In a constantly changing regulatory environment, having a well planned contingency strategy is vital for successful Food and Drug Administration (FDA) negotiations. Today, this is more important than ever. The FDA is asking companies to prepare Risk Evaluation and Mitigation Strategies (REMS) to help ensure patient safety, and has issued a documentation template, but has yet to provide further guidance to the industry on how such REMS should be developed.
To date, current REMS programs range from Medication Guides for patients to stakeholder educational programs (known as Communications Plans) to systems that control prescribing and use (e.g., registries) also known as Elements to Assure Safe Use (EASU). Expertise about these precedents combined with science-based methods (such as failure modes and effects analysis) can define a REMS that effectively mitigates risk with the least burden to stakeholders. The next step is to prepare for successful regulatory approval. A proactively developed contingency plan may be a valuable strategy to consider prior to negotiating with the FDA. This strategy also serves to provide internal alignment of the various functional groups (e.g., Regulatory, Safety, Medical, Commercial) helping mitigate unanticipated issues at the 11th hour.
The staging or gradual escalation of contingency strategies is one approach for Sponsors to consider for the FDA negotiations process. For example, if the baseline REMS is a Medication Guide + Assessment, one REMS contingency may include the development of a series of more rigorous metrics to evaluate program effectiveness, as compared to the original Assessment Plan. Another REMS staged contingency strategy could be the proactive development of a Communication Plan and elements such as a Dear Health Care Provider (HCP) Letter and HCP Brochure.
Another contingency planning strategy could be the use of a science-based methodology to validate the utility of specific REMS components (if such a method was not used during the original design). REMS components can also be pre-tested with stakeholders to demonstrate the acceptability, usability, and comprehension of the interventions. Furthermore, the use adult learning principles and multiple distribution vehicles of program elements can help in the transfer REMS messages to the broadest possible target audience.
A carefully prepared contingency plan can expedite and support decision-making through the negotiations/approval process. By anticipating potential scenarios and responses to each, Sponsors can rapidly and efficiently modify their REMS design while avoiding delays that could occur when addressing unexpected requests.