Risk Evaluation and Mitigation Strategy (REMS)

The FDA is taking action to protect patients from harm caused by high risk drugs by requiring Risk Evaluation and Mitigation Strategies (REMS) from drug manufacturers. While REMS applies to all drugs that have a high risk, opioids are at the center of a public health crisis. REMS represents a careful balance between continued access to these required medications and steps implemented to reduce risks.

Title IX, Subtitle A, Section 901 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) authorizes the FDA to require the submission of a REMS for an approved drug if the FDA becomes aware of new safety information and determines that such a strategy is necessary to ensure that the benefits of the drug outweigh the risks. This provision took effect on March 25, 2008.

A company’s REMS plan must contain a Medication Guide to assure safe use. If the FDA determines that the Medication Guide is not sufficient to mitigate the serious risks, then the REMS plan must also include other risk-management tools. Training is one of these tools. Training must be conducted by accredited, independent, continuing medical-education providers, to the extent practicable. Prescribers participating in the training must complete a knowledge-assessment in order to receive a certificate. The sponsor of the training (the drug manufacturer) must maintain a list of the prescribers who have obtained certification; provide the list to those needing to verify that a prescriber has obtained the required certification; and retrain and recertify the prescribers periodically, at a specified interval. The manufacturer’s REMS must ensure that the medication is only dispensed by specially certified pharmacies, practitioners, or healthcare settings (e.g., hospitals), and that the drug is dispensed to patients with documentation of safe use. The sponsor must also provide prescribers with information that can be used to educate patients in safe use, storage and disposal of high risk drugs.

In addition, the REMS must include an Implementation System to monitor and evaluate execution of the plan. The Implementation System should address any findings of noncompliance or findings that suggest an increase in risk. The Implementation System should include:

  • A database of all enrolled entities, including prescribers, pharmacies, practitioners, healthcare settings, and patients.
  • A plan to ensure that only certified pharmacies, practitioners and healthcare settings distribute and dispense the medication and that only certified prescribers are prescribing.
  • A plan to monitor and conduct audits of certified pharmacies, practitioners, and healthcare settings to ensure that they dispense the medication only after documenting safe-use conditions.
  • Post-marketing surveillance: o Pharmacovigilance—adverse events o Collection and analysis of surveillance data
  • Surveillance data o High-volume prescribers o Identity and profile of prescribers o Prescription-monitoring programs to identify potential abuse
  • Monitoring and intervention o Distribution chain o Monitoring of patients to identify misuse or abuse
  • Implementation of an Expert Advisory Group

On May 16, 2011, the FDA met with members of the Industry Working Group (IWG) and other sponsors of long-acting and extended-release opioids. Their agenda included:

  • Prescriber training
  • Medication Guides
  • REMS assessment plans
  • Administrative requirements

When the FDA requires REMS, manufacturers need to ask themselves:

  • What precisely does the FDA expect?
  • What are the best practices that will help ensure that our REMS program is both effective and compliant—from risk identification to implementation and communication?

Answering these two questions is the first step in developing an effective REMS. Whether executed in-house or by a thirdparty provider, efforts must be comprehensive and accurate.

  • Bill Buzzeo

    Bill Buzzeo is an authority on regulatory requirements facing today's pharmaceutical industry, specifically those involving the Prescription Drug Marketing Act (PDMA); international, federal, and state transparency and reporting requirements; and the Controlled Substances Act (CSA).


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