When a REMS is Necessary: FDA Finalizes Guidance

Regulatory NewsRegulatory News | 04 April 2019 |  By 

The US Food and Drug Administration (FDA) on Thursday finalized guidance from 2016 detailing the factors that the agency uses to determine whether a risk evaluation and mitigation strategy (REMS) is necessary for a drug.

As defined by the guidance, a REMS is a required risk management plan that can include one or more elements to ensure that the benefits of a drug outweigh its risks. Such elements can include a medication guide, a package insert or a communication plan

And though the use of a REMS is decided on a case-by-case basis, the 10-page guidance explains how the Food and Drug Administration Amendments Act (FDAAA) requires FDA to consider the following six factors in deciding whether to require a REMS: 
  • “The seriousness of any known or potential adverse events that may be related to the drug and the background incidence of such events in the population likely to use the drug;
  • The expected benefit of the drug with respect to the disease or condition;
  • The seriousness of the disease or condition that is to be treated with the drug;
  • Whether the drug is a new molecular entity;
  • The expected or actual duration of treatment with the drug; and
  • The estimated size of the population likely to use the drug.”
“All six factors are considered together to inform FDA’s REMS decision making process and no single factor is determinative as to whether a REMS is necessary. The relative importance or weight of each factor is a case specific inquiry,” the guidance says.

The guidance also delves into each of the six factors, as well as additional considerations including the potential burden on the health care delivery system and patient access.

In terms of changes between the draft and final versions, FDA received six comments on the draft guidance seeking further information on how FDA weighs the six factors when determining if a REMS is necessary, minor clarifying comments on how the six factors are applied and comments suggesting that FDA should expand on which REMS elements or tools should be used when it is determined that a REMS is necessary.

“Clarifying edits were made to address the comments as appropriate. Additionally, edits were made to streamline the guidance, extraneous background information was removed, and the title was modified for clarity,” the agency said.

Other REMS Draft Guidance Comments

In addition to the final guidance on determining when a REMS is necessary, industry groups PhRMA and the Association for Accessible Medicines (AAM), as well as several biopharma companies, are seeking changes to FDA draft guidance on survey methodologies to assess REMS goals.

The 23-page draft guidance provides recommendations on conducting REMS assessment surveys to evaluate patient or health care provider knowledge of REMS-related information, such as the serious risks and safe use of a medication. 

In its comments, PhRMA, while commending FDA for the guidance, requests that it include additional information for the use of surveys in assessing attitudes related to risk minimization practices. PhRMA also said it believes that the draft guidance’s recommendations regarding eligibility requirements for survey participants are too restrictive.

AAM took issue with the fact that the recommendations in the guidance are easier to implement in a brand REMS context than for single, shared system REMS or separate shared REMS that have multiple abbreviated new drug applicant (ANDA) participants. “For example, sharing of safety data can get very complex when the data has to be pooled among multiple sponsors within a class of products. An example, the Transmucosal Immediate-Release Fentanyl (TIRF) REMS encountered this very issue,” AAM said.

Pfizer, meanwhile, calls on FDA to provide sponsors with guidance on when a survey should be conducted, among other requests.

And Novartis took issue with FDA’s suggestion to include open-ended questions in the survey. “This type of question is challenging to manage for sponsors due to adverse event monitoring and reporting requirements,” the company said.

REMS: FDA’s Application of Statutory Factors in Determining When a REMS Is Necessary: Guidance for Industry


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Tags: FDAAA, guidance, REMS

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