Inspection Acceptable?

A division's decision to file an NDA begins the review process and, when needed, initiates a request for a preapproval inspection of the sponsor's manufacturing facilities and clinical trial sites. During such inspections, FDA investigators audit manufacturing-related statements and commitments made in the NDA against the sponsor's manufacturing practices. More specifically, the FDA conducts inspections to:

• verify the accuracy and completeness of the manufacturing-related information submitted in the NDA;

• evaluate the manufacturing controls for the preapproval batches upon which information provided in the NDA is based;

• evaluate the manufacturer's compliance with Current Good Manufacturing Practices (CGMPs) and manufacturing-related commitments made in the NDA; and

• collect a variety of drug samples for analysis by FDA field and CDER laboratories. These samples may be subjected to several analyses, including methods validation, methods verification, and forensic screening for substitution.

According to CDER policy, product-specific preapproval inspections generally are conducted for products: (1) that are new chemical or molecular entities; (2) that have narrow therapeutic ranges; (3) that represent the first approval for the applicant; or (4) that are sponsored by a company with a history of CGMP problems or that has not been the subject of a CGMP inspection over a considerable period. More specific guidance on CDER's preapproval inspection program is available from CDER's Compliance Program Guide 7346.832.

The results of the preapproval inspection may also affect the final approval decision. When such inspections discover significant CGMP problems or other issues, the reviewing division may withhold approval until these issues are addressed and corrected. The division's response to such deficiencies is likely to depend on several factors, including the nature of the problem, the prognosis for the problem's correction, and the potential effect of the problem on the safety and efficacy of the drug.