FDA will continue to use remote inspection tools to assess pending applications

The US Food and Drug Administration (FDA) issued a draft guidance at the end of September 2023 that formalizes its plans for using alternative tools to assess drug manufacturing facilities compliance with good manufacturing practices (GMPs) as it eases out of pandemic mode.  The Agency intends to build on the “success” of using these tools during the COVID-19 pandemic.  Alternative methods can include a remote regulatory assessment (RRA), which is a remote assessment of an establishment or its records, performing remote interactive evaluations (RIE) of facilities, or requesting information from foreign regulatory partners through mutual recognition agreements (MRA).

Michael Kopcha, Director of the Center for Drug Evaluation and Research’s (CDER) Office of Pharmaceutical Quality (OPQ), said that the guidance “will help the agency maintain operational flexibility to support review of drug applications and facility evaluations which could result in timely approval of drugs and facilitate the availability of new, generic, and biosimilar drugs for patients.  FDA successfully used alternative tools to evaluate facilities during the COVID-19 pandemic, and we will continue to use these tools when and where appropriate.”

The guidance applies to new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), or a supplement to these applications.  Excluded from its scope are post-approval inspections, surveillance inspections, follow-up, for-cause inspections, and bioresearch monitoring inspections (BIMO).  The guidance fulfills part of the agreement reached between FDA and industry in the Prescription Drug User Fee Act (PDUFA VII) and the Biosimilar User Fee Act (BsUFA III) deals.  Under the agreements, FDA pledged to issue guidance on the use of alternative tools to evaluate manufacturing facilities named in pending applications.

FDA will weigh multiple factors in deciding whether to inspect onsite or use alternative methods.  The factors include whether the facility has a drug inspection history, whether the product addresses an urgent need, or whether an onsite inspection is not feasible due to travel restrictions.  FDA said for an RRA, a response from the facility is mandatory.  Refusal to comply may result in delayed action on the application due to the Agency not having the necessary information to approve the application.  Failure to respond may also result in a Complete Response Letter (CRL) to the manufacturer, according to the Agency.

Another alternative method that the Agency may employ is conducting Remote Interactive Evaluations (RIEs), which can include remote livestreaming video of operations, teleconferences, or screen sharing.  It note that while a company’s participation in a RRA is mandatory, an RIE is voluntary.  FDA may opt for an RIE when visual observation of a product or its manufacturing operations and virtual engagement with staff would enable a decision on an application the guidance added.  For an RIE, facilities should evaluate their capabilities to interact with FDA using technologies such as remote livestreaming, teleconferences, and screen sharing, according to FDA.  “If a facility is unable to support a virtual interaction or if FDA determines that virtual interaction during an RIE does not permit a sufficient examination of the facility or of a corrective action, FDA may terminate the RIE and instead conduct an inspection or use other available tools.”  A facility may decline participate in an RIE, but such a decision may “prolong a decision on an application.”

Another alternative tool FDA may use is to request an existing drug inspection report from a foreign partner through an MRA (Mutual Recognition Agreement).  The Agency said it may ask for such inspection reports in cases where the facility does not have an FDA inspection history or if prior FDA inspection coverage was limited.  FDA has not recognized PAIs or PLIs conducted by a foreign regulatory authority in the context of a MRA but added that it “does collaborate with regulatory authorities and assesses shared inspection information to support application decisions.”  FDA may use one or more of these alternative tools to assess applications, according to the Agency.

The draft replaces earlier guidance on RRAs released in September 2022, and an earlier draft on RIEs issued in April 2021.  Stakeholders could submit comments on the draft guidance on regulations.gov under docket no. FDA-2023-D-3031 until 21 November 2023.

REFERENCE:  Regulatory Focus (A RAPS Publication; Regulatory News); 22 SEP 2023; Joanne S. Eglovitch