FDA kicks off GDUFA III reauthorization process
In a public meeting held via webcast, officials of the FDA kicked off the process for reauthorizing the Generic Drug User Fee Amendments (GDUFA). The meeting, which included presentations by members of industry and the public, is the first of many that will shape the agency’s third GDUFA program.
GDUFA II, authorized in 2017, expires at the end of September 2022. The GDUFA II agreement had two major objectives in speeding access to generic drugs, said Maryll Toufanian, director of the Office of Generic Drug Policy at CDER’s Office of Generic Drugs (OGD) at the meeting. The first was to reduce the number of review cycles to approval, and the second was to increase the number of generic drugs approved while maintaining safety and quality standards.
To that end, GDUFA II included a new pre-abbreviated new drug application (ANDA) program designed to smooth development and review of ANDAs for complex generics; new review goals were also set for priority ANDA submissions. Other updates in GDUFA II included more accountability and reporting requirements, a modification of the user fee structure, and provisions for small business relief.
GDUFA II by the numbers
Diving into the “numbers behind the numbers,” said Toufanian, reveals that the total number of communications with applicants exceeds 20,000. In all, 264 pre-ANDA program meetings have been held, with 113 pre-ANDA requests received in FY 2019 alone. “Use of the pre-ANDA meeting program continues to grow,” said Robert Lionberger, PhD, director of the Office of Research and Standards at OGD, adding that FDA has exceeded its GDUFA II goals in this area.
Sally Choe, PhD, OGD Director, noted on FDA’s website that product-specific guidances can increase the efficiency and cost-effectiveness of generic drug development “by identifying the most appropriate methodology and evidence needed to support a specific generic drug’s comparison with the brand name drug during FDA’s assessment process, which can streamline product approvals.” Over 1,900 such product-specific guidances have been published by FDA as of June 2020.
During GDUFA II, said Toufanian, OGD received 8,450 items of controlled correspondence. Lionberger noted that about 40% of controlled correspondence regards complex products, and about 7% of controlled correspondence regards “complex controls;” with a goal date of 120 rather than 60 days.
Toufanian characterized GDUFA II as having achieved “a healthy generic program” that has achieved “the most predictable and transparent assessment process to date.” Still, she said, “There is still work to be done to further enhance efficiency, transparency, and gain more first-cycle approvals” in the next cycle of GDUFA authorization.
A key area of focus for OGD will be the growing arena of complex generic drug products which, said Michael Kopcha, director of CDER’s Office of Pharmaceutical Quality, “are harder to ‘genericize’ and often have less market competition.” Lionberger pointed out that it is key to continue moving complex generic drug applications through the system, with an eye to keeping pace with product developments that add complexity. “Pre-ANDA meetings support innovative approaches to bioequivalence that can accelerate access to complex generics,” he said.
Industry seeks certainty – with flexibility
When it came time for industry presentations, Scott Tomsky, Teva’s vice president of regulatory affairs and genetics for North America, found ample room for improvement in the generics approval process. In GDUFA III, FDA needs to take additional steps to increase the number of first-cycle approvals, especially for complex generics. Tomsky cited a 2019 Government Accountability Office report finding a 12% average rate of first-cycle approvals, with “most applications taking at least three review cycles to reach approval.”
“One of the biggest challenges Teva still encounters is with FDA’s regulatory uncertainty; it’s pretty debilitating,” said Tomsky. “This has a tremendous impact on Teva forecasts and business decisions related to planning for launch as well as product selection.
“Why is it this way? Does it have to be? Complex generics may be more akin to their new drug counterparts in the type of review required. It’s notable that the FDA office of new drugs is able to approve over 90% of applications even for new molecular entities on the first round of review.”
Tomsky suggested that the goal date should be set from the date of filing, rather from the submission date for complex generic applications, as is the case with new molecular entities. That, he said, “would provide the agency a bit more time to do a substantive review.”
Adjustments should have the effect of keeping an application in play even if the goal date is missed: “This would allow the Office of Generic Drugs the flexibility to miss a goal date when they feel they can work toward an approval. It can only work if sponsors have more insight into their review process, and confidence and clarity to where an application review stands if the goal date is missed. The application cannot fall into oblivion, as often is the case today when the goal date is missed,” said Tomsky.
Tomsky called the creation of the pre-ANDA process “one of the best results of GDUFA II,” since it gives sponsors early insight into agency thinking. In contrast, mid-cycle review meetings, he said, “are currently a lost opportunity” that constitute a poor use of FDA and industry resources and a “lost opportunity to reduce the likelihood or need for a subsequent review cycle.” according to Tomsky, the meetings currently don’t have the back-and-forth exchange that was envisioned.
Throughout, Tomsky asked for more flexibility from the agency and a more certain and reliable path to first-cycle approval. “My commercial colleagues walk a tightrope of possibility which is made even more treacherous by the constant shifting wind of FDA regulation for generic medicines,” he said. “You often hear FDA asking why the number of launches doesn’t correlate with the number of approvals. When the approval process drags on or becomes too unpredictable to support the business case, the product won’t launch. It’s that simple.”
GDUFA negotiation meetings are not open for public viewing or attendance, though publicly posted meeting minutes are made available after stakeholder meetings, Kopcha noted. “After negotiations with the generic drug industry, FDA will send the agreed-upon recommendations to Congress, and Congress will hold hearings that include testimony from FDA experts, the generic drug industry, and other interested parties,” he said.
RAPS: First published in Regulatory Focus™ by the Regulatory Affairs Professionals Society, the largest global organization of and for those involved with the regulation of healthcare products. Click here for more information.