FDA Inspections Back Up To Speed (Except Those Now Deemed Unnecessary)

Those of us who work frequently on FDA inspections of drug and medical device manufacturing facilities have noticed an uptick in regular inspections after a dramatic falloff during the first two years of COVID.  That impression was corroborated this week at the GMP by the Sea conference when Douglas Throckmorton, Deputy Director for Regulatory Programs at FDA’s Center for Drug Evaluation and Research, stated that domestic FDA inspections of facilities have been performed at “standard operational levels” since October 2021.  He added that FDA’s foreign offices have also resumed performing inspections for nearly six months now, except in China, where Zero-COVID policies complicate logistics and scheduling.

More surprising was Dr. Throckmorton’s statement that one area of FDA inspections has been deliberately and significantly reduced from pre-COVID levels: inspections that are required of facilities manufacturing drug products or drug components (like Active Pharmaceutical Ingredients) prior to approval of a new Drug Application, Abbreviated New Drug Application, or Biologics License Application.  These are called Pre-Approval Inspections, and, when COVID difficulties would otherwise delay inspections leading to drug approvals, numerous applicants have struggled with trying to expedite these inspections, or to convince FDA that the PAIs are unnecessary.  Dr. Throckmorton stated that the number of required PAIs has been reduced by about 50%, as a result of re-examining the necessity of so many PAIs (he said PAIs used to be required for about 20% of applications).

Both he and Alonza Cruse, the Director of the FDA office responsible for, among other things, facility inspections (he heads the Office of Pharmaceutical Quality Operations), emphasized that a lot of the changes effectuated in response to COVID will be permanent.  The agency has re-examined whether, from a risk perspective, so many on-site inspections are necessary, either because the risk of problems at a particular facility is low, or because alternatives (such as records inspections or what FDA refers to as “remote interactive evaluations”) can substitute for on-site inspections.

Mr. Cruse also mentioned that FDA has been putting a premium on performing PAIs – or on finding alternatives – to permit FDA to take action on drug applications by the PDUFA (Prescription Drug User Fee Act) and GDUFA (Generic Drug User Fee Act) date goals.

In response to my question, Mr. Cruse said that FDA has performed probably fewer than 10 of what FDA calls “Remote Interactive Evaluations” at drug manufacturing facilities since the FDA guidance was issued permitting these forms of virtual inspections.  Mr. Cruse pledged that the frequency of these inspections would increase.

The GMP by the Sea conference is a regular conference (it was held annually until COVID hit) sponsored by PharmaConference (www.pharmaconference.com).