When is a REMS Necessary: FDA Explains in Draft Guidance

Regulatory NewsRegulatory News | 30 September 2016 |  By 

The draft guidance from the US Food and Drug Administration (FDA), unveiled earlier this month, tries to further explain the application of its risk evaluation and mitigation strategy (REMS) regulatory paradigm, which can delay generic drug competition.

A REMS, which may be a medication guide, a patient package insert, and/or a communication plan is a required risk management strategy to help FDA ensure that the benefits of a drug outweigh the risks.

FDA may require a more stringent version of a REMS, with elements to assure safe use (ETASU), which can include, for example, requirements that prescribers have particular training or experience, that patients using the drug are monitored, or that the drug be dispensed to patients with evidence or other documentation of safe use conditions.

Generic Drug Delays

But some of these requirements can actually end up delaying generic competition.

As the Generic Pharmaceutical Association (GPhA) said in a 2014 report: "Nearly 40 percent of new FDA approvals are subject to REMS, and brand manufacturers have also begun imposing distribution restrictions on non-REMS products. Government, consumers, and private payors are already missing out on sizeable health care savings from misuse of these programs. Specifically, REMS and non-REMS strategies to restrict access to brand drug samples represent lost savings on small-molecule drugs of at least $5.4 billion annually."

The way the system works means brand manufacturers can prevent generic competitors from accessing their products because of certain REMS elements so generic applicants cannot access what they need for bioequivalence testing and development.


In June, Sen. Patrick Leahy (D-VT) and 11 bipartisan colleagues introduced a bill to try to help generic drugmakers facing delay tactics be able to bring action in federal court for injunctive relief (i.e. to obtain samples needed to make the generic, or to enter court-supervised negotiations for a shared safety protocol). The bill, which has not been acted on since it was introduced, also would authorize judges to award damages to deter future delays.

Draft Guidance

The 14-page draft, known as “FDA’s Application of Statutory Factors in Determining When a REMS Is Necessary,” offers some explanation for how it tries to address the burden of the REMS program.

In the final section on patient access, FDA says it understands that REMS, particularly those with ETASU, "may impose some measure of burden on patients and/or health care providers. When considering this burden on patient access and the health care delivery system, FDA takes into account existing REMS elements for other drugs with similar risks and whether the REMS under consideration can be designed to be compatible with established medical drug distribution, procurement, and dispensing systems."

FDA also says it considers how patients access health care, including whether patients are in rural or underserved areas, and whether the REMS may impose access issues, as well as treatment interruption or delays, particularly for those with serious or life-threatening conditions.

Particularly "for a REMS that requires additional procedures and controls in the patient care process," FDA says it considers the "characteristics, experience, and size of the likely prescriber population; how the drug will likely be dispensed in the setting in which it will likely be used; and the patient population likely to use the drug.

“If an adverse event is determined to be drug-associated, FDA may determine that treatment with the drug unacceptably increases the frequency and/or severity of the adverse event in the patient population and that this risk needs to be mitigated through a REMS.”

For outpatient drugs, FDA says it considers the degree to which patients can be expected to reliably recognize symptoms as being associated with a drug and to take necessary actions to address adverse events.

“If, for example, FDA expects that a drug will likely be used in a setting where patient monitoring and certain medical equipment are not available, and believes that such measures are needed to mitigate the risks associated with the use of the drug, FDA may require a REMS with ETASU to limit use of the drug to settings in which these measures are available,” the draft says.

FDA also points to the example of a once-a-month oral dosage form of a drug that was previously only available as a daily oral dosage form and now may offer a qualitative benefit in terms of convenience to the patient and adherence to medication therapy, but may have a different risk profile (e.g., “a new risk associated with the new formulation, or with the longer half-life of the drug”) that makes it more likely that FDA would determine that a REMS is necessary.

Comments on the guidance are due 21 November 2016.


© 2023 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy