21 USC 360 - Conditional approval of new animal drugs for minor use and minor species and certain new animal drugs

Collapse to view only § 360ccc. Conditional approval of new animal drugs for minor use and minor species and certain new animal drugs

§ 360ccc. Conditional approval of new animal drugs for minor use and minor species and certain new animal drugs
§ 360ccc-1. Index of legally marketed unapproved new animal drugs for minor species
§ 360ccc-2. Designated new animal drugs for minor use or minor species

§ 360ccc. Conditional approval of new animal drugs for minor use and minor species and certain new animal drugs

(a) Application requirements

(1)

(A) Except as provided in paragraph (3), any person may file with the Secretary an application for conditional approval of—

(i) a new animal drug intended for a minor use or a minor species; or

(ii) a new animal drug not intended for a minor use or minor species—(I) that is intended to treat a serious or life-threatening disease or condition or addresses an unmet animal or human health need; and(II) for which the Secretary determines that a demonstration of effectiveness would require a complex or particularly difficult study or studies.

(B) The Secretary shall, not later than September 30, 2019, issue guidance or regulations further clarifying the criteria specified in subparagraph (A)(ii).

(D) New animal drugs for which conditional approval is sought under this section are subject to the same safety standards that would be applied to new animal drugs under section 360b(d) of this title (including, for antimicrobial new animal drugs, with respect to antimicrobial resistance).

(2) The applicant shall submit to the Secretary as part of an application for the conditional approval of a new animal drug—

(A) all information necessary to meet the requirements of section 360b(b)(1) of this title except section 360b(b)(1)(A) of this title;

(B) full reports of investigations which have been made to show whether or not such drug is safe under section 360b(d) of this title (including, for an antimicrobial new animal drug, with respect to antimicrobial resistance) and there is a reasonable expectation of effectiveness for use;

(D) projections of expected need and the justification for that expectation based on the best information available;

(E) information regarding the quantity of drug expected to be distributed on an annual basis to meet the expected need; and

(F) a commitment that the applicant will conduct additional investigations to meet the requirements for the full demonstration of effectiveness under section 360b(d)(1)(E) of this title within 5 years.

(3)

(A) A person may not file an application under paragraph (1) if—

(i) the application seeks conditional approval of a new animal drug that is contained in, or is a product of, a transgenic animal.1

1 So in original. The period probably should be a semicolon.

(ii) the person has previously filed an application for conditional approval under paragraph (1) for the same drug in the same dosage form for the same intended use whether or not subsequently conditionally approved by the Secretary under subsection (b); or

(iii) the person obtained the application, or data or other information contained therein, directly or indirectly from the person who filed for conditional approval under paragraph (1) for the same drug in the same dosage form for the same intended use whether or not subsequently conditionally approved by the Secretary under subsection (b).

(B) A person may not file an application under paragraph (1)(A)(ii) if the application seeks conditional approval of a new animal drug that contains an antimicrobial active ingredient.

(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 may require.

(b) Order of approval or hearingWithin 180 days after the filing of an application pursuant to subsection (a), or such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall either—

(1) issue an order, effective for one year, conditionally approving the application if the Secretary finds that none of the grounds for denying conditional approval, specified in subsection (c) of this section applies and publish a Federal Register notice of the conditional approval, or

(2) give the applicant notice of an opportunity for an informal hearing on the question whether such application can be conditionally approved.

(c) Order of approval or refusal after hearingIf the Secretary finds, after giving the applicant notice and an opportunity for an informal hearing, that—

(1) any of the provisions of section 360b(d)(1)(A) through (D) or (F) through (I) of this title are applicable;

(2) the information submitted to the Secretary as part of the application and any other information before the Secretary with respect to such drug, is insufficient to show that there is a reasonable expectation that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof; or

(3) another person has received approval under section 360b of this title for the same drug in the same dosage form for the same intended use, and that person is able to assure the availability of sufficient quantities of the drug to meet the needs for which the drug is intended;

the Secretary shall issue an order refusing to conditionally approve the application. If, after such notice and opportunity for an informal hearing, the Secretary finds that paragraphs (1) through (3) do not apply, the Secretary shall issue an order conditionally approving the application effective for one year and publish a Federal Register notice of the conditional approval. Any order issued under this subsection refusing to conditionally approve an application shall state the findings upon which it is based.

