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Electronic Code of Federal Regulations

e-CFR data is current as of November 12, 2019

Title 21Chapter ISubchapter E → Part 516


Title 21: Food and Drugs


PART 516—NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES


Contents

Subpart A—General Provisions

§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 designation.
§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 designation.
§516.26   Amendment to MUMS-drug designation.
§516.27   Change in sponsorship.
§516.28   Publication of MUMS-drug designations.
§516.29   Termination of MUMS-drug designation.
§516.30   Annual reports for a MUMS-designated drug.
§516.31   Scope of MUMS-drug exclusive marketing rights.
§516.34   FDA recognition of exclusive marketing rights.
§516.36   Insufficient quantities of MUMS-designated drugs.
§516.52   Availability for public disclosure of data and information in requests.

Subpart C—Index of Legally Marketed Unapproved 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 determination of eligibility for indexing.
§516.133   Denying a request for determination of eligibility for indexing.
§516.135   Granting a request for determination 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 information in an index file.

Subpart D [Reserved]

Subpart E—Conditionally Approved New Animal Drugs For Minor Use and Minor Species

§516.1684   Paclitaxel.
§516.2065   Rabacfosadine.

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 Cosmetic 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 Animal Drug.

(3) Subpart C [Reserved]

(4) Subpart D [Reserved]

(b) References in this part to regulatory sections of the Code of Federal Regulations are to Chapter I of Title 21, unless otherwise noted.

§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 marketing rights.

§516.3   Definitions.

(a) The definitions and interpretations 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 pharmacological action of the drug substance.

Functionally superior means that a drug has been shown to provide a significant therapeutic or physiologic advantage over that provided by a conditionally-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 otherwise the same drug. Generally, this would represent the same kind of evidence needed to support a comparative effectiveness claim for two different drugs; in most cases, direct comparative 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 otherwise the same drug, in a substantial portion of the target population, for example, by the elimination of an ingredient or contaminant that is associated with relatively frequent adverse effects. In some cases, direct comparative clinical trials will be necessary.

Infrequently, as used in the minor use definition, means a disease or condition that is uncommon or that occurs only sporadically on an annualized basis.

Limited geographical areas, as used in the minor use definition, means regions of the United States distinguished by physical, chemical, or biological factors that limit the distribution 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 species.

Minor use means the intended use of a drug in a major species for an indication 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 specified 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 conditional 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 hydrogen or coordination bonds) or other noncovalent derivative such as a complex, chelate or clathrate is not the 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 conditionally 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 approved, or approved MUMS drug, 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 conditionally approved or approved MUMS drug for the same intended use, it is not considered the same drug. This criterion will be applied as follows to different kinds of macromolecules:

(A) Two protein drugs would be considered 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 sequence; other potentially important differences, such as different glycosylation patterns or different tertiary structures, would not cause the drugs to be considered different unless the subsequent drug is shown to be functionally 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 postpolymerization modifications, unless the subsequent drug is shown to be functionally superior.

(C) Two polynucleotide drugs consisting of two or more distinct nucleotides would be considered the same if they had an identical sequence of purine and pyrimidine bases (or their derivatives) bound to an identical sugar backbone (ribose, deoxyribose, or modifications of these sugars), unless the subsequent drug is shown to be functionally superior.

(D) Closely related, complex partly definable drugs with similar pharmacologic 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 designation, indexing, or conditional approval is sought, that is determined to be the same as (or not different from) a previously designated, conditionally approved, or approved intended use of a MUMS drug. Same intended use is established 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 organisms of that disease or condition when the causative organisms involved can reliably be shown to be clinically significant causes of the disease or condition.

(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; 70,000 dogs; 120,000 cats; 310,000 cattle; 1,450,000 pigs; 14,000,000 turkeys; and 72,000,000 chickens.

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, organization, or association). Sponsor also means the person responsible for an investigation of a new animal drug (in this context, the sponsor may be an individual, partnership, corporation, or Government agency or may be a manufacturer, scientific institution, or an investigator regularly and lawfully engaged in the investigation of new animal drugs). Sponsor also means the person submitting or receiving approval for a new animal drug application (in this context, the sponsor may be an individual, partnership, organization, or association). In all contexts, the sponsor is responsible for compliance 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]

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 requirements for submissions to FDA of requests for designation of a new animal drug for a minor use or a minor species.

