The CDER Small Business and Industry Assistance (SBIA) presented a two-day seminar on April 12-13, 2023, celebrating the first 10 years of GDUFA.  With the Office of Generic Drugs and industry now operating under the third iteration of GDUFA, the presentations by FDA Agency covered a lot of ground in an effort to highlight the evolution of review practice as we have moved through GDUFA I and II years and now into GDUFA III.  While much of the information in the presentations was not new and is covered in the GDUFA III commitment letter, I thought it would be helpful to provide some of the not-so-recognizable changes over the years that were discussed (and could be easily missed) and I have selected a few for this first “Did You Know” article.  Most of the information was taken directly from the presentation slides.

DMFs

Under GDUFA I & II, solicited Drug Master Files (DMF) amendments were not picked up for assessment when there was no open ANDA review cycle. However, under GDUFA III, FDA will assess solicited DMF amendments related to original ANDAs and PASs upon receipt, even if the original ANDA or PAS in which the DMF is referenced is not currently under assessment. Priority will be given to the amendments related to ANDAs for which acceptability of the DMF assessment may result in an approval.

In the Review of DMFs before the receipt of an ANDA or its amendments, the request for review should be submitted six (6) months prior to the ANDA’s planned submission date. The review request is to be submitted by the DMF holder and is available to newly submitted DMFs and previously unreviewed DMFs. There is also a requirement that certain conditions should be met, as stated in the GDUFA III Commitment letter.

Reclassification of a facility based complete response letter (CRL) major amendment letter

Upon submission of a Facility-Based Major CRL Amendment, an applicant can request that FDA reclassify the Major Amendment to Minor (M2m) when applicable criteria are met. Requests must be made at the time of CRL response amendment submission; if not, the request will be denied.  Also. the CRL must be less than one (1) year old. The only exception to these conditions is for a product where there is a documented drug shortage or is for a product currently in use to meet a public health emergency.

You must include in your CRL response why the facility deficiency is resolved and explain why no additional facility assessment is needed.  Obviously, the FDA will need to agree with your assessment and thus the request could be denied.  FDA notes that a MaPP will be forthcoming to further describe the process and the Agency’s thinking on this issue.

 Submissions with facilities not ready for inspection

Prior to GDUFA III, if any site was not ready for inspection, the agency would refuse-to-receive the application at the filing stage but, under GDUFA III, if any site is indicated as not ready for inspection, the goal date will be set at 15 months. While FDA will conduct its initial filing review, a substantive review of the application will not begin until all facilities are ready for inspection.

If the applicant submits an amendment with Form FDA 356h indicating that all facilities are ready for inspection, while goal date is 15 months after original submission, the new goal date will be set based on the date of that amendment submission (8 months for a priority review application and 10 months for a standard review application) at which time a substantive review of the application will begin. If no amendment indicating all facilities are ready for inspection is received by 30 days before the 15-month goal date, the goal date will be changed to 30 months after the original submission.

Well, that’s it for today’s “Did You Know”, we will be back with other tidbits from some of the other presentations.