FDA details plans to expand remote regulatory assessments

USA – The US Food and Drug Administration (FDA) released draft guidance that formalizes its plans for using remote regulatory assessments (RRAs) for FDA-regulated products to supplement onsite inspections as it eases out of pandemic response mode, Regulatory Focus reports.

The guidance covers triggers for when FDA will request or require remote assessments and how these audits will be coordinated with onsite inspections.

These tools are not intended to replace onsite inspections but instead, the guidance “lays out how we intend to leverage this tool to advance our mission as we further incorporate modernized approaches to protecting public health” said FDA Commissioner Robert Califf and Judith McMeekin, associate commissioner for regulatory affairs.

FDA officials hinted at an earlier meeting that this hybrid inspection model incorporating both onsite and remote interactive evaluations would be here to stay in the post-pandemic world.

This guidance replaces FDA’s draft guidance issued at the height of the pandemic on its approach to remote inspections.

The 17-page guidance, which is in question-and-answer format, defines who may be subject to an RRA; situations in which FDA may initiate or request a remote evaluation; whether RRAs will be used to supplement onsite inspections; what records or other information FDA may request, and the timeframe for submitting the records to FDA.

Through RRAs, the agency has been able to identify unreported adverse events, gather information to add products to import alerts and evaluate the status of companies correcting issues from a previous inspection.

RRAs may include a request for records, or interactive evaluations of an FDA-regulated establishments, which could include the use of livestreaming video, and can be either voluntary or mandatory.

Over the past two years, the agency has performed over 1,470 domestic and 600 foreign inspections through these tools as pandemic-related travel restrictions set in and investigators could not get to sites to inspect.

Califf and McMeekin also touted the benefits of these interactive evaluations, stating that these tools have “been a valuable tool in the nation’s response to the public health emergency, as we’ve fast-tracked their wide use to help get critical medical products to the front lines in the fight against the pandemic while keeping normal business operations moving.”

Through RRAs, the agency has been able to identify unreported adverse events, gather information to add products to import alerts and evaluate the status of companies correcting issues from a previous inspection.

The remote evaluations have also assisted the agency in making regulatory decisions for product premarket submissions, they added.

The agency has requested additional authorities to expand the ability to use remote regulatory tools across all commodities as part its FY2023 budget request.

Triggers for conducting remote inspections

FDA said RRAs may be initiated when investigators cannot conduct an inspection due to pandemic-related travel limitations, natural disasters or other “unstable situations” making travel infeasible.

RRAs can also be initiated to support regulatory decisions. Examples include preparing for an already planned inspection, following up on a consumer complaint or assisting in verifying that an establishment has completed certain corrective actions, such as responding to a previous inspection.

The agency plans to leverage a risk-based approach to determine whether to initiate an RRA. Such risk factors may include the location of the firm, its inspection history, complexity of the product and process, and travel restrictions.

FDA does not plan to conduct RRAs and on-site inspections simultaneously. Instead, an RRA could precede or prompt an inspection.

“When an RRA precedes an inspection, FDA will generally conclude the RRA prior to initiating the inspection. FDA may combine any information gained from the RRA with any resulting observations from the subsequent inspection.

In such circumstance, FDA would confirm any observations from the RRA during the inspection before including them on the Form FDA 483 Inspectional Observations.”

Declining RRA request will lead to applications delays

Declining a voluntary RRA request will not result in enforcement action, but doing so may delay a timely decision on applications for a product’s approval, clearance or authorization due to insufficient information about the establishment’s activities.

There would be more dire consequences for declining mandatory RRAs. FDA said that an establishment may be in violation of the Food, Drug, and Cosmetic Act (FD&C Act) by declining a mandatory RRA and imported drugs from the establishment may be subject to refusal.

If an importer refuses FDA’s written request for records under 21 CFR 1.510(b)(3) or 1.512(b)(5)(ii)(C), the importer may be in violation of section 805 of the FD&C Act and their products refused entry to the US.

Technology expectations highlighted

FDA’s expectations for technological capabilities for RRAs will vary depending on the type of evaluation conducted and its scope; while certain RRAs may involve records requests, other RRAs may require additional technological capability.

For example, if FDA determines the RRA could include live streaming video, companies should expect inquiries about hardware or internet connectivity to assess IT operability, security and privacy controls to protect the confidentiality of the data.

Further, the quality of the remote connection, such as connectivity, image quality and types of cameras used should be adequate for FDA to review the requested records and documents.

Examples of records the agency may request during a voluntary or mandatory RRA can include batch records, as well as product-specific information, including such periodic product reviews, product quality reports and equipment records.

Other records include process validation records and reports, test results, product complaints or other information related to compliance with current Good Manufacturing Practice (cGMP) requirements.

Other types of documents can include batch summaries, a summary of discrepancies and investigations related to manufacturing and testing, as well as SOPs and records generated by the establishment to document control of quality systems.

Upon completion of an RRA, FDA may have a meeting with the establishment’s management to present a written list of RRA observations. FDA will not issue a Form FDA 483, Inspectional Observations, following an RRA.

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