On September 11, 2025, the U.S. Food and Drug Administration (FDA or the Agency) issued the final guidance for industry, Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications.1 The final guidance updates the September 2023 draft guidance on this topic, and fulfills FDA's user fee commitments to issue guidance on the use of alternatives to inspections to assess manufacturing facilities identified in pending applications and to incorporate best practices based on FDA's experience with these alternative tools during the COVID-19 pandemic. FDA also views this policy as helping the agency maintain operational flexibility to support timely facility evaluations and application decisions. Based on comments received on the draft guidance, FDA finalized the guidance with additional clarifications. These include:
- The expected timeframes for facilities to respond to section 704(a)(4) of the Federal Food, Drug, and Cosmetics Act's record requests
- The timing for when facilities may receive requests from FDA to use a remote subject matter expert (SME) during an inspection
- How the Agency will coordinate logistical considerations and technologies with facilities in connection with the use of alternative tools
- The potential consequences if a facility declines to permit FDA's use of remote SME or cannot support the virtual interaction2
The guidance explains how FDA intends to use "alternative tools" with respect to assessing drug manufacturing facilities identified in a marketing application (or supplement).3 What FDA means by "alternative tools" is the methods that the Agency will use in advance, or in lieu of, an inspection or to support an inspection of a drug manufacturing facility that is identified in a marketing application to assess compliance with applicable laws and regulations. For example, the alternative tools may be used to confirm that the facilities used in manufacturing are operated in conformity with current good manufacturing practices.
During the COVID-19 pandemic, FDA gained experience with alternative tools, such as remote interactive evaluations (RIEs, which are essentially real-time remote inspections using video), review of foreign regulatory inspection reports, and records/information requests under the "704(a)(4) authority," deployed in the context of decisions regarding preapproval (PAI) and prelicense (PLI) inspections.4 Based on these experiences and successes, FDA plans to continue the risk-based use of alternative tools and "certain virtual technological capabilities" in the inspectional contexts defined in the guidance.
As noted above, FDA may use alternative tools in advance or in lieu of an inspection in addition to supporting a PAI or PLI. The Agency's use of alternative tools under the guidance is limited to the assessment of drug manufacturing facilities identified in a marketing application. It does not cover post-approval inspections, surveillance inspections without preapproval or prelicense components, follow-up and compliance inspections (e.g., for-cause inspections), or bioresearch monitoring inspections (i.e., BIMO inspections).
The use of alternative tools remains at FDA's discretion — as was the case in the draft guidance, applicants may not request that FDA use alternative tools. Factors that weigh on whether FDA may use alternative tools include the following — any or a combination may suffice:
- The facility in question has been inspected by FDA or a trusted foreign regulatory partner (under a mutual recognition agreement) and the proposed operations in the application are the same as or sufficiently related to the scope of a prior inspection.
- The application-specific risks or applicable facility operations can be assessed, adequately, through alternative tools.
- The product addresses an urgent need, such as a drug shortage or critical public health need.
- An inspection is not feasible due to travel limitations such as pandemics, natural disasters, or instability that prevents travel.
FDA notes that in support of Executive Order 14293, Regulatory Relief to Promote Domestic Production of Critical Medicines,5 the Agency intends to prioritize its use of alternative tools when a facility is located in the United States and when FDA determines that the use of an alternative tool is appropriate in advance or in lieu of an inspection or to support a PAI or a PLI.
The alternative tools that FDA may deploy include the following:
- 704(a)(4) records requests (mandatory) or RIE during application assessment (voluntary): these alternative tools can be used to conduct a remote regulatory assessment (RRA)
- Collaborating with foreign regulatory partners, including through information sharing (e.g., inspection reports and other information from a foreign partner through mutual recognition or other arrangements) and potential collaborative inspection assessments by a foreign regulator with FDA remote participation.
- Supplementing a PAI or PLI with remote SMEs.
With respect to 704(a)(4) records requests, provision of the requested records or other information is required. Providing sufficient information is similarly critical: supplying insufficient information to FDA may delay application action if FDA does not have enough information to make a regulatory determination; result in FDA sending a complete response letter to the applicant if FDA cannot confirm that application deficiencies have been satisfactorily addressed; or carry other potential regulatory or legal consequences.
FDA emphasizes that the facility should "carefully consider" FDA's request and respond within the timeframe that FDA specifies. FDA intends that such timeframes be "reasonable," and provides examples, such as 15 U.S. business days or within 30 U.S. business days if translation is requested, but potentially fewer than 15 U.S. business days in time-sensitive situations.
In contrast, participation in RIEs is voluntary, and FDA will obtain the facility's consent to conduct the RIE before commencing the RIE. Such evaluations may be used when visual observation and virtual engagement with facility staff may help FDA make an application decision. In particular, FDA may try to use an RIE to observe certain manufacturing observations (i.e., to conduct an RIE when a facility is producing the application product), and if so, FDA will coordinate the RIE scheduling to coincide with the manufacturing operations. Although a RIE is voluntary and firms may decline participation in an RIE or an RIE request, there may be practical consequences to non-participation. FDA's guidance here pairs with FDA's related RRA and RIE guidances, which we have previously evaluated (see Arnold & Porter's October 2023 and June 2025 Advisories for more information).
Regarding collaboration and engagement with trusted foreign regulatory partners and the Agency's reliance on these partners as part of its alternative tools framework, FDA has not fully leveraged the potential that mutual recognition agreements offer — FDA has not yet recognized PAIs or PLIs conducted by a foreign regulator. Yet the Agency may recognize inspection reports from foreign regulators and assess inspection information to support application decisions. FDA notes how the use of innovative regulatory approaches and virtual interactive tools by foreign regulators could lead to increased inspection collaboration between regulatory authorities across countries and more harmonized marketing authorization decisions for drug products.
FDA also highlights the role of remote SMEs in supplementing on-site inspection teams during PAIs and PLIs, particularly when in-person participation is not feasible. Remote SMEs can provide real-time expertise through livestream video, screen sharing, and teleconferences to address specific issues to address inspection-specific issues. While participation is voluntary, FDA cautions that declining to cooperate can delay application decisions. The final guidance clarifies and expands on several points from the draft by noting that FDA will generally notify facilities in advance when planning to use a remote SME, request written confirmation of a facility's willingness to agree to engage, and outline coordination expectations. FDA specifies that the Agency's on-site inspection team will begin the inspection before virtually connecting the remote SME and will notify the facility before disconnecting them, a change that will help improve transparency, efficiency, and accountability in the process.
As FDA continues to integrate alternative tools into its inspection and oversight processes, companies should prepare to engage with these tools by treating FDA's requests for records, to participate in RIEs, or other assessments, both mandatory and voluntary, with the same care and seriousness as traditional inspections. This should entail ensuring that all responses are accurate, complete, and responsive, with thorough documentation of all information maintained. Facilities are expected to submit any responses or corrective actions to FDA within 15 U.S. business days for consideration in the application process. Any responses received afterwards may be deferred for further assessment in the next application cycle.
FDA is currently accepting online or written comments on the final Alternative Tools Guidance.
Footnotes
1 FDA Guidance for Industry, Alternative Tools: Assessing Drug Manufacturing
Facilities Identified in Pending Applications (Sept.
2025).
2 Federal Register, Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications; Guidance for Industry; Availability (Sept. 12, 2025).
3 This can include a new drug application, abbreviated new drug application, biologics license application, or supplement thereto.
4 Alternative Tools Guidance at 3.
5 Executive Order 14293, Regulatory Relief to Promote Domestic Production of Critical Medicines (May 5, 2025).
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