FDA Releases Proposed PDUFA VIII Commitment Letter

On August 14, 2026, the U.S. Food and Drug Administration (FDA) published a notice seeking public input on the proposed eighth commitment letter for the Prescription Drug User Fee Act (PDUFA VIII), which would cover fiscal years (FY) 2028 through 2032 (proposed Commitment Letter).¹ The current PDUFA VII authorization expires in September 2027, and new legislation will be required for FDA to continue collecting prescription drug user fees after that date. FDA will hold a hybrid public meeting on September 16, 2026, and written comments are due October 16, 2026.

Assuming the letter is finalized in its current form, the draft Commitment Letter will include new enhancements, including a discretionary one-time goal date extension and additional opportunities for engagement around manufacturing deficiencies. It will carry forward certain PDUFA VII initiatives (e.g., cell and gene therapies), and will deemphasize or eliminate certain PDUFA VII initiatives (e.g., the START Pilot). The negotiated commitment letter proposes to revise review and meeting practices, transition several regulatory science initiatives into routine processes, continue to use regulatory science tools to support drug development and regulatory review, create a Chemistry, Manufacturing, and Controls (CMC) facility lifecycle program, among other notable changes for the upcoming cycle. The federal register notice announcing the proposed letter also teased certain changes in user fee structures — notably, a fee-based incentives for U.S.-based clinical trials and a new supplement fee for non-orphan indications. Key takeaways include:

• Review process and communications. FDA proposes new mechanisms aimed at reducing avoidable complete response actions, missed goal dates, and review-clock extensions, including a broad third-party assessment of first-cycle review and a process for prioritizing pivotal protocols. FDA is also adding a mechanism to provide a one-time goal date extension based on post-inspection meeting responses to deficiencies identified in a pre-approval or pre-license inspection. The agency is focused on efficiency and transparency, and has made small additions to certain provisions, such as providing more context about what triggered an information request after a Late-Cycle Meeting. 
• More formalized sponsor engagement. The proposal would expand opportunities for multi-divisional meetings and create new CMC-focused engagements before and after inspection.
• PDUFA VII evolution. Certain PDUFA VII initiatives will be sustained, albeit modified: e.g., a continued focus on supporting cell and gene therapy product development and review, and transitioning Model-Informed Drug Development (MIDD) and rare-disease endpoint development (RDEA) into formal pathways.
• Changes to user fee setting and management. FDA proposes changes to fee-setting and resource-management mechanisms as well as application-fee, orphan, and small-business provisions that could materially affect certain sponsors. Such changes must be enacted through upcoming legislation.

FDA’s Proposed PDUFA VIII Enhancements

Pivotal Protocol Prioritization

To help sponsors obtain feedback on critical study-design questions before trial initiation, FDA proposes a process for prioritizing review of “Pivotal Protocols.” FDA describes these as protocols for studies intended to form the primary basis of an efficacy claim in a marketing application. A sponsor would identify the submission as a “Pivotal Protocol” in the cover letter, document the planned study start date, and include critical questions requiring FDA responses to enable study initiation. FDA would prioritize qualifying protocols consistent with timelines in the relevant CDER MAPP and CBER SOPP and would update those documents by the end of FY 2028.²

Meeting Management Goals

FDA proposes two substantive changes to formal meeting management. First, the commitment letter would expressly recognize multi-divisional meetings for products being developed under multiple investigational new drugs (INDs) across multiple therapeutic areas. A sponsor could request a multi-divisional meeting within an existing PDUFA meeting type with the goal to improve efficiency and seek alignment across participating divisions when a product raises cross-division issues.

Second, for pre-IND, Type C, Type D, and INitial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs (INTERACT) meetings, a sponsor requesting a face-to-face format would be expected to explain why that format is warranted. If FDA concludes that a written response is sufficient, the agency would provide a specific rationale. 

FDA also proposes a third-party assessment of these meeting-format “enhancements” that would also include a list of issues regarding communications between sponsors and the agency, including best practices with respect to “written response only” meetings versus face-to-face. FDA would commit to revising its formal meetings guidance by September 30, 2028 to address multi-divisional meetings and written-response procedures.³

Apart from these formal meeting management goals, the proposed Commitment Letter also includes meaningful small changes for applicants that may facilitate efficiency in the review process. Of note, for information requests (IRs) issued by the review team to an applicant after a Late-Cycle Meeting, FDA intends to include a description of the issue that triggered the IR to provide context for the applicant when collecting the requested information. 