(d) Effective period; renewal; refusal of renewalA conditional approval under this section is effective for a 1-year period and is thereafter renewable by the Secretary annually for up to 4 additional 1-year terms. A conditional approval shall be in effect for no more than 5 years from the date of approval under subsection (b)(1) or (c) of this section unless extended as provided for in subsection (h) of this section. The following shall also apply:

(1) No later than 90 days from the end of the 1-year period for which the original or renewed conditional approval is effective, the applicant may submit a request to renew a conditional approval for an additional 1-year term.

(2) A conditional approval shall be deemed renewed at the end of the 1-year period, or at the end of a 90-day extension that the Secretary may, at the Secretary’s discretion, grant by letter in order to complete review of the renewal request, unless the Secretary determines before the expiration of the 1-year period or the 90-day extension that—

(A) the applicant failed to submit a timely renewal request;

(B) the request fails to contain sufficient information to show that—

(i) the applicant is making sufficient progress toward meeting approval requirements under section 360b(d)(1)(E) of this title, and is likely to be able to fulfill those requirements and obtain an approval under section 360b of this title before the expiration of the 5-year maximum term of the conditional approval;

(ii) the quantity of the drug that has been distributed is consistent with the conditionally approved intended use and conditions of use, unless there is adequate explanation that ensures that the drug is only used for its intended purpose; or

(iii) the same drug in the same dosage form for the same intended use has not received approval under section 360b of this title, or if such a drug has been approved, that the holder of the approved application is unable to assure the availability of sufficient quantities of the drug to meet the needs for which the drug is intended; or

(3) If the Secretary determines before the end of the 1-year period or the 90-day extension, if granted, that a conditional approval should not be renewed, the Secretary shall issue an order refusing to renew the conditional approval, and such conditional approval shall be deemed withdrawn and no longer in effect. The Secretary shall thereafter provide an opportunity for an informal hearing to the applicant on the issue whether the conditional approval shall be reinstated.

(4)

(A) In the case of an application under subsection (a) with respect to a drug for which the Secretary provides notice to the sponsor that the Secretary intends to issue a scientific and medical evaluation and recommend controls under the Controlled Substances Act [21 U.S.C. 801 et seq.], conditional approval of such application shall not take effect until the interim final rule controlling the drug is issued in accordance with section 201(j) of the Controlled Substances Act [21 U.S.C. 811(j)].

(B) For purposes of this section, with respect to an application described in subparagraph (A), the term “date of approval” shall mean the later of—

(i) the date an application under subsection (a) is conditionally approved under subsection (b); or

(ii) the date of issuance of the interim final rule controlling the drug.

(e) Withdrawal of conditional approval

(1) The Secretary shall issue an order withdrawing conditional approval of an application filed pursuant to subsection (a) if the Secretary finds that another person has received approval under section 360b of this title for the same drug in the same dosage form for the same intended use and that person is able to assure the availability of sufficient quantities of the drug to meet the needs for which the drug is intended.

(2) The Secretary shall, after due notice and opportunity for an informal hearing to the applicant, issue an order withdrawing conditional approval of an application filed pursuant to subsection (a) if the Secretary finds that—

(A) any of the provisions of section 360b(e)(1)(A) through (B) or (D) through (F) of this title are applicable; or

(B) on the basis of new information before the Secretary with respect to such drug, evaluated together with the evidence available to the Secretary when the application was conditionally approved, that there is not a reasonable expectation that such drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling thereof.

(3) The Secretary may also, after due notice and opportunity for an informal hearing to the applicant, issue an order withdrawing conditional approval of an application filed pursuant to subsection (a) if the Secretary finds that any of the provisions of section 360b(e)(2) of this title are applicable.

(f) Labeling

(1) The label and labeling of a new animal drug with a conditional approval under this section shall for the conditionally approved use—

(A) bear the statement, “conditionally approved by FDA pending a full demonstration of effectiveness under application number”; and

(B) contain such other information as prescribed by the Secretary.

