Open FDA Plans for Nonbiological Complex Drugs: GAO
The Government Accountability Office (GAO) says FDA should announce its plans to issue and revise product-specific guidance for drugs that are nonbiological and complex. FDA agreed with the recommendation that was included in a GAO report assessing the FDA process for reviewing generic versions of nonbiological complex drugs (NBCDs).
The report (1) identifies the scientific challenges the review of generic versions of NBCDs may present and (2) identifies and evaluates steps FDA has taken that may help address the challenges related to the review of generic NBCDs.
In the process, GAO says it identified several steps that have been taken that may help address the challenges associated with reviews to determine equivalence of generic NBCDs to their branded counterparts. “However,” it says, “stakeholders disagreed about whether these steps have been sufficient. For example, to facilitate the entry of generic drugs on the market, including NBCDs, FDA issued product-specific guidance documents to industry, providing recommendations on how to demonstrate equivalence to certain products. While some stakeholders cited product-specific guidance as helpful, representatives of four brand sponsors said the guidance does not adequately address the scientific complexities of NBCDs. Further, guidance for NBCDs was revised numerous times without any advance notification to industry, according to representatives of generic drug sponsors.”
GAO says the lack of advance communication on guidance issuance and subsequent revisions can create setbacks for generic drug sponsors. For example, it says, it may take considerable time, effort, and other resources for sponsors to update their applications to market a generic drug in response to unexpected changes in guidance. And this could delay or prevent the entry of some generics to the market.
Responding to the GAO report. FDA commissioner Scott Gottlieb says the agency agrees with the GAO recommendation and is actively working to accomplish it through new policies that are already underway. Such efforts are part of his new Drug Competition Action Plan, Gottlieb says, and steps taken under the GDUFA 2 reauthorization.
He says the agency will focus resources specifically intended to aid generic drug developers of complex products, including efforts as part of the pre-ANDA program through which specialized advice can be provided on the generic drug development pathway and timely development of new product-specific guidance for complex generics.
The agency is also working to develop additional guidance for industry with the aim of clarifying “sameness” requirements for ANDAs, Gottlieb says. “We believe that guidance in this area may be particularly helpful for complex generics, including specific guidance on drug-device combination products,” he says. “The specific request outlined in GAO’s current report is that FDA publicly announce its plans to issue or revise such guidances for complex generics. FDA is actively working to do just that. We believe that increased transparency on product-specific requirements gives manufacturers seeking to develop generic copies of complex drugs a better opportunity to efficiently allocate resources.”
Meanwhile, bipartisan leaders of the House Energy and Commerce Committee’s subcommittee on health said they were encouraged by GAO’s assertion that FDA has taken steps to address the challenges of approving generic versions of nonbiologic complex drugs.
“We hope moving forward that FDA will continue to offer the generic industry additional guidance on complex products,” said Reps. Michael Burgess (R-TX) and Gene Green (D-TX), “and will begin to consistently share information about its plans to issue and revise guidance with the public. GAO’s recommendations deserve thoughtful consideration; a transparent and consistent regulatory environment is crucial to ensure patients will have access to a competitive market of safe and effective products.”