OGD officials offer advice on ANDAs, post-CRL scientific meetings

To ensure the US Food and Drug Administration (FDA) accepts scientific meeting requests related to a complete response letter (CRL) related to a bioequivalence issue for a generic drug, sponsors should make certain that their submissions are thorough. Additionally, there should not be any issues present in the submission that could be adequately resolved through controlled correspondence, according to Arun Agrawal, a pharmacologist at the Office of Bioequivalence in the Office of Generic Drugs (OGD).

Agrawal and colleagues offered advice to sponsors on abbreviated new drug applications (ANDAs) and reviewed common practices to avoid having their Form 356h rejected during FDA’s Generic Drugs Forum on 10 April in Bethesda, MD.

Criteria for getting meetings granted

Agrawal stated that, in most cases, sponsors' requests are deemed eligible for a scientific meeting after receiving a CRL.

Between October 2022 and December 2024, FDA received 41 post-CRL meeting requests. Out of these, 29 requests, or 71%, met the necessary criteria and were granted meetings, while 12 requests, or 29%, did not meet the criteria.

Out of the 41 submitted post-CRL meeting requests, 88% were for complex drug products, while five requests, or 12%, were for non-complex drug products.
FDA considers a generic drug to be a complex product if it has complex active ingredients, such as peptides or polymeric compounds; a complex mixture of APIs; involves complex routes of delivery; or if they are complex drug-device combination products, such as pre-filled auto injectors or metered-dose inhalers.

Most of the meeting requests concerned a new bioequivalence study, an alternative BE approach, or a new approach to demonstrate the sameness of a complex API.

Some common reasons why FDA denies meeting requests include:

The meeting package is incomplete.
The product does not meet the criteria for a complex product.
The meeting request does not meet one or more of the criteria outlined in GDUFA III commitment letter.
The request raises issues that can be adequately addressed through a controlled correspondence.
The submitted questions are considered review issues or responses to CRL deficiencies.
The submitted information requires a pre-review of new data or in vivo BE study protocols.

Agrawal said FDA may also grant meeting requests for products where there is uncertainty concerning the approval pathway.

At the front end: ANDA acceptance

Onyeka Ihezie, regulatory business process manager for the Division of Regulatory and Business Process Management I (DRBPMI) in the Office of Program and Regulatory Operations (OPRO), said the Form 356h is the “front facing” form for the ANDA submission and needs to be accurate. This form should accompany all original ANDAs as well as postmarket supplement applications.

One common issue with these submissions is that sponsors only submit a short version of the form meant for quality-related submissions, instead of the full version.

Another problem is that the form is missing in the post-approval space for a supplement where sponsors are submitting a grouping of supplements. She noted that a full Form 356h is needed for all supplements.

Thaoly Nguyen, regulatory business process manager for DRBPMIII within OPRO said that another issue is when facilities are listed on the Form 356h but are not reflected in the relevant section of the Common Technical Document’s (CTD) Module 3.

OGD officials offer advice on ANDAs, post-CRL scientific meetings

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