§516.12   Purpose.

This subpart establishes standards and procedures for determining eligibility for designation and the associated 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 Office 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 identified 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 conditional approval or approval as stated in the approval letter of an application for a MUMS-designated drug, no conditional 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 request for designation of a MUMS drug must be addressed to the Director of the Office of Minor Use and Minor Species Animal Drug Development. Submissions not including all elements specified in §516.20 will be returned to the sponsor without review.

§516.16   Eligibility to request designation.

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 request 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 species must submit each request in the form and containing the information required in paragraph (b) of this section. While a request for designation may involve multiple intended uses, each request for designation must constitute a separate submission. A sponsor may request MUMS-drug designation 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 request 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 specific.

(2) The name and address of the sponsor; the name of the sponsor's primary contact person and/or permanent-resident U.S. agent including title, address, and telephone number; the established name (and proprietary name, if any) of the active pharmaceutical ingredient 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 intended use for which the drug is being or will be investigated.

(4) A description of the drug and dosage form.

(5) A discussion of the scientific rationale 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 unpublished and published papers, and other relevant data that are available to the sponsor, whether positive, negative, or inconclusive.

(6) A specific description of the product 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 appended authoritative references, to demonstrate that such use is a minor use.

(8) A statement that the sponsor submitting the request is the real party in interest of the development and the intended or actual production and sales of the product.

(9) A statement that the sponsor acknowledges that, upon granting a request for MUMS designation, FDA will make information regarding the designation 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 designation as a minor use in a major species 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 number of animals (annualized). This documentation must include the following information:

(a) The estimated total number of animals to which the drug could potentially be administered on an annual basis for the treatment, control, or prevention of the disease or condition for which the drug is being developed, including animals administered the drug as part of herd or flock treatment, together with a list of the sources (including dates of information provided and literature citations) for the estimate.

(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, requestors must demonstrate that administration 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 information provided and literature citations) for the justification that administration 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 represent 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 Development.

§516.23   Timing of requests for MUMS-drug designation.

A sponsor may request MUMS-drug designation at any time in the drug development process prior to the submission of an application for either conditional approval or approval of the MUMS drug for which designation is being requested.

§516.24   Granting MUMS-drug designation.

(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 designation 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 intended use as one that already has a MUMS-drug designation but has not yet been conditionally approved or approved.

(3) The drug is the same drug in the same dosage form for the same intended use as one that is already conditionally approved or approved. A drug that FDA has found to be functionally superior is not considered the same drug as an already conditionally approved 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 development in a timely manner, and

(iii) Any other information required under §516.20.

(b) FDA may refuse to grant a request 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 sponsor 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, information arising from FDA recommendations, or other unforeseen developments.

(b) FDA will grant the amendment if it finds:

(1) That the initial designation request was made in good faith;

(2) That the amendment is intended to make the MUMS-drug designated intended use conform to the results of new and unexpected findings in research 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 sponsorship of a MUMS-designated drug to another person. A change of sponsorship will also transfer the designation status of the drug which will remain in effect 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 following information in writing and obtain 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 specify the date of the transfer. The former sponsor shall also certify in writing to FDA that a complete copy of the request for MUMS-drug designation, including any amendments to the request, and correspondence relevant to 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 sponsorship is intended to be effective;

(iii) A statement that the new sponsor 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 sponsor understands and accepts the responsibilities 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 another 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 publicly available list of MUMS-designated drugs. This list will be placed on file at the FDA Division of Dockets Management, and will contain the following information for each MUMS-designated drug:

(a) The name and address of the sponsor;

(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 intended use for which MUMS-drug designation was granted; and

(e) The date designation was granted.

§516.29   Termination of MUMS-drug designation.

(a) The sponsor of a MUMS-designated 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 approved MUMS-designated drug sponsor must notify FDA at least 1 year before it intends to discontinue the manufacture of such MUMS drug. FDA must terminate designation upon such notification.

(c) MUMS designation shall terminate upon the expiration of any applicable period of exclusive marketing rights under this subpart.

