21 U.S.C. § 351 — Adulterated drugs and devices

Page 155 TITLE 21—FOOD AND DRUGS § 351 tion of an article of food that was the subject of a recall under section 350l(b) of this title or a public health advisory described in para- graph (1). (Pub. L. 111–353, title II, § 206(f), Jan. 4, 2011, 124 Stat. 3943.) Editorial Notes REFERENCES IN TEXT Subsection (a), referred to in par. (1), means subsec. (a) of section 206 of Pub. L. 111–353. CODIFICATION Section was enacted as part of the FDA Food Safety Modernization Act, and not as part of the Federal Food, Drug, and Cosmetic Act which comprises this chapter. Statutory Notes and Related Subsidiaries CONSTRUCTION Nothing in this section to be construed to alter juris- diction and authorities established under certain other Acts or in a manner inconsistent with international agreements to which the United States is a party, see sections 2251 and 2252 of this title. § 350m. Requirements for critical food (a) Notification of meaningful disruption for crit- ical food (1) In general A manufacturer of a critical food (as defined in section 321(ss) of this title) shall notify the Secretary of a permanent discontinuance in the manufacture or an interruption of the manufacture of such food that is likely to lead to a meaningful disruption in the supply of such food in the United States, and the rea- sons for such discontinuance or interruption, as soon as practicable, but not later than 5 business days after such discontinuance or such interruption. (2) Distribution of information Not later than 5 calendar days after receiv- ing a notification under paragraph (1), if the Secretary has determined that such dis- continuance or interruption has resulted, or is likely to result, in a shortage of such critical food, the Secretary shall distribute, to the Secretary of Agriculture and to the maximum extent practicable to the appropriate entities, as determined by the Secretary through such means as the Secretary determines appro- priate, information on such shortage. (3) Confidentiality Nothing in this subsection authorizes the Secretary to disclose any information that is a trade secret or confidential information sub- ject to section 552(b)(4) of title 5 or section 1905 of title 18. (4) Meaningful disruption In this subsection, the term ‘‘meaningful disruption’’— (A) means a change in production that is reasonably likely to lead to a significant re- duction in the supply of a critical food by a manufacturer that affects the ability of the manufacturer to meet expected demand for its product; and (B) does not include interruptions in man- ufacturing due to matters such as routine maintenance, changes or discontinuance of flavors, colors, or other insignificant formu- lation characteristics, or insignificant changes in manufacturing so long as the manufacturer expects to resume operations in a short period of time. (b) Risk management plans Each manufacturer of a critical food shall de- velop, maintain, and implement, as appropriate, a redundancy risk management plan that identi- fies and evaluates risks to the supply of the food, as applicable, for each establishment in which such food is manufactured. A risk man- agement plan under this subsection— (1) may identify and evaluate risks to the supply of more than one critical food, or crit- ical food category, manufactured at the same establishment; (2) may identify mechanisms by which the manufacturer would mitigate the impacts of a supply disruption through alternative produc- tion sites, alternative suppliers, stockpiling of inventory, or other means; and (3) shall be subject to inspection and copying by the Secretary pursuant to an inspection under section 374 of this title. (c) Failure to meet requirements (1) In general If a person fails to submit information re- quired under, and in accordance with, sub- section (a)— (A) the Secretary shall issue a letter to such person informing such person of such failure; and (B) not later than 45 calendar days after the issuance of a letter under subparagraph (A), subject to paragraph (2), the Secretary shall make available to the public on the website of the Food and Drug Administra- tion, with appropriate redactions made to protect the information described in sub- section (a)(3)— (i) the letter issued under subparagraph (A); and (ii) at the request of such person, any re- sponse to such letter such person sub- mitted to the Secretary. (2) Exception If the Secretary determines that the letter under paragraph (1) was issued in error or, after review of such response, the person had a reasonable basis for not submitting a notifica- tion as required under subsection (a), the re- quirements of paragraph (1)(B) shall not apply. (June 25, 1938, ch. 675, § 424, as added Pub. L. 117–328, div. FF, title III, § 3401(k), Dec. 29, 2022, 136 Stat. 5844.) SUBCHAPTER V—DRUGS AND DEVICES PART A—DRUGS AND DEVICES § 351. Adulterated drugs and devices A drug or device shall be deemed to be adulter- ated— Page 156 TITLE 21—FOOD AND DRUGS § 351 (a) Poisonous, insanitary, etc., ingredients; ade- quate 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 manufac- ture, processing, packing, or holding do not con- form to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the