--- kind: "section" citation: "21 U.S.C. § 360b" title: "21" title_heading: "Food and Drugs" number: "360b" heading: "New animal drugs" release: "119-102" date: "2026-07-12" url: "https://uscodex.org/usc/21/360b" units: - "Chapter 9 — Federal Food, Drug, and Cosmetic Act" - "Subchapter V — Drugs and Devices" - "Part A — Drugs and Devices" --- # §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](/usc/21/321.md?p=v) shall, with respect to any particular use or intended use of such [drug](/usc/21/321.md?p=g-1), be deemed unsafe for purposes of [section 351(a)(5) of this title](/usc/21/351.md) and [section 342(a)(2)(C)(ii) of this title](/usc/21/342.md) unless— - (A) there is in effect an approval of an application filed pursuant to [subsection (b)](#b) with respect to such use or intended use of such [drug](/usc/21/321.md?p=g-1), and such [drug](/usc/21/321.md?p=g-1), its [labeling](/usc/21/321.md?p=m), and such use conform to such approved application; - (B) there is in effect a conditional approval of an application filed pursuant to [section 360ccc of this title](/usc/21/360ccc.md) with respect to such use or intended use of such [drug](/usc/21/321.md?p=g-1), and such [drug](/usc/21/321.md?p=g-1), its [labeling](/usc/21/321.md?p=m), and such use conform to such conditionally approved application; - (C) there is in effect an index listing pursuant to [section 360ccc–1 of this title](/usc/21/360ccc–1.md) with respect to such use or intended use of such [drug](/usc/21/321.md?p=g-1) in a [minor species](/usc/21/321.md?p=oo), and such [drug](/usc/21/321.md?p=g-1), its [labeling](/usc/21/321.md?p=m), and such use conform to such index listing; or - (D) there is in effect an authorization pursuant to [section 360bbb–3 of this title](/usc/21/360bbb–3.md) with respect to such use or intended use of such [drug](/usc/21/321.md?p=g-1), and such [drug](/usc/21/321.md?p=g-1), its [labeling](/usc/21/321.md?p=m), and such use conform to any conditions of such authorization. A [new animal drug](/usc/21/321.md?p=v) shall also be deemed unsafe for such purposes in the event of removal from the establishment of a [manufacturer](/usc/21/360hh.md?p=3), packer, or distributor of such [drug](/usc/21/321.md?p=g-1) for use in the manufacture of [animal feed](/usc/21/321.md?p=w) in any [State](/usc/21/321.md?p=a-1) unless at the time of such removal such [manufacturer](/usc/21/360hh.md?p=3), packer, or distributor has an unrevoked written statement from the consignee of such [drug](/usc/21/321.md?p=g-1), or notice from the [Secretary](/usc/21/321.md?p=d), to the effect that, with respect to the use of such [drug](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w), such consignee (i) holds a license issued under [subsection (m)](#m) and has in its possession current approved [labeling](/usc/21/321.md?p=m) for such [drug](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w); or (ii) will, if the consignee is not a user of the [drug](/usc/21/321.md?p=g-1), ship such [drug](/usc/21/321.md?p=g-1) only to a holder of a license issued under [subsection (m)](#m). - (2) An [animal feed](/usc/21/321.md?p=w) bearing or containing a [new animal drug](/usc/21/321.md?p=v) shall, with respect to any particular use or intended use of such [animal feed](/usc/21/321.md?p=w) be deemed unsafe for purposes of [section 351(a)(6) of this title](/usc/21/351.md) unless— - (A) there is in effect— - (i) an approval of an application filed pursuant to [subsection (b)](#b) with respect to such [drug](/usc/21/321.md?p=g-1), as used in such [animal feed](/usc/21/321.md?p=w), and such [animal feed](/usc/21/321.md?p=w) and its [labeling](/usc/21/321.md?p=m), [distribution](/usc/21/360eee.md?p=5), holding, and use conform to such approved application; - (ii) a conditional approval of an application filed pursuant to [section 360ccc of this title](/usc/21/360ccc.md) with respect to such [drug](/usc/21/321.md?p=g-1), as used in such [animal feed](/usc/21/321.md?p=w), and such [animal feed](/usc/21/321.md?p=w) and its [labeling](/usc/21/321.md?p=m), [distribution](/usc/21/360eee.md?p=5), holding, and use conform to such conditionally approved application; or - (iii) an index listing pursuant to [section 360ccc–1 of this title](/usc/21/360ccc–1.md) with respect to such [drug](/usc/21/321.md?p=g-1), as used in such [animal feed](/usc/21/321.md?p=w), and such [animal feed](/usc/21/321.md?p=w) and its [labeling](/usc/21/321.md?p=m), [distribution](/usc/21/360eee.md?p=5), holding, and use conform to such index listing; and - (B) such [animal feed](/usc/21/321.md?p=w) is manufactured at a site for which there is in effect a license issued pursuant to [subsection (m)(1)](#m-1) to manufacture such [animal feed](/usc/21/321.md?p=w). - (3) A [new animal drug](/usc/21/321.md?p=v) or an [animal feed](/usc/21/321.md?p=w) bearing or containing a [new animal drug](/usc/21/321.md?p=v) shall not be deemed unsafe for the purposes of [section 351(a)(5)](/usc/21/351.md) 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)](#j). - (4) - (A) Except as provided in [subparagraph (B)](#a-4-B), if an approval of an application filed under [subsection (b)](#b) is in effect with respect to a particular use or intended use of a [new animal drug](/usc/21/321.md?p=v), the [drug](/usc/21/321.md?p=g-1) shall not be deemed unsafe for the purposes of [paragraph (1)](#a-1) and shall be exempt from the requirements of [section 352(f) of this title](/usc/21/352.md?p=f) with respect to a different use or intended use of the [drug](/usc/21/321.md?p=g-1), other than a use in or on [animal feed](/usc/21/321.md?p=w), if such use or intended use— - (i) is by or on the lawful written or oral order of a [licensed](/usc/21/360eee.md?p=9) veterinarian within the context of a veterinarian-client-patient relationship, as defined by the [Secretary](/usc/21/321.md?p=d); and - (ii) is in compliance with regulations promulgated by the [Secretary](/usc/21/321.md?p=d) that establish the conditions for such different use or intended use. The regulations promulgated by the [Secretary](/usc/21/321.md?p=d) under [clause (ii)](#a-4-A-ii) may prohibit particular uses of an animal [drug](/usc/21/321.md?p=g-1) and shall not permit such different use of an animal [drug](/usc/21/321.md?p=g-1) if the [labeling](/usc/21/321.md?p=m) of another animal [drug](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=d) finds that there is a reasonable probability that a use of an animal [drug](/usc/21/321.md?p=g-1) [authorized](/usc/21/360eee.md?p=2) under [subparagraph (A)](#a-4-A) may present a risk to the public health, the [Secretary](/usc/21/321.md?p=d) may— - (i) establish a [safe](/usc/21/321.md?p=u) level for a residue of an animal [drug](/usc/21/321.md?p=g-1) when it is used for such different use [authorized](/usc/21/360eee.md?p=2) by [subparagraph (A)](#a-4-A); and - (ii) require the development of a practical, analytical method for the detection of residues of such [drug](/usc/21/321.md?p=g-1) above the [safe](/usc/21/321.md?p=u) level established under [clause (i)](#a-4-B-i). The use of an animal [drug](/usc/21/321.md?p=g-1) that results in residues exceeding a [safe](/usc/21/321.md?p=u) level established under [clause (i)](#a-4-B-i) shall be considered an unsafe use of such [drug](/usc/21/321.md?p=g-1) under [paragraph (1)](#a-1). [Safe](/usc/21/321.md?p=u) levels may be established under [clause (i)](#a-4-B-i) either by regulation or order. - (C) The [Secretary](/usc/21/321.md?p=d) may by general regulation provide access to the records of veterinarians to ascertain any use or intended use [authorized](/usc/21/360eee.md?p=2) under [subparagraph (A)](#a-4-A) that the [Secretary](/usc/21/321.md?p=d) has determined may present a risk to the public health. - (D) If the [Secretary](/usc/21/321.md?p=d) finds, after affording an opportunity for public comment, that a use of an animal [drug](/usc/21/321.md?p=g-1) [authorized](/usc/21/360eee.md?p=2) under [subparagraph (A)](#a-4-A) presents a risk to the public health or that an analytical method required under [subparagraph (B)](#a-4-B) has not been developed and submitted to the [Secretary](/usc/21/321.md?p=d), the [Secretary](/usc/21/321.md?p=d) may, by order, prohibit any such use. - (5) If the approval of an application filed under [section 355 of this title](/usc/21/355.md) is in effect, the [drug](/usc/21/321.md?p=g-1) under such application shall not be deemed unsafe for purposes of [paragraph (1)](#a-1) and shall be exempt from the requirements of [section 352(f) of this title](/usc/21/352.md?p=f) with respect to a use or intended use of the [drug](/usc/21/321.md?p=g-1) in animals if such use or intended use— - (A) is by or on the lawful written or oral order of a [licensed](/usc/21/360eee.md?p=9) veterinarian within the context of a veterinarian-client-patient relationship, as defined by the [Secretary](/usc/21/321.md?p=d); and - (B) is in compliance with regulations promulgated by the [Secretary](/usc/21/321.md?p=d) that establish the conditions for the use or intended use of the [drug](/usc/21/321.md?p=g-1) in animals. - (6) For purposes of [section 342(a)(2)(D)](/usc/21/342.md)[^1] of this title, a use or intended use of a [new animal drug](/usc/21/321.md?p=v) shall not be deemed unsafe under this section if the [Secretary](/usc/21/321.md?p=d) establishes a tolerance for such [drug](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=d) shall rely on data sufficient to demonstrate that a proposed tolerance is [safe](/usc/21/321.md?p=u) based on similar [food](/usc/21/321.md?p=f) safety criteria used by the [Secretary](/usc/21/321.md?p=d) to establish tolerances for applications for [new animal drugs](/usc/21/321.md?p=v) filed under [subsection (b)(1)](#b-1). The [Secretary](/usc/21/321.md?p=d) may consider and rely on data submitted by the [drug](/usc/21/321.md?p=g-1) [manufacturer](/usc/21/360hh.md?p=3), including data submitted to appropriate regulatory authorities in any country where the [new animal drug](/usc/21/321.md?p=v) 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](/usc/21/321.md?p=d) to establish a tolerance for applications for [new animal drugs](/usc/21/321.md?p=v) filed under [subsection (b)(1)](#b-1). For purposes of this paragraph, “relevant international organization” means the Codex Alimenterius[^2] Commission or other international organization deemed appropriate by the [Secretary](/usc/21/321.md?p=d). The [Secretary](/usc/21/321.md?p=d) may, under procedures specified by regulation, revoke a tolerance established under this paragraph if information demonstrates that the use of the [new animal drug](/usc/21/321.md?p=v) under actual use conditions results in [food](/usc/21/321.md?p=f) 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](/usc/21/321.md?p=e) may file with the [Secretary](/usc/21/321.md?p=d) an application with respect to any intended use or uses of a [new animal drug](/usc/21/321.md?p=v). Such [person](/usc/21/321.md?p=e) shall submit to the [Secretary](/usc/21/321.md?p=d) as a part of the application (A) full reports of investigations which have been made to show whether or not such [drug](/usc/21/321.md?p=g-1) is [safe](/usc/21/321.md?p=u) and effective for use; (B) a full list of the articles used as components of such [drug](/usc/21/321.md?p=g-1); (C) a full statement of the composition of such [drug](/usc/21/321.md?p=g-1); (D) a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such [drug](/usc/21/321.md?p=g-1); (E) such samples of such [drug](/usc/21/321.md?p=g-1) and of the articles used as components thereof, of any [animal feed](/usc/21/321.md?p=w) for use in or on which such [drug](/usc/21/321.md?p=g-1) is intended, and of the edible portions or [products](/usc/21/360eee.md?p=13) (before or after slaughter) of animals to which such [drug](/usc/21/321.md?p=g-1) (directly or in or on [animal feed](/usc/21/321.md?p=w)) is intended to be administered, as the [Secretary](/usc/21/321.md?p=d) may require; (F) specimens of the [labeling](/usc/21/321.md?p=m) proposed to be used for such [drug](/usc/21/321.md?p=g-1), or in case such [drug](/usc/21/321.md?p=g-1) is intended for use in [animal feed](/usc/21/321.md?p=w), proposed [labeling](/usc/21/321.md?p=m) appropriate for such use, and specimens of the [labeling](/usc/21/321.md?p=m) for the [drug](/usc/21/321.md?p=g-1) to be manufactured, packed, or distributed by the applicant; (G) a description of practicable methods for determining the quantity, if any, of such [drug](/usc/21/321.md?p=g-1) in or on [food](/usc/21/321.md?p=f), and any substance formed in or on [food](/usc/21/321.md?p=f), because of its use; and (H) the proposed tolerance or withdrawal period or other use restrictions for such [drug](/usc/21/321.md?p=g-1) if any tolerance or withdrawal period or other use restrictions are required in order to assure that the proposed use of such [drug](/usc/21/321.md?p=g-1) will be [safe](/usc/21/321.md?p=u). The applicant shall file with the application the patent number and the expiration date of any patent which