Makary lauds user fees as FDA begins GDUFA IV reauthorization process

The US Food and Drug Administration (FDA) on Friday began the reauthorization process for the next iteration of the Generic Drug User Fee Amendments (GDUFA IV) with a public meeting to gather input from stakeholders ahead of negotiations with industry.

Most of FDA’s user fee programs, including those for prescription and generic drugs, medical devices, and biosimilars, are set to expire on 30 September 2027. The agency is required to engage in lengthy negotiations with industry to agree to commitment letters for the programs, which inform the legislation that Congress must pass to reauthorize the programs for another five years.

Historically, the reauthorization process has served as an opportunity for Congress to enact major FDA reform packages, including the recent FDA Reauthorization Act of 2017 and Food and Drug Omnibus Reform Act of 2022.

Despite recent comments from Health and Human Services Secretary Robert Kennedy Jr. critical of FDA’s user fee programs, both FDA officials and industry speakers stressed the importance of the GDUFA program in bringing affordable generic drugs to market and promoting innovation.

FDA Commissioner Marty Makary began the meeting with an anecdote about the pre-user fee times.

“They were not pretty,” Makary said. “There would be applications brought in by truck and dropped off – paper applications – giant boxes of applications were getting dropped off. One individual has said that when they had personally dropped [an application off] they could see an application from nearly a year ago still in the receiving area.”

Makary called out the “massive variability in the responsiveness of the FDA, burdened with a variable number of applications and uncertain adaptability of the funding, pre-user fees,” and stressed that “there’s a pretty important role for the user fees.”

Makary noted that “affordability of drugs is a massive priority” for President Donald Trump.

“Along with congressionally-appropriated funding, the support of the GDUFA user fees, paid by the generic drug industry, has helped the FDA to take a number of actions to increase better predictability and the timeliness of our assessment of these drug applications,” he said, adding that as of 31 May, FDA had approved or tentatively approved 2,465 abbreviated new drug applications under GDUFA III.

“That’s pretty remarkable,” Makary said.

Evolution of GDUFA

Iilun Murphy, director of the Office of Generic Drugs (OGD) within the Center for Drug Evaluation and Research (CDER), said that user fee revenue “has become increasingly vital to the [generic drug] program’s sustainability. The program has evolved from 45% user fee funding in 2013 to over 80% in 2024.”

Murphy also noted the enormous savings brought by generic drugs. “In 2023, the US healthcare system saved over $400 billion from the availability of generic medicines. For every dollar invested in the generic drug program, approximately $580 in savings are generated,” she said.

Going forward, Murphy said the agency wants to “accelerate approval processes through embracing novel technologies, in order to expand patient access many product categories.”

Robert Lionberger, director of the Office of Research and Standards within OGD, explained the importance of the generic drug science and research program, which was created under GDUFA.

“This is especially important for … complex generics. For these products, the normal things we do for simple tablets and capsules, looking at the blood levels after oral administration, just aren’t there, they aren’t available, they aren’t relevant. So, we have to do something else, and that something else has to be based on a strong scientific foundation,” he said.

When he first joined FDA more than 20 years ago, Lionberger said there were some types of products that couldn’t be made generic due to a lack of science. “You can’t have a generic for a peptide, you can’t have a generic for an inhaler, you can’t have a generic for a complex injectable. We just don’t know how to do these things, and over my career, we’ve really made so much progress on this, and I think the GDUFA science and research program has been essential to the development of this whole area of complex generics,” he said.

Lionberger noted that between 2004 and 2024, there has been a significant shift toward complex generics in ANDA submissions, with topical drugs, injectable solutions, and other complex generics accounting for a greater share of submissions. He also touted the approval of the first generic dry powder inhalers, long-acting injectables, and recombinant peptides within the last decade, which he attributed in part due to advancements in regulatory science supported by GDUFA.

Inspections

Ivy Sweeney, acting director of the office of Human and Animal Drug Inspectorate, noted that FDA conducts about 12,000 domestic and 3,000 foreign inspections each year, and that foreign inspections are typically preannounced. Sweeney said that logistical issues, obtaining visas, personnel safety, and jurisdiction- and sovereignty-related issues often necessitate pre-announced inspections in other countries.

In 2022, FDA began its foreign unannounced inspection pilot for inspections in India and China, Sweeney said. The agency also conducts some foreign unannounced inspections in other countries, though she said these have been “limited in nature.” In May, FDA announced it plans to expand the use of foreign unannounced inspections, though it is unclear how it will resolve some of the challenges that have limited its ability to do so in the past.

However, Sweeney noted that, “Over the last five years, the number of foreign unannounced drug inspections has been steadily increasing, in part due to the pilot.” In FY 2024, she said, about 89% of domestic were unannounced, and 12% of foreign drug inspections were unannounced.

Sweeney added that the foreign unannounced inspection pilot is about 56% complete as of June 2025, with staffing, logistics, and costs being the biggest challenges in running the pilot. Additionally, Sweeney said the agency experienced some slowdowns due to post-COVID issues in China, which have largely been resolved, and due to ongoing process changes internally and support staff limitations within CDER.

While FDA has said that no inspectors were laid off during the recent reduction in force (RIF), its inspection team has been impacted by other departures, early retirements, and a federal hiring freeze. Sweeney said her office has resumed hiring investigators.

“We are hopeful the importance of the investigative role to public safety will allow us to fully staff the drug inspectorate and address any losses of attrition we have seen this year,” she said.

Industry remarks

Giuseppe Randazzo, senior vice president of sciences and regulatory affairs for the Association for Accessible Medicines (AAM) said GDUFA has “played an essential role in strengthening the generic drug review process and helping to ensure that patients have timely access to safe, effective, and affordable medicines.”

“Continued investment in the generic drug program is critical in maintaining both access and affordability in the American healthcare system,” he added.

“Since the enactment of GDUFA I in 2012, the influx of resources from user fees has contributed to substantial progress in improving the efficiency and effectiveness of the generic drug review program,” Randazzo said, noting that the original backlog of more than 2,000 ANDAs has been eliminated and approval times have decreased significantly since the GDUFA program began.

Randazzo also praised the subsequent GDUFA programs for their impact on improving first-cycle approval rates.

“Structured opportunities for communication such as pre-submission meetings, mid-cycle review updates, post-complete response letter meetings, and post-warning letter meetings provide industry with critical information about FDA’s expectations so they can be addressed more quickly, with the goal of fewer assessment cycles, conserving both FDA and industry resources,” he said.

FDA

Makary lauds user fees as FDA begins GDUFA IV reauthorization process

Related topics

Recommended content

Welcome to the new RAPS Digital Experience