Expediting Drug Development and Enhancing the Use of Regulatory Science Tools

FDA proposes to continue and expand the Rare Disease Endpoint Advancement (RDEA) program, transitioning from a limited pilot in FYs 2028 to 2029 to Type C-RDEA meetings in FYs 2030 to 2032. The MIDD Paired Meeting Program would similarly move toward Type C-MIDD meetings by the end of FY 2030. The Complex Innovative Design program would be incorporated into standard review practice, and FDA would continue to support sponsor engagement on real-world evidence through established formal meeting pathways.⁴

Regulatory Science Tools to Support Drug Development and Regulatory Review

The proposed Commitment Letter shifts FDA’s regulatory-science initiatives from the pilot, demonstration, and capacity-building phases emphasized in PDUFA VII toward integration into routine review practices. The proposed text expressly provides that FDA will integrate lessons learned from prior work on benefit-risk assessment, complex innovative designs (CIDs), digital health technologies (DHTs), biomarker qualification, MIDD, patient-focused drug development (PFDD), and real-world evidence (RWE).

The most significant change pertains to MIDD and RWE: PDUFA VIII moves away from limited-access pilot models toward routine sponsor engagement. Similarly, rather than continuing PDUFA VII’s Advancing RWE pilot as a separate program, PDUFA VIII provides that RWE submissions will be handled through existing established review practices and ordinary formal meetings with relevant subject-matter experts. FDA also commits to continued annual reporting on RWE submissions and, where appropriate, describing the characteristics of such evidence that contributed to findings of substantial evidence of effectiveness for new indications.

FDA also proposes to shift its PFDD focus from developing methods and infrastructure toward demonstrating how patient experience data affects actual regulatory decisions, including through case studies, a public meeting, continued training, and disclosure in review documents of patient experience data considered by FDA. The bioinformatics provisions similarly move from the initial stages in PDUFA VII to maintaining specialized expertise, computing and cloud resources, and global harmonization efforts through PDUFA VIII. 

Enhancement and Modernization of the FDA Drug Safety System

The proposed Commitment Letter retains a performance goal under which FDA reviews and provides concurrence or comments on 90% of REMS assessment methods and protocols within 90 days of receipt. FDA would also support the Sentinel 3.0 operating model through continued investment in data infrastructure, processes, tools, and reviewer training.⁵

CMC and Inspections

PDUFA VIII proposes to continue CMC enhancements and experiences gained through PDUFA VII commitments and will continue to support FDA’s efforts in enhancing communication during product development and application review.

As communicated in the Federal Register notice, to support the timely development and availability of new and innovative products, FDA proposes to introduce a risk-based lifecycle approach to identifying and addressing manufacturing facility deficiencies. Both FDA and regulated industry acknowledge the criticality of CMC facility issues, and the reality that manufacturing facility deficiencies can result in Complete Response Letters (CRLs) and additional review cycles. To help prevent or mitigate these issues, or foster early resolution, the proposed Commitment Letter proposes a “CMC facility lifecycle program.” This program is grounded in new and enhanced engagement mechanisms between FDA and industry that may occur before, during, and after an application review cycle. The opportunity for sponsors and FDA to communicate about these issues in a formalized setting, such as the meetings highlighted below, represents a meaningful development in advancing resolution of outstanding facility issues and bringing products to market. Key elements are summarized below.

• FDA Guidance. FDA will strive to publish draft guidance by October 1, 2028 describing the implementation of the CMC facility lifecycle program. It may cover topics such as readiness for a pre-approval inspection (PAI) or pre-license inspection (PLI); CMC facility pre-submission, post-PAI/PLI, and post-Action meeting procedures and associated timelines and best practices; and how to self-assess facility readiness, among other topics. The readiness criteria set forth in the guidance may facilitate eligibility for post-PAI or post-PLI meetings.
• Meetings. The proposed Commitment Letter outlines several different types of meetings, as well as associated timelines and procedures. The categories of meetings are discussed below.
  • CMC Facility Pre-Submission Meetings for NDAs and BLAs, Including Supplements. Applicants may request a single CMC Facility Pre-submission meeting to discuss manufacturing facilities for a proposed application submission. This meeting may occur three to six months before an application submission, though this timeframe may be flexible.
    These meetings may cover information about the manufacturing supply chain with a focus on the relationships and interdependence of manufacturing facilities and the operations intended for the application product, awareness and mitigation of associated risks, and information from prior inspections conducted by FDA and other regulators. This information may inform FDA’s risk-based approach in making decisions for facility evaluations and inspections.
  • Post-PAI or Post-PLI Meetings for Original NDAs or BLAs. The intent of this meeting is to ensure transparency and facilitate resolution of inspection deficiencies by the application goal date. Only original applications, not supplements, are eligible for this engagement. After a PAI or PLI, FDA intends to tell the applicant when Form 483 observations may result in a CRL. The applicant may request a meeting to discuss the inspection findings that may affect application approval, their corrective actions, and whether the corrective actions are responsive to issues that may affect application approvability. Although FDA will strive to complete the meeting to facilitate first-cycle approval, the agency may extend the goal date by three months (but only one extension may be granted).
  • Post-Action Meetings. If deficiencies in a PAI or PLI result in FDA issuing a CRL for an NDA or BLA (including a CMC supplement), the applicant may request a Type A post-action meeting to discuss the deficiencies that should be corrected before the application can be approved.
• Enhanced Inspection Communications. FDA intends to communicate, at least 60 days in advance of a PAI or PLI — and no later than mid-cycle — that the agency needs to conduct an inspection when the product in the application is being manufactured. This applies to original applications, not supplements.
• CMC Facility Lifecycle Workshop. FDA intends to contract with an independent third party to hold a public workshop by September 30, 2030. This workshop will focus on program implementation and its impact on facility readiness and reduction of facility deficiencies.
• Third-Party Assessment. The third-party with whom FDA has contracted for the public workshop will perform an assessment involving FDA staff and sponsor interviews, will evaluate the program’s effect on facility-issue driven CRLs, and will assess feedback from the workshop and draft a report summarizing the foregoing. FDA will publish the final report no later than nine months after the close of the public workshop comment period. Next steps may include proposed timeframes to develop or revise policy documents.