claims the [new animal drug](/usc/21/321.md?p=v) for which the applicant filed the application or which claims a method of using such [drug](/usc/21/321.md?p=g-1) and with respect to which a claim of patent infringement could reasonably be asserted if a [person](/usc/21/321.md?p=e) not [licensed](/usc/21/360eee.md?p=9) by the owner engaged in the manufacture, use, or sale of the [drug](/usc/21/321.md?p=g-1). If an application is filed under this subsection for a [drug](/usc/21/321.md?p=g-1) and a patent which claims such [drug](/usc/21/321.md?p=g-1) or a method of using such [drug](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=d) shall publish information submitted under the two preceding sentences. - (2) Any [person](/usc/21/321.md?p=e) may file with the [Secretary](/usc/21/321.md?p=d) an abbreviated application for the approval of a [new animal drug](/usc/21/321.md?p=v). An abbreviated application shall contain the information required by [subsection (n)](#n). - (3) Any [person](/usc/21/321.md?p=e) intending to file an application under [paragraph (1)](#b-1), [section 360ccc of this title](/usc/21/360ccc.md), or a request for an investigational exemption under [subsection (j)](#j) shall be entitled to one or more conferences prior to such submission to reach an agreement acceptable to the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=d) and the applicant or requestor unless (A) the [Secretary](/usc/21/321.md?p=d) and the applicant or requestor mutually agree to modify the requirement, or (B) the [Secretary](/usc/21/321.md?p=d) by written order determines that a substantiated scientific requirement essential to the determination of safety or effectiveness of the animal [drug](/usc/21/321.md?p=g-1) involved has appeared after the conference. No later than 25 calendar days after each such conference, the [Secretary](/usc/21/321.md?p=d) shall provide a written order setting forth a scientific justification specific to the animal [drug](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=g-1). Nothing in this paragraph shall be construed as compelling the [Secretary](/usc/21/321.md?p=d) to require a field investigation. - (4) Beginning on October 1, 2018, all applications or submissions pursuant to this subsection shall be submitted by electronic means in such format as the [Secretary](/usc/21/321.md?p=d) may require. - (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)](#b), or such additional period as may be agreed upon by the [Secretary](/usc/21/321.md?p=d) and the applicant, the [Secretary](/usc/21/321.md?p=d) 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)](#d) applies, or (B) give the applicant notice of an opportunity for a hearing before the [Secretary](/usc/21/321.md?p=d) under [subsection (d)](#d) 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](/usc/21/321.md?p=d) and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the [Secretary](/usc/21/321.md?p=d)’s order thereon shall be issued within ninety days after the date fixed by the [Secretary](/usc/21/321.md?p=d) for filing final briefs. - (2) - (A) Subject to [subparagraph (C)](#c-2-C), the [Secretary](/usc/21/321.md?p=d) shall approve an abbreviated application for a [drug](/usc/21/321.md?p=g-1) unless the [Secretary](/usc/21/321.md?p=d) finds— - (i) the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of the [drug](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=m) are not reasonably certain to be followed in practice or, except as provided in [subparagraph (B)](#c-2-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](/usc/21/321.md?p=m) or published pursuant to [subsection (i)](#i)) have been previously approved for the approved [new animal drug](/usc/21/321.md?p=v) 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](/usc/21/321.md?p=v) referred to in the application; - (iv) - (I) if the application is for a [drug](/usc/21/321.md?p=g-1) whose active ingredients, route of administration, dosage form, strength, or use with other animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w) is the same as the active ingredients, route of administration, dosage form, strength, or use with other animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w) of the approved [new animal drug](/usc/21/321.md?p=v) 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](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w) is the same as that of the approved [new animal drug](/usc/21/321.md?p=v), or - (II) if the application is for a [drug](/usc/21/321.md?p=g-1) whose active ingredients, route of administration, dosage form, strength, or use with other animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w) is different from that of the approved [new animal drug](/usc/21/321.md?p=v) referred to in the application, no petition to file an application for the [drug](/usc/21/321.md?p=g-1) with the different active ingredients, route of administration, dosage form, strength, or use with other animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w) was approved under [subsection (n)(3)](#n-3); - (v) if the application was filed pursuant to the approval of a petition under [subsection (n)(3)](#n-3), the application did not contain the information required by the [Secretary](/usc/21/321.md?p=d) respecting the active ingredients, route of administration, dosage form, strength, or use with other animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w) which is not the same; - (vi) information submitted in the application is insufficient to show that the [drug](/usc/21/321.md?p=g-1) is bioequivalent to the approved [new animal drug](/usc/21/321.md?p=v) referred to in the application, or if the application is filed under a petition approved pursuant to [subsection (n)(3)](#n-3), information submitted in the application is insufficient to show that the active ingredients of the [new animal drug](/usc/21/321.md?p=v) are of the same pharmacological or therapeutic class as the pharmacological or therapeutic class of the approved [new animal drug](/usc/21/321.md?p=v) and that the [new animal drug](/usc/21/321.md?p=v) can be expected to have the same therapeutic effect as the approved [new animal drug](/usc/21/321.md?p=v) when used in accordance with the [labeling](/usc/21/321.md?p=m); - (vii) information submitted in the application is insufficient to show that the [labeling](/usc/21/321.md?p=m) proposed for the [drug](/usc/21/321.md?p=g-1) is the same as the [labeling](/usc/21/321.md?p=m) approved for the approved [new animal drug](/usc/21/321.md?p=v) referred to in the application except for changes required because of differences approved under a petition filed under [subsection (n)(3)](#n-3), because of a different withdrawal period, or because the [drug](/usc/21/321.md?p=g-1) and the approved [new animal drug](/usc/21/321.md?p=v) are produced or distributed by different [manufacturers](/usc/21/360hh.md?p=3); - (viii) information submitted in the application or any other information available to the [Secretary](/usc/21/321.md?p=d) shows that (I) the inactive ingredients of the [drug](/usc/21/321.md?p=g-1) are unsafe for use under the conditions prescribed, recommended, or suggested in the [labeling](/usc/21/321.md?p=m) proposed for the [drug](/usc/21/321.md?p=g-1), (II) the composition of the [drug](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=g-1) for [food](/usc/21/321.md?p=f) producing animals, the inactive ingredients of the [drug](/usc/21/321.md?p=g-1) or its composition may be unsafe with respect to human [food](/usc/21/321.md?p=f) safety; - (ix) the approval under [subsection (b)(1)](#b-1) of the approved [new animal drug](/usc/21/321.md?p=v) referred to in the application filed under [subsection (b)(2)](#b-2) has been withdrawn or suspended for grounds described in [paragraph (1)](#e-1) of subsection (e), the [Secretary](/usc/21/321.md?p=d) has published a notice of a hearing to withdraw approval of the approved [new animal drug](/usc/21/321.md?p=v) for such grounds, the approval under this paragraph of the [new animal drug](/usc/21/321.md?p=v) for which the application under [subsection (b)(2)](#b-2) was filed has been withdrawn or suspended under [subparagraph (G)](#c-2-G) for such grounds, or the [Secretary](/usc/21/321.md?p=d) has determined that the approved [new animal drug](/usc/21/321.md?p=v) has been withdrawn from sale for safety or effectiveness reasons; - (x) the application does not meet any other requirement of [subsection (n)](#n); or - (xi) the application contains an untrue statement of material fact. - (B) If the [Secretary](/usc/21/321.md?p=d) finds that a [new animal drug](/usc/21/321.md?p=v) for which an application is submitted under [subsection (b)(2)](#b-2) is bioequivalent to the approved [new animal drug](/usc/21/321.md?p=v) referred to in such application and that residues of the [new animal drug](/usc/21/321.md?p=v) are consistent with the tolerances established for such approved [new animal drug](/usc/21/321.md?p=v) but at a withdrawal period which is different than the withdrawal period approved for such approved [new animal drug](/usc/21/321.md?p=v), the [Secretary](/usc/21/321.md?p=d) may establish, on the basis of information submitted, such different withdrawal period as the withdrawal period for the [new animal drug](/usc/21/321.md?p=v) for purposes of the approval of such application for such [drug](/usc/21/321.md?p=g-1). - (C) Within 180 days of the initial receipt of an application under [subsection (b)(2)](#b-2) or within such additional period as may be agreed upon by the [Secretary](/usc/21/321.md?p=d) and the applicant, the [Secretary](/usc/21/321.md?p=d) shall approve or disapprove the application. - (D) The approval of an application filed under [subsection (b)(2)](#b-2) 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) 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), the approval may be made effective on the date certified under [clause (iii)](#c-2-D-iii). - (iii) If the applicant made a certification described in clause (iv) of subsection (n)(1)(G), 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) 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)](#n-2-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 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 [section 271(e)(4)(A) of title 35](/usc/35/271.md?p=e-4-A), or - (III) the court grants a preliminary injunction prohibiting the applicant from engaging in the commercial manufacture or sale of the [drug](/usc/21/321.md?p=g-1) 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)](#n-2-B) is received, no action may be brought under [section 2201 of title 28](/usc/28/2201.md) for a declaratory judgment with respect to the patent. Any action brought under [section 2201 of title 28](/usc/28/2201.md) shall be brought in the judicial district where the defendant has its principal place of business or a regular and established place of business. - (iv) If the application contains a certification described in clause (iv) of subsection (n)(1)(G) and is for a [drug](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=d) receives notice from the applicant under the previous application of the first commercial marketing of the [drug](/usc/21/321.md?p=g-1) under the previous application, or - (II) the date of a decision of a court in an action described in subclause (III)[^3] holding the patent which is the subject of the certification to be invalid or not infringed, whichever is earlier. - (E) If the [Secretary](/usc/21/321.md?p=d) decides to disapprove an application, the [Secretary](/usc/21/321.md?p=d) shall give the applicant notice of an opportunity for a hearing before the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=d) and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the [Secretary](/usc/21/321.md?p=d)’s order thereon shall be issued within 90 days after the date fixed by the [Secretary](/usc/21/321.md?p=d) for filing final briefs. - (F) - (i) If an application submitted under [subsection (b)(1)](#b-1) for a [drug](/usc/21/321.md?p=g-1), no active moiety (as defined by the [Secretary](/usc/21/321.md?p=d) in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) of which has been approved in any other application under [subsection (b)(1)](#b-1), is approved after November 16, 1988, no application may be submitted under [subsection (b)(2)](#b-2) which refers to the [drug](/usc/21/321.md?p=g-1) for which the [subsection (b)(1)](#b-1) application was submitted before the expiration of 5 years from the date of the approval of the application under [subsection (b)(1)](#b-1), except that such an application may be submitted under [subsection (b)(2)](#b-2) after the expiration of 4 years from the date of the approval of the [subsection (b)(1)](#b-1) application if it contains a certification of patent invalidity or noninfringement described in clause (iv) of subsection (n)(1)(G). The approval of such an application shall be made effective in accordance with [subparagraph (B)](#c-2-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)](#b) application, the 