21 CFR § 516.1-516.2980. New animal drugs for minor use and minor species

132 21 CFR Ch. I (4–1–23 Edition) Pt. 516 the Commissioner’s findings and con clusions shall be included in the record certified by the Commissioner. PART 516—NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Subpart A—General Provisions Sec. 516.1 Scope. 516.2 Purpose. 516.3 Definitions. Subpart B—Designation of a Minor Use or Minor Species New Animal Drug 516.11 Scope of this subpart. 516.12 Purpose. 516.13 Definitions. 516.14 Submission of requests for designa tion. 516.16 Eligibility to request designation. 516.20 Content and format of a request for MUMS-drug designation. 516.21 Documentation of minor use status. 516.22 Permanent-resident U.S. agent for foreign sponsor. 516.23 Timing of requests for MUMS-drug designation. 516.24 Granting MUMS-drug designation. 516.25 Refusal to grant MUMS-drug designa tion. 516.26 Amendment to MUMS-drug designa tion. 516.27 Change in sponsorship. 516.28 Publication of MUMS-drug designa tions. 516.29 Termination of MUMS-drug designa tion. 516.30 Annual reports for a MUMS-des ignated drug. 516.31 Scope of MUMS-drug exclusive mar keting rights. 516.34 FDA recognition of exclusive mar keting rights. 516.36 Insufficient quantities of MUMS-des ignated drugs. 516.52 Availability for public disclosure of data and information in requests. Subpart C—Index of Legally Marketed Un approved New Animal Drugs for Minor Species 516.111 Scope of this subpart. 516.115 Definitions. 516.117 Submission of correspondence under this subpart. 516.119 Permanent-resident U.S. agent for foreign requestors and holders. 516.121 Meetings. 516.123 Informal conferences regarding agency administrative actions. 516.125 Investigational use of minor species new animal drugs to support indexing. 516.129 Content and format of a request for determination of eligibility for indexing. 516.131 Refuse to file a request for deter mination of eligibility for indexing. 516.133 Denying a request for determination of eligibility for indexing. 516.135 Granting a request for determina tion of eligibility for indexing. 516.137 Notification of decision regarding eligibility for indexing. 516.141 Qualified expert panels. 516.143 Written report. 516.145 Content and format of a request for addition to the index. 516.147 Refuse to file a request for addition to the index. 516.149 Denying a request for addition to the index. 516.151 Granting a request for addition to the index. 516.153 Notification of decision regarding index listing. 516.155 Labeling of indexed drugs. 516.157 Publication of the index and content of an index listing. 516.161 Modifications to indexed drugs. 516.163 Change in ownership of an index file. 516.165 Records and reports. 516.167 Removal from the index. 516.171 Confidentiality of data and informa tion in an index file. Subpart D [Reserved] Subpart E—Conditionally Approved New Animal Drugs For Minor Use and Minor Species 516.498 Crofelemer. 516.812 Enrofloxacin. 516.1012 Fuzapladib. 516.1684 Paclitaxel. 516.1780 Pimobendan. 516.1858 Potassium bromide. 516.2980 Verdinexor. AUTHORITY: 21 U.S.C. 360ccc–1, 360ccc–2, 371. SOURCE: 72 FR 41017, July 26, 2007, unless otherwise noted. Subpart A—General Provisions § 516.1 Scope. (a) This part implements section 573 of the Federal Food, Drug, and Cos metic Act (the act) (21 U.S.C. 360ccc–2) and contains the following subparts: (1) Subpart A—General Provisions. (2) Subpart B—Designation of a Minor Use or Minor Species New Ani mal Drug. (3) Subpart C [Reserved] (4) Subpart D [Reserved] VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00142 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 133 Food and Drug Administration, HHS ยง 516.3 (b) References in this part to regu latory sections of the Code of Federal Regulations are to Chapter I of Title 21, unless otherwise noted. ยง 516.2 Purpose. This part establishes standards and procedures for implementing section 573 of the act, including designation of minor use or minor species new animal drugs and associated exclusive mar keting rights. ยง 516.3 Definitions. (a) The definitions and interpreta tions contained in section 201 of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321) apply to those terms when used in this part. (b) The following definitions of terms apply to all subparts of part 516: Active moiety means the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the pharma cological action of the drug substance. Functionally superior means that a drug has been shown to provide a sig nificant therapeutic or physiologic ad vantage over that provided by a condi tionally-approved or approved MUMS drug, that is otherwise the same drug, in one or more of the following ways: (i) The drug has been shown to be more effective, as assessed by effect on a clinically meaningful endpoint in adequate and well-controlled clinical trials, than a conditionally approved or approved MUMS drug, that is other wise the same drug. Generally, this would represent the same kind of evi dence needed to support a comparative effectiveness claim for two different drugs; in most cases, direct compara tive clinical trials will be necessary; or (ii) The drug has been shown to be safer than a conditionally-approved or approved MUMS drug, that is other wise the same drug, in a substantial portion of the target population, for example, by the elimination of an in gredient or contaminant that is associ ated with relatively frequent adverse effects. In some cases, direct compara tive clinical trials will be necessary. Infrequently, as used in the minor use definition, means a disease or condi tion that is uncommon or that occurs only sporadically on an annualized basis. Limited geographical areas, as used in the minor use definition, means re gions of the United States distin guished by physical, chemical, or bio logical factors that limit the distribu tion of a disease or condition. Major species means cattle, horses, swine, chickens, turkeys, dogs, and cats. Minor species means animals, other than humans, that are not major spe cies. Minor use means the intended use of a drug in a major species for an indica tion that occurs infrequently and in only a small number of animals or in limited geographical areas and in only a small number of animals annually. MUMS drug means a new animal drug, as defined in section 201 of the act, intended for a minor use or for use in a minor species. Same dosage form means the same as one of the dosage form categories spec ified in the following parts of this chapter: (i) Part 520: Oral dosage form new animal drugs (excluding use in animal feeds as specified in part 558 of this chapter). (ii) Part 522: Implantation or injectable dosage form new animal drugs. (iii) Part 524: Ophthalmic and topical dosage form new animal drugs. (iv) Part 526: Intramammary dosage forms. (v) Part 529: Certain other dosage form new animal drugs. (vi) Part 558: New animal drugs for use in animal feeds. Same drug means a MUMS drug for which designation, indexing, or condi tional approval is sought that meets the following criteria: (i) If it is a MUMS drug composed of small molecules and contains the same active moiety as a prior designated, conditionally-approved, or approved MUMS drug, even if the particular ester or salt (including a salt with hy drogen or coordination bonds) or other noncovalent derivative such as a com plex, chelate or clathrate is not the VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00143 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 134 21 CFR Ch. I (4–1–23 Edition) § 516.3 same, it is considered the same drug; except that, if the prior MUMS drug is conditionally approved or approved and the second MUMS drug is shown to be functionally superior to the condi tionally approved or approved MUMS drug for the same intended use, it is not considered the same drug. (ii) If it is a MUMS drug composed of large molecules (macromolecules) and contains the same principal molecular structural features (but not necessarily all of the same structural features) as a prior designated, conditionally ap proved, or approved MUMS drug, it is considered the same drug; except that, if the prior MUMS drug is condi tionally approved or approved and the second MUMS drug is shown to be func tionally superior to the conditionally approved or approved MUMS drug for the same intended use, it is not consid ered the same drug. This criterion will be applied as follows to different kinds of macromolecules: (A) Two protein drugs would be con sidered the same if the only differences in structure between them were due to post-translational events or infidelity of translation or transcription or were minor differences in amino acid se quence; other potentially important differences, such as different glycosyl ation patterns or different tertiary structures, would not cause the drugs to be considered different unless the subsequent drug is shown to be func tionally superior. (B) Two polysaccharide drugs would be considered the same if they had identical saccharide repeating units, even if the number of units were to vary and even if there were postpolym erization modifications, unless the sub sequent drug is shown to be function ally superior. (C) Two polynucleotide drugs con sisting of two or more distinct nucleo tides would be considered the same if they had an identical sequence of pu rine and pyrimidine bases (or their de rivatives) bound to an identical sugar backbone (ribose, deoxyribose, or modi fications of these sugars), unless the subsequent drug is shown to be func tionally superior. (D) Closely related, complex partly definable drugs with similar pharmaco logic intent would be considered the same unless the subsequent drug is shown to be functionally superior. Same intended use means an intended use of a MUMS drug, for which designa tion, indexing, or conditional approval is sought, that is determined to be the same as (or not different from) a pre viously designated, conditionally ap proved, or approved intended use of a MUMS drug. Same intended use is es tablished by comparing two intended uses and not by simply comparing the specific language by means of which the intent is established in labeling in accordance with the following criteria: (i) Two intended uses are considered the same if one of the intended uses falls completely within the scope of the other. (ii) For intended uses associated with diseases or conditions with multiple causative organisms, two intended uses are not considered the same when they involve different causative organisms or different subsets of causative orga nisms of that disease or condition when the causative organisms involved can reliably be shown to be clinically sig nificant causes of the disease or condi tion. (iii) Two intended uses of a drug are not considered the same if they involve different intended species or different definable subpopulations (including ‘‘production classes’’) of a species. Small number of animals means equal to or less than 50,000 horses; 80,000 dogs; 150,000 cats; 310,000 cattle; 1,450,000 pigs; 14,000,000 turkeys; and 72,000,000 chick ens. Sponsor means the person requesting designation for a MUMS drug who must be the real party in interest of the development and the intended or actual production and sales of such drug (in this context, the sponsor may be an individual, partnership, organiza tion, or association). Sponsor also means the person responsible for an in vestigation of a new animal drug (in this context, the sponsor may be an in dividual, partnership, corporation, or Government agency or may be a manu facturer, scientific institution, or an investigator regularly and lawfully en gaged in the investigation of new ani mal drugs). Sponsor also means the VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00144 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 135 Food and Drug Administration, HHS § 516.20 person submitting or receiving ap proval for a new animal drug applica tion (in this context, the sponsor may be an individual, partnership, organiza tion, or association). In all contexts, the sponsor is responsible for compli ance with applicable provisions of the act and regulations. [72 FR 41017, July 26, 2007, as amended at 74 FR 43050, Aug. 25, 2009; 75 FR 69588, Nov. 15, 2010; 87 FR 56589, Sept. 15, 2022] Subpart B—Designation of a Minor Use or Minor Species New Animal Drug § 516.11 Scope of this subpart. This subpart implements section 573 of the act. Specifically, this subpart sets forth the procedures and require ments for submissions to FDA of re quests for designation of a new animal drug for a minor use or a minor spe cies. § 516.12 Purpose. This subpart establishes standards and procedures for determining eligi bility for designation and the associ ated incentives and benefits described in section 573 of the act, including a 7 year period of exclusive marketing rights. § 516.13 Definitions. The following definitions of terms apply only in the context of subpart B of this part: Director means the Director of the Of fice of Minor Use and Minor Species Animal Drug Development of the FDA Center for Veterinary Medicine. Intended use means the intended treatment, control or prevention of a disease or condition, or the intention to affect the structure or function of the body of animals within an identi fied species, subpopulation of a species, or collection of species. MUMS-designated drug means a new animal drug, as defined in section 201 of the act, intended for a minor use or for use in a minor species that has been designated under section 573 of the act. MUMS-drug exclusive marketing rights or exclusive marketing rights means that, effective on the date