FDA Issues Guidance on Alternative Tools for Assessing Drug Manufacturing Facilities in Pending Applications

The guidance, issued by the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research, outlines a risk-based framework for deploying these tools, particularly in situations where traditional on-site inspections are impractical or infeasible.

Key Takeaways

• The FDA formalizes the use of alternative assessment tools, building on practices developed during the COVID-19 pandemic to support timely and effective evaluation of manufacturing facilities named in new drug applications, abbreviated new drug applications, and biologics license applications.
• The guidance emphasizes a risk-based approach, considering factors such as facility inspection history, product-specific risks, urgency of public health needs, and feasibility of travel.
• Alternative tools include RRAs, information sharing and collaborative inspections with trusted foreign regulatory partners, and the use of remote FDA subject matter experts (SMEs) to support on-site inspections.
• The guidance does not apply to post-approval, surveillance, follow-up, or bioresearch monitoring inspections.

Background

The FDA’s authority to collect user fees under the Prescription Drug User Fee Act (PDUFA) and the Biosimilar User Fee Act (BsUFA) supports timely review of drug applications. In response to challenges posed by the COVID-19 pandemic, the FDA expanded its use of alternative tools to assess manufacturing facilities when on-site inspections were not feasible. The current guidance fulfills commitments under PDUFA VII and BsUFA III to incorporate these best practices into routine operations.

Risk-Based Use of Alternative Tools

The FDA employs a risk-based approach to determine when alternative tools may be used in advance of, in lieu of, or to support pre-approval inspections or pre-license inspections. Factors influencing this determination include the following.

• The facility’s prior inspection history (by the FDA or trusted foreign regulators) and similarity of proposed operations to previously inspected activities.
• The ability to adequately assess application-specific risks through alternative means.
• The presence of urgent public health needs, such as drug shortages.
• Infeasibility of on-site inspection due to travel limitations or other extraordinary circumstances.

Considerations for Implementation

RRAs

RRAs involve the remote examination of facilities and records to evaluate compliance with FDA requirements. The FDA may request records under section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act, with mandatory facility response within specified timeframes. RRAs may also include voluntary remote interactive evaluations (RIEs) using livestreaming, teleconferences, or screen sharing. Participation in RIEs is voluntary, but declining may delay application decisions.

Inspections by Trusted Foreign Regulatory Partners

The FDA may leverage inspection reports and information from foreign regulatory authorities under mutual recognition agreements to inform its facility assessments. Collaborative inspections, where FDA personnel participate remotely alongside foreign inspectors, are being piloted to enhance efficiency and reduce redundancy.

Use of Remote FDA SMEs

The FDA may supplement on-site inspection teams with remote SMEs when specialized expertise is required and on-site participation is not feasible. Facility agreement is voluntary, but refusal may prolong application review. Virtual technologies must enable effective real-time engagement between remote SMEs, on-site inspectors, and facility staff.

Impact on Application Review

The use of alternative tools is intended to help the FDA meet user fee goal dates and make timely regulatory decisions. Observations identified through alternative tools may be communicated in writing to facilities, with a recommended response period of 15 US business days. If alternative tools do not provide sufficient information, the FDA may require an on-site inspection, potentially impacting application timelines.

Conclusion

The FDA’s guidance on alternative tools for assessing drug manufacturing facilities in pending applications reflects a shift toward greater operational flexibility and technology-driven oversight. Applicants should ensure readiness for both traditional inspections and alternative assessment methods as the FDA continues to refine its risk-based approach to facility evaluation in support of timely access to safe and effective medicines.