21 U.S.C. § 360ccc — Conditional approval of new animal

Page 442 TITLE 21—FOOD AND DRUGS § 360ccc tunity for an informal hearing, to be held not later than 10 days after the date of issuance of the order, on whether adequate evidence exists to justify an amendment to the order, and what actions are required by such amended order pursuant to subparagraph (3). (3) Order resolution After an order is issued according to the process under paragraphs (1) and (2), the Sec- retary shall, except as provided in paragraph (4)— (A) vacate the order, if the Secretary de- termines that inadequate grounds exist to support the actions required by the order; (B) continue the order ceasing distribution of the controlled substance until a date spec- ified in such order; or (C) amend the order to require a recall of the controlled substance, including any re- quirements to notify appropriate persons, a timetable for the recall to occur, and a schedule for updates to be provided to the Secretary regarding such recall. (4) Risk assessment If the Secretary determines that the risk of recalling a controlled substance presents a greater health risk than the health risk of not recalling such controlled substance from use, an amended order under subparagraph (B) or (C) of paragraph (3) shall not include either a recall order for, or an order to cease distribu- tion of, such controlled substance, as applica- ble. (5) Action following order Any person who is subject to an order pursu- ant to subparagraph (B) or (C) of paragraph (3) shall immediately cease distribution of or re- call, as applicable, the controlled substance and provide notification as required by such order. (b) Notice to persons affected If the Secretary determines necessary, the Secretary may require the person subject to an order pursuant to paragraph (1) or an amended order pursuant to subparagraph (B) or (C) of paragraph (3) to provide either a notice of a re- call order for, or an order to cease distribution of, such controlled substance, as applicable, under this section to appropriate persons, in- cluding persons who manufacture, distribute, import, or offer for sale such product that is the subject of an order and to the public. In pro- viding such notice, the Secretary may use the assistance of health professionals who pre- scribed or dispensed such controlled substances. (c) Nondelegation An order described in subsection (a)(3) shall be ordered by the Secretary or an official des- ignated by the Secretary. An official may not be so designated under this section unless the offi- cial is the Director of the Center for Drug Eval- uation and Research or an official senior to such Director. (d) Savings clause Nothing contained in this section shall be con- strued as limiting— (1) the authority of the Secretary to issue an order to cease distribution of, or to recall, any drug under any other provision of this chapter or the Public Health Service Act [42 U.S.C. 201 et seq.]; or (2) the ability of the Secretary to request any person to perform a voluntary activity re- lated to any drug subject to this chapter or the Public Health Service Act. (June 25, 1938, ch. 675, § 569D, as added Pub. L. 115–271, title III, § 3012(b), Oct. 24, 2018, 132 Stat. 3935.) Editorial Notes REFERENCES IN TEXT The Public Health Service Act, referred to in subsec. (d), is act July 1, 1944, ch. 373, 58 Stat. 682, which is clas- sified generally to chapter 6A (§ 201 et seq.) of Title 42, The Public Health and Welfare. For complete classi- fication of this Act to the Code, see Short Title note set out under section 201 of Title 42 and Tables. PART F—NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES § 360ccc. Conditional approval of new animal drugs for minor use and minor species and certain new animal drugs (a) Application requirements (1)(A) Except as provided in paragraph (3), any person may file with the Secretary an applica- tion for conditional approval of— (i) a new animal drug intended for a minor use or a minor species; or (ii) a new animal drug not intended for a minor use or minor species— (I) that is intended to treat a serious or life-threatening disease or condition or ad- dresses an unmet animal or human health need; and (II) for which the Secretary determines that a demonstration of effectiveness would require a complex or particularly difficult study or studies. (B) The Secretary shall, not later than Sep- tember 30, 2019, issue guidance or regulations further clarifying the criteria specified in sub- paragraph (A)(ii). (C) An application under this paragraph shall comply in all respects with the provisions of sec- tion 360b of this title except for subsections (a)(4), (b)(2), (c)(1), (c)(2), (c)(3), (d)(1), (e), (h), and (n) of such section unless otherwise stated in this section, and any additional provisions of this section. (D) New animal drugs for which conditional approval is sought under this section are subject to the same safety standards