(d) FDA may terminate designation if it independently determines that the sponsor is not actively pursuing conditional approval or approval with due diligence. At a minimum, due diligence must be demonstrated by:

(1) Submission of annual progress reports in a timely manner in accordance with §516.30 that demonstrate that the sponsor is progressing in accordance with the drug development plan submitted to the agency under §516.20 and

(2) Compliance with all applicable requirements of part 511 of this chapter.

(e) Designation of a conditionally approved or approved MUMS-designated drug and the associated exclusive marketing 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 contained an untrue statement of material fact; or

(2) The request for designation omitted 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 dosage form, for the same intended use becomes conditionally approved or approved 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 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-designated for a minor use in a major species, its designation will not be terminated on the grounds that the number of animals to which the drug could potentially be administered on an annual basis for the treatment, control, or prevention of the disease or condition for which the drug is being developed, including animals administered the drug as part of herd or flock treatment, subsequently increases.

(i) When a MUMS-drug designation is terminated, FDA will notify the sponsor in writing and will give public notice 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 designation and annually thereafter until approval, the sponsor of a MUMS-designated drug shall submit a brief progress report on the drug to the investigational new animal drug file addressed 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 description of studies initiated, ongoing, and completed, and a short summary of the status or results of such studies;

(b) A description of the investigational plan for the coming year, as well as any anticipated difficulties in development, testing, and marketing; and

(c) A brief discussion of any changes that may affect the MUMS-designated drug status of the product. For example, situations in which testing data demonstrate that the proposed intended use is inappropriate due to unexpected issues of safety or effectiveness.

§516.31   Scope of MUMS-drug exclusive marketing rights.

(a) After conditional approval or approval 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 abbreviated application for the same drug in the same dosage form for the same intended use before the expiration of 7 years after the date of conditional approval or approval as stated in the approval letter from FDA, except that such an application can be conditionally approved or approved sooner if, and at such time as, any of the following 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 marketing rights provides written consent to FDA to conditionally approve or approve another application before the expiration of 7 years; or

(4) The sponsor fails to assure a sufficient quantity of the drug in accordance with section 573 of the act and §516.36.

(b) If an application for a MUMS drug cannot be approved until the expiration of the period of exclusive marketing of a MUMS-designated drug, FDA will so notify the sponsor in writing.

§516.34   FDA recognition of exclusive marketing rights.

(a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely written notice recognizing exclusive marketing rights when an application for a MUMS-designated drug has been conditionally approved or approved. The written notice will inform the sponsor of the requirements for maintaining MUMS-designated drug exclusive marketing rights for the full 7-year term. This notice will generally be contained in the letter conditionally approving or approving the application.

(b) When an application is conditionally 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 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 conditionally-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 insufficiency 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 assure the availability of sufficient quantities of the MUMS-designated drug within a reasonable time to meet the needs for which the drug was designated; or

(2) Provide FDA in writing the sponsor's consent for the conditional approval or approval of other applications for the same drug before the expiration 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 conclusions and will constitute final agency action. An order terminating designation and associated exclusive marketing rights may issue whether or not there are other sponsors that can assure the availability of alternative sources of supply. Such an order will not withdraw the conditional approval or approval of an application. Once terminated under this section, neither designation, nor exclusive marketing rights may be reinstated.

§516.52   Availability for public disclosure of data and information in requests.

(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 request unless the existence of the request has been previously publicly disclosed or acknowledged.

(b) Whether or not the existence of a pending request for designation has been publicly disclosed or acknowledged, no data or information in the request are available for public disclosure prior to final FDA action on the request.

(c) Except as provided in paragraph (d) of this section, upon final FDA action on a request for designation, the public availability of data and information in the request will be determined in accordance with part 20 of this chapter 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 periodically. In accordance with §516.29, FDA will give public notice of the termination of all MUMS-drug designations.

Subpart C—Index of Legally Marketed Unapproved New Animal 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 legally marketed unapproved new animal drugs. This subpart applies only to minor species and not to minor use in major species. This index is only available for new animal drugs intended for use in a minor species for which there is a reasonable certainty that the animal or edible products from the animal will not be consumed by humans or food-producing animals and for new animal drugs intended for use only in a hatchery, tank, pond, or other similar contained man-made structure in an early, nonfood life stage of a food-producing 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 antimicrobial 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 indexing 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 Medicine.

