FDA Risk Evaluation and Mitigation Strategies (REMS): Description and Effect on Generic Drug Development

Summary

The Food and Drug Administration (FDA) regulates the safety and effectiveness of drug products sold in the United States. The statutory standard for FDA approval is that a drug is safe and effective for its intended use. FDA’s determination that a drug is safe does not signify an absence of risk but rather that the drug’s clinical benefits outweigh its known and potential risks.

For most drugs, FDA has generally considered routine risk minimization measures to be sufficient; for example, updated labeling based on new information from postmarket surveillance. In certain cases, however, the agency has recommended or required additional measures to minimize drug risk. Early risk management programs at FDA, voluntarily instituted by manufacturers, included elements such as education for patients and providers, and restrictions on distribution. In 2007, the FDA Amendments Act (FDAAA) expanded the risk management authority of FDA, authorizing the agency to require for certain drugs, under specified conditions, risk evaluation and mitigation strategies (REMS). REMS is a required risk management plan that uses risk mitigation strategies beyond FDA-approved professional labeling. As part of a REMS, a drug manufacturer may be required to provide certain information to patients (e.g., a medication guide) and health care providers (e.g., a communication plan) or to impose restriction on a drug’s sale and distribution via one or more “Elements to Assure Safe Use” (ETASU).

A REMS-restricted distribution program controls the chain of supply so that the drugs are provided only to patients with prescriptions from authorized physicians or pharmacies under specified conditions. Although the law prohibits the holder of an approved new drug or biologics license application (i.e., the brand company) from using ETASU “to block or delay approval of an application,” FDA, the Federal Trade Commission, generic drug manufacturers, and some Members of Congress have expressed concern that brand companies are using REMS to prevent or delay generic drugs from entering the market. A 2014 study sponsored by the Generic Pharmaceutical Association (GPhA; recently renamed as the Association for Affordable Medicines [AAM]) estimated that misuse of REMS and other restricted distribution programs costs the United States $5.4 billion annually, with the federal government bearing a third of this burden. REMS have come up in the context of user fee reauthorization, with the Director of the Center for Drug Evaluation and Research at FDA testifying that some brand drug manufacturers have used REMS and distribution restrictions to delay or refuse to sell quantities of a brand-name drug to generic product developers, potentially delaying consumer access to less expensive generic drugs. Without the brand-name drug against which to test bioequivalence of the generic product, the generic product developer cannot complete the required application to FDA. Others argue that REMS are rare, and that FDA only requires REMS with restricted distribution for drugs that would otherwise not be allowed on the market due to safety risks.

In the 114th Congress, two bills were introduced to keep brand companies from using REMS to prevent or delay generic drugs from entering the market: the Fair Access for Safe and Timely Generics Act of 2015 (or the FAST Generics Act of 2015 [H.R. 2841]) and the Creating and Restoring Equal Access to Equivalent Samples Act of 2016 (or the CREATES Act of 2016 [S. 3056]). As of the date of this report, neither of these two bills has been reintroduced in the 115th Congress. However, in the 115th Congress, two bills have been introduced that address generic drug development: the Lower Drug Costs through Competition Act (H.R. 749) and the Increasing Competition in Pharmaceuticals Act (S. 297). Both bills contain a provision titled “Study on REMS,” which would require GAO to conduct a study on REMS and its implementation; the study would examine, among other things, the “burden associated with REMS,” including on generic drug manufacturers.”