GAO to FDA: Publish Plans to Issue or Revise Guidance on Complex Generic Drugs
The US Government Accountability Office (GAO) on Tuesday called on the US Food and Drug Administration (FDA) to announce plans to issue or revise guidance for complex generic drugs and FDA said it agrees with the recommendation and is working to do just that.
The 50-page GAO report comes as FDA has sought to improve the way it reviews and approves these complex generic drugs, which can have a complex formulation, active ingredient, route of delivery, dosage form or be used in combination with a device.
But according to GAO, some companies have criticized FDA’s progress in bringing generic versions of these complex drugs to market.
"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 [nonbiological complex drugs]," GAO said. "Further, guidance for some NBCDs was revised numerous times without any advance notification to industry, according to representatives of generic drug sponsors."
GAO noted that FDA, stakeholders and the literature it reviewed said that there are difficulties in establishing that the brand and generic active ingredients are equivalent if the drug’s structure and other properties cannot be fully characterized.
But there was disagreement over the extent of this challenge.
"Though the majority of stakeholders agreed demonstrating pharmaceutical equivalence is a challenge, representatives of three stakeholder groups (brand, generic, and external expert group) stated it is challenging, but only in certain circumstances," GAO said.
In addition, stakeholders told GAO that there are tools available to characterize drugs, though, "there is disagreement as to what critical quality attributes—those essential to a drug’s performance and safety—should be measured in order to demonstrate pharmaceutical equivalence."
GAO also found that FDA approved generic versions of five of 28 drugs identified as complex generics prior to fiscal year 2017 and considered a range of data when assessing equivalence to the relevant brand-name drug.
In its defense, FDA noted the publication of 1,541 product-specific guidances for generic drugs since 2007 and that it’s undertaking an economic analysis to evaluate the impact of its Drug Competition Action plan.
"Looking forward, we’re working to develop additional guidance for industry with the aim of clarifying 'sameness' requirements for ANDAs [abbreviated new drug applications]," FDA Commissioner Scott Gottlieb said in a statement. "We believe that guidance in this area may be particularly helpful for complex generics; including specific guidance on drug-device combination products."