year and once during the month of December of each year the following information:
(A) A list of each drug or device introduced by the registrant for commercial distribution which has not been included in any list previously filed by him with the Secretary under this subparagraph or paragraph (1) of this subsection. A list under this subparagraph shall list a drug or device by its established name (as defined in
(B) If since the date the registrant last made a report under this paragraph (or if he has not made a report under this paragraph, since February 1, 1973) he has discontinued the manufacture, preparation, propagation, compounding, or processing for commercial distribution of a drug or device included in a list filed by him under subparagraph (A) or paragraph (1); notice of such discontinuance, the date of such discontinuance, and the identity (by established name (as defined in
(C) If since the date the registrant reported pursuant to subparagraph (B) a notice of discontinuance he has resumed the manufacture, preparation, propagation, compounding, or processing for commercial distribution of the drug or device with respect to which such notice of discontinuance was reported; notice of such resumption, the date of such resumption, the identity of such drug or device (each by established name (as defined in
(D) Any material change in any information previously submitted pursuant to this paragraph or paragraph (1).
(3) The Secretary may also require each registrant under this section to submit a list of each drug product which (A) the registrant is manufacturing, preparing, propagating, compounding, or processing for commercial distribution, and (B) contains a particular ingredient. The Secretary may not require the submission of such a list unless he has made a finding that the submission of such a list is necessary to carry out the purposes of this chapter.
(k) Report preceding introduction of devices into interstate commerce
Each person who is required to register under this section and who proposes to begin the introduction or delivery for introduction into interstate commerce for commercial distribution of a device intended for human use shall, at least ninety days before making such introduction or delivery, report to the Secretary or person who is accredited under
(1) the class in which the device is classified under
(2) action taken by such person to comply with requirements under
(l) Exemption from reporting requirements
A report under subsection (k) of this section is not required for a device intended for human use that is exempted from the requirements of this subsection under subsection (m) of this section or is within a type that has been classified into class I under
(m) List of exempt class II devices; determination by Secretary; publication in Federal Register
(1) Not later than 60 days after November 21, 1997, the Secretary shall publish in the Federal Register a list of each type of class II device that does not require a report under subsection (k) of this section to provide reasonable assurance of safety and effectiveness. Each type of class II device identified by the Secretary as not requiring the report shall be exempt from the requirement to provide a report under subsection (k) of this section as of the date of the publication of the list in the Federal Register.
(2) Beginning on the date that is 1 day after the date of the publication of a list under this subsection, the Secretary may exempt a class II device from the requirement to submit a report under subsection (k) of this section, upon the Secretary's own initiative or a petition of an interested person, if the Secretary determines that such report is not necessary to assure the safety and effectiveness of the device. The Secretary shall publish in the Federal Register notice of the intent of the Secretary to exempt the device, or of the petition, and provide a 30-day period for public comment. Within 120 days after the issuance of the notice in the Federal Register, the Secretary shall publish an order in the Federal Register that sets forth the final determination of the Secretary regarding the exemption of the device that was the subject of the notice. If the Secretary fails to respond to a petition within 180 days of receiving it, the petition shall be deemed to be granted.
(n) Review of report; time for determination by Secretary
The Secretary shall review the report required in subsection (k) of this section and make a determination under
(June 25, 1938, ch. 675, §510, as added
Amendments
1997—Subsec. (g).
Subsec. (g)(4), (5).
Subsec. (i).
Subsec. (j)(1)(A), (D).
Subsec. (k).
Subsecs. (l), (m).
Subsec. (n).
1976—Subsec. (a)(1).
Subsecs. (b) to (d).
Subsec. (e).
Subsec. (g)(1) to (3).
Subsec. (h).
Subsec. (i).
Subsec. (j)(1).
Subsec. (j)(1)(A).
Subsec. (j)(1)(B).
Subsec. (j)(1)(B)(i).
Subsec. (j)(1)(B)(ii).
Subsec. (j)(1)(C).
Subsec. (j)(1)(D).
Subsec. (j)(2).
Subsec. (k).
1972—Subsec. (e).
Subsec. (f).
Subsec. (i).
Subsec. (j).
1970—Subsec. (a).
Subsec. (b).
Subsec. (c).
Subsec. (d).
1965—
Subsec. (a)(2), (3).
Subsecs. (b), (c).
Subsec. (d).
Effective Date of 1997 Amendment
Amendment by sections 206(a), 209(a), 213(b), and 417 of
Effective Date of 1972 Amendment
Section 5 of
Effective Date of 1970 Amendment
Amendment by
Effective Date of 1965 Amendment
Amendment by
Savings Provision
Amendment by
Congressional Declaration of Need for Registration and Inspection of Drug Establishments
Section 301 of
Declaration of Policy of Drug Listing Act of 1972
Section 2 of
Registration of Certain Persons Owning or Operating Drug Establishments Prior to Oct. 10, 1962
Section 303 of
Section Referred to in Other Sections
This section is referred to in
§360a. Repealed. Pub. L. 91–513, title II, §701(a), Oct. 27, 1970, 84 Stat. 1281
Section, act June 25, 1938, ch. 675, §511, as added July 15, 1965,
Effective Date of Repeal
Repeal by
Savings Provision
Repeal not to affect or abate any prosecutions for violation of law or any civil seizures or forfeitures and injunctive proceedings commenced prior to the effective date of such repeal, and all administrative proceedings pending before the Bureau of Narcotics and Dangerous Drugs [now Drug Enforcement Administration] on Oct. 27, 1970, to be continued and brought to final determination in accord with laws and regulations in effect prior to Oct. 27, 1970, see section 702 of
§360b. New animal drugs
(a) Unsafe new animal drugs and animal feed containing such drugs; conditions of safety; exemption of drugs for research; import tolerances
(1) A new animal drug shall, with respect to any particular use or intended use of such drug, be deemed unsafe for the purposes of
(A) there is in effect an approval of an application filed pursuant to subsection (b) of this section with respect to such use or intended use of such drug, and
(B) such drug, its labeling, and such use conform to such approved application.
A new animal drug shall also be deemed unsafe for such purposes in the event of removal from the establishment of a manufacturer, packer, or distributor of such drug for use in the manufacture of animal feed in any State unless at the time of such removal such manufacturer, packer, or distributor has an unrevoked written statement from the consignee of such drug, or notice from the Secretary, to the effect that, with respect to the use of such drug in animal feed, such consignee (i) holds a license issued under subsection (m) of this section and has in its possession current approved labeling for such drug in animal feed; or (ii) will, if the consignee is not a user of the drug, ship such drug only to a holder of a license issued under subsection (m) of this section.
(2) An animal feed bearing or containing a new animal drug shall, with respect to any particular use or intended use of such animal feed be deemed unsafe for the purposes of
(A) there is in effect an approval of an application filed pursuant to subsection (b) of this section with respect to such drug, as used in such animal feed,
(B) such animal feed is manufactured at a site for which there is in effect a license issued pursuant to subsection (m)(1) of this section to manufacture such animal feed, and
(C) such animal feed and its labeling, distribution, holding, and use conform to the conditions and indications of use published pursuant to subsection (i) of this section.
(3) A new animal drug or an animal feed bearing or containing a new animal drug shall not be deemed unsafe for the purposes of section 351(a)(5) or (6) of this title if such article is for investigational use and conforms to the terms of an exemption in effect with respect thereto under subsection (j) of this section.
(4)(A) Except as provided in subparagraph (B), if an approval of an application filed under subsection (b) of this section is in effect with respect to a particular use or intended use of a new animal drug, the drug shall not be deemed unsafe for the purposes of paragraph (1) and shall be exempt from the requirements of
(i) is by or on the lawful written or oral order of a licensed veterinarian within the context of a veterinarian-client-patient relationship, as defined by the Secretary; and
(ii) is in compliance with regulations promulgated by the Secretary that establish the conditions for such different use or intended use.
The regulations promulgated by the Secretary under clause (ii) may prohibit particular uses of an animal drug and shall not permit such different use of an animal drug if the labeling of another animal drug that contains the same active ingredient and which is in the same dosage form and concentration provides for such different use.
(B) If the Secretary finds that there is a reasonable probability that a use of an animal drug authorized under subparagraph (A) may present a risk to the public health, the Secretary may—
(i) establish a safe level for a residue of an animal drug when it is used for such different use authorized by subparagraph (A); and
(ii) require the development of a practical, analytical method for the detection of residues of such drug above the safe level established under clause (i).
The use of an animal drug that results in residues exceeding a safe level established under clause (i) shall be considered an unsafe use of such drug under paragraph (1). Safe levels may be established under clause (i) either by regulation or order.
(C) The Secretary may by general regulation provide access to the records of veterinarians to ascertain any use or intended use authorized under subparagraph (A) that the Secretary has determined may present a risk to the public health.
(D) If the Secretary finds, after affording an opportunity for public comment, that a use of an animal drug authorized under subparagraph (A) presents a risk to the public health or that an analytical method required under subparagraph (B) has not been developed and submitted to the Secretary, the Secretary may, by order, prohibit any such use.
(5) If the approval of an application filed under
(A) is by or on the lawful written or oral order of a licensed veterinarian within the context of a veterinarian-client-patient relationship, as defined by the Secretary; and
(B) is in compliance with regulations promulgated by the Secretary that establish the conditions for the use or intended use of the drug in animals.
(6) For purposes of section 342(a)(2)(D) 1 of this title, a use or intended use of a new animal drug shall not be deemed unsafe under this section if the Secretary establishes a tolerance for such drug and any edible portion of any animal imported into the United States does not contain residues exceeding such tolerance. In establishing such tolerance, the Secretary shall rely on data sufficient to demonstrate that a proposed tolerance is safe based on similar food safety criteria used by the Secretary to establish tolerances for applications for new animal drugs filed under subsection (b)(1) of this section. The Secretary may consider and rely on data submitted by the drug manufacturer, including data submitted to appropriate regulatory authorities in any country where the new animal drug is lawfully used or data available from a relevant international organization, to the extent such data are not inconsistent with the criteria used by the Secretary to establish a tolerance for applications for new animal drugs filed under subsection (b)(1) of this section. For purposes of this paragraph, "relevant international organization" means the Codex Alimenterius Commission or other international organization deemed appropriate by the Secretary. The Secretary may, under procedures specified by regulation, revoke a tolerance established under this paragraph if information demonstrates that the use of the new animal drug under actual use conditions results in food being imported into the United States with residues exceeding the tolerance or if scientific evidence shows the tolerance to be unsafe.
(b) Filing application for uses of new animal drug; contents; patent information; abbreviated application; presubmission conference
(1) Any person may file with the Secretary an application with respect to any intended use or uses of a new animal drug. Such person shall submit to the Secretary as a part of the application (A) full reports of investigations which have been made to show whether or not such drug is safe and effective for use; (B) a full list of the articles used as components of such drug; (C) a full statement of the composition of such drug; (D) a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such drug; (E) such samples of such drug and of the articles used as components thereof, of any animal feed for use in or on which such drug is intended, and of the edible portions or products (before or after slaughter) of animals to which such drug (directly or in or on animal feed) is intended to be administered, as the Secretary may require; (F) specimens of the labeling proposed to be used for such drug, or in case such drug is intended for use in animal feed, proposed labeling appropriate for such use, and specimens of the labeling for the drug to be manufactured, packed, or distributed by the applicant; (G) a description of practicable methods for determining the quantity, if any, of such drug in or on food, and any substance formed in or on food, because of its use; and (H) the proposed tolerance or withdrawal period or other use restrictions for such drug if any tolerance or withdrawal period or other use restrictions are required in order to assure that the proposed use of such drug will be safe. The applicant shall file with the application the patent number and the expiration date of any patent which claims the new animal drug for which the applicant filed the application or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug. If an application is filed under this subsection for a drug and a patent which claims such drug or a method of using such drug is issued after the filing date but before approval of the application, the applicant shall amend the application to include the information required by the preceding sentence. Upon approval of the application, the Secretary shall publish information submitted under the two preceding sentences.
(2) Any person may file with the Secretary an abbreviated application for the approval of a new animal drug. An abbreviated application shall contain the information required by subsection (n) of this section.
(3) Any person intending to file an application under paragraph (1) or a request for an investigational exemption under subsection (j) of this section shall be entitled to one or more conferences prior to such submission to reach an agreement acceptable to the Secretary establishing a submission or an investigational requirement, which may include a requirement for a field investigation. A decision establishing a submission or an investigational requirement shall bind the Secretary and the applicant or requestor unless (A) the Secretary and the applicant or requestor mutually agree to modify the requirement, or (B) the Secretary by written order determines that a substantiated scientific requirement essential to the determination of safety or effectiveness of the animal drug involved has appeared after the conference. No later than 25 calendar days after each such conference, the Secretary shall provide a written order setting forth a scientific justification specific to the animal drug and intended uses under consideration if the agreement referred to in the first sentence requires more than one field investigation as being essential to provide substantial evidence of effectiveness for the intended uses of the drug. Nothing in this paragraph shall be construed as compelling the Secretary to require a field investigation.
(c) Period for submission and approval of application; period for notice and expedition of hearing; period for issuance of order; abbreviated applications; withdrawal periods; effective date of approval; relationship to other applications; withdrawal or suspension of approval; bioequivalence; filing of additional patent information
(1) Within one hundred and eighty days after the filing of an application pursuant to subsection (b) of this section, or such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall either (A) issue an order approving the application if he then finds that none of the grounds for denying approval specified in subsection (d) of this section applies, or (B) give the applicant notice of an opportunity for a hearing before the Secretary under subsection (d) of this section on the question whether such application is approvable. If the applicant elects to accept the opportunity for a hearing by written request within thirty days after such notice, such hearing shall commence not more than ninety days after the expiration of such thirty days unless the Secretary and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the Secretary's order thereon shall be issued within ninety days after the date fixed by the Secretary for filing final briefs.
(2)(A) Subject to subparagraph (C), the Secretary shall approve an abbreviated application for a drug unless the Secretary finds—
(i) the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of the drug are inadequate to assure and preserve its identity, strength, quality, and purity;
(ii) the conditions of use prescribed, recommended, or suggested in the proposed labeling are not reasonably certain to be followed in practice or, except as provided in subparagraph (B), information submitted with the application is insufficient to show that each of the proposed conditions of use or similar limitations (whether in the labeling or published pursuant to subsection (i) of this section) have been previously approved for the approved new animal drug referred to in the application;
(iii) information submitted with the application is insufficient to show that the active ingredients are the same as those of the approved new animal drug referred to in the application;
(iv)(I) if the application is for a drug whose active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed is the same as the active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed of the approved new animal drug referred to in the application, information submitted in the application is insufficient to show that the active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed is the same as that of the approved new animal drug, or
(II) if the application is for a drug whose active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed is different from that of the approved new animal drug referred to in the application, no petition to file an application for the drug with the different active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed was approved under subsection (n)(3) of this section;
(v) if the application was filed pursuant to the approval of a petition under subsection (n)(3) of this section, the application did not contain the information required by the Secretary respecting the active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed which is not the same;
(vi) information submitted in the application is insufficient to show that the drug is bioequivalent to the approved new animal drug referred to in the application, or if the application is filed under a petition approved pursuant to subsection (n)(3) of this section, information submitted in the application is insufficient to show that the active ingredients of the new animal drug are of the same pharmacological or therapeutic class as the pharmacological or therapeutic class of the approved new animal drug and that the new animal drug can be expected to have the same therapeutic effect as the approved new animal drug when used in accordance with the labeling;
(vii) information submitted in the application is insufficient to show that the labeling proposed for the drug is the same as the labeling approved for the approved new animal drug referred to in the application except for changes required because of differences approved under a petition filed under subsection (n)(3) of this section, because of a different withdrawal period, or because the drug and the approved new animal drug are produced or distributed by different manufacturers;
(viii) information submitted in the application or any other information available to the Secretary shows that (I) the inactive ingredients of the drug are unsafe for use under the conditions prescribed, recommended, or suggested in the labeling proposed for the drug, (II) the composition of the drug is unsafe under such conditions because of the type or quantity of inactive ingredients included or the manner in which the inactive ingredients are included, or (III) in the case of a drug for food producing animals, the inactive ingredients of the drug or its composition may be unsafe with respect to human food safety;
(ix) the approval under subsection (b)(1) of this section of the approved new animal drug referred to in the application filed under subsection (b)(2) of this section has been withdrawn or suspended for grounds described in paragraph (1) of subsection (e) of this section, the Secretary has published a notice of a hearing to withdraw approval of the approved new animal drug for such grounds, the approval under this paragraph of the new animal drug for which the application under subsection (b)(2) of this section was filed has been withdrawn or suspended under subparagraph (G) for such grounds, or the Secretary has determined that the approved new animal drug has been withdrawn from sale for safety or effectiveness reasons;
(x) the application does not meet any other requirement of subsection (n) of this section; or
(xi) the application contains an untrue statement of material fact.
(B) If the Secretary finds that a new animal drug for which an application is submitted under subsection (b)(2) of this section is bioequivalent to the approved new animal drug referred to in such application and that residues of the new animal drug are consistent with the tolerances established for such approved new animal drug but at a withdrawal period which is different than the withdrawal period approved for such approved new animal drug, the Secretary may establish, on the basis of information submitted, such different withdrawal period as the withdrawal period for the new animal drug for purposes of the approval of such application for such drug.
(C) Within 180 days of the initial receipt of an application under subsection (b)(2) of this section or within such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall approve or disapprove the application.
(D) The approval of an application filed under subsection (b)(2) of this section shall be made effective on the last applicable date determined under the following:
(i) If the applicant only made a certification described in clause (i) or (ii) of subsection (n)(1)(G) of this section or in both such clauses, the approval may be made effective immediately.
(ii) If the applicant made a certification described in clause (iii) of subsection (n)(1)(G) of this section, the approval may be made effective on the date certified under clause (iii).
(iii) If the applicant made a certification described in clause (iv) of subsection (n)(1)(G) of this section, the approval shall be made effective immediately unless an action is brought for infringement of a patent which is the subject of the certification before the expiration of 45 days from the date the notice provided under subsection (n)(2)(B)(i) of this section is received. If such an action is brought before the expiration of such days, the approval shall be made effective upon the expiration of the 30 month period beginning on the date of the receipt of the notice provided under subsection (n)(2)(B) of this section or such shorter or longer period as the court may order because either party to the action failed to reasonably cooperate in expediting the action, except that if before the expiration of such period—
(I) the court decides that such patent is invalid or not infringed, the approval shall be made effective on the date of the court decision,
(II) the court decides that such patent has been infringed, the approval shall be made effective on such date as the court orders under
(III) the court grants a preliminary injunction prohibiting the applicant from engaging in the commercial manufacture or sale of the drug until the court decides the issues of patent validity and infringement and if the court decides that such patent is invalid or not infringed, the approval shall be made effective on the date of such court decision.
In such an action, each of the parties shall reasonably cooperate in expediting the action. Until the expiration of 45 days from the date the notice made under subsection (n)(2)(B) of this section is received, no action may be brought under
(iv) If the application contains a certification described in clause (iv) of subsection (n)(1)(G) of this section and is for a drug for which a previous application has been filed under this subsection containing such a certification, the application shall be made effective not earlier than 180 days after—
(I) the date the Secretary receives notice from the applicant under the previous application of the first commercial marketing of the drug under the previous application, or
(II) the date of a decision of a court in an action described in subclause (III) 2 holding the patent which is the subject of the certification to be invalid or not infringed,
whichever is earlier.
(E) If the Secretary decides to disapprove an application, the Secretary shall give the applicant notice of an opportunity for a hearing before the Secretary on the question of whether such application is approvable. If the applicant elects to accept the opportunity for hearing by written request within 30 days after such notice, such hearing shall commence not more than 90 days after the expiration of such 30 days unless the Secretary and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the Secretary's order thereon shall be issued within 90 days after the date fixed by the Secretary for filing final briefs.
(F)(i) If an application submitted under subsection (b)(1) of this section for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under subsection (b)(1) of this section, is approved after November 16, 1988, no application may be submitted under subsection (b)(2) of this section which refers to the drug for which the subsection (b)(1) application was submitted before the expiration of 5 years from the date of the approval of the application under subsection (b)(1) of this section, except that such an application may be submitted under subsection (b)(2) of this section after the expiration of 4 years from the date of the approval of the subsection (b)(1) application if it contains a certification of patent invalidity or noninfringement described in clause (iv) of subsection (n)(1)(G) of this section. The approval of such an application shall be made effective in accordance with subparagraph (B) except that, if an action for patent infringement is commenced during the one-year period beginning 48 months after the date of the approval of the subsection (b) application, the 30 month period referred to in subparagraph (D)(iii) shall be extended by such amount of time (if any) which is required for seven and one-half years to have elapsed from the date of approval of the subsection (b) application.
(ii) If an application submitted under subsection (b)(1) of this section for a drug, which includes an active ingredient (including any ester or salt of the active ingredient) that has been approved in another application approved under such subsection, is approved after November 16, 1988, and if such application contains substantial evidence of the effectiveness of the drug involved, any studies of animal safety, or, in the case of food producing animals, human food safety studies (other than bioequivalence or residue studies) required for the approval of the application and conducted or sponsored by the applicant, the Secretary may not make the approval of an application submitted under subsection (b)(2) of this section for the conditions of approval of such drug in the subsection (b)(1) application effective before the expiration of 3 years from the date of the approval of the application under subsection (b)(1) of this section for such drug.
(iii) If a supplement to an application approved under subsection (b)(1) of this section is approved after November 16, 1988, and the supplement contains substantial evidence of the effectiveness of the drug involved, any studies of animal safety, or, in the case of food producing animals, human food safety studies (other than bioequivalence or residue studies) required for the approval of the supplement and conducted or sponsored by the person submitting the supplement, the Secretary may not make the approval of an application submitted under subsection (b)(2) of this section for a change approved in the supplement effective before the expiration of 3 years from the date of the approval of the supplement.
(iv) An applicant under subsection (b)(1) of this section who comes within the provisions of clause (i) of this subparagraph as a result of an application which seeks approval for a use solely in non-food producing animals, may elect, within 10 days of receiving such approval, to waive clause (i) of this subparagraph, in which event the limitation on approval of applications submitted under subsection (b)(2) of this section set forth in clause (ii) of this subparagraph shall be applicable to the subsection (b)(1) application.
(v) If an application (including any supplement to a new animal drug application) submitted under subsection (b)(1) of this section for a new animal drug for a food-producing animal use, which includes an active ingredient (including any ester or salt of the active ingredient) which has been the subject of a waiver under clause (iv) is approved after November 16, 1988, and if the application contains substantial evidence of the effectiveness of the drug involved, any studies of animal safety, or human food safety studies (other than bioequivalence or residue studies) required for the new approval of the application and conducted or sponsored by the applicant, the Secretary may not make the approval of an application (including any supplement to such application) submitted under subsection (b)(2) of this section for the new conditions of approval of such drug in the subsection (b)(1) application effective before the expiration of five years from the date of approval of the application under subsection (b)(1) of this section for such drug. The provisions of this paragraph shall apply only to the first approval for a food-producing animal use for the same applicant after the waiver under clause (iv).
(G) If an approved application submitted under subsection (b)(2) of this section for a new animal drug refers to a drug the approval of which was withdrawn or suspended for grounds described in paragraph (1) or (2) of subsection (e) of this section or was withdrawn or suspended under this subparagraph or which, as determined by the Secretary, has been withdrawn from sale for safety or effectiveness reasons, the approval of the drug under this paragraph shall be withdrawn or suspended—
(i) for the same period as the withdrawal or suspension under subsection (e) of this section or this subparagraph, or
(ii) if the approved new animal drug has been withdrawn from sale, for the period of withdrawal from sale or, if earlier, the period ending on the date the Secretary determines that the withdrawal from sale is not for safety or effectiveness reasons.
(H) For purposes of this paragraph:
(i) The term "bioequivalence" means the rate and extent to which the active ingredient or therapeutic ingredient is absorbed from a new animal drug and becomes available at the site of drug action.
(ii) A new animal drug shall be considered to be bioequivalent to the approved new animal drug referred to in its application under subsection (n) of this section if—
(I) the rate and extent of absorption of the drug do not show a significant difference from the rate and extent of absorption of the approved new animal drug referred to in the application when administered at the same dose of the active ingredient under similar experimental conditions in either a single dose or multiple doses;
(II) the extent of absorption of the drug does not show a significant difference from the extent of absorption of the approved new animal drug referred to in the application when administered at the same dose of the active ingredient under similar experimental conditions in either a single dose or multiple doses and the difference from the approved new animal drug in the rate of absorption of the drug is intentional, is reflected in its proposed labeling, is not essential to the attainment of effective drug concentrations in use, and is considered scientifically insignificant for the drug in attaining the intended purposes of its use and preserving human food safety; or
(III) in any case in which the Secretary determines that the measurement of the rate and extent of absorption or excretion of the new animal drug in biological fluids is inappropriate or impractical, an appropriate acute pharmacological effects test or other test of the new animal drug and, when deemed scientifically necessary, of the approved new animal drug referred to in the application in the species to be tested or in an appropriate animal model does not show a significant difference between the new animal drug and such approved new animal drug when administered at the same dose under similar experimental conditions.
If the approved new animal drug referred to in the application for a new animal drug under subsection (n) of this section is approved for use in more than one animal species, the bioequivalency information described in subclauses (I), (II), and (III) shall be obtained for one species, or if the Secretary deems appropriate based on scientific principles, shall be obtained for more than one species. The Secretary may prescribe the dose to be used in determining bioequivalency under subclause (I), (II), or (III). To assure that the residues of the new animal drug will be consistent with the established tolerances for the approved new animal drug referred to in the application under subsection (b)(2) of this section upon the expiration of the withdrawal period contained in the application for the new animal drug, the Secretary shall require bioequivalency data or residue depletion studies of the new animal drug or such other data or studies as the Secretary considers appropriate based on scientific principles. If the Secretary requires one or more residue studies under the preceding sentence, the Secretary may not require that the assay methodology used to determine the withdrawal period of the new animal drug be more rigorous than the methodology used to determine the withdrawal period for the approved new animal drug referred to in the application. If such studies are required and if the approved new animal drug, referred to in the application for the new animal drug for which such studies are required, is approved for use in more than one animal species, such studies shall be conducted for one species, or if the Secretary deems appropriate based on scientific principles, shall be conducted for more than one species.
(3) If the patent information described in subsection (b)(1) of this section could not be filed with the submission of an application under subsection (b)(1) of this section because the application was filed before the patent information was required under subsection (b)(1) of this section or a patent was issued after the application was approved under such subsection, the holder of an approved application shall file with the Secretary the patent number and the expiration date of any patent which claims the new animal drug for which the application was filed or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug. If the holder of an approved application could not file patent information under subsection (b)(1) of this section because it was not required at the time the application was approved, the holder shall file such information under this subsection not later than 30 days after November 16, 1988, and if the holder of an approved application could not file patent information under subsection (b)(1) of this section because no patent had been issued when an application was filed or approved, the holder shall file such information under this subsection not later than 30 days after the date the patent involved is issued. Upon the submission of patent information under this subsection, the Secretary shall publish it.
