GAO Report: Reference and Generic Sponsors Look Differently at FDA REMS Enforcement

Perhaps not surprisingly, officials from generic drug companies, reference product companies, the FDA, and the Federal Trade Commission (FTC) have different opinions about the usefulness of various actions the federal government has taken to prevent abuses of risk evaluation and mitigation strategies (REMS), according to a recently released Government Accounting Office (GAO) report.

According to the FDA and the FTC, drugs with and without REMS have been the subject of practices that can delay or prevent generic drug development and marketing. Such practices include limiting access to samples of reference standard drugs that generic companies need and delaying negotiations for creating required shared systems.

GAO was asked to review drugs subject to REMS and drug companies’ experience with these practices, and report on the FDA and FTC’s efforts to address these practices, as well as industry stakeholders’ views regarding these efforts.

The FDA has the authority to act concerning drugs with serious safety concerns to ensure that a drug’s benefits outweigh its risks. As of March 18, 2019, FDA approved 74 active REMS that cover 523 drugs; 143 are reference standard drugs, which are needed by generic drug companies to conduct bioequivalence testing. Of these 143, 64 have at least 1 approved generic that is also subject to REMS. Ten of the REMS are shared systems that allow healthcare providers to obtain information from multiple companies on a drug’s risks and satisfy other administrative requirements through a single system.

The FDA has taken a variety of actions to address practices by reference product firms that may limit access to their samples, but stakeholders interviewed by the GAO had differing opinions about how well these actions work in practice.

In 2014, the FDA issued draft guidance on how generic companies could obtain a letter stating that the agency would not consider it a REMS violation to provide reference standard drug samples to the generic company requesting the letter. The FDA does not issue such letters for drugs without REMS.

However, 3 of the 4 generic companies GAO interviewed said these letters were not useful because there is no mandate requiring the sharing of samples. On the other side, officials from 3 of 5 reference drug companies said the letters addressed their safety concerns about providing samples to generic companies.

In February 2019, the FDA published a list of drug companies whose reference drugs were the subject of access inquires made to the FDA by generic drug companies. One of the 4 generic companies GAO spoke with said the FDA’s list was helpful, and 1 reference drug company said it was unclear why it was included on the list.

FTC has reviewed inquiries it received from the FDA and generic companies and has filed amicus briefs in 2 cases involving drugs with REMS. But the agency has not brought a case charging a drug company with violating federal antitrust law for refusing to provide samples.

The FDA has also issued waivers and related guidance that allowed generic companies to develop a separate but comparable REMS system in order to address practices that may stall negotiations between 2 manufacturers for creating required shared systems.

In interviews with the GAO, officials from 1 generic company said that the respective reference drug companies would not meet with them to negotiate the development of a required shared system; officials from another generic company said the negotiation process with the reference product firm company lasted almost 2 years.

Meanwhile, 4 of 5 reference drug officials interviewed had a different view; 3 of the 4 said that developing a shared system is difficult, challenging, and complex.