Holder means the requestor of an index listing after the request is granted 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 sequence 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 sequence of the genome has been modified solely by selective breeding.

(b) The definitions of the following terms are given in §514.3 of this chapter:

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 chapter:

Same dosage form.

Same drug.

Same intended use.

§516.117   Submission of correspondence under this subpart.

Unless directed otherwise by FDA, all correspondence relating to any aspect of the new animal drug indexing process described in this subpart must be addressed to the Director, OMUMS. The initial correspondence for a particular 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 provided 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. 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 represent any number of requestors or holders. The name and address of the permanent-resident U.S. agent shall be submitted to the Director, OMUMS, and included in the index file.

§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 Director, OMUMS, specify the participants attending on behalf of the requestor or potential requestor, and contain a proposed agenda for the meeting.

(c) Within 30 days of receiving a request 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 regarding agency administrative actions.

(a) Should FDA make an initial decision denying a request for determination of eligibility for indexing, terminating an investigational exemption, determining that a qualified expert panel does not meet the selection criteria, 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 informal conference for review of the decision.

(b) The written notice will include information for scheduling the informal conference and state that a written request for a conference must be made within 60 days of the date FDA sends its notice.

(c) Within 45 days of receiving a request for an informal conference, FDA will schedule and hold the informal conference at a time agreeable to both FDA and the person making the request.

(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 designee, excluding the Director of the Office 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 response 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 officer of the submitted written response.

(f) The purpose of an informal conference is to discuss scientific and factual issues. It will involve a discussion of FDA's initial decision and any written response to that decision.

(g) Internal agency review of a decision must be based on the information in the administrative file. If the person requesting an informal conference presents new information not in the file, the matter will be returned to the appropriate lower level in the agency for reevaluation based on the new information.

(h) Informal conferences under this part are not subject to the separation of functions rules in §10.55 of this chapter.

(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 opportunity 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 report.

(4) All correspondence and memoranda of any and all meetings between the participants and the presiding officer.

(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 decision.

§516.125   Investigational use of minor species new animal drugs to support 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 investigational use is for the purpose of:

(1) Demonstrating human food safety under section 572(a)(1)(B) of the act;

(2) Demonstrating safety with respect 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 assessment under section 572(c)(1)(E) of the act; or

(4) Obtaining approval of a new animal drug application or abbreviated new animal drug application under section 512(b) of the act.

(b) Correspondence and information associated with investigations described 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 investigational use described in paragraph (a) of this section, shall meet the requirements of this section. For such investigations, 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 animals are not to be used for food for humans or other animals unless authorization 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 Investigational Exemption for a New Animal Drug for Index Listing” and each request for indexing shall be examined with respect to the reliability of information 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 investigation shall not be granted an opportunity for a regulatory hearing before FDA pursuant to part 16 of this chapter. 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 request for addition to the index would have been denied, FDA will remove the new animal drug from the index in accordance 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 described in paragraph (c) of this section shall be sent to the Director, OMUMS, in accordance with the provisions of this section.

§516.129   Content and format of a request for determination of eligibility 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 intended use as a drug that is already approved or conditionally approved; and

(4) Must be submitted separately.

(b) A request for determination of eligibility for indexing may involve multiple intended uses and/or multiple minor species. However, if a request for determination of eligibility for indexing that contains multiple intended uses and/or multiple minor species cannot be granted in any part, the entire request will be denied.

(c) A requestor must submit two copies of a dated request signed by the authorized contact person for determination 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 components and composition;

(3) A statement of the intended use(s) of the new animal drug in the identified minor species or groups of minor species;

(4) A statement of the proposed conditions of use associated with the stated intended use(s) of the new animal drug, including the proposed dosage, route of administration, contraindications, warnings, and any other significant 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 annual 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 animal 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-producing minor species, and information to demonstrate food safety in accordance with the standards of section 512(d) of the act and §514.111 of this chapter (including, for an antimicrobial new animal drug, with respect 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 sufficient to demonstrate that the requestor has established appropriate specifications for the manufacture and control of the new animal drug and that the requestor has an understanding of current good manufacturing practices;

(9) Either a claim for categorical exclusion under §25.30 or §25.33 of this chapter or an environmental assessment 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 contact person or permanent-resident U.S. agent.