30 month period referred to in [subparagraph (D)(iii)](#c-2-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)](#b) application. - (ii) If an application submitted under [subsection (b)(1)](#b-1) for a [drug](/usc/21/321.md?p=g-1), which includes an active moiety (as defined by the [Secretary](/usc/21/321.md?p=d) in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) 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](/usc/21/321.md?p=g-1) involved, any studies of animal safety, or, in the case of [food](/usc/21/321.md?p=f) producing animals, human [food](/usc/21/321.md?p=f) safety studies (other than bioequivalence studies or residue depletion studies, except residue depletion studies for [minor uses](/usc/21/321.md?p=pp) or [minor species](/usc/21/321.md?p=oo)) required for the approval of the application and conducted or sponsored by the applicant, the [Secretary](/usc/21/321.md?p=d) may not make the approval of an application submitted under [subsection (b)(2)](#b-2) for the conditions of approval of such [drug](/usc/21/321.md?p=g-1) in the [subsection (b)(1)](#b-1) application effective before the expiration of 3 years from the date of the approval of the application under [subsection (b)(1)](#b-1) for such [drug](/usc/21/321.md?p=g-1). - (iii) If a supplement to an application approved under [subsection (b)(1)](#b-1) is approved after November 16, 1988, and the supplement contains substantial evidence of the effectiveness of the [drug](/usc/21/321.md?p=g-1) involved, any studies of animal safety, or, in the case of [food](/usc/21/321.md?p=f) producing animals, human [food](/usc/21/321.md?p=f) safety studies (other than bioequivalence studies or residue depletion studies, except residue depletion studies for [minor uses](/usc/21/321.md?p=pp) or [minor species](/usc/21/321.md?p=oo)) required for the approval of the supplement and conducted or sponsored by the [person](/usc/21/321.md?p=e) submitting the supplement, the [Secretary](/usc/21/321.md?p=d) may not make the approval of an application submitted under [subsection (b)(2)](#b-2) 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)](#b-1) 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](/usc/21/321.md?p=f) 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)](#b-2) set forth in clause (ii) of this subparagraph shall be applicable to the [subsection (b)(1)](#b-1) application. - (v) If an application (including any supplement to a [new animal drug](/usc/21/321.md?p=v) application) submitted under [subsection (b)(1)](#b-1) for a [new animal drug](/usc/21/321.md?p=v) for a [food](/usc/21/321.md?p=f)-producing animal use, which includes an active moiety (as defined by the [Secretary](/usc/21/321.md?p=d) in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) which has been the subject of a waiver under [clause (iv)](#c-2-F-iv) is approved after November 16, 1988, and if the application contains substantial evidence of the effectiveness of the [drug](/usc/21/321.md?p=g-1) involved, any studies of animal safety, or human [food](/usc/21/321.md?p=f) safety studies (other than bioequivalence studies or residue depletion studies, except residue depletion studies for [minor uses](/usc/21/321.md?p=pp) or [minor species](/usc/21/321.md?p=oo)) required for the new approval of the application and conducted or sponsored by the applicant, the [Secretary](/usc/21/321.md?p=d) may not make the approval of an application (including any supplement to such application) submitted under [subsection (b)(2)](#b-2) for the new conditions of approval of such [drug](/usc/21/321.md?p=g-1) in the [subsection (b)(1)](#b-1) application effective before the expiration of five years from the date of approval of the application under [subsection (b)(1)](#b-1) for such [drug](/usc/21/321.md?p=g-1). The provisions of this paragraph shall apply only to the first approval for a [food](/usc/21/321.md?p=f)-producing animal use for the same applicant after the waiver under [clause (iv)](#c-2-F-iv). - (G) If an approved application submitted under [subsection (b)(2)](#b-2) for a [new animal drug](/usc/21/321.md?p=v) refers to a [drug](/usc/21/321.md?p=g-1) the approval of which was withdrawn or suspended for grounds described in paragraph [(1)](#e-1) or [(2)](#e-2) of subsection (e) or was withdrawn or suspended under this subparagraph or which, as determined by the [Secretary](/usc/21/321.md?p=d), has been withdrawn from sale for safety or effectiveness reasons, the approval of the [drug](/usc/21/321.md?p=g-1) under this paragraph shall be withdrawn or suspended— - (i) for the same period as the withdrawal or suspension under [subsection (e)](#e) or this subparagraph, or - (ii) if the approved [new animal drug](/usc/21/321.md?p=v) has been withdrawn from sale, for the period of withdrawal from sale or, if earlier, the period ending on the date the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=v) and becomes available at the site of [drug](/usc/21/321.md?p=g-1) action. - (ii) A [new animal drug](/usc/21/321.md?p=v) shall be considered to be bioequivalent to the approved [new animal drug](/usc/21/321.md?p=v) referred to in its application under [subsection (n)](#n) if— - (I) the rate and extent of absorption of the [drug](/usc/21/321.md?p=g-1) do not show a significant difference from the rate and extent of absorption of the approved [new animal drug](/usc/21/321.md?p=v) 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](/usc/21/321.md?p=g-1) does not show a significant difference from the extent of absorption of the approved [new animal drug](/usc/21/321.md?p=v) 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](/usc/21/321.md?p=v) in the rate of absorption of the [drug](/usc/21/321.md?p=g-1) is intentional, is reflected in its proposed [labeling](/usc/21/321.md?p=m), is not essential to the attainment of effective [drug](/usc/21/321.md?p=g-1) concentrations in use, and is considered scientifically insignificant for the [drug](/usc/21/321.md?p=g-1) in attaining the intended purposes of its use and preserving human [food](/usc/21/321.md?p=f) safety; or - (III) in any case in which the [Secretary](/usc/21/321.md?p=d) determines that the measurement of the rate and extent of absorption or excretion of the [new animal drug](/usc/21/321.md?p=v) in biological fluids is inappropriate or impractical, an appropriate acute pharmacological effects test or other test of the [new animal drug](/usc/21/321.md?p=v) and, when deemed scientifically necessary, of the approved [new animal drug](/usc/21/321.md?p=v) 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](/usc/21/321.md?p=v) and such approved [new animal drug](/usc/21/321.md?p=v) when administered at the same dose under similar experimental conditions. If the approved [new animal drug](/usc/21/321.md?p=v) referred to in the application for a [new animal drug](/usc/21/321.md?p=v) under [subsection (n)](#n) is approved for use in more than one animal species, the bioequivalency information described in subclauses [(I)](#c-2-H-ii-I), [(II)](#c-2-H-ii-II), and [(III)](#c-2-H-ii-III) shall be obtained for one species, or if the [Secretary](/usc/21/321.md?p=d) deems appropriate based on scientific principles, shall be obtained for more than one species. The [Secretary](/usc/21/321.md?p=d) may prescribe the dose to be used in determining bioequivalency under subclause [(I)](#c-2-H-ii-I), [(II)](#c-2-H-ii-II), or [(III)](#c-2-H-ii-III). To assure that the residues of the [new animal drug](/usc/21/321.md?p=v) will be consistent with the established tolerances for the approved [new animal drug](/usc/21/321.md?p=v) referred to in the application under [subsection (b)(2)](#b-2) upon the expiration of the withdrawal period contained in the application for the [new animal drug](/usc/21/321.md?p=v), the [Secretary](/usc/21/321.md?p=d) shall require bioequivalency data or residue depletion studies of the [new animal drug](/usc/21/321.md?p=v) or such other data or studies as the [Secretary](/usc/21/321.md?p=d) considers appropriate based on scientific principles. If the [Secretary](/usc/21/321.md?p=d) requires one or more residue studies under the preceding sentence, the [Secretary](/usc/21/321.md?p=d) may not require that the assay methodology used to determine the withdrawal period of the [new animal drug](/usc/21/321.md?p=v) be more rigorous than the methodology used to determine the withdrawal period for the approved [new animal drug](/usc/21/321.md?p=v) referred to in the application. If such studies are required and if the approved [new animal drug](/usc/21/321.md?p=v), referred to in the application for the [new animal drug](/usc/21/321.md?p=v) 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](/usc/21/321.md?p=d) deems appropriate based on scientific principles, shall be conducted for more than one species. - (3) If the patent information described in [subsection (b)(1)](#b-1) could not be filed with the submission of an application under [subsection (b)(1)](#b-1) because the application was filed before the patent information was required under [subsection (b)(1)](#b-1) or a patent was issued after the application was approved under such subsection, the holder of an approved application shall file with the [Secretary](/usc/21/321.md?p=d) the patent number and the expiration date of any patent which claims the [new animal drug](/usc/21/321.md?p=v) for which the application was filed or which claims a method of using such [drug](/usc/21/321.md?p=g-1) and with respect to which a claim of patent infringement could reasonably be asserted if a [person](/usc/21/321.md?p=e) not [licensed](/usc/21/360eee.md?p=9) by the owner engaged in the manufacture, use, or sale of the [drug](/usc/21/321.md?p=g-1). If the holder of an approved application could not file patent information under [subsection (b)(1)](#b-1) 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)](#b-1) 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](/usc/21/321.md?p=d) shall publish it. - (4) A [drug](/usc/21/321.md?p=g-1) manufactured in a pilot or other small facility may be used to demonstrate the safety and effectiveness of the [drug](/usc/21/321.md?p=g-1) and to obtain approval for the [drug](/usc/21/321.md?p=g-1) prior to manufacture of the [drug](/usc/21/321.md?p=g-1) in a larger facility, unless the [Secretary](/usc/21/321.md?p=d) makes a determination that a full scale production facility is necessary to ensure the safety or effectiveness of the [drug](/usc/21/321.md?p=g-1). - (d) **Grounds for refusing application; approval of application; factors; “substantial evidence” defined; combination drugs—** - (1) If the [Secretary](/usc/21/321.md?p=d) finds, after due notice to the applicant in accordance with [subsection (c)](#c) 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](/usc/21/321.md?p=d) pursuant to [subsection (b)](#b), do not include adequate tests by all methods reasonably applicable to show whether or not such [drug](/usc/21/321.md?p=g-1) is [safe](/usc/21/321.md?p=u) for use under the conditions prescribed, recommended, or suggested in the proposed [labeling](/usc/21/321.md?p=m) thereof; - (B) the results of such tests show that such [drug](/usc/21/321.md?p=g-1) is unsafe for use under such conditions or do not show that such [drug](/usc/21/321.md?p=g-1) is [safe](/usc/21/321.md?p=u) 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](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=g-1), he has insufficient information to determine whether such [drug](/usc/21/321.md?p=g-1) is [safe](/usc/21/321.md?p=u) 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](/usc/21/321.md?p=g-1), there is a lack of substantial evidence that the [drug](/usc/21/321.md?p=g-1) will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the proposed [labeling](/usc/21/321.md?p=m) thereof; - (F) upon the basis of information submitted to the [Secretary](/usc/21/321.md?p=d) as part of the application or any other information before the [Secretary](/usc/21/321.md?p=d) with respect to such [drug](/usc/21/321.md?p=g-1), any use prescribed, recommended, or suggested in [labeling](/usc/21/321.md?p=m) proposed for such [drug](/usc/21/321.md?p=g-1) will result in a residue of such [drug](/usc/21/321.md?p=g-1) in excess of a tolerance found by the [Secretary](/usc/21/321.md?p=d) to be [safe](/usc/21/321.md?p=u) for such [drug](/usc/21/321.md?p=g-1); - (G) the application failed to contain the patent information prescribed by [subsection (b)(1)](#b-1); - (H) based on a fair evaluation of all material facts, such [labeling](/usc/21/321.md?p=m) is false or misleading in any particular; or - (I) such [drug](/usc/21/321.md?p=g-1) induces cancer when ingested by man or animal or, after tests which are appropriate for the evaluation of the safety of such [drug](/usc/21/321.md?p=g-1), induces cancer in man or animal, except that the foregoing provisions of this subparagraph shall not apply with respect to such [drug](/usc/21/321.md?p=g-1) if the [Secretary](/usc/21/321.md?p=d) finds