A REMS Update From FDA

Applied Clinical Trials

On Tuesday June 15th FDA’s Mary Willy, PhD, Senior Risk Management Analyst, Team Leader, CDER, will provide an agency perspective on the first round of REMS evaluation results during the 4 p.m. session “REMS Evaluations: What Have We Learned?” Unable to speak with Dr. Willy, Applied Clinical Trials conducted the following Q&A with staff members from FDA’s Office of Regulatory Policy, Office of Surveillance and Epidemiology, and Office of New Drugs. Answers were also compiled by the agency using March 2010 Congressional testimony from Joshua M. Sharfstein, MD, Principal Deputy Commissioner, FDA.

Q: How would you assess the REMS initiative thus far?

A: The authority to require REMS provides FDA a very useful set of tools that can be used to reduce the risks of marketed products, while allowing patients to benefit from life-saving and other beneficial treatments that could not be safely marketed without a risk management program. We have learned that designing and implementing the most comprehensive REMS requires a careful balancing of the need to adequately manage risks and also to maintain patient access to important medications.

Q: FDA seems to have put fear into sponsors about REMS, but companies are at a loss until the last hours if they need one or not. How do we help guide pharmaceutical companies moving forward in preparing for the right REMS?

A: REMS should be considered when the usual tools to mitigate a risk (labeling) are not thought to be sufficient to address an identified risk. FDA notifies sponsors of the requirement of a REMS as soon as possible in the review process.

Q: If you had to assign REMS a grade, what grade would you give it and why?

A: It is not possible to grade the REMS program given the complexity and variability of the elements across approved REMS. Through experience, we have developed a draft Guidance for Industry: Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications. We have learned of areas of the REMS program that need improvement and are holding a public meeting to hear from stakeholders to see if they have concerns that FDA can address.

Q: Looking within, what are some of the challenges the agency faces in running REMS successfully and meeting its intended goals?

A: While we cannot speak to the challenges in running REMS successfully, we can speak to the challenges associated with the implementation of the REMS provisions. Implementation challenges include ensuring consistency in the handling of safety problems with all products, including over-the-counter (OTC) products and generic drugs; the lack of clarity in certain provisions of the law with respect to REMS; and burdens imposed on application holders and the Agency that do not contribute significantly to drug safety.

Q: Some within industry say that post-market safety demands are causing drug lag at FDA, how would you respond to this statement?

A: FDA is aware of the pharmaceutical industry’s concern about new drug approval delays partially due to some medications being approved with a REMS to ensure that the benefits of the drug outweighs the risk. We are continuing to increase our experience with implementation of the REMS authority in the preapproval setting. FDA is committed to addressing the concerns we have heard, and we are working on updating our procedures under the 21st Century Review processes to factor in considerations for REMS during the review of drug applications.