FDA sheds light on criteria for approving PAIs based on remote inspections

Pharmaceutical manufacturers that have their applications denied by the US Food and Drug Administration (FDA) based on remote preapproval inspections (PAIs) span application types and geographic areas, with most of these rejections targeting an ANDA site with multiple applications.

Lane Christensen, branch chief in FDA’s Office of Pharmaceutical Quality in the Center for Drug Evaluation and Research, shed light on the agency’s use of remote inspections through the use of remote interactive evaluations (RIEs) and record requests at the FDA’s Generic Forum, sponsored by the agency’s Small Business and Industry Assistance (SBIA).

The pandemic prompted the agency to rely heavily on remote inspections, said Christensen, noting that since March 2020, records review has been used to conduct over 1,000 inspections, which includes 670 surveillance inspections, and 330 preapproval inspections. The agency recommended that 75 of the 330 applications be withheld based on a PAI using the records request mechanism and has issued 35 import alerts following RIEs.

Remote regulatory assessments are not going away anyone soon; last July, the agency announced plans to use a combination of remote regulatory assessments and onsite inspections going forward as it eases out of the pandemic mode (RELATED: FDA describes plans to expand remote regulatory assessments, Regulatory Focus, 22 July 2022).

Firms that have received withhold recommendations span application types and regions. Applicants are located throughout Europe and Asia, including India, Germany, Italy, Canada, China, France, Croatia, Spain and Austria.

Christensen said that 60% of the withhold recommendations were issued to ANDA applicants, and a smaller number were issued to new drug applications, biological license applications, manufacturers of active pharmaceutical ingredients (APIs) and preapproval supplements.

A year after FDA has issued withhold recommendations, about half of those were still pending and were either awaiting an onsite inspection or additional information from the sponsors.

Christensen described the circumstances for approving applications at two foreign sites. The first facility was using a new unit operation called hot melt extrusion, the other was for a firm requesting approval a drug-device combination product, a new type of product for the facility.

Officials were able to discuss these products with subject matter experts and able to visualize their operations though virtual connections.

In another case, FDA denied withheld approval of an application at a foreign site that manufactures prefilled syringes. The reason for the denial was the firm’s previous history of compliance problems, having received a warning letter. FDA decided to withhold approval of the applications until it could conduct an onsite inspection.

To ensure a successful RIE, Christensen said it is important for manufacturers to pay as much attention to these audits as an onsite inspection. Manufacturers should also organize and submit the requested documents in “easy-to-understand” formats. It is also important to have subject matter experts available to answer the inspector’s questions. Sponsors should clarify any requests that are not fully understood, especially for requests involving a high volume of records.

Generic Drug Forum

FDA sheds light on criteria for approving PAIs based on remote inspections

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