Advancing Next Generation Cell and Gene Therapies

While FDA continues to focus on the cell and gene therapy program (CGTP), the agency’s focus is shifting from growth to maintenance. For PDUFA VIII, FDA will retain and strengthen its staff capacity and utilize existing resources to sustain the CGTP for direct review and certain supportive activities, and focus on hiring staff with specialized expertise necessary to facilitate the development and advancement of cell and gene therapies. In lieu of the various programs and targets issued for PDUFA VII, FDA staff will continue to engage in outreach and solicit views from stakeholders, participate in external collaborations, and target engagement in specific areas. For example, CBER staff will focus on developing safety and efficacy information for rare disease products, including through existing and new approaches, and will continue to advance approaches to evaluate efficacy in small patient populations. CBER will also advance sponsors leveraging their prior knowledge and public knowledge across CMC, non-clinical, and clinical spheres to support product development and application review.

FDA will also continue to seek input regarding issues faced by cell and gene therapy product developers, including the use of novel endpoints and the role of less defined natural histories, to support the development and approval of such products.

Assessment of the Program, Efficacy Supplements, and Communications

FDA proposes a broad third-party assessment of first-cycle review processes, outcomes, and FDA-sponsor communications. Beginning in FY 2028, the assessment would examine new molecular entity (NME) New Drug Applications (NDAs) and original Biologics License Applications (BLAs) submitted during PDUFA VII and PDUFA VIII, including the timing and basis of approvals and complete responses, major amendments and clock extensions, and the completeness and timing of key communications. For efficacy supplements, the assessment would focus specifically on labeling communications. It would also evaluate communications related to pivotal protocols during development. The stated objective is to identify trends and best practices and generate actionable recommendations to help FDA and sponsors reduce avoidable complete responses, missed goal dates, and review-clock extensions.⁶

Fee Mechanisms

Although the changes discussed herein are not covered by the proposed Commitment Letter, certain notable PDUFA VIII fee structure changes discussed in the Federal Register will be pursued through legislation. The first pertains to onshoring incentives. PDUFA VIII would update the fee structure such that sponsors would receive a 50% reduction in the application fee if the application includes clinical data from at least one phase 1 trial anchored in the United States initiated after October 1, 2027. PDUFA VIII also proposes to update the eligibility for the small business waiver to only companies based in the United States (i.e., applicants created or organized under the laws of any state).

The second relates to orphan products. PDUFA VIII would modify the fee structure to charge sponsors a fee, equal to 50% of the full application fee, for the first supplement seeking approval for a non-orphan indication for an application that was subject to the orphan application fee exception. The orphan program fee exemption would also be limited to products approved only for orphan indications.

Looking Ahead

The pivotal-protocol process, multi-divisional meetings, and new CMC facility engagements will reward earlier identification of issues that would have otherwise resulted in CRLs. Moreover, the CMC lifecycle proposal creates additional opportunities for communication, but the usefulness of those opportunities will depend on inspection-readiness planning and the ability to respond rapidly to inspection findings.

FDA will hold a hybrid public meeting on September 16, 2026, and written comments are due October 16, 2026. Please contact the authors of this Advisory or your regular Arnold & Porter contact if you have questions or would like to discuss how this proposed PDUFA VIII commitment letter may impact your business.

Footnotes

1. FDA, Reauthorization of the Prescription Drug User Fee Act; Public Meeting; Request for Comments, Docket No. FDA-2026-N-8163 (Aug. 14, 2026).

2. Federal Register Notice at 11-12; Proposed Commitment Letter § I.J, at 18.

3. Federal Register Notice at 12; Proposed Commitment Letter § I.K.1.f, .2.a, .9, .10.

4. Federal Register Notice at 12-13; Proposed Commitment Letter § I.L.3, .5, .7, at 27-36.

5. Federal Register Notice at 13; Proposed Commitment Letter § I.M, at 37-38.

6. Proposed Commitment Letter § I.C, at 11-12 (July 31, 2026).