FDA updates policies for reviewing ANDAs

Source: Raps

The US Food and Drug Administration (FDA) has revised its manual of policies and procedures (MAPP) for conducting a filing review of an abbreviated new drug application (ANDA) by the Office of Generic Drugs’ (OGD) Division of Filing Review (DFR).
 
This revision is the first since 2017 and went into effect on 3 October 2023.
 
FDA evaluates each submitted ANDA individually to determine whether the ANDA can be received. Received ANDAs have been verified as complete applications that contain all the required data sets and supporting information, the updated policy notes.
 
“The receipt of an ANDA means that FDA made a threshold determination that the ANDA is a substantially complete application, that is, an ANDA that on its face is sufficiently complete to permit a substantive review,” the agency wrote.
 
“Substantially complete” means that the application contains everything required under section 505(j)(2)(A) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and none of the deficiencies described in in 21 CFR 314.101(d) and (e).
 
After this initial review, the reviewer determines whether to accept the ANDA or whether it needs additional work. If more information is needed, the reviewer will send an Information Request (IR) to the applicant, allowing them to address the problematic areas. The reviewer also has the option to issue a refuse-to-receive notification.

Filing checklist
 
The revisions to the policy include an updated ANDA Filing Checklist, which the agency said will help DFR Reviewers assess the information and data in ANDA submissions. The new checklist includes modules for DFR reviewers to use to identify required and recommended content on each application.
 
Module 1 reviews administrative information, including all signatures, patent certifications and exclusivity certifications, and the product comparison demonstrating “sameness” or differences related to the reference drug.
 
Module 2 examines all of the data summaries, including bioequivalence and dissolution data for each proposed strength.
 
Modules 3.2.S and 3.2.P include drug substance and product information, such as molecular characterization and data on drug manufacturing (including complete information on all facilities involved with the manufacture and testing of the active pharmaceutical ingredient).
 
These sections also should contain complete information on the proposed packaging and the container closure system, including the specification and test data of each component, packaging configuration and sizes, container closure testing, and source of supply and the suppliers’ address. Stability data for the finished dosage form, including the stability protocol and expiration dating period, post-approval stability protocol and commitment, and stability data and batch numbers, are also included here.
 
Module 3.2.R relates to regional information. DFR reviewers will consider executed batch records with manufacturing and packaging reconciliation, and the methods validation package (if applicable). There is no Module 4 in the updated MAPP.

Module 5 addresses all of the clinical data, including pharmacokinetic, bioequivalence and in vitro testing; safety and adverse event profiles; and Institutional Review Board information. Module 5 also allows the reviewer to list any deficiencies noted in the review and to document whether the ANDA has been received, issued an IR, or issued a refuse-to-receive notification.

Some items on the reviewer checklist, while recommended in a guidance or elsewhere to assist applicants in preparing a high-quality ANDA, are not considered to be “threshold” matters for determining whether an ANDA is complete. These include:

• a cover letter with a summary of the submission, special requests, and application-specific references
• notation of any required Risk Evaluation and Mediation Strategy (REMS) in the cover letter
• whether the sponsor has requested a proprietary name for the product
• Type II Drug Master File numbers for the active pharmaceutical ingredients
• tabular formatting for lists of all impurities and potential degradation products
• certificates of analysis for test and reference products of the bioequivalence strength
• case report forms (though clinical data files should describe all patients who were dropped from the analysis population, demonstrated protocol deviations or experienced serious adverse events).