(2) The Secretary shall, through regulation or guidance, determine under what conditions an intended use that is the subject of a conditional approval under this section may be included in the same product label with any intended use approved under section 360b of this title.

(g) Amendment of application

(h) Order of approval after conditional approval period termination180 days prior to the termination date established under subsection (d) of this section, an applicant shall have submitted all the information necessary to support a complete new animal drug application in accordance with section 360b(b)(1) of this title or the conditional approval issued under this section is no longer in effect. Following review of this information, the Secretary shall either—

(1) issue an order approving the application under section 360b(c) of this title if the Secretary finds that none of the grounds for denying approval specified in section 360b(d)(1) of this title applies, or

(2) give the applicant an opportunity for a hearing before the Secretary under section 360b(d) of this title on the question whether such application can be approved.

Upon issuance of an order approving the application, product labeling and administrative records of approval shall be modified accordingly. If the Secretary has not issued an order under section 360b(c) of this title approving such application prior to the termination date established under subsection (d) of this section, the conditional approval issued under this section is no longer in effect unless the Secretary grants an extension of an additional 180-day period so that the Secretary can complete review of the application. The decision to grant an extension is committed to the discretion of the Secretary and not subject to judicial review.

(i) Judicial review

(j) Definition

(k) Sunset

(1) The Secretary’s authority to grant conditional approval of new animal drugs not intended for a minor use or minor species pursuant to subsection (a)(1)(A)(ii) terminates on October 1, 2028.

(2) The Secretary—

(A) may not accept any new applications for such conditional approval pursuant to subsection (a)(1)(A)(ii) on or after such date; and

(B) may continue all activities under this section with respect to drugs that were conditionally approved pursuant to 2

2 So in original. The word “subsection” probably should appear.

(a)(1)(A)(ii) prior to such date.

(3) The Secretary may, until October 1, 2032, accept applications for approval under 3

3 So in original. The word “section” probably should appear.

360b of this title of drugs conditionally approved pursuant to 2 (a)(1)(A)(ii).

(June 25, 1938, ch. 675, § 571, as added Pub. L. 108–282, title I, § 102(b)(4), Aug. 2, 2004, 118 Stat. 892; amended Pub. L. 114–89, § 2(a)(3)(B), Nov. 25, 2015, 129 Stat. 699; Pub. L. 115–234, title III, §§ 301(b), 304(a), Aug. 14, 2018, 132 Stat. 2436.)

§ 360ccc–1. Index of legally marketed unapproved new animal drugs for minor species

(a) Establishment and span

(1) The Secretary shall establish an index limited to—

(A) new animal drugs intended for use in a minor species for which there is a reasonable certainty that the animal or edible products from the animal will not be consumed by humans or food-producing animals; and

(B) new animal drugs intended for use only in a hatchery, tank, pond, or other similar contained man-made structure in an early, non-food life stage of a food-producing minor species, where safety for humans is demonstrated in accordance with the standard of section 360b(d) of this title (including, for an antimicrobial new animal drug, with respect to antimicrobial resistance).

(2) The index shall not include a new animal drug that is contained in or a product of a transgenic animal.

(b) Conferences

(1) Any person may submit a request to the Secretary for a determination whether a new animal drug may be eligible for inclusion in the index. Such a request shall include—

(A) information regarding the need for the new animal drug, the species for which the new animal drug is intended, the proposed intended use and conditions of use, and anticipated annual distribution;

(B) information to support the conclusion that the proposed use meets the conditions of subparagraph (A) or (B) of subsection (a)(1) of this section;

(D) a description of the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such new animal drug;

(E) an environmental assessment that meets the requirements of the National Environmental Policy Act of 1969 [42 U.S.C. 4321 et seq.], as amended, and as defined in 21 CFR Part 25, as it appears on August 2, 2004, and amended thereafter or information to support a categorical exclusion from the requirement to prepare an environmental assessment;

(F) information sufficient to support the conclusion that the proposed use of the new animal drug is safe under section 360b(d) of this title with respect to individuals exposed to the new animal drug through its manufacture or use; and

(G) such other information as the Secretary may deem necessary to make this eligibility determination.

(2) Within 90 days after the submission of a request for a determination of eligibility for indexing based on subsection (a)(1)(A) of this section, or 180 days for a request submitted based on subsection (a)(1)(B) of this section, the Secretary shall grant or deny the request, and notify the person who requested such determination of the Secretary’s decision. The Secretary shall grant the request if the Secretary finds that—

(A) the same drug in the same dosage form for the same intended use is not approved or conditionally approved;

(B) the proposed use of the drug meets the conditions of subparagraph (A) or (B) of subsection (a)(1), as appropriate;

(C) the person requesting the determination has established appropriate specifications for the manufacture and control of the new animal drug and has demonstrated an understanding of the requirements of current good manufacturing practices;

(D) the new animal drug will not significantly affect the human environment; and

(E) the new animal drug is safe with respect to individuals exposed to the new animal drug through its manufacture or use.

If the Secretary denies the request, the Secretary shall thereafter provide due notice and an opportunity for an informal conference. A decision of the Secretary to deny an eligibility request following an informal conference shall constitute final agency action subject to judicial review.

(d) Request for addition to index

(1) With respect to a new animal drug for which the Secretary has made a determination of eligibility under subsection (c), the person who made such a request may ask that the Secretary add the new animal drug to the index established under subsection (a). The request for addition to the index shall include—

(A) a copy of the Secretary’s determination of eligibility issued under subsection (c);

(B) a written report that meets the requirements in subsection (d)(2) of this section;

(D) facsimile labeling;

(E) anticipated annual distribution of the new animal drug;

(F) a written commitment to manufacture the new animal drug and animal feeds bearing or containing such new animal drug according to current good manufacturing practices;

(G) a written commitment to label, distribute, and promote the new animal drug only in accordance with the index entry;

(H) upon specific request of the Secretary, information submitted to the expert panel described in paragraph (3); and

(I) any additional requirements that the Secretary may prescribe by general regulation or specific order.

(2) The report required in paragraph (1) shall—

(A) be authored by a qualified expert panel;

(B) include an evaluation of all available target animal safety and effectiveness information, including anecdotal information;

(C) state the expert panel’s opinion regarding whether the benefits of using the new animal drug for the proposed use in a minor species outweigh its risks to the target animal, taking into account the harm being caused by the absence of an approved or conditionally approved new animal drug for the minor species in question;

(D) include information from which labeling can be written; and

(E) include a recommendation regarding whether the new animal drug should be limited to use under the professional supervision of a licensed veterinarian.

(3) A qualified expert panel, as used in this section, is a panel that—

(A) is composed of experts qualified by scientific training and experience to evaluate the target animal safety and effectiveness of the new animal drug under consideration;

(B) operates external to FDA; and

The Secretary shall define the criteria for selection of a qualified expert panel and the procedures for the operation of the panel by regulation.

(4) Within 180 days after the receipt of a request for listing a new animal drug in the index, the Secretary shall grant or deny the request. The Secretary shall grant the request if the request for indexing continues to meet the eligibility criteria in subsection (a) and the Secretary finds, on the basis of the report of the qualified expert panel and other information available to the Secretary, that the benefits of using the new animal drug for the proposed use in a minor species outweigh its risks to the target animal, taking into account the harm caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question. If the Secretary denies the request, the Secretary shall thereafter provide due notice and the opportunity for an informal conference. The decision of the Secretary following an informal conference shall constitute final agency action subject to judicial review.

(e) Index contents; publication

(1) The index established under subsection (a) shall include the following information for each listed drug—

(A) the name and address of the person who holds the index listing;

(B) the name of the drug and the intended use and conditions of use for which it is being indexed;

(D) conditions and any limitations that the Secretary deems necessary regarding use of the drug.

(2) The Secretary shall publish the index, and revise it periodically.

(3) The Secretary may establish by regulation a process for reporting changes in the conditions of manufacturing or labeling of indexed products.

(f) Removal from index; suspended listing

(1) If the Secretary finds, after due notice to the person who requested the index listing and an opportunity for an informal conference, that—

(A) the expert panel failed to meet the requirements as set forth by the Secretary by regulation;

(B) on the basis of new information before the Secretary, evaluated together with the evidence available to the Secretary when the new animal drug was listed in the index, the benefits of using the new animal drug for the indexed use do not outweigh its risks to the target animal;

(D) the manufacture of the new animal drug is not in accordance with current good manufacturing practices;

(E) the labeling, distribution, or promotion of the new animal drug is not in accordance with the index entry;

(F) the conditions and limitations of use associated with the index listing have not been followed; or

(G) the request for indexing contains any untrue statement of material fact,

the Secretary shall remove the new animal drug from the index. The decision of the Secretary following an informal conference shall constitute final agency action subject to judicial review.

(2) If the Secretary finds that there is a reasonable probability that the use of the drug would present a risk to the health of humans or other animals, the Secretary may—

(A) suspend the listing of such drug immediately;

(B) give the person listed in the index prompt notice of the Secretary’s action; and

The decision of the Secretary following an informal conference shall constitute final agency action subject to judicial review.

(g) Regulations concerning exemptions for investigational use

(h) Labeling contentsThe labeling of a new animal drug that is the subject of an index listing shall state, prominently and conspicuously—

(1) “LEGAL STATUS—In order to be legally marketed, a new animal drug intended for a minor species must be Approved, Conditionally Approved, or Indexed by the Food and Drug Administration. THIS PRODUCT IS INDEXED—MIF #” (followed by the applicable minor species index file number and a period) “Extra-label use is prohibited.”;

(2) except in the case of new animal drugs indexed for use in an early life stage of a food-producing animal, “This product is not to be used in animals intended for use as food for humans or food-producing animals.”; and

(3) such other information as may be prescribed by the Secretary in the index listing.

(i) Records and reports

(1) In the case of any new animal drug for which an index listing pursuant to subsection (a) is in effect, the person who has an index listing shall establish and maintain such records, and make such reports to the Secretary, of data relating to experience, and other data or information, received or otherwise obtained by such person with respect to such drug, or with respect to animal feeds bearing or containing such drug, as the Secretary may by general regulation, or by order with respect to such listing, prescribe on the basis of a finding that such records and reports are necessary in order to enable the Secretary to determine, or facilitate a determination, whether there is or may be ground for invoking subsection (f). Such regulation or order shall provide, where the Secretary deems it to be appropriate, for the examination, upon request, by the persons to whom such regulation or order is applicable, of similar information received or otherwise obtained by the Secretary.

(2) Every person required under this subsection to maintain records, and every person in charge or custody thereof, shall, upon request of an officer or employee designated by the Secretary, permit such officer or employee at all reasonable times to have access to and copy and verify such records.

(j) Public disclosure of safety and effectiveness data

(1) Safety and effectiveness data and information which has been submitted in support of a request for a new animal drug to be indexed under this section and which has not been previously 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 drug indexed in accordance with the request,

(B) if the Secretary has determined that such drug cannot be indexed and all legal appeals have been exhausted,

(D) if the Secretary has determined that such drug is not a new animal drug.

(2) Any request for data and information pursuant to paragraph (1) shall include a verified statement by the person making the request that any data or information received under such paragraph shall not be disclosed by such person to any other person—

(A) for the purpose of, or as part of a plan, scheme, or device for, obtaining the right to make, use, or market, or making, using, or marketing, outside the United States, the drug identified in the request for indexing; and

(B) without obtaining from any person to whom the data and information are disclosed an identical verified statement, a copy of which is to be provided by such person to the Secretary, which meets the requirements of this paragraph.

(k) Date of determination in the case of recommended controls under the CSA

(June 25, 1938, ch. 675, § 572, as added Pub. L. 108–282, title I, § 102(b)(4), Aug. 2, 2004, 118 Stat. 896; amended Pub. L. 114–89, § 2(a)(3)(C), Nov. 25, 2015, 129 Stat. 699; Pub. L. 115–234, title III, § 302, Aug. 14, 2018, 132 Stat. 2436; Pub. L. 117–286, § 4(a)(158), Dec. 27, 2022, 136 Stat. 4323.)

