House User Fee Mark-Up: Few Tweaks, But Concerns About ALS And Accelerated Approval
Executive Summary
Clinical trial diversity, FDA hiring authority, and inactive ingredient disclosure provisions all get slight modifications. The bill glides through committee, but not without some complaints about agency performance.
Despite concerns from the brand industry, no major changes were made to provisions in the US Food and Drug Administration’s user fee reauthorization bill allowing generic drug sponsors more inactive ingredient information as it breezed to the House floor.
The bill would require the FDA to tell generic drug sponsors whether their products are qualitatively and quantitatively the same as the reference product, and if not, give the exact amount of the deviation of each inactive ingredient.
Some Republicans, as well as the Pharmaceutical Research and Manufacturers of America, suggested the provision could force the FDA to reveal confidential commercial information. (Also see "Inactive Ingredient Disclosure Expansion In House User Fee Bill Poised For Changes" - Pink Sheet, 11 May, 2022.)
House Energy and Commerce Committee Chair Frank Pallone, D-NJ, said during the 18 May full committee mark-up of the bill that he worked with GOP leaders to clarify the section before it was unanimously sent to the House floor. The updated bill added a reference to federal regulations, but the major disclosure mandate remained intact.
The Association for Accessible Medicines remains supportive of the provision. PhRMA indicated that its concerns remain and that the group is working with Congress to address them, suggesting the provision still may not be safe from further amendment.
Hiring Authority, Clinical Trial Diversity Adjustments Also Included
Another small addition to the bill would expand the FDA’s special hiring authority to include all products regulated by the FDA instead of only medical products. Lawmakers said the change is intended to help the agency recruit and retain staff for food regulation, particularly those working on infant formula, which is now in shortage. The provision also would require an agency-wide strategic workforce plan.
The 2016 21st Century Cures Act allowed the FDA to hire some new people at salaries outside the federal schedule in an effort to improve recruitment and retention. (Also see "US FDA Expands 'Cures' Hiring Authority To Fill Variety Of Open Positions" - Pink Sheet, 4 Nov, 2019.)
The updated bill also included minor revisions to the provision improving diversity in clinical trials. Like the draft bill, the amended version requires sponsors to submit a diversity action plan to the FDA “as soon as practicable.” The amendment specifies it should be no later than when the sponsor seeks feedback regarding a phase III or other pivotal study of the drug.
The amendment also revises the deadlines for trial diversity guidances. A final guidance must be issued no later than nine months after closing the comment period on the draft, three months longer than the original version of legislation had given the agency. (Also see "Clinical Trial Diversity: User Fee Bill Wants FDA’s Assessment Of Whether It Needs More Authority" - Pink Sheet, 4 May, 2022.)
An amendment adding pediatric study requirements for combination cancer drugs also was added. (See sidebar.)
Schakowsky Pushes For More FDA Flexibility With ALS Drugs
Rep. Jan Schakowsky, D-IL, raised concerns about access to amyotrophic lateral sclerosis (ALS) drugs during the mark-up, an issue not addressed in the bill, but still a source of pressure on the FDA.
Schakowsky said ALS advocates continue to see barriers to treatments even though they are safe and effective and the FDA has yet to use the regulatory flexibility for the products it promised in guidance.
“I urge the FDA use the 2019 guidelines and to move forward on ALS treatments that have made their safety and efficacy available,” she said.
The FDA guidance indicated that traditional study designs may not be necessary for potential ALS treatments, as well as that strategies could be used to minimize placebo exposure. (Also see "US FDA Reassures ALS Patients In Final Development Guidance" - Pink Sheet, 23 Sep, 2019.)
The FDA has been under pressure from advocates to approve ALS treatments faster. Stakeholders were vocal during a March advisory committee meeting on Amylyx Pharmaceuticals, Inc.’s AMX0035, arguing they should not have to wait for completion of a Phase III trial before product approval.
Most committee members disagreed, saying that there was a compelling unmet need, but efficacy had not been established. (Also see "Thoughts After Amylyx AMX0035 Committee: How Special Is ALS At FDA?" - Pink Sheet, 4 Apr, 2022.)
Schakowsky also said that while she welcomed the accelerated approval reforms included in the user fee bill, the program could be further strengthened by requiring advisory committee meetings for all products using the pathway. She warned that the FDA’s declining use of advisory committee meetings was dangerous.
“We have to see that these advisory committees are considered in more cases,” Schakowsky said.
Indeed, the few advisory committee that have been held this year, save COVID-19 and oncology products, seemed focused on providing sponsors a chance to argue against FDA rejection of an application. (Also see "US FDA Advisory Committees As The Court Of Appeals" - Pink Sheet, 9 May, 2022.) FDA officials are planning reforms. (Also see "US FDA’s Califf Expects Advisory Committee Reform Talk ‘About A Year From Now’" - Pink Sheet, 29 Apr, 2022.)
Schakowsky’s idea that advisory committees could improve accelerated approval process would seem to be challenged by the fact that FDA’s most controversial accelerated approval, Aduhelm, itself went before an advisory committee – with the agency ultimately ignoring the panel’s recommendation not to approval the Alzheimer’s product. (Also see "Aduhelm Approval Firestorm Raises Question: What Are US FDA Advisory Committees For, Anyway?" - Pink Sheet, 11 Jun, 2021.)
The House bill would streamline the accelerated approval pathway withdrawal process, and helps the FDA ensure post-approval studies are completed in a timely manner. (Also see "User Fee Bill’s Accelerated Approval Reform Provisions Watered Down, But Could Speed Withdrawals" - Pink Sheet, 4 May, 2022.)
Gliding Towards Enactment
Committee members praised each other throughout the mark-up for the bipartisan nature of its passage. In keeping with that approach, Rep. Brett Guthrie, R-KY, the ranking member of the Energy and Commerce Health Subcommittee, introduced the updated bill, rather than subcommittee chair Anna Eshoo, D-CA.
Lawmakers want the bill to move through Congress quickly, but the Senate draft user fee bill is significantly different – though the policy riders complement, rather than compete with, the House provisions, suggesting negotiations between the two chambers will likely not need to be that extensive. (Also see "Accelerated Approval, Clinical Trial Diversity Provisions Left Out Of Senate User Fee Bill" - Pink Sheet, 17 May, 2022.)
The Senate bill would clarify some aspects of first interchangeable exclusivity for biosimilars and create new regulations for cosmetics, dietary supplements and lab-developed tests. Those provisions were left out of the House bill. (Also see "Senate’s US FDA User Fee Bill Answers Biosimilar Interchangeable Exclusivity Questions" - Pink Sheet, 17 May, 2022.)
The prescription drug, generic drug, and biosimilar user fees will expire 30 September, but lawmakers want the programs reauthorized earlier to avoid forcing the FDA to notify employees whose salaries are supported by user fees that they could be laid off. Such a move could lower morale and cause some agency staff to leave for other positions.
Brenda Sandburg contributed to this report.