of FDA condi tional approval or approval as stated in the approval letter of an application for a MUMS-designated drug, no condi tional approval or approval will be given to a subsequent application for the same drug, in the same dosage form, for the same intended use for 7 years, except as otherwise provided by law or in this subpart. § 516.14 Submission of requests for designation. All correspondence relating to a re quest for designation of a MUMS drug must be addressed to the Director of the Office of Minor Use and Minor Spe cies Animal Drug Development. Sub missions not including all elements specified in § 516.20 will be returned to the sponsor without review. § 516.16 Eligibility to request designa tion. The person requesting designation must be the sponsor and the real party in interest of the development and the intended or actual production and sales of the drug or the permanent-resident U.S. agent for such a sponsor. § 516.20 Content and format of a re quest for MUMS-drug designation. (a) A sponsor that submits a request for designation of a new animal drug intended for a minor use or minor spe cies must submit each request in the form and containing the information required in paragraph (b) of this sec tion. While a request for designation may involve multiple intended uses, each request for designation must con stitute a separate submission. A spon sor may request MUMS-drug designa tion of a previously unapproved drug, or a new intended use or dosage form for an already conditionally approved or approved drug. Only one sponsor may receive MUMS-drug designation of the same drug, in the same dosage form, for the same intended use. (b) A sponsor must submit two copies of a completed, dated, and signed re quest for designation that contains the following information: (1) A request for designation of a new animal drug for a minor use or use in a minor species, which must be spe cific. (2) The name and address of the spon sor; the name of the sponsor’s primary VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00145 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 136 21 CFR Ch. I (4–1–23 Edition) § 516.21 contact person and/or permanent-resi dent U.S. agent including title, ad dress, and telephone number; the estab lished name (and proprietary name, if any) of the active pharmaceutical in gredient of the drug; and the name and address of the source of the active pharmaceutical ingredient of the drug. (3) A description of the proposed in tended use for which the drug is being or will be investigated. (4) A description of the drug and dos age form. (5) A discussion of the scientific ra tionale for the intended use of the drug; specific reference, including date(s) of submission, to all data from nonclinical laboratory studies, clinical investigations, copies of pertinent un published and published papers, and other relevant data that are available to the sponsor, whether positive, nega tive, or inconclusive. (6) A specific description of the prod uct development plan for the drug, its dosage form, and its intended use. (7) If the drug is intended for a minor use in a major species, documentation in accordance with § 516.21, with ap pended authoritative references, to demonstrate that such use is a minor use. (8) A statement that the sponsor sub mitting the request is the real party in interest of the development and the in tended or actual production and sales of the product. (9) A statement that the sponsor ac knowledges that, upon granting a re quest for MUMS designation, FDA will make information regarding the des ignation publicly available as specified in § 516.28. [72 FR 41017, July 26, 2007, as amended at 75 FR 69588, Nov. 15, 2010; 77 FR 18685, Mar. 28, 2012] § 516.21 Documentation of minor use status. So that FDA can determine whether a drug qualifies for MUMS-drug des ignation as a minor use in a major spe cies under section 573 of the act, the sponsor shall include in its request to FDA for MUMS-drug designation under § 516.20 documentation demonstrating that the use is limited to a small num ber of animals (annualized). This docu mentation must include the following information: (a) The estimated total number of animals to which the drug could poten tially be administered on an annual basis for the treatment, control, or pre vention of the disease or condition for which the drug is being developed, in cluding animals administered the drug as part of herd or flock treatment, to gether with a list of the sources (in cluding dates of information provided and literature citations) for the esti mate. (b) The estimated total number of animals referred to in paragraph (a) of this section may be further reduced to only a subset of the estimated total number of animals if administration of the drug is only medically justified for this subset. To establish this, reques tors must demonstrate that adminis tration of the drug to animals subject to the disease or condition for which the drug is being developed other than the subset is not medically justified. The sponsor must also include a list of the sources (including dates of infor mation provided and literature cita tions) for the justification that admin istration of the drug to animals other than the targeted subset is medically inappropriate. [72 FR 41017, July 26, 2007, as amended at 74 FR 43050, Aug. 25, 2009] § 516.22 Permanent-resident U.S. agent for foreign sponsor. Every foreign sponsor that seeks MUMS-drug designation shall name a permanent resident of the United States as the sponsor’s agent upon whom service of all processes, notices, orders, decisions, requirements, and other communications may be made on behalf of the sponsor. Notifications of changes in such agents or changes of address of agents should preferably be provided in advance, but not later than 60 days after the effective date of such changes. The permanent-resident U.S. agent may be an individual, firm, or domestic corporation and may rep resent any number of sponsors. The name and address of the permanent resident U.S. agent shall be provided to the Director of the Office of Minor Use and Minor Species Animal Drug Devel opment. VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00146 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 137 Food and Drug Administration, HHS § 516.27 § 516.23 Timing of requests for MUMS drug designation. A sponsor may request MUMS-drug designation at any time in the drug de velopment process prior to the submis sion of an application for either condi tional approval or approval of the MUMS drug for which designation is being requested. § 516.24 Granting MUMS-drug designa tion. (a) FDA may grant the request for MUMS-drug designation if none of the reasons described in § 516.25 for refusal to grant such a request apply. (b) When a request for MUMS-drug designation is granted, FDA will notify the sponsor in writing and will give public notice of the MUMS-drug des ignation in accordance with § 516.28. § 516.25 Refusal to grant MUMS-drug designation. (a) FDA will refuse to grant a request for MUMS-drug designation if any of the following reasons apply: (1) The drug is not intended for use in a minor species or FDA determines that there is insufficient evidence to demonstrate that the drug is intended for a minor use in a major species. (2) The drug is the same drug in the same dosage form for the same in tended use as one that already has a MUMS-drug designation but has not yet been conditionally approved or ap proved. (3) The drug is the same drug in the same dosage form for the same in tended use as one that is already condi tionally approved or approved. A drug that FDA has found to be functionally superior is not considered the same drug as an already conditionally ap proved or approved drug even if it is otherwise the same drug in the same dosage form for the same intended use. (4) The sponsor has failed to provide: (i) A credible scientific rationale in support of the intended use, (ii) Sufficient information about the product development plan for the drug, its dosage form, and its intended use to establish that adherence to the plan can lead to successful drug develop ment in a timely manner, and (iii) Any other information required under § 516.20. (b) FDA may refuse to grant a re quest for MUMS-drug designation if the request for designation contains an untrue statement of material fact or omits material information. § 516.26 Amendment to MUMS-drug designation. (a) At any time prior to conditional approval or approval of an application for a MUMS-designated drug, the spon sor may apply for an amendment to the designated intended use if the proposed change is due to new and unexpected findings in research on the drug, infor mation arising from FDA recommenda tions, or other unforeseen develop ments. (b) FDA will grant the amendment if it finds: (1) That the initial designation re quest was made in good faith; (2) That the amendment is intended to make the MUMS-drug designated in tended use conform to the results of new and unexpected findings in re search on the drug, information arising from FDA recommendations, or other unforeseen developments; and (3) In the case of a minor use, that as of the date of the submission of the amendment request, the amendment would not result in the intended use of the drug no longer being considered a minor use. § 516.27 Change in sponsorship. (a) A sponsor may transfer sponsor ship of a MUMS-designated drug to an other person. A change of sponsorship will also transfer the designation sta tus of the drug which will remain in ef fect for the new sponsor subject to the same conditions applicable to the former sponsor provided that at the time of a potential transfer, the new and former sponsors submit the fol lowing information in writing and ob tain permission from FDA: (1) The former sponsor shall submit a letter to FDA that documents the transfer of sponsorship of the MUMS designated drug. This letter shall speci fy the date of the transfer. The former sponsor shall also certify in writing to FDA that a complete copy of the re quest for MUMS-drug designation, in cluding any amendments to the re quest, and correspondence relevant to VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00147 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 138 21 CFR Ch. I (4–1–23 Edition) § 516.28 the MUMS-drug designation, has been provided to the new sponsor. (2) The new sponsor shall submit a letter or other document containing the following information: (i) A statement accepting the MUMS drug designated file or application; (ii) The date that the change in spon sorship is intended to be effective; (iii) A statement that the new spon sor has a complete copy of the request for MUMS-drug designation, including any amendments to the request and any correspondence relevant to the MUMS-drug designation; (iv) A statement that the new spon sor understands and accepts the re sponsibilities of a sponsor of a MUMS designated drug established elsewhere in this subpart; (v) The name and address of a new primary contact person or permanent resident U.S. agent; and (vi) Evidence that the new sponsor is capable of actively pursuing approval with due diligence. (b) No sponsor may relieve itself of responsibilities under the act or under this subpart by assigning rights to an other person without: (1) Assuring that the new sponsor will carry out such responsibilities; and (2) Obtaining prior permission from FDA. § 516.28 Publication of MUMS-drug designations. FDA will periodically update a pub licly available list of MUMS-designated drugs. This list will be placed on file at the FDA Division of Dockets Manage ment, and will contain the following information for each MUMS-designated drug: (a) The name and address of the spon sor; (b) The established name and trade name, if any, of the drug; (c) The dosage form of the drug; (d) The species and the proposed in tended use for which MUMS-drug des ignation was granted; and (e) The date designation was granted. § 516.29 Termination of MUMS-drug designation. (a) The sponsor of a MUMS-des ignated drug must notify FDA of any decision to discontinue active pursuit of conditional approval or approval of such MUMS drug. FDA must terminate the designation upon such notification. (b) A conditionally-approved or ap proved MUMS-designated drug sponsor must notify FDA at least 1 year before it intends to discontinue the manufac ture of such MUMS drug. FDA must terminate designation upon such noti fication. (c) MUMS designation shall termi nate upon the expiration of any appli cable period of exclusive marketing rights under this subpart. (d) FDA may terminate designation if it independently determines that the sponsor is not actively pursuing condi tional approval or approval with due diligence. At a minimum, due diligence must be demonstrated by: (1) Submission of annual progress re ports in a timely manner in accordance with § 516.30 that demonstrate that the sponsor is progressing in accordance with the drug development plan sub mitted to the agency under § 516.20 and (2) Compliance with all applicable re quirements of part 511 of this chapter. (e) Designation of a conditionally ap proved or approved MUMS-designated drug and the associated exclusive mar keting rights may be terminated if the sponsor is unable to provide sufficient quantities of the drug to meet the needs for which it is designated. (f) FDA may also terminate MUMS drug designation for any drug if the agency finds that: (1) The request for designation con tained an untrue statement of material fact; or (2) The request for designation omit ted material information required by this subpart; or (3) FDA subsequently finds that the