On August 23, 2021, the Food and Drug Administration released the PDUFA VII commitment letter, which contains the agency’s performance goals for the five-year window (Fiscal Year 2023 to 2027) covered by the next iteration of the Prescription Drug User Fee Agreement (PDUFA).
In the first two decades since PDUFA’s initial authorization in 1992, the patient voice was not part of the review chorus. That changed markedly beginning a decade ago when, in 2011, the FDA included performance metrics in the PDUFA V commitment letter that laid the foundation for the agency’s Patient-Focused Drug Development (PFDD) initiative.
With the advent of preference studies and other methodologies to provide some quantitative depictions of patient perspectives, the patient voice has rightfully evolved to become an important perspective across the range of medication development and regulatory reviews.
The PDUFA VII commitment letter continues this embrace of PFDD and patient engagement by including several specific performance goals within the package. While this alert does not address companion citations in the commitment letter regarding benefit-risk assessments in regulatory decision making, the incorporation of objective patient input metrics can strongly inform review processes by providing patient expectations of benefit as well as relative tolerance of risk elements to supplement or supplant traditional medical measures from clinical trials.
As PDUFA VII moves toward Congress — which must enact legislation to authorize the user fee package by the end of September 2022 to preserve the significant level of User Fee support which supplements (and far exceeds) appropriations for FDA — patient engagement policies will likely continue to see much attention and implementation in review processes, approval deliberations and (ideally) in product labeling. Following is an overview of the PFDD and related objectives included in the current letter.
The commitment letter recognizes the growing interest in applying PFDD to development of cell and gene-based therapies, which are overseen by the Center for Biologics Evaluation and Research (CBER), in addition to its extant incorporation for small molecules and biologics. Much of FDA’s patient engagement agenda has to-date resided within the Center for Drug Research and Evaluation (CDER) and the Center for Devices and Radiological Health (CDRH).
To expand PFDD into gene and cell-based therapy reviews, the performance letter commits CBER to convening a PFDD meeting by the end of FY 2023 “to better understand patient perspectives on gene therapy products, including cell-mediated gene therapy.” The meeting will include a report and will explore whether tools or methods are needed to capture patient experience data pertaining to such therapies.
A meeting and subsequent report are not novel approaches, and under the stated timeframe, any such CBER report would likely not emerge until early 2024. However, this provision signals a recognition that CBER will need to engage more broadly in patient engagement activities and could open a door for patients and industry stakeholders to dialogue with the Center to advance development of tools focused on gene therapy applications.
Beyond this performance metric, the commitment letter includes several other criteria that FDA says “will build on the successes of its efforts on Patient Focused Drug Development (PFDD), benefit-risk assessment in regulatory decision making, and the drug development tools qualification pathway for biomarkers.” Specific metrics contained in the letter include:
- Consulting with external experts by using the Intergovernmental Personnel Act to support review of patient experience data.
- Expanding outreach to internal personnel and sponsors, including with guidances, to build understanding and use of such approaches in regulatory reviews.
- Issue a Request for Information (RFI) by June 2023 on “methodological issues, including the submission and evaluation of patient experience data in the context of the benefit-risk assessment and product labeling.”
- Convene at least two workshops focused on methodological issues during FY 24 and FY 25, and summarize priorities emanating from the RFI and workshops by the end of FY 26.
- By the end of FY 26, publish a draft guidance “on use and submission of patient preference information to support regulatory decision making” with a goal of issuing final guidance within 16 months from the close of the comment period.
In addition to these concrete metrics, the commitment letter speaks to work FDA has done to incorporate benefit-risk assessments, which incorporate patient preference data as part of the review process, including the work by CDER to include the benefit-risk framework within review templates. FDA did not make specific commitments pertaining to advancing the benefit-risk assessment through legislation currently before Congress, known as the BENEFIT Act, that would incorporate in statute PFDD and related data as a component of these assessments, as well as obligate tracking and transparency of such measures.
Analysis and Next Steps
The inclusion of multiple PFDD and related metrics within the PDUFA VII commitment letter is a positive indicator of FDA’s continued interest in and embrace of advancing the use of such tools. The provisions build upon the past two commitment levels and complement recent and continued congressional interest in legislation to further the field.
As we head more squarely into the PDUFA VII legislative window, we anticipate Congress will continue to look favorably upon patient engagement and PFDD. How far legislators may wish to go with additional statutory provisions is a key lingering question that will come into sharper focus over the months ahead. If not already actively engaged, stakeholders interested in advancing patient engagement legislation as part of PDUFA VII should move quickly over the coming weeks particularly as we fast approach the year-out window.
Stay tuned for our additional observations about other elements of the commitment letter and related matters which can help weave together the interplay of complex factors from investigator, industry, patient and regulator perspectives that, with collaborative best practices, enhance product development activities and seek to deliver innovations more rapidly to waiting patients.