§516.131   Refuse to file a request for determination of eligibility for indexing.

(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 request.

(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 lacking.

§516.133   Denying a request for determination of eligibility for indexing.

(a) FDA will deny a request for determination of eligibility for indexing if it determines upon the basis of the request evaluated together with any other information before it with respect to the new animal drug that:

(1) The same drug in the same dosage form for the same intended use is already approved or conditionally approved;

(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 animal 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-producing minor species, and there is insufficient 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 resistance);

(3) The new animal drug is contained in or is a product of a transgenic animal;

(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 requestor has an understanding of current 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 establish that the requested action is subject 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 exposed 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 determination of eligibility for indexing if it contains any untrue statement of a material fact or omits material information.

(c) When a request for determination of eligibility for indexing is denied, FDA will notify the requestor in accordance with §516.137.

§516.135   Granting a request for determination of eligibility for indexing.

(a) FDA will grant the request for determination of eligibility for indexing if none of the reasons described in §516.133 for denying such a request applies.

(b) When a request for determination of eligibility for indexing is granted, FDA will notify the requestor in accordance with §516.137.

§516.137   Notification of decision regarding eligibility for indexing.

(a) Within 90 days after the filing of a request for a determination of eligibility for indexing based on §516.129(c)(7)(i), or 180 days for a request based on §516.129(c)(7)(ii), FDA shall grant or deny the request, and notify the requestor of FDA's decision in writing.

(b) If FDA denies the request, FDA shall provide due notice and an opportunity for an informal conference as described in §516.123 regarding its decision. A decision of FDA to deny a request for determination of eligibility for indexing following an informal conference 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 animal drug to the index. A qualified expert panel may not be established until FDA has determined that the new animal drug is eligible for indexing. The requestor must choose members for the qualified expert panel in accordance with selection criteria listed in paragraph (b) of this section and submit information about these proposed members to FDA. FDA must determine whether the proposed qualified expert panel meets the selection criteria prior to the panel beginning its work. Qualified 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 qualified expert panel. (1) A qualified expert panel member must be an expert qualified 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 working 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 written statement provided by the requestor stating his or her duties and responsibilities with respect to reviewing 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 determination to allow participation notwithstanding an otherwise disqualifying financial interest, a qualified expert panel member must not have a conflict of interest or the appearance of a conflict of interest, as described in paragraph (g) of this section.

(c) Requestor responsibilities. (1) The requestor must:

(i) Choose members for the qualified expert panel in accordance with selection 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 working knowledge of the information.

(iii) Provide each potential expert panel member a written statement describing the purpose and scope of his or her participation on the qualified expert panel and obtain certification that he or she has read and understood the information. The written statement should describe the duties and responsibilities of qualified expert panels and their members established by paragraphs (e) and (f) of this section, including the need to prepare a written report under §516.143.

(iv) Obtain information from each potential expert panel member demonstrating that he or she is qualified by training and experience to evaluate the target animal safety and effectiveness of the new animal drug under consideration. This information can be obtained from a comprehensive curriculum vitae or similar document.

(v) Notify each potential expert panel member that he or she must submit information 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 members and sufficient information about each proposed member for FDA to determine 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 selection criteria, the requestor must provide to the panel all information known by the requestor that is relevant to a determination of the target animal safety and the effectiveness of the new animal drug at issue. In addition, 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 expert 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 determine whether the proposed revised qualified expert panel meets the selection 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 report, or the product is added to the index, whichever occurs later, and make them available to a duly authorized employee of the agency at all reasonable times.

(d) FDA responsibilities. (1) FDA will determine whether the requestor's proposed qualified expert panel meets the selection criteria listed in paragraph (b) of this section. FDA will expeditiously inform the requestor, in writing, of its determination. If FDA determines that the qualified expert panel does not meet the selection criteria, FDA will provide due notice and an opportunity for an informal conference as described in §516.123. A determination by FDA that a proposed qualified expert panel does not meet the selection criteria following an informal conference shall constitute final agency action subject to judicial review.