that, under the conditions of use specified in proposed [labeling](/usc/21/321.md?p=m) and reasonably certain to be followed in practice (i) such [drug](/usc/21/321.md?p=g-1) will not adversely affect the animals for which it is intended, and (ii) no residue of such [drug](/usc/21/321.md?p=g-1) will be found (by methods of examination prescribed or approved by the [Secretary](/usc/21/321.md?p=d) by regulations, which regulations shall not be subject to subsections [(c)](#c), [(d)](#d), and [(h)](#h)), in any edible portion of such animals after slaughter or in any [food](/usc/21/321.md?p=f) 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](/usc/21/321.md?p=d) finds that subparagraphs [(A)](#d-1-A) through [(I)](#d-1-I) do not apply, he shall issue an order approving the application. - (2) In determining whether such [drug](/usc/21/321.md?p=g-1) is [safe](/usc/21/321.md?p=u) for use under the conditions prescribed, recommended, or suggested in the proposed [labeling](/usc/21/321.md?p=m) thereof, the [Secretary](/usc/21/321.md?p=d) shall consider, among other relevant factors, (A) the probable consumption of such [drug](/usc/21/321.md?p=g-1) and of any substance formed in or on [food](/usc/21/321.md?p=f) because of the use of such [drug](/usc/21/321.md?p=g-1), (B) the cumulative effect on man or animal of such [drug](/usc/21/321.md?p=g-1), 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](/usc/21/321.md?p=g-1), are appropriate for the use of animal experimentation data, and (D) whether the conditions of use prescribed, recommended, or suggested in the proposed [labeling](/usc/21/321.md?p=m) are reasonably certain to be followed in practice. Any order issued under this subsection refusing to approve an application shall [state](/usc/21/321.md?p=a-1) 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)](#b-3) 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](/usc/21/321.md?p=g-1) involved, on the basis of which it could fairly and reasonably be concluded by such experts that the [drug](/usc/21/321.md?p=g-1) will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the [labeling](/usc/21/321.md?p=m) or proposed [labeling](/usc/21/321.md?p=m) thereof. - (4) In a case in which an animal [drug](/usc/21/321.md?p=g-1) contains more than one active ingredient, or the [labeling](/usc/21/321.md?p=m) of the [drug](/usc/21/321.md?p=g-1) prescribes, recommends, or suggests use of the [drug](/usc/21/321.md?p=g-1) in combination with one or more other animal [drugs](/usc/21/321.md?p=g-1), and the active ingredients or [drugs](/usc/21/321.md?p=g-1) intended for use in the combination have previously been separately approved pursuant to an application submitted under [subsection (b)(1)](#b-1) for particular uses and conditions of use for which they are intended for use in the combination— - (A) the [Secretary](/usc/21/321.md?p=d) shall not issue an order under paragraph [(1)(A)](#d-1-A), [(1)(B)](#d-1-B), or [(1)(D)](#d-1-D) refusing to approve the application for such combination on human [food](/usc/21/321.md?p=f) safety grounds unless the [Secretary](/usc/21/321.md?p=d) finds that the application fails to establish that— - (i) none of the active ingredients or [drugs](/usc/21/321.md?p=g-1) intended for use in the combination, respectively, at the longest withdrawal time of any of the active ingredients or [drugs](/usc/21/321.md?p=g-1) in the combination, respectively, exceeds its established tolerance; or - (ii) none of the active ingredients or [drugs](/usc/21/321.md?p=g-1) in the combination interferes with the methods of analysis for another of the active ingredients or [drugs](/usc/21/321.md?p=g-1) in the combination, respectively; - (B) the [Secretary](/usc/21/321.md?p=d) shall not issue an order under paragraph [(1)(A)](#d-1-A), [(1)(B)](#d-1-B), or [(1)(D)](#d-1-D) refusing to approve the application for such combination on target animal safety grounds unless the [Secretary](/usc/21/321.md?p=d) finds that— - (i) - (I) there is a substantiated scientific issue, specific to one or more of the active ingredients or animal [drugs](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=e) 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](/usc/21/321.md?p=d) as part of the application; and - (ii) based on the [Secretary](/usc/21/321.md?p=d)’s evaluation of the information contained in the application with respect to the issues identified in clauses [(i)(I)](#d-4-B-i-I) and (II), paragraph [(1)(A)](#d-1-A), (B), or (D) apply; - (C) except in the case of a combination that contains a nontopical antibacterial ingredient or animal [drug](/usc/21/321.md?p=g-1), the [Secretary](/usc/21/321.md?p=d) shall not issue an order under [paragraph (1)(E)](#d-1-E) refusing to approve an application for a combination animal [drug](/usc/21/321.md?p=g-1) intended for use other than in [animal feed](/usc/21/321.md?p=w) or drinking water unless the [Secretary](/usc/21/321.md?p=d) finds that the application fails to demonstrate that— - (i) there is substantial evidence that any active ingredient or animal [drug](/usc/21/321.md?p=g-1) intended only for the same use as another active ingredient or animal [drug](/usc/21/321.md?p=g-1) in the combination makes a contribution to labeled effectiveness; - (ii) each active ingredient or animal [drug](/usc/21/321.md?p=g-1) intended for at least one use that is different from all other active ingredients or animal [drugs](/usc/21/321.md?p=g-1) used in the combination provides appropriate concurrent use for the intended target population; or - (iii) where based on scientific information the [Secretary](/usc/21/321.md?p=d) has reason to believe the active ingredients or animal [drugs](/usc/21/321.md?p=g-1) may be physically incompatible or have disparate dosing regimens, such active ingredients or animal [drugs](/usc/21/321.md?p=g-1) are physically compatible or do not have disparate dosing regimens; and - (D) the [Secretary](/usc/21/321.md?p=d) shall not issue an order under [paragraph (1)(E)](#d-1-E) refusing to approve an application for a combination animal [drug](/usc/21/321.md?p=g-1) intended for use in [animal feed](/usc/21/321.md?p=w) or drinking water unless the [Secretary](/usc/21/321.md?p=d) finds that the application fails to demonstrate that— - (i) there is substantial evidence that any active ingredient or animal [drug](/usc/21/321.md?p=g-1) intended only for the same use as another active ingredient or animal [drug](/usc/21/321.md?p=g-1) in the combination makes a contribution to the labeled effectiveness; - (ii) each of the active ingredients or animal [drugs](/usc/21/321.md?p=g-1) intended for at least one use that is different from all other active ingredients or animal [drugs](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=g-1), there is substantial evidence that each of the nontopical antibacterial ingredients or animal [drugs](/usc/21/321.md?p=g-1) makes a contribution to the labeled effectiveness, except that for purposes of this clause, antibacterial ingredient or animal [drug](/usc/21/321.md?p=g-1) does not include the ionophore or arsenical classes of animal [drugs](/usc/21/321.md?p=g-1); or - (iv) where based on scientific information the [Secretary](/usc/21/321.md?p=d) has reason to believe the active ingredients or animal [drugs](/usc/21/321.md?p=g-1) intended for use in drinking water may be physically incompatible, such active ingredients or animal [drugs](/usc/21/321.md?p=g-1) intended for use in drinking water are physically compatible. - (5) In reviewing an application that proposes a change to add an intended use for a [minor use](/usc/21/321.md?p=pp) or a [minor species](/usc/21/321.md?p=oo) to an approved [new animal drug](/usc/21/321.md?p=v) application, the [Secretary](/usc/21/321.md?p=d) shall reevaluate only the relevant information in the approved application to determine whether the application for the [minor use](/usc/21/321.md?p=pp) or [minor species](/usc/21/321.md?p=oo) can be approved. A decision to approve the application for the [minor use](/usc/21/321.md?p=pp) or [minor species](/usc/21/321.md?p=oo) is not, implicitly or explicitly, a reaffirmation of the approval of the original application. - (e) **Withdrawal of approval; grounds; immediate suspension upon finding imminent hazard to health of man or animals—** - (1) The [Secretary](/usc/21/321.md?p=d) shall, after due notice and opportunity for hearing to the applicant, issue an order withdrawing approval of an application filed pursuant to [subsection (b)](#b) with respect to any [new animal drug](/usc/21/321.md?p=v) if the [Secretary](/usc/21/321.md?p=d) finds— - (A) that experience or scientific data show that such [drug](/usc/21/321.md?p=g-1) is unsafe for use under the conditions of use upon the basis of which the application was approved or the condition of use [authorized](/usc/21/360eee.md?p=2) under [subsection (a)(4)(A)](#a-4-A); - (B) that new evidence not contained in such application or not available to the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=d) when the application was approved, shows that such [drug](/usc/21/321.md?p=g-1) is not shown to be [safe](/usc/21/321.md?p=u) 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)](#d) applies to such [drug](/usc/21/321.md?p=g-1); - (C) on the basis of new information before him with respect to such [drug](/usc/21/321.md?p=g-1), evaluated together with the evidence available to him when the application was approved, that there is a lack of substantial evidence that such [drug](/usc/21/321.md?p=g-1) will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the [labeling](/usc/21/321.md?p=m) thereof; - (D) the patent information prescribed by [subsection (c)(3)](#c-3) was not filed within 30 days after the receipt of written notice from the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=d) (or in his absence the officer acting as [Secretary](/usc/21/321.md?p=d)) finds that there is an imminent hazard to the health of man or of the animals for which such [drug](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=v) under this section if the [Secretary](/usc/21/321.md?p=d) 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 (l)](#l), or the applicant has refused to permit access to, or copying or [verification](/usc/21/360eee.md?p=28) of, such records as required by [paragraph (2)](#e-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](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=m) of such [drug](/usc/21/321.md?p=g-1), 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](/usc/21/321.md?p=d) specifying the matter complained of. - (3) Any order under this subsection shall [state](/usc/21/321.md?p=a-1) the findings upon which it is based. - (f) **Revocation of order refusing, withdrawing or suspending approval of application—** Whenever the [Secretary](/usc/21/321.md?p=d) finds that the facts so require, he shall revoke any previous order under subsection [(d)](#d), [(e)](#e), or [(m)](#m), or [section 360ccc(c)](/usc/21/360ccc.md?p=c), (d), or (e) of this title 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](/usc/21/321.md?p=d) issued under this section, or [section 360ccc of this title](/usc/21/360ccc.md) (other than orders issuing, amending, or repealing regulations) shall be served (1) in [person](/usc/21/321.md?p=e) by any officer or employee of the [department](/usc/21/321.md?p=c) designated by the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=d). - (h) **Appeal from order—** An appeal may be taken by the applicant from an order of the [Secretary](/usc/21/321.md?p=d) refusing or withdrawing approval of an application filed under subsection [(b)](#b) or [(m)](#m) of this section. The provisions of subsection (h) of [section 355 of this title](/usc/21/355.md) shall govern any such appeal. - (i) **Publication in Federal Register; effective date and revocation or suspension of regulation—** When a [new animal drug](/usc/21/321.md?p=v) application filed pursuant to [subsection (b)](#b) or [section 360ccc of this title](/usc/21/360ccc.md) is approved, the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=v) covered by such application, including any tolerance and withdrawal period or other use restrictions and, if such [new animal drug](/usc/21/321.md?p=v) is intended for use in [animal feed](/usc/21/321.md?p=w), appropriate purposes and conditions of use (including special [labeling](/usc/21/321.md?p=m) requirements and any requirement that an [animal feed](/usc/21/321.md?p=w) bearing or containing the [new animal drug](/usc/21/321.md?p=v) be limited to use under the professional supervision of a [licensed](/usc/21/360eee.md?p=9) veterinarian) applicable to any [animal feed](/usc/21/321.md?p=w) for use in which such [drug](/usc/21/321.md?p=g-1) is approved, and such other information, upon the basis of which such application was approved, as the [Secretary](/usc/21/321.md?p=d) deems necessary to assure the [safe](/usc/21/321.md?p=u) and effective use of such [drug](/usc/21/321.md?p=g-1). Upon withdrawal of approval of such [new