(4) A drug manufactured in a pilot or other small facility may be used to demonstrate the safety and effectiveness of the drug and to obtain approval for the drug prior to manufacture of the drug in a larger facility, unless the Secretary makes a determination that a full scale production facility is necessary to ensure the safety or effectiveness of the drug.
(d) Grounds for refusing application; approval of application; factors; "substantial evidence" defined; combination drugs
(1) If the Secretary finds, after due notice to the applicant in accordance with subsection (c) of this section and giving him an opportunity for a hearing, in accordance with said subsection, that—
(A) the investigations, reports of which are required to be submitted to the Secretary pursuant to subsection (b) of this section, do not include adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof;
(B) the results of such tests show that such drug is unsafe for use under such conditions or do not show that such drug is safe for use under such conditions;
(C) the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such drug are inadequate to preserve its identity, strength, quality, and purity;
(D) upon the basis of the information submitted to him as part of the application, or upon the basis of any other information before him with respect to such drug, he has insufficient information to determine whether such drug is safe for use under such conditions;
(E) evaluated on the basis of the information submitted to him as part of the application and any other information before him with respect to such drug, there is a lack of substantial evidence that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof;
(F) upon the basis of information submitted to the Secretary as part of the application or any other information before the Secretary with respect to such drug, any use prescribed, recommended, or suggested in labeling proposed for such drug will result in a residue of such drug in excess of a tolerance found by the Secretary to be safe for such drug;
(G) the application failed to contain the patent information prescribed by subsection (b)(1) of this section;
(H) based on a fair evaluation of all material facts, such labeling is false or misleading in any particular; or
(I) such drug induces cancer when ingested by man or animal or, after tests which are appropriate for the evaluation of the safety of such drug, induces cancer in man or animal, except that the foregoing provisions of this subparagraph shall not apply with respect to such drug if the Secretary finds that, under the conditions of use specified in proposed labeling and reasonably certain to be followed in practice (i) such drug will not adversely affect the animals for which it is intended, and (ii) no residue of such drug will be found (by methods of examination prescribed or approved by the Secretary by regulations, which regulations shall not be subject to subsections (c), (d), and (h) of this section), in any edible portion of such animals after slaughter or in any food yielded by or derived from the living animals;
he shall issue an order refusing to approve the application. If, after such notice and opportunity for hearings, the Secretary finds that subparagraphs (A) through (I) do not apply, he shall issue an order approving the application.
(2) In determining whether such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof, the Secretary shall consider, among other relevant factors, (A) the probable consumption of such drug and of any substance formed in or on food because of the use of such drug, (B) the cumulative effect on man or animal of such drug, taking into account any chemically or pharmacologically related substance, (C) safety factors which in the opinion of experts, qualified by scientific training and experience to evaluate the safety of such drugs, are appropriate for the use of animal experimentation data, and (D) whether the conditions of use prescribed, recommended, or suggested in the proposed labeling are reasonably certain to be followed in practice. Any order issued under this subsection refusing to approve an application shall state the findings upon which it is based.
(3) As used in this section, the term "substantial evidence" means evidence consisting of one or more adequate and well controlled investigations, such as—
(A) a study in a target species;
(B) a study in laboratory animals;
(C) any field investigation that may be required under this section and that meets the requirements of subsection (b)(3) of this section if a presubmission conference is requested by the applicant;
(D) a bioequivalence study; or
(E) an in vitro study;
by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and reasonably be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.
(4) In a case in which an animal drug contains more than one active ingredient, or the labeling of the drug prescribes, recommends, or suggests use of the drug in combination with one or more other animal drugs, and the active ingredients or drugs intended for use in the combination have previously been separately approved for particular uses and conditions of use for which they are intended for use in the combination—
(A) the Secretary shall not issue an order under paragraph (1)(A), (1)(B), or (1)(D) refusing to approve the application for such combination on human food safety grounds unless the Secretary finds that the application fails to establish that—
(i) none of the active ingredients or drugs intended for use in the combination, respectively, at the longest withdrawal time of any of the active ingredients or drugs in the combination, respectively, exceeds its established tolerance; or
(ii) none of the active ingredients or drugs in the combination interferes with the methods of analysis for another of the active ingredients or drugs in the combination, respectively;
(B) the Secretary shall not issue an order under paragraph (1)(A), (1)(B), or (1)(D) refusing to approve the application for such combination on target animal safety grounds unless the Secretary finds that—
(i)(I) there is a substantiated scientific issue, specific to one or more of the active ingredients or animal drugs in the combination, that cannot adequately be evaluated based on information contained in the application for the combination (including any investigations, studies, or tests for which the applicant has a right of reference or use from the person by or for whom the investigations, studies, or tests were conducted); or
(II) there is a scientific issue raised by target animal observations contained in studies submitted to the Secretary as part of the application; and
(ii) based on the Secretary's evaluation of the information contained in the application with respect to the issues identified in clauses (i)(I) and (II), paragraph (1)(A), (B), or (D) apply;
(C) except in the case of a combination that contains a nontopical antibacterial ingredient or animal drug, the Secretary shall not issue an order under paragraph (1)(E) refusing to approve an application for a combination animal drug intended for use other than in animal feed or drinking water unless the Secretary finds that the application fails to demonstrate that—
(i) there is substantial evidence that any active ingredient or animal drug intended only for the same use as another active ingredient or animal drug in the combination makes a contribution to labeled effectiveness;
(ii) each active ingredient or animal drug intended for at least one use that is different from all other active ingredients or animal drugs used in the combination provides appropriate concurrent use for the intended target population; or
(iii) where based on scientific information the Secretary has reason to believe the active ingredients or animal drugs may be physically incompatible or have disparate dosing regimens, such active ingredients or animal drugs are physically compatible or do not have disparate dosing regimens; and
(D) the Secretary shall not issue an order under paragraph (1)(E) refusing to approve an application for a combination animal drug intended for use in animal feed or drinking water unless the Secretary finds that the application fails to demonstrate that—
(i) there is substantial evidence that any active ingredient or animal drug intended only for the same use as another active ingredient or animal drug in the combination makes a contribution to the labeled effectiveness;
(ii) each of the active ingredients or animal drugs intended for at least one use that is different from all other active ingredients or animal drugs used in the combination provides appropriate concurrent use for the intended target population;
(iii) where a combination contains more than one nontopical antibacterial ingredient or animal drug, there is substantial evidence that each of the nontopical antibacterial ingredients or animal drugs makes a contribution to the labeled effectiveness, except that for purposes of this clause, antibacterial ingredient or animal drug does not include the ionophore or arsenical classes of animal drugs; or
(iv) where based on scientific information the Secretary has reason to believe the active ingredients or animal drugs intended for use in drinking water may be physically incompatible, such active ingredients or animal drugs intended for use in drinking water are physically compatible.
(e) Withdrawal of approval; grounds; immediate suspension upon finding imminent hazard to health of man or animals
(1) The Secretary shall, after due notice and opportunity for hearing to the applicant, issue an order withdrawing approval of an application filed pursuant to subsection (b) of this section with respect to any new animal drug if the Secretary finds—
(A) that experience or scientific data show that such drug is unsafe for use under the conditions of use upon the basis of which the application was approved or the condition of use authorized under subsection (a)(4)(A) of this section;
(B) that new evidence not contained in such application or not available to the Secretary until after such application was approved, or tests by new methods, or tests by methods not deemed reasonably applicable when such application was approved, evaluated together with the evidence available to the Secretary when the application was approved, shows that such drug is not shown to be safe for use under the conditions of use upon the basis of which the application was approved or that subparagraph (I) of paragraph (1) of subsection (d) of this section applies to such drug;
(C) on the basis of new information before him with respect to such drug, evaluated together with the evidence available to him when the application was approved, that there is a lack of substantial evidence that such drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling thereof;
(D) the patent information prescribed by subsection (c)(3) of this section was not filed within 30 days after the receipt of written notice from the Secretary specifying the failure to file such information;
(E) that the application contains any untrue statement of a material fact; or
(F) that the applicant has made any changes from the standpoint of safety or effectiveness beyond the variations provided for in the application unless he has supplemented the application by filing with the Secretary adequate information respecting all such changes and unless there is in effect an approval of the supplemental application. The supplemental application shall be treated in the same manner as the original application.
If the Secretary (or in his absence the officer acting as Secretary) finds that there is an imminent hazard to the health of man or of the animals for which such drug is intended, he may suspend the approval of such application immediately, and give the applicant prompt notice of his action and afford the applicant the opportunity for an expedited hearing under this subsection; but the authority conferred by this sentence to suspend the approval of an application shall not be delegated.
(2) The Secretary may also, after due notice and opportunity for hearing to the applicant, issue an order withdrawing the approval of an application with respect to any new animal drug under this section if the Secretary finds—
(A) that the applicant has failed to establish a system for maintaining required records, or has repeatedly or deliberately failed to maintain such records or to make required reports in accordance with a regulation or order under subsection (1) of this section, or the applicant has refused to permit access to, or copying or verification of, such records as required by paragraph (2) of such subsection;
(B) that on the basis of new information before him, evaluated together with the evidence before him when the application was approved, the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of such drug are inadequate to assure and preserve its identity, strength, quality, and purity and were not made adequate within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of; or
(C) that on the basis of new information before him, evaluated together with the evidence before him when the application was approved, the labeling of such drug, based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of.
(3) Any order under this subsection shall state the findings upon which it is based.
(f) Revocation of order refusing, withdrawing or suspending approval of application
Whenever the Secretary finds that the facts so require, he shall revoke any previous order under subsection (d), (e), or (m) of this section refusing, withdrawing, or suspending approval of an application and shall approve such application or reinstate such approval, as may be appropriate.
(g) Service of orders
Orders of the Secretary issued under this section (other than orders issuing, amending, or repealing regulations) shall be served (1) in person by any officer or employee of the department designated by the Secretary or (2) by mailing the order by registered mail or by certified mail addressed to the applicant or respondent at his last known address in the records of the Secretary.
(h) Appeal from order
An appeal may be taken by the applicant from an order of the Secretary refusing or withdrawing approval of an application filed under subsection (b) or (m) of this section. The provisions of subsection (h) of
(i) Publication in Federal Register; effective date and revocation or suspension of regulation
When a new animal drug application filed pursuant to subsection (b) of this section is approved, the Secretary shall by notice, which upon publication shall be effective as a regulation, publish in the Federal Register the name and address of the applicant and the conditions and indications of use of the new animal drug covered by such application, including any tolerance and withdrawal period or other use restrictions and, if such new animal drug is intended for use in animal feed, appropriate purposes and conditions of use (including special labeling requirements and any requirement that an animal feed bearing or containing the new animal drug be limited to use under the professional supervision of a licensed veterinarian) applicable to any animal feed for use in which such drug is approved, and such other information, upon the basis of which such application was approved, as the Secretary deems necessary to assure the safe and effective use of such drug. Upon withdrawal of approval of such new animal drug application or upon its suspension, the Secretary shall forthwith revoke or suspend, as the case may be, the regulation published pursuant to this subsection (i) insofar as it is based on the approval of such application.
(j) Exemption of drugs for research; discretionary and mandatory conditions
To the extent consistent with the public health, the Secretary shall promulgate regulations for exempting from the operation of this section new animal drugs, and animal feeds bearing or containing new animal drugs, intended solely for investigational use by experts qualified by scientific training and experience to investigate the safety and effectiveness of animal drugs. Such regulations may, in the discretion of the Secretary, among other conditions relating to the protection of the public health, provide for conditioning such exemption upon the establishment and maintenance of such records, and the making of such reports to the Secretary, by the manufacturer or the sponsor of the investigation of such article, of data (including but not limited to analytical reports by investigators) obtained as a result of such investigational use of such article, as the Secretary finds will enable him to evaluate the safety and effectiveness of such article in the event of the filing of an application pursuant to this section. Such regulations, among other things, shall set forth the conditions (if any) upon which animals treated with such articles, and any products of such animals (before or after slaughter), may be marketed for food use.
(k) Food containing new animal drug considered unadulterated while approval of application for such drug is effective
While approval of an application for a new animal drug is effective, a food shall not, by reason of bearing or containing such drug or any substance formed in or on the food because of its use in accordance with such application (including the conditions and indications of use prescribed pursuant to subsection (i) of this section), be considered adulterated within the meaning of clause (1) of
(l) Records and reports; required information; regulations and orders; examination of data; access to records
(1) In the case of any new animal drug for which an approval of an application filed pursuant to subsection (b) of this section is in effect, the applicant shall establish and maintain such records, and make such reports to the Secretary, of data relating to experience, including experience with uses authorized under subsection (a)(4)(A) of this section, and other data or information, received or otherwise obtained by such applicant with respect to such drug, or with respect to animal feeds bearing or containing such drug, as the Secretary may by general regulation, or by order with respect to such application, prescribe on the basis of a finding that such records and reports are necessary in order to enable the Secretary to determine, or facilitate a determination, whether there is or may be ground for invoking subsection (e) or subsection (m)(4) of this section. Such regulation or order shall provide, where the Secretary deems it to be appropriate, for the examination, upon request, by the persons to whom such regulation or order is applicable, of similar information received or otherwise obtained by the Secretary.
(2) Every person required under this subsection to maintain records, and every person in charge or custody thereof, shall, upon request of an officer or employee designated by the Secretary, permit such officer or employee at all reasonable times to have access to and copy and verify such records.
(m) Feed mill licenses
(1) Any person may file with the Secretary an application for a license to manufacture animal feeds bearing or containing new animal drugs. Such person shall submit to the Secretary as part of the application (A) a full statement of the business name and address of the specific facility at which the manufacturing is to take place and the facility's registration number, (B) the name and signature of the responsible individual or individuals for that facility, (C) a certification that the animal feeds bearing or containing new animal drugs are manufactured and labeled in accordance with the applicable regulations published pursuant to subsection (i) of this section, and (D) a certification that the methods used in, and the facilities and controls used for, manufacturing, processing, packaging, and holding such animal feeds are in conformity with current good manufacturing practice as described in
(2) Within 90 days after the filing of an application pursuant to paragraph (1), or such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall (A) issue an order approving the application if the Secretary then finds that none of the grounds for denying approval specified in paragraph (3) applies, or (B) give the applicant notice of an opportunity for a hearing before the Secretary under paragraph (3) on the question whether such application is approvable. The procedure governing such a hearing shall be the procedure set forth in the last two sentences of subsection (c)(1) of this section.
(3) If the Secretary, after due notice to the applicant in accordance with paragraph (2) and giving the applicant an opportunity for a hearing in accordance with such paragraph, finds, on the basis of information submitted to the Secretary as part of the application, on the basis of a preapproval inspection, or on the basis of any other information before the Secretary—
(A) that the application is incomplete, false, or misleading in any particular;
(B) that the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such animal feed are inadequate to preserve the identity, strength, quality, and purity of the new animal drug therein; or
(C) that the facility manufactures animal feeds bearing or containing new animal drugs in a manner that does not accord with the specifications for manufacture or labels animal feeds bearing or containing new animal drugs in a manner that does not accord with the conditions or indications of use that are published pursuant to subsection (i) of this section,
the Secretary shall issue an order refusing to approve the application. If, after such notice and opportunity for hearing, the Secretary finds that subparagraphs (A) through (C) do not apply, the Secretary shall issue an order approving the application. An order under this subsection approving an application for a license to manufacture animal feeds bearing or containing new animal drugs shall permit a facility to manufacture only those animal feeds bearing or containing new animal drugs for which there are in effect regulations pursuant to subsection (i) of this section relating to the use of such drugs in or on such animal feed.
(4)(A) The Secretary shall, after due notice and opportunity for hearing to the applicant, revoke a license to manufacture animal feeds bearing or containing new animal drugs under this subsection if the Secretary finds—
(i) that the application for such license contains any untrue statement of a material fact; or
(ii) that the applicant has made changes that would cause the application to contain any untrue statements of material fact or that would affect the safety or effectiveness of the animal feeds manufactured at the facility unless the applicant has supplemented the application by filing with the Secretary adequate information respecting all such changes and unless there is in effect an approval of the supplemental application.
If the Secretary (or in the Secretary's absence the officer acting as the Secretary) finds that there is an imminent hazard to the health of humans or of the animals for which such animal feed is intended, the Secretary may suspend the license immediately, and give the applicant prompt notice of the action and afford the applicant the opportunity for an expedited hearing under this subsection; but the authority conferred by this sentence shall not be delegated.
(B) The Secretary may also, after due notice and opportunity for hearing to the applicant, revoke a license to manufacture animal feed under this subsection if the Secretary finds—
(i) that the applicant has failed to establish a system for maintaining required records, or has repeatedly or deliberately failed to maintain such records or to make required reports in accordance with a regulation or order under paragraph (5)(A) of this subsection or
(ii) that on the basis of new information before the Secretary, evaluated together with the evidence before the Secretary when such license was issued, the methods used in, or the facilities and controls used for, the manufacture, processing, packing, and holding of such animal feed are inadequate to assure and preserve the identity, strength, quality, and purity of the new animal drug therein, and were not made adequate within a reasonable time after receipt of written notice from the Secretary, specifying the matter complained of;
(iii) that on the basis of new information before the Secretary, evaluated together with the evidence before the Secretary when such license was issued, the labeling of any animal feeds, based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of; or
(iv) that on the basis of new information before the Secretary, evaluated together with the evidence before the Secretary when such license was issued, the facility has manufactured, processed, packed, or held animal feed bearing or containing a new animal drug adulterated under
(C) The Secretary may also revoke a license to manufacture animal feeds under this subsection if an applicant gives notice to the Secretary of intention to discontinue the manufacture of all animal feed covered under this subsection and waives an opportunity for a hearing on the matter.
(D) Any order under this paragraph shall state the findings upon which it is based.
(5) When a license to manufacture animal feeds bearing or containing new animal drugs has been issued—
(A) the applicant shall establish and maintain such records, and make such reports to the Secretary, or (at the option of the Secretary) to the appropriate person or persons holding an approved application filed under subsection (b) of this section, as the Secretary may by general regulation, or by order with respect to such application, prescribe on the basis of a finding that such records and reports are necessary in order to enable the Secretary to determine, or facilitate a determination, whether there is or may be ground for invoking subsection (e) of this section or paragraph (4); and
(B) every person required under this subsection to maintain records, and every person in charge or custody thereof, shall, upon request of an officer or employee designated by the Secretary, permit such officer or employee at all reasonable times to have access to and copy and verify such records.
(6) To the extent consistent with the public health, the Secretary may promulgate regulations for exempting from the operation of this subsection facilities that manufacture, process, pack, or hold animal feeds bearing or containing new animal drugs.
(n) Abbreviated applications for new animal drugs; contents, filing, etc.; lists of approved drugs
(1) An abbreviated application for a new animal drug shall contain—
(A)(i) except as provided in clause (ii), information to show that the conditions of use or similar limitations (whether in the labeling or published pursuant to subsection (i) of this section) prescribed, recommended, or suggested in the labeling proposed for the new animal drug have been previously approved for a new animal drug listed under paragraph (4) (hereinafter in this subsection referred to as an "approved new animal drug"), and
(ii) information to show that the withdrawal period at which residues of the new animal drug will be consistent with the tolerances established for the approved new animal drug is the same as the withdrawal period previously established for the approved new animal drug or, if the withdrawal period is proposed to be different, information showing that the residues of the new animal drug at the proposed different withdrawal period will be consistent with the tolerances established for the approved new animal drug;
(B)(i) information to show that the active ingredients of the new animal drug are the same as those of the approved new animal drug, and
(ii) if the approved new animal drug has more than one active ingredient, and if one of the active ingredients of the new animal drug is different from one of the active ingredients of the approved new animal drug and the application is filed pursuant to the approval of a petition filed under paragraph (3)—
(I) information to show that the other active ingredients of the new animal drug are the same as the active ingredients of the approved new animal drug,
(II) information to show either that the different active ingredient is an active ingredient of another approved new animal drug or of an animal drug which does not meet the requirements of
(III) such other information respecting the different active ingredients as the Secretary may require;
(C)(i) if the approved new animal drug is permitted to be used with one or more animal drugs in animal feed, information to show that the proposed uses of the new animal drug with other animal drugs in animal feed are the same as the uses of the approved new animal drug, and
(ii) if the approved new animal drug is permitted to be used with one or more other animal drugs in animal feed, and one of the other animal drugs proposed for use with the new animal drug in animal feed is different from one of the other animal drugs permitted to be used in animal feed with the approved new animal drug, and the application is filed pursuant to the approval of a petition filed under paragraph (3)—
(I) information to show either that the different animal drug proposed for use with the approved new animal drug in animal feed is an approved new animal drug permitted to be used in animal feed or does not meet the requirements of
(II) information to show that other animal drugs proposed for use with the new animal drug in animal feed are the same as the other animal drugs permitted to be used with the approved new animal drug, and
(III) such other information respecting the different animal drug or combination with respect to which the petition was filed as the Secretary may require,
(D) information to show that the route of administration, the dosage form, and the strength of the new animal drug are the same as those of the approved new animal drug or, if the route of administration, the dosage form, or the strength of the new animal drug is different and the application is filed pursuant to the approval of a petition filed under paragraph (3), such information respecting the route of administration, dosage form, or strength with respect to which the petition was filed as the Secretary may require;
(E) information to show that the new animal drug is bioequivalent to the approved new animal drug, except that if the application is filed pursuant to the approval of a petition filed under paragraph (3) for the purposes described in subparagraph (B) or (C), information to show that the active ingredients of the new animal drug are of the same pharmacological or therapeutic class as the pharmacological or therapeutic class of the approved new animal drug and that the new animal drug can be expected to have the same therapeutic effect as the approved new animal drug when used in accordance with the labeling;
(F) information to show that the labeling proposed for the new animal drug is the same as the labeling approved for the approved new animal drug except for changes required because of differences approved under a petition filed under paragraph (3), because of a different withdrawal period, or because the new animal drug and the approved new animal drug are produced or distributed by different manufacturers;
(G) the items specified in clauses (B) through (F) of subsection (b)(1) of this section;
(H) a certification, in the opinion of the applicant and to the best of his knowledge, with respect to each patent which claims the approved new animal drug or which claims a use for such approved new animal drug for which the applicant is seeking approval under this subsection and for which information is required to be filed under subsection (b)(1) or (c)(3) of this section—
(i) that such patent information has not been filed,
(ii) that such patent has expired,
(iii) of the date on which such patent will expire, or
(iv) that such patent is invalid or will not be infringed by the manufacture, use, or sale of the new animal drug for which the application is filed; and
(I) if with respect to the approved new animal drug information was filed under subsection (b)(1) or (c)(3) of this section for a method of use patent which does not claim a use for which the applicant is seeking approval of an application under subsection (c)(2) of this section, a statement that the method of use patent does not claim such a use.
The Secretary may not require that an abbreviated application contain information in addition to that required by subparagraphs (A) through (I).
(2)(A) An applicant who makes a certification described in paragraph (1)(G)(iv) shall include in the application a statement that the applicant will give the notice required by subparagraph (B) to—
(i) each owner of the patent which is the subject of the certification or the representative of such owner designated to receive such notice, and
(ii) the holder of the approved application under subsection (c)(1) of this section for the drug which is claimed by the patent or a use of which is claimed by the patent or the representative of such holder designated to receive such notice.
(B) The notice referred to in subparagraph (A) shall state that an application, which contains data from bioequivalence studies, has been filed under this subsection for the drug with respect to which the certification is made to obtain approval to engage in the commercial manufacture, use, or sale of such drug before the expiration of the patent referred to in the certification. Such notice shall include a detailed statement of the factual and legal basis of the applicant's opinion that the patent is not valid or will not be infringed.
(C) If an application is amended to include a certification described in paragraph (1)(G)(iv), the notice required by subparagraph (B) shall be given when the amended application is filed.
(3) If a person wants to submit an abbreviated application for a new animal drug—
(A) whose active ingredients, route of administration, dosage form, or strength differ from that of an approved new animal drug, or
(B) whose use with other animal drugs in animal feed differs from that of an approved new animal drug,
such person shall submit a petition to the Secretary seeking permission to file such an application. The Secretary shall approve a petition for a new animal drug unless the Secretary finds that—
(C) investigations must be conducted to show the safety and effectiveness, in animals to be treated with the drug, of the active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed which differ from the approved new animal drug, or
(D) investigations must be conducted to show the safety for human consumption of any residues in food resulting from the proposed active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed for the new animal drug which is different from the active ingredients, route of administration, dosage form, strength, or use with other animal drugs in animal feed of the approved new animal drug.
The Secretary shall approve or disapprove a petition submitted under this paragraph within 90 days of the date the petition is submitted.
(4)(A)(i) Within 60 days of November 16, 1988, the Secretary shall publish and make available to the public a list in alphabetical order of the official and proprietary name of each new animal drug which has been approved for safety and effectiveness before November 16, 1988.
(ii) Every 30 days after the publication of the first list under clause (i) the Secretary shall revise the list to include each new animal drug which has been approved for safety and effectiveness under subsection (c) of this section during the 30 day period.
(iii) When patent information submitted under subsection (b)(1) or (c)(3) of this section respecting a new animal drug included on the list is to be published by the Secretary, the Secretary shall, in revisions made under clause (ii), include such information for such drug.
(B) A new animal drug approved for safety and effectiveness before November 16, 1988, or approved for safety and effectiveness under subsection (c) of this section shall, for purposes of this subsection, be considered to have been published under subparagraph (A) on the date of its approval or November 16, 1988, whichever is later.
(C) If the approval of a new animal drug was withdrawn or suspended under subsection (c)(2)(G) of this section or for grounds described in subsection (e) of this section or if the Secretary determines that a drug has been withdrawn from sale for safety or effectiveness reasons, it may not be published in the list under subparagraph (A) or, if the withdrawal or suspension occurred after its publication in such list, it shall be immediately removed from such list—
(i) for the same period as the withdrawal or suspension under subsection (c)(2)(G) or (e) of this section, or
(ii) if the listed drug has been withdrawn from sale, for the period of withdrawal from sale or, if earlier, the period ending on the date the Secretary determines that the withdrawal from sale is not for safety or effectiveness reasons.
A notice of the removal shall be published in the Federal Register.
(5) If an application contains the information required by clauses (A), (G), and (H) of subsection (b)(1) of this section and such information—
(A) is relied on by the applicant for the approval of the application, and
(B) is not information derived either from investigations, studies, or tests conducted by or for the applicant or for which the applicant had obtained a right of reference or use from the person by or for whom the investigations, studies, or tests were conducted,
such application shall be considered to be an application filed under subsection (b)(2) of this section.
