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REMS or RiskMAP or what?

On 30 September 2009, the FDA issued a new draft guidance for industry: Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications. The guidance describes the content and format of a REMS, which the FDA was authorized to require by provisions of the FDA Amendments Act (FDAAA) passed in 2008. FDAAA states that any drug or biologic for which the FDA “determines that a REMS is necessary to ensure that the benefits of a drug outweigh the risks” will require a REMS before receiving approval. A REMS can include a Medication Guide, a Patient Package Insert, a communication plan, elements to assure safe use (ETASU), an implementation system, and a timetable for assessment of the REMS.

Because of the class-wide REMS being created for long-acting opioid products, there has been some confusion as to whether non-opioid products requiring a risk-management strategy will require a REMS or whether they will continue to require risk minimization action plans (RiskMAPs). Our conclusion: They will require a REMS. For most new drug and biological products, the new REMS guidance supersedes the old guidance about RiskMAPs; products that would have been approved before with a new RiskMAP will now be approved with a REMS.

However, there is one caveat: some products that were approved before 25 March 2008 (the day the provisions of the FDAAA took effect) still have a RiskMAP. Only those products that the FDA determined had “elements to assure safe use,” such as required patient monitoring or special training for health care providers, were required to have their RiskMAPs replaced with a REMS. Products that now have a REMS but previously had RiskMAPs include Letairis (ambrisentan) and Tracleer (bosentan).

What effect does this have on new drug applications? For Abbreviated New Drug Applications (ANDAs), the FDA says that it means that any product with a reference listed drug (RLD) that has a RiskMAP will also require a RiskMAP. Any product with an RLD that has a REMS will require a REMS.

The FDA’s list of approved REMS is located at: