Abolition of Approvable, Not-Approvable Letters Will Increase Uncertainty
The FDA is doing away with “approvable” and “not-approvable” letters to drug companies as of Aug. 11, replacing them with “complete response letters” when CDER cannot approve a drug.
In issuing its final rule, the agency said, “Our intent in replacing approvable and not-approvable letters with complete response letters is to adopt a more consistent and neutral mechanism to convey that we cannot approve an application in its present form. We believe that issuance of complete response letters will provide a more consistent approach to informing sponsors of changes that must be made before an application can be approved, with no implication as to the ultimate approvability of the application.”
Based on comments it received on the proposed rule, which appeared in the July 2004 Federal Register, the FDA made changes to the final rule. For example, it will give applicants more time to resubmit an application, no longer regarding failure to resubmit within a year as a request to withdraw the application.
The final rule also states that resubmission of an NDA supplement other than for efficacy constitutes an agreement to start a new review cycle.
Complete response letters to drugmakers will:
- State that the FDA will not approve the NDA or ANDA in its present form;
- Describe all specific deficiencies that the FDA has identified in the application, except when the agency determines the data submitted are inadequate to support approval. Deficiencies may be minor — for example, requiring labeling changes — or major, requiring additional clinical trials;
- Include a complete review of data in the NDA or ANDA and any amendments; and
- If possible, recommend actions the applicant might take to make the application eligible for approval.
This change has been a long time coming, but it is unlikely to make drug manufacturers happy as it will increase the level of uncertainty they face, Clinton Hermes, senior vice president and general counsel of St. Jude Children’s Research Hospital, said.
The final rule can be viewed at www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2004-N-0510-nfr.pdf.