PDUFA VII commitment letter: RWE, rare diseases see renewed attention

Regulatory NewsRegulatory News | 23 August 2021 |  By 

The US Food and Drug Administration (FDA) on Monday released the commitment letter outlining performance goals and procedures for the upcoming reauthorization of the Prescription Drug User Fee Amendments for FYs 2023-2027 (PDUFA VII).
The agency also announced a public meeting on the reauthorization, scheduled for the afternoon of 28 September. Registration for the meeting, which will be held virtually, is free.
Many of the concepts and programs the agency discussed with the pharmaceutical industry during the months of reauthorization negotiations have made it into the newly published commitment letter. (RELATED: PDUFA VII negotiations wind up; CMC, IT modernization issues resolved, Regulatory Focus 23 March 2021)
New enhancements for this sixth PDUFA reauthorization, broadly, address product review support for FDA’s Center for Biologics Evaluation and Research (CBR), premarket review and postmarketing evaluation, development of new regulatory decision tools, digital health and informatics, financial issues, and chemistry, manufacturing and controls (CMC) topics.
Rare disease support, split review program get green lights
A pilot program to identify novel endpoints for rare diseases that was discussed in January 2021 is fleshed out in the commitment letter. “Though difficult to establish, well-developed efficacy endpoints, especially those that could apply to other rare diseases with similar manifestations, drive the general advancement of rare disease drug development,” according to FDA’s Federal Register announcement of the upcoming meeting. (RELATED: Rare diseases, STAR expansion considered in PDUFA VII premarket negotiations, Regulatory Focus 16 April 2021)
FDA’s proposed pilot program would support “efficacy endpoint development for drugs that treat rare diseases by offering additional engagement opportunities with the Agency to sponsors of development programs that meet specific criteria.”
FDA is also proposing an increase in staffing to meet the rapid expansion of submissions for cell and gene therapy products. Increasing staff capacity will overcome existing resource limitations, allowing staff to spend additional time on meetings and submission reviews including those with breakthrough or regenerative medicine advanced therapy designations, expand stakeholder outreach, invest in new policy and guidance, and facilitate development and use of regulatory tools and scientific technologies,” wrote the agency.
A pilot of the Split Real-Time Application Review (STAR) program is proposed for certain efficacy supplements. Splitting the application into two components submitted about 2 months apaart should help shorten turnaround from the date the submission is completed to FDA’s action date.
New meeting types; Combo product updates
Two new meeting types are also floated in the commitment letter. A Type D meeting would allow discussion of up to two focused topics, giving the sponsor quicker feedback on sticking points. The proposed INTERACT meeting would address IND situations “where a sponsor is facing a novel, challenging issue that might otherwise delay progress of the product towards entry into the clinic in the absence of this early FDA input.”
The commitment letter would “generally” include allergenic extract products into the PDUFA program, giving a 1-year runway for this action. The agency proposes that if these products are licensed after 1 October 2022, they should be included in the user fee program.
Combination products are an area where regulatory science may lag behind the drug-device and biologics-device products that industry is developing. To help with the review of human factors validation studies — critical to ensuring a finished combination product will be safe and effective — the commitment letter proposes that FDA update its human factor validation study protocols.
In another move that tracks with recent trends in drug and device development, FDA is proposing a new pilot program to “improve the quality and acceptability” of real-world evidence-based strategies to support intended new labeling claims such as new indications; the pilot would also support the development of strategies to use real-world evidence in post-approval settings. These proposed actions help meet FDA’s obligations under Section 3022 of the 21st Century Cures Act.
Sentinel initiative gets a refresh
PDUFA VII user fees will also go toward support of such drug safety activities as the modernization of FDA’s Sentinel initiative, to include incorporating more real-world evidence into Sentinel’s analytic strategies.
“Given the accelerated development of certain human drug products, FDA also proposes a new pilot program to facilitate the expedited CMC development of products under an IND based upon the anticipated clinical benefit of earlier patient access to products,” according to the FDA notice.
A new pre-approval review of post-marketing requirements is proposed in the commitment letter, and sponsors “would also have the opportunity to request a review of existing PMRs for release,” as well.
Review goal dates updated
In the commitment letter, FDA also lays out the time frames within which it will act on 90% of new drug application (NDA) and biologics license application (BLA) submissions and resubmissions, setting deadlines for each type of submission.
For standard new molecular entity (NME) NDA and BLA submissions, the agency is committing to reviewing and acting on 90% of submissions within 10 months of the 60-day submission filing date. For priority NME submissions, the commitment letter trims the time frame to 6 months.
The time frames are also 10 months and 6 months for agency action on standard and priority non-NME NDAs, respectively, and for standard and priority efficacy supplements. FDA commits to acting on at least 90% of Class 1 resubmissions of original applications within 2 months of receipt and extends the time frame to 6 months for Class 2 resubmissions.
The commitment letter also outlines time frames for efficacy supplements and manufacturing supplements, and addresses the review of performance goal extensions.
Editor’s note: Focus will feature more analysis of the PDUFA VII commitment letter, including the proposed fee breakdown, later this week.
PDUFA VII commitment letter
Federal Register Notice


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