animal drug](/usc/21/321.md?p=v) application or upon its suspension or upon failure to renew a conditional approval under [section 360ccc of this title](/usc/21/360ccc.md), the [Secretary](/usc/21/321.md?p=d) shall forthwith revoke or suspend, as the case may be, the regulation published pursuant to this [subsection (i)](#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](/usc/21/321.md?p=d) shall promulgate regulations for exempting from the operation of this section [new animal drugs](/usc/21/321.md?p=v), and [animal feeds](/usc/21/321.md?p=w) bearing or containing [new animal drugs](/usc/21/321.md?p=v), intended solely for investigational use by experts qualified by scientific training and experience to investigate the safety and effectiveness of animal [drugs](/usc/21/321.md?p=g-1). Such regulations may, in the discretion of the [Secretary](/usc/21/321.md?p=d), 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](/usc/21/321.md?p=d), by the [manufacturer](/usc/21/360hh.md?p=3) or the [sponsor](/usc/21/360fff.md?p=8) 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](/usc/21/321.md?p=d) 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](/usc/21/360eee.md?p=13) of such animals (before or after slaughter), may be marketed for [food](/usc/21/321.md?p=f) 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](/usc/21/321.md?p=v) is effective, a [food](/usc/21/321.md?p=f) shall not, by reason of bearing or containing such [drug](/usc/21/321.md?p=g-1) or any substance formed in or on the [food](/usc/21/321.md?p=f) because of its use in accordance with such application (including the conditions and indications of use prescribed pursuant to [subsection (i)](#i)), be considered adulterated within the meaning of clause (1) of [section 342(a) of this title](/usc/21/342.md?p=a). - (l) **Records and reports; required information; regulations and orders; examination of data; access to records—** - (1) In the case of any [new animal drug](/usc/21/321.md?p=v) for which an approval of an application filed pursuant to [subsection (b)](#b) or [section 360ccc of this title](/usc/21/360ccc.md) is in effect, the applicant shall establish and maintain such records, and make such reports to the [Secretary](/usc/21/321.md?p=d), of data relating to experience, including experience with uses [authorized](/usc/21/360eee.md?p=2) under [subsection (a)(4)(A)](#a-4-A), and other data or information, received or otherwise obtained by such applicant with respect to such [drug](/usc/21/321.md?p=g-1), or with respect to [animal feeds](/usc/21/321.md?p=w) bearing or containing such [drug](/usc/21/321.md?p=g-1), as the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=d) to determine, or facilitate a determination, whether there is or may be ground for invoking [subsection (e)](#e) or [subsection (m)(4)](#m-4) of this section. Such regulation or order shall provide, where the [Secretary](/usc/21/321.md?p=d) deems it to be appropriate, for the examination, upon request, by the [persons](/usc/21/321.md?p=e) to whom such regulation or order is applicable, of similar information received or otherwise obtained by the [Secretary](/usc/21/321.md?p=d). - (2) Every [person](/usc/21/321.md?p=e) required under this subsection to maintain records, and every [person](/usc/21/321.md?p=e) in charge or custody thereof, shall, upon request of an officer or employee designated by the [Secretary](/usc/21/321.md?p=d), permit such officer or employee at all reasonable times to have access to and copy and [verify](/usc/21/360eee.md?p=28) such records. - (3) - (A) In the case of each [new animal drug](/usc/21/321.md?p=v) described in [paragraph (1)](#l-1) that contains an antimicrobial active ingredient, the [sponsor](/usc/21/360fff.md?p=8) of the [drug](/usc/21/321.md?p=g-1) shall submit an annual report to the [Secretary](/usc/21/321.md?p=d) on the amount of each antimicrobial active ingredient in the [drug](/usc/21/321.md?p=g-1) that is sold or distributed for use in [food](/usc/21/321.md?p=f)-producing animals, including information on any distributor-labeled [product](/usc/21/360eee.md?p=13). - (B) Each report under this paragraph shall specify the amount of each antimicrobial active ingredient— - (i) by container size, strength, and dosage form; - (ii) by quantities distributed domestically and quantities exported; and - (iii) by dosage form, including, for each such dosage form, a listing of the target animals, indications, and production classes that are specified on the approved [label](/usc/21/321.md?p=k) of the [product](/usc/21/360eee.md?p=13). - (C) Each report under this paragraph shall— - (i) be submitted not later than March 31 each year; - (ii) cover the period of the preceding calendar year; and - (iii) include separate information for each month of such calendar year. - (D) The [Secretary](/usc/21/321.md?p=d) may share information reported under this paragraph with the Antimicrobial Resistance Task Force established under [section 247d–5 of title 42](/usc/42/247d–5.md). - (E) The [Secretary](/usc/21/321.md?p=d) shall make summaries of the information reported under this paragraph publicly available, except that— - (i) the summary data shall be reported by antimicrobial class, and no class with fewer than 3 distinct [sponsors](/usc/21/360fff.md?p=8) of approved applications shall be independently reported; and - (ii) the data shall be reported in a manner consistent with protecting both national security and confidential business information. - (m) **Feed mill licenses—** - (1) Any [person](/usc/21/321.md?p=e) may file with the [Secretary](/usc/21/321.md?p=d) an application for a license to manufacture [animal feeds](/usc/21/321.md?p=w) bearing or containing [new animal drugs](/usc/21/321.md?p=v). Such [person](/usc/21/321.md?p=e) shall submit to the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=w) bearing or containing [new animal drugs](/usc/21/321.md?p=v) are manufactured and labeled in accordance with the applicable regulations published pursuant to [subsection (i)](#i) or for indexed [new animal drugs](/usc/21/321.md?p=v) in accordance with the index listing published pursuant to [section 360ccc–1(e)(2) of this title](/usc/21/360ccc–1.md?p=e-2) and the [labeling](/usc/21/321.md?p=m) requirements set forth in [section 360ccc–1(h) of this title](/usc/21/360ccc–1.md?p=h), and (D) a certification that the methods used in, and the facilities and controls used for, manufacturing, processing, packaging, and holding such [animal feeds](/usc/21/321.md?p=w) are in conformity with current good manufacturing practice as described in [section 351(a)(2)(B) of this title](/usc/21/351.md). - (2) Within 90 days after the filing of an application pursuant to [paragraph (1)](#m-1), or such additional period as may be agreed upon by the [Secretary](/usc/21/321.md?p=d) and the applicant, the [Secretary](/usc/21/321.md?p=d) shall (A) issue an order approving the application if the [Secretary](/usc/21/321.md?p=d) then finds that none of the grounds for denying approval specified in [paragraph (3)](#m-3) applies, or (B) give the applicant notice of an opportunity for a hearing before the [Secretary](/usc/21/321.md?p=d) under [paragraph (3)](#m-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)](#c-1). - (3) If the [Secretary](/usc/21/321.md?p=d), after due notice to the applicant in accordance with [paragraph (2)](#m-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](/usc/21/321.md?p=d) as part of the application, on the basis of a preapproval inspection, or on the basis of any other information before the [Secretary](/usc/21/321.md?p=d)— - (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](/usc/21/321.md?p=w) are inadequate to preserve the identity, strength, quality, and purity of the [new animal drug](/usc/21/321.md?p=v) therein; or - (C) that the facility manufactures [animal feeds](/usc/21/321.md?p=w) bearing or containing [new animal drugs](/usc/21/321.md?p=v) in a manner that does not accord with the specifications for manufacture or [labels](/usc/21/321.md?p=k) [animal feeds](/usc/21/321.md?p=w) bearing or containing [new animal drugs](/usc/21/321.md?p=v) in a manner that does not accord with the conditions or indications of use that are published pursuant to [subsection (i)](#i) or an index listing pursuant to [section 360ccc–1(e) of this title](/usc/21/360ccc–1.md?p=e), the [Secretary](/usc/21/321.md?p=d) shall issue an order refusing to approve the application. If, after such notice and opportunity for hearing, the [Secretary](/usc/21/321.md?p=d) finds that subparagraphs [(A)](#m-3-A) through [(C)](#m-3-C) do not apply, the [Secretary](/usc/21/321.md?p=d) shall issue an order approving the application. An order under this subsection approving an application for a license to manufacture [animal feeds](/usc/21/321.md?p=w) bearing or containing [new animal drugs](/usc/21/321.md?p=v) shall permit a facility to manufacture only those [animal feeds](/usc/21/321.md?p=w) bearing or containing [new animal drugs](/usc/21/321.md?p=v) for which there are in effect regulations pursuant to [subsection (i)](#i) or an index listing pursuant to [section 360ccc–1(e) of this title](/usc/21/360ccc–1.md?p=e) relating to the use of such [drugs](/usc/21/321.md?p=g-1) in or on such [animal feed](/usc/21/321.md?p=w). - (4) - (A) The [Secretary](/usc/21/321.md?p=d) shall, after due notice and opportunity for hearing to the applicant, revoke a license to manufacture [animal feeds](/usc/21/321.md?p=w) bearing or containing [new animal drugs](/usc/21/321.md?p=v) under this subsection if the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=w) manufactured at the facility unless the applicant has supplemented the application by filing with the [Secretary](/usc/21/321.md?p=d) adequate information respecting all such changes and unless there is in effect an approval of the supplemental application. If the [Secretary](/usc/21/321.md?p=d) (or in the [Secretary](/usc/21/321.md?p=d)’s absence the officer acting as the [Secretary](/usc/21/321.md?p=d)) finds that there is an imminent hazard to the health of humans or of the animals for which such [animal feed](/usc/21/321.md?p=w) is intended, the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=d) may also, after due notice and opportunity for hearing to the applicant, revoke a license to manufacture [animal feed](/usc/21/321.md?p=w) under this subsection if the [Secretary](/usc/21/321.md?p=d) 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 [section 354(a)(3)(A) of this title](/usc/21/354.md?p=a-3-A), or the applicant has refused to permit access to, or copying or [verification](/usc/21/360eee.md?p=28) of, such records as required by [subparagraph (B)](#m-4-B) of such paragraph or [section 354(a)(3)(B) of this title](/usc/21/354.md?p=a-3-B); - (ii) that on the basis of new information before the [Secretary](/usc/21/321.md?p=d), evaluated together with the evidence before the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=w) are inadequate to assure and preserve the identity, strength, quality, and purity of the [new animal drug](/usc/21/321.md?p=v) therein, and were not made adequate within a reasonable time after receipt of written notice from the [Secretary](/usc/21/321.md?p=d), specifying the matter complained of; - (iii) that on the basis of new information before the [Secretary](/usc/21/321.md?p=d), evaluated together with the evidence before the [Secretary](/usc/21/321.md?p=d) when such license was issued, the [labeling](/usc/21/321.md?p=m) of any [animal feeds](/usc/21/321.md?p=w), 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](/usc/21/321.md?p=d) specifying the matter complained of; or - (iv) that on the basis of new information before the [Secretary](/usc/21/321.md?p=d), evaluated together with the evidence before the [Secretary](/usc/21/321.md?p=d) when such license was issued, the facility has manufactured, processed, packed, or held [animal feed](/usc/21/321.md?p=w) bearing or containing a [new animal drug](/usc/21/321.md?p=v) adulterated under [section 351(a)(6) of this title](/usc/21/351.md) and the facility did not discontinue the manufacture, processing, packing, or holding of such [animal feed](/usc/21/321.md?p=w) within a reasonable time after receipt of written notice from the [Secretary](/usc/21/321.md?p=d) specifying the matter complained of. - (C) The [Secretary](/usc/21/321.md?p=d) may also revoke a license to manufacture [animal feeds](/usc/21/321.md?p=w) under this subsection if an applicant gives notice to the [Secretary](/usc/21/321.md?p=d) of intention to discontinue the manufacture of all [animal feed](/usc/21/321.md?p=w) covered under this subsection and waives an opportunity for a hearing on the matter. - (D) Any order under this paragraph shall [state](/usc/21/321.md?p=a-1) the findings upon which it is based. - (5) When a license to manufacture [animal feeds](/usc/21/321.md?p=w) bearing or containing [new animal drugs](/usc/21/321.md?p=v) has been issued— - (A) the applicant shall establish and maintain