Stakeholders Seek Increased User Fee Support for Biologics

A surge in applications to test and develop new cellular and gene therapies is overwhelming staff at FDA’s Center for Biologics Evaluation and Research (CBER) and prompting calls from manufacturers and research organizations to increase funding for these programs. At the public meeting to kick off negotiations for renewing the Prescription Drug User Fee Act (PDUFA) before the current program expires in September 2022, patient advocates, research experts, and industry similarly called for more user fee revenues to support CBER programs to advance these innovative therapies.

User fee payments now fund more than 70% of the cost of FDA’s new drug review program, up from about 7% of its budget in 1993. Manufacturers pay more than $1 billion a year, primarily through annual program fees. The Center for Drug Evaluation and Research (CDER) is slated to receive $680 million this year to support its new drug review program, while CBER gets $135 million; smaller amounts fund the review of medical devices combined with drugs and inspections by FDA’s field force, while a hefty portion supports a wide range of agency activities, services, and facilities.

The smaller amount for CBER reflects the relatively few biologics license applications (BLAs) it has reviewed under PDUFA-only three applications by the Office of Tissues and Advanced Therapies (OTAT) in 2019, compared to more than 100 new drug applications (NDAs) and BLAs vetted by CDER (PDUFA does not support CBER regulation of vaccines and blood products). But now CBER is overseeing more than 900 active investigational new drug applications (INDs) for cellular and gene therapies, with some 200 new submissions anticipated this year. In addition, OTAT manages FDA’s high-profile program for vetting regenerative medicines advanced therapies (RMATs) and awarding the RMAT designation to products meeting set standards.

In June, OTAT director Wilson Bryan reported at the Biotechnology Innovation Organization’s (BIO) digital annual conference a “huge escalation” in his office’s workload prior to the pandemic, with a tripling of INDs for gene therapies in the past three years. And while research in these new treatments has slowed in recent months, that has been supplanted, he noted, by more interest in using cellular therapies and intravenous immunoglobulin to treat COVID-19.

CBER Director Peter Marks similarly noted at BIO that CBER was meeting user fee goal dates overall, despite the need to shift personnel and resources to deal with the pandemic. Some early meetings intended to assist sponsors in designing research programs for new therapies had to be delayed or cancelled, he acknowledged, but most regulatory activities were moving forward.

At the PDUFA public meeting, Rachel Sher, vice-president of the National Organization for Rare Disorders (NORD), noted that CBER officials expect to be called on to review and approve some 40–60 innovative gene and tissue-based therapies over the next 10 years. Jeff Allen, president of Friends of Cancer Research, similarly called for added support for the review of cell and gene therapies, as did Robert Falb, head of the Alliance for Regenerative Medicine. Cartier Esham, executive vice president of BIO, cited the greater demand on CBER personnel and requests for added meetings with sponsors in backing increased resources for CBER. The funds also would help clarify expedited pathways and expand standards for advanced manufacturing processes and technologies for gene therapies.

Seeking agreement

The July PDUFA public meeting kicks off a year-long process for FDA and industry to negotiate program goals and fee structure for PDUFA VII well before the current program expires. FDA also will regularly meet with representatives of consumer and patient organizations, research entities, and healthcare organizations to hear their concerns and priorities for changes in current PDUFA programs and new fee-supported initiatives. The aim is to present Congress with a user fee agreement by the middle of next year so that the legislators can write and approve authorizing legislation by early 2022 and avoid any lapse in FDA user fee collections.

A main goal for both CDER and CBER is to recruit and train additional staff to assess its wide array of innovative products, building on provisions in the current PDUFA program for filling more than 200 agency positions over five years and for retaining experts at the agency. FDA has found it very difficult to expand staff in a very tight job market and through the agency’s cumbersome hiring process. The initial hiring goals for CBER were one-fifth that for CDER, but few new recruits have come on board.

Stakeholders at the public meeting also supported broader use of real-world evidence and innovative clinical trial methods to advance new therapies and for FDA to expand electronic communications systems in research and regulatory programs. A prominent theme is for the agency to incorporate innovations and changes adopted for dealing with the COVID-19 pandemic into ongoing research policies and regulatory programs. Manufacturers and other stakeholders have until August 23 to submit comments on the process to a public docket, which will provide the basis for the ongoing discussions.