FDA finalizes guidance on alternative inspection tools

The US Food and Drug Administration (FDA) on Thursday finalized its guidance on the use of alternative tools for conducting preapproval inspections (PAI) or prelicense inspections (PLIs) in lieu of onsite inspections of drug manufacturing facilities that are named in pending applications.

These alternative methods can include remote regulatory assessments (RRA), which is a remote assessment of an establishment or its records, remote interactive evaluations (RIE) of facilities, or requesting information from foreign regulatory partners through mutual recognition agreements (MRA).

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 postapproval inspections, surveillance inspections, follow-up, for-cause inspections, and bioresearch monitoring inspections.

The guidance contains some changes from a draft version issued in September 2023, when the agency formalized its plans for using alternative tools to assess drug manufacturing facilities’ compliance with good manufacturing practices (GMPs). (RELATED: FDA will continue to use remote inspection tools to assess pending applications, Regulatory Focus 22 September 2023)

Among the changes are a clarification on the recommended timeframe for facilities to respond to records requests under section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act.

The final version adds a new footnote stating that “FDA intends to set a reasonable time frame. For example, FDA may request that the facility respond within 15 U.S. business days (or within 30 U.S. business days when language translation of records is requested. In certain circumstances, as reasonable, FDA may request that a facility respond to the records request in a time frame of fewer than 15 U.S. business days to accommodate the needs of the specific request (e.g., to meet an application goal date, deadline, or for other time-sensitive reasons).”

The final guidance also clarified that its alternative tools apply to both foreign and domestic facilities. The agency also clarified that declining a request to use remote resources to facilitate a remote subject matter expert (SME) during an inspection “may prolong a decision on an application.” The agency added that it may use its own equipment to support a virtual SME’s participation or to proceed without their involvement.

Additionally, while the agency said it will provide a written list of RRA observations to firms detailing the conditions or practices observed through the use of alternative tools, FDA said it will detail objectionable conditions or practices observed during inspections, including those featuring a remote SME, via a Form 483.

In its comments on the draft guidance, the Biotechnology Industry Organization (BIO) asked FDA to clarify the types of postapproval inspections that are excluded from the guidance, noting that “there are instances when a PLI/PAI is combined with a surveillance inspection. This seems to infer that these types of combined inspections would not use the alternative tools, leading to potential inefficiencies and multiple visits/requests by FDA.”

In response, FDA added a footnote explaining that it “conducts risk-based postapproval inspections to focus on a specific drug or biological product and evaluate its process validation, changes to its manufacturing processing, changes submitted to the application, and the execution of supporting activities according to application commitments and CGMP requirements, among other possible reasons.”

FDA also declined to follow a recommendation from the Pharmaceutical Research and Manufacturers of America (PhRMA), which asked the agency to combine the guidance with two others related to remote regulatory assessments and remote interactive evaluations. PhRMA also called on the agency to publish a manual of policies and procedures detailing its risk-based approach for determining when an inspection is necessary.

FDA agreed to requests from the Parenteral Drug Association (PDA) to not record virtual interactions with a remote subject matter expert (SME) conducted via livestream video, screen sharing, and teleconferencing.

PDA noted that “many of the processes and documentation reviewed by FDA are proprietary and reveal company intellectual property. If FDA intends to create a record of the video, screen sharing, etc., it would be prudent to inform the entity inspected. Local regulations in some countries (e.g., Germany) restrict the recording of personnel in the workplace.”

In a new footnote, FDA states that it “does not intend to record virtual interactions with a remote SME conducted via livestreaming video, screen sharing, and teleconference.”

Final guidance

FDA finalizes guidance on alternative inspection tools

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