(o) "Patent" defined
For purposes of this section, the term "patent" means a patent issued by the United States Patent and Trademark Office.
(p) Safety and effectiveness data
(1) Safety and effectiveness data and information which has been submitted in an application filed under subsection (b)(1) of this section for a drug and which has not previously been disclosed to the public shall be made available to the public, upon request, unless extraordinary circumstances are shown—
(A) if no work is being or will be undertaken to have the application approved,
(B) if the Secretary has determined that the application is not approvable and all legal appeals have been exhausted,
(C) if approval of the application under subsection (c) of this section is withdrawn and all legal appeals have been exhausted,
(D) if the Secretary has determined that such drug is not a new drug, or
(E) upon the effective date of the approval of the first application filed under subsection (b)(2) of this section which refers to such drug or upon the date upon which the approval of an application filed under subsection (b)(2) of this section which refers to such drug could be made effective if such an application had been filed.
(2) Any request for data and information pursuant to paragraph (1) shall include a verified statement by the person making the request that any data or information received under such paragraph shall not be disclosed by such person to any other person—
(A) for the purpose of, or as part of a plan, scheme, or device for, obtaining the right to make, use, or market, or making, using, or marketing, outside the United States, the drug identified in the application filed under subsection (b)(1) of this section, and
(B) without obtaining from any person to whom the data and information are disclosed an identical verified statement, a copy of which is to be provided by such person to the Secretary, which meets the requirements of this paragraph.
(June 25, 1938, ch. 675, §512, as added
References in Text
Amendments
1999—Subsec. (o).
1998—Subsec. (d)(4)(D)(iii).
1997—Subsec. (c)(4).
1996—Subsec. (a)(1).
"(A) there is in effect an approval of an application filed pursuant to subsection (b) of this section with respect to such use or intended use of such drug, and
"(B) such drug, its labeling, and such use conform to such approved application.
A new animal drug shall also be deemed unsafe for such purposes in the event of removal from the establishment of a manufacturer, packer, or distributor of such drug for use in the manufacture of animal feed in any State unless at the time of such removal such manufacturer, packer, or distributor has an unrevoked written statement from the consignee of such drug, or notice from the Secretary, to the effect that, with respect to the use of such drug in animal feed, such consignee—
"(i) is the holder of an approved application under subsection (m) of this section; or
"(ii) will, if the consignee is not a user of the drug, ship such drug only to a holder of an approved application under subsection (m) of this section."
Subsec. (a)(2).
"(A) there is in effect an approval of an application filed pursuant to subsection (b) of this section with respect to such drugs, as used in such animal feed,
"(B) there is in effect an approval of an application pursuant to subsection (m)(1) of this section with respect to such animal feed, and
"(C) such animal feed, its labeling, and such use conform to the conditions and indications of use published pursuant to subsection (i) of this section and to the application with respect thereto approved under subsection (m) of this section."
Subsec. (a)(6).
Subsec. (b)(3).
Subsec. (c)(2)(F)(ii), (iii).
Subsec. (c)(2)(F)(v).
Subsec. (d)(1)(F).
Subsec. (d)(3).
Subsec. (d)(4).
Subsec. (i).
Subsec. (m).
1994—Subsec. (a)(4), (5).
Subsec. (e)(1)(A).
Subsec. (l)(1).
1993—Subsec. (c)(2)(A)(ii).
Subsec. (c)(2)(F)(i).
Subsec. (c)(2)(H)(ii).
Subsec. (d)(1).
Subsec. (n)(1).
1991—Subsec. (e)(1)(B).
1988—Subsec. (a)(1)(C).
Subsec. (b).
Subsec. (c).
Subsec. (d)(1).
Subsec. (d)(1)(G) to (I).
Subsec. (e)(1)(D) to (F).
Subsecs. (n) to (p).
Effective Date of 1999 Amendment
Amendment by
Effective Date of 1997 Amendment
Amendment by
Effective Date of 1994 Amendment
Section 2(d) of
Effective Date of 1988 Amendment
Section 108 of
Effective Date and Transitional Provisions
Section 108 of
"(a) Except as otherwise provided in this section, the amendments made by the foregoing sections [see Short Title of 1968 Amendment note set out under
"(b)(1) As used in this subsection, the term 'effective date' means the effective date specified in subsection (a) of this section; the term 'basic Act' means the Federal Food, Drug, and Cosmetic Act [this chapter]; and other terms used both in this section and the basic Act shall have the same meaning as they have, or had, at the time referred to in the context, under the basic Act.
"(2) Any approval, prior to the effective date, of a new animal drug or of an animal feed bearing or containing a new animal drug, whether granted by approval of a new-drug application, master file, antibiotic regulation, or food additive regulations, shall continue in effect, and shall be subject to change in accordance with the provisions of the basic Act as amended by this Act [see Short Title of 1968 Amendment note set out under
"(3) In the case of any drug (other than a drug subject to section 512(n) of the basic Act as amended by this Act) [subsection (n) of this section] intended for use in animals other than man which, on October 9, 1962, (A) was commercially used or sold in the United States, (B) was not a new drug as defined by section 201(p) of the basic Act [
"(4) Regulations providing for fees (and advance deposits to cover fees) which on the day preceding the effective date applicable under subsection (a) of this section were in effect pursuant to section 507 of the basic Act [
Regulations
Section 2(e) of
"(1)
"(2)
"(A) further define the term 'adequate and well controlled', as used in subsection (d)(3) of section 512 of such Act, to require that field investigations be designed and conducted in a scientifically sound manner, taking into account practical conditions in the field and differences between field conditions and laboratory conditions;
"(B) further define the term 'substantial evidence', as defined in subsection (d)(3) of such section, in a manner that encourages the submission of applications and supplemental applications; and
"(C) take into account the proposals contained in the citizen petition (FDA Docket No. 91P–0434/CP) jointly submitted by the American Veterinary Medical Association and the Animal Health Institute, dated October 21, 1991.
Until the regulations required by subparagraph (A) are issued, nothing in the regulations published at 21 C.F.R. 514.111(a)(5) (April 1, 1996) shall be construed to compel the Secretary of Health and Human Services to require a field investigation under section 512(d)(1)(E) of the Federal Food, Drug, and Cosmetic Act (
Section 2(c) of
Section 103 of
"(a)
"(b)
Drugs Intended for Minor Species and Minor Uses
Section 2(f) of
Transitional Provision Regarding Implementation of Pub. L. 104–250 ; Approved Medicated Feed Application Deemed License
Section 6(c) of
Drugs Primarily Manufactured Using Biotechnology
Section 106 of
Section Referred to in Other Sections
This section is referred to in
1 See References in Text note below.
2 So in original. Probably should be "clause (iii)(III)".
§360c. Classification of devices intended for human use
(a) Classes of devices
(1) There are established the following classes of devices intended for human use:
(A)
(i) A device for which the controls authorized by or under
(ii) A device for which insufficient information exists to determine that the controls referred to in clause (i) are sufficient to provide reasonable assurance of the safety and effectiveness of the device or to establish special controls to provide such assurance, but because it—
(I) is not purported or represented to be for a use in supporting or sustaining human life or for a use which is of substantial importance in preventing impairment of human health, and
(II) does not present a potential unreasonable risk of illness or injury,
is to be regulated by the controls referred to in clause (i).
(B)
(C)
(i) it (I) cannot be classified as a class I device because insufficient information exists to determine that the application of general controls are sufficient to provide reasonable assurance of the safety and effectiveness of the device, and (II) cannot be classified as a class II device because insufficient information exists to determine that the special controls described in subparagraph (B) would provide reasonable assurance of its safety and effectiveness, and
(ii)(I) is purported or represented to be for a use in supporting or sustaining human life or for a use which is of substantial importance in preventing impairment of human health, or
(II) presents a potential unreasonable risk of illness or injury,
is to be subject, in accordance with
If there is not sufficient information to establish a performance standard for a device to provide reasonable assurance of its safety and effectiveness, the Secretary may conduct such activities as may be necessary to develop or obtain such information.
(2) For purposes of this section and
(A) with respect to the persons for whose use the device is represented or intended,
(B) with respect to the conditions of use prescribed, recommended, or suggested in the labeling of the device, and
(C) weighing any probable benefit to health from the use of the device against any probable risk of injury or illness from such use.
(3)(A) Except as authorized by subparagraph (B), the effectiveness of a device is, for purposes of this section and
(B) If the Secretary determines that there exists valid scientific evidence (other than evidence derived from investigations described in subparagraph (A))—
(i) which is sufficient to determine the effectiveness of a device, and
(ii) from which it can fairly and responsibly be concluded by qualified experts that the device will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling of the device,
then, for purposes of this section and
(C) In making a determination of a reasonable assurance of the effectiveness of a device for which an application under
(D)(i) The Secretary, upon the written request of any person intending to submit an application under
(ii) Any clinical data, including one or more well-controlled investigations, specified in writing by the Secretary for demonstrating a reasonable assurance of device effectiveness shall be specified as result of a determination by the Secretary that such data are necessary to establish device effectiveness. The Secretary shall consider, in consultation with the applicant, the least burdensome appropriate means of evaluating device effectiveness that would have a reasonable likelihood of resulting in approval.
(iii) The determination of the Secretary with respect to the specification of valid scientific evidence under clauses (i) and (ii) shall be binding upon the Secretary, unless such determination by the Secretary could be contrary to the public health.
(b) Classification panels
(1) For purposes of—
(A) determining which devices intended for human use should be subject to the requirements of general controls, performance standards, or premarket approval, and
(B) providing notice to the manufacturers and importers of such devices to enable them to prepare for the application of such requirements to devices manufactured or imported by them,
the Secretary shall classify all such devices (other than devices classified by subsection (f) of this section) into the classes established by subsection (a) of this section. For the purpose of securing recommendations with respect to the classification of devices, the Secretary shall establish panels of experts or use panels of experts established before May 28, 1976, or both. Section 14 of the Federal Advisory Committee Act shall not apply to the duration of a panel established under this paragraph.
(2) The Secretary shall appoint to each panel established under paragraph (1) persons who are qualified by training and experience to evaluate the safety and effectiveness of the devices to be referred to the panel and who, to the extent feasible, possess skill in the use of, or experience in the development, manufacture, or utilization of, such devices. The Secretary shall make appointments to each panel so that each panel shall consist of members with adequately diversified expertise in such fields as clinical and administrative medicine, engineering, biological and physical sciences, and other related professions. In addition, each panel shall include as nonvoting members a representative of consumer interests and a representative of interests of the device manufacturing industry. Scientific, trade, and consumer organizations shall be afforded an opportunity to nominate individuals for appointment to the panels. No individual who is in the regular full-time employ of the United States and engaged in the administration of this chapter may be a member of any panel. The Secretary shall designate one of the members of each panel to serve as chairman thereof.
(3) Panel members (other than officers or employees of the United States), while attending meetings or conferences of a panel or otherwise engaged in its business, shall be entitled to receive compensation at rates to be fixed by the Secretary, but not at rates exceeding the daily equivalent of the rate in effect for grade GS–18 of the General Schedule, for each day so engaged, including traveltime; and while so serving away from their homes or regular places of business each member may be allowed travel expenses (including per diem in lieu of subsistence) as authorized by
(4) The Secretary shall furnish each panel with adequate clerical and other necessary assistance.
(5) Classification panels covering each type of device shall be scheduled to meet at such times as may be appropriate for the Secretary to meet applicable statutory deadlines.
(6)(A) Any person whose device is specifically the subject of review by a classification panel shall have—
(i) the same access to data and information submitted to a classification panel (except for data and information that are not available for public disclosure under
(ii) the opportunity to submit, for review by a classification panel, information that is based on the data or information provided in the application submitted under
(iii) the same opportunity as the Secretary to participate in meetings of the panel.
(B) Any meetings of a classification panel shall provide adequate time for initial presentations and for response to any differing views by persons whose devices are specifically the subject of a classification panel review, and shall encourage free and open participation by all interested persons.
(7) After receiving from a classification panel the conclusions and recommendations of the panel on a matter that the panel has reviewed, the Secretary shall review the conclusions and recommendations, shall make a final decision on the matter in accordance with
(8) A classification panel under this subsection shall not be subject to the annual chartering and annual report requirements of the Federal Advisory Committee Act.
(c) Classification panel organization and operation
(1) The Secretary shall organize the panels according to the various fields of clinical medicine and fundamental sciences in which devices intended for human use are used. The Secretary shall refer a device to be classified under this section to an appropriate panel established or authorized to be used under subsection (b) of this section for its review and for its recommendation respecting the classification of the device. The Secretary shall by regulation prescribe the procedure to be followed by the panels in making their reviews and recommendations. In making their reviews of devices, the panels, to the maximum extent practicable, shall provide an opportunity for interested persons to submit data and views on the classification of the devices.
(2)(A) Upon completion of a panel's review of a device referred to it under paragraph (1), the panel shall, subject to subparagraphs (B) and (C), submit to the Secretary its recommendation for the classification of the device. Any such recommendation shall (i) contain (I) a summary of the reasons for the recommendation, (II) a summary of the data upon which the recommendation is based, and (III) an identification of the risks to health (if any) presented by the device with respect to which the recommendation is made, and (ii) to the extent practicable, include a recommendation for the assignment of a priority for the application of the requirements of
(B) A recommendation of a panel for the classification of a device in class I shall include a recommendation as to whether the device should be exempted from the requirements of
(C) In the case of a device which has been referred under paragraph (1) to a panel, and which—
(i) is intended to be implanted in the human body or is purported or represented to be for a use in supporting or sustaining human life, and
(ii)(I) has been introduced or delivered for introduction into interstate commerce for commercial distribution before May 28, 1976, or
(II) is within a type of device which was so introduced or delivered before such date and is substantially equivalent to another device within that type,
such panel shall recommend to the Secretary that the device be classified in class III unless the panel determines that classification of the device in such class is not necessary to provide reasonable assurance of its safety and effectiveness. If a panel does not recommend that such a device be classified in class III, it shall in its recommendation to the Secretary for the classification of the device set forth the reasons for not recommending classification of the device in such class.
(3) The panels shall submit to the Secretary within one year of the date funds are first appropriated for the implementation of this section their recommendations respecting all devices of a type introduced or delivered for introduction into interstate commerce for commercial distribution before May 28, 1976.
(d) Panel recommendation; publication; priorities
(1) Upon receipt of a recommendation from a panel respecting a device, the Secretary shall publish in the Federal Register the panel's recommendation and a proposed regulation classifying such device and shall provide interested persons an opportunity to submit comments on such recommendation and the proposed regulation. After reviewing such comments, the Secretary shall, subject to paragraph (2), by regulation classify such device.
(2)(A) A regulation under paragraph (1) classifying a device in class I shall prescribe which, if any, of the requirements of
(B) A device described in subsection (c)(2)(C) of this section shall be classified in class III unless the Secretary determines that classification of the device in such class is not necessary to provide reasonable assurance of its safety and effectiveness. A proposed regulation under paragraph (1) classifying such a device in a class other than class III shall be accompanied by a full statement of the reasons of the Secretary (and supporting documentation and data) for not classifying such device in such class and an identification of the risks to health (if any) presented by such device.
(3) In the case of devices classified in class II and devices classified under this subsection in class III and described in
(e) Classification changes
(1) Based on new information respecting a device, the Secretary may, upon his own initiative or upon petition of an interested person, by regulation (A) change such device's classification, and (B) revoke, because of the change in classification, any regulation or requirement in effect under
(2) By regulation promulgated under paragraph (1), the Secretary may change the classification of a device from class III—
(A) to class II if the Secretary determines that special controls would provide reasonable assurance of the safety and effectiveness of the device and that general controls would not provide reasonable assurance of the safety and effectiveness of the device, or
(B) to class I if the Secretary determines that general controls would provide reasonable assurance of the safety and effectiveness of the device.
(f) Initial classification and reclassification of certain devices
(1) Any device intended for human use which was not introduced or delivered for introduction into interstate commerce for commercial distribution before May 28, 1976, is classified in class III unless—
(A) the device—
(i) is within a type of device (I) which was introduced or delivered for introduction into interstate commerce for commercial distribution before such date and which is to be classified pursuant to subsection (b) of this section, or (II) which was not so introduced or delivered before such date and has been classified in class I or II, and
(ii) is substantially equivalent to another device within such type, or
(B) the Secretary in response to a petition submitted under paragraph (3) has classified such device in class I or II.
A device classified in class III under this paragraph shall be classified in that class until the effective date of an order of the Secretary under paragraph (2) or (3) classifying the device in class I or II.
(2)(A) Any person who submits a report under
(B)(i) Not later than 60 days after the date of the submission of the request under subparagraph (A), the Secretary shall by written order classify the device involved. Such classification shall be the initial classification of the device for purposes of paragraph (1) and any device classified under this paragraph shall be a predicate device for determining substantial equivalence under paragraph (1).
(ii) A device that remains in class III under this subparagraph shall be deemed to be adulterated within the meaning of
(C) Within 30 days after the issuance of an order classifying a device under this paragraph, the Secretary shall publish a notice in the Federal Register announcing such classification.
(3)(A) The Secretary may initiate the reclassification of a device classified into class III under paragraph (1) of this subsection or the manufacturer or importer of a device classified under paragraph (1) may petition the Secretary (in such form and manner as he shall prescribe) for the issuance of an order classifying the device in class I or class II. Within thirty days of the filing of such a petition, the Secretary shall notify the petitioner of any deficiencies in the petition which prevent the Secretary from making a decision on the petition.
(B)(i) Upon determining that a petition does not contain any deficiency which prevents the Secretary from making a decision on the petition, the Secretary may for good cause shown refer the petition to an appropriate panel established or authorized to be used under subsection (b) of this section. A panel to which such a petition has been referred shall not later than ninety days after the referral of the petition make a recommendation to the Secretary respecting approval or denial of the petition. Any such recommendation shall contain (I) a summary of the reasons for the recommendation, (II) a summary of the data upon which the recommendation is based, and (III) an identification of the risks to health (if any) presented by the device with respect to which the petition was filed. In the case of a petition for a device which is intended to be implanted in the human body or which is purported or represented to be for a use in supporting or sustaining human life, the panel shall recommend that the petition be denied unless the panel determines that the classification in class III of the device is not necessary to provide reasonable assurance of its safety and effectiveness. If the panel recommends that such petition be approved, it shall in its recommendation to the Secretary set forth its reasons for such recommendation.
(ii) The requirements of paragraphs (1) and (2) of subsection (c) of this section (relating to opportunities for submission of data and views and recommendations respecting priorities and exemptions from
(C)(i) Within ninety days from the date the Secretary receives the recommendation of a panel respecting a petition (but not later than 210 days after the filing of such petition) the Secretary shall by order deny or approve the petition. If the Secretary approves the petition, the Secretary shall order the classification of the device into class I or class II in accordance with the criteria prescribed by subsection (a)(1)(A) or (a)(1)(B) of this section. In the case of a petition for a device which is intended to be implanted in the human body or which is purported or represented to be for a use in supporting or sustaining human life, the Secretary shall deny the petition unless the Secretary determines that the classification in class III of the device is not necessary to provide reasonable assurance of its safety and effectiveness. An order approving such petition shall be accompanied by a full statement of the reasons of the Secretary (and supporting documentation and data) for approving the petition and an identification of the risks to health (if any) presented by the device to which such order applies.
(ii) The requirements of paragraphs (1) and (2)(A) of subsection (d) of this section (relating to publication of recommendations, opportunity for submission of comments, and exemption from
(4) If a manufacturer reports to the Secretary under
(A) which the Secretary has classified as a class III device under subsection (b) of this section,
(B) which was introduced or delivered for introduction into interstate commerce for commercial distribution before December 1, 1990, and
(C) for which no final regulation requiring premarket approval has been promulgated under
the manufacturer shall certify to the Secretary that the manufacturer has conducted a reasonable search of all information known or otherwise available to the manufacturer respecting such other device and has included in the report under
(5) The Secretary may not withhold a determination of the initial classification of a device under paragraph (1) because of a failure to comply with any provision of this chapter unrelated to a substantial equivalence decision, including a finding that the facility in which the device is manufactured is not in compliance with good manufacturing requirements as set forth in regulations of the Secretary under
(g) Information
Within sixty days of the receipt of a written request of any person for information respecting the class in which a device has been classified or the requirements applicable to a device under this chapter, the Secretary shall provide such person a written statement of the classification (if any) of such device and the requirements of this chapter applicable to the device.
(h) Definitions
For purposes of this section and
(1) a reference to "general controls" is a reference to the controls authorized by or under
(2) a reference to "class I", "class II", or "class III" is a reference to a class of medical devices described in subparagraph (A), (B), or (C) of subsection (a)(1) of this section, and
(3) a reference to a "panel under
(i) Substantial equivalence
(1)(A) For purposes of determinations of substantial equivalence under subsection (f) of this section and
(i) has the same technological characteristics as the predicate device, or
(ii)(I) has different technological characteristics and the information submitted that the device is substantially equivalent to the predicate device contains information, including appropriate clinical or scientific data if deemed necessary by the Secretary or a person accredited under
(B) For purposes of subparagraph (A), the term "different technological characteristics" means, with respect to a device being compared to a predicate device, that there is a significant change in the materials, design, energy source, or other features of the device from those of the predicate device.
(C) To facilitate reviews of reports submitted to the Secretary under
(D) Whenever the Secretary requests information to demonstrate that devices with differing technological characteristics are substantially equivalent, the Secretary shall only request information that is necessary to making substantial equivalence determinations. In making such request, the Secretary shall consider the least burdensome means of demonstrating substantial equivalence and request information accordingly.
(E)(i) Any determination by the Secretary of the intended use of a device shall be based upon the proposed labeling submitted in a report for the device under
(I) that there is a reasonable likelihood that the device will be used for an intended use not identified in the proposed labeling for the device; and
(II) that such use could cause harm.
(ii) Such determination shall—
(I) be provided to the person who submitted the report within 10 days from the date of the notification of the Director's concerns regarding the proposed labeling;
(II) specify the limitations on the use of the device not included in the proposed labeling; and
(III) find the device substantially equivalent if the requirements of subparagraph (A) are met and if the labeling for such device conforms to the limitations specified in subclause (II).
(iii) The responsibilities of the Director under this subparagraph may not be delegated.
(iv) This subparagraph has no legal effect after the expiration of the five-year period beginning on November 21, 1997.
(F) Not later than 270 days after November 21, 1997, the Secretary shall issue guidance specifying the general principles that the Secretary will consider in determining when a specific intended use of a device is not reasonably included within a general use of such device for purposes of a determination of substantial equivalence under subsection (f) of this section or
(2) A device may not be found to be substantially equivalent to a predicate device that has been removed from the market at the initiative of the Secretary or that has been determined to be misbranded or adulterated by a judicial order.
(3)(A) As part of a submission under
(B) Any summary under subparagraph (A) respecting a device shall contain detailed information regarding data concerning adverse health effects and shall be made available to the public by the Secretary within 30 days of the issuance of a determination that such device is substantially equivalent to another device.
(June 25, 1938, ch. 675, §513, as added
References in Text
The Federal Advisory Committee Act, referred to in subsec. (b)(1), (8), is
Amendments
1997—Subsec. (a)(3)(A).
Subsec. (a)(3)(C), (D).
Subsec. (b)(5) to (8).
Subsec. (f)(1).
Subsec. (f)(1)(B).
Subsec. (f)(2) to (4).
Subsec. (f)(5).
Subsec. (i)(1)(A)(ii).
Subsec. (i)(1)(C) to (E).
Subsec. (i)(1)(F).
1993—Subsec. (b)(3).
1992—Subsec. (f)(3).
1990—Subsec. (a)(1)(A)(ii).
Subsec. (a)(1)(B).
Subsec. (a)(1)(C)(i).
Subsec. (e).
Subsec. (f).
Subsec. (f)(2)(A).
Subsec. (f)(2)(B)(i).
Subsec. (f)(3).
Subsec. (i).
Effective Date of 1997 Amendment
Amendment by
Short Title of 1976 Amendment
Regulations
Section 12(b) of
Daily Wear Soft or Daily Wear Nonhydrophilic Plastic Contact Lenses
Section 4(b)(3) of
"(A) Notwithstanding section 520(l)(5) of the Federal Food, Drug, and Cosmetic Act [
"(B) The Secretary of Health and Human Services may by notice published in the Federal Register extend the two-year period prescribed by subparagraph (A) for a lens for an additional period not to exceed one year.
"(C)(i) Before classifying a lens in class II pursuant to subparagraph (A), the Secretary of Health and Human Services shall pursuant to section 513(a)(1)(B) of such Act assure that appropriate regulatory safeguards are in effect which provide reasonable assurance of the safety and effectiveness of such lens, including clinical and preclinical data if deemed necessary by the Secretary.
"(ii) Prior to classifying a lens in class I pursuant to subparagraph (A), the Secretary shall assure that appropriate regulatory safeguards are in effect which provide reasonable assurance of the safety and effectiveness of such lens, including clinical and preclinical data if deemed necessary by the Secretary.
"(D) Notwithstanding section 520(l)(5) of such Act, if the Secretary of Health and Human Services has not made the finding and published the finding required by subparagraph (A) within 36 months of the date of the enactment of this subparagraph [Nov. 28, 1990], the Secretary shall issue an order placing the lens in class II.
"(E) Any person adversely affected by a final regulation under this paragraph revising the classification of a lens may challenge the revision of the classification of such lens only by filing a petition under section 513(e) for a classification change."
References in Other Laws to GS–16, 17, or 18 Pay Rates
References in laws to the rates of pay for GS–16, 17, or 18, or to maximum rates of pay under the General Schedule, to be considered references to rates payable under specified sections of Title 5, Government Organization and Employees, see section 529 [title I, §101(c)(1)] of
Section Referred to in Other Sections
This section is referred to in
§360d. Performance standards
(a) Reasonable assurance of safe and effective performance; periodic evaluation
(1) The special controls required by
(2) A performance standard established under subsection (b) of this section for a device—
(A) shall include provisions to provide reasonable assurance of its safe and effective performance;
(B) shall, where necessary to provide reasonable assurance of its safe and effective performance, include—
(i) provisions respecting the construction, components, ingredients, and properties of the device and its compatibility with power systems and connections to such systems,
(ii) provisions for the testing (on a sample basis or, if necessary, on an individual basis) of the device or, if it is determined that no other more practicable means are available to the Secretary to assure the conformity of the device to the standard, provisions for the testing (on a sample basis or, if necessary, on an individual basis) by the Secretary or by another person at the direction of the Secretary,
(iii) provisions for the measurement of the performance characteristics of the device,
(iv) provisions requiring that the results of each or of certain of the tests of the device required to be made under clause (ii) show that the device is in conformity with the portions of the standard for which the test or tests were required, and
(v) a provision requiring that the sale and distribution of the device be restricted but only to the extent that the sale and distribution of a device may be restricted under a regulation under
(C) shall, where appropriate, require the use and prescribe the form and content of labeling for the proper installation, maintenance, operation, and use of the device.