drug in fact had not been eligible for MUMS-drug designation at the time of submission of the request; (4) The same drug, in the same dos age form, for the same intended use be comes conditionally approved or ap proved for another sponsor; or (5) FDA withdraws the conditional approval or approval of the application for the new animal drug. (g) For a conditionally approved or approved drug, termination of MUMS drug designation also terminates the VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00148 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 139 Food and Drug Administration, HHS § 516.34 sponsor’s exclusive marketing rights for the drug but does not withdraw the conditional approval or approval of the drug’s application. (h) Where a drug has been MUMS-des ignated for a minor use in a major spe cies, its designation will not be termi nated on the grounds that the number of animals to which the drug could po tentially be administered on an annual basis for the treatment, control, or pre vention of the disease or condition for which the drug is being developed, in cluding animals administered the drug as part of herd or flock treatment, sub sequently increases. (i) When a MUMS-drug designation is terminated, FDA will notify the spon sor in writing and will give public no tice of the termination of the MUMS drug designation. § 516.30 Annual reports for a MUMS designated drug. Within 14 months after the date on which a MUMS drug is granted des ignation and annually thereafter until approval, the sponsor of a MUMS-des ignated drug shall submit a brief progress report on the drug to the in vestigational new animal drug file ad dressed to the Director of the Office of Minor Use and Minor Species Animal Drug Development that includes the following information: (a) A short account of the progress of drug development including a descrip tion of studies initiated, ongoing, and completed, and a short summary of the status or results of such studies; (b) A description of the investiga tional plan for the coming year, as well as any anticipated difficulties in devel opment, testing, and marketing; and (c) A brief discussion of any changes that may affect the MUMS-designated drug status of the product. For exam ple, situations in which testing data demonstrate that the proposed in tended use is inappropriate due to un expected issues of safety or effective ness. § 516.31 Scope of MUMS-drug exclusive marketing rights. (a) After conditional approval or ap proval of an application for a MUMS designated drug in the dosage form and for the intended use for which MUMS drug designation has been granted, FDA will not conditionally approve or approve another application or abbre viated application for the same drug in the same dosage form for the same in tended use before the expiration of 7 years after the date of conditional ap proval or approval as stated in the ap proval letter from FDA, except that such an application can be condi tionally approved or approved sooner if, and at such time as, any of the fol lowing occurs: (1) FDA terminates the MUMS-drug designation and associated exclusive marketing rights under § 516.29; or (2) FDA withdraws the conditional approval or approval of the application for the drug for any reason; or (3) The sponsor with exclusive mar keting rights provides written consent to FDA to conditionally approve or ap prove another application before the expiration of 7 years; or (4) The sponsor fails to assure a suffi cient quantity of the drug in accord ance with section 573 of the act and § 516.36. (b) If an application for a MUMS drug cannot be approved until the expira tion of the period of exclusive mar keting of a MUMS-designated drug, FDA will so notify the sponsor in writ ing. § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if ap plicable) timely written notice recog nizing exclusive marketing rights when an application for a MUMS-designated drug has been conditionally approved or approved. The written notice will in form the sponsor of the requirements for maintaining MUMS-designated drug exclusive marketing rights for the full 7-year term. This notice will gen erally be contained in the letter condi tionally approving or approving the ap plication. (b) When an application is condi tionally approved or approved for a MUMS-designated drug that qualifies for exclusive marketing rights, FDA will publish this information in the FEDERAL REGISTER at the time of the conditional approval or approval. This notice will generally be contained in VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00149 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 140 21 CFR Ch. I (4–1–23 Edition) § 516.36 the notice of conditional approval or approval of the application. § 516.36 Insufficient quantities of MUMS-designated drugs. (a) Under section 573 of the act, whenever FDA has reason to believe that sufficient quantities of a condi tionally-approved or approved, MUMS designated drug to meet the needs for which the drug was designated cannot be assured by the sponsor, FDA will so notify the sponsor of this possible in sufficiency and will offer the sponsor the following options, one of which must be exercised by a time that FDA specifies: (1) Provide FDA information and data regarding how the sponsor can as sure the availability of sufficient quan tities of the MUMS-designated drug within a reasonable time to meet the needs for which the drug was des ignated; or (2) Provide FDA in writing the spon sor’s consent for the conditional ap proval or approval of other applica tions for the same drug before the expi ration of the 7-year period of exclusive marketing rights. (b) If, within the time that FDA specifies, the sponsor fails to consent to the conditional approval or approval of other applications and if FDA finds that the sponsor has not shown that it can assure the availability of sufficient quantities of the MUMS-designated drug to meet the needs for which the drug was designated, FDA will issue a written order terminating designation of the MUMS drug and the associated exclusive marketing rights. This order will state FDA’s findings and conclu sions and will constitute final agency action. An order terminating designa tion and associated exclusive mar keting rights may issue whether or not there are other sponsors that can as sure the availability of alternative sources of supply. Such an order will not withdraw the conditional approval or approval of an application. Once ter minated under this section, neither designation, nor exclusive marketing rights may be reinstated. § 516.52 Availability for public disclo sure of data and information in re quests. (a) FDA will not publicly disclose the existence of a request for MUMS-drug designation under section 573 of the act prior to final FDA action on the re quest unless the existence of the re quest has been previously publicly dis closed or acknowledged. (b) Whether or not the existence of a pending request for designation has been publicly disclosed or acknowl edged, no data or information in the re quest are available for public disclo sure prior to final FDA action on the request. (c) Except as provided in paragraph (d) of this section, upon final FDA ac tion on a request for designation, the public availability of data and informa tion in the request will be determined in accordance with part 20 of this chap ter and other applicable statutes and regulations. (d) In accordance with § 516.28, FDA will make a cumulative list of all MUMS-drug designations available to the public and update such list periodi cally. In accordance with § 516.29, FDA will give public notice of the termi nation of all MUMS-drug designations. Subpart C—Index of Legally Mar keted Unapproved New Ani mal Drugs for Minor Species SOURCE: 72 FR 69121, Dec. 6, 2007, unless otherwise noted. § 516.111 Scope of this subpart. This subpart implements section 572 of the act and provides standards and procedures to establish an index of le gally marketed unapproved new animal drugs. This subpart applies only to minor species and not to minor use in major species. This index is only avail able for new animal drugs intended for use in a minor species for which there is a reasonable certainty that the ani mal or edible products from the animal will not be consumed by humans or food-producing animals and for new animal drugs intended for use only in a hatchery, tank, pond, or other similar contained man-made structure in an VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00150 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 141 Food and Drug Administration, HHS § 516.119 early, nonfood life stage of a food-pro ducing minor species, where safety for humans is demonstrated in accordance with the standard of section 512(d) of the act (including, for an antimicrobial new animal drug, with respect to anti microbial resistance). The index shall not include a new animal drug that is contained in, or a product of, a transgenic animal. Among its topics, this subpart sets forth the standards and procedures for: (a) Investigational exemptions for in dexing purposes; (b) Submissions to FDA of requests for determination of eligibility of a new animal drug for indexing; (c) Establishment and operation of expert panels; (d) Submissions to FDA of requests for addition of a new animal drug to the index; (e) Modifications to index listings; (f) Publication of the index; and (g) Records and reports. § 516.115 Definitions. (a) The following definitions of terms apply only in the context of subpart C of this part: Director OMUMS means the Director of the Office of Minor Use and Minor Species Animal Drug Development of the FDA Center for Veterinary Medi cine. Holder means the requestor of an index listing after the request is grant ed and the new animal drug is added to the index. Index means FDA’s list of legally marketed unapproved new animal drugs for minor species. Intended use has the same meaning as that given in § 516.13 of this chapter. Qualified expert panel means a panel that is composed of experts qualified by scientific training and experience to evaluate the target animal safety and effectiveness of a new animal drug under consideration for indexing. Requestor means the person making a request for determination of eligibility for indexing or a request for addition to the index. Transgenic animal means an animal whose genome contains a nucleotide se quence that has been intentionally modified in vitro, and the progeny of such an animal, provided that the term ‘transgenic animal’ does not include an animal of which the nucleotide se quence of the genome has been modi fied solely by selective breeding. (b) The definitions of the following terms are given in § 514.3 of this chap ter: Adverse drug experience. Product defect/manufacturing defect. Serious adverse drug experience. Unexpected adverse drug experience. (c) The definitions of the following terms are given in § 516.3 of this chap ter: Same dosage form. Same drug. Same intended use. § 516.117 Submission of correspond ence under this subpart. Unless directed otherwise by FDA, all correspondence relating to any as pect of the new animal drug indexing process described in this subpart must be addressed to the Director, OMUMS. The initial correspondence for a par ticular index listing should include the name and address of the authorized contact person. Notifications of changes in such person or changes of address of such person should be pro vided in a timely manner. § 516.119 Permanent-resident U.S. agent for foreign requestors and holders. Every foreign requestor and holder shall name a permanent resident of the United States as their agent upon whom service of all processes, notices, orders, decisions, requirements, and other communications may be made on behalf of the requestor or holder. Noti fications of changes in such agents or changes of address of agents should preferably be provided in advance, but not later than 60 days after the effec tive date of such changes. The perma nent resident U.S. agent may be an in dividual, firm, or domestic corporation and may represent any number of re questors or holders. The name and ad dress of the permanent-resident U.S. agent shall be submitted to the Direc tor, OMUMS, and included in the index file. VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00151 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 142 21 CFR Ch. I (4–1–23 Edition) § 516.121 § 516.121 Meetings. (a) A requestor or potential requestor is entitled to one or more meetings to discuss the requirements for indexing a new animal drug. (b) Requests for such meetings should be in writing, be addressed to the Di rector, OMUMS, specify the partici pants attending on behalf of the re questor or potential requestor, and contain a proposed agenda for the meeting. (c) Within 30 days of receiving a re quest for a meeting, FDA will attempt to schedule the meeting at a time agreeable to both FDA and the person making the request. § 516.123 Informal conferences regard ing agency administrative actions. (a) Should FDA make an initial deci sion denying a request for determina tion of eligibility for indexing, termi nating an investigational exemption, determining that a qualified expert panel does not meet the selection cri teria, denying a request for addition to the index, or removing a new animal drug from the index, FDA will give written notice that specifies the grounds for the initial decision and provides an opportunity for an infor mal conference for review of the deci sion. (b) The written notice will include in formation for scheduling the informal conference and state that a written re quest for a conference must be