FDA’s Four Possible Outcomes for No-PAIs Provide Strategic Openings  

FDA announced that in cases it is unable to conduct on-site Pre-Approval Inspections (PAIs), there are four possible outcomes for the applicants. This is to clarify a previous guidance document on the topic released last month. Applicants to plan and strategize accordingly. In a no-PAI situation, FDA may (1) approve the application, (2) issue a Complete Response (CR) letter with specific GMP deficiencies, (3) issue a CR with no specific deficiencies but concerns about the site compliance due to inability to verify, or (4) delay any decision on the application. Except for the case when FDA approves the application, in all other cases, the application will not be approved with or without specific reasons, directly owing to the lack of PAI. This provides some strategic considerations. If possible, applicants should assure that their manufacturing sites have a good history with FDA. The sites may have passed previous FDA inspections, actively involved in manufacture of other prescription products, and have no pending compliance comments from FDA. If there were comments raised by the FDA in the past for a site, it is critical that applicant assess the CAPA initiated in response to the FDA findings have been independently verified to completely address FDA’s concerns. In cases where the site has never been inspected, it is imperative that the applicant present independent cGMP certification reports and complete documents, may be accompanied with pictures and videos, demonstrating GMP compliance. Without the above, be prepared for long delays in approval without or without CR letters.