What a difference a year makes…
In early 2008, the topic of risk management was greeted with aversion by most pharmaceutical managers responsible for commercial activities. “If I encounter a drug with genuine safety concerns, I’ll call you” was a frequent response.
Today, everyone is talking about risk management… and for good reason. The FDA Amendment Act (FDAAA) of 2007 granted FDA sweeping new authority to require Risk Evaluation and Mitigation Strategies (REMS) of any product at any stage of lifecycle. In response to FDAAA, industry had three immediate questions:
- What determines if REMS will be necessary?
- How actively will FDA implement the REMS provisions?
- Who should be thinking about risk management?
In the course of 2008, the answers to those questions emerged.
A REMS is necessary if interventions beyond labeling are necessary to adequately mitigate risk. The ultimate arbiter of that assessment is FDA, but industry sponsors can influence the decision with rigorous benefit-risk assessments and contingency planning.
The question of how actively FDA would implement REMS provisions was answered by the fact that one-third of all new chemical entities approved in 2008 required a REMS.
Finally, based on the performance of 2008, who should be thinking about risk management?
- Everyone involved in late stage development of any product. If the probability of an NCE requiring a REMS is 1 in 3, every pre-launch commercialization team should develop contingency plans to avoid delay if a REMS is required for registration.
A special comment goes to teams developing 505.b.2 products. Even though the molecule may have extensive data supporting a favorable benefit-risk profile, the new medication delivery system may introduce new hazards to the patient. FDA has requested several sponsors in this situation to conduct failure mode and effects analysis (FMEA) to determine whether a REMS is necessary.
- The brand team of any currently marketed product with serous adverse events (SAEs). Recalling that a REMS is necessary if interventions beyond labeling are required to adequately mitigate risk, brand teams should both continually update the benefit-risk profile of their products and consider developing REMS contingency plans.
These answers lead to one follow-up question. With whom should you consult if you need to plan for a REMS? In light of the emerging importance of REMS, many service providers and consultants are offering REMS support. Here are some criteria to help you assess the options:
Experience. Have they successfully designed REMS and risk management programs for five or ten or more products? If so, there is significant benefit from the cross-product experience.
Expertise. Do the staff members have risk management expertise? Are they published? Are they recognized among their risk management peers?
Methods. Does the company utilize validated evidence-based methods (such as FMEA) to reliably develop successful programs?
Independence. If the REMS program designer has a vested interest in operating the REMS elements after program launch, there may be concern about bias in the program design.
HCP Collaboration. Successful REMS programs are designed collaboratively with your customer – healthcare providers. Does the company have a process to accomplish this?
Flexibility. It is easy to be prescriptive when designing a REMS, with a “it needs to be this way” mentality. It is far more difficult, but also more effective, to offer a process and a culture to customize planning in a way that balances the needs of regulators, patient safety, and corporate performance.
For more information, please visit www.paragonrx.com or contact me.