that would be ap- plied to new animal drugs under section 360b(d) of this title (including, for antimicrobial new animal drugs, with respect to antimicrobial re- sistance). (2) The applicant shall submit to the Sec- retary as part of an application for the condi- tional approval of a new animal drug— (A) all information necessary to meet the re- quirements of section 360b(b)(1) of this title except section 360b(b)(1)(A) of this title; (B) full reports of investigations which have been made to show whether or not such drug is safe under section 360b(d) of this title (in- Page 443 TITLE 21—FOOD AND DRUGS § 360ccc 1 So in original. The period probably should be a semicolon. cluding, for an antimicrobial new animal drug, with respect to antimicrobial resistance) and there is a reasonable expectation of effective- ness for use; (C) data for establishing a conditional dose; (D) projections of expected need and the jus- tification for that expectation based on the best information available; (E) information regarding the quantity of drug expected to be distributed on an annual basis to meet the expected need; and (F) a commitment that the applicant will conduct additional investigations to meet the requirements for the full demonstration of ef- fectiveness under section 360b(d)(1)(E) of this title within 5 years. (3)(A) A person may not file an application under paragraph (1) if— (i) the application seeks conditional ap- proval of a new animal drug that is contained in, or is a product of, a transgenic animal.1 (ii) the person has previously filed an appli- cation for conditional approval under para- graph (1) for the same drug in the same dosage form for the same intended use whether or not subsequently conditionally approved by the Secretary under subsection (b); or (iii) the person obtained the application, or data or other information contained therein, directly or indirectly from the person who filed for conditional approval under paragraph (1) for the same drug in the same dosage form for the same intended use whether or not sub- sequently conditionally approved by the Sec- retary under subsection (b). (B) A person may not file an application under paragraph (1)(A)(ii) if the application seeks con- ditional approval of a new animal drug that con- tains an antimicrobial active ingredient. (4) Beginning on October 1, 2018, all applica- tions or submissions pursuant to this subsection shall be submitted by electronic means in such format as the Secretary may require. (b) Order of approval or hearing Within 180 days after the filing of an applica- tion pursuant to subsection (a), or such addi- tional period as may be agreed upon by the Sec- retary and the applicant, the Secretary shall ei- ther— (1) issue an order, effective for one year, con- ditionally approving the application if the Secretary finds that none of the grounds for denying conditional approval, specified in sub- section (c) of this section applies and publish a Federal Register notice of the conditional approval, or (2) give the applicant notice of an oppor- tunity for an informal hearing on the question whether such application can be conditionally approved. (c) Order of approval or refusal after hearing If the Secretary finds, after giving the appli- cant notice and an opportunity for an informal hearing, that— (1) any of the provisions of section 360b(d)(1)(A) through (D) or (F) through (I) of this title are applicable; (2) the information submitted to the Sec- retary as part of the application and any other information before the Secretary with respect to such drug, is insufficient to show that there is a reasonable expectation 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 la- beling thereof; or (3) another person has received approval under section 360b of this title for the same drug in the same dosage form for the same in- tended use, and that person is able to assure the availability of sufficient quantities of the drug to meet the needs for which the drug is intended; the Secretary shall issue an order refusing to conditionally approve the application. If, after such notice and opportunity for an informal hearing, the Secretary finds that paragraphs (1) through (3) do not apply, the Secretary shall issue an order conditionally approving the appli- cation effective for one year and publish a Fed- eral Register notice of the conditional approval. Any order issued under this subsection refusing to conditionally approve an application shall state the findings upon which it is based. (d) Effective period; renewal; refusal of renewal A conditional approval under this section is effective for a 1-year period and is thereafter re- newable by the Secretary annually for up to 4 additional 1-year terms. A conditional approval shall be in effect for no more than 5 years from the date of approval under subsection (b)(1) or (c) of this section unless extended as provided for in subsection (h) of this section. The fol- lowing