Source: https://www.ecfr.gov/cgi-bin/retrieveECFR?gp=&mc=true&n=pt21.6.516&r=PART&ty=HTML
Timestamp: 2020-04-05 14:45:53
Document Index: 547454755

Matched Legal Cases: ['art 516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', 'art 516', 'art 520', 'art 558', 'art 522', 'art 524', 'art 526', 'art 529', 'art 558', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', '§516', 'art 20', '§516', '§516', '§510']

Title 21 → Chapter I → Subchapter E → Part 516
§516.1 Scope.
§516.2 Purpose.
§516.3 Definitions.
§516.11 Scope of this subpart.
§516.12 Purpose.
§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.
§516.28 Publication of MUMS-drug designations.
§516.30 Annual reports for a MUMS-designated drug.
§516.31 Scope of MUMS-drug exclusive marketing rights.
§516.52 Availability for public disclosure of data and information in requests.
Subpart E—Conditionally Approved New Animal Drugs For Minor Use and Minor Species
§516.1684 Paclitaxel.
§516.2065 Rabacfosadine.
Source: 72 FR 41017, July 26, 2007, unless otherwise noted.
(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]
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.
(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]
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.
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.
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.
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.
(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]
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]
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.
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.
(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.
(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.
(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.
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:
(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.
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;
(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.
(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.
(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.
(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.
Source: 72 FR 57200, Oct. 9, 2007, unless otherwise noted.
(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.
[79 FR 18158, Apr. 1, 2014]
(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.
[82 FR 12169, Mar. 1, 2017]