It Is All About the “Risk”

Is there a Pre-Approval Inspection (PAI)? When will it be?  Will our site be inspected?  The anxiety-tinged queries from production (and management) personnel start almost as soon as an application is submitted, and until now regulatory personnel had little answers to offer except vague reassurances like, “We have to wait and see” or “It’s up to OPQ”.   But Tuesday, at the GRx+Biosims 2019 conference talk on FDA’s Integrated Facility Evaluations, Vidya Pai, Acting Branch Chief of the newly minted Office of Pharmaceutical Manufacturing Assessment (OPMA), managed to lift the veil on the inner workings of PAI risk assessment  and as a result provide industry with, if not a prediction of if or when there will be a PAI, at least a greater understanding of how that decision is reached.

Pai’s talk centered on the recent (September 2019) PAI inspection program revisions made to reflect the CDER-ORA agreement implementing “A Concept of Operations (ConOps)” to provide “Integrated Quality Assessment (IQA)” across all FDA teams.  An impressive conceptual initiative intended to assure “one quality voice” is heard from FDA.  But of particular interest to this attendee was the informative description of the Agency’s risk assessment process that determines whether a PAI will be conducted.  Turns out it is a multi-faceted risk assessment with multiple FDA teams contributing to the final determination.  In addition to the typical (expected) review of a manufacturing site’s inspection history, risk considerations of product type, critical quality attributes, proposed manufacturing process, identified critical process parameters and submission data quality are all included and contribute to the final risk assessment determination as to whether a PAI is required.

An even bigger bonus than the risk assessment description were the target time frames provided. It was learned that the Agency strives to complete the PAI determination within the first two months after filing review and to complete the PAI inspection by the time of the mid cycle review.

So now, although a definitive when or who will conduct a PAI still cannot be provided when faced with those inevitable questions, at least the effort it takes for FDA to make the decision can be explained and the target deadlines FDA aims to meet can be conveyed.  It is amazing how reassuring a bit of insight can be; good on the new OPMA for helping to soothe the anxious PAI beast.