(2) If FDA determines that a qualified expert panel no longer meets the selection 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 determination and provide due notice and an opportunity for an informal conference as described in §516.123. A determination by FDA, following an informal conference, that a qualified expert panel no longer meets the selection 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 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 criteria described in paragraph (b) of this section.

(2) Act in accordance with generally accepted professional and ethical business practices.

(3) Review all information relevant to a determination of the target animal safety and effectiveness of the new animal drug provided by the requestor. The panel should also consider all relevant information otherwise known by the panel members, including anecdotal 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 signature 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 described in paragraph (g) of this section to FDA for its consideration. Such information 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 qualified expert panel leader. (1) The qualified expert panel leader must ensure that the activities of the panel are performed 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 written report and all notes or minutes relating to panel deliberations to the requestor.

(4) The qualified expert panel leader must maintain a copy of the written report and all notes or minutes relating to panel deliberations that are submitted to the requestor for 2 years after the report is submitted. Such records must be made available to a duly authorized employee of the agency for inspection at all reasonable times.

(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 objectivity in serving on the qualified expert panel or could create an unfair competitive advantage for a person or organization.

(2) Factors relevant to whether there is a conflict of interest or the appearance of a conflict of interest include whether the qualified expert panel member, their spouse, their minor children, their general partners, or any organizations in which they serve as an officer, director, trustee, general partner or employee:

(i) Is currently receiving or seeking funding from the requestor through a contract or research grant (either directly or indirectly through another entity, such as a university).

(ii) Has any employment, contractual, or other financial arrangement with the requestor other than receiving a reasonable fee for serving as a member of the qualified expert panel.

(iii) Has any ownership or financial interest in any drug, drug manufacturer, or drug distributor which will benefit from either a favorable or unfavorable 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 favorable 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 opinion.

(viii) Receives payment for services related to preparing information the requestor presents to the qualified expert panel, other than for services related 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 member must submit to the Director, OMUMS, the following information relating to themselves, their spouse, their minor children, their general partners, or any organizations in which they serve as an officer, director, trustee, general partner or employee, regarding the following issues to the extent that they are, in any way, relevant to the subject of the review of the qualified expert panel:

(i) Investments (for example, stocks, bonds, retirement plans, trusts, partnerships, sector funds, etc.), including for each the following: Name of the firm, type of investment, owner (self, spouse, etc.), number of shares / current value.

(ii) Employment (full or part time, current or under negotiation), including 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 negotiation), including for each the following: Type of agreement, product under study and indications, amount of remuneration (institution/self), time period, sponsor (government, firm, institution, individual), role of the person (site investigator, principal investigator, co-investigator, partner, no involvement, other), awardee.

(v) Patents/royalties/trademarks, including for each the following: Description, name of firm involved, income received.

(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, trustee, general partner or employee, have had, at any time in the past, involvement of the kind noted in paragraph (g)(3)(i) through (g)(3)(vii) of this section with respect to the animal drug that is the subject of the qualified expert panel review.

(ix) Whether there are any other involvements (other kinds of relationships) 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 satisfactory when there is no relevant information to submit.

(xi) A certification statement signed by the potential qualified expert panel member to the effect that all information submitted is true and complete to the best of their knowledge, that they have read and understood their obligations as an expert panel member, and that they will notify FDA and the requestor 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 qualified 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 qualified expert panel meeting the requirements 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, include either a citation to published literature or a summary of the information;

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

(e) Be signed, or otherwise approved in writing, by all panel members, in accordance with §516.141; and

(f) If the panel unanimously concludes 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-approved new animal drug for the minor species in question, the written report shall:

(1) Provide draft labeling that includes all conditions of use and limitations of use of the new animal drug deemed necessary by the panel to assure that the benefits of use of the new animal drug outweigh the risks, or provide narrative information from which such labeling can be written by the requestor; and

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

§516.145   Content and format of a request 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 copies of a dated request signed by the authorized 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 determination that the proposed qualified expert panel meets the selection criteria provided for in §516.141(b);

(3) A written report that meets the requirements of §516.143;

(4) A proposed index entry that contains the information described in §516.157;

(5) Proposed labeling, including representative 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 total quantity of active ingredient, after indexing;

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

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

(9) The name and address of the contact 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, indications, and recommended dosage.