re- quirements 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 com- pounded positron emission tomography drug and the methods used in, or the facilities and con- trols 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 chap- ter as to safety and has the identity and strength, and meets the quality and purity char- acteristics, 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 inju- rious 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 section 379e(a) of this title, or (B) it is a color additive the intended use of which in or on drugs or de- vices is for purposes of coloring only and is un- safe within the meaning of section 379e(a) of this title; or (5) if it is a new animal drug which is unsafe within the meaning of section 360b of this title; or (6) if it is an animal feed bearing or con- taining a new animal drug, and such animal feed is unsafe within the meaning of section 360b of this title. (b) Strength, quality, or purity differing from of- ficial 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 determina- tion 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 Sec- retary shall bring such fact to the attention of the appropriate body charged with the revision of such compendium, and if such body fails with- in a reasonable time to prescribe tests or meth- ods of assay which, in the judgment of the Sec- retary, are sufficient for purposes of this para- graph, then the Secretary shall promulgate reg- ulations prescribing appropriate tests or meth- ods of assay in accordance with which such de- termination 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 Pharma- copoeia and the Homoeopathic Pharmacopoeia of the United States it shall be subject to the re- quirements 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 para- graph (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 sub- stance 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 section 360d of this title unless such device is in all respects in con- formity with such standard. (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 section 360d(c) of this title unless such device is in all respects in conformity with such standard. (f) Certain class III devices (1) If it is a class III device— (A)(i) which is required by an order issued under subsection (b) of section 360e of this title to have an approval under such section of an application for premarket approval and which is not exempt from section 360e of this title under section 360j(g) of this title, and (ii)(I) for which an application for premarket approval or a notice of completion of a prod- uct development protocol was not filed with the Secretary within the ninety-day period be- ginning on the date of the issuance of such order, or (II) for which such an application was filed and approval of the application has been de- nied, suspended, or withdrawn, or such a no- tice was filed and has been declared not com- pleted or the approval of the device under the protocol has been withdrawn; (B)(i) which was classified under section 360c(f) of this title into class III, which under section 360e(a) of this title is required to have in effect an approved application for pre- market approval, and which is not exempt from section 360e of this title under section 360j(g) of this title, and Page 157 TITLE 21—FOOD AND DRUGS § 351 1 So in original. Probably should be ‘‘subparagraph’’. (ii) which has an application which has been suspended or is otherwise not in effect; or (C) which was classified under section 360j(l) of this title into class III, which under such section is required to have in effect an ap- proved application under section 360e of this title, and which has an application which has been suspended or is otherwise not in effect. (2)(A) In the case of a device classified under section 360c(f) of this title into class III and in- tended solely for investigational use, paragraph 1 (1)(B) shall not apply with respect to such device during the period ending on the ninetieth day after the date of the promulgation of the regula- tions prescribing the procedures and conditions required by section 360j(g)(2) of this title. (B) In the case of a device subject to an order issued under subsection (b) of section 360e of this title, paragraph 1 (1) shall not apply with respect to such device during the period ending— (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 section 360c of this title, or (ii) on the ninetieth day after the date of the issuance of such order, whichever occurs later. (3) In the case of a device with respect to which a regulation was promulgated under sec- tion 360e(b) of this title prior to July 9, 2012, a reference in this subsection to an order issued under section 360e(b) of this title shall be deemed to include such regulation. (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 con- formity with applicable requirements under sec- tion 360j(f)(1) of this title or an applicable condi- tion prescribed by an order under section 360j(f)(2) of this title. (i) Failure to comply with requirements under which device was exempted for investiga- tional use If it is a device for which an exemption has been granted under section 360j(g) of this title for investigational use and the