(3) The Secretary shall provide for periodic evaluation of performance standards established under subsection (b) of this section to determine if such standards should be changed to reflect new medical, scientific, or other technological data.
(4) In carrying out his duties under this subsection and subsection (b) of this section, the Secretary shall, to the maximum extent practicable—
(A) use personnel, facilities, and other technical support available in other Federal agencies,
(B) consult with other Federal agencies concerned with standard-setting and other nationally or internationally recognized standard-setting entities, and
(C) invite appropriate participation, through joint or other conferences, workshops, or other means, by informed persons representative of scientific, professional, industry, or consumer organizations who in his judgment can make a significant contribution.
(b) Establishment of a standard
(1)(A) The Secretary shall publish in the Federal Register a notice of proposed rulemaking for the establishment, amendment, or revocation of any performance standard for a device.
(B) A notice of proposed rulemaking for the establishment or amendment of a performance standard for a device shall—
(i) set forth a finding with supporting justification that the performance standard is appropriate and necessary to provide reasonable assurance of the safety and effectiveness of the device,
(ii) set forth proposed findings with respect to the risk of illness or injury that the performance standard is intended to reduce or eliminate,
(iii) invite interested persons to submit to the Secretary, within 30 days of the publication of the notice, requests for changes in the classification of the device pursuant to
(iv) invite interested persons to submit an existing performance standard for the device, including a draft or proposed performance standard, for consideration by the Secretary.
(C) A notice of proposed rulemaking for the revocation of a performance standard shall set forth a finding with supporting justification that the performance standard is no longer necessary to provide reasonable assurance of the safety and effectiveness of a device.
(D) The Secretary shall provide for a comment period of not less than 60 days.
(2) If, after publication of a notice in accordance with paragraph (1), the Secretary receives a request for a change in the classification of the device, the Secretary shall, within 60 days of the publication of the notice, after consultation with the appropriate panel under
(3)(A) After the expiration of the period for comment on a notice of proposed rulemaking published under paragraph (1) respecting a performance standard and after consideration of such comments and any report from an advisory committee under paragraph (5), the Secretary shall (i) promulgate a regulation establishing a performance standard and publish in the Federal Register findings on the matters referred to in paragraph (1), or (ii) publish a notice terminating the proceeding for the development of the standard together with the reasons for such termination. If a notice of termination is published, the Secretary shall (unless such notice is issued because the device is a banned device under
(B) A regulation establishing a performance standard shall set forth the date or dates upon which the standard shall take effect, but no such regulation may take effect before one year after the date of its publication unless (i) the Secretary determines that an earlier effective date is necessary for the protection of the public health and safety, or (ii) such standard has been established for a device which, effective upon the effective date of the standard, has been reclassified from class III to class II. Such date or dates shall be established so as to minimize, consistent with the public health and safety, economic loss to, and disruption or dislocation of, domestic and international trade.
(4)(A) The Secretary, upon his own initiative or upon petition of an interested person may by regulation, promulgated in accordance with the requirements of paragraphs (1), (2), and (3)(B) of this subsection, amend or revoke a performance standard.
(B) The Secretary may declare a proposed amendment of a performance standard to be effective on and after its publication in the Federal Register and until the effective date of any final action taken on such amendment if he determines that making it so effective is in the public interest. A proposed amendment of a performance standard made so effective under the preceding sentence may not prohibit, during the period in which it is so effective, the introduction or delivery for introduction into interstate commerce of a device which conforms to such standard without the change or changes provided by such proposed amendment.
(5)(A) The Secretary—
(i) may on his own initiative refer a proposed regulation for the establishment, amendment, or revocation of a performance standard, or
(ii) shall, upon the request of an interested person which demonstrates good cause for referral and which is made before the expiration of the period for submission of comments on such proposed regulation refer such proposed regulation,
to an advisory committee of experts, established pursuant to subparagraph (B), for a report and recommendation with respect to any matter involved in the proposed regulation which requires the exercise of scientific judgment. If a proposed regulation is referred under this subparagraph to an advisory committee, the Secretary shall provide the advisory committee with the data and information on which such proposed regulation is based. The advisory committee shall, within sixty days of the referral of a proposed regulation and after independent study of the data and information furnished to it by the Secretary and other data and information before it, submit to the Secretary a report and recommendation respecting such regulation, together with all underlying data and information and a statement of the reason or basis for the recommendation. A copy of such report and recommendation shall be made public by the Secretary.
(B) The Secretary shall establish advisory committees (which may not be panels under
(c) Recognition of standard
(1)(A) In addition to establishing a performance standard under this section, the Secretary shall, by publication in the Federal Register, recognize all or part of an appropriate standard established by a nationally or internationally recognized standard development organization for which a person may submit a declaration of conformity in order to meet a premarket submission requirement or other requirement under this chapter to which such standard is applicable.
(B) If a person elects to use a standard recognized by the Secretary under subparagraph (A) to meet the requirements described in such subparagraph, the person shall provide a declaration of conformity to the Secretary that certifies that the device is in conformity with such standard. A person may elect to use data, or information, other than data required by a standard recognized under subparagraph (A) to meet any requirement regarding devices under this chapter.
(2) The Secretary may withdraw such recognition of a standard through publication of a notice in the Federal Register if the Secretary determines that the standard is no longer appropriate for meeting a requirement regarding devices under this chapter.
(3)(A) Subject to subparagraph (B), the Secretary shall accept a declaration of conformity that a device is in conformity with a standard recognized under paragraph (1) unless the Secretary finds—
(i) that the data or information submitted to support such declaration does not demonstrate that the device is in conformity with the standard identified in the declaration of conformity; or
(ii) that the standard identified in the declaration of conformity is not applicable to the particular device under review.
(B) The Secretary may request, at any time, the data or information relied on by the person to make a declaration of conformity with respect to a standard recognized under paragraph (1).
(C) A person making a declaration of conformity with respect to a standard recognized under paragraph (1) shall maintain the data and information demonstrating conformity of the device to the standard for a period of two years after the date of the classification or approval of the device by the Secretary or a period equal to the expected design life of the device, whichever is longer.
(June 25, 1938, ch. 675, §514, as added
Amendments
1997—Subsec. (a)(1).
Subsec. (a)(2).
Subsec. (a)(3).
Subsec. (a)(4).
Subsec. (c).
1993—Subsec. (b)(4)(B), (5)(A)(ii).
1992—Subsec. (b)(4)(B), (5)(A)(ii).
1990—Subsec. (a)(1).
Subsec. (b).
"(1) A proceeding for the development of a performance standard for a device shall be initiated by the Secretary by the publication in the Federal Register of notice of the opportunity to submit to the Secretary a request (within fifteen days of the date of the publication of the notice) for a change in the classification of the device based on new information relevant to its classification.
"(2) If, after publication of a notice pursuant to paragraph (1) the Secretary receives a request for a change in the device's classification, he shall, within sixty days of the publication of such notice and after consultation with the appropriate panel under
Subsec. (b)(1), (2).
"(1)(A) After publication pursuant to subsection (c) of this section of a notice respecting a performance standard for a device, the Secretary shall either—
"(i) publish, in the Federal Register in a notice of proposed rulemaking, a proposed performance standard for the device (I) developed by an offeror under such notice and accepted by the Secretary, (II) developed under subsection (c)(4) of this section, (III) accepted by the Secretary under subsection (d) of this section, or (IV) developed by him under subsection (f) of this section, or
"(ii) issue a notice in the Federal Register that the proceeding is terminated together with the reasons for such termination.
"(B) If the Secretary issues under subparagraph (A)(ii) a notice of termination of a proceeding to establish a performance standard for a device, he shall (unless such notice is issued because the device is a banned device under
"(2) A notice of proposed rulemaking for the establishment of a performance standard for a device published under paragraph (1)(A)(i) shall set forth proposed findings with respect to the degree of the risk of illness or injury designed to be eliminated or reduced by the proposed standard and the benefit to the public from the device."
Subsec. (b)(3)(A)(i).
Subsec. (b)(4)(A).
Subsec. (b)(4)(B).
Subsec. (b)(5)(A)(ii).
Subsecs. (c) to (f).
Subsec. (g).
1976—Subsec. (a).
Effective Date of 1997 Amendment
Amendment by
References in Other Laws to GS–16, 17, or 18 Pay Rates
References in laws to the rates of pay for GS–16, 17, or 18, or to maximum rates of pay under the General Schedule, to be considered references to rates payable under specified sections of Title 5, Government Organization and Employees, see section 529 [title I, §101(c)(1)] of
Termination of Advisory Committees
Advisory committees in existence on Jan. 5, 1973, to terminate not later than the expiration of the 2-year period following Jan. 5, 1973, and advisory committees established after Jan. 5, 1973, to terminate not later than the expiration of the 2-year period beginning on the date of their establishment, unless in the case of a committee established by the President or an officer of the Federal Government, such committee is renewed by appropriate action prior to the expiration of such 2-year period, or in the case of a committee established by Congress, its duration is otherwise provided by law. See section 14 of
Section Referred to in Other Sections
This section is referred to in
§360e. Premarket approval
(a) General requirement
A class III device—
(1) which is subject to a regulation promulgated under subsection (b) of this section; or
(2) which is a class III device because of
is required to have, unless exempt under
(b) Regulation to require premarket approval
(1) In the case of a class III device which—
(A) was introduced or delivered for introduction into interstate commerce for commercial distribution before May 28, 1976; or
(B) is (i) of a type so introduced or delivered, and (ii) is substantially equivalent to another device within that type,
the Secretary shall by regulation, promulgated in accordance with this subsection, require that such device have an approval under this section of an application for premarket approval.
(2)(A) A proceeding for the promulgation of a regulation under paragraph (1) respecting a device shall be initiated by the publication in the Federal Register of a notice of proposed rulemaking. Such notice shall contain—
(i) the proposed regulation;
(ii) proposed findings with respect to the degree of risk of illness or injury designed to be eliminated or reduced by requiring the device to have an approved application for premarket approval and the benefit to the public from use of the device;
(iii) opportunity for the submission of comments on the proposed regulation and the proposed findings; and
(iv) opportunity to request a change in the classification of the device based on new information relevant to the classification of the device.
(B) If, within fifteen days after publication of a notice under subparagraph (A), the Secretary receives a request for a change in the classification of a device, he shall, within sixty days of the publication of such notice and after consultation with the appropriate panel under
(3) After the expiration of the period for comment on a proposed regulation and proposed findings published under paragraph (2) and after consideration of comments submitted on such proposed regulation and findings, the Secretary shall (A) promulgate such regulation and publish in the Federal Register findings on the matters referred to in paragraph (2)(A)(ii), or (B) publish a notice terminating the proceeding for the promulgation of the regulation together with the reasons for such termination. If a notice of termination is published, the Secretary shall (unless such notice is issued because the device is a banned device under
(4) The Secretary, upon his own initiative or upon petition of an interested person, may by regulation amend or revoke any regulation promulgated under this subsection. A regulation to amend or revoke a regulation under this subsection shall be promulgated in accordance with the requirements prescribed by this subsection for the promulgation of the regulation to be amended or revoked.
(c) Application for premarket approval
(1) Any person may file with the Secretary an application for premarket approval for a class III device. Such an application for a device shall contain—
(A) full reports of all information, published or known to or which should reasonably be known to the applicant, concerning investigations which have been made to show whether or not such device is safe and effective;
(B) a full statement of the components, ingredients, and properties and of the principle or principles of operation, of such device;
(C) a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and, when relevant, packing and installation of, such device;
(D) an identifying reference to any performance standard under
(E) such samples of such device and of components thereof as the Secretary may reasonably require, except that where the submission of such samples is impracticable or unduly burdensome, the requirement of this subparagraph may be met by the submission of complete information concerning the location of one or more such devices readily available for examination and testing;
(F) specimens of the labeling proposed to be used for such device; and
(G) such other information relevant to the subject matter of the application as the Secretary, with the concurrence of the appropriate panel under
(2) Upon receipt of an application meeting the requirements set forth in paragraph (1), the Secretary—
(A) may on the Secretary's own initiative, or
(B) shall, upon the request of an applicant unless the Secretary finds that the information in the application which would be reviewed by a panel substantially duplicates information which has previously been reviewed by a panel appointed under
refer such application to the appropriate panel under
(d) Action on application for premarket approval
(1)(A) As promptly as possible, but in no event later than one hundred and eighty days after the receipt of an application under subsection (c) of this section (except as provided in
(i) issue an order approving the application if he finds that none of the grounds for denying approval specified in paragraph (2) of this subsection applies; or
(ii) deny approval of the application if he finds (and sets forth the basis for such finding as part of or accompanying such denial) that one or more grounds for denial specified in paragraph (2) of this subsection apply.
In making the determination whether to approve or deny the application, the Secretary shall rely on the conditions of use included in the proposed labeling as the basis for determining whether or not there is a reasonable assurance of safety and effectiveness, if the proposed labeling is neither false nor misleading. In determining whether or not such labeling is false or misleading, the Secretary shall fairly evaluate all material facts pertinent to the proposed labeling.
(B)(i) The Secretary may not enter into an agreement to extend the period in which to take action with respect to an application submitted for a device subject to a regulation promulgated under subsection (b) of this section unless he finds that the continued availability of the device is necessary for the public health.
(ii) An order approving an application for a device may require as a condition to such approval that the sale and distribution of the device be restricted but only to the extent that the sale and distribution of a device may be restricted under a regulation under
(iii) The Secretary shall accept and review statistically valid and reliable data and any other information from investigations conducted under the authority of regulations required by
(I) the data or information is derived from investigations of an earlier version of the device, the device has been modified during or after the investigations (but prior to submission of an application under subsection (c) of this section) and such a modification of the device does not constitute a significant change in the design or in the basic principles of operation of the device that would invalidate the data or information; or
(II) the data or information relates to a device approved under this section, is available for use under this chapter, and is relevant to the design and intended use of the device for which the application is pending.
(2) The Secretary shall deny approval of an application for a device if, upon the basis of the information submitted to the Secretary as part of the application and any other information before him with respect to such device, the Secretary finds that—
(A) there is a lack of a showing of reasonable assurance that such device is safe under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof;
(B) there is a lack of a showing of reasonable assurance that the device is effective under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof;
(C) the methods used in, or the facilities or controls used for, the manufacture, processing, packing, or installation of such device do not conform to the requirements of
(D) based on a fair evaluation of all material facts, the proposed labeling is false or misleading in any particular; or
(E) such device is not shown to conform in all respects to a performance standard in effect under
Any denial of an application shall, insofar as the Secretary determines to be practicable, be accompanied by a statement informing the applicant of the measures required to place such application in approvable form (which measures may include further research by the applicant in accordance with one or more protocols prescribed by the Secretary).
(3)(A)(i) The Secretary shall, upon the written request of an applicant, meet with the applicant, not later than 100 days after the receipt of an application that has been filed as complete under subsection (c) of this section, to discuss the review status of the application.
(ii) The Secretary shall, in writing and prior to the meeting, provide to the applicant a description of any deficiencies in the application that, at that point, have been identified by the Secretary based on an interim review of the entire application and identify the information that is required to correct those deficiencies.
(iii) The Secretary shall notify the applicant promptly of—
(I) any additional deficiency identified in the application, or
(II) any additional information required to achieve completion of the review and final action on the application,
that was not described as a deficiency in the written description provided by the Secretary under clause (ii).
(B) The Secretary and the applicant may, by mutual consent, establish a different schedule for a meeting required under this paragraph.
(4) An applicant whose application has been denied approval may, by petition filed on or before the thirtieth day after the date upon which he receives notice of such denial, obtain review thereof in accordance with either paragraph (1) or (2) of subsection (g) of this section, and any interested person may obtain review, in accordance with paragraph (1) or (2) of subsection (g) of this section, of an order of the Secretary approving an application.
(5) In order to provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating human diseases or conditions, the Secretary shall provide review priority for devices—
(A) representing breakthrough technologies,
(B) for which no approved alternatives exist,
(C) which offer significant advantages over existing approved alternatives, or
(D) the availability of which is in the best interest of the patients.
(6)(A)(i) A supplemental application shall be required for any change to a device subject to an approved application under this subsection that affects safety or effectiveness, unless such change is a modification in a manufacturing procedure or method of manufacturing and the holder of the approved application submits a written notice to the Secretary that describes in detail the change, summarizes the data or information supporting the change, and informs the Secretary that the change has been made under the requirements of
(ii) The holder of an approved application who submits a notice under clause (i) with respect to a manufacturing change of a device may distribute the device 30 days after the date on which the Secretary receives the notice, unless the Secretary within such 30-day period notifies the holder that the notice is not adequate and describes such further information or action that is required for acceptance of such change. If the Secretary notifies the holder that a supplemental application is required, the Secretary shall review the supplement within 135 days after the receipt of the supplement. The time used by the Secretary to review the notice of the manufacturing change shall be deducted from the 135-day review period if the notice meets appropriate content requirements for premarket approval supplements.
(B)(i) Subject to clause (ii), in reviewing a supplement to an approved application, for an incremental change to the design of a device that affects safety or effectiveness, the Secretary shall approve such supplement if—
(I) nonclinical data demonstrate that the design modification creates the intended additional capacity, function, or performance of the device; and
(II) clinical data from the approved application and any supplement to the approved application provide a reasonable assurance of safety and effectiveness for the changed device.
(ii) The Secretary may require, when necessary, additional clinical data to evaluate the design modification of the device to provide a reasonable assurance of safety and effectiveness.
(e) Withdrawal and temporary suspension of approval of application
(1) The Secretary shall, upon obtaining, where appropriate, advice on scientific matters from a panel or panels under
(A) that such device is unsafe or ineffective under the conditions of use prescribed, recommended, or suggested in the labeling thereof;
(B) on the basis of new information before him with respect to such device, evaluated together with the evidence available to him when the application was approved, that there is a lack of a showing of reasonable assurance that the device is safe or effective under the conditions of use prescribed, recommended, or suggested in the labeling thereof;
(C) that the application contained or was accompanied by an untrue statement of a material fact;
(D) that the applicant (i) has failed to establish a system for maintaining records, or has repeatedly or deliberately failed to maintain records or to make reports, required by an applicable regulation under
(E) on the basis of new information before him with respect to such device, evaluated together with the evidence before him when the application was approved, that the methods used in, or the facilities and controls used for, the manufacture, processing, packing, or installation of such device do not conform with the requirements of
(F) on the basis of new information before him, evaluated together with the evidence before him when the application was approved, that the labeling of such device, based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice from the Secretary of such fact; or
(G) on the basis of new information before him, evaluated together with the evidence before him when the application was approved, that such device is not shown to conform in all respects to a performance standard which is in effect under
(2) The holder of an application subject to an order issued under paragraph (1) withdrawing approval of the application may, by petition filed on or before the thirtieth day after the date upon which he receives notice of such withdrawal, obtain review thereof in accordance with either paragraph (1) or (2) of subsection (g) of this section.
(3) If, after providing an opportunity for an informal hearing, the Secretary determines there is reasonable probability that the continuation of distribution of a device under an approved application would cause serious, adverse health consequences or death, the Secretary shall by order temporarily suspend the approval of the application approved under this section. If the Secretary issues such an order, the Secretary shall proceed expeditiously under paragraph (1) to withdraw such application.
(f) Product development protocol
(1) In the case of a class III device which is required to have an approval of an application submitted under subsection (c) of this section, such device shall be considered as having such an approval if a notice of completion of testing conducted in accordance with a product development protocol approved under paragraph (4) has been declared completed under paragraph (6).
(2) Any person may submit to the Secretary a proposed product development protocol with respect to a device. Such a protocol shall be accompanied by data supporting it. If, within thirty days of the receipt of such a protocol, the Secretary determines that it appears to be appropriate to apply the requirements of this subsection to the device with respect to which the protocol is submitted, the Secretary—
(A) may, at the initiative of the Secretary, refer the proposed protocol to the appropriate panel under
(B) shall so refer such protocol upon the request of the submitter, unless the Secretary finds that the proposed protocol and accompanying data which would be reviewed by such panel substantially duplicate a product development protocol and accompanying data which have previously been reviewed by such a panel.
(3) A proposed product development protocol for a device may be approved only if—
(A) the Secretary determines that it is appropriate to apply the requirements of this subsection to the device in lieu of the requirement of approval of an application submitted under subsection (c) of this section; and
(B) the Secretary determines that the proposed protocol provides—
(i) a description of the device and the changes which may be made in the device,
(ii) a description of the preclinical trials (if any) of the device and a specification of (I) the results from such trials to be required before the commencement of clinical trials of the device, and (II) any permissible variations in preclinical trials and the results therefrom,
(iii) a description of the clinical trials (if any) of the device and a specification of (I) the results from such trials to be required before the filing of a notice of completion of the requirements of the protocol, and (II) any permissible variations in such trials and the results therefrom,
(iv) a description of the methods to be used in, and the facilities and controls to be used for, the manufacture, processing, and, when relevant, packing and installation of the device,
(v) an identifying reference to any performance standard under
(vi) if appropriate, specimens of the labeling proposed to be used for such device,
(vii) such other information relevant to the subject matter of the protocol as the Secretary, with the concurrence of the appropriate panel or panels under
(viii) a requirement for submission of progress reports and, when completed, records of the trials conducted under the protocol which records are adequate to show compliance with the protocol.
(4) The Secretary shall approve or disapprove a proposed product development protocol submitted under paragraph (2) within one hundred and twenty days of its receipt unless an additional period is agreed upon by the Secretary and the person who submitted the protocol. Approval of a protocol or denial of approval of a protocol is final agency action subject to judicial review under
(5) At any time after a product development protocol for a device has been approved pursuant to paragraph (4), the person for whom the protocol was approved may submit a notice of completion—
(A) stating (i) his determination that the requirements of the protocol have been fulfilled and that, to the best of his knowledge, there is no reason bearing on safety or effectiveness why the notice of completion should not become effective, and (ii) the data and other information upon which such determination was made, and
(B) setting forth the results of the trials required by the protocol and all the information required by subsection (c)(1) of this section.
(6)(A) The Secretary may, after providing the person who has an approved protocol and opportunity for an informal hearing and at any time prior to receipt of notice of completion of such protocol, issue a final order to revoke such protocol if he finds that—
(i) such person has failed substantially to comply with the requirements of the protocol,
(ii) the results of the trials obtained under the protocol differ so substantially from the results required by the protocol that further trials cannot be justified, or
(iii) the results of the trials conducted under the protocol or available new information do not demonstrate that the device tested under the protocol does not present an unreasonable risk to health and safety.
(B) After the receipt of a notice of completion of an approved protocol the Secretary shall, within the ninety-day period beginning on the date such notice is received, by order either declare the protocol completed or declare it not completed. An order declaring a protocol not completed may take effect only after the Secretary has provided the person who has the protocol opportunity for an informal hearing on the order. Such an order may be issued only if the Secretary finds—
(i) such person has failed substantially to comply with the requirements of the protocol,
(ii) the results of the trials obtained under the protocol differ substantially from the results required by the protocol, or
(iii) there is a lack of a showing of reasonable assurance of the safety and effectiveness of the device under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof.
(C) A final order issued under subparagraph (A) or (B) shall be in writing and shall contain the reasons to support the conclusions thereof.
(7) At any time after a notice of completion has become effective, the Secretary may issue an order (after due notice and opportunity for an informal hearing to the person for whom the notice is effective) revoking the approval of a device provided by a notice of completion which has become effective as provided in subparagraph (B) if he finds that any of the grounds listed in subparagraphs (A) through (G) of subsection (e)(1) of this section apply. Each reference in such subparagraphs to an application shall be considered for purposes of this paragraph as a reference to a protocol and the notice of completion of such protocol, and each reference to the time when an application was approved shall be considered for purposes of this paragraph as a reference to the time when a notice of completion took effect.
(8) A person who has an approved protocol subject to an order issued under paragraph (6)(A) revoking such protocol, a person who has an approved protocol with respect to which an order under paragraph (6)(B) was issued declaring that the protocol had not been completed, or a person subject to an order issued under paragraph (7) revoking the approval of a device may, by petition filed on or before the thirtieth day after the date upon which he receives notice of such order, obtain review thereof in accordance with either paragraph (1) or (2) of subsection (g) of this section.
(g) Review
(1) Upon petition for review of—
(A) an order under subsection (d) of this section approving or denying approval of an application or an order under subsection (e) of this section withdrawing approval of an application, or
(B) an order under subsection (f)(6)(A) of this section revoking an approved protocol, under subsection (f)(6)(B) of this section declaring that an approved protocol has not been completed, or under subsection (f)(7) of this section revoking the approval of a device,
the Secretary shall, unless he finds the petition to be without good cause or unless a petition for review of such order has been submitted under paragraph (2), hold a hearing, in accordance with
(2)(A) Upon petition for review of—
(i) an order under subsection (d) of this section approving or denying approval of an application or an order under subsection (e) of this section withdrawing approval of an application, or
(ii) an order under subsection (f)(6)(A) of this section revoking an approved protocol, under subsection (f)(6)(B) of this section declaring that an approved protocol has not been completed, or under subsection (f)(7) of this section revoking the approval of a device,
the Secretary shall refer the application or protocol subject to the order and the basis for the order to an advisory committee of experts established pursuant to subparagraph (B) for a report and recommendation with respect to the order. The advisory committee shall, after independent study of the data and information furnished to it by the Secretary and other data and information before it, submit to the Secretary a report and recommendation, together with all underlying data and information and a statement of the reasons or basis for the recommendation. A copy of such report shall be promptly supplied by the Secretary to any person who petitioned for such referral to the advisory committee.
(B) The Secretary shall establish advisory committees (which may not be panels under
(C) The Secretary shall make public the report and recommendation made by an advisory committee with respect to an application and shall by order, stating the reasons therefor, either affirm the order referred to the advisory committee or reverse such order and, if appropriate, approve or deny approval of the application, reinstate the application's approval, approve the protocol, or place in effect a notice of completion.
(h) Service of orders
Orders of the Secretary under this section shall be served (1) in person by any officer or employee of the department designated by the Secretary, or (2) by mailing the order by registered mail or certified mail addressed to the applicant at his last known address in the records of the Secretary.