such records, and make such reports to the [Secretary](/usc/21/321.md?p=d), or (at the option of the [Secretary](/usc/21/321.md?p=d)) to the appropriate [person](/usc/21/321.md?p=e) or [persons](/usc/21/321.md?p=e) holding an approved application filed under [subsection (b)](#b), as the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=d) to determine, or facilitate a determination, whether there is or may be ground for invoking [subsection (e)](#e) or [paragraph (4)](#m-4); and - (B) every [person](/usc/21/321.md?p=e) required under this subsection to maintain records, and every [person](/usc/21/321.md?p=e) in charge or custody thereof, shall, upon request of an officer or employee designated by the [Secretary](/usc/21/321.md?p=d), permit such officer or employee at all reasonable times to have access to and copy and [verify](/usc/21/360eee.md?p=28) such records. - (6) To the extent consistent with the public health, the [Secretary](/usc/21/321.md?p=d) may promulgate regulations for exempting from the operation of this subsection facilities that manufacture, process, pack, or hold [animal feeds](/usc/21/321.md?p=w) bearing or containing [new animal drugs](/usc/21/321.md?p=v). - (n) **Abbreviated applications for new animal drugs; contents, filing, etc.; lists of approved drugs—** - (1) An abbreviated application for a [new animal drug](/usc/21/321.md?p=v) shall contain— - (A) - (i) except as provided in [clause (ii)](#n-1-A-ii), information to show that the conditions of use or similar limitations (whether in the [labeling](/usc/21/321.md?p=m) or published pursuant to [subsection (i)](#i)) prescribed, recommended, or suggested in the [labeling](/usc/21/321.md?p=m) proposed for the [new animal drug](/usc/21/321.md?p=v) have been previously approved for a [new animal drug](/usc/21/321.md?p=v) listed under [paragraph (4)](#n-4) (hereinafter in this subsection referred to as an “approved [new animal drug](/usc/21/321.md?p=v)”), and - (ii) information to show that the withdrawal period at which residues of the [new animal drug](/usc/21/321.md?p=v) will be consistent with the tolerances established for the approved [new animal drug](/usc/21/321.md?p=v) is the same as the withdrawal period previously established for the approved [new animal drug](/usc/21/321.md?p=v) or, if the withdrawal period is proposed to be different, information showing that the residues of the [new animal drug](/usc/21/321.md?p=v) at the proposed different withdrawal period will be consistent with the tolerances established for the approved [new animal drug](/usc/21/321.md?p=v); - (B) - (i) information to show that the active ingredients of the [new animal drug](/usc/21/321.md?p=v) are the same as those of the approved [new animal drug](/usc/21/321.md?p=v), and - (ii) if the approved [new animal drug](/usc/21/321.md?p=v) has more than one active ingredient, and if one of the active ingredients of the [new animal drug](/usc/21/321.md?p=v) is different from one of the active ingredients of the approved [new animal drug](/usc/21/321.md?p=v) and the application is filed pursuant to the approval of a petition filed under [paragraph (3)](#n-3)— - (I) information to show that the other active ingredients of the [new animal drug](/usc/21/321.md?p=v) are the same as the active ingredients of the approved [new animal drug](/usc/21/321.md?p=v), - (II) information to show either that the different active ingredient is an active ingredient of another approved [new animal drug](/usc/21/321.md?p=v) or of an animal [drug](/usc/21/321.md?p=g-1) which does not meet the requirements of [section 321(v) of this title](/usc/21/321.md?p=v), and - (III) such other information respecting the different active ingredients as the [Secretary](/usc/21/321.md?p=d) may require; - (C) - (i) if the approved [new animal drug](/usc/21/321.md?p=v) is permitted to be used with one or more animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w), information to show that the proposed uses of the [new animal drug](/usc/21/321.md?p=v) with other animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w) are the same as the uses of the approved [new animal drug](/usc/21/321.md?p=v), and - (ii) if the approved [new animal drug](/usc/21/321.md?p=v) is permitted to be used with one or more other animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w), and one of the other animal [drugs](/usc/21/321.md?p=g-1) proposed for use with the [new animal drug](/usc/21/321.md?p=v) in [animal feed](/usc/21/321.md?p=w) is different from one of the other animal [drugs](/usc/21/321.md?p=g-1) permitted to be used in [animal feed](/usc/21/321.md?p=w) with the approved [new animal drug](/usc/21/321.md?p=v), and the application is filed pursuant to the approval of a petition filed under [paragraph (3)](#n-3)— - (I) information to show either that the different animal [drug](/usc/21/321.md?p=g-1) proposed for use with the approved [new animal drug](/usc/21/321.md?p=v) in [animal feed](/usc/21/321.md?p=w) is an approved [new animal drug](/usc/21/321.md?p=v) permitted to be used in [animal feed](/usc/21/321.md?p=w) or does not meet the requirements of [section 321(v) of this title](/usc/21/321.md?p=v) when used with another animal [drug](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w), - (II) information to show that other animal [drugs](/usc/21/321.md?p=g-1) proposed for use with the [new animal drug](/usc/21/321.md?p=v) in [animal feed](/usc/21/321.md?p=w) are the same as the other animal [drugs](/usc/21/321.md?p=g-1) permitted to be used with the approved [new animal drug](/usc/21/321.md?p=v), and - (III) such other information respecting the different animal [drug](/usc/21/321.md?p=g-1) or combination with respect to which the petition was filed as the [Secretary](/usc/21/321.md?p=d) may require, - (D) information to show that the route of administration, the dosage form, and the strength of the [new animal drug](/usc/21/321.md?p=v) are the same as those of the approved [new animal drug](/usc/21/321.md?p=v) or, if the route of administration, the dosage form, or the strength of the [new animal drug](/usc/21/321.md?p=v) is different and the application is filed pursuant to the approval of a petition filed under [paragraph (3)](#n-3), such information respecting the route of administration, dosage form, or strength with respect to which the petition was filed as the [Secretary](/usc/21/321.md?p=d) may require; - (E) information to show that the [new animal drug](/usc/21/321.md?p=v) is bioequivalent to the approved [new animal drug](/usc/21/321.md?p=v), except that if the application is filed pursuant to the approval of a petition filed under [paragraph (3)](#n-3) for the purposes described in subparagraph [(B)](#n-1-B) or [(C)](#n-1-C), information to show that the active ingredients of the [new animal drug](/usc/21/321.md?p=v) are of the same pharmacological or therapeutic class as the pharmacological or therapeutic class of the approved [new animal drug](/usc/21/321.md?p=v) and that the [new animal drug](/usc/21/321.md?p=v) can be expected to have the same therapeutic effect as the approved [new animal drug](/usc/21/321.md?p=v) when used in accordance with the [labeling](/usc/21/321.md?p=m); - (F) information to show that the [labeling](/usc/21/321.md?p=m) proposed for the [new animal drug](/usc/21/321.md?p=v) is the same as the [labeling](/usc/21/321.md?p=m) approved for the approved [new animal drug](/usc/21/321.md?p=v) except for changes required because of differences approved under a petition filed under [paragraph (3)](#n-3), because of a different withdrawal period, or because the [new animal drug](/usc/21/321.md?p=v) and the approved [new animal drug](/usc/21/321.md?p=v) are produced or distributed by different [manufacturers](/usc/21/360hh.md?p=3); - (G) the items specified in clauses (B) through (F) of subsection (b)(1); - (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](/usc/21/321.md?p=v) or which claims a use for such approved [new animal drug](/usc/21/321.md?p=v) for which the applicant is seeking approval under this subsection and for which information is required to be filed under subsection [(b)(1)](#b-1) or [(c)(3)](#c-3)— - (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](/usc/21/321.md?p=v) for which the application is filed; and - (I) if with respect to the approved [new animal drug](/usc/21/321.md?p=v) information was filed under subsection [(b)(1)](#b-1) or [(c)(3)](#c-3) 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)](#c-2), a statement that the method of use patent does not claim such a use. The [Secretary](/usc/21/321.md?p=d) may not require that an abbreviated application contain information in addition to that required by subparagraphs [(A)](#n-1-A) through [(I)](#n-1-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)](#n-2-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)](#c-1) for the [drug](/usc/21/321.md?p=g-1) 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)](#n-2-A) shall [state](/usc/21/321.md?p=a-1) that an application, which contains data from bioequivalence studies, has been filed under this subsection for the [drug](/usc/21/321.md?p=g-1) with respect to which the certification is made to obtain approval to engage in the commercial manufacture, use, or sale of such [drug](/usc/21/321.md?p=g-1) 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)](#n-2-B) shall be given when the amended application is filed. - (3) If a [person](/usc/21/321.md?p=e) wants to submit an abbreviated application for a [new animal drug](/usc/21/321.md?p=v)— - (A) whose active ingredients, route of administration, dosage form, or strength differ from that of an approved [new animal drug](/usc/21/321.md?p=v), or - (B) whose use with other animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w) differs from that of an approved [new animal drug](/usc/21/321.md?p=v), such [person](/usc/21/321.md?p=e) shall submit a petition to the [Secretary](/usc/21/321.md?p=d) seeking permission to file such an application. The [Secretary](/usc/21/321.md?p=d) shall approve a petition for a [new animal drug](/usc/21/321.md?p=v) unless the [Secretary](/usc/21/321.md?p=d) finds that— - (C) investigations must be conducted to show the safety and effectiveness, in animals to be treated with the [drug](/usc/21/321.md?p=g-1), of the active ingredients, route of administration, dosage form, strength, or use with other animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w) which differ from the approved [new animal drug](/usc/21/321.md?p=v), or - (D) investigations must be conducted to show the safety for human consumption of any residues in [food](/usc/21/321.md?p=f) resulting from the proposed active ingredients, route of administration, dosage form, strength, or use with other animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w) for the [new animal drug](/usc/21/321.md?p=v) which is different from the active ingredients, route of administration, dosage form, strength, or use with other animal [drugs](/usc/21/321.md?p=g-1) in [animal feed](/usc/21/321.md?p=w) of the approved [new animal drug](/usc/21/321.md?p=v). The [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=d) shall publish and make available to the public a list in alphabetical order of the official and proprietary name of each [new animal drug](/usc/21/321.md?p=v) 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)](#n-4-A-i) the [Secretary](/usc/21/321.md?p=d) shall revise the list to include each [new animal drug](/usc/21/321.md?p=v) which has been approved for safety and effectiveness under [subsection (c)](#c) during the 30 day period. - (iii) When patent information submitted under subsection [(b)(1)](#b-1) or [(c)(3)](#c-3) respecting a [new animal drug](/usc/21/321.md?p=v) included on the list is to be published by the [Secretary](/usc/21/321.md?p=d), the [Secretary](/usc/21/321.md?p=d) shall, in revisions made under [clause (ii)](#n-4-A-ii), include such information for such [drug](/usc/21/321.md?p=g-1). - (B) A [new animal drug](/usc/21/321.md?p=v) approved for safety and effectiveness before November 16, 1988, or approved for safety and effectiveness under [subsection (c)](#c) shall, for purposes of this subsection, be considered to have been published under [subparagraph (A)](#n-4-A) on the date of its approval or November 16, 1988, whichever is later. - (C) If the approval of a [new animal drug](/usc/21/321.md?p=v) was withdrawn or suspended under [subsection (c)(2)(G)](#c-2-G) or for grounds described in [subsection (e)](#e) or if the [Secretary](/usc/21/321.md?p=d) determines that a [drug](/usc/21/321.md?p=g-1) has been withdrawn from sale for safety or effectiveness reasons, it may not be published in the list under [subparagraph (A)](#n-4-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)](#c-2-G) or [(e)](#e), or - (ii) if the listed [drug](/usc/21/321.md?p=g-1) has been withdrawn from sale, for the period of withdrawal from sale or, if earlier, the period ending on the date the [Secretary](/usc/21/321.md?p=d) 