made within 60 days of the date FDA sends its notice. (c) Within 45 days of receiving a re quest for an informal conference, FDA will schedule and hold the informal conference at a time agreeable to both FDA and the person making the re quest. (d) Such an informal conference will be conducted by a presiding officer who will be the Director of the Center for Veterinary Medicine or his or her des ignee, excluding the Director of the Of fice of Minor Use and Minor Species Animal Drug Development and other persons significantly involved in the initial decision. (e) The person requesting an informal conference must provide a written re sponse to FDA’s initial decision at least 2 weeks prior to the date of the scheduled meeting. Generally, this written response would be attached to the request for an informal conference. At the option of the person requesting an informal conference, such written response to FDA’s initial decision may act in lieu of a face-to-face meeting. In this case, the informal conference will consist of a review by the presiding of ficer of the submitted written response. (f) The purpose of an informal con ference is to discuss scientific and fac tual issues. It will involve a discussion of FDA’s initial decision and any writ ten response to that decision. (g) Internal agency review of a deci sion must be based on the information in the administrative file. If the person requesting an informal conference pre sents new information not in the file, the matter will be returned to the ap propriate lower level in the agency for reevaluation based on the new informa tion. (h) Informal conferences under this part are not subject to the separation of functions rules in § 10.55 of this chap ter. (i) The rules of evidence do not apply to informal conferences. No motions or objections relating to the admissibility of information and views will be made or considered, but any party to the conference may comment upon or rebut all such data, information and views. (j) [Reserved] (k) The presiding officer will prepare a written report regarding the subject of the informal conference that states and describes the basis for his or her findings. Whenever time permits, the parties to the informal conference will have 30 days to review and comment on the report. (l) The administrative record of the informal conference will consist of: (1) The notice providing an oppor tunity for an informal conference and the written response to the notice. (2) All written information and views submitted to the presiding officer at the conference or, at the discretion of the presiding officer, thereafter. (3) The presiding officer’s written re port. (4) All correspondence and memo randa of any and all meetings between VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00152 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 143 Food and Drug Administration, HHS § 516.125 the participants and the presiding offi cer. (m) The administrative record of the informal conference is closed to the submission of information at the close of the conference, unless the presiding officer specifically permits additional time for further submission. (n) The administrative record of the informal conference specified herein constitutes the exclusive record for de cision. § 516.125 Investigational use of minor species new animal drugs to sup port indexing. (a) The investigational use of a new animal drug or animal feed bearing or containing a new animal drug intended solely for investigational use in minor species shall meet the requirements of part 511 of this chapter if the investiga tional use is for the purpose of: (1) Demonstrating human food safety under section 572(a)(1)(B) of the act; (2) Demonstrating safety with re spect to individuals exposed to the new animal drug through its manufacture and use under section 572(c)(1)(F) of the act; (3) Conducting an environmental as sessment under section 572(c)(1)(E) of the act; or (4) Obtaining approval of a new ani mal drug application or abbreviated new animal drug application under sec tion 512(b) of the act. (b) Correspondence and information associated with investigations de scribed in paragraph (a) of this section shall not be sent to the Director, OMUMS, but shall be submitted to FDA in accordance with the provisions of part 511 of this chapter. (c) The investigational use of a new animal drug or animal feed bearing or containing a new animal drug intended solely for investigational use in minor species, other than for an investiga tional use described in paragraph (a) of this section, shall meet the require ments of this section. For such inves tigations, all provisions of part 511 of this chapter apply with the following modifications: (1) Under § 511.1(a)(1) of this chapter, the label statement is as follows: ‘‘Caution. Contains a new animal drug for investigational use only in laboratory animals or for tests in vitro in support of index listing. Not for use in humans.’’ (2) Under § 511.1(b)(1) of this chapter, the label statement is as follows: ‘‘Caution. Contains a new animal drug for use only in investigational animals in clinical trials in support of index listing. Not for use in humans. Edible products of investigational ani mals are not to be used for food for hu mans or other animals unless author ization has been granted by the U.S. Food and Drug Administration or by the U.S. Department of Agriculture.’’ (3) Under § 511.1(b)(4) of this chapter, the notice is titled ‘‘Notice of Claimed Investigational Exemption for a New Animal Drug for Index Listing’’ and is submitted in duplicate to the Director, OMUMS. (4) Under § 511.1(c)(3) of this chapter, if an investigator is determined to be ineligible to receive new animal drugs, each ‘‘Notice of Claimed Investiga tional Exemption for a New Animal Drug for Index Listing’’ and each re quest for indexing shall be examined with respect to the reliability of infor mation submitted by the investigator. (5) Under § 511.1(c)(4) and (d)(2) of this chapter, with respect to termination of exemptions, the sponsor of an inves tigation shall not be granted an oppor tunity for a regulatory hearing before FDA pursuant to part 16 of this chap ter. Instead, the sponsor shall have an opportunity for an informal conference as described in § 516.123. (6) Under § 511.1(c)(5) of this chapter, if the Commissioner of Food and Drugs determines, after the unreliable data submitted by the investigator are eliminated from consideration, that the data remaining are such that a re quest for addition to the index would have been denied, FDA will remove the new animal drug from the index in ac cordance with § 516.167. (d) The investigational use of a new animal drug or animal feed bearing or containing a new animal drug subject to paragraph (c) of this section shall not be subject to the good laboratory practice requirements in part 58 of this chapter. (e) Correspondence and information associated with investigations de scribed in paragraph (c) of this section VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00153 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 144 21 CFR Ch. I (4–1–23 Edition) § 516.129 shall be sent to the Director, OMUMS, in accordance with the provisions of this section. § 516.129 Content and format of a re quest for determination of eligi bility for indexing. (a) Each request for determination of eligibility: (1) May involve only one drug (or one combination of drugs) in one dosage form; (2) May not involve a new animal drug that is contained in or a product of a transgenic animal; (3) May not involve the same drug in the same dosage form for the same in tended use as a drug that is already ap proved or conditionally approved; and (4) Must be submitted separately. (b) A request for determination of eli gibility for indexing may involve mul tiple intended uses and/or multiple minor species. However, if a request for determination of eligibility for index ing that contains multiple intended uses and/or multiple minor species can not be granted in any part, the entire request will be denied. (c) A requestor must submit two cop ies of a dated request signed by the au thorized contact person for determina tion of eligibility for indexing that contains the following: (1) Identification of the minor species or groups of minor species for which the new animal drug is intended; (2) Information regarding drug com ponents and composition; (3) A statement of the intended use(s) of the new animal drug in the identi fied minor species or groups of minor species; (4) A statement of the proposed con ditions of use associated with the stat ed intended use(s) of the new animal drug, including the proposed dosage, route of administration, contraindica tions, warnings, and any other signifi cant limitations associated with the intended use(s) of the new animal drug; (5) A brief discussion of the need for the new animal drug for the intended use(s); (6) An estimate of the anticipated an nual distribution of the new animal drug, in terms of the total quantity of active ingredient, after indexing; (7) Information to establish that the new animal drug is intended for use: (i) In a minor species for which there is a reasonable certainty that the ani mal or edible products from the animal will not be consumed by humans or food-producing animals; or (ii) In a hatchery, tank, pond, or other similar contained man-made structure in (which includes on) an early, non-food life stage of a food-pro ducing minor species, and information to demonstrate food safety in accord ance with the standards of section 512(d) of the act and § 514.111 of this chapter (including, for an anti microbial new animal drug, with re spect to antimicrobial resistance); (8) A description of the methods used in, and the facilities and controls used for, the manufacture, processing and packing of the new animal drug suffi cient to demonstrate that the re questor has established appropriate specifications for the manufacture and control of the new animal drug and that the requestor has an under standing of current good manufac turing practices; (9) Either a claim for categorical ex clusion under § 25.30 or § 25.33 of this chapter or an environmental assess ment under § 25.40 of this chapter; (10) Information sufficient to support the conclusion that the new animal drug is safe under section 512(d) of the act with respect to individuals exposed to the new animal drug through its manufacture and use; and (11) The name and address of the con tact person or permanent-resident U.S. agent. § 516.131 Refuse to file a request for determination of eligibility for in dexing. (a) If a request for determination of eligibility for indexing contains all of the information required by § 516.129, FDA shall file it, and the filing date shall be the date FDA receives the re quest. (b) If a request for a determination of eligibility lacks any of the information required by § 516.129, FDA will not file it, but will inform the requestor in writing within 30 days of receiving the request as to what information is lack ing. VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00154 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 145 Food and Drug Administration, HHS § 516.141 § 516.133 Denying a request for deter mination of eligibility for indexing. (a) FDA will deny a request for deter mination of eligibility for indexing if it determines upon the basis of the re quest evaluated together with any other information before it with re spect to the new animal drug that: (1) The same drug in the same dosage form for the same intended use is al ready approved or conditionally ap proved; (2) There is insufficient information to demonstrate that the new animal drug is intended for use: (i) In a minor species for which there is a reasonable certainty that the ani mal or edible products from the animal will not be consumed by humans or food-producing animals, or (ii) In a hatchery, tank, pond, or other similar contained man-made structure in (which includes on) an early, non-food life stage of a food-pro ducing minor species, and there is in sufficient evidence to demonstrate safety for humans in accordance with the standard of section 512(d) of the act and § 514.111 of this chapter (including, for an antimicrobial new animal drug, with respect to antimicrobial resist ance); (3) The new animal drug is contained in or is a product of a transgenic ani mal; (4) There is insufficient information to demonstrate that the requestor has established appropriate specifications for the manufacture and control of the new animal drug and that the re questor has an understanding of cur rent good manufacturing practices; (5) The requester fails to submit an adequate environmental assessment under § 25.40 of this chapter or fails to provide sufficient information to estab lish that the requested action is sub ject to categorical exclusion under § 25.30 or § 25.33 of this chapter; (6) There is insufficient information to determine that the new animal drug is safe with respect to individuals ex posed to the new animal drug through its manufacture or use; or (7) The request for determination of eligibility for indexing fails to contain any other information required under the provisions of § 516.129. (b) FDA may deny a request for de termination of eligibility for indexing if it contains any untrue statement of a material fact or omits material infor mation. (c) When a request for determination of eligibility for indexing is denied, FDA will notify the requestor in ac cordance with § 516.137. § 516.135 Granting a request for deter mination of eligibility for indexing. (a) FDA will grant the request for de termination of eligibility for indexing if none of the reasons described in § 516.133 for denying such a request ap plies. (b) When a request for determination of eligibility for indexing is granted, FDA will notify the requestor in ac cordance with § 516.137. § 516.137 Notification of decision re garding eligibility for indexing. (a) Within 90 days after the filing of a request for a determination of eligi bility for indexing based on § 516.129(c)(7)(i), or 180 days for a re quest based on § 516.129(c)(7)(ii), FDA shall grant or deny the request, and no tify the requestor of FDA’s decision in writing. (b) If FDA denies the request, FDA shall provide due notice and an oppor tunity for an informal conference as described in § 516.123 regarding its deci sion. A decision of FDA to deny a re quest for determination of eligibility for indexing following an informal con ference shall constitute final agency action subject to judicial review. § 516.141 Qualified expert panels. (a) Establishment of a qualified expert panel. Establishing a qualified expert panel is the first step in the process of requesting the addition of a new ani mal drug to the index. A qualified ex pert panel may not be established until FDA has determined that the new ani mal drug is eligible for indexing. The requestor must choose members for the qualified expert panel in accordance with selection criteria listed in para graph (b) of this section and submit in formation about these proposed mem bers to FDA. FDA must determine whether the proposed qualified expert panel meets the selection criteria prior VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00155 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 146 21 CFR Ch. I (4–1–23 Edition) § 516.141 to the panel beginning its work. Quali fied expert panels operate external to FDA and are not subject to the Federal Advisory Committee Act, as amended, 5 U.S.C. App. (b) Criteria for the selection of a quali fied expert panel. (1) A qualified expert panel member must be an expert quali fied by training and experience to evaluate a significant aspect of target animal safety or effectiveness of the new animal drug under consideration. (2) A qualified expert panel member must certify that he or she has a work ing knowledge of section 572 of the act (the indexing provisions of the statute) and this subpart, and that he or she has also read and understood a clear writ ten statement provided by the re questor stating his or her duties and responsibilities with respect to review ing the new animal drug proposed for addition to the index. (3) A qualified expert panel member may not be an FDA employee. (4) A qualified expert panel must have at least three members. (5) A qualified expert panel must have members with a range of expertise such that the panel, as a whole, is qualified by training and experience to evaluate the target animal safety and effectiveness of the new animal drug under consideration. (6) Unless FDA makes a determina tion to allow participation notwith standing an otherwise disqualifying fi nancial interest, a qualified expert panel member must not have a conflict of interest or the appearance of a con flict of interest, as described in para graph (g) of this section. (c) Requestor responsibilities. (1) The requestor must: (i) Choose members for the qualified expert panel in accordance with selec tion criteria listed in paragraph (b) of this section. (ii) Provide each potential expert panel member a copy of section 572 of the act (the indexing provisions of the statute) and this subpart and obtain certification that he or she has a work ing knowledge of the information. (iii) Provide each potential expert panel member a written statement de scribing the purpose and scope of his or her participation on the qualified ex pert panel and obtain certification that he or she has read and understood the information. The written statement should describe the duties and respon sibilities of qualified expert panels and their members established by para graphs (e) and (f) of this section, in cluding the need to prepare a written report under § 516.143. (iv) Obtain information from each po tential expert panel member dem onstrating that he or she is qualified by training and experience to evaluate the target animal safety and effective ness of the new animal drug under con sideration. This information can be ob tained from a comprehensive cur riculum vitae or similar document. (v) Notify each potential expert panel member that he or she must submit in formation relating to potential conflict of interest directly to FDA in a timely manner, as required in paragraph (e)(6) of this section. (2) The requestor must submit, in writing, the names and addresses of the proposed qualified expert panel mem bers and sufficient information about each proposed member for FDA to de termine whether the panel meets the selection criteria listed in paragraphs (b)(1) through (b)(5) of this section. (3) After FDA has determined that the qualified expert panel meets the se lection criteria, the requestor must provide to the panel all information known by the requestor that is rel evant to a determination of the target animal safety and the effectiveness of the new animal drug at issue. In addi tion, the requestor must notify FDA of the name of the qualified expert panel leader. (4) The requestor must immediately notify FDA if it believes a qualified ex pert panel member no longer meets the selection criteria listed in paragraph (b) of this section or is otherwise not in compliance with the requirements of this section. (5) If a qualified expert panel member cannot complete the review for which he or she was selected, the requestor must either choose a replacement or justify the continued work of the panel in the absence of the lost panelist. In either case, the requestor must submit sufficient information for FDA to de termine whether the proposed revised VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00156 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 147 Food and Drug Administration, HHS § 516.141 qualified expert panel meets the selec tion criteria listed in paragraphs (b)(1) through (b)(5) of this section. (6) The requestor must keep copies of all information provided to, or received from, qualified expert panel members, including the written report, for 2 years after the completion of the re port, or the product is added to the index, whichever occurs later, and make them available to a duly author ized employee of the agency at all rea sonable times. (d) FDA responsibilities. (1) FDA will determine whether the requestor’s pro posed qualified expert panel meets the selection criteria listed in paragraph (b) of this section. FDA will expedi tiously inform the requestor, in writ ing, of its determination. If FDA deter mines that the qualified expert panel does not meet the selection criteria, FDA will provide due notice and an op portunity for an informal conference as described in § 516.123. A determination by FDA that a proposed qualified ex pert panel does not meet the selection criteria following an informal con ference shall constitute final agency action subject to judicial review. (2) If FDA determines that a qualified expert panel no longer meets the selec tion criteria listed in paragraph (b) of this section or that the panel or its members are not in compliance with the requirements of this section, the agency will expeditiously inform the requestor, in writing, of this deter mination and provide due notice and an opportunity for an informal conference as described in § 516.123. A determina tion by FDA, following an informal conference, that a qualified expert panel no longer meets the selection cri teria listed in paragraph (b) of this sec tion or that the panel or its members are not in compliance with the require ments of this section shall constitute final agency action subject to judicial review. (e) Responsibilities of a qualified expert panel member. A qualified expert panel member must do the following: (1) Continue to meet all selection cri teria described in paragraph (b) of this section. (2) Act in accordance with generally accepted professional and ethical busi ness practices. (3) Review all information relevant to a determination of the target ani mal safety and effectiveness of the new animal drug provided by the requestor. The panel should also consider all rel evant information otherwise known by the panel members, including anec dotal information. (4) Participate in the preparation of the written report of the findings of the qualified expert panel, described in § 516.143. (5) Sign, or otherwise approve in writing, the written report. Such sig nature or other written approval will serve as certification that the written report meets the requirements of the written report in § 516.143. (6) Provide the information relating to potential conflict of interest de scribed in paragraph (g) of this section to FDA for its consideration. Such in formation should be submitted directly to the Director, OMUMS, when notified by the requestor. (7) Immediately notify the requestor and FDA of any change in conflict of interest status. (8) Certify at the time of submission of the written report that there has been no change in conflict of interest status, or identify and document to FDA any such change. (f) Additional responsibilities of a quali fied expert panel leader. (1) The qualified expert panel leader must ensure that the activities of the panel are per formed efficiently and in accordance with generally accepted professional and ethical business practices. (2) The qualified expert panel leader serves as the principal point of contact between representatives of the agency and the panel. (3) The qualified expert panel leader is responsible for submitting the writ ten report and all notes or minutes re lating to panel deliberations to the re questor. (4) The qualified expert panel leader must maintain a copy of the written report and all notes or minutes relat ing to panel deliberations that are sub mitted to the requestor for 2 years after the report is submitted. Such records must be made available to a duly authorized employee of the agen cy for inspection at all reasonable times. VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00157 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 148 21 CFR Ch. I (4–1–23 Edition) § 516.141 (g) Prevention of conflicts of interest. (1) For the purposes of this subpart, FDA will consider a conflict of interest to be any financial or other interest that could impair a person’s objec tivity in serving on the qualified expert panel or could create an unfair com petitive advantage for a person or orga nization. (2) Factors relevant to whether there is a conflict of interest or the appear ance of a conflict of interest include whether the qualified expert panel member, their spouse, their minor chil dren, their general partners, or any or ganizations in which they serve as an officer, director, trustee, general part ner or employee: (i) Is currently receiving or seeking funding from the requestor through a contract or research grant (either di rectly or indirectly through another entity, such as a university). (ii) Has any employment, contrac tual, or other financial arrangement with the requestor other than receiving a reasonable fee for serving as a mem ber of the qualified expert panel. (iii) Has any ownership or financial interest in any drug, drug manufac turer, or drug distributor which will benefit from either a favorable or unfa vorable evaluation or opinion. (iv) Has any ownership or financial interest in the new animal drug being reviewed by the qualified expert panel. (v) Has participated in the design, manufacture, or distribution of any drug that will benefit from either a fa vorable or unfavorable opinion of the qualified expert panel. (vi) Has provided within 1 year any consultative services regarding the new animal drug being reviewed by the qualified expert panel. (vii) Has entered into an agreement in which fees charged or accepted are contingent upon the panel member making a favorable evaluation or opin ion. (viii) Receives payment for services related to preparing information the requestor presents to the qualified ex pert panel, other than for services re lated to the written report described in § 516.143. (3) To permit FDA to make a decision regarding potential conflict of interest, a potential qualified expert panel mem ber must submit to the Director, OMUMS, the following information re lating to themselves, their spouse, their minor children, their general partners, or any organizations in which they serve as an officer, director, trust ee, general partner or employee, re garding the following issues to the ex tent that they are, in any way, rel evant to the subject of the review of the qualified expert panel: (i) Investments (for example, stocks, bonds, retirement plans, trusts, part nerships, sector funds, etc.), including for each the following: Name of the firm, type of investment, owner (self, spouse, etc.), number of shares / cur rent value. (ii) Employment (full or part time, current or under negotiation), includ ing for each the following: Name of the firm, relationship (self, spouse, etc.), position in firm, date employment or negotiation began. (iii) Consultant/advisor (current or under negotiation), including for each the following: Name of the firm, topic/ issue, amount received, date initiated. (iv) Contracts, grants, Cooperation Research and Development Agreement (CRADAs) (current or under negotia tion), including for each the following: Type of agreement, product under study and indications, amount of remu neration (institution/self), time period, sponsor (government, firm, institution, individual), role of the person (site in vestigator, principal investigator, co investigator, partner, no involvement, other), awardee. (v) Patents/royalties/trademarks, in cluding for each the following: Descrip tion, name of firm involved, income re ceived. (vi) Expert witness (last 12 months or under negotiation), including for each the following: For or against, name of firm, issue, amount received. (vii) Speaking/writing (last 12 months or under negotiation), including for each the following: Firm, topic/issue, amount received (honorarium/travel), date. (viii) Whether the potential qualified expert panel member, their spouse, their minor children, their general partners or any organizations in which they serve as an officer, director, trust ee, general partner or employee, have VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00158 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 149 Food and Drug Administration, HHS § 516.145 had, at any time in the past, involve ment of the kind noted in paragraph (g)(3)(i) through (g)(3)(vii) of this sec tion with respect to the animal drug that is the subject of the qualified ex pert panel review. (ix) Whether there are any other in volvements (other kinds of relation ships) that would give the appearance of a conflict of interest which have not been described in paragraph (g)(3)(i) through (g)(3)(viii) of this section. (x) In all cases, a response of ‘‘no,’’ ‘‘none,’’ or ‘‘not applicable’’ is satisfac tory when there is no relevant informa tion to submit. (xi) A certification statement signed by the potential qualified expert panel member to the effect that all informa tion submitted is true and complete to the best of their knowledge, that they have read and understood their obliga tions as an expert panel member, and that they will notify FDA and the re questor of any change in their conflict of interest status. (4) The fact that a qualified expert panel member receives a reasonable fee for services as a member of the quali fied expert panel, provided that the fee is no more than commensurate with the value of the time that the member devotes to the review process, does not constitute a conflict of interest or the appearance of a conflict of interest. § 516.143 Written report. The written report required in § 516.145(b)(3) shall: (a) Be written in English by a quali fied expert panel meeting the require ments of § 516.141; (b) Describe the panel’s evaluation of all available target animal safety and effectiveness information relevant to the proposed use of the new animal drug, including anecdotal information; (c) For all information considered, including anecdotal information, in clude either a citation to published lit erature or a summary of the informa tion; (d) State the panel’s opinion regard ing 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-ap proved new animal drug for the minor species in question; (e) Be signed, or otherwise approved in writing, by all panel members, in ac cordance with § 516.141; and (f) If the panel unanimously con cludes 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 being caused by the absence of an approved or conditionally-ap proved new animal drug for the minor species in question, the written report shall: (1) Provide draft labeling that in cludes all conditions of use and limita tions of use of the new animal drug deemed necessary by the panel to as sure that the benefits of use of the new animal drug outweigh the risks, or pro vide narrative information from which such labeling can be written by the re questor; and (2) Include a recommendation regard ing whether the new animal drug should be limited to use under the pro fessional supervision of a licensed vet erinarian. § 516.145 Content and format of a re quest for addition to the index. (a) A requestor may request addition of a new animal drug to the index only after the new animal drug has been granted eligibility for indexing. (b) A requestor shall submit two cop ies of a dated request signed by the au thorized contact for addition of a new animal drug to the index that contains the following: (1) A copy of FDA’s determination of eligibility issued under § 516.137; (2) A copy of FDA’s written deter mination that the proposed qualified expert panel meets the selection cri teria provided for in § 516.141(b); (3) A written report that meets the requirements of § 516.143; (4) A proposed index entry that con tains the information described in § 516.157; (5) Proposed labeling, including rep resentative labeling proposed to be used for Type B and Type C medicated feeds if the drug is intended for use in the manufacture of medicated feeds; (6) Anticipated annual distribution of the new animal drug, in terms of the VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00159 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 150 21 CFR Ch. I (4–1–23 Edition) § 516.147 total quantity of active ingredient, after indexing; (7) A written commitment to manu facture the new animal drug and ani mal feeds bearing or containing such new animal drug according to current good manufacturing practices; (8) A written commitment to label, distribute, and promote the new ani mal drug only in accordance with the index entry; (9) The name and address of the con tact person or permanent-resident U.S. agent; and (10) A draft Freedom of Information summary which includes the following information: (i) A general information section that contains the name and address of the requestor and a description of the drug, route of administration, indica tions, and recommended dosage. (ii) A list of the names and affili ations of the members of the qualified expert panel, not including their ad dresses or other contact information. (iii) A summary of the findings of the qualified expert panel concerning the target animal safety and effectiveness of the drug. (iv) Citations of all publicly-available literature considered by the qualified expert panel. (v) For an early life stage of a food producing minor species animal, a human food safety summary. (c) Upon specific request by FDA, the requestor shall submit the information described in § 516.141 that it submitted to the qualified expert panel. Any such information not in English should be accompanied by an English trans lation. § 516.147 Refuse to file a request for addition to the index. (a) If a request for addition to the index contains all of the information required by § 516.145(b), FDA shall file it, and the filing date shall be the date FDA receives the request. (b) If a request for addition to the index lacks any of the information re quired by § 516.145, FDA will not file it, but will inform the requestor in writ ing within 30 days of receiving the re quest as to what information is lack ing. § 516.149 Denying a request for addi tion to the index. (a) FDA will deny a request for addi tion to the index if it finds the fol lowing: (1) The same drug in the same dosage form for the same intended use is al ready approved or conditionally ap proved; (2) On the basis of new information, the new animal drug no longer meets the conditions for eligibility for index ing; (3) The request for indexing fails to contain information required under the provisions of § 516.145; (4) The qualified expert panel fails to meet any of the selection criteria list ed in § 516.141(b); (5) The written report of the qualified expert panel and other information available to FDA is insufficient to per mit FDA to determine that the bene fits of using the new animal drug for the proposed use in a minor species outweigh its risks to the target ani mal, taking into account the harm caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question; (6) On the basis of the report of the qualified expert panel and other infor mation available to FDA, the benefits of using the new animal drug for the proposed use in a minor species do not outweigh its risks to the target ani mal, taking into account the harm caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question; or (7) The request contains any untrue statement of a material fact or omits material information. (b) When a request for addition to the index is denied, FDA will notify the re questor in accordance with § 516.153. § 516.151 Granting a request for addi tion to the index. (a) FDA will grant the request for ad dition of a new animal drug to the index if none of the reasons described in § 516.149 for denying such a request applies. (b) When a request for addition of a new animal drug to the index is grant ed, FDA will notify the requestor in ac cordance with § 516.153. VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00160 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 151 Food and Drug Administration, HHS § 516.161 § 516.153 Notification of decision re garding index listing. (a) Within 180 days after the filing of a request for addition of a new animal drug to the index, FDA shall grant or deny the request and notify the re questor of FDA’s decision in writing. (b) If FDA denies the request for ad dition of a new animal drug to the index, FDA shall provide due notice and an opportunity for an informal conference as described in § 516.123. A decision of FDA to deny a request to index a new animal drug following an informal conference shall constitute final agency action subject to judicial review. § 516.155 Labeling of indexed drugs. (a) The labeling of an indexed drug that is found to be eligible for indexing under § 516.129(c)(7)(i) shall state, prominently and conspicuously: ‘‘NOT APPROVED BY FDA.—Legally marketed as an FDA indexed product. Extra-label use is prohibited.’’ ‘‘This product is not to be used in animals intended for use as food for humans or other animals.’’ (b) The labeling of an indexed drug that was found to be eligible for index ing for use in an early, non-food life stage of a food-producing minor species animal, under § 516.129(c)(7)(ii), shall state, prominently and conspicuously: ‘‘NOT APPROVED BY FDA.—Legally marketed as an FDA indexed product. Extra-label use is prohibited.’’ (c) The labeling of an indexed drug shall contain such other information as may be prescribed in the index listing. § 516.157 Publication of the index and content of an index listing. (a) FDA will make the list of indexed drugs available through the FDA Web site at http://www.fda.gov. A printed copy can be obtained by writing to the Freedom of Information Staff or by vis iting FDA’s Freedom of Information Staff’s Public Reading Room at the ad dress listed on the Agency’s Web site at http://www.fda.gov. (b) The list will contain the following information for each indexed drug: (1) The name and address of the per son who holds the index listing; (2) The name of the drug and the in tended use and conditions of use for which it is indexed; (3) Product labeling; and (4) Conditions and any limitations that FDA deems necessary regarding use of the drug. [72 FR 69121, Dec. 6, 2007; 76 FR 31470, June 1, 2011, as amended at 79 FR 68115, Nov. 14, 2014] § 516.161 Modifications to indexed drugs. (a) After a drug is listed in the index, certain modifications to the index list ing may be requested. Any modifica tion of an index listing may not cause an indexed drug to be a different drug (or different combination of drugs) or a different dosage form. If such modifica tion is requested, FDA will notify the holder that a new index listing is re quired for the new drug or dosage form. (b) Modifications to the indexed drug will fall under one of three categories and must be submitted as follows: (1) Urgent changes. (i) The following modifications to an indexed drug or its labeling should be made as soon as pos sible, and a request to modify the in dexed drug should be concurrently sub mitted: (A) The addition to package labeling, promotional labeling, or prescription drug advertising of additional warning, contraindication, side effect, or cau tionary information. (B) The deletion from package label ing, promotional labeling, and drug ad vertising of false, misleading, or unsup ported indications for use or claims for effectiveness. (C) Changes in manufacturing meth ods or controls required to correct product or manufacturing defects that may result in serious adverse drug events. (ii) The modifications described in paragraph (b)(1)(i) of this section must be submitted to the Director, OMUMS, in the form of a request for modifica tion of an indexed drug, and must con tain sufficient information to permit FDA to determine the need for the modification and whether the modi fication appropriately addresses the need. (iii) FDA will take no action against an indexed drug or index holder solely because modifications of the kinds de scribed in paragraph (b)(1)(i) of this section are placed into effect by the VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00161 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 152 21 CFR Ch. I (4–1–23 Edition) § 516.163 holder prior to receipt of a written no tice granting the request if all the fol lowing conditions are met: (A) A request to modify the indexed drug providing a full explanation of the basis for the modifications has been submitted, plainly marked on the mail ing cover and on the request as follows: ‘‘Special indexing request— modifica tions being effected;’’ (B) The holder specifically informs FDA of the date on which such modi fications are to be effected and submits two printed copies of any revised label ing to be placed in use, and (C) All promotional labeling and all drug advertising are promptly revised consistent with modifications made in the labeling on or within the indexed drug package. (2) Significant changes. (i) The fol lowing modifications to an indexed drug or its labeling may be made only after a request has been submitted to and subsequently granted by FDA: (A) Addition of an intended use. (B) Addition of a species. (C) Addition or alteration of an ac tive ingredient. (D) Alteration of the concentration of an active ingredient. (E) Alteration of dose or dosage regi men. (F) Alteration of prescription or over-the-counter status. (ii) Each modification described in paragraph (b)(2)(i) of this section must go through the same review process as an original index listing and is subject to the same standards for review. (iii) Each submission of a request for a modification described in paragraph (b)(2)(i) of this section should contain only one type of modification unless one modification is actually neces sitated by another, such as a modifica tion of dose necessitated by a modifica tion of the concentration of an active ingredient. Submissions relating to ad dition of an intended use for an exist ing species or addition of a species should be submitted separately, but each such submission may include mul tiple additional intended uses and/or multiple additional species. (3) Minor changes. All modifications other than those described in para graphs (b)(1) and (b)(2) of this section including, but not limited to, formula tion, labeling, and manufacturing methods and controls (at the same level of detail that these were de scribed in the request for determina tion of eligibility for indexing) must be submitted as part of the annual in dexed drug experience report or as oth erwise required by § 516.165. (c) When changes affect the index listing, it will be updated accordingly. § 516.163 Change in ownership of an index file. (a) A holder may transfer ownership of a drug’s index file to another person. (1) The former owner shall submit in writing to FDA a statement that all rights in the index file have been trans ferred, giving the name and address of the new owner and the date of the transfer. The former owner shall also certify that a complete copy of the fol lowing, to the extent that they exist at the time of the transfer of ownership, has been provided to the new owner: (i) The request for determination of eligibility; (ii) The request for addition to the index; (iii) Any modifications to the index listing; (iv) Any records and reports under § 516.165; and (v) All correspondence with FDA rel evant to the indexed drug and its index listing. (2) The new owner shall submit the following information in writing to FDA: (i) The date that the change in own ership is effective; (ii) A statement that the new owner has a complete copy of all documents listed in paragraph (a)(1) of this section to the extent that they exist at the time of the transfer of ownership; (iii) A statement that the new owner understands and accepts the respon sibilities of a holder of an indexed drug; (iv) The name and address of a new primary contact person or permanent resident U.S. agent; and (v) A list of labeling changes associ ated with the change of ownership (e.g., a new trade name) as draft label ing, with complete final printed label ing to be submitted in the indexed drug annual report in accordance with §§ 516.161 and 516.165. VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00162 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 153 Food and Drug Administration, HHS § 516.165 (b) Upon receiving the necessary in formation to support a change of own ership of a drug’s index file, FDA will update its publicly-available listing in accordance with § 516.157. § 516.165 Records and reports. (a) Scope and purpose. (1) The record keeping and reporting requirements of this section apply to all holders of in dexed drugs, including indexed drugs intended for use in medicated feeds. (2) A holder is not required to report information under this section if the holder has reported the same informa tion under § 514.80 of this chapter. (3) The records and reports referred to in this section are in addition to those required by the current good manufacturing practice regulations in parts 211, 225, and 226 of this chapter. (4) FDA will review the records and reports required in this section to de termine, or facilitate a determination, whether there may be grounds for re moving a drug from the index under section 572(f) of the act. (b) Recordkeeping requirements. (1) Each holder of an indexed drug must establish and maintain complete files containing full records of all informa tion pertinent to the safety or effec tiveness of the indexed drug. Such records must include information from foreign and domestic sources. (2) The holder must, upon request from any authorized FDA officer or employee, at all reasonable times, per mit such officer or employee to have access to copy and to verify all such records. (c) Reporting requirements—(1) Three day indexed drug field alert report. The holder must inform the appropriate FDA District Office or local FDA resi dent post of any product or manufac turing defects that may result in seri ous adverse drug events within 3 work ing days of first becoming aware that such a defect may exist. The holder may initially provide this information by telephone or other electronic com munication means, with prompt writ ten followup. The mailing cover must be plainly marked ‘‘3–Day Indexed Drug Field Alert Report.’’ (2) Fifteen-day indexed drug alert re port. The holder must submit a report on each serious, unexpected adverse drug event, regardless of the source of the information. The holder must sub mit the report within 15 working days of first receiving the information. The mailing cover must be plainly marked ‘‘15–Day Indexed Drug Alert Report.’’ (3) Annual indexed drug experience re port. The holder must submit this re port every year on the anniversary date of the letter granting the request for addition of the new animal drug to the index, or within 60 days thereafter. The report must contain data and in formation for the full reporting period. Any previously submitted information contained in the report must be identi fied as such. The holder may ask FDA to change the date of submission and, after approval of such request, file such reports by the new filing date. The re port must contain the following: (i) The number of distributed units of each size, strength, or potency (e.g., 100,000 bottles of 100 5-milligram tab lets; 50,000 10-milliliter vials of 5- per cent solution) distributed during the reporting period. This information must be presented in two categories: Quantities distributed domestically and quantities exported. This informa tion must include any distributor-la beled product. (ii) If the labeling has changed since the last report, include a summary of those changes and the holder’s and dis tributor’s current package labeling, in cluding any package inserts. For large size package labeling or large shipping cartons, submit a representative copy (e.g., a photocopy of pertinent areas of large feed bags). If the labeling has not changed since the last report, include a statement of such fact. (iii) A summary of any changes made during the reporting period in the methods used in, and facilities and con trols used for, manufacture, processing, and packing. This information must be presented in the same level of detail that it was presented in the request for determination of eligibility for index ing. Do not include changes that have already been submitted under § 516.161. (iv) Nonclinical laboratory studies and clinical data not previously re ported under this section. (v) Adverse drug experiences not pre viously reported under this section. VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00163 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 154 21 CFR Ch. I (4–1–23 Edition) § 516.167 (vi) Any other information pertinent to safety or effectiveness of the in dexed drug not previously reported under this section. (4) Distributor’s statement. At the time of initial distribution of an indexed drug by a distributor, the holder must submit a report containing the fol lowing: (i) The distributor’s current product labeling. This must be identical to that in the index listing except for a dif ferent and suitable proprietary name (if used) and the name and address of the distributor. The name and address of the distributor must be preceded by an appropriate qualifying phrase such as ‘‘manufactured for’’ or ‘‘distributed by.’’ (ii) A signed statement by the dis tributor stating: (A) The category of the distributor’s operations (e.g., wholesale or retail); (B) That the distributor will dis tribute the drug only under the indexed drug labeling; (C) That the distributor will promote the indexed drug only for use under the conditions stated in the index listing; and (D) If the indexed drug is a prescrip tion new animal drug, that the dis tributor is regularly and lawfully en gaged in the distribution or dispensing of prescription products. (5) Other reporting. FDA may by order require that a holder submit informa tion in addition to that required by this section or that the holder submit the same information but at different times or reporting periods. § 516.167 Removal from the index. (a) After due notice to the holder of the index listing and an opportunity for an informal conference as described in § 516.123, FDA shall remove a new animal drug from the index if FDA finds that: (1) The same drug in the same dosage form for the same intended use has been approved or conditionally ap proved; (2) The expert panel failed to meet the requirements in § 516.141; (3) On the basis of new information before FDA, evaluated together with the evidence available to FDA 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 ani mal, taking into account the harm caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question; (4) Any of the conditions in § 516.133(a)(2), (5), or (6) are present; (5) The manufacture of the new ani mal drug is not in accordance with cur rent good manufacturing practices; (6) The labeling, distribution, or pro motion of the new animal drug is not in accordance with the index listing; (7) The conditions and limitations of use associated with the index listing have not been followed; or (8) Any information used to support the request for addition to the index contains any untrue statement of ma terial fact. (b) The agency may partially remove an indexing listing if, in the opinion of the agency, such partial removal would satisfactorily resolve a safety or effec tiveness issue otherwise warranting re moval of the listing under section 572(f)(1)(B) of the act. (c) FDA may immediately suspend a new animal drug from the index if FDA determines 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 agency will subsequently provide due notice and an opportunity for an informal conference as described in § 516.123. (d) A decision of FDA to remove a new animal drug from the index fol lowing an informal conference, if any, shall constitute final agency action subject to judicial review. § 516.171 Confidentiality of data and information in an index file. (a) For purposes of this section, the index file includes all data and infor mation submitted to or incorporated by reference into the index file, such as data and information related to inves tigational use exemptions under § 516.125, requests for determination of eligibility for indexing, requests for ad dition to the index, modifications to indexed drugs, changes in ownership, reports submitted under § 516.165, and master files. The availability for public disclosure of any record in the index VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00164 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 155 Food and Drug Administration, HHS § 516.171 file shall be handled in accordance with the provisions of this section. (b) The existence of an index file will not be disclosed by FDA before an index listing has been made public by FDA, unless it has previously been pub licly disclosed or acknowledged by the requestor. (c) If the existence of an index file has not been publicly disclosed or ac knowledged, no data or information in the index file are available for public disclosure. (d) If the existence of an index file has been publicly disclosed or acknowl edged before an index listing has been made public by FDA, no data or infor mation contained in the file will be available for public disclosure before such index listing is made public, but the agency may, at its discretion, dis close a brief summary of such selected portions of the safety and effectiveness data as are appropriate for public con sideration of a specific pending issue, e.g., at an open session of a Food and Drug Administration advisory com mittee or pursuant to an exchange of important regulatory information with a foreign government. (e) After FDA sends a written notice to the requestor granting a request for addition to the index, the following data and information in the index file are available for public disclosure un less extraordinary circumstances are shown: (1) All safety and effectiveness data and information previously disclosed to the public, as defined in § 20.81 of this chapter. (2) A summary or summaries of the safety and effectiveness data and infor mation submitted with or incorporated by reference in the index file. Such summaries do not constitute the full information described under section 572(c) and (d) of the act on which the safety or effectiveness of the drug may be determined. Such summaries will be based on the draft Freedom of Informa tion summary submitted under § 516.145, which will be reviewed and, where appropriate, revised by FDA. (3) A protocol for a test or study, un