(i) Revision
(1) Before December 1, 1995, the Secretary shall by order require manufacturers of devices, which were introduced or delivered for introduction into interstate commerce for commercial distribution before May 28, 1976, and which are subject to revision of classification under paragraph (2), to submit to the Secretary a summary of and citation to any information known or otherwise available to the manufacturer respecting such devices, including adverse safety or effectiveness information which has not been submitted under
(2) After the issuance of an order under paragraph (1) but before December 1, 1995, the Secretary shall publish a regulation in the Federal Register for each device—
(A) which the Secretary has classified as a class III device, and
(B) for which no final regulation has been promulgated under subsection (b) of this section,
revising the classification of the device so that the device is classified into class I or class II, unless the regulation requires the device to remain in class III. In determining whether to revise the classification of a device or to require a device to remain in class III, the Secretary shall apply the criteria set forth in
(3) The Secretary shall, as promptly as is reasonably achievable, but not later than 12 months after the effective date of the regulation requiring a device to remain in class III, establish a schedule for the promulgation of a subsection (b) of this section regulation for each device which is subject to the regulation requiring the device to remain in class III.
(June 25, 1938, ch. 675, §515, as added
Amendments
1997—Subsec. (d)(1)(A).
Subsec. (d)(1)(B)(iii).
Subsec. (d)(3), (4).
Subsec. (d)(5).
Subsec. (d)(6).
Subsec. (f)(2).
1993—Subsec. (c)(2)(A).
1990—Subsec. (c)(2).
Subsec. (e).
Subsec. (e)(3).
Subsec. (i).
Effective Date of 1997 Amendment
Amendment by
Termination of Advisory Committees
Advisory committees in existence on Jan. 5, 1973, to terminate not later than the expiration of the 2-year period following Jan. 5, 1973, and advisory committees established after Jan. 5, 1973, to terminate not later than the expiration of the 2-year period beginning on the date of their establishment, unless in the case of a committee established by the President or an officer of the Federal Government, such committee is renewed by appropriate action prior to the expiration of such 2-year period, or in the case of a committee established by Congress, its duration is otherwise provided by law. See section 14 of
References in Other Laws to GS–16, 17, or 18 Pay Rates
References in laws to the rates of pay for GS–16, 17, or 18, or to maximum rates of pay under the General Schedule, to be considered references to rates payable under specified sections of Title 5, Government Organization and Employees, see section 529 [title I, §101(c)(1)] of
Section Referred to in Other Sections
This section is referred to in
§360f. Banned devices
(a) General rule
Whenever the Secretary finds, on the basis of all available data and information, that—
(1) a device intended for human use presents substantial deception or an unreasonable and substantial risk of illness or injury; and
(2) in the case of substantial deception or an unreasonable and substantial risk of illness or injury which the Secretary determined could be corrected or eliminated by labeling or change in labeling and with respect to which the Secretary provided written notice to the manufacturer specifying the deception or risk of illness or injury, the labeling or change in labeling to correct the deception or eliminate or reduce such risk, and the period within which such labeling or change in labeling was to be done, such labeling or change in labeling was not done within such period;
he may initiate a proceeding to promulgate a regulation to make such device a banned device.
(b) Special effective date
The Secretary may declare a proposed regulation under subsection (a) of this section to be effective upon its publication in the Federal Register and until the effective date of any final action taken respecting such regulation if (1) he determines, on the basis of all available data and information, that the deception or risk of illness or injury associated with the use of the device which is subject to the regulation presents an unreasonable, direct, and substantial danger to the health of individuals, and (2) before the date of the publication of such regulation, the Secretary notifies the manufacturer of such device that such regulation is to be made so effective. If the Secretary makes a proposed regulation so effective, he shall, as expeditiously as possible, give interested persons prompt notice of his action under this subsection, provide reasonable opportunity for an informal hearing on the proposed regulation, and either affirm, modify, or revoke such proposed regulation.
(June 25, 1938, ch. 675, §516, as added
Amendments
1990—Subsec. (a).
Section Referred to in Other Sections
This section is referred to in
§360g. Judicial review
(a) Petition; record
Not later than thirty days after—
(1) the promulgation of a regulation under
(2) the promulgation of a regulation under
(3) the issuance of an order under
(4) the promulgation of a regulation under paragraph (3) of
(5) the promulgation of a regulation under
(6) the issuance of an order under
(7) an order under
(8) an order pursuant to
(9) a regulation under
any person adversely affected by such regulation or order may file a petition with the United States Court of Appeals for the District of Columbia or for the circuit wherein such person resides or has his principal place of business for judicial review of such regulation or order. A copy of the petition shall be transmitted by the clerk of the court to the Secretary or other officer designated by him for that purpose. The Secretary shall file in the court the record of the proceedings on which the Secretary based his regulation or order as provided in
(b) Additional data, views, and arguments
If the petitioner applies to the court for leave to adduce additional data, views, or arguments respecting the regulation or order being reviewed and shows to the satisfaction of the court that such additional data, views, or arguments are material and that there were reasonable grounds for the petitioner's failure to adduce such data, views, or arguments in the proceedings before the Secretary, the court may order the Secretary to provide additional opportunity for the oral presentation of data, views, or arguments and for written submissions. The Secretary may modify his findings, or make new findings by reason of the additional data, views, or arguments so taken and shall file with the court such modified or new findings, and his recommendation, if any, for the modification or setting aside of the regulation or order being reviewed, with the return of such additional data, views, or arguments.
(c) Standard for review
Upon the filing of the petition under subsection (a) of this section for judicial review of a regulation or order, the court shall have jurisdiction to review the regulation or order in accordance with
(d) Finality of judgments
The judgment of the court affirming or setting aside, in whole or in part, any regulation or order shall be final, subject to review by the Supreme Court of the United States upon certiorari or certification, as provided in
(e) Remedies
The remedies provided for in this section shall be in addition to and not in lieu of any other remedies provided by law.
(f) Statement of reasons
To facilitate judicial review under this section or under any other provision of law of a regulation or order issued under
(June 25, 1938, ch. 675, §517, as added
Amendments
1997—Subsec. (a)(8).
Subsec. (a)(9).
Subsec. (a)(10).
1992—Subsec. (a)(10).
1990—Subsec. (a)(8) to (10).
Effective Date of 1997 Amendment
Amendment by
§360h. Notification and other remedies
(a) Notification
If the Secretary determines that—
(1) a device intended for human use which is introduced or delivered for introduction into interstate commerce for commercial distribution presents an unreasonable risk of substantial harm to the public health, and
(2) notification under this subsection is necessary to eliminate the unreasonable risk of such harm and no more practicable means is available under the provisions of this chapter (other than this section) to eliminate such risk,
the Secretary may issue such order as may be necessary to assure that adequate notification is provided in an appropriate form, by the persons and means best suited under the circumstances involved, to all health professionals who prescribe or use the device and to any other person (including manufacturers, importers, distributors, retailers, and device users) who should properly receive such notification in order to eliminate such risk. An order under this subsection shall require that the individuals subject to the risk with respect to which the order is to be issued be included in the persons to be notified of the risk unless the Secretary determines that notice to such individuals would present a greater danger to the health of such individuals than no such notification. If the Secretary makes such a determination with respect to such individuals, the order shall require that the health professionals who prescribe or use the device provide for the notification of the individuals whom the health professionals treated with the device of the risk presented by the device and of any action which may be taken by or on behalf of such individuals to eliminate or reduce such risk. Before issuing an order under this subsection, the Secretary shall consult with the persons who are to give notice under the order.
(b) Repair, replacement, or refund
(1)(A) If, after affording opportunity for an informal hearing, the Secretary determines that—
(i) a device intended for human use which is introduced or delivered for introduction into interstate commerce for commercial distribution presents an unreasonable risk of substantial harm to the public health,
(ii) there are reasonable grounds to believe that the device was not properly designed or manufactured with reference to the state of the art as it existed at the time of its design or manufacture,
(iii) there are reasonable grounds to believe that the unreasonable risk was not caused by failure of a person other than a manufacturer, importer, distributor, or retailer of the device to exercise due care in the installation, maintenance, repair, or use of the device, and
(iv) the notification authorized by subsection (a) of this section would not by itself be sufficient to eliminate the unreasonable risk and action described in paragraph (2) of this subsection is necessary to eliminate such risk,
the Secretary may order the manufacturer, importer, or any distributor of such device, or any combination of such persons, to submit to him within a reasonable time a plan for taking one or more of the actions described in paragraph (2). An order issued under the preceding sentence which is directed to more than one person shall specify which person may decide which action shall be taken under such plan and the person specified shall be the person who the Secretary determines bears the principal, ultimate financial responsibility for action taken under the plan unless the Secretary cannot determine who bears such responsibility or the Secretary determines that the protection of the public health requires that such decision be made by a person (including a device user or health professional) other than the person he determines bears such responsibility.
(B) The Secretary shall approve a plan submitted pursuant to an order issued under subparagraph (A) unless he determines (after affording opportunity for an informal hearing) that the action or actions to be taken under the plan or the manner in which such action or actions are to be taken under the plan will not assure that the unreasonable risk with respect to which such order was issued will be eliminated. If the Secretary disapproves a plan, he shall order a revised plan to be submitted to him within a reasonable time. If the Secretary determines (after affording opportunity for an informal hearing) that the revised plan is unsatisfactory or if no revised plan or no initial plan has been submitted to the Secretary within the prescribed time, the Secretary shall (i) prescribe a plan to be carried out by the person or persons to whom the order issued under subparagraph (A) was directed, or (ii) after affording an opportunity for an informal hearing, by order prescribe a plan to be carried out by a person who is a manufacturer, importer, distributor, or retailer of the device with respect to which the order was issued but to whom the order under subparagraph (A) was not directed.
(2) The actions which may be taken under a plan submitted under an order issued under paragraph (1) are as follows:
(A) To repair the device so that it does not present the unreasonable risk of substantial harm with respect to which the order under paragraph (1) was issued.
(B) To replace the device with a like or equivalent device which is in conformity with all applicable requirements of this chapter.
(C) To refund the purchase price of the device (less a reasonable allowance for use if such device has been in the possession of the device user for one year or more—
(i) at the time of notification ordered under subsection (a) of this section, or
(ii) at the time the device user receives actual notice of the unreasonable risk with respect to which the order was issued under paragraph (1),
whichever first occurs).
(3) No charge shall be made to any person (other than a manufacturer, importer, distributor or retailer) for availing himself of any remedy, described in paragraph (2) and provided under an order issued under paragraph (1), and the person subject to the order shall reimburse each person (other than a manufacturer, importer, distributor, or retailer) who is entitled to such a remedy for any reasonable and foreseeable expenses actually incurred by such person in availing himself of such remedy.
(c) Reimbursement
An order issued under subsection (b) of this section with respect to a device may require any person who is a manufacturer, importer, distributor, or retailer of the device to reimburse any other person who is a manufacturer, importer, distributor, or retailer of such device for such other person's expenses actually incurred in connection with carrying out the order if the Secretary determines such reimbursement is required for the protection of the public health. Any such requirement shall not affect any rights or obligations under any contract to which the person receiving reimbursement or the person making such reimbursement is a party.
(d) Effect on other liability
Compliance with an order issued under this section shall not relieve any person from liability under Federal or State law. In awarding damages for economic loss in an action brought for the enforcement of any such liability, the value to the plaintiff in such action of any remedy provided him under such order shall be taken into account.
(e) Recall authority
(1) If the Secretary finds that there is a reasonable probability that a device intended for human use would cause serious, adverse health consequences or death, the Secretary shall issue an order requiring the appropriate person (including the manufacturers, importers, distributors, or retailers of the device)—
(A) to immediately cease distribution of such device, and
(B) to immediately notify health professionals and device user facilities of the order and to instruct such professionals and facilities to cease use of such device.
The order shall provide the person subject to the order with an opportunity for an informal hearing, to be held not later than 10 days after the date of the issuance of the order, on the actions required by the order and on whether the order should be amended to require a recall of such device. If, after providing an opportunity for such a hearing, the Secretary determines that inadequate grounds exist to support the actions required by the order, the Secretary shall vacate the order.
(2)(A) If, after providing an opportunity for an informal hearing under paragraph (1), the Secretary determines that the order should be amended to include a recall of the device with respect to which the order was issued, the Secretary shall, except as provided in subparagraphs (B) and (C), amend the order to require a recall. The Secretary shall specify a timetable in which the device recall will occur and shall require periodic reports to the Secretary describing the progress of the recall.
(B) An amended order under subparagraph (A)—
(i) shall—
(I) not include recall of a device from individuals, and
(II) not include recall of a device from device user facilities if the Secretary determines that the risk of recalling such device from the facilities presents a greater health risk than the health risk of not recalling the device from use, and
(ii) shall provide for notice to individuals subject to the risks associated with the use of such device.
In providing the notice required by clause (ii), the Secretary may use the assistance of health professionals who prescribed or used such a device for individuals. If a significant number of such individuals cannot be identified, the Secretary shall notify such individuals pursuant to
(3) The remedy provided by this subsection shall be in addition to remedies provided by subsections (a), (b), and (c) of this section.
(June 25, 1938, ch. 675, §518, as added
Amendments
1992—Subsec. (b)(1)(A)(ii).
1990—Subsec. (e).
Section Referred to in Other Sections
This section is referred to in
§360i. Records and reports on devices
(a) General rule
Every person who is a manufacturer or importer of a device intended for human use shall establish and maintain such records, make such reports, and provide such information, as the Secretary may by regulation reasonably require to assure that such device is not adulterated or misbranded and to otherwise assure its safety and effectiveness. Regulations prescribed under the preceding sentence—
(1) shall require a device manufacturer or importer to report to the Secretary whenever the manufacturer or importer receives or otherwise becomes aware of information that reasonably suggests that one of its marketed devices—
(A) may have caused or contributed to a death or serious injury, or
(B) has malfunctioned and that such device or a similar device marketed by the manufacturer or importer would be likely to cause or contribute to a death or serious injury if the malfunction were to recur;
(2) shall define the term "serious injury" to mean an injury that—
(A) is life threatening,
(B) results in permanent impairment of a body function or permanent damage to a body structure, or
(C) necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure;
(3) shall require reporting of other significant adverse device experiences as determined by the Secretary to be necessary to be reported;
(4) shall not impose requirements unduly burdensome to a device manufacturer or importer taking into account his cost of complying with such requirements and the need for the protection of the public health and the implementation of this chapter;
(5) which prescribe the procedure for making requests for reports or information shall require that each request made under such regulations for submission of a report or information to the Secretary state the reason or purpose for such request and identify to the fullest extent practicable such report or information;
(6) which require submission of a report or information to the Secretary shall state the reason or purpose for the submission of such report or information and identify to the fullest extent practicable such report or information;
(7) may not require that the identity of any patient be disclosed in records, reports, or information required under this subsection unless required for the medical welfare of an individual, to determine the safety or effectiveness of a device, or to verify a record, report, or information submitted under this chapter; and
(8) may not require a manufacturer or importer of a class I device to—
(A) maintain for such a device records respecting information not in the possession of the manufacturer or importer, or
(B) to submit for such a device to the Secretary any report or information—
(i) not in the possession of the manufacturer or importer, or
(ii) on a periodic basis,
unless such report or information is necessary to determine if the device should be reclassified or if the device is adulterated or misbranded. and 1
In prescribing such regulations, the Secretary shall have due regard for the professional ethics of the medical profession and the interests of patients. The prohibitions of paragraph (7) of this subsection continue to apply to records, reports, and information concerning any individual who has been a patient, irrespective of whether or when he ceases to be a patient. The Secretary shall by regulation require distributors to keep records and make such records available to the Secretary upon request. Paragraphs (4) and (8) apply to distributors to the same extent and in the same manner as such paragraphs apply to manufacturers and importers.
(b) User reports
(1)(A) Whenever a device user facility receives or otherwise becomes aware of information that reasonably suggests that a device has or may have caused or contributed to the death of a patient of the facility, the facility shall, as soon as practicable but not later than 10 working days after becoming aware of the information, report the information to the Secretary and, if the identity of the manufacturer is known, to the manufacturer of the device. In the case of deaths, the Secretary may by regulation prescribe a shorter period for the reporting of such information.
(B) Whenever a device user facility receives or otherwise becomes aware of—
(i) information that reasonably suggests that a device has or may have caused or contributed to the serious illness of, or serious injury to, a patient of the facility, or
(ii) other significant adverse device experiences as determined by the Secretary by regulation to be necessary to be reported,
the facility shall, as soon as practicable but not later than 10 working days after becoming aware of the information, report the information to the manufacturer of the device or to the Secretary if the identity of the manufacturer is not known.
(C) Each device user facility shall submit to the Secretary on an annual basis a summary of the reports made under subparagraphs (A) and (B). Such summary shall be submitted on January 1 of each year. The summary shall be in such form and contain such information from such reports as the Secretary may require and shall include—
(i) sufficient information to identify the facility which made the reports for which the summary is submitted,
(ii) in the case of any product which was the subject of a report, the product name, serial number, and model number,
(iii) the name and the address of the manufacturer of such device, and
(iv) a brief description of the event reported to the manufacturer.
(D) For purposes of subparagraphs (A), (B), and (C), a device user facility shall be treated as having received or otherwise become aware of information with respect to a device of that facility when medical personnel who are employed by or otherwise formally affiliated with the facility receive or otherwise become aware of information with respect to that device in the course of their duties.
(2) The Secretary may not disclose the identity of a device user facility which makes a report under paragraph (1) except in connection with—
(A) an action brought to enforce
(B) a communication to a manufacturer of a device which is the subject of a report under paragraph (1).
This paragraph does not prohibit the Secretary from disclosing the identity of a device user facility making a report under paragraph (1) or any information in such a report to employees of the Department of Health and Human Services, to the Department of Justice, or to the duly authorized committees and subcommittees of the Congress.
(3) No report made under paragraph (1) by—
(A) a device user facility,
(B) an individual who is employed by or otherwise formally affiliated with such a facility, or
(C) a physician who is not required to make such a report,
shall be admissible into evidence or otherwise used in any civil action involving private parties unless the facility, individual, or physician who made the report had knowledge of the falsity of the information contained in the report.
(4) A report made under paragraph (1) does not affect any obligation of a manufacturer who receives the report to file a report as required under subsection (a) of this section.
(5) With respect to device user facilities:
(A) The Secretary shall by regulation plan and implement a program under which the Secretary limits user reporting under paragraphs (1) through (4) to a subset of user facilities that constitutes a representative profile of user reports for device deaths and serious illnesses or serious injuries.
(B) During the period of planning the program under subparagraph (A), paragraphs (1) through (4) continue to apply.
(C) During the period in which the Secretary is providing for a transition to the full implementation of the program, paragraphs (1) through (4) apply except to the extent that the Secretary determines otherwise.
(D) On and after the date on which the program is fully implemented, paragraphs (1) through (4) do not apply to a user facility unless the facility is included in the subset referred to in subparagraph (A).
(E) Not later than 2 years after November 21, 1997, the Secretary shall submit to the Committee on Commerce of the House of Representatives, and to the Committee on Labor and Human Resources of the Senate, a report describing the plan developed by the Secretary under subparagraph (A) and the progress that has been made toward the implementation of the plan.
(6) For purposes of this subsection:
(A) The term "device user facility" means a hospital, ambulatory surgical facility, nursing home, or outpatient treatment facility which is not a physician's office. The Secretary may by regulation include an outpatient diagnostic facility which is not a physician's office in such term.
(B) The terms "serious illness" and "serious injury" mean illness or injury, respectively, that—
(i) is life threatening,
(ii) results in permanent impairment of a body function or permanent damage to a body structure, or
(iii) necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure.
(c) Persons exempt
Subsection (a) of this section shall not apply to—
(1) any practitioner who is licensed by law to prescribe or administer devices intended for use in humans and who manufactures or imports devices solely for use in the course of his professional practice;
(2) any person who manufactures or imports devices intended for use in humans solely for such person's use in research or teaching and not for sale (including any person who uses a device under an exemption granted under
(3) any other class of persons as the Secretary may by regulation exempt from subsection (a) of this section upon a finding that compliance with the requirements of such subsection by such class with respect to a device is not necessary to (A) assure that a device is not adulterated or misbranded or (B) otherwise to assure its safety and effectiveness.
(d) Repealed. Pub. L. 105–115, title II, §213(a)(2), Nov. 21, 1997, 111 Stat. 2347
(e) Device tracking
(1) The Secretary may by order require a manufacturer to adopt a method of tracking a class II or class III device—
(A) the failure of which would be reasonably likely to have serious adverse health consequences; or
(B) which is—
(i) intended to be implanted in the human body for more than one year, or
(ii) a life sustaining or life supporting device used outside a device user facility.
(2) Any patient receiving a device subject to tracking under paragraph (1) may refuse to release, or refuse permission to release, the patient's name, address, social security number, or other identifying information for the purpose of tracking.
(f) Reports of removals and corrections
(1) Except as provided in paragraph (2), the Secretary shall by regulation require a manufacturer or importer of a device to report promptly to the Secretary any correction or removal of a device undertaken by such manufacturer or importer if the removal or correction was undertaken—
(A) to reduce a risk to health posed by the device, or
(B) to remedy a violation of this chapter caused by the device which may present a risk to health.
A manufacturer or importer of a device who undertakes a correction or removal of a device which is not required to be reported under this paragraph shall keep a record of such correction or removal.
(2) No report of the corrective action or removal of a device may be required under paragraph (1) if a report of the corrective action or removal is required and has been submitted under subsection (a) of this section.
(3) For purposes of paragraphs (1) and (2), the terms "correction" and "removal" do not include routine servicing.
(June 25, 1938, ch. 675, §519, as added
Amendments
1997—Subsec. (a).
Subsec. (a)(4).
Subsec. (a)(7).
Subsec. (a)(8).
Subsec. (a)(9).
Subsec. (b)(1)(C).
Subsec. (b)(2)(A).
Subsec. (b)(2)(B).
Subsec. (b)(2)(C).
Subsec. (b)(5), (6).
Subsec. (d).
"(1) the manufacturer, importer, or distributor did file a certain number of such reports, or
"(2) the manufacturer, importer, or distributor did not file any report under subsection (a) of this section."
Subsec. (e).
"(1) a device the failure of which would be reasonably likely to have serious adverse health consequences and which is (A) a permanently implantable device, or (B) a life sustaining or life supporting device used outside a device user facility, or
"(2) any other device which the Secretary may designate,
shall adopt a method of device tracking."
Subsec. (f)(1).
1993—Subsec. (a).
1992—Subsec. (a).
Subsec. (b)(1)(A).
Subsec. (b)(1)(B).
Subsec. (b)(5)(B)(iii).
1990—Subsec. (a)(6).
Subsecs. (b), (c).
Subsecs. (d), (e).
Subsec. (f).
Effective Date of 1997 Amendment
Section 211 of
Amendment by section 213(a), (c) of
Effective Date of 1992 Amendment
Section 2(b) of
Section 5(b) of
"(1) 1 year after the date of the enactment of this Act [June 16, 1992]; or
"(2) on the effective date of regulations of the Secretary to implement such amendments,
whichever occurs first."
Effective Date of 1990 Amendment
Section 2(c) of
"(1) upon the effective date of regulations promulgated under subsection (b) [set out below], or
"(2) upon the expiration of 12 months from the date of the enactment of this Act [Nov. 28, 1990],
whichever occurs first."
Section 3(a)(2) of
Section 3(b)(3) of
[For effective date of amendment by
Regulations
Section 2(b) of
Section 3(c) of
"(1)(A) Not later than 9 months after the date of the enactment of this Act [Nov. 28, 1990], the Secretary of Health and Human Services shall issue proposed regulations—
"(i) to require distributors of devices to establish and maintain records and to make reports (including reports required by part 803 of title 21 of the Code of Federal Regulations) under section 519(a)(6) of the Federal Food, Drug, and Cosmetic Act [
"(ii) to implement section 519(e) of such Act.
The Secretary may exempt from regulations described in clause (i) classes of distributors of class I and class II devices from whom reports are not necessary for the protection of the public health.
"(B) Regulations under subparagraph (A) shall—
"(i) require appropriate methods for maintenance of records to ensure that patients who receive devices can be provided the notification required by such Act [this chapter],
"(ii) require that manufacturers adopt effective methods of tracking devices,
"(iii) take into account the position of distributors in the device distribution process, and
"(iv) include such other requirements as the Secretary deems necessary for the adoption of an effective user tracking program under section 519(e) of such Act.
"(2) Not later than 18 months after the date of the enactment of this Act, the Secretary shall issue final regulations to implement sections [sic] 519(a)(6) of the Federal Food, Drug, and Cosmetic Act. If the Secretary does not promulgate such final regulations upon the expiration of such 18 months, the Congress finds that there is good cause for the proposed regulations to be considered as the final regulations without response to comment because the implementation of sections [sic] 519(a)(6) of such Act is essential to protect the health of patients who use such devices. Consequently, in such event, the proposed regulations issued under paragraph (1) shall become final regulations as of the expiration of such 18 months. There shall be promptly published in the Federal Register notice of the new status of the proposed regulations.
"(3) Not later than November 28, 1992, the Secretary shall issue final regulations to implement section 519(e) of the Federal Food, Drug, and Cosmetic Act. If the Secretary does not promulgate such final regulations by November 28, 1992, the Congress finds that there is good cause for the proposed regulations to be considered as the final regulations without response to comment because the implementation of section 519(e) of such Act is essential to protect the health of patients who use devices. In such event, the proposed regulations issued under paragraph (1) shall become the issued final regulations on November 29, 1992. There shall be promptly published in the Federal Register notice of the new status of the proposed regulations."
[For effective date of amendment by
Information Concerning Reporting Requirements for Device User Facilities
Section 2(d) of
Study of Reporting Requirements; Compliance by Device User Facilities; Actions by Manufacturers; Cost Effectiveness; Recommendations
Section 2(e) of
Report to Congress on Reporting Requirements for Device User Facilities
Section 2(f) of
Section Referred to in Other Sections
This section is referred to in
1 So in original. The word "and" probably should not appear.
§360j. General provisions respecting control of devices intended for human use
(a) General rule
Any requirement authorized by or under
(b) Custom devices
(A)(i) is intended for use by an individual patient named in such order of such physician or dentist (or other specially qualified person so designated) and is to be made in a specific form for such patient, or
(ii) is intended to meet the special needs of such physician or dentist (or other specially qualified person so designated) in the course of the professional practice of such physician or dentist (or other specially qualified person so designated), and
(B) is not generally available to or generally used by other physicians or dentists (or other specially qualified persons so designated).
(c) Trade secrets
Any information reported to or otherwise obtained by the Secretary or his representative under
(d) Notices and findings
Each notice of proposed rulemaking under
(1) the manner in which interested persons may examine data and other information on which the notice or findings is based, and
(2) the period within which interested persons may present their comments on the notice or findings (including the need therefor) orally or in writing, which period shall be at least sixty days but may not exceed ninety days unless the time is extended by the Secretary by a notice published in the Federal Register stating good cause therefor.
(e) Restricted devices
(1) The Secretary may by regulation require that a device be restricted to sale, distribution, or use—
(A) only upon the written or oral authorization of a practitioner licensed by law to administer or use such device, or
(B) upon such other conditions as the Secretary may prescribe in such regulation,
if, because of its potentiality for harmful effect or the collateral measures necessary to its use, the Secretary determines that there cannot otherwise be reasonable assurance of its safety and effectiveness. No condition prescribed under subparagraph (B) may restrict the use of a device to persons with specific training or experience in its use or to persons for use in certain facilities unless the Secretary determines that such a restriction is required for the safe and effective use of the device. No such condition may exclude a person from using a device solely because the person does not have the training or experience to make him eligible for certification by a certifying board recognized by the American Board of Medical Specialties or has not been certified by such a Board. A device subject to a regulation under this subsection is a restricted device.
(2) The label of a restricted device shall bear such appropriate statements of the restrictions required by a regulation under paragraph (1) as the Secretary may in such regulation prescribe.
(f) Good manufacturing practice requirements
(1)(A) The Secretary may, in accordance with subparagraph (B), prescribe regulations requiring that the methods used in, and the facilities and controls used for, the manufacture, pre-production design validation (including a process to assess the performance of a device but not including an evaluation of the safety or effectiveness of a device), packing, storage, and installation of a device conform to current good manufacturing practice, as prescribed in such regulations, to assure that the device will be safe and effective and otherwise in compliance with this chapter.
(B) Before the Secretary may promulgate any regulation under subparagraph (A) he shall—
(i) afford the advisory committee established under paragraph (3) an opportunity to submit recommendations to him with respect to the regulation proposed to be promulgated;
(ii) afford opportunity for an oral hearing; and
(iii) ensure that such regulation conforms, to the extent practicable, with internationally recognized standards defining quality systems, or parts of the standards, for medical devices.
The Secretary shall provide the advisory committee a reasonable time to make its recommendation with respect to proposed regulations under subparagraph (A).
(2)(A) Any person subject to any requirement prescribed by regulations under paragraph (1) may petition the Secretary for an exemption or variance from such requirement. Such a petition shall be submitted to the Secretary in such form and manner as he shall prescribe and shall—
(i) in the case of a petition for an exemption from a requirement, set forth the basis for the petitioner's determination that compliance with the requirement is not required to assure that the device will be safe and effective and otherwise in compliance with this chapter,
(ii) in the case of a petition for a variance from a requirement, set forth the methods proposed to be used in, and the facilities and controls proposed to be used for, the manufacture, packing, storage, and installation of the device in lieu of the methods, facilities, and controls prescribed by the requirement, and
(iii) contain such other information as the Secretary shall prescribe.
(B) The Secretary may refer to the advisory committee established under paragraph (3) any petition submitted under subparagraph (A). The advisory committee shall report its recommendations to the Secretary with respect to a petition referred to it within sixty days of the date of the petition's referral. Within sixty days after—
(i) the date the petition was submitted to the Secretary under subparagraph (A), or
(ii) if the petition was referred to an advisory committee, the expiration of the sixty-day period beginning on the date the petition was referred to the advisory committee,
whichever occurs later, the Secretary shall by order either deny the petition or approve it.
(C) The Secretary may approve—
(i) a petition for an exemption for a device from a requirement if he determines that compliance with such requirement is not required to assure that the device will be safe and effective and otherwise in compliance with this chapter, and
(ii) a petition for a variance for a device from a requirement if he determines that the methods to be used in, and the facilities and controls to be used for, the manufacture, packing, storage, and installation of the device in lieu of the methods, controls, and facilities prescribed by the requirement are sufficient to assure that the device will be safe and effective and otherwise in compliance with this chapter.
An order of the Secretary approving a petition for a variance shall prescribe such conditions respecting the methods used in, and the facilities and controls used for, the manufacture, packing, storage, and installation of the device to be granted the variance under the petition as may be necessary to assure that the device will be safe and effective and otherwise in compliance with this chapter.
(D) After the issuance of an order under subparagraph (B) respecting a petition, the petitioner shall have an opportunity for an informal hearing on such order.
(3) The Secretary shall establish an advisory committee for the purpose of advising and making recommendations to him with respect to regulations proposed to be promulgated under paragraph (1)(A) and the approval or disapproval of petitions submitted under paragraph (2). The advisory committee shall be composed of nine members as follows:
(A) Three of the members shall be appointed from persons who are officers or employees of any State or local government or of the Federal Government.
(B) Two of the members shall be appointed from persons who are representative of interests of the device manufacturing industry; two of the members shall be appointed from persons who are representative of the interests of physicians and other health professionals; and two of the members shall be representative of the interests of the general public.
Members of the advisory committee who are not officers or employees of the United States, while attending conferences or meetings of the committee or otherwise engaged in its business, shall be entitled to receive compensation at rates to be fixed by the Secretary, which rates may not exceed the daily equivalent of the rate in effect for grade GS–18 of the General Schedule, for each day (including traveltime) they are so engaged; and while so serving away from their homes or regular places of business each member may be allowed travel expenses, including per diem in lieu of subsistence, as authorized by
(g) Exemption for devices for investigational use
(1) It is the purpose of this subsection to encourage, to the extent consistent with the protection of the public health and safety and with ethical standards, the discovery and development of useful devices intended for human use and to that end to maintain optimum freedom for scientific investigators in their pursuit of that purpose.
(2)(A) The Secretary shall, within the one hundred and twenty-day period beginning on May 28, 1976, by regulation prescribe procedures and conditions under which devices intended for human use may upon application be granted an exemption from the requirements of
(B) The conditions prescribed pursuant to subparagraph (A) shall include the following:
(i) A requirement that an application be submitted to the Secretary before an exemption may be granted and that the application be submitted in such form and manner as the Secretary shall specify.
(ii) A requirement that the person applying for an exemption for a device assure the establishment and maintenance of such records, and the making of such reports to the Secretary of data obtained as a result of the investigational use of the device during the exemption, as the Secretary determines will enable him to assure compliance with such conditions, review the progress of the investigation, and evaluate the safety and effectiveness of the device.
(iii) Such other requirements as the Secretary may determine to be necessary for the protection of the public health and safety.
(C) Procedures and conditions prescribed pursuant to subparagraph (A) for an exemption may appropriately vary depending on (i) the scope and duration of clinical testing to be conducted under such exemption, (ii) the number of human subjects that are to be involved in such testing, (iii) the need to permit changes to be made in the device subject to the exemption during testing conducted in accordance with a clinical testing plan required under paragraph (3)(A), and (iv) whether the clinical testing of such device is for the purpose of developing data to obtain approval for the commercial distribution of such device.
(3) Procedures and conditions prescribed pursuant to paragraph (2)(A) shall require, as a condition to the exemption of any device to be the subject of testing involving human subjects, that the person applying for the exemption—
(A) submit a plan for any proposed clinical testing of the device and a report of prior investigations of the device (including, where appropriate, tests on animals) adequate to justify the proposed clinical testing—
(i) to the local institutional review committee which has been established in accordance with regulations of the Secretary to supervise clinical testing of devices in the facilities where the proposed clinical testing is to be conducted, or
(ii) to the Secretary, if—
(I) no such committee exists, or
(II) the Secretary finds that the process of review by such committee is inadequate (whether or not the plan for such testing has been approved by such committee),
for review for adequacy to justify the commencement of such testing; and, unless the plan and report are submitted to the Secretary, submit to the Secretary a summary of the plan and a report of prior investigations of the device (including, where appropriate, tests on animals);
(B) promptly notify the Secretary (under such circumstances and in such manner as the Secretary prescribes) of approval by a local institutional review committee of any clinical testing plan submitted to it in accordance with subparagraph (A);
(C) in the case of a device to be distributed to investigators for testing, obtain signed agreements from each of such investigators that any testing of the device involving human subjects will be under such investigator's supervision and in accordance with subparagraph (D) and submit such agreements to the Secretary; and
(D) assure that informed consent will be obtained from each human subject (or his representative) of proposed clinical testing involving such device, except where subject to such conditions as the Secretary may prescribe, the investigator conducting or supervising the proposed clinical testing of the device determines in writing that there exists a life threatening situation involving the human subject of such testing which necessitates the use of such device and it is not feasible to obtain informed consent from the subject and there is not sufficient time to obtain such consent from his representative.
The determination required by subparagraph (D) shall be concurred in by a licensed physician who is not involved in the testing of the human subject with respect to which such determination is made unless immediate use of the device is required to save the life of the human subject of such testing and there is not sufficient time to obtain such concurrence.
(4)(A) An application, submitted in accordance with the procedures prescribed by regulations under paragraph (2), for an exemption for a device (other than an exemption from
(B) The Secretary may disapprove an application only if he finds that the investigation with respect to which the application is submitted does not conform to procedures and conditions prescribed under regulations under paragraph (2). Such a notification shall contain the order of disapproval and a complete statement of the reasons for the Secretary's disapproval of the application and afford the applicant opportunity for an informal hearing on the disapproval order.
(5) The Secretary may by order withdraw an exemption granted under this subsection for a device if the Secretary determines that the conditions applicable to the device under this subsection for such exemption are not met. Such an order may be issued only after opportunity for an informal hearing, except that such an order may be issued before the provision of an opportunity for an informal hearing if the Secretary determines that the continuation of testing under the exemption with respect to which the order is to be issued will result in an unreasonable risk to the public health.
(6)(A) Not later than 1 year after November 21, 1997, the Secretary shall by regulation establish, with respect to a device for which an exemption under this subsection is in effect, procedures and conditions that, without requiring an additional approval of an application for an exemption or the approval of a supplement to such an application, permit—
(i) developmental changes in the device (including manufacturing changes) that do not constitute a significant change in design or in basic principles of operation and that are made in response to information gathered during the course of an investigation; and
(ii) changes or modifications to clinical protocols that do not affect—
(I) the validity of data or information resulting from the completion of an approved protocol, or the relationship of likely patient risk to benefit relied upon to approve a protocol;
(II) the scientific soundness of an investigational plan submitted under paragraph (3)(A); or
(III) the rights, safety, or welfare of the human subjects involved in the investigation.
(B) Regulations under subparagraph (A) shall provide that a change or modification described in such subparagraph may be made if—
(i) the sponsor of the investigation determines, on the basis of credible information (as defined by the Secretary) that the applicable conditions under subparagraph (A) are met; and
(ii) the sponsor submits to the Secretary, not later than 5 days after making the change or modification, a notice of the change or modification.
(7)(A) In the case of a person intending to investigate the safety or effectiveness of a class III device or any implantable device, the Secretary shall ensure that the person has an opportunity, prior to submitting an application to the Secretary or to an institutional review committee, to submit to the Secretary, for review, an investigational plan (including a clinical protocol). If the applicant submits a written request for a meeting with the Secretary regarding such review, the Secretary shall, not later than 30 days after receiving the request, meet with the applicant for the purpose of reaching agreement regarding the investigational plan (including a clinical protocol). The written request shall include a detailed description of the device, a detailed description of the proposed conditions of use of the device, a proposed plan (including a clinical protocol) for determining whether there is a reasonable assurance of effectiveness, and, if available, information regarding the expected performance from the device.
(B) Any agreement regarding the parameters of an investigational plan (including a clinical protocol) that is reached between the Secretary and a sponsor or applicant shall be reduced to writing and made part of the administrative record by the Secretary. Any such agreement shall not be changed, except—
(i) with the written agreement of the sponsor or applicant; or
(ii) pursuant to a decision, made in accordance with subparagraph (C) by the director of the office in which the device involved is reviewed, that a substantial scientific issue essential to determining the safety or effectiveness of the device involved has been identified.
(C) A decision under subparagraph (B)(ii) by the director shall be in writing, and may be made only after the Secretary has provided to the sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant are present and at which the director documents the scientific issue involved.
(h) Release of information respecting safety and effectiveness
(1) The Secretary shall promulgate regulations under which a detailed summary of information respecting the safety and effectiveness of a device which information was submitted to the Secretary and which was the basis for—
(A) an order under
(B) an order under
(C) an order approving an application under subsection (g) of this section for an exemption for the device from
shall be made available to the public upon issuance of the order. Summaries of information made available pursuant to this paragraph respecting a device shall include information respecting any adverse effects on health of the device.
(2) The Secretary shall promulgate regulations under which each advisory committee established under
(3) Except as provided in paragraph (4), any information respecting a device which is made available pursuant to paragraph (1) or (2) of this subsection (A) may not be used to establish the safety or effectiveness of another device for purposes of this chapter by any person other than the person who submitted the information so made available, and (B) shall be made available subject to subsection (c) of this section.
(4)(A) Any information contained in an application for premarket approval filed with the Secretary pursuant to
(i) approving another device;
(ii) determining whether a product development protocol has been completed, under
(iii) establishing a performance standard or special control under this chapter; or
(iv) classifying or reclassifying another device under
(B) The publicly available detailed summaries of information respecting the safety and effectiveness of devices required by paragraph (1)(A) shall be available for use by the Secretary as the evidentiary basis for the agency actions described in subparagraph (A).
(i) Proceedings of advisory panels and committees
Each panel under
(j) Traceability
Except as provided in
(k) Research and development
The Secretary may enter into contracts for research, testing, and demonstrations respecting devices and may obtain devices for research, testing, and demonstration purposes without regard to section 3324(a) and (b) of title 31 and
(l) Transitional provisions for devices considered as new drugs
(1) Any device intended for human use—
(A) for which on May 28, 1976 (hereinafter in this subsection referred to as the "enactment date") an approval of an application submitted under
(B) for which such an application was filed on or before the enactment date and with respect to which application no order of approval or refusing to approve had been issued on such date under subsection (c) or (d) of such section;
(C) for which on the enactment date an exemption under subsection (i) of such section was in effect;
(D) which is within a type of device described in subparagraph (A), (B), or (C) and is substantially equivalent to another device within that type;
(E) which the Secretary in a notice published in the Federal Register before the enactment date has declared to be a new drug subject to
(F) with respect to which on the enactment date an action is pending in a United States court under
is classified in class III unless the Secretary in response to a petition submitted under paragraph (2) has classified such device in class I or II.
(2) The Secretary may initiate the reclassification of a device classified into class III under paragraph (1) of this subsection or the manufacturer or importer of a device classified under paragraph (1) may petition the Secretary (in such form and manner as he shall prescribe) for the issuance of an order classifying the device in class I or class II. Within thirty days of the filing of such a petition, the Secretary shall notify the petitioner of any deficiencies in the petition which prevent the Secretary from making a decision on the petition. Except as provided in paragraph (3)(D)(ii), within one hundred and eighty days after the filing of a petition under this paragraph, the Secretary shall, after consultation with the appropriate panel under
(3)(A) In the case of a device which is described in paragraph (1)(A) and which is in class III—
(i) such device shall on the enactment date be considered a device with an approved application under
(ii) the requirements applicable to such device before the enactment date under
(B) In the case of a device which is described in paragraph (1)(B) and which is in class III, an application for such device shall be considered as having been filed under
(C) A device which is described in paragraph (1)(C) and which is in class III shall be considered a new drug until the expiration of the ninety-day period beginning on the date of the promulgation of regulations under subsection (g) of this section. After the expiration of such period such device is required, unless exempt under subsection (g) of this section, to have in effect an approved application under
(D)(i) Except as provided in clauses (ii) and (iii), a device which is described in subparagraph (D), (E), or (F) of paragraph (1) and which is in class III is required, unless exempt under subsection (g) of this section, to have on and after sixty days after the enactment date in effect an approved application under
(ii) If—
(I) a petition is filed under paragraph (2) for a device described in subparagraph (D), (E), or (F) of paragraph (1), or
(II) an application for premarket approval is filed under
within the sixty-day period beginning on the enactment date (or within such greater period as the Secretary, after making the finding required under
(iii) In the case of a device which is described in subparagraph (E) of paragraph (1), which the Secretary in a notice published in the Federal Register after March 31, 1976, declared to be a new drug subject to
(I) the device shall, after eighteen months after the enactment date, have in effect an approved application under
(II) the Secretary may, during the period beginning one hundred and eighty days after the enactment date and ending eighteen months after such date, restrict the use of the device to investigational use by experts qualified by scientific training and experience to investigate the safety and effectiveness of such device, and to investigational use in accordance with the requirements applicable under regulations under subsection (g) of this section to investigational use of devices granted an exemption under such subsection.
If the requirements under subsection (g) of this section are made applicable to the investigational use of such a device, they shall be made applicable in such a manner that the device shall be made reasonably available to physicians meeting appropriate qualifications prescribed by the Secretary.
(4) Repealed.
(5)(A) Before December 1, 1991, the Secretary shall by order require manufacturers of devices described in paragraph (1), which are subject to revision of classification under subparagraph (B), to submit to the Secretary a summary of and citation to any information known or otherwise available to the manufacturers respecting the devices, including adverse safety or effectiveness information which has not been submitted under
(B) Except as provided in subparagraph (C), after the issuance of an order under subparagraph (A) but before December 1, 1992, the Secretary shall publish a regulation in the Federal Register for each device which is classified in class III under paragraph (1) revising the classification of the device so that the device is classified into class I or class II, unless the regulation requires the device to remain in class III. In determining whether to revise the classification of a device or to require a device to remain in class III, the Secretary shall apply the criteria set forth in
(C) The Secretary may by notice published in the Federal Register extend the period prescribed by subparagraph (B) for a device for an additional period not to exceed 1 year.
(m) Humanitarian device exemption
(1) To the extent consistent with the protection of the public health and safety and with ethical standards, it is the purpose of this subsection to encourage the discovery and use of devices intended to benefit patients in the treatment and diagnosis of diseases or conditions that affect fewer than 4,000 individuals in the United States.
(2) The Secretary may grant a request for an exemption from the effectiveness requirements of
(A) the device is designed to treat or diagnose a disease or condition that affects fewer than 4,000 individuals in the United States,
(B) the device would not be available to a person with a disease or condition referred to in subparagraph (A) unless the Secretary grants such an exemption and there is no comparable device, other than under this exemption, available to treat or diagnose such disease or condition, and
(C) the device will not expose patients to an unreasonable or significant risk of illness or injury and the probable benefit to health from the use of the device outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.
The request shall be in the form of an application submitted to the Secretary. Not later than 75 days after the date of the receipt of the application, the Secretary shall issue an order approving or denying the application.
(3) No person granted an exemption under paragraph (2) with respect to a device may sell the device for an amount that exceeds the costs of research and development, fabrication, and distribution of the device.
(4) Devices granted an exemption under paragraph (2) may only be used—
(A) in facilities that have established, in accordance with regulations of the Secretary, a local institutional review committee to supervise clinical testing of devices in the facilities, and
(B) if, before the use of a device, an institutional review committee approves the use in the treatment or diagnosis of a disease or condition referred to in paragraph (2)(A), unless a physician determines in an emergency situation that approval from a local institutional review committee can not be obtained in time to prevent serious harm or death to a patient.
In a case described in subparagraph (B) in which a physician uses a device without an approval from an institutional review committee, the physician shall, after the use of the device, notify the chairperson of the local institutional review committee of such use. Such notification shall include the identification of the patient involved, the date on which the device was used, and the reason for the use.
(5) The Secretary may require a person granted an exemption under paragraph (2) to demonstrate continued compliance with the requirements of this subsection if the Secretary believes such demonstration to be necessary to protect the public health or if the Secretary has reason to believe that the criteria for the exemption are no longer met.
(6) The Secretary may suspend or withdraw an exemption from the effectiveness requirements of
(June 25, 1938, ch. 675, §520, as added
References in Text
Section 14 of the Federal Advisory Committee Act, referred to in subsec. (f)(3), is section 14 of
Codification
In subsec. (k), "section 3324(a) and (b) of title 31" substituted for reference to section 3648 of the Revised Statutes (
Amendments
1997—Subsec. (f)(1)(B)(iii).
Subsec. (g)(6), (7).
Subsec. (h)(4).
Subsec. (l).
Subsec. (l)(4).
"(A) In the case of such a device which is classified into class I, such requirements shall apply to such device until the effective date of the regulation classifying the device into such class.
"(B) In the case of such a device which is classified into class II, such requirements shall apply to such device until the effective date of a performance standard applicable to the device under
"(C) In the case of such a device which is classified into class III, such requirements shall apply to such device until the date on which the device is required to have in effect an approved application under
Subsec. (m)(2).
Subsec. (m)(4).
Subsec. (m)(4)(B).
Subsec. (m)(5).
Subsec. (m)(6).
1992—Subsec. (g)(2)(A).
1990—Subsec. (c).
Subsec. (f)(1)(A).
Subsec. (h)(3).
Subsec. (h)(4).
Subsec. (i).
Subsec. (j).
Subsec. (l)(2).
Subsec. (l)(5).
Subsec. (m).
Effective Date of 1997 Amendment
Amendment by sections 201(a), 203, 216(a)(1), and 410(a) of
Effective Date of 1990 Amendment
Section 14(b) of
Report on Humanitarian Device Exemptions
Section 14(c) of
References in Other Laws to GS–16, 17, or 18 Pay Rates
References in laws to the rates of pay for GS–16, 17, or 18, or to maximum rates of pay under the General Schedule, to be considered references to rates payable under specified sections of Title 5, Government Organization and Employees, see section 529 [title I, §101(c)(1)] of
Section Referred to in Other Sections
This section is referred to in
§360k. State and local requirements respecting devices
(a) General rule
Except as provided in subsection (b) of this section, no State or political subdivision of a State may establish or continue in effect with respect to a device intended for human use any requirement—
(1) which is different from, or in addition to, any requirement applicable under this chapter to the device, and
(2) which relates to the safety or effectiveness of the device or to any other matter included in a requirement applicable to the device under this chapter.
(b) Exempt requirements
Upon application of a State or a political subdivision thereof, the Secretary may, by regulation promulgated after notice and opportunity for an oral hearing, exempt from subsection (a) of this section, under such conditions as may be prescribed in such regulation, a requirement of such State or political subdivision applicable to a device intended for human use if—
(1) the requirement is more stringent than a requirement under this chapter which would be applicable to the device if an exemption were not in effect under this subsection; or
(2) the requirement—
(A) is required by compelling local conditions, and
(B) compliance with the requirement would not cause the device to be in violation of any applicable requirement under this chapter.
(June 25, 1938, ch. 675, §521, as added
Section Referred to in Other Sections
This section is referred to in
§360l. Postmarket surveillance
(a) In general
The Secretary may by order require a manufacturer to conduct postmarket surveillance for any device of the manufacturer which is a class II or class III device the failure of which would be reasonably likely to have serious adverse health consequences or which is intended to be—
(1) implanted in the human body for more than one year, or
(2) a life sustaining or life supporting device used outside a device user facility.
(b) Surveillance approval
Each manufacturer required to conduct a surveillance of a device shall, within 30 days of receiving an order from the Secretary prescribing that the manufacturer is required under this section to conduct such surveillance, submit, for the approval of the Secretary, a plan for the required surveillance. The Secretary, within 60 days of the receipt of such plan, shall determine if the person designated to conduct the surveillance has appropriate qualifications and experience to undertake such surveillance and if the plan will result in the collection of useful data that can reveal unforeseen adverse events or other information necessary to protect the public health. The Secretary, in consultation with the manufacturer, may by order require a prospective surveillance period of up to 36 months. Any determination by the Secretary that a longer period is necessary shall be made by mutual agreement between the Secretary and the manufacturer or, if no agreement can be reached, after the completion of a dispute resolution process as described in
(June 25, 1938, ch. 675, §522, as added
Amendments
1997—
1992—Subsec. (b).
Effective Date of 1997 Amendment
Section 212 of
Section Referred to in Other Sections
This section is referred to in
§360m. Accredited persons
(a) In general
(1) Review and classification of devices
Not later than 1 year after November 21, 1997, the Secretary shall, subject to paragraph (3), accredit persons for the purpose of reviewing reports submitted under
(2) Requirements regarding review
(A) In general
In making a recommendation to the Secretary under paragraph (1), an accredited person shall notify the Secretary in writing of the reasons for the recommendation.
(B) Time period for review
Not later than 30 days after the date on which the Secretary is notified under subparagraph (A) by an accredited person with respect to a recommendation of an initial classification of a device, the Secretary shall make a determination with respect to the initial classification.
(C) Special rule
The Secretary may change the initial classification under
(3) Certain devices
(A) In general
An accredited person may not be used to perform a review of—
(i) a class III device;
(ii) a class II device which is intended to be permanently implantable or life sustaining or life supporting; or
(iii) a class II device which requires clinical data in the report submitted under
(B) Adjustment
In determining for a year the ratio described in subparagraph (A)(iii), the Secretary shall not include in the numerator class III devices that the Secretary reclassified into class II, and the Secretary shall include in the denominator class II devices for which reports under
(b) Accreditation
(1) Programs
The Secretary shall provide for such accreditation through programs administered by the Food and Drug Administration, other government agencies, or by other qualified nongovernment organizations.
(2) Accreditation
(A) In general
Not later than 180 days after November 21, 1997, the Secretary shall establish and publish in the Federal Register criteria to accredit or deny accreditation to persons who request to perform the duties specified in subsection (a) of this section. The Secretary shall respond to a request for accreditation within 60 days of the receipt of the request. The accreditation of such person shall specify the particular activities under subsection (a) of this section for which such person is accredited.
(B) Withdrawal of accreditation
The Secretary may suspend or withdraw accreditation of any person accredited under this paragraph, after providing notice and an opportunity for an informal hearing, when such person is substantially not in compliance with the requirements of this section or poses a threat to public health or fails to act in a manner that is consistent with the purposes of this section.
(C) Performance auditing
To ensure that persons accredited under this section will continue to meet the standards of accreditation, the Secretary shall—
(i) make onsite visits on a periodic basis to each accredited person to audit the performance of such person; and
(ii) take such additional measures as the Secretary determines to be appropriate.
(D) Annual report
The Secretary shall include in the annual report required under
(3) Qualifications
An accredited person shall, at a minimum, meet the following requirements:
(A) Such person may not be an employee of the Federal Government.
(B) Such person shall be an independent organization which is not owned or controlled by a manufacturer, supplier, or vendor of devices and which has no organizational, material, or financial affiliation with such a manufacturer, supplier, or vendor.
(C) Such person shall be a legally constituted entity permitted to conduct the activities for which it seeks accreditation.
(D) Such person shall not engage in the design, manufacture, promotion, or sale of devices.
(E) The operations of such person shall be in accordance with generally accepted professional and ethical business practices and shall agree in writing that as a minimum it will—
(i) certify that reported information accurately reflects data reviewed;
(ii) limit work to that for which competence and capacity are available;
(iii) treat information received, records, reports, and recommendations as proprietary information;
(iv) promptly respond and attempt to resolve complaints regarding its activities for which it is accredited; and
(v) protect against the use, in carrying out subsection (a) of this section with respect to a device, of any officer or employee of the person who has a financial conflict of interest regarding the device, and annually make available to the public disclosures of the extent to which the person, and the officers and employees of the person, have maintained compliance with requirements under this clause relating to financial conflicts of interest.
