Last week, the United States Food and Drug Administration’s Center for Veterinary Medicine (CVM) issued Draft Guidance for Industry No. 285, “Manufacture of Batches in Support of Original NADAs, ANADAs, and CNADAs” (Draft Guidance). The Draft Guidance applies to all original new animal drug application (NADAs), abbreviated new animal drug application (ANADAs), and conditional new animal drug applications (CNADAs)—as well as their associated investigational new animal drug files and generic investigational new animal drug files. The Draft Guidance provides recommendations for the primary batches of drug product that must be manufactured to support such applications.
I. Background
New animal drugs generally cannot be legally marketed unless they are the subject of an approved NADA, ANADA, or CNADA. In the Chemistry, Manufacturing, and Controls (CMC) technical section of such applications, applicants must provide full information about the manufacture of the new animal drug substance and new animal drug product. See FDCA Section 512 and 21 C.F.R. Part 514. Under existing CVM regulations, animal drug manufacturing processes must be able to produce drug product batches of consistent identity, strength, quality, and purity. 21 C.F.R. § 514.1(b)(5). To demonstrate this capability, applicants must manufacture primary batches of drug product as part of the original application.
II. Draft Guidance
The Draft Guidance provides recommendations for the batches that applicants must manufacture as part of the original NADA, ANADA, or CNADA application. Specifically, the Draft Guidance addresses selection of batches, drug substance source, drug product manufacture, and considerations for changes in drug substance source or drug product manufacturing site after manufacture of primary batches.
Selection of Batches
Under current good manufacturing practices (CGMPs), sponsors should manufacture at least three primary batches of drug product in support of the approval of all original NADAs, ANADAs, and CNADAs. CVM recommends that these batches be of the same formulation and packaged in the same container closure system as intended for marketing.[1] While sponsors may use bracketing[2] in certain cases[3] to select the primary batches manufactured and placed on stability, applicants should document the appropriate justification for such bracketing.
Drug Substance Source
CVM recommends that applicants manufacture the primary batches of drug product using a single source of drug substance that is the same as that intended for commercial production. To the extent possible, CVM recommends using two or more different batches of drug substance from the same source.
Drug Product Manufacture
While primary batches may be manufactured at pilot scale, CVM also recommends manufacturing the batches at the same site and under CGMPs using the same or comparable processes, controls, and equipment as intended for commercial batches. The CMC technical section of NADA, ANADA, and CNADA applications should include the following information:
- Executed batch records for primary batches,
- A blank master batch record for the intended commercial batch size, and
- At least six months of stability data (at both long-term and accelerated storage condition).
CVM recommends using the primary batches of drug product reported in the CMC technical section when performing any target animal safety or effectiveness studies, bioequivalence studies, and human food safety studies intended to support the application.
Considerations for Changes in Drug Substance Source or Drug Product Manufacturing Site After Manufacture of Primary Batches
If an applicant is unable to manufacture primary batches at the same site and using the same drug substance source as that intended for commercial production, the applicant should request a meeting with CVM’s Office of New Animal Drug Evaluation’s (ONADE) Division of Manufacturing Technologies. The applicant should also assess the risk of the proposed change(s) to product quality. The Draft Guidance outlines several general points that applicants should consider when assessing risk, including (1) the comparability of drug substance and quality from each drug substance source; (2) the similarity of raw materials, equipment, and manufacturing processes across multiple sites; and (3) compliance with CGMPs at the time of drug substance or drug product batch manufacture.
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CVM is accepting comments on the draft guidance until May 17, 2024 through www.regulations.gov (Docket No. FDA-2024-D-1054).
If you have any questions concerning the material discussed in this client alert, please contact the members of our Animal Food and Drug practice.
[1] For animal drugs intended for a minor use or a minor species (MUMS animal drugs), CVM advises the sponsor to contact the Office of New Animal Drug Evaluation’s (ONADE) Division of Manufacturing Technologies to discuss the appropriate number of batches to support approval.
[2] Bracketing is the practice of manufacturing only batches on the extremes of certain design factors of the marketed product (e.g., in terms of container size, strength, and/or fill).
[3] CVM does not recommend using bracketing for new biotechnological or biological animal drug products of different strengths.
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