shall also apply: (1) No later than 90 days from the end of the 1-year period for which the original or renewed conditional approval is effective, the applicant may submit a request to renew a conditional approval for an additional 1-year term. (2) A conditional approval shall be deemed renewed at the end of the 1-year period, or at the end of a 90-day extension that the Sec- retary may, at the Secretary’s discretion, grant by letter in order to complete review of the renewal request, unless the Secretary de- termines before the expiration of the 1-year period or the 90-day extension that— (A) the applicant failed to submit a timely renewal request; (B) the request fails to contain sufficient information to show that— (i) the applicant is making sufficient progress toward meeting approval require- ments under section 360b(d)(1)(E) of this title, and is likely to be able to fulfill those requirements and obtain an approval under section 360b of this title before the expiration of the 5-year maximum term of the conditional approval; (ii) the quantity of the drug that has been distributed is consistent with the conditionally approved intended use and conditions of use, unless there is adequate explanation that ensures that the drug is only used for its intended purpose; or (iii) the same drug in the same dosage form for the same intended use has not re- Page 444 TITLE 21—FOOD AND DRUGS § 360ccc ceived approval under section 360b of this title, or if such a drug has been approved, that the holder of the approved application is unable to assure the availability of suf- ficient quantities of the drug to meet the needs for which the drug is intended; or (C) any of the provisions of section 360b(e)(1)(A) through (B) or (D) through (F) of this title are applicable. (3) If the Secretary determines before the end of the 1-year period or the 90-day exten- sion, if granted, that a conditional approval should not be renewed, the Secretary shall issue an order refusing to renew the condi- tional approval, and such conditional approval shall be deemed withdrawn and no longer in effect. The Secretary shall thereafter provide an opportunity for an informal hearing to the applicant on the issue whether the conditional approval shall be reinstated. (4)(A) In the case of an application under subsection (a) with respect to a drug for which the Secretary provides notice to the sponsor that the Secretary intends to issue a scientific and medical evaluation and recommend con- trols under the Controlled Substances Act [21 U.S.C. 801 et seq.], conditional approval of such application shall not take effect until the interim final rule controlling the drug is issued in accordance with section 201(j) of the Controlled Substances Act [21 U.S.C. 811(j)]. (B) For purposes of this section, with respect to an application described in subparagraph (A), the term ‘‘date of approval’’ shall mean the later of— (i) the date an application under sub- section (a) is conditionally approved under subsection (b); or (ii) the date of issuance of the interim final rule controlling the drug. (e) Withdrawal of conditional approval (1) The Secretary shall issue an order with- drawing conditional approval of an application filed pursuant to subsection (a) if the Secretary finds that another person has received approval under section 360b of this title for the same drug in the same dosage form for the same intended use and that person is able to assure the avail- ability of sufficient quantities of the drug to meet the needs for which the drug is intended. (2) The Secretary shall, after due notice and opportunity for an informal hearing to the ap- plicant, issue an order withdrawing conditional approval of an application filed pursuant to sub- section (a) if the Secretary finds that— (A) any of the provisions of section 360b(e)(1)(A) through (B) or (D) through (F) of this title are applicable; or (B) on the basis of new information before the Secretary with respect to such drug, eval- uated together with the evidence available to the Secretary when the application was condi- tionally approved, that there is not a reason- able expectation that such drug will have the effect it purports or is represented to have under the conditions of use prescribed, rec- ommended, or suggested in the labeling there- of. (3) The Secretary may also, after due notice and opportunity for an informal hearing to the applicant, issue an order withdrawing condi- tional approval of an application filed pursuant to subsection (a) if the Secretary finds that any of the provisions of section 360b(e)(2) of this title are applicable. (f) Labeling (1) The label and labeling of a new animal drug with a conditional approval under this section shall for the conditionally approved use— (A) bear the statement, ‘‘conditionally ap- proved by FDA pending a full demonstration of effectiveness under application number’’; and (B) contain such other information as pre- scribed by