Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications

Status: Draft

Date: September 2009

Target Audience: Industry sponsors and applicants

Laws Referenced:

  • Section 505-1 of the Federal Food, Drug, and Cosmetic Act (FDCA)
  • Section 505(b) of the FDCA
  • Section 505(j) of FDCA
  • Section 351 of the Public Health Service Act (PHS Act)
  • Title IX, Subtitle A, section 901 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) (Public Law 110-85)
  • Sections 909(b)(1) through 909(b)(3) of FDAAA
  • Title 21 of the Code of Federal Regulations (21 CFR), sections 314.520 and 601.42
  • 21 CFR, part 208


Some drug or biological products, despite having a product label that describes the benefits and risks, may require additional information that describes how to use the product in such a way that the risks are minimized. This guidance describes the purpose of risk evaluation and mitigation strategy (REMS), a plan that describes what a sponsor is doing to provide current safety-related information that contributes to the benefit portion of the risk-benefit ratio (ie, the drug or biological product has more benefits than risks). The guidance also describes what to include in a REMS and recommended sponsor-FDA communication strategies so that the FDA has current safety-related information for drug or biological products that support the risk-benefit ratio.


Under a 2007 statute of FDAAA, the FDA can require a drug sponsor to submit a REMS for certain drug or biological products in situations where the FDA determines that additional supporting information is necessary for appropriate use of the drug. Examples of such information include: instructions to the pharmacist, recommending a particular lab test result before starting the drug or biological treatment, or providing additional risk-related information to healthcare professionals (eg, information sheets) so they can make an informed decision about treatment. The FDA also has the authority to require a sponsor to revise the label and/or the REMS based on the information provided in it. In addition, the FDA may require a sponsor to show how it is achieving its objectives; for example, a sponsor may need to evaluate the effectiveness of its information sheet that encourages safe use of the product by monitoring how many healthcare professionals are using the information sheet.


A REMS generally includes the following elements, although some may not be applicable:

  • Product name and information
  • Objectives
  • A schedule that describes when assessments are submitted to the FDA
  • Medication guide
  • Patient package insert
  • Recommendations for healthcare providers in using the drug or biological product as intended to minimize risks
  • Other information that encourages appropriate use of the drug or biological product in order to minimize risk (elements to assure safe use)

A REMS template is found on the FDA Website.

Parts of a REMS:

A REMS is subdivided into 2 parts – a proposed REMS (what the sponsor promises to do) and a REMS supporting document (background and information that supports the proposed REMS).

The first type is important because the FDA will enforce the content contained in the proposed REMS. Failure to provide a REMS when required by the FDA has consequences, such as financial penalties, having the drug or biological product labeled misbranded, and/or prohibiting shipment across state lines.


This statute from FDAAA fits in nicely with the FDA’s goal of making drug or biological product information more accessible to the public. It is also another way of periodically monitoring safety. The use of REMS may prevent a drug or biological product that is beneficial to a small subset of the population from being withdrawn because of adverse effects.

For more information on this issue, contact the Kulkarni Law Firm.