FDA’s Alternative Tools Guidance Promises a Flexible Approach for Manufacturing Facility Assessments

On September 12, 2025, the U.S. Food and Drug Administration (FDA) issued its much-anticipated guidance, Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications.¹ This guidance document represents the culmination of lessons learned during the Covid-19 pandemic and sets forth a risk-based framework for using remote and collaborative tools in lieu of, or in support of, traditional on-site inspections for pending applications. While its impact outside of the preapproval context is unclear, we anticipate that FDA will use the alternative tools described in this guidance to streamline manufacturing facility assessments, especially for domestic manufacturing facilities under the Pre-Check and Commissioner’s Priority Review Voucher programs.²

Background and Purpose

The guidance arises from commitments in the Prescription Drug User Fee Act (PDUFA VII) and Biosimilar User Fee Act (BsUFA III). FDA pledged to clarify how alternative tools may be leveraged to evaluate facilities listed in new drug applications (NDAs), abbreviated new drug applications (ANDAs), and biologics license applications (BLAs). The agency’s stated intent is to maintain timely approval decisions without compromising product quality and patient safety.

The Alternative Tools Framework

FDA now explicitly affirms that tools beyond the traditional on-site preapproval or prelicense inspection can support facility evaluations for pending applications. These tools include

• Remote Regulatory Assessments (RRAs): FDA’s guidance describes RRAs as “an examination of an FDA-regulated establishment and/or its records, conducted entirely remotely, to evaluate compliance with applicable FDA requirements.” RRAs can be conducted as remote record requests under FDCA §704(a)(4), which are mandatory, or remote interactive evaluations (RIEs), which are voluntary. Notably, while participation in an RIE is voluntary, FDA notes that RIEs may be the “quickest means for FDA to assess a facility’s activities,” and thus “declining to participate in an RIE may prolong a decision on an application.”
• Trusted Foreign Partner Inspections: While FDA’s mutual recognition program does not apply to preapproval or prelicense inspections, the guidance indicates that FDA may rely on inspection reports from trusted partners during facility assessments. Interestingly, the guidance references a pilot program where FDA may participate remotely in collaborative inspections led by trusted and capable foreign regulatory authorities.     
• Remote Subject Matter Experts (SMEs): On-site FDA teams may be supplemented with remote FDA SMEs, connecting virtually to provide technical expertise during inspections.

This layered toolkit offers FDA greater flexibility to meet user fee deadlines, address public health needs, and manage global manufacturing challenges.

Legal and Regulatory Considerations

The potential for increased flexibility and efficiency during application reviews is appealing. But companies should carefully review the options outlined in this guidance to fully understand the potential legal and regulatory implications. For example:

• Obligations Under Records Requests: Failure to comply fully or timely with a Section §704(a)(4) records request may lead to delays, complete response letters, or potential regulatory action. Companies should evaluate and verify that they have systems in place to comply with and respond to such records requests.
• Voluntary vs. Mandatory Participation: While responding to RIEs is voluntary, declining to participate can prolong application decisions. Strategic consideration of reputational and timing effects is essential.
• Global Harmonization: Reliance on foreign regulatory partners introduces both opportunities (reduced duplicative inspections) and risks (divergence in inspectional scope or findings). Companies with a presence in multiple jurisdictions should ensure their systems are robust across their network of sites.  
• Transparency and Technology: FDA’s emphasis on alternative tools raises important technology considerations under the umbrella of inspection readiness. Manufacturing facilities should consider their technical capability to support remote interactive evaluations, including facility tours, and remote SME participation, including secure livestreaming, teleconferences, and digital record-sharing. 

Our Thoughts

This guidance is an important development for companies seeking approval for manufacturing-facility-related applications. While the alternative tools described in the guidance are already in use, it is no accident that this guidance is being published shortly after FDA announced the Pre-Check program and the Commissioner’s Priority Review Voucher program.³ FDA is looking to streamline the application review process, especially for new manufacturing facilities in the U.S. Companies can and should leverage the flexibility of these alternative tools to streamline regulatory timelines and approval pathways. 

At the same time, manufacturing facilities should modernize their approaches to inspection readiness to navigate this evolving regulatory environment. Companies should develop internal protocols to manage FDA requests efficiently, train staff for virtual engagements, and maintain open lines of communication with regulators. While this guidance provides valuable flexibility, it also imposes new compliance obligations that require proactive planning.

¹ Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications Guidance for Industry, September 2025, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/alternative-tools-assessing-drug-manufacturing-facilities-identified-pending-applications?utm_medium=email&utm_source=govdelivery.

² Johnson, James R., Fanelli, Christopher A., Varrone, Michael, Harris, Mia R., FDA Launches “PreCheck” Program to Support U.S. Pharmaceutical Manufacturing: What Industry Stakeholders Should Know dated August 13, 2025.

³ Ibid.