(ii) A list of the names and affiliations of the members of the qualified expert panel, not including their addresses 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 translation.

§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 required by §516.145, FDA will not file it, but will inform the requestor in writing within 30 days of receiving the request as to what information is lacking.

§516.149   Denying a request for addition to the index.

(a) FDA will deny a request for addition to the index if it finds the following:

(1) The same drug in the same dosage form for the same intended use is already approved or conditionally approved;

(2) On the basis of new information, the new animal drug no longer meets the conditions for eligibility for indexing;

(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 listed in §516.141(b);

(5) The written report of the qualified expert panel and other information available to FDA is insufficient to permit FDA to determine that the benefits of using the new animal drug for the proposed use in a minor species outweigh its risks to the target animal, taking into account the harm caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question;

(6) On the basis of the report of the qualified expert panel and other information 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 animal, taking into account the harm caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question; 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 requestor in accordance with §516.153.

§516.151   Granting a request for addition to the index.

(a) FDA will grant the request for addition 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 granted, FDA will notify the requestor in accordance with §516.153.

§516.153   Notification of decision regarding 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 requestor of FDA's decision in writing.

(b) If FDA denies the request for addition 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 indexing 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 visiting FDA's Freedom of Information Staff's Public Reading Room at the address 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 person who holds the index listing;

(2) The name of the drug and the intended 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 listing may be requested. Any modification 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 modification is requested, FDA will notify the holder that a new index listing is required 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 possible, and a request to modify the indexed drug should be concurrently submitted:

(A) The addition to package labeling, promotional labeling, or prescription drug advertising of additional warning, contraindication, side effect, or cautionary information.

(B) The deletion from package labeling, promotional labeling, and drug advertising of false, misleading, or unsupported indications for use or claims for effectiveness.

(C) Changes in manufacturing methods 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 modification of an indexed drug, and must contain sufficient information to permit FDA to determine the need for the modification and whether the modification appropriately addresses the need.

(iii) FDA will take no action against an indexed drug or index holder solely because modifications of the kinds described in paragraph (b)(1)(i) of this section are placed into effect by the holder prior to receipt of a written notice granting the request if all the following 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 mailing cover and on the request as follows: “Special indexing request— modifications being effected;”

(B) The holder specifically informs FDA of the date on which such modifications are to be effected and submits two printed copies of any revised labeling 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 following 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 active ingredient.

(D) Alteration of the concentration of an active ingredient.

(E) Alteration of dose or dosage regimen.

(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 necessitated by another, such as a modification of dose necessitated by a modification of the concentration of an active ingredient. Submissions relating to addition of an intended use for an existing species or addition of a species should be submitted separately, but each such submission may include multiple additional intended uses and/or multiple additional species.

(3) Minor changes. All modifications other than those described in paragraphs (b)(1) and (b)(2) of this section including, but not limited to, formulation, labeling, and manufacturing methods and controls (at the same level of detail that these were described in the request for determination of eligibility for indexing) must be submitted as part of the annual indexed drug experience report or as otherwise 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 transferred, 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 following, 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 relevant 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 ownership 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 responsibilities 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 associated with the change of ownership (e.g., a new trade name) as draft labeling, with complete final printed labeling to be submitted in the indexed drug annual report in accordance with §§516.161 and 516.165.

(b) Upon receiving the necessary information to support a change of ownership 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 recordkeeping and reporting requirements of this section apply to all holders of indexed 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 information 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 determine, or facilitate a determination, whether there may be grounds for removing 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 information pertinent to the safety or effectiveness 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, permit 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 resident post of any product or manufacturing defects that may result in serious adverse drug events within 3 working days of first becoming aware that such a defect may exist. The holder may initially provide this information by telephone or other electronic communication means, with prompt written followup. The mailing cover must be plainly marked “3-Day Indexed Drug Field Alert Report.”