person who was granted such exemption or any investigator who uses such device under such exemption fails to comply with a requirement prescribed by or under such section. (j) Delayed, denied, or limited inspection; refusal to permit entry or inspection If it is a drug or device and it has been manu- factured, processed, packed, or held in any fac- tory, warehouse, or establishment and the owner, operator, or agent of such factory, ware- house, or establishment delays, denies, or limits an inspection, or refuses to permit entry or in- spection. For purposes of paragraph (a)(2)(B), the term ‘‘current good manufacturing practice’’ includes the implementation of oversight and controls over the manufacture of drugs to ensure quality, including managing the risk of and establishing the safety of raw materials, materials used in the manufacturing of drugs, and finished drug products. (June 25, 1938, ch. 675, § 501, 52 Stat. 1049; Pub. L. 86–618, title I, § 102(b)(1), July 12, 1960, 74 Stat. 398; Pub. L. 87–781, title I, § 101, Oct. 10, 1962, 76 Stat. 780; Pub. L. 90–399, § 101(a), July 13, 1968, 82 Stat. 343; Pub. L. 94–295, §§ 3(d), 9(b)(1), May 28, 1976, 90 Stat. 576, 583; Pub. L. 101–629, § 9(b), Nov. 28, 1990, 104 Stat. 4521; Pub. L. 102–571, title I, § 107(8), Oct. 29, 1992, 106 Stat. 4499; Pub. L. 105–115, title I, § 121(b)(1), title II, § 204(c), Nov. 21, 1997, 111 Stat. 2320, 2336; Pub. L. 112–144, title VI, § 608(b)(2), title VII, §§ 707(a), 711, July 9, 2012, 126 Stat. 1058, 1068, 1071; Pub. L. 115–52, title VII, § 702(c), Aug. 18, 2017, 131 Stat. 1056.) Editorial Notes AMENDMENTS 2017—Par. (j). Pub. L. 115–52 inserted ‘‘or device’’ after ‘‘drug’’. 2012—Pub. L. 112–144, § 711, inserted concluding provi- sions. Par. (f)(1)(A)(i). Pub. L. 112–144, § 608(b)(2)(A)(i), sub- stituted ‘‘an order issued’’ for ‘‘a regulation promul- gated’’. Par. (f)(1)(A)(ii)(I). Pub. L. 112–144, § 608(b)(2)(A)(ii), substituted ‘‘issuance of such order’’ for ‘‘promulgation of such regulation’’. Par. (f)(2)(B). Pub. L. 112–144, § 608(b)(2)(B), sub- stituted ‘‘an order issued’’ for ‘‘a regulation promul- gated’’ in introductory provisions and ‘‘issuance of such order’’ for ‘‘promulgation of such regulation’’ in subcl. (ii). Par. (f)(3). Pub. L. 112–144, § 608(b)(2)(C), added subpar. (3). Par. (j). Pub. L. 112–144, § 707(a), added par. (j). 1997—Par. (a)(2)(C). Pub. L. 105–115, § 121(b)(1), inserted ‘‘; or (C) if it is a compounded positron emission to- mography drug and the methods used in, or the facili- ties and controls used for, its compounding, processing, packing, or holding do not conform to or are not oper- ated or administered in conformity with the positron emission tomography compounding standards and the official monographs of the United States Pharma- copoeia to assure that such drug meets the require- ments of this chapter as to safety and has the identity and strength, and meets the quality and purity charac- teristics, that it purports or is represented to possess;’’ before ‘‘or (3)’’. Par. (e). Pub. L. 105–115, § 204(c), designated existing provisions as subpar. (1) and added subpar. (2). 1992—Par. (a)(4). Pub. L. 102–571 substituted ‘‘379e(a)’’ for ‘‘376(a)’’ in cls. (A) and (B). 1990—Par. (f)(1). Pub. L. 101–629, § 9(b), which directed the amendment of subpars. (A) to (C) of par. (f), was ex- ecuted by making the amendments in cls. (A) to (C) of subpar. (1) of par. (f) as follows to reflect the probable intent of Congress: in cl. (A)(ii)(II), substituted ‘‘, suspended, or withdrawn’’ for ‘‘or withdrawn’’; in cl. (B)(ii), substituted ‘‘which has an application which has been suspended or is otherwise not in effect’’ for ‘‘which does not have such an application in effect’’; and in cl. (C), substituted ‘‘which has an application which has been suspended or is otherwise not in effect’’ for ‘‘which does not have such an application in effect’’. 1976—Par. (a). Pub. L. 94–295, § 9(b)(1), substituted ‘‘(3) if its’’ for ‘‘(3) if it is a drug and its’’ in cl. (3), sub- stituted ‘‘(4) if (A) it bears or contains’’ for ‘‘(4) if (A) it is a drug which bears or contains’’ in cl. (4)(A), and substituted ‘‘drugs or devices’’ for ‘‘drugs’’ in cl. (4)(B). Pars. (e) to (i). Pub. L. 94–295, § 3(d), added pars. (e) to (i). Page 158 TITLE 21—FOOD AND DRUGS § 352 1 So in original. The term ‘‘health care economic information’’ appears only in par. (1). 1968—Par. (a). Pub. L. 90–399 added cls. (5) and (6). 1962—Par. (a). Pub. L. 87–781 designated existing pro- visions of cl. (2) as (A) and added (B). 1960—Par. (a). Pub. L. 86–618 substituted provisions in cl. (4) relating to unsafe color additives for provisions which related to a coal-tar color other than one from a batch that has been certified in accordance with regu- lations as provided by section 354 of this title. Statutory Notes and Related Subsidiaries EFFECTIVE AND TERMINATION DATES OF 1997 AMENDMENT Pub. L. 105–115, title I, § 121(b)(2), Nov. 21, 1997, 111 Stat. 2320, provided that: ‘‘Section 501(a)(2)(C) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 351(a)(2)(C)) shall not apply 4 years after the date of en- actment of this Act [Nov. 21, 1997] or 2 years after the date on which the Secretary of Health and Human Services establishes the requirements described in sub- section (c)(1)(B) [section 121(c)(1)(B) of Pub. L. 105–115, set out as a note under section 355 of this title], which- ever is later.’’ Amendment by Pub. L. 105–115 effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of Pub. L. 105–115, set out as an Effective Date of 1997 Amendment note under section 321 of this title. EFFECTIVE DATE OF 1968 AMENDMENT Amendment by Pub. L. 90–399 effective on first day of thirteenth calendar month after July 13, 1968, see sec- tion 108(a) of Pub. L. 90–399, set out as an Effective Date and Transitional Provisions note under section 360b of this title. EFFECTIVE DATE OF 1962 AMENDMENT; EXCEPTIONS Amendment by Pub. L. 87–781 effective on first day of seventh calendar month following October 1962, see sec- tion 107 of Pub. L. 87–781, set out as a note under sec- tion 321 of this title. EFFECTIVE DATE OF 1960 AMENDMENT Amendment by Pub. L. 86–618 effective July 12, 1960, subject to the provisions of section 203 of Pub. L. 86–618, see section 202 of Pub. L. 86–618, set out as a note under section 379e of this title. EFFECTIVE DATE; POSTPONEMENT Par. (a)(4) effective Jan. 1, 1940, see act June 23, 1939, ch. 242, 53 Stat. 853, set out as an Effective Date; Post- ponement in Certain Cases note under section 301 of this title. APPROVAL BY REGULATION PRIOR TO JULY 9, 2012 Pub. L. 112–144, title VI, § 608(b)(3), July 9, 2012, 126 Stat. 1059, provided that: ‘‘The amendments made by this subsection [amending this section and section 360e of this title] shall have no effect on a regulation that was promulgated prior to the date of enactment of this Act [July 9, 2012] requiring that a device have an ap- proval under section 515 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360e) of an application for pre- market approval.’’ GUIDANCE Pub. L. 112–144, title VII, § 707(b), July 9, 2012, 126 Stat. 1068, provided that: ‘‘Not later than 1 year after the date of enactment of this section [July 9, 2012], the Secretary of Health and Human Services shall issue guidance that defines the circumstances that would constitute delaying, denying, or limiting inspection, or refusing to permit entry or inspection, for purposes of section 501(j) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 351(j)] (as added by subsection (a)).’’ Executive Documents TRANSFER OF FUNCTIONS For transfer of functions of Federal Security Admin- istrator 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 notes set out under section 321 of this title. § 352. Misbranded drugs and devices A drug or device shall be deemed to be mis- branded— (a) False or misleading label (1) If its labeling is false or misleading in any particular. Health care economic information provided to a payor, formulary committee, or other similar entity with knowledge and exper- tise in the area of health care economic anal- ysis, carrying out its responsibilities for the se- lection of drugs or devices for coverage or reim- bursement, shall not be considered to be false or misleading under this paragraph if the health care economic information relates to an indica- tion approved under section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42 for such drug or device, is based on competent and reliable scientific evidence, and includes, where applicable, a conspicuous and prominent state- ment describing any material differences be- tween the health care economic information and the labeling approved for the drug or device under section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42. The requirements set forth in section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42 shall not apply to health care economic information pro- vided to such a payor, committee, or entity in accordance with this paragraph. Information that is relevant to the substantiation of the health care economic information presented pursuant to this paragraph shall be made avail- able to the Secretary upon request. (2)(A) For purposes of this paragraph,1 the term ‘‘health care economic information’’ means any analysis (including the clinical data, inputs, clinical or other assumptions, methods, results, and other components underlying or comprising the analysis) that identifies, meas- ures, or describes the economic consequences, which may be based on the separate or aggre- gated clinical consequences of the represented health outcomes, of the use of a drug or device. Such analysis may be comparative to the use of another drug or device, to another health care intervention, or to no intervention. (B) Such term does not include any analysis that relates only to an indication that is not ap- proved under section 355, 360(k), 360c(f)(2), or 360e of this title or section 262 of title 42 for such drug or device. (b) Package form; contents of label If in package form unless it bears a label con- taining (1) the name and place of business of the manufacturer, packer, or distributor; and (2) an accurate statement of the quantity of the con- tents in terms of weight, measure, or numerical count: Provided, That under clause (2) of this paragraph reasonable variations shall be per- mitted, and exemptions as to small packages shall be established, by regulations prescribed by the Secretary.