(4) Selection of accredited persons
The Secretary shall provide each person who chooses to use an accredited person to receive a
(5) Compensation of accredited persons
Compensation for an accredited person shall be determined by agreement between the accredited person and the person who engages the services of the accredited person, and shall be paid by the person who engages such services.
(c) Duration
The authority provided by this section terminates—
(1) 5 years after the date on which the Secretary notifies Congress that at least 2 persons accredited under subsection (b) of this section are available to review at least 60 percent of the submissions under
(2) 4 years after the date on which the Secretary notifies Congress that the Secretary has made a determination described in paragraph (2)(B) of subsection (a) of this section for at least 35 percent of the devices that are subject to review under paragraph (1) of such subsection,
whichever occurs first.
(June 25, 1938, ch. 675, §523, as added
Effective Date
Section effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of
Reports on Program of Accreditation
Section 210(d) of
"(1)
"(A)
"(B)
"(2)
Section Referred to in Other Sections
This section is referred to in
Part B—Drugs for Rare Diseases or Conditions
Part Referred to in Other Sections
This part is referred to in title 42 sections 236, 1395l.
§360aa. Recommendations for investigations of drugs for rare diseases or conditions
(a) Request by sponsor; response by Secretary
The sponsor of a drug for a disease or condition which is rare in the States may request the Secretary to provide written recommendations for the non-clinical and clinical investigations which must be conducted with the drug before—
(1) it may be approved for such disease or condition under
(2) if the drug is a biological product, it may be licensed for such disease or condition under
If the Secretary has reason to believe that a drug for which a request is made under this section is a drug for a disease or condition which is rare in the States, the Secretary shall provide the person making the request written recommendations for the non-clinical and clinical investigations which the Secretary believes, on the basis of information available to the Secretary at the time of the request under this section, would be necessary for approval of such drug for such disease or condition under
(b) Regulations
The Secretary shall by regulation promulgate procedures for the implementation of subsection (a) of this section.
(June 25, 1938, ch. 675, §525, as added
Amendments
1997—Subsec. (a).
Subsec. (a)(1) to (3).
1985—Subsec. (a).
Effective Date of 1985 Amendment
Section 8 of
"(a)
"(b)
Study
Congressional Findings
Section 1(b) of
"(1) there are many diseases and conditions, such as Huntington's disease, myoclonus, ALS (Lou Gehrig's disease), Tourette syndrome, and muscular dystrophy which affect such small numbers of individuals residing in the United States that the diseases and conditions are considered rare in the United States;
"(2) adequate drugs for many of such diseases and conditions have not been developed;
"(3) drugs for these diseases and conditions are commonly referred to as 'orphan drugs';
"(4) because so few individuals are affected by any one rare disease or condition, a pharmaceutical company which develops an orphan drug may reasonably expect the drug to generate relatively small sales in comparison to the cost of developing the drug and consequently to incur a financial loss;
"(5) there is reason to believe that some promising orphan drugs will not be developed unless changes are made in the applicable Federal laws to reduce the costs of developing such drugs and to provide financial incentives to develop such drugs; and
"(6) it is in the public interest to provide such changes and incentives for the development of orphan drugs."
§360bb. Designation of drugs for rare diseases or conditions
(a) Request by sponsor; preconditions; "rare disease or condition" defined
(1) The manufacturer or the sponsor of a drug may request the Secretary to designate the drug as a drug for a rare disease or condition. A request for designation of a drug shall be made before the submission of an application under
(A) if an application for such drug is approved under
(B) if a license for such drug is issued under
the approval, certification, or license would be for use for such disease or condition, the Secretary shall designate the drug as a drug for such disease or condition. A request for a designation of a drug under this subsection shall contain the consent of the applicant to notice being given by the Secretary under subsection (b) of this section respecting the designation of the drug.
(2) For purposes of paragraph (1), the term "rare disease or condition" means any disease or condition which (A) affects less than 200,000 persons in the United States, or (B) affects more than 200,000 in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from sales in the United States of such drug. Determinations under the preceding sentence with respect to any drug shall be made on the basis of the facts and circumstances as of the date the request for designation of the drug under this subsection is made.
(b) Notification of discontinuance of drug or application as condition
A designation of a drug under subsection (a) of this section shall be subject to the condition that—
(1) if an application was approved for the drug under
(2) if an application has not been approved for the drug under
(c) Notice to public
Notice respecting the designation of a drug under subsection (a) of this section shall be made available to the public.
(d) Regulations
The Secretary shall by regulation promulgate procedures for the implementation of subsection (a) of this section.
(June 25, 1938, ch. 675, §526, as added
Amendments
1997—Subsec. (a)(1).
Subsec. (b)(1).
Subsec. (b)(2).
1988—Subsec. (a)(1).
Subsecs. (b) to (d).
1985—Subsec. (a)(1).
1984—Subsec. (a)(2).
Effective Date of 1985 Amendment
Amendment by
Section Referred to in Other Sections
This section is referred to in
§360cc. Protection for drugs for rare diseases or conditions
(a) Exclusive approval, certification, or license
Except as provided in subsection (b) of this section, if the Secretary—
(1) approves an application filed pursuant to
(2) issues a license under
for a drug designated under
(b) Exceptions
If an application filed pursuant to
(1) the Secretary finds, after providing the holder notice and opportunity for the submission of views, that in such period the holder of the approved application or of the license cannot assure the availability of sufficient quantities of the drug to meet the needs of persons with the disease or condition for which the drug was designated; or
(2) such holder provides the Secretary in writing the consent of such holder for the approval of other applications or the issuance of other licenses before the expiration of such seven-year period.
(June 25, 1938, ch. 675, §527, as added
Amendments
1997—Subsec. (a).
Subsec. (b).
Subsec. (b)(1).
Subsec. (b)(2).
1993—Subsec. (b).
1985—
Subsec. (a).
Subsec. (b).
1984—Subsecs. (a), (b).
Effective Date of 1985 Amendment
Amendment by
Section Referred to in Other Sections
This section is referred to in
§360dd. Open protocols for investigations of drugs for rare diseases or conditions
If a drug is designated under
(June 25, 1938, ch. 675, §528, as added
§360ee. Grants and contracts for development of drugs for rare diseases and conditions
(a) Authority of Secretary
The Secretary may make grants to and enter into contracts with public and private entities and individuals to assist in (1) defraying the costs of qualified testing expenses incurred in connection with the development of drugs for rare diseases and conditions, (2) defraying the costs of developing medical devices for rare diseases or conditions, and (3) defraying the costs of developing medical foods for rare diseases or conditions.
(b) Definitions
For purposes of subsection (a) of this section:
(1) The term "qualified testing" means—
(A) human clinical testing—
(i) which is carried out under an exemption for a drug for a rare disease or condition under
(ii) which occurs after the date such drug is designated under
(B) preclinical testing involving a drug for a rare disease or condition which occurs after the date such drug is designated under
(2) The term "rare disease or condition" means (1) in the case of a drug, any disease or condition which (A) affects less than 200,000 persons in the United States, or (B) affects more than 200,000 in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from sales in the United States of such drug, (2) in the case of a medical device, any disease or condition that occurs so infrequently in the United States that there is no reasonable expectation that a medical device for such disease or condition will be developed without assistance under subsection (a) of this section, and (3) in the case of a medical food, any disease or condition that occurs so infrequently in the United States that there is no reasonable expectation that a medical food for such disease or condition will be developed without assistance under subsection (a) of this section. Determinations under the preceding sentence with respect to any drug shall be made on the basis of the facts and circumstances as of the date the request for designation of the drug under
(3) The term "medical food" means a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.
(c) Authorization of appropriations
For grants and contracts under subsection (a) of this section there are authorized to be appropriated $10,000,000 for fiscal year 1988, $12,000,000 for fiscal year 1989,1 $14,000,000 for fiscal year 1990.
(
Codification
Section was enacted as part of the Orphan Drug Act, and not as part of the Federal Food, Drug, and Cosmetic Act which comprises this chapter.
Amendments
1997—Subsec. (b)(1)(A)(ii), (B).
1988—Subsec. (a).
Subsec. (b)(2).
Subsec. (b)(3).
Subsec. (c).
1985—Subsec. (a).
Subsec. (b)(1).
Subsec. (c).
1984—Subsec. (b)(2).
Effective Date of 1985 Amendment
Amendment by
Section Referred to in Other Sections
This section is referred to in
1 So in original. Probably should be followed by "and".
Part C—Electronic Product Radiation Control
Codification
This part was classified to subpart 3 (§263c et seq.) of part F of subchapter II of
Part Referred to in Other Sections
This part is referred to in title 15 section 2080.
§360hh. Definitions
As used in this part—
(1) the term "electronic product radiation" means—
(A) any ionizing or non-ionizing electromagnetic or particulate radiation, or
(B) any sonic, infrasonic, or ultrasonic wave, which is emitted from an electronic product as the result of the operation of an electronic circuit in such product;
(2) the term "electronic product" means (A) any manufactured or assembled product which, when in operation, (i) contains or acts as part of an electronic circuit and (ii) emits (or in the absence of effective shielding or other controls would emit) electronic product radiation, or (B) any manufactured or assembled article which is intended for use as a component, part, or accessory of a product described in clause (A) and which when in operation emits (or in the absence of effective shielding or other controls would emit) such radiation;
(3) the term "manufacturer" means any person engaged in the business of manufacturing, assembling, or importing of electronic products;
(4) the term "commerce" means (A) commerce between any place in any State and any place outside thereof; and (B) commerce wholly within the District of Columbia; and
(5) the term "State" includes the District of Columbia, the Commonwealth of Puerto Rico, the Northern Mariana Islands, the Virgin Islands, Guam, and American Samoa.
(June 25, 1938, ch. 675, §531, formerly act July 1, 1944, ch. 373, title III, §531, formerly §355, as added
Codification
Section was classified to
Amendments
1993—
1990—
1976—Par. (5).
Short Title
For short title of
Transfer of Subpart; Construction
Section 19(c) of
Definition of "Secretary" and "Department"
Section 3 of
Noninterference With Other Federal Agencies
Section 4 of
Section Referred to in Other Sections
This section is referred to in
§360ii. Program of control
(a) Establishment
The Secretary shall establish and carry out an electronic product radiation control program designed to protect the public health and safety from electronic product radiation. As a part of such program, he shall—
(1) pursuant to
(2) plan, conduct, coordinate, and support research, development, training, and operational activities to minimize the emissions of and the exposure of people to, unnecessary electronic product radiation;
(3) maintain liaison with and receive information from other Federal and State departments and agencies with related interests, professional organizations, industry, industry and labor associations, and other organizations on present and future potential electronic product radiation;
(4) study and evaluate emissions of, and conditions of exposure to, electronic product radiation and intense magnetic fields;
(5) develop, test, and evaluate the effectiveness of procedures and techniques for minimizing exposure to electronic product radiation; and
(6) consult and maintain liaison with the Secretary of Commerce, the Secretary of Defense, the Secretary of Labor, the Atomic Energy Commission, and other appropriate Federal departments and agencies on (A) techniques, equipment, and programs for testing and evaluating electronic product radiation, and (B) the development of performance standards pursuant to
(b) Powers of Secretary
In carrying out the purposes of subsection (a) of this section, the Secretary is authorized to—
(1)(A) collect and make available, through publications and other appropriate means, the results of, and other information concerning, research and studies relating to the nature and extent of the hazards and control of electronic product radiation; and (B) make such recommendations relating to such hazards and control as he considers appropriate;
(2) make grants to public and private agencies, organizations, and institutions, and to individuals for the purposes stated in paragraphs (2), (4), and (5) of subsection (a) of this section;
(3) contract with public or private agencies, institutions, and organizations, and with individuals, without regard to
(4) procure (by negotiation or otherwise) electronic products for research and testing purposes, and sell or otherwise dispose of such products.
(c) Record keeping
(1) Each recipient of assistance under this part pursuant to grants or contracts entered into under other than competitive bidding procedures shall keep such records as the Secretary shall prescribe, including records which fully disclose the amount and disposition by such recipient of the proceeds of such assistance, the total cost of the project or undertaking in connection with which such assistance is given or used, and the amount of that portion of the cost of the project or undertaking supplied by other sources, and such other records as will facilitate an effective audit.
(2) The Secretary and the Comptroller General of the United States, or any of their duly authorized representatives, shall have access for the purpose of audit and examination to any books, documents, papers, and records of the recipients that are pertinent to the grants or contracts entered into under this part under other than competitive bidding procedures.
(June 25, 1938, ch. 675, §532, formerly act July 1, 1944, ch. 373, title III, §532, formerly §356, as added
Codification
Section was classified to
Amendments
1993—
1990—Subsec. (a)(1), (6).
Subsec. (b)(3).
Subsec. (c)(1), (2).
Transfer of Functions
Atomic Energy Commission abolished and functions transferred by
Noninterference With Other Federal Agencies
Enactment of this section not to be construed to supersede or limit the functions under any other provision of law or any officer or agency of the United States, see section 4 of
§360jj. Studies by Secretary
(a) Report to Congress
The Secretary shall conduct the following studies, and shall make a report or reports of the results of such studies to the Congress on or before January 1, 1970, and from time to time thereafter as he may find necessary, together with such recommendations for legislation as he may deem appropriate:
(1) A study of present State and Federal control of health hazards from electronic product radiation and other types of ionizing radiation, which study shall include, but not be limited to—
(A) control of health hazards from radioactive materials other than materials regulated under the Atomic Energy Act of 1954 [
(B) any gaps and inconsistencies in present controls;
(C) the need for controlling the sale of certain used electronic products, particularly antiquated X-ray equipment, without upgrading such products to meet the standards for new products or separate standards for used products;
(D) measures to assure consistent and effective control of the aforementioned health hazards;
(E) measures to strengthen radiological health programs of State governments; and
(F) the feasibility of authorizing the Secretary to enter into arrangements with individual States or groups of States to define their respective functions and responsibilities for the control of electronic product radiation and other ionizing radiation;
(2) A study to determine the necessity for the development of standards for the use of nonmedical electronic products for commercial and industrial purposes; and
(3) A study of the development of practicable procedures for the detection and measurement of electronic product radiation which may be emitted from electronic products manufactured or imported prior to the effective date of any applicable standard established pursuant to this part.
(b) Participation of other Federal agencies
In carrying out these studies, the Secretary shall invite the participation of other Federal departments and agencies having related responsibilities and interests, State governments—particularly those of States which regulate radioactive materials under section 274 of the Atomic Energy Act of 1954, as amended [
(c) Organization of studies and participation
The Secretary or his designee shall organize the studies and the participation of the invited participants as he deems best. Any dissent from the findings and recommendations of the Secretary shall be included in the report if so requested by the dissenter.
(June 25, 1938, ch. 675, §533, formerly act July 1, 1944, ch. 373, title III, §533, formerly §357, as added
References in Text
The Atomic Energy Act of 1954, referred to in subsec. (a)(1)(A), is act Aug. 1, 1946, ch. 724, as added by act Aug. 30, 1954, ch. 1073, §1,
Codification
Section was classified to
Amendments
1993—
1990—Subsec. (a)(3).
Noninterference With Other Federal Agencies
Enactment of this section not to be construed to supersede or limit the functions under any other provision of law of any officer or agency of the United States, see section 4 of
§360kk. Performance standards for electronic products
(a) Promulgation of regulations
(1) The Secretary shall by regulation prescribe performance standards for electronic products to control the emission of electronic product radiation from such products if he determines that such standards are necessary for the protection of the public health and safety. Such standards may include provisions for the testing of such products and the measurement of their electronic product radiation emissions, may require the attachment of warning signs and labels, and may require the provision of instructions for the installation, operation, and use of such products. Such standards may be prescribed from time to time whenever such determinations are made, but the first of such standards shall be prescribed prior to January 1, 1970. In the development of such standards, the Secretary shall consult with Federal and State departments and agencies having related responsibilities or interests and with appropriate professional organizations and interested persons, including representatives of industries and labor organizations which would be affected by such standards, and shall give consideration to—
(A) the latest available scientific and medical data in the field of electronic product radiation;
(B) the standards currently recommended by (i) other Federal agencies having responsibilities relating to the control and measurement of electronic product radiation, and (ii) public or private groups having an expertise in the field of electronic product radiation;
(C) the reasonableness and technical feasibility of such standards as applied to a particular electronic product;
(D) the adaptability of such standards to the need for uniformity and reliability of testing and measuring procedures and equipment; and
(E) in the case of a component, or accessory described in paragraph (2)(B) of
(2) The Secretary may prescribe different and individual performance standards, to the extent appropriate and feasible, for different electronic products so as to recognize their different operating characteristics and uses.
(3) The performance standards prescribed under this section shall not apply to any electronic product which is intended solely for export if (A) such product and the outside of any shipping container used in the export of such product are labeled or tagged to show that such product is intended for export, and (B) such product meets all the applicable requirements of the country to which such product is intended for export.
(4) The Secretary may by regulation amend or revoke any performance standard prescribed under this section.
(5) The Secretary may exempt from the provisions of this section any electronic product intended for use by departments or agencies of the United States provided such department or agency has prescribed procurement specifications governing emissions of electronic product radiation and provided further that such product is of a type used solely or predominantly by departments or agencies of the United States.
(b) Administrative procedure
The provisions of subchapter II of
(c) Publication in Federal Register
Each regulation prescribing, amending, or revoking a standard shall specify the date on which it shall take effect which, in the case of any regulation prescribing, or amending any standard, may not be sooner than one year or not later than two years after the date on which such regulation is issued, unless the Secretary finds, for good cause shown, that an earlier or later effective date is in the public interest and publishes in the Federal Register his reason for such finding, in which case such earlier or later date shall apply.
(d) Judicial review
(1) In a case of actual controversy as to the validity of any regulation issued under this section prescribing, amending, or revoking a performance standard, any person who will be adversely affected by such regulation when it is effective may at any time prior to the sixtieth day after such regulation is issued file a petition with the United States court of appeals for the circuit wherein such person resides or has his principal place of business, for a judicial review of such regulation. A copy of the petition shall be forthwith transmitted by the clerk of the court to the Secretary or other officer designated by him for that purpose. The Secretary thereupon shall file in the court the record of the proceedings on which the Secretary based the regulation, as provided in
(2) If the petitioner applies to the court for leave to adduce additional evidence, and shows to the satisfaction of the court that such additional evidence is material and that there were reasonable grounds for the failure to adduce such evidence in the proceeding before the Secretary, the court may order such additional evidence (and evidence in rebuttal thereof) to be taken before the Secretary, and to be adduced upon the hearing, in such manner and upon such terms and conditions as to the court may seem proper. The Secretary may modify his findings, or make new findings, by reason of the additional evidence so taken, and he shall file such modified or new findings, and his recommendations, if any, for the modification or setting aside of his original regulation, with the return of such additional evidence.
(3) Upon the filing of the petition referred to in paragraph (1) of this subsection, the court shall have jurisdiction to review the regulation in accordance with
(4) The judgment of the court affirming or setting aside, in whole or in part, any such regulation of the Secretary shall be final, subject to review by the Supreme Court of the United States upon certiorari or certification as provided in
(5) Any action instituted under this subsection shall survive, notwithstanding any change in the person occupying the office of Secretary or any vacancy in such office.
(6) The remedies provided for in this subsection shall be in addition to and not substitution for any other remedies provided by law.
(e) Availability of record
A certified copy of the transcript of the record and administrative proceedings under this section shall be furnished by the Secretary to any interested party at his request, and payment of the costs thereof, and shall be admissible in any criminal, exclusion of imports, or other proceeding arising under or in respect of this part irrespective of whether proceedings with respect to the regulation have previously been initiated or become final under this section.
(f) Technical Electronic Product Radiation Safety Standards Committee
(1)(A) The Secretary shall establish a Technical Electronic Product Radiation Safety Standards Committee (hereafter in this part referred to as the "Committee") which he shall consult before prescribing any standard under this section. The Committee shall be appointed by the Secretary, after consultation with public and private agencies concerned with the technical aspect of electronic product radiation safety, and shall be composed of fifteen members each of whom shall be technically qualified by training and experience in one or more fields of science or engineering applicable to electronic product radiation safety, as follows:
(i) Five members shall be selected from governmental agencies, including State and Federal Governments;
(ii) Five members shall be selected from the affected industries after consultation with industry representatives; and
(iii) Five members shall be selected from the general public, of which at least one shall be a representative of organized labor.
(B) The Committee may propose electronic product radiation safety standards to the Secretary for his consideration. All proceedings of the Committee shall be recorded and the record of each such proceeding shall be available for public inspection.
(2) Payments to members of the Committee who are not officers or employees of the United States pursuant to subsection (c) of
(g) Review and evaluation
The Secretary shall review and evaluate on a continuing basis testing programs carried out by industry to assure the adequacy of safeguards against hazardous electronic product radiation and to assure that electronic products comply with standards prescribed under this section.
(h) Product certification
Every manufacturer of an electronic product to which is applicable a standard in effect under this section shall furnish to the distributor or dealer at the time of delivery of such product, in the form of a label or tag permanently affixed to such product or in such manner as approved by the Secretary, the certification that such product conforms to all applicable standards under this section. Such certification shall be based upon a test, in accordance with such standard, of the individual article to which it is attached or upon a testing program which is in accord with good manufacturing practice and which has not been disapproved by the Secretary (in such manner as he shall prescribe by regulation) on the grounds that it does not assure the adequacy of safeguards against hazardous electronic product radiation or that it does not assure that electronic products comply with the standards prescribed under this section.
(June 25, 1938, ch. 675, §534, formerly act July 1, 1944, ch. 373, title III, §534, formerly §358, as added
Codification
Section was classified to
Amendments
1993—
Subsec. (f)(2).
1990—Subsec. (a)(1)(E).
Subsecs. (e), (f)(1)(A).
1970—Subsec. (f)(2).
Noninterference With Other Federal Agencies
Enactment of this section not to be construed to supersede or limit the functions under any other provision of law of any officer or agency of the United States, see section 4 of
Section Referred to in Other Sections
This section is referred to in
§360ll. Notification of defects in and repair or replacement of electronic products
(a) Notification; exemption
(1) Every manufacturer of electronic products who discovers that an electronic product produced, assembled, or imported by him has a defect which relates to the safety of use of such product by reason of the emission of electronic product radiation, or that an electronic product produced, assembled, or imported by him on or after the effective date of an applicable standard prescribed pursuant to
(2) If, in the opinion of such manufacturer, the defect or failure to comply is not such as to create a significant risk of injury, including genetic injury, to any person, he may, at the time of giving notice to the Secretary of such defect or failure to comply, apply to the Secretary for an exemption from the requirement of notice to the persons specified in subsection (b) of this section. If such application states reasonable grounds for such exemption, the Secretary shall afford such manufacturer an opportunity to present his views and evidence in support of the application, the burden of proof being on the manufacturer. If, after such presentation, the Secretary is satisfied that such defect or failure to comply is not such as to create a significant risk of injury, including genetic injury, to any person, he shall exempt such manufacturer from the requirement of notice to the persons specified in subsection (b) of this section and from the requirements of repair or replacement imposed by subsection (f) of this section.
(b) Method of notification
The notification (other than to the Secretary) required by paragraph (1) of subsection (a) of this section shall be accomplished—
(1) by certified mail to the first purchaser of such product for purposes other than resale, and to any subsequent transferee of such product; and
(2) by certified mail or other more expeditious means to the dealers or distributors of such manufacturer to whom such product was delivered.
(c) Requisite elements of notification
The notifications required by paragraph (1) of subsection (a) of this section shall contain a clear description of such defect or failure to comply with an applicable standard, an evaluation of the hazard reasonably related to such defect or failure to comply, and a statement of the measures to be taken to repair such defect. In the case of a notification to a person referred to in subsection (b) of this section, the notification shall also advise the person of his rights under subsection (f) of this section.
(d) Copies to Secretary of communications by manufacturers to dealers or distributors regarding defects
Every manufacturer of electronic products shall furnish to the Secretary a true or representative copy of all notices, bulletins, and other communications to the dealers or distributors of such manufacturer or to purchasers (or subsequent transferees) of electronic products of such manufacturer regarding any such defect in such product or any such failure to comply with a standard applicable to such product. The Secretary shall disclose to the public so much of the information contained in such notice or other information obtained under
(e) Notice from Secretary to manufacturer of defects or failure to comply with standards
If through testing, inspection, investigation, or research carried out pursuant to this part, or examination of reports submitted pursuant to
(1) does not comply with an applicable standard prescribed pursuant to
(2) contains a defect which relates to the safety of use of such product by reason of the emission of electronic product radiation;
he shall immediately notify the manufacturer of such product of such defect or failure to comply. The notice shall contain the findings of the Secretary and shall include all information upon which the findings are based. The Secretary shall afford such manufacturer an opportunity to present his views and evidence in support thereof, to establish that there is no failure of compliance or that the alleged defect does not exist or does not relate to safety of use of the product by reason of the emission of such radiation hazard. If after such presentation by the manufacturer the Secretary determines that such product does not comply with an applicable standard prescribed pursuant to
(f) Correction of defects
If any electronic product is found under subsection (a) or (e) of this section to fail to comply with an applicable standard prescribed under this part or to have a defect which relates to the safety of use of such product, and the notification specified in subsection (c) of this section is required to be furnished on account of such failure or defect, the manufacturer of such product shall (1) without charge, bring such product into conformity with such standard or remedy such defect and provide reimbursement for any expenses for transportation of such product incurred in connection with having such product brought into conformity or having such defect remedied, (2) replace such product with a like or equivalent product which complies with each applicable standard prescribed under this part and which has no defect relating to the safety of its use, or (3) make a refund of the cost of such product. The manufacturer shall take the action required by this subsection in such manner, and with respect to such persons, as the Secretary by regulations shall prescribe.
(g) Effective date
This section shall not apply to any electronic product that was manufactured before October 18, 1968.
(June 25, 1938, ch. 675, §535, formerly act July 1, 1944, ch. 373, title III, §535, formerly §359, as added
Codification
Section was classified to
Amendments
1993—
1990—Subsec. (a)(1).
Subsec. (d).
Subsec. (e).
Subsec. (f).
Noninterference With Other Federal Agencies
Enactment of this section not to be construed to supersede or limit the functions under any other provision of law of any officer or agency of the United States, see section 4 of
Section Referred to in Other Sections
This section is referred to in
§360mm. Imports
(a) Refusal of admission to noncomplying electronic products
Any electronic product offered for importation into the United States which fails to comply with an applicable standard prescribed under this part, or to which is not affixed a certification in the form of a label or tag in conformity with
(b) Bond
If it appears to the Secretary of Health and Human Services that any electronic product refused admission pursuant to subsection (a) of this section can be brought into compliance with applicable standards prescribed pursuant to
(c) Liability of owner or consignee for expenses connected with refusal of admission
All expenses (including travel, per diem or subsistence, and salaries of officers or employees of the United States) in connection with the destruction provided for in subsection (a) of this section and the supervision of operations provided for in subsection (b) of this section, and all expenses in connection with the storage, cartage, or labor with respect to any electronic product refused admission pursuant to subsection (a) of this section, shall be paid by the owner or consignee, and, in event of default, shall constitute a lien against any future importations made by such owner or consignee.