less it is shown to fall within the ex emption established for trade secrets and confidential commercial informa tion in § 20.61 of this chapter. (4) Adverse reaction reports, product experience reports, consumer com plaints, and other similar data and in formation, after deletion of the fol lowing: (i) Names and any information that would identify the person using the product. (ii) Names and any information that would identify any third party involved with the report, such as a veterinarian. (5) A list of all active ingredients and any inactive ingredients previously disclosed to the public as defined in § 20.81 of this chapter. (6) An assay method or other analyt ical method, unless it serves no regu latory or compliance purpose and is shown to fall within the exemption es tablished in § 20.61 of this chapter. (7) All correspondence and written summaries of oral discussions relating to the index file, in accordance with the provisions of part 20 of this chap ter. (f) The following data and informa tion in an index file are not available for public disclosure unless they have been previously disclosed to the public as defined in § 20.81 of this chapter, or they relate to a product or ingredient that has been abandoned and they no longer represent a trade secret or con fidential commercial or financial infor mation as defined in § 20.61 of this chap ter: (1) Manufacturing methods or proc esses, including quality control proce dures. (2) Production, sales, distribution, and similar data and information, ex cept that any compilation of such data and information aggregated and pre pared in a way that does not reveal data or information which is not avail able for public disclosure under this provision is available for public disclo sure. (3) Quantitative or semiquantitative formulas. (g) Subject to the disclosure provi sions of this section, the agency shall regard the contents of an index file as confidential information unless specifi cally notified in writing by the holder of the right to disclose, to reference, or otherwise utilize such information on behalf of another named person. VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00165 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 156 21 CFR Ch. I (4–1–23 Edition) § 516.498 (h) For purposes of this regulation, safety and effectiveness data include all studies and tests of an animal drug on animals and all studies and tests on the animal drug for identity, stability, purity, potency, and bioavailability. (i) Safety and effectiveness data and information that have not been pre viously disclosed to the public are available for public disclosure at the time any of the following events occurs unless extraordinary circumstances are shown: (1) No work is being or will be under taken to have the drug indexed in ac cordance with the request. (2) A final determination is made that the drug cannot be indexed and all legal appeals have been exhausted. (3) The drug has been removed from the index and all legal appeals have been exhausted. (4) A final determination has been made that the animal drug is not a new animal drug. Subpart D [Reserved] Subpart E—Conditionally Ap proved New Animal Drugs For Minor Use and Minor Species SOURCE: 72 FR 57200, Oct. 9, 2007, unless otherwise noted. § 516.498 Crofelemer. (a) Specifications. Each delayed-re lease tablet contains 125 milligrams (mg) crofelemer. (b) Sponsor. See No. 086149 in § 510.600(c) of this chapter. (c) Conditions of use—(1) Amount. Ad minister 1 tablet orally twice daily for 3 days for dogs weighing ≤140 pounds. Administer 2 tablets orally twice daily for 3 days for dogs weighing >140 pounds. (2) Indications for use. For the treat ment of chemotherapy-induced diar rhea in dogs. (3) Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian. It is a violation of Federal law to use this product other than as directed in the labeling. [87 FR 17944, Mar. 29, 2022. Redesignated at 88 FR 16546, Mar. 20, 2023] § 516.812 Enrofloxacin. (a) Specifications. Each milliliter (mL) of solution contains 100 milli grams (mg) enrofloxacin. (b) Sponsor. See No. 058198 in § 510.600(c) of this chapter. (c) Conditions of use in cattle—(1) Amount. Administer, by subcutaneous injection, a single dose of 12.5 mg/kilo gram of body weight (5.7 mL/100 pounds of body weight). Administered dose vol ume should not exceed 20 mL per injec tion site. (2) Indications for use. For the treat ment of clinical anaplasmosis associ ated with Anaplasma marginale in re placement dairy heifers under 20 months of age and all classes of beef cattle except beef calves less than 2 months of age and beef bulls intended for breeding (any age). Not for use in any other class of dairy cattle or in veal calves. (3) Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian. Federal law pro hibits the extra-label use of this drug in food-producing animals. Cattle in tended for human consumption must not be slaughtered within 28 days from the last treatment. This product is not approved for use in female dairy cattle 20 months of age or older including dry dairy cows. Use in these cattle may cause drug residues in milk and/or in calves born to these cows. A with drawal period has not been established for this product in pre-ruminating calves. Do not use in calves to be proc essed for veal. [86 FR 13184, Mar. 8, 2021, as amended at 87 FR 58960, Sept. 29, 2022] § 516.1012 Fuzapladib. (a) Specifications. The drug is pro vided as a powder for injection that is reconstituted with 3.5 milliliter (mL) of provided diluent to a final con centration of 4 milligrams (mg) fuzapladib sodium per mL. (b) Sponsor. See No. 064642 in § 510.600(c) of this chapter. (c) Conditions of use—(1) Amount. Ad minister at a dosage of 0.4 mg (0.1 mL) per kilogram of body weight once daily for 3 consecutive days by intravenous (IV) injection over 15 seconds to 1 minute. VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00166 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 157 Food and Drug Administration, HHS § 516.2980 (2) Indications for use in dogs. For the management of clinical signs associ ated with acute onset of pancreatitis in dogs. (3) Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian. It is a violation of Federal law to use this product other than as directed in the labeling. [88 FR 16546, Mar. 20, 2023] § 516.1684 Paclitaxel. (a) Specifications. Each vial of powder contains 60 milligrams (mg) paclitaxel. Each milliliter of constituted solution contains 1 mg paclitaxel. (b) Sponsor. See No. 052818 in 510.600(c) of this chapter. (c) Conditions of use in dogs—(1) Amount. Administer 150 mg per square meter of body surface area intra venously over 15 to 30 minutes, once every 3 weeks, for up to 4 doses. (2) Indications for use. For the treat ment of nonresectable stage III, IV, or V mammary carcinoma in dogs that have not received previous chemo therapy or radiotherapy. For the treat ment of resectable and nonresectable squamous cell carcinoma in dogs that have not received previous chemo therapy or radiotherapy. (3) Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian. It is a violation of Federal law to use this product other than as directed in the labeling. [79 FR 18158, Apr. 1, 2014] § 516.1780 Pimobendan. (a) Specifications. Each chewable tab let contains 1.25, 2.5, 5, or 10 milligrams (mg) pimobendan. (b) Sponsor. See No. 000010 in § 510.600(c) of this chapter. (c) Conditions of use—(1) Amount. Ad minister orally at a total daily dose of 0.23 mg per pound (0.5 mg per kilogram) body weight, using a suitable combina tion of whole or half tablets. The total daily dose should be divided into two portions administered approximately 12 hours apart. (2) Indications for use in dogs. For the delay of onset of congestive heart fail ure in dogs with Stage B2 preclinical myxomatous mitral valve disease (2019 ACVIM Consensus Statement). Stage B2 preclinical myxomatous mitral valve disease (MMVD) refers to dogs with asymptomatic MMVD that have a moderate or loud mitral murmur due to mitral regurgitation and cardio megaly. (3) Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian. It is a violation of Federal law to use this product other than as directed in the labeling. [87 FR 76421, Dec. 14, 2022] § 516.1858 Potassium bromide. (a) Specifications. Each chewable tab let contains 250 or 500 milligrams (mg) potassium bromide. (b) Sponsor. See No. 055246 in § 510.600(c) of this chapter. (c) Conditions of use—(1) Amount. Ad minister 25 to 68 mg per kilogram (11 to 31 mg per pound) of body weight once daily. The dosage can be divided and should be adjusted to clinical response. (2) Indications for use. For the control of seizures associated with idiopathic epilepsy in dogs. (3) Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian. It is a violation of Federal law to use this product other than as directed in the labeling. [86 FR 57996, Oct. 20, 2021] § 516.2980 Verdinexor. (a) Specifications. Each tablet con tains 2.5, 10, or 50 milligrams (mg) verdinexor. (b) Sponsor. See No. 086121 in § 510.600(c) of this chapter. (c) Conditions of use—(1) Amount. Ad minister verdinexor tablets orally at an initial dose of 1.25 mg per kilogram (mg/kg) of body weight twice per week with at least 72 hours between doses. If tolerated after 2 weeks, increase the dose to 1.5 mg/kg twice per week with at least 72 hours between doses. (2) Indications for use. For the treat ment of lymphoma in dogs. (3) Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian. It is a violation of Federal law to use this product other than as directed in the labeling. [86 FR 57996, Oct. 20, 2021] VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00167 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B 158 21 CFR Ch. I (4–1–23 Edition) Pt. 520 PART 520—ORAL DOSAGE FORM NEW ANIMAL DRUGS Sec. 520.23 Acepromazine. 520.28 Acetazolamide. 520.38 Albendazole oral dosage forms. 520.38a Albendazole suspension. 520.38b Albendazole paste. 520.43 Afoxolaner. 520.48 Altrenogest. 520.62 Aminopentamide. 520.82 Aminopropazine oral dosage forms. 520.82a Aminopropazine. 520.82b Aminopropazine and neomycin. 520.88 Amoxicillin oral dosage forms. 520.88a Amoxicillin trihydrate film-coated tablets. 520.88b Amoxicillin trihydrate for oral sus pension. 520.88c Amoxicillin trihydrate oral suspen sion. 520.88d Amoxicillin trihydrate soluble pow der. 520.88e Amoxicillin trihydrate boluses. 520.88f Amoxicillin trihydrate tablets. 520.88g Amoxicillin trihydrate and clavulanate potassium tablets. 520.88h Amoxicillin trihydrate and clavulanate potassium for oral suspen sion. 520.90 Ampicillin oral dosage forms. 520.90a Ampicillin tablets. 520.90b Ampicillin capsules. 520.90c Ampicillin boluses. 520.100 Amprolium. 520.110 Apramycin sulfate soluble powder. 520.154 Bacitracin oral dosage forms. 520.154a Bacitracin methylenedisalicylate. 520.154b Bacitracin methylenedisalicylate and streptomycin sulfate powder. 520.154c Bacitracin zinc soluble powder. 520.170 Bexagliflozin. 520.222 Bunamidine hydrochloride. 520.246 Butorphanol tablets. 520.260 n-Butyl chloride. 520.284 Cambendazole oral dosage forms. 520.284a Cambendazole suspension. 520.284b Cambendazole pellets. 520.284c Cambendazole paste. 520.292 Capromorelin. 520.301 Caramiphen ethanedisulfonate and ammonium chloride tablets. 520.302 Carnidazole tablets. 520.304 Carprofen. 520.314 Cefadroxil. 520.370 Cefpodoxime tablets. 520.376 Cephalexin. 520.390 Chloramphenicol oral dosage forms. 520.390a Chloramphenicol tablets. 520.390b Chloramphenicol capsules. 520.390c Chloramphenicol palmitate oral suspension. 520.420 Chlorothiazide. 520.434 Chlorphenesin carbamate tablets. 520.441 Chlortetracycline powder. 520.443 Chlortetracycline tablets and boluses. 520.445 Chlortetracycline and sulfamethazine powder. 520.446 Clindamycin capsules and tablets. 520.447 Clindamycin solution. 520.452 Clenbuterol syrup. 520.455 Clomipramine. 520.462 Clorsulon drench. 520.522 Cyclosporine. 520.530 Cythioate oral liquid. 520.531 Cythioate tablets. 520.534 Decoquinate. 520.538 Deracoxib. 520.540 Dexamethasone oral dosage forms. 520.540a Dexamethasone powder. 520.540b Dexamethasone tablets and boluses. 520.540c Dexamethasone chewable tablets. 520.563 Diatrizoate. 520.580 Dichlorophene and toluene. 520.581 Dichlorophene tablets. 520.596 Dichlorvos powder. 520.598 Dichlorvos tablets. 520.600 Dichlorvos capsules and pellets. 520.602 Dichlorvos gel. 520.606 Diclazuril. 520.608 Dicloxacillin. 520.620 Diethylcarbamazine oral dosage forms. 520.622 Diethylcarbamazine citrate oral dos age forms. 520.622a Diethylcarbamazine citrate tablets. 520.622b Diethylcarbamazine citrate syrup. 520.622c Diethylcarbamazine citrate chew able tablets. 520.623 Diethylcarbamazine and oxibendazole chewable tablets. 520.645 Difloxacin. 520.666 Dirlotapide. 520.763 Dithiazanine oral dosage forms. 520.763a Dithiazanine tablets. 520.763b Dithiazanine powder. 520.763c Dithiazanine iodide and piperazine citrate suspension. 520.766 Domperidone. 520.784 Doxylamine. 520.804 Enalapril. 520.812 Enrofloxacin. 520.816 Epsiprantel. 520.823 Erythromycin. 520.852 Estriol. 520.863 Ethylisobutrazine. 520.870 Etodolac. 520.903 Febantel oral dosage forms. 520.903a Febantel paste. 520.903b Febantel suspension. 520.903c Febantel and praziquantel paste. 520.903d Febantel tablets. 520.905 Fenbendazole oral dosage forms. 520.905a Fenbendazole suspension. 520.905b Fenbendazole granules. 520.905c Fenbendazole paste. 520.905d Fenbendazole powder. 520.928 Firocoxib. 520.930 Firocoxib paste. 520.955 Florfenicol. VerDate Sep<11>2014 16:35 May 05, 2023 Jkt 259076 PO 00000 Frm 00168 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT PC31aw or le y on L A P 50 LW 1R 2 w ith $ $ JO B