§ 360ccc–2. Designated new animal drugs for minor use or minor species

(a) Designation

(1) The manufacturer or the sponsor of a new animal drug for a minor use or use in a minor species may request that the Secretary declare that drug a “designated new animal drug”. A request for designation of a new animal drug shall be made before the submission of an application under section 360b(b) of this title or section 360ccc of this title for the new animal drug.

(2) The Secretary may declare a new animal drug a “designated new animal drug” if—

(A) it is intended for a minor use or use in a minor species; and

(B) the same drug in the same dosage form for the same intended use is not approved under section 360b or 360ccc of this title or designated under this section at the time the request is made.

(3) Regarding the termination of a designation—

(A) the sponsor of a new animal drug shall notify the Secretary of any decision to discontinue active pursuit of approval under section 360b or 360ccc of this title of an application for a designated new animal drug. The Secretary shall terminate the designation upon such notification;

(B) the Secretary may also terminate designation if the Secretary independently determines that the sponsor is not actively pursuing approval under section 360b or 360ccc of this title with due diligence;

(C) the sponsor of an approved designated new animal drug shall notify the Secretary of any discontinuance of the manufacture of such new animal drug at least one year before discontinuance. The Secretary shall terminate the designation upon such notification; and

(D) the designation shall terminate upon the expiration of any applicable exclusivity period under subsection (c).

(4) Notice respecting the designation or termination of designation of a new animal drug shall be made available to the public.

(b) Grants and contracts for development of designated new animal drugs

(1) The Secretary may make grants to and enter into contracts with public and private entities and individuals to assist in defraying the costs of qualified safety and effectiveness testing expenses and manufacturing expenses incurred in connection with the development of designated new animal drugs.

(2) For purposes of paragraph (1) of this section—

(A) The term “qualified safety and effectiveness testing” means testing—

(i) which occurs after the date such new animal drug is designated under this section and before the date on which an application with respect to such drug is submitted under section 360b of this title; and

(ii) which is carried out under an investigational exemption under section 360b(j) of this title.

(B) The term “manufacturing expenses” means expenses incurred in developing processes and procedures associated with manufacture of the designated new animal drug which occur after the new animal drug is designated under this section and before the date on which an application with respect to such new animal drug is submitted under section 360b or 360ccc of this title.

(1) Except as provided in subsection (c)(2), if the Secretary approves or conditionally approves an application for a designated new animal drug, the Secretary may not approve or conditionally approve another application submitted for such new animal drug with the same intended use as the designated new animal drug for another applicant before the expiration of seven years from the date of approval or conditional approval of the application.

(2) If an application filed pursuant to section 360b of this title or section 360ccc of this title is approved for a designated new animal drug, the Secretary may, during the 7-year exclusivity period beginning on the date of the application approval or conditional approval, approve or conditionally approve another application under section 360b of this title or section 360ccc of this title for such drug for such minor use or minor species for another applicant if—

(A) the Secretary finds, after providing the holder of such an approved application notice and opportunity for the submission of views, that in the granted exclusivity period the holder of the approved application cannot assure the availability of sufficient quantities of the drug to meet the needs for which the drug was designated; or

(B) such holder provides written consent to the Secretary for the approval or conditional approval of other applications before the expiration of such exclusivity period.

(3) For purposes of determining the 7-year period of exclusivity under paragraph (1) for a drug for which the Secretary intends to issue a scientific and medical evaluation and recommend controls under the Controlled Substances Act [21 U.S.C. 801 et seq.], the drug shall not be considered approved or conditionally approved until the date that the interim final rule controlling the drug is issued in accordance with section 201(j) of the Controlled Substances Act [21 U.S.C. 811(j)].

(June 25, 1938, ch. 675, § 573, as added Pub. L. 108–282, title I, § 102(b)(4), Aug. 2, 2004, 118 Stat. 900; amended Pub. L. 114–89, § 2(a)(4), Nov. 25, 2015, 129 Stat. 700.)