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) 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](/usc/21/321.md?p=e) 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)](#b-2). - (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)](#b-1) or [section 360ccc(a) of this title](/usc/21/360ccc.md?p=a) for a [drug](/usc/21/321.md?p=g-1) 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](/usc/21/321.md?p=d) has determined that the application is not approvable and all legal appeals have been exhausted, - (C) if approval of the application under [subsection (c)](#c) is withdrawn and all legal appeals have been exhausted, - (D) if the [Secretary](/usc/21/321.md?p=d) has determined that such [drug](/usc/21/321.md?p=g-1) is not a [new drug](/usc/21/321.md?p=p), or - (E) upon the effective date of the approval of the first application filed under [subsection (b)(2)](#b-2) which refers to such [drug](/usc/21/321.md?p=g-1) or upon the date upon which the approval of an application filed under [subsection (b)(2)](#b-2) which refers to such [drug](/usc/21/321.md?p=g-1) could be made effective if such an application had been filed. - (2) Any request for data and information pursuant to [paragraph (1)](#p-1) shall include a verified statement by the [person](/usc/21/321.md?p=e) making the request that any data or information received under such paragraph shall not be disclosed by such [person](/usc/21/321.md?p=e) to any other [person](/usc/21/321.md?p=e)— - (A) for the purpose of, or as part of a plan, scheme, or [device](/usc/21/321.md?p=h-1) for, obtaining the right to make, use, or market, or making, using, or marketing, outside the United States, the [drug](/usc/21/321.md?p=g-1) identified in the application filed under [subsection (b)(1)](#b-1) or [section 360ccc(a) of this title](/usc/21/360ccc.md?p=a), and - (B) without obtaining from any [person](/usc/21/321.md?p=e) to whom the data and information are disclosed an identical verified statement, a copy of which is to be provided by such [person](/usc/21/321.md?p=e) to the [Secretary](/usc/21/321.md?p=d), which meets the requirements of this paragraph. - (q) **Date of approval in the case of recommended controls under the CSA—** - (1) **In general—** In the case of an application under [subsection (b)](#b) with respect to a [drug](/usc/21/321.md?p=g-1) for which the [Secretary](/usc/21/321.md?p=d) provides notice to the [sponsor](/usc/21/360fff.md?p=8) that the [Secretary](/usc/21/321.md?p=d) intends to issue a scientific and medical evaluation and recommend controls under the Controlled Substances Act [[21 U.S.C. 801](/usc/21/801.md) et seq.], approval of such application shall not take effect until the interim final rule controlling the [drug](/usc/21/321.md?p=g-1) is issued in accordance with section 201(j) of the Controlled Substances Act [[21 U.S.C. 811(j)](/usc/21/811.md?p=j)]. - (2) **Date of approval—** For purposes of this section, with respect to an application described in [paragraph (1)](#q-1), the term “date of approval” shall mean the later of— - (A) the date an application under [subsection (b)](#b) is approved under [subsection (c)](#c); or - (B) the date of issuance of the interim final rule controlling the [drug](/usc/21/321.md?p=g-1). ## Footnotes [^1]: See References in Text note below. [^2]: So in original. Probably should be “Alimentarius”. [^3]: So in original. Probably should be “clause (iii)(III)”. ## Source credit (June 25, 1938, ch. 675, § 512, as added Pub. L. 90–399, § 101(b), July 13, 1968, 82 Stat. 343; amended Pub. L. 100–670, title I, §§ 101, 102, 104, 107(a)(2), Nov. 16, 1988, 102 Stat. 3971, 3981, 3982, 3984; Pub. L. 102–108, § 2(e), Aug. 17, 1991, 105 Stat. 550; Pub. L. 103–80, § 3(r), Aug. 13, 1993, 107 Stat. 777; Pub. L. 103–396, § 2(a), (b)(2), (3), Oct. 22, 1994, 108 Stat. 4153, 4154; Pub. L. 104–250, §§ 2(a)–(d), 3, 4, 5(c), 6(a), (b), Oct. 9, 1996, 110 Stat. 3151–3153, 3155–3157; Pub. L. 105–115, title I, § 124(b), Nov. 21, 1997, 111 Stat. 2325; Pub. L. 105–277, div. A, § 101(a) [title VII, § 737], Oct. 21, 1998, 112 Stat. 2681, 2681–30; Pub. L. 106–113, div. B, § 1000(a)(9) [title IV, § 4732(b)(11)], Nov. 29, 1999, 113 Stat. 1536, 1501A–584; Pub. L. 108–282, title I, § 102(b)(2), (3), (5)(I)–(S), Aug. 2, 2004, 118 Stat. 892, 903, 904; Pub. L. 110–316, title I, § 105(a), Aug. 14, 2008, 122 Stat. 3513; Pub. L. 114–89, § 2(a)(3)(A), Nov. 25, 2015, 129 Stat. 699; Pub. L. 114–255, div. A, title III, § 3088(b), Dec. 13, 2016, 130 Stat. 1149; Pub. L. 115–234, title III, § 301(a), Aug. 14, 2018, 132 Stat. 2436; Pub. L. 117–9, § 1(a)(2), Apr. 23, 2021, 135 Stat. 257.) ## Notes ### Editorial Notes ### References in Text Section 342(a)(2) of this title, referred to in subsec. (a)(6), was amended by Pub. L. 104–170, title IV, § 404, Aug. 3, 1996, 110 Stat. 1514, and, as so amended, no longer contains a subcl. (D). See section 342(a)(2)(C)(ii) of this title. The Controlled Substances Act, referred to in subsec. (q)(1), 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 2021—Subsec. (c)(2)(F). Pub. L. 117–9 substituted “active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations))” for “active ingredient (including any ester or salt of the active ingredient)” in cls. (i), (ii), and (v). 2018—Subsec. (b)(4). Pub. L. 115–234 added par. (4). 2016—Subsec. (a)(1)(D). Pub. L. 114–255 added subpar. (D). 2015—Subsec. (q). Pub. L. 114–89 added subsec. (q). 2008—Subsec. (l)(3). Pub. L. 110–316 added par. (3). 2004—Subsec. (a)(1), (2). Pub. L. 108–282, § 102(b)(5)(I), added pars. (1) and (2) and struck out former pars. (1) and (2) which deemed as unsafe new animal drugs and animal feed bearing or containing a new animal drug which did not have in effect certain approvals. Subsec. (b)(3). Pub. L. 108–282, § 102(b)(5)(J), substituted “under paragraph (1), section 360ccc of this title, or a request for an investigational exemption under subsection (j)” for “under paragraph (1) or a request for an investigational exemption under subsection (j)”. Subsec. (c)(2)(F)(ii), (iii), (v). Pub. L. 108–282, § 102(b)(2), substituted “(other than bioequivalence studies or residue depletion studies, except residue depletion studies for minor uses or minor species)” for “(other than bioequivalence or residue studies)”. Subsec. (d)(4). Pub. L. 108–282, § 102(b)(5)(K), substituted “have previously been separately approved pursuant to an application submitted under subsection (b)(1)” for “have previously been separately approved” in introductory provisions. Subsec. (d)(5). Pub. L. 108–282, § 102(b)(3), added par. (5). Subsec. (f). Pub. L. 108–282, § 102(b)(5)(L), substituted “subsection (d), (e), or (m), or section 360ccc(c), (d), or (e) of this title” for “subsection (d), (e), or (m)”. Subsec. (g). Pub. L. 108–282, § 102(b)(5)(M), substituted “this section, or section 360ccc of this title” for “this section”. Subsec. (i). Pub. L. 108–282, § 102(b)(5)(N), substituted “subsection (b) or section 360ccc of this title” for “subsection (b)” and inserted “or upon failure to renew a conditional approval under section 360ccc of this title” after “or upon its suspension”. Subsec. (l)(1). Pub. L. 108–282, § 102(b)(5)(O), substituted “subsection (b) or section 360ccc of this title” for “subsection (b)”. Subsec. (m)(1)(C). Pub. L. 108–282, § 102(b)(5)(P), substituted “applicable regulations published pursuant to subsection (i) or for indexed new animal drugs in accordance with the index listing published pursuant to section 360ccc–1(e)(2) of this title and the labeling requirements set forth in section 360ccc–1(h) of this title” for “applicable regulations published pursuant to subsection (i)”. Subsec. (m)(3). Pub. L. 108–282, § 102(b)(5)(Q), inserted “or an index listing pursuant to section 360ccc–1(e) of this title” after “subsection (i)” in subpar. (C) and concluding provisions. Subsec. (p)(1), (2)(A). Pub. L. 108–282, § 102(b)(5)(R), (S), substituted “subsection (b)(1) or section 360ccc(a) of this title” for “subsection (b)(1)”. 1999—Subsec. (o). Pub. L. 106–113 substituted “United States Patent and Trademark Office” for “Patent and Trademark Office of the Department of Commerce”. 1998—Subsec. (d)(4)(D)(iii). Pub. L. 105–277 inserted before semicolon “, except that for purposes of this clause, antibacterial ingredient or animal drug does not include the ionophore or arsenical classes of animal drugs”. 1997—Subsec. (c)(4). Pub. L. 105–115 added par. (4). 1996—Subsec. (a)(1). Pub. L. 104–250, § 6(a), amended par. (1) generally. Prior to amendment, par. (1) read as follows: “A new animal drug shall, with respect to any particular use or intended use of such drug, be deemed unsafe for the purposes of section 351(a)(5) and section 342(a)(2)(D) of this title unless— “(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). Pub. L. 104–250, § 6(a), amended par. (2) generally. Prior to amendment, par. (2) read as follows: “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 section 351(a)(6) of this title unless— “(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). Pub. L. 104–250, § 4, added par. (6). Subsec. (b)(3). Pub. L. 104–250, § 2(d), added par. (3). Subsec. (c)(2)(F)(ii), (iii). Pub. L. 104–250, § 2(b)(1), substituted “substantial evidence of the effectiveness of the drug involved, any studies of animal safety, or,” for “reports of new clinical or field investigations (other than bioequivalence or residue studies) and,” and “required for the approval” for “essential to the approval”. Subsec. (c)(2)(F)(v). Pub. L. 104–250, § 2(b)(2), substituted “clause (iv)” for “subparagraph (B)(iv)” in two places, “substantial evidence of the effectiveness of the drug involved, any studies of animal safety,” for “reports of clinical or field investigations” and “required for the new approval” for “essential to the new approval”. Subsec. (d)(1)(F). Pub. L. 104–250, § 3, amended subpar. (F) generally. Prior to amendment, subpar. (F) read as follows: “upon the basis of the information submitted to him as part of the application or any other information before him with respect to such drug, the tolerance limitation proposed, if any, exceeds that reasonably required to accomplish the physical or other technical effect for which the drug is intended;”. Subsec. (d)(3). Pub. L. 104–250, § 2(a), amended par. (3) generally. Prior to amendment, par. (3) read as follows: “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 field investigation, 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.” Subsec. (d)(4). Pub. L. 104–250, § 2(c), added par. (4). Subsec. (i). Pub. L. 104–250, § 5(c), inserted “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” after “(including special labeling requirements”. Subsec. (m). Pub. L. 104–250, § 6(b), amended subsec. (m) generally, substituting provisions relating to application for feed mill licenses, including approval, refusal, revocation, and suspension of such licenses, and provisions for record and reporting requirements for, as well as exemption from, such licenses, for provisions relating to application for uses of animal feed containing new animal drug, including required contents, approval, refusal, and withdrawal of approval or suspension of such usage applications, and provisions for record and reporting requirements of such usage applications. 1994—Subsec. (a)(4), (5). Pub. L. 103–396, § 2(a), added pars. (4) and (5). Subsec. (e)(1)(A). Pub. L. 103–396, § 2(b)(2), inserted before semicolon at end “or the condition of use authorized under subsection (a)(4)(A)”. Subsec. (l)(1). Pub. L. 103–396, § 2(b)(3), substituted “relating to experience, including experience with uses authorized under subsection (a)(4)(A),” for “relating to experience”. 1993—Subsec. (c)(2)(A)(ii). Pub. L. 103–80, § 3(r)(1), inserted “in” after “except as provided”. Subsec. (c)(2)(F)(i). Pub. L. 103–80, § 3(r)(2), substituted “subparagraph (D)(iii)” for “subparagraph (C)(iii)”. Subsec. (c)(2)(H)(ii). Pub. L. 103–80, § 3(r)(3), substituted “subclauses” for “subclause” after “bioequivalency information described in” in concluding provisions. Subsec. (d)(1). Pub. L. 103–80, § 3(r)(4), substituted “subparagraphs (A) through (I)” for “subparagraphs (A) through (G)” in concluding provisions. Subsec. (n)(1). Pub. L. 103–80, § 3(r)(5), substituted “section 321(v) of this title” for “section 321(w) of this title” in subpars. (B)(ii)(II) and (C)(ii)(I) and substituted “through (I)” for “through (H)” in concluding provisions. 1991—Subsec. (e)(1)(B). Pub. L. 102–108 substituted “(I)” for “(H)”. 