(d) Designation of agent for purposes of service
It shall be the duty of every manufacturer offering an electronic product for importation into the United States to designate in writing an agent upon whom service of all administrative and judicial processes, notices, orders, decisions, and requirements may be made for and on behalf of said manufacturer, and to file such designation with the Secretary, which designation may from time to time be changed by like writing, similarly filed. Service of all administrative and judicial processes, notices, orders, decisions, and requirements may be made upon said manufacturer by service upon such designated agent at his office or usual place of residence with like effect as if made personally upon said manufacturer, and in default of such designation of such agent, service of process, notice, order, requirement, or decision in any proceeding before the Secretary or in any judicial proceeding for enforcement of this part or any standards prescribed pursuant to this part may be made by posting such process, notice, order, requirement, or decision in the Office of the Secretary or in a place designated by him by regulation.
(June 25, 1938, ch. 675, §536, formerly act July 1, 1944, ch. 373, title III, §536, formerly §360, as added
Codification
Section was classified to
Amendments
1993—
1992—Subsecs. (a), (b).
1990—Subsec. (a).
Subsec. (b).
Subsec. (d).
Noninterference With Other Federal Agencies
Enactment of this section not to be construed to supersede or limit the functions under any other provision of law of any officer or agency of the United States, see section 4 of
§360nn. Inspection, records, and reports
(a) Inspection of premises
If the Secretary finds for good cause that the methods, tests, or programs related to electronic product radiation safety in a particular factory, warehouse, or establishment in which electronic products are manufactured or held, may not be adequate or reliable, officers or employees duly designated by the Secretary, upon presenting appropriate credentials and a written notice to the owner, operator, or agent in charge, are thereafter authorized (1) to enter, at reasonable times, any area in such factory, warehouse, or establishment in which the manufacturer's tests (or testing programs) required by
(b) Record keeping
Every manufacturer of electronic products shall establish and maintain such records (including testing records), make such reports, and provide such information, as the Secretary may reasonably require to enable him to determine whether such manufacturer has acted or is acting in compliance with this part and standards prescribed pursuant to this part and shall, upon request of an officer or employee duly designated by the Secretary, permit such officer or employee to inspect appropriate books, papers, records, and documents relevant to determining whether such manufacturer has acted or is acting in compliance with standards prescribed pursuant to this part.
(c) Disclosure of technical data
Every manufacturer of electronic products shall provide to the Secretary such performance data and other technical data related to safety as may be required to carry out the purposes of this part. The Secretary is authorized to require the manufacturer to give such notification of such performance and technical data at the time of original purchase to the ultimate purchaser of the electronic product, as he determines necessary to carry out the purposes of this part after consulting with the affected industry.
(d) Public nature of reports
Accident and investigation reports made under this part by any officer, employee, or agent of the Secretary shall be available for use in any civil, criminal, or other judicial proceeding arising out of such accident. Any such officer, employee, or agent may be required to testify in such proceedings as to the facts developed in such investigations. Any such report shall be made available to the public in a manner which need not identify individuals. All reports on research projects, demonstration projects, and other related activities shall be public information.
(e) Trade secrets
The Secretary or his representative shall not disclose any information reported to or otherwise obtained by him, pursuant to subsection (a) or (b) of this section, which concerns any information which contains or relates to a trade secret or other matter referred to in
(f) Information required to identify and locate first purchasers of electronic products
The Secretary may by regulation (1) require dealers and distributors of electronic products, to which there are applicable standards prescribed under this part and the retail prices of which is not less than $50, to furnish manufacturers of such products such information as may be necessary to identify and locate, for purposes of
(June 25, 1938, ch. 675, §537, formerly act July 1, 1944, ch. 373, title III, §537, formerly §360A, as added
Codification
Section was classified to
Amendments
1993—
1990—Subsec. (a).
Subsecs. (b) to (e).
Subsec. (f).
Noninterference With Other Federal Agencies
Enactment of this section not to be construed to supersede or limit the functions under any other provision of law of any officer or agency of the United States, see section 4 of
Section Referred to in Other Sections
This section is referred to in
§360oo. Prohibited acts
(a) It shall be unlawful—
(1) for any manufacturer to introduce, or to deliver for introduction, into commerce, or to import into the United States, any electronic product which does not comply with an applicable standard prescribed pursuant to
(2) for any person to fail to furnish any notification or other material or information required by
(3) for any person to fail or to refuse to establish or maintain records required by this part or to permit access by the Secretary or any of his duly authorized representatives to, or the copying of, such records, or to permit entry or inspection, as required by or pursuant to
(4) for any person to fail or to refuse to make any report required pursuant to
(5) for any person (A) to fail to issue a certification as required by
(b) The Secretary may exempt any electronic product, or class thereof, from all or part of subsection (a) of this section, upon such conditions as he may find necessary to protect the public health or welfare, for the purpose of research, investigations, studies, demonstrations, or training, or for reasons of national security.
(June 25, 1938, ch. 675, §538, formerly act July 1, 1944, ch. 373, title III, §538, formerly §360B, as added
Codification
Section was classified to
Amendments
1993—
1990—Subsec. (a)(1).
Subsec. (a)(2).
Subsec. (a)(3).
Subsec. (a)(4).
Subsec. (a)(5).
Noninterference With Other Federal Agencies
Enactment of this section not to be construed to supersede or limit the functions under any other provision of law of any officer or agency of the United States, see section 4 of
Section Referred to in Other Sections
This section is referred to in
§360pp. Enforcement
(a) Jurisdiction of courts
The district courts of the United States shall have jurisdiction, for cause shown, to restrain violations of
(b) Penalties
(1) Any person who violates
(2) Any such civil penalty may on application be remitted or mitigated by the Secretary. In determining the amount of such penalty, or whether it should be remitted or mitigated and in what amount, the appropriateness of such penalty to the size of the business of the person charged and the gravity of the violation shall be considered. The amount of such penalty, when finally determined, may be deducted from any sums owing by the United States to the person charged.
(c) Venue; process
Actions under subsections (a) and (b) of this section may be brought in the district court of the United States for the district wherein any act or omission or transaction constituting the violation occurred, or in such court for the district where the defendant is found or transacts business, and process in such cases may be served in any other district of which the defendant is an inhabitant or wherever the defendant may be found.
(d) Warnings
Nothing in this part shall be construed as requiring the Secretary to report for the institution of proceedings minor violations of this part whenever he believes that the public interest will be adequately served by a suitable written notice or warning.
(e) Compliance with regulations
Except as provided in the first sentence of
(f) Additional remedies
The remedies provided for in this part shall be in addition to and not in substitution for any other remedies provided by law.
(June 25, 1938, ch. 675, §539, formerly act July 1, 1944, ch. 373, title III, §539, formerly §360C, as added
Codification
Section was classified to
Amendments
1993—
1990—Subsec. (a).
Subsec. (b)(1).
Subsec. (d).
Subsec. (e).
Subsec. (f).
Noninterference With Other Federal Agencies
Enactment of this section not to be construed to supersede or limit the functions under any other provision of law of any officer or agency of the United States, see section 4 of
§360qq. Repealed. Pub. L. 105–362, title VI, §601(a)(2)(A), Nov. 10, 1998, 112 Stat. 3285
Section, act June 25, 1938, ch. 675, §540, formerly act July 1, 1944, ch. 373, title III, §540, formerly §360D, as added
§360rr. Federal-State cooperation
The Secretary is authorized (1) to accept from State and local authorities engaged in activities related to health or safety or consumer protection, on a reimbursable basis or otherwise, any assistance in the administration and enforcement of this part which he may request and which they may be able and willing to provide and, if so agreed, may pay in advance or otherwise for the reasonable cost of such assistance, and (2) he may, for the purpose of conducting examinations, investigations, and inspections, commission any officer or employee of any such authority as an officer of the Department.
(June 25, 1938, ch. 675, §541, formerly act July 1, 1944, ch. 373, title III, §541, formerly §360E, as added
Codification
Section was classified to
Amendments
1993—
1990—
Noninterference With Other Federal Agencies
Enactment of this section not to be construed to supersede or limit the functions under any other provision of law of any officer or agency of the United States, see section 4 of
§360ss. State standards
Whenever any standard prescribed pursuant to
(June 25, 1938, ch. 675, §542, formerly act July 1, 1944, ch. 373, title III, §542, formerly §360F, as added
Codification
Section was classified to
Amendments
1993—
1990—
Noninterference With Other Federal Agencies
Enactment of this section not to be construed to supersede or limit the functions under any other provision of law of any officer or agency of the United States, see section 4 of
Section Referred to in Other Sections
This section is referred to in
Part D—Dissemination of Treatment Information
Termination of Part
For termination of part by section 401(e) of
§360aaa. Requirements for dissemination of treatment information on drugs or devices
(a) In general
Notwithstanding
(1) a health care practitioner;
(2) a pharmacy benefit manager;
(3) a health insurance issuer;
(4) a group health plan; or
(5) a Federal or State governmental agency;
written information concerning the safety, effectiveness, or benefit of a use not described in the approved labeling of a drug or device if the manufacturer meets the requirements of subsection (b) of this section.
(b) Specific requirements
A manufacturer may disseminate information under subsection (a) of this section on a new use only if—
(1)(A) in the case of a drug, there is in effect for the drug an application filed under subsection (b) or (j) of
(B) in the case of a device, the device is being commercially distributed in accordance with a regulation under subsection (d) or (e) of
(2) the information meets the requirements of
(3) the information to be disseminated is not derived from clinical research conducted by another manufacturer or if it was derived from research conducted by another manufacturer, the manufacturer disseminating the information has the permission of such other manufacturer to make the dissemination;
(4) the manufacturer has, 60 days before such dissemination, submitted to the Secretary—
(A) a copy of the information to be disseminated; and
(B) any clinical trial information the manufacturer has relating to the safety or effectiveness of the new use, any reports of clinical experience pertinent to the safety of the new use, and a summary of such information;
(5) the manufacturer has complied with the requirements of
(6) the manufacturer includes along with the information to be disseminated under this subsection—
(A) a prominently displayed statement that discloses—
(i) that the information concerns a use of a drug or device that has not been approved or cleared by the Food and Drug Administration;
(ii) if applicable, that the information is being disseminated at the expense of the manufacturer;
(iii) if applicable, the name of any authors of the information who are employees of, consultants to, or have received compensation from, the manufacturer, or who have a significant financial interest in the manufacturer;
(iv) the official labeling for the drug or device and all updates with respect to the labeling;
(v) if applicable, a statement that there are products or treatments that have been approved or cleared for the use that is the subject of the information being disseminated pursuant to subsection (a)(1) of this section; and
(vi) the identification of any person that has provided funding for the conduct of a study relating to the new use of a drug or device for which such information is being disseminated; and
(B) a bibliography of other articles from a scientific reference publication or scientific or medical journal that have been previously published about the use of the drug or device covered by the information disseminated (unless the information already includes such bibliography).
(c) Additional information
If the Secretary determines, after providing notice of such determination and an opportunity for a meeting with respect to such determination, that the information submitted by a manufacturer under subsection (b)(3)(B) of this section, with respect to the use of a drug or device for which the manufacturer intends to disseminate information, fails to provide data, analyses, or other written matter that is objective and balanced, the Secretary may require the manufacturer to disseminate—
(1) additional objective and scientifically sound information that pertains to the safety or effectiveness of the use and is necessary to provide objectivity and balance, including any information that the manufacturer has submitted to the Secretary or, where appropriate, a summary of such information or any other information that the Secretary has authority to make available to the public; and
(2) an objective statement of the Secretary, based on data or other scientifically sound information available to the Secretary, that bears on the safety or effectiveness of the new use of the drug or device.
(June 25, 1938, ch. 675, §551, as added
Termination of Section
For termination of section by section 401(e) of
Effective and Termination Dates
Section 401(d) of
Section 401(e) of
Regulations
Section 401(c) of
Studies and Reports
Section 401(f) of
"(1)
"(A)
"(B)
"(2)
"(A)
"(i) the effectiveness of such subchapter with respect to the provision of useful scientific information to health care practitioners;
"(ii) the quality of the information being disseminated pursuant to the provisions of such subchapter;
"(iii) the quality and usefulness of the information provided, in accordance with such subchapter, by the Secretary or by the manufacturer at the request of the Secretary; and
"(iv) the impact of such subchapter on research in the area of new uses, indications, or dosages, particularly the impact on pediatric indications and rare diseases.
"(3)
"(A)
"(B)
Section Referred to in Other Sections
This section is referred to in
§360aaa–1. Information authorized to be disseminated
(a) Authorized information
A manufacturer may disseminate information under
(1) is in the form of an unabridged—
(A) reprint or copy of an article, peer-reviewed by experts qualified by scientific training or experience to evaluate the safety or effectiveness of the drug or device involved, which was published in a scientific or medical journal (as defined in
(B) reference publication, described in subsection (b) of this section, that includes information about a clinical investigation with respect to the drug or device that would be considered to be scientifically sound by experts qualified by scientific training or experience to evaluate the safety or effectiveness of the drug or device that is the subject of such a clinical investigation; and
(2) is not false or misleading and would not pose a significant risk to the public health.
(b) Reference publication
A reference publication referred to in subsection (a)(1)(B) of this section is a publication that—
(1) has not been written, edited, excerpted, or published specifically for, or at the request of, a manufacturer of a drug or device;
(2) has not been edited or significantly influenced by such a manufacturer;
(3) is not solely distributed through such a manufacturer but is generally available in bookstores or other distribution channels where medical textbooks are sold;
(4) does not focus on any particular drug or device of a manufacturer that disseminates information under
(5) presents materials that are not false or misleading.
(June 25, 1938, ch. 675, §552, as added
Termination of Section
For termination of section by section 401(e) of
Section Referred to in Other Sections
This section is referred to in
§360aaa–2. Establishment of list of articles and publications disseminated and list of providers that received articles and reference publications
(a) In general
A manufacturer may disseminate information under
(1) a list containing the titles of the articles and reference publications relating to the new use of drugs or devices that were disseminated by the manufacturer to a person described in
(2) a list that identifies the categories of providers (as described in
(b) Records
A manufacturer that disseminates information under
(June 25, 1938, ch. 675, §553, as added
Termination of Section
For termination of section by section 401(e) of
§360aaa–3. Requirement regarding submission of supplemental application for new use; exemption from requirement
(a) In general
A manufacturer may disseminate information under
(1)(A) the manufacturer has submitted to the Secretary a supplemental application for such use; or
(B) the manufacturer meets the condition described in subsection (b) or (c) of this section (relating to a certification that the manufacturer will submit such an application); or
(2) there is in effect for the manufacturer an exemption under subsection (d) of this section from the requirement of paragraph (1).
(b) Certification on supplemental application; condition in case of completed studies
For purposes of subsection (a)(1)(B) of this section, a manufacturer may disseminate information on a new use if the manufacturer has submitted to the Secretary an application containing a certification that—
(1) the studies needed for the submission of a supplemental application for the new use have been completed; and
(2) the supplemental application will be submitted to the Secretary not later than 6 months after the date of the initial dissemination of information under
(c) Certification on supplemental application; condition in case of planned studies
(1) In general
For purposes of subsection (a)(1)(B) of this section, a manufacturer may disseminate information on a new use if—
(A) the manufacturer has submitted to the Secretary an application containing—
(i) a proposed protocol and schedule for conducting the studies needed for the submission of a supplemental application for the new use; and
(ii) a certification that the supplemental application will be submitted to the Secretary not later than 36 months after the date of the initial dissemination of information under
(B) the Secretary has determined that the proposed protocol is adequate and that the schedule for completing such studies is reasonable.
(2) Progress reports on studies
A manufacturer that submits to the Secretary an application under paragraph (1) shall submit to the Secretary periodic reports describing the status of the studies involved.
(3) Extension of time regarding planned studies
The period of 36 months authorized in paragraph (1)(A)(ii) for the completion of studies may be extended by the Secretary if—
(A) the Secretary determines that the studies needed to submit such an application cannot be completed and submitted within 36 months; or
(B) the manufacturer involved submits to the Secretary a written request for the extension and the Secretary determines that the manufacturer has acted with due diligence to conduct the studies in a timely manner, except that an extension under this subparagraph may not be provided for more than 24 additional months.
(d) Exemption from requirement of supplemental application
(1) In general
For purposes of subsection (a)(2) of this section, a manufacturer may disseminate information on a new use if—
(A) the manufacturer has submitted to the Secretary an application for an exemption from meeting the requirement of subsection (a)(1) of this section; and
(B)(i) the Secretary has approved the application in accordance with paragraph (2); or
(ii) the application is deemed under paragraph (3)(A) to have been approved (unless such approval is terminated pursuant to paragraph (3)(B)).
(2) Conditions for approval
The Secretary may approve an application under paragraph (1) for an exemption if the Secretary makes a determination described in subparagraph (A) or (B), as follows:
(A) The Secretary makes a determination that, for reasons defined by the Secretary, it would be economically prohibitive with respect to such drug or device for the manufacturer to incur the costs necessary for the submission of a supplemental application. In making such determination, the Secretary shall consider (in addition to any other considerations the Secretary finds appropriate)—
(i) the lack of the availability under law of any period during which the manufacturer would have exclusive marketing rights with respect to the new use involved; and
(ii) the size of the population expected to benefit from approval of the supplemental application.
(B) The Secretary makes a determination that, for reasons defined by the Secretary, it would be unethical to conduct the studies necessary for the supplemental application. In making such determination, the Secretary shall consider (in addition to any other considerations the Secretary finds appropriate) whether the new use involved is the standard of medical care for a health condition.
(3) Time for consideration of application; deemed approval
(A) In general
The Secretary shall approve or deny an application under paragraph (1) for an exemption not later than 60 days after the receipt of the application. If the Secretary does not comply with the preceding sentence, the application is deemed to be approved.
(B) Termination of deemed approval
If pursuant to a deemed approval under subparagraph (A) a manufacturer disseminates written information under
(e) Requirements regarding applications
Applications under this section shall be submitted in the form and manner prescribed by the Secretary.
(June 25, 1938, ch. 675, §554, as added
Termination of Section
For termination of section by section 401(e) of
Section Referred to in Other Sections
This section is referred to in
§360aaa–4. Corrective actions; cessation of dissemination
(a) Postdissemination data regarding safety and effectiveness
(1) Corrective actions
With respect to data received by the Secretary after the dissemination of information under
(2) Responsibilities of manufacturers to submit data
After a manufacturer disseminates information under
(b) Cessation of dissemination
(1) Failure of manufacturer to comply with requirements
The Secretary may order a manufacturer to cease the dissemination of information pursuant to
(2) Supplemental applications
The Secretary may order a manufacturer to cease the dissemination of information pursuant to
(A) in the case of a manufacturer that has submitted a supplemental application for a new use pursuant to
(B) in the case of a manufacturer that has submitted a certification under
(C) in the case of a manufacturer that has submitted a certification under
(3) Termination of deemed approval of exemption regarding supplemental applications
If under
(c) Corrective actions by manufacturers
(1) In general
In any case in which under this section the Secretary orders a manufacturer to cease disseminating information, the Secretary may order the manufacturer to take action to correct the information that has been disseminated, except as provided in paragraph (2).
(2) Termination of deemed approval of exemption regarding supplemental applications
In the case of an order under subsection (b)(3) of this section to cease disseminating information, the Secretary may not order the manufacturer involved to take action to correct the information that has been disseminated unless the Secretary determines that the new use described in the information would pose a significant risk to the public health.
(June 25, 1938, ch. 675, §555, as added
Termination of Section
For termination of section by section 401(e) of
Section Referred to in Other Sections
This section is referred to in
§360aaa–5. Definitions
For purposes of this part:
(1) The term "health care practitioner" means a physician, or other individual who is a provider of health care, who is licensed under the law of a State to prescribe drugs or devices.
(2) The terms "health insurance issuer" and "group health plan" have the meaning given such terms under
(3) The term "manufacturer" means a person who manufactures a drug or device, or who is licensed by such person to distribute or market the drug or device.
(4) The term "new use"—
(A) with respect to a drug, means a use that is not included in the labeling of the approved drug; and
(B) with respect to a device, means a use that is not included in the labeling for the approved or cleared device.
(5) The term "scientific or medical journal" means a scientific or medical publication—
(A) that is published by an organization—
(i) that has an editorial board;
(ii) that utilizes experts, who have demonstrated expertise in the subject of an article under review by the organization and who are independent of the organization, to review and objectively select, reject, or provide comments about proposed articles; and
(iii) that has a publicly stated policy, to which the organization adheres, of full disclosure of any conflict of interest or biases for all authors or contributors involved with the journal or organization;
(B) whose articles are peer-reviewed and published in accordance with the regular peer-review procedures of the organization;
(C) that is generally recognized to be of national scope and reputation;
(D) that is indexed in the Index Medicus of the National Library of Medicine of the National Institutes of Health; and
(E) that is not in the form of a special supplement that has been funded in whole or in part by one or more manufacturers.
(June 25, 1938, ch. 675, §556, as added
Termination of Section
For termination of section by section 401(e) of
Section Referred to in Other Sections
This section is referred to in
§360aaa–6. Rules of construction
(a) Unsolicited request
Nothing in
(b) Dissemination of information on drugs or devices not evidence of intended use
Notwithstanding subsection (a), (f), or (o) of
(c) Patent protection
Nothing in
(d) Authorization for dissemination of articles and fees for reprints of articles
Nothing in
(June 25, 1938, ch. 675, §557, as added
Termination of Section
For termination of section by section 401(e) of
Part E—General Provisions Relating to Drugs and Devices
§360bbb. Expanded access to unapproved therapies and diagnostics
(a) Emergency situations
The Secretary may, under appropriate conditions determined by the Secretary, authorize the shipment of investigational drugs or investigational devices for the diagnosis, monitoring, or treatment of a serious disease or condition in emergency situations.
(b) Individual patient access to investigational products intended for serious diseases
Any person, acting through a physician licensed in accordance with State law, may request from a manufacturer or distributor, and any manufacturer or distributor may, after complying with the provisions of this subsection, provide to such physician an investigational drug or investigational device for the diagnosis, monitoring, or treatment of a serious disease or condition if—
(1) the licensed physician determines that the person has no comparable or satisfactory alternative therapy available to diagnose, monitor, or treat the disease or condition involved, and that the probable risk to the person from the investigational drug or investigational device is not greater than the probable risk from the disease or condition;
(2) the Secretary determines that there is sufficient evidence of safety and effectiveness to support the use of the investigational drug or investigational device in the case described in paragraph (1);
(3) the Secretary determines that provision of the investigational drug or investigational device will not interfere with the initiation, conduct, or completion of clinical investigations to support marketing approval; and
(4) the sponsor, or clinical investigator, of the investigational drug or investigational device submits to the Secretary a clinical protocol consistent with the provisions of
(c) Treatment investigational new drug applications and treatment investigational device exemptions
Upon submission by a sponsor or a physician of a protocol intended to provide widespread access to an investigational drug or investigational device for eligible patients (referred to in this subsection as an "expanded access protocol"), the Secretary shall permit such investigational drug or investigational device to be made available for expanded access under a treatment investigational new drug application or treatment investigational device exemption if the Secretary determines that—
(1) under the treatment investigational new drug application or treatment investigational device exemption, the investigational drug or investigational device is intended for use in the diagnosis, monitoring, or treatment of a serious or immediately life-threatening disease or condition;
(2) there is no comparable or satisfactory alternative therapy available to diagnose, monitor, or treat that stage of disease or condition in the population of patients to which the investigational drug or investigational device is intended to be administered;
(3)(A) the investigational drug or investigational device is under investigation in a controlled clinical trial for the use described in paragraph (1) under an investigational drug application in effect under
(B) all clinical trials necessary for approval of that use of the investigational drug or investigational device have been completed;
(4) the sponsor of the controlled clinical trials is actively pursuing marketing approval of the investigational drug or investigational device for the use described in paragraph (1) with due diligence;
(5) in the case of an investigational drug or investigational device described in paragraph (3)(A), the provision of the investigational drug or investigational device will not interfere with the enrollment of patients in ongoing clinical investigations under
(6) in the case of serious diseases, there is sufficient evidence of safety and effectiveness to support the use described in paragraph (1); and
(7) in the case of immediately life-threatening diseases, the available scientific evidence, taken as a whole, provides a reasonable basis to conclude that the investigational drug or investigational device may be effective for its intended use and would not expose patients to an unreasonable and significant risk of illness or injury.
A protocol submitted under this subsection shall be subject to the provisions of
(d) Termination
The Secretary may, at any time, with respect to a sponsor, physician, manufacturer, or distributor described in this section, terminate expanded access provided under this section for an investigational drug or investigational device if the requirements under this section are no longer met.
(e) Definitions
In this section, the terms "investigational drug", "investigational device", "treatment investigational new drug application", and "treatment investigational device exemption" shall have the meanings given the terms in regulations prescribed by the Secretary.
(June 25, 1938, ch. 675, §561, as added
Effective Date
Section effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of
Section Referred to in Other Sections
This section is referred to in title 42 section 282.
§360bbb–1. Dispute resolution
If, regarding an obligation concerning drugs or devices under this Act or section 351 of the Public Health Service Act [
(June 25, 1938, ch. 675, §562, as added
References in Text
This Act, referred to in text, is the Federal Food, Drug, and Cosmetic Act, act June 25, 1938, ch. 675,
Effective Date
Section effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of
Section Referred to in Other Sections
This section is referred to in
§360bbb–2. Classification of products
(a) Request
A person who submits an application or submission (including a petition, notification, and any other similar form of request) under this chapter for a product, may submit a request to the Secretary respecting the classification of the product as a drug, biological product, device, or a combination product subject to
(b) Statement
Not later than 60 days after the receipt of the request described in subsection (a) of this section, the Secretary shall determine the classification of the product under subsection (a) of this section, or the component of the Food and Drug Administration that will regulate the product, and shall provide to the person a written statement that identifies such classification or such component, and the reasons for such determination. The Secretary may not modify such statement except with the written consent of the person, or for public health reasons based on scientific evidence.
(c) Inaction of Secretary
If the Secretary does not provide the statement within the 60-day period described in subsection (b) of this section, the recommendation made by the person under subsection (a) of this section shall be considered to be a final determination by the Secretary of such classification of the product, or the component of the Food and Drug Administration that will regulate the product, as applicable, and may not be modified by the Secretary except with the written consent of the person, or for public health reasons based on scientific evidence.
(June 25, 1938, ch. 675, §563, as added
Effective Date
Section effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of