As follow-up to our October post on pre-approval and pre-licensure inspections impacting U.S. Food and Drug Administration (FDA) drug and biologic approvals, this blog post discusses FDA’s recently announced temporary policy set forth in its December 2020 guidance on review timelines for company responses to a Complete Response letter (CRL) for applications requiring the conduct of manufacturing or bioresearch monitoring (BIMO) program site facility inspections prior to approval. This guidance augments FDA’s August 2020 guidance, which described FDA’s intent to issue a CRL or defer action on an application until an inspection can be completed.
FDA acknowledges in its recent guidance that it is “facing difficulties” in conducting inspections during the COVID-19 pandemic. Industry has felt the impact of this with delayed approvals of new therapies in 2020 as a result of these inspection delays. While FDA has sought to use alternative tools to mitigate the need for in-person inspections (e.g., requesting records and other information directly from facilities and requesting existing inspection reports from trusted foreign regulators), FDA indicated in its December 2020 guidance that these inspection-alternatives “can be as resource intensive as inspections, if not more,” thereby presenting a challenge to timely completion of required pre-approval and pre-license inspections during the application review period.
To provide greater transparency on expected timeline impacts for company complete responses where FDA issued a CRL either (a) due to its inability to perform a required inspection because of COVID-19, or (b) where the inspection involves the use of time- and resource-intensive alternative tools, the Agency provides the below timeline expectations in its December 2020 guidance for the review of applicant responses to CRLs:
- NDAs & BLAs: Resubmissions of original applications and efficacy supplements for NDAs and BLAs will be subject to a Class 2 review timeline of 6 months, which is “consistent with existing policies and practices when a facility inspection is required.”
- Biosimilars & NDA & BLA manufacturing supplements: There will be no changes in the review timelines for resubmissions of original applications, supplements with clinical data, and manufacturing supplements for biosimilars, or for resubmissions of manufacturing supplements for NDAs and BLAs.
- ANDAs: Regardless of whether the CRL contains a major deficiency, amendments to original ANDAs and amendments to prior approval supplements for approved ANDAs will be treated as major amendments, subject to the timelines provided in FDA’s July 2018 guidance on Generic Drug User Fee Amendments (GDUFA).
The December 2020 guidance enables applicants to better plan for approval timeline delay contingencies as they proceed through FDA’s review process. Comments on the December 2020 guidance may be submitted to the docket for Agency consideration here.