1988—Subsec. (a)(1)(C). Pub. L. 100–670, § 107(a)(2), struck out subpar. (C) which read as follows: “in the case of a new animal drug subject to subsection (n) of this section and not exempted therefrom by regulations it is from a batch with respect to which a certificate or release issued pursuant to subsection (n) of this section is in effect with respect to such drug.” Subsec. (b). Pub. L. 100–670, §§ 101(a), 102(a), designated existing provisions as par. (1), redesignated cls. (1) to (8) as cls. (A) to (H), respectively, added par. (2), and inserted provisions at end of par. (1) which require applicant to file with application, patent number and expiration date of any patent which claims new animal drug, to amend application to include such information if patent which claims such drug or method of using such drug is issued after filing date but before approval of application, and to publish such information upon approval. Subsec. (c). Pub. L. 100–670, §§ 101(c), 102(b)(1), designated existing provisions as par. (1), redesignated cls. (1) and (2) as cls. (A) and (B), respectively, and added pars. (2) and (3). Subsec. (d)(1). Pub. L. 100–670, § 102(b)(3), substituted “(G)” for “(H)” in last sentence. Subsec. (d)(1)(G) to (I). Pub. L. 100–670, § 102(b)(2), added subpar. (G) and redesignated former subpars. (G) and (H) as (H) and (I), respectively. Subsec. (e)(1)(D) to (F). Pub. L. 100–670, § 102(b)(4), added subpar. (D) and redesignated former subpars. (D) and (E) as (E) and (F), respectively. Subsecs. (n), (o). Pub. L. 100–670, § 101(b), added subsecs. (n) and (o) and struck out former subsec. (n) which related to certification of new drugs containing penicillin, streptomycin, chlortetracycline, chloramphenicol, or bacitracin, and release prior to certification. Subsec. (p). Pub. L. 100–670, § 104, added subsec. (p). ### Statutory Notes and Related Subsidiaries ### Effective Date of 1999 Amendment Amendment by Pub. L. 106–113 effective 4 months after Nov. 29, 1999, see section 1000(a)(9) [title IV, § 4731] of Pub. L. 106–113, set out as a note under section 1 of Title 35, Patents. ### Effective Date of 1997 Amendment 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 a note under section 321 of this title. ### Effective Date of 1994 Amendment Pub. L. 103–396, § 2(d), Oct. 22, 1994, 108 Stat. 4154, provided that: “The amendments made by this section [amending this section and section 331 of this title] shall take effect upon the adoption of the final regulations under subsection (c) [set out below].” [Final regulations were dated Oct. 22, 1996, filed Nov. 6, 1996, published Nov. 7, 1996, 61 F.R. 57732, and effective Dec. 9, 1996.] ### Effective Date of 1988 Amendment Pub. L. 100–670, title I, § 108, Nov. 16, 1988, 102 Stat. 3984, provided that: “The Secretary of Health and Human Services may not make an approval of an application submitted under section 512(b)(2) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360b(b)(2)) effective before January 1, 1991.” ### Effective Date and Transitional Provisions Pub. L. 90–399, § 108, July 13, 1968, 82 Stat. 353, as amended by Pub. L. 108–282, title I, § 102(b)(5)(T), Aug. 2, 2004, 118 Stat. 905, provided that: Except as otherwise provided in this section, the amendments made by the foregoing sections [see Short Title of 1968 Amendment note set out under section 301 of this title] shall take effect on the first day of the thirteenth calendar month which begins after the date of enactment of this Act [July 13, 1968]. 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. 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 section 301 of this title]. 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 [section 321(p) of this title] as then in force, and (C) was not covered by an effective application under section 505 of that Act [section 355 of this title], the words ‘effectiveness’ and ‘effective’ contained in section 201(v) to the basic Act [sic] [section 321(v) of this title] shall not apply to such drug when intended solely for use under conditions prescribed, recommended, or suggested in labeling with respect to such drug on that day. 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 [section 357 of this title] shall, except as the Secretary may otherwise prescribe, be deemed to apply also under section 512(n) of the basic Act [subsection (n) of this section], and appropriations of fees (and of advance deposits to cover fees) available for the purposes specified in such section 507 [section 357 of this title] as in effect prior to the effective date shall also be available for the purposes specified in section 512(n) [subsection (n) of this section], including preparatory work or proceedings prior to that date.” ### Regulations Pub. L. 104–250, § 2(e), Oct. 9, 1996, 110 Stat. 3154, provided that: In general.—Not later than 6 months after the date of enactment of this Act [Oct. 9, 1996], the Secretary of Health and Human Services shall issue proposed regulations implementing the amendments made by this Act as described in paragraph (2)(A) of this subsection, and not later than 18 months after the date of enactment of this Act, the Secretary shall issue final regulations implementing such amendments. Not later than 12 months after the date of enactment of this Act, the Secretary shall issue proposed regulations implementing the other amendments made by this Act as described in paragraphs (2)(B) and (2)(C) of this subsection, and not later than 24 months after the date of enactment of this Act, the Secretary shall issue final regulations implementing such amendments. Contents.—In issuing regulations implementing the amendments made by this Act [see Short Title of 1996 Amendments note set out under section 301 of this title], and in taking an action to review an application for approval of a new animal drug under section 512 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360b), or a request for an investigational exemption for a new animal drug under subsection (j) of such section, that is pending or has been submitted prior to the effective date of the regulations, the Secretary shall— 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; 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 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 (21 U.S.C. 360b(d)(1)(E)) or to apply any of its provisions in a manner inconsistent with the considerations for scientifically sound field investigations set forth in subparagraph (A).” Pub. L. 103–396, § 2(c), Oct. 22, 1994, 108 Stat. 4154, provided that: “Not later than 2 years after the date of the enactment of this Act [Oct. 22, 1994], the Secretary of Health and Human Services shall promulgate regulations to implement paragraphs (4)(A) and (5) of section 512(a) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 360b(a)(4)(A), (5)] (as amended by subsection (a)).” Pub. L. 100–670, title I, § 103, Nov. 16, 1988, 102 Stat. 3982, provided that: General Rule.—The Secretary of Health and Human Services shall promulgate, in accordance with the notice and comment requirements of section 553 of title 5, United States Code, such regulations as may be necessary for the administration of section 512 of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 360b], as amended by sections 101 through 103 of this title, within one year of the date of enactment of this Act [Nov. 16, 1988]. Transition.—During the period beginning 60 days after the date of enactment of this Act [Nov. 16, 1988] and ending on the date regulations promulgated under subsection (a) take effect, abbreviated new animal drug applications may be submitted in accordance with the provisions of section 314.55 and part 320 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 512(c) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 360b(c)] before the date of enactment of this Act. If any such provision of section 314.55 or part 320 is inconsistent with the requirements of section 512 of the Federal Food, Drug, and Cosmetic Act (as amended by this title), the Secretary shall consider the application under the applicable requirements of section 512 (as so amended).” ### Guidance Addressing Investigation Designs Pub. L. 115–234, title III, § 305, Aug. 14, 2018, 132 Stat. 2440, provided that: In General.—For purposes of assisting sponsors in incorporating complex adaptive and other novel investigation designs, data from foreign countries, real world evidence (including ongoing surveillance activities, observational studies, and registry data), biomarkers, and surrogate endpoints (referred to in this section as ‘elements of investigations’) into proposed clinical investigation protocols and applications for new animal drugs under sections 512 and 571 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360b; 360ccc), the Secretary of Health and Human Services (referred to in this section as the ‘Secretary’) shall issue guidance addressing the use of such elements of investigations in the development and regulatory review of such new animal drugs. Contents.—The guidance under subsection (a) shall address how the Secretary will evaluate the elements of investigations proposed or submitted pursuant to section 512(b)(1)(A) of the Federal Food, Drug, and Cosmetic Act or to meet the commitment under section 571(a)(2)(F) of such Act, and how sponsors of such applications may obtain feedback from the Secretary on technical issues related to such investigations prior to the submission of an application to the Secretary. Meeting.—Prior to issuing the guidance under subsection (a), the Secretary shall consult with stakeholders, including representatives of regulated industry, consumer groups, academia, veterinarians, and food producers, through a public meeting to be held not later than 1 year after the date of enactment of this Act [Aug. 14, 2018]. Timing.—The Secretary shall issue a draft guidance under subsection (a) not later than 1 year after the date of the public meeting under subsection (c), and shall finalize such guidance not later than 1 year after the date on which the public comment period on such draft guidance ends.” ### Antimicrobial Animal Drug Distribution Reports Pub. L. 110–316, title I, § 105(b), (c), Aug. 14, 2008, 122 Stat. 3514, provided that: First Report.—For each new animal drug that is subject to the reporting requirement under section 512(l)(3) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 360b(l)(3)], as added by subsection (a), and for which an approval of an application filed pursuant to section 512(b) or 571 of such Act [21 U.S.C. 360b(b), 360ccc] is in effect on the date of the enactment of this title [Aug. 14, 2008], the Secretary of Health and Human Services shall require the sponsor of the drug to submit the first report under such section 512(l)(3) for the drug not later than March 31, 2010. Separate Report.—The reports required under section 512(l)(3) of the Federal Food, Drug, and Cosmetic Act, as added by subsection (a), shall be separate from periodic drug experience reports that are required under section 514.80(b)(4) of title 21, Code of Federal Regulations (as in effect on the date of the enactment of this title).” ### Drugs Intended for Minor Species and Minor Uses Pub. L. 104–250, § 2(f), Oct. 9, 1996, 110 Stat. 3154, provided that: “The Secretary of Health and Human Services shall consider legislative and regulatory options for facilitating the approval under section 512 of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 360b] of animal drugs intended for minor species and for minor uses and, within 18 months after the date of enactment of this Act [Oct. 9, 1996], announce proposals for legislative or regulatory change to the approval process under such section for animal drugs intended for use in minor species or for minor uses.” ### Transitional Provision Regarding Implementation of Pub. L. 104–250; Approved Medicated Feed Application Deemed License Pub. L. 104–250, § 6(c), Oct. 9, 1996, 110 Stat. 3160, provided that: “A person engaged in the manufacture of animal feeds bearing or containing new animal drugs who holds at least one approved medicated feed application for an animal feed bearing or containing new animal drugs, the manufacture of which was not otherwise exempt from the requirement for an approved medicated feed application on the date of the enactment of this Act [Oct. 9, 1996], shall be deemed to hold a license for the manufacturing site identified in the approved medicated feed application. The revocation of license provisions of section 512(m)(4) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 360b(m)(4)], as amended by this Act, shall apply to such licenses. Such license shall expire within 18 months from the date of enactment of this Act unless the person submits to the Secretary a completed license application for the manufacturing site accompanied by a copy of an approved medicated feed application for such site, which license application shall be deemed to be approved upon receipt by the Secretary.” ### Drugs Primarily Manufactured Using Biotechnology Pub. L. 100–670, title I, § 106, Nov. 16, 1988, 102 Stat. 3984, provided that: “Notwithstanding section 512(b)(2) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 360b(b)(2)], the Secretary of Health and Human Services may not approve an abbreviated application submitted under such section for a new animal drug which is primarily manufactured using recombinant DNA, recombinant RNA, hybridoma technology, or other processes involving site specific genetic manipulation techniques.”