the Secretary. (2) The Secretary shall, through regulation or guidance, determine under what conditions an intended use that is the subject of a conditional approval under this section may be included in the same product label with any intended use approved under section 360b of this title. (g) Amendment of application A conditionally approved new animal drug ap- plication may not be amended or supplemented to add indications for use. (h) Order of approval after conditional approval period termination 180 days prior to the termination date estab- lished under subsection (d) of this section, an applicant shall have submitted all the informa- tion necessary to support a complete new ani- mal drug application in accordance with section 360b(b)(1) of this title or the conditional ap- proval issued under this section is no longer in effect. Following review of this information, the Secretary shall either— (1) issue an order approving the application under section 360b(c) of this title if the Sec- retary finds that none of the grounds for deny- ing approval specified in section 360b(d)(1) of this title applies, or (2) give the applicant an opportunity for a hearing before the Secretary under section 360b(d) of this title on the question whether such application can be approved. Upon issuance of an order approving the applica- tion, product labeling and administrative records of approval shall be modified accord- ingly. If the Secretary has not issued an order under section 360b(c) of this title approving such application prior to the termination date estab- lished under subsection (d) of this section, the conditional approval issued under this section is no longer in effect unless the Secretary grants an extension of an additional 180-day period so that the Secretary can complete review of the application. The decision to grant an extension is committed to the discretion of the Secretary and not subject to judicial review. (i) Judicial review The decision of the Secretary under subsection (c), (d), or (e) of this section refusing or with- drawing conditional approval of an application shall constitute final agency action subject to judicial review. (j) Definition In this section and section 360ccc–1 of this title, the term ‘‘transgenic animal’’ means an Page 445 TITLE 21—FOOD AND DRUGS § 360ccc 2 So in original. The word ‘‘subsection’’ probably should ap- pear. 3 So in original. The word ‘‘section’’ probably should appear. animal whose genome contains a nucleotide se- quence that has been intentionally modified in vitro, and the progeny of such an animal; Pro- vided that the term ‘‘transgenic animal’’ does not include an animal of which the nucleotide sequence of the genome has been modified solely by selective breeding. (k) Sunset (1) The Secretary’s authority to grant condi- tional approval of new animal drugs not in- tended for a minor use or minor species pursu- ant to subsection (a)(1)(A)(ii) terminates on Oc- tober 1, 2028. (2) The Secretary— (A) may not accept any new applications for such conditional approval pursuant to sub- section (a)(1)(A)(ii) on or after such date; and (B) may continue all activities under this section with respect to drugs that were condi- tionally approved pursuant to 2 (a)(1)(A)(ii) prior to such date. (3) The Secretary may, until October 1, 2032, accept applications for approval under 3 360b of this title of drugs conditionally approved pursu- ant to 2 (a)(1)(A)(ii). (June 25, 1938, ch. 675, § 571, as added Pub. L. 108–282, title I, § 102(b)(4), Aug. 2, 2004, 118 Stat. 892; amended Pub. L. 114–89, § 2(a)(3)(B), Nov. 25, 2015, 129 Stat. 699; Pub. L. 115–234, title III, §§ 301(b), 304(a), Aug. 14, 2018, 132 Stat. 2436.) Editorial Notes REFERENCES IN TEXT The Controlled Substances Act, referred to in subsec. (d)(4)(A), is title II of Pub. L. 91–513, Oct. 27, 1970, 84 Stat. 1242, which is classified principally to subchapter I (§ 801 et seq.) of chapter 13 of this title. For complete classification of this Act to the Code, see Short Title note set out under section 801 of this title and Tables. AMENDMENTS 2018—Pub. L. 115–234, § 304(a)(1), substituted ‘‘species and certain new animal drugs’’ for ‘‘species’’ in section catchline. Subsec. (a)(1). Pub. L. 115–234, § 304(a)(2)(A), amended par. (1) generally. Prior to amendment, par. (1) read as follows: ‘‘Except as provided in paragraph (3) of this section, any person may file with the Secretary an ap- plication for conditional approval of a new animal drug intended for a minor use or a minor species. Such an application may not be a supplement to an application approved under section 360b of this title. Such applica- tion must comply in all respects with the provisions of section 360b of this title except sections 360b(a)(4), 360b(b)(2), 360b(c)(1), 360b(c)(2), 360b(c)(3), 360b(d)(1), 360b(e), 360b(h), and 360b(n) of this title unless other- wise stated in this section, and any additional provi- sions of this section. New animal drugs are subject to application of the same safety standards that would be applied to such drugs under section 360b(d) of this title (including, for antimicrobial new animal drugs, with respect to antimicrobial resistance).’’ Subsec. (a)(3). Pub. L. 115–234, § 304(a)(2)(B), des- ignated existing provisions as subpar. (A), redesignated former subpars. (A) to (C) as cls. (i) to (iii), respec- tively, of subpar. (A), and added subpar. (B). Subsec. (a)(4). Pub. L. 115–234, § 301(b), added par. (4). Subsec. (f)(1). Pub. L. 115–234, § 304(a)(3)(A), inserted ‘‘for the conditionally approved use’’ after ‘‘shall’’ in introductory provisions. Subsec. (f)(2). Pub. L. 115–234, § 304(a)(3)(B), sub- stituted ‘‘The Secretary shall, through regulation or guidance, determine under what conditions an intended use’’ for ‘‘An intended use’’ and ‘‘may be included’’ for ‘‘shall not be included’’. Subsec. (k). Pub. L. 115–234, § 304(a)(4), added subsec. (k). 2015—Subsec. (d)(4). Pub. L. 114–89 added par. (4). Statutory Notes and Related Subsidiaries FINDINGS Pub. L. 108–282, title I, § 102(a), Aug. 2, 2004, 118 Stat. 891, provided that: ‘‘Congress makes the following find- ings: ‘‘(1) There is a severe shortage of approved new ani- mal drugs for use in minor species. ‘‘(2) There is a severe shortage of approved new ani- mal drugs for treating animal diseases and conditions that occur infrequently or in limited geographic areas. ‘‘(3) Because of the small market shares, low-profit margins involved, and capital investment required, it is generally not economically feasible for new animal drug applicants to pursue approvals for these species, diseases, and conditions. ‘‘(4) Because the populations for which such new animal drugs are intended may be small and condi- tions of animal management may vary widely, it is often difficult to design and conduct studies to estab- lish drug safety and effectiveness under traditional new animal drug approval processes. ‘‘(5) It is in the public interest and in the interest of animal welfare to provide for special procedures to allow the lawful use and marketing of certain new animal drugs for minor species and minor uses that take into account these special circumstances and that ensure that such drugs do not endanger animal or public health. ‘‘(6) Exclusive marketing rights for clinical testing expenses have helped encourage the development of ‘orphan’ drugs for human use, and comparable incen- tives should encourage the development of new ani- mal drugs for minor species and minor uses.’’ REGULATIONS Pub. L. 108–282, title I, § 102(b)(6), Aug. 2, 2004, 118 Stat. 905, provided that: ‘‘On the date of enactment of this Act [Aug. 2, 2004], the Secretary of Health and Human Services shall implement sections 571 and 573 of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 360ccc, 360ccc–2] and subsequently publish imple- menting regulations. Not later than 12 months after the date of enactment of this Act, the Secretary shall issue proposed regulations to implement section 573 of the Federal Food, Drug, and Cosmetic Act (as added by this Act), and not later than 24 months after the date of enactment of this Act, the Secretary shall issue final regulations implementing section 573 of the Federal Food, Drug, and Cosmetic Act. Not later than 18 months after the date of enactment of this Act, the Secretary shall issue proposed regulations to imple- ment section 572 of the Federal Food, Drug, and Cos- metic Act (as added by this Act) [21 U.S.C. 360ccc–1], and not later than 36 months after the date of enact- ment of this Act, the Secretary shall issue final regula- tions implementing section 572 of the Federal Food, Drug, and Cosmetic Act. Not later than 30 months after the date of enactment of this Act, the Secretary shall issue proposed regulations to implement section 571 of the Federal Food, Drug, and Cosmetic Act (as added by this Act), and not later than 42 months after the date of enactment of this Act, the Secretary shall issue final regulations implementing section 571 of the Federal Food, Drug, and Cosmetic Act. These timeframes shall be extended by 12 months for each fiscal year, in which the funds authorized to be appropriated under sub- section (i) [no subsection (i) of section 102 has been en- acted] are not in fact appropriated.’’ Page 446 TITLE 21—FOOD AND DRUGS § 360ccc–1 § 360ccc–1. Index of legally marketed unapproved new animal drugs for minor species (a) Establishment and content (1) The Secretary shall establish an index lim- ited to— (A) new animal drugs intended for use in a minor species for which there is a reasonable certainty that the animal or edible products from the animal will not be consumed by hu- mans or food-producing animals; and (B) new animal drugs intended for use only in a hatchery, tank, pond, or other similar contained man-made structure in an early, non-food life stage of a food-producing minor species, where safety for humans is dem- onstrated in accordance with the standard of section 360b(d) of this title (including, for an antimicrobial new animal drug, with respect to antimicrobial resistance). (2) The index shall not include a new animal drug that is contained in or a product of a transgenic animal. (b) Conferences Any person intending to file a request under this section shall be entitled to one or more con- ferences to discuss the requirements for index- ing a new animal drug. (c) Request for determination of eligibility for in- clusion in index (1) Any person may submit a request to the Secretary for a determination whether a new animal drug may be eligible for inclusion in the index. Such a request shall include— (A) information regarding the need for the new animal drug, the species for which the new animal drug is intended, the proposed in- tended use and conditions of use, and antici- pated annual distribution; (B) information to support the conclusion that the proposed use meets the conditions of subparagraph (A) or (B) of subsection (a)(1) of this section; (C) information regarding the components and composition of the new animal drug; (D) a description of the methods used in, and the facilities and controls used for, the manu- facture, processing, and packing of such new animal drug; (E) an environmental assessment that meets the requirements of the National Environ- mental Policy Act of 1969 [42 U.S.C. 4321 et seq.], as amended, and as defined in 21 CFR Part 25, as it appears on August 2, 2004, and amended thereafter or information to support a categorical exclusion from the requirement to prepare an environmental assessment; (F) information sufficient to support the conclusion that the proposed use of the new animal drug is safe under section 360b(d) of this title with respect to individuals exposed to the new animal drug through its manufac- ture or use; and (G) such other information as the Secretary may deem necessary to make this eligibility determination. (2) Within 90 days after the submission of a re- quest for a determination of eligibility for in- dexing based on subsection (a)(1)(A) of this sec- tion, or 180 days for a request submitted based on subsection (a)(1)(B) of this section, the Sec- retary shall grant or deny the request, and no- tify the person who requested such determina- tion of the Secretary’s decision. The Secretary shall grant the request if the Secretary finds that— (A) the same drug in the same dosage form for the same intended use is not approved or conditionally approved; (B) the proposed use of the drug meets the conditions of subparagraph (A) or (B) of sub- section (a)(1), as appropriate; (C) the person requesting the determination has established appropriate specifications for the manufacture and control of the new ani- mal drug and has demonstrated an under- standing of the requirements of current good manufacturing practices; (D) the new animal drug will not signifi- cantly affect the human environment; and (E) the new animal drug is safe with respect to individuals exposed to the new animal drug through its manufacture or use. If the Secretary denies the request, the Sec- retary shall thereafter provide due notice and an opportunity for an informal conference. A deci- sion of the Secretary to deny an eligibility re- quest following an informal conference shall constitute final agency action subject to judi- cial review. (d) Request for addition to index (1) With respect to a new animal drug for which the Secretary has made a determination of eligibility under subsection (c), the person who made such a request may ask that the Sec- retary add the new animal drug to the index es- tablished under subsection (a). The request for addition to the index shall include— (A) a copy of the Secretary’s determination of eligibility issued under subsection (c); (B) a written report that meets the require- ments in subsection (d)(2) of this section; (C) a proposed index entry; (D) facsimile labeling; (E) anticipated annual distribution of the new animal drug; (F) a written commitment to manufacture the new animal drug and animal feeds bearing or containing such new animal drug according to current good manufacturing practices; (G) a written commitment to label, dis- tribute, and promote the new animal drug only in accordance with the index entry; (H) upon specific request of the Secretary, information submitted to the expert panel de- scribed in paragraph (3); and (I) any additional requirements that the Secretary may prescribe by general regulation or specific order. (2) The report required in paragraph (1) shall— (A) be authored by a qualified expert panel; (B) include an evaluation of all available target animal safety and effectiveness infor- mation, including anecdotal information; (C) state the expert panel’s opinion regard- ing whether the benefits of using the new ani- mal drug for the proposed use in a minor spe- cies outweigh its risks to the target animal,