(2) Fifteen-day indexed drug alert report. The holder must submit a report on each serious, unexpected adverse drug event, regardless of the source of the information. The holder must submit 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 report. The holder must submit this report 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 information for the full reporting period. Any previously submitted information contained in the report must be identified 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 report 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 tablets; 50,000 10-milliliter vials of 5- percent solution) distributed during the reporting period. This information must be presented in two categories: Quantities distributed domestically and quantities exported. This information must include any distributor-labeled product.

(ii) If the labeling has changed since the last report, include a summary of those changes and the holder's and distributor's current package labeling, including 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 controls 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 indexing. Do not include changes that have already been submitted under §516.161.

(iv) Nonclinical laboratory studies and clinical data not previously reported under this section.

(v) Adverse drug experiences not previously reported under this section.

(vi) Any other information pertinent to safety or effectiveness of the indexed 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 following:

(i) The distributor's current product labeling. This must be identical to that in the index listing except for a different 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 distributor stating:

(A) The category of the distributor's operations (e.g., wholesale or retail);

(B) That the distributor will distribute 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 prescription new animal drug, that the distributor is regularly and lawfully engaged in the distribution or dispensing of prescription products.

(5) Other reporting. FDA may by order require that a holder submit information 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 approved;

(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 animal, taking into account the harm caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question;

(4) Any of the conditions in §516.133(a)(2), (5), or (6) are present;

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

(6) The labeling, distribution, or promotion 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 material 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 effectiveness issue otherwise warranting removal 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 following 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 information submitted to or incorporated by reference into the index file, such as data and information related to investigational use exemptions under §516.125, requests for determination of eligibility for indexing, requests for addition 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 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 publicly disclosed or acknowledged by the requestor.

(c) If the existence of an index file has not been publicly disclosed or acknowledged, 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 acknowledged before an index listing has been made public by FDA, no data or information contained in the file will be available for public disclosure before such index listing is made public, but the agency may, at its discretion, disclose a brief summary of such selected portions of the safety and effectiveness data as are appropriate for public consideration of a specific pending issue, e.g., at an open session of a Food and Drug Administration advisory committee 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 unless 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 information 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 Information summary submitted under §516.145, which will be reviewed and, where appropriate, revised by FDA.

(3) A protocol for a test or study, unless it is shown to fall within the exemption established for trade secrets and confidential commercial information in §20.61 of this chapter.

(4) Adverse reaction reports, product experience reports, consumer complaints, and other similar data and information, after deletion of the following:

(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 analytical method, unless it serves no regulatory or compliance purpose and is shown to fall within the exemption established 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 chapter.

(f) The following data and information 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 confidential commercial or financial information as defined in §20.61 of this chapter:

(1) Manufacturing methods or processes, including quality control procedures.

(2) Production, sales, distribution, and similar data and information, except that any compilation of such data and information aggregated and prepared in a way that does not reveal data or information which is not available for public disclosure under this provision is available for public disclosure.

(3) Quantitative or semiquantitative formulas.

(g) Subject to the disclosure provisions of this section, the agency shall regard the contents of an index file as confidential information unless specifically notified in writing by the holder of the right to disclose, to reference, or otherwise utilize such information on behalf of another named person.

(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 previously 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 undertaken to have the drug indexed in accordance 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 Approved New Animal Drugs For Minor Use and Minor Species

Source: 72 FR 57200, Oct. 9, 2007, unless otherwise noted.

§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 intravenously over 15 to 30 minutes, once every 3 weeks, for up to 4 doses.

(2) Indications for use. For the treatment of nonresectable stage III, IV, or V mammary carcinoma in dogs that have not received previous chemotherapy or radiotherapy. For the treatment of resectable and nonresectable squamous cell carcinoma in dogs that have not received previous chemotherapy 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]

§516.2065   Rabacfosadine.

(a) Specifications. Each vial of powder contains 16.4 milligrams (mg) rabacfosadine. Each milliliter of constituted solution contains 8.2 mg rabacfosadine.

(b) Sponsor. See No. 086072 in §510.600(c) of this chapter.

(c) Conditions of use in dogs—(1) Amount. Administer rabacfosadine at 1 mg/kilogram body weight as a 30-minute intravenous infusion, once every 3 weeks, for up to 5 doses.

(2) Indications for use. For the treatment 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.

[82 FR 12169, Mar. 1, 2017]

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