FDA, Industry Map New R&D Initiatives under Next User Fee Program

Amidst a very busy time for the agency, FDA formally unveiled its plan for revising and renewing its fee program for drugs and biologics, with an eye to gaining Congressional approval early next year. The program announced August 23, 2021, is set to collect more than $1 billion in annual fees to support additional staffers and multiple initiatives in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). The aim is to build on the current fee program, so that Congress will reauthorize the Prescription Drug User Fee Act (PDUFA VII) in time for it to be operational by October 1, 2022.

The specifics for PDUFA VII, which will run from FY 2023 through 2027, are spelled out in the new Commitment Letter negotiated this past year by FDA and industry leaders. This lengthy description of proposals and policies will be further discussed at a virtual FDA public meeting at the end of September. The aim is to provide stakeholders with an opportunity to learn more about program changes and to weigh in on proposed enhancements, in comments due October 28, 2021.

Along with specifying the fees industry will pay for FY 2023 through 2027 and relevant changes to timeframes for CDER and CBER to review and approve applications for new drugs and biologics, the 71-page PDUFA VII letter describes many new and expanded initiatives for enhancing oversight of certain therapies and for improving regulatory practices. There are additional pilot programs, timeframes for issuing new guidances, and an expanded range of FDA-sponsor meetings to smooth the path to approval for new therapies. A specific change extends the fee program to allergenic extract products under a one-year phase-in process at CBER. Oversight of combination products would be enhanced by policies governing human factor validation study protocols. The plan also outlines improvements in the process for assessing REMS (Risk Evaluation and Mitigation Strategies) and enhancements for hiring and retaining staffers in CDER and CBER.

Rare diseases & gene therapies

To support the development of new treatments for rare diseases, FDA proposes a Split Real Time Application Review (STAR) pilot program to streamline the review process for new rare disease endpoints by allowing sponsors to split an efficacy supplement into two components. CDER and CBER also would provide faster staff input on certain novel issues raised during development through two new types of meetings with sponsors.

PDUFA VII also aims to enhance CBER oversight of cell and gene therapies (CGT) by expanding staff and resources for its Office of Tissues & Advanced Therapies (OTAT). One goal is to increase opportunities for manufacturers to gain added FDA feedback on these complex products. CBER also would issue guidance on clinical trial design for CGTs, on capturing post-approval safety and efficacy data, and on information needed in post-approval studies for Regenerative Medicine Advanced Therapies (RMATs).

Advancing production

Another strategy for avoiding delays in the development and approval of innovative products aims to enhance the review of drug manufacturing quality and to advance innovative manufacturing technologies. The user fee program would expedite the development of chemistry, manufacturing, and controls (CMC) data for products likely to provide notable patient benefit, with a focus on science and risk-based approaches through a CMC Development & Readiness Pilot to accelerate assessment of manufacturing data for relevant complex products. Related to this, FDA will hold a public workshop to discuss best practices, barriers, and overall strategies for advancing innovative manufacturing.

FDA also aims to limit development delays related to manufacturing operations by reviewing and updating tools for inspecting biopharma facilities. Building on the increased use of alternative oversight approaches adopted during the pandemic, FDA will issue new guidance on the use of additional facility assessment tools, including plant records and reports from other regulatory authorities.

An important PDUFA initiative will support broader use of real-world evidence (RWE), particularly to meet post-approval study requirements. One new pilot will provide early advice on the acceptability of such data in added labeling claims and indications for approved products. Another is to advance the use of RWE by seeking agreement on what data, study designs and regulatory approaches can generate RWE that will support regulatory decisions. FDA and sponsors will work to address post-marketing required studies (PMRs) earlier in the pre-market setting and to establish processes for manufacturers to be released from PMR requirements deemed no longer necessary.

Related to this is added user fee support for incorporating more RWE into FDA’s Sentinel System to enhance post-market monitoring. Similarly, FDA seeks to advance its use of digital health technologies (DHTs) in drug development and review, building on broader agency plans for leveraging cloud technologies and related approaches through its Technology & Data Modernization Action Plan. CBER, in particular, will move to replace its older IT system as part of FDA’s IT modernization initiative.

Pharmaceutical and biotech manufacturers strongly support and are willing to pay considerable sums to fund the numerous demonstration projects, policy updates and added meetings designed to further speed new medicines to patients. The PDUFA “goal dates” for FDA to approve a pending NDA or BLA are carefully watched by all concerned players for indications that a new therapy is moving forward as expected or may run into delays.