Today we want to focus on key lessons learned from our clients’ experiences. We are very grateful to these clients for allowing us to share their experiences with you so that you can do a better job in your REMS process.
Let’s begin with something that happened recently as we were working with a client during the tight 90-day period before they presented their PDUFA.
Expect the Unexpected
As we work with our clients on their REMS process, we are learning a lot about the uncertainties of interfacing with an internal FDA process that is itself a work in process. One thing that has become very apparent is that no matter how much advanced preparation you believe you have done, the FDA might just surprise you. As we well know, there are a number of different divisions within the FDA that will jump into a REMS review process at different points in time . Sometimes expectedly and sometimes not. When these individuals feel they must enter the REMS review process, prior communications and agreements with other divisions might be totally changed.
So one lesson we are learning is that throughout your REMS preparation and review process, changes are going to happen, and you will need to be very nimble to respond quickly.
How can you and your team approach the final 4-6 weeks prior to your PDUFA date to be able to rapidly address and respond to the FDA’s late breaking feedback?
First, begin with an entirely new attitude toward contingency planning. We, along with our clients, have found it very helpful to think about different scenarios and contingency options not as a sidebar to the discussion but rather as one of the most important parts of the planning and preparation process. We are finding that, all too often, one of your contingency plan options will end up becoming your primary plan. So, we suggest giving it the new respect it deserves.
Second, make extra resources available to be able to respond rapidly to any eventuality. What we have experienced is a variety of sudden, last minute changes in FDA position and urgent requests that required urgent company response. They seem to include all sorts of things, such as:
- Elimination of REMS program elements
- Addition of new REMS elements
- Changes to product indications and contraindications that change the content of the REMS tools
- Need for additional assessment protocols and surveys
- Additional post-marketing study requirements
Being proactive, having a contingency plan in place and establishing a “rapid response” team ready to respond to these potential “surprises” is key to avoiding an approval delay.
“Lessons Learned” of What Worked
Some “Lessons Learned” or “REMS GEMS” worth sharing to help reduce uncertainty, disruption and approval delays include:
- Having proactive communication with FDA
- Pre-scheduling frequent, interim meetings with FDA
- Forwarding “draft” documents and materials for FDA comment on an ongoing basis
- Forming a multidisciplinary “rapid response” team during the REMS finalization phase to respond to changes that often occur within days of the PDUFA date
A few other suggestions to put into your tool kit might include:
- Technology re-development may not be possible at the last minute, but surrogates can be offered
- Content changes need to be made rapidly and consistently throughout the REMS document, supporting document, tools and assessment instruments, therefore, version control and quality assurance are essential
- Pre-drafting backup content, tools and protocols may be useful in the event rapid customization and inclusion are required
What is now becoming clear in the new world of REMS 2.0 is that you must plan for a wider, broader number of changes than you were expecting. REMS finalization is not a linear process but rather an iterative one. You never want to be blindsided; it is better to be over-prepared, waiting and ready for whatever might be coming.
As the “airplane pilot” for “landing” your REMS, you need to practice and train for the unexpected incident that you hope you never have to face. And you expect your backup systems will work in an emergency. But by expecting the unexpected, you’ll be ready for the last minute surprise that your systems didn’t anticipate, avoid the crash, and be able to maneuver a landing in the Hudson River!
We hope these are helpful and we would love to hear from you about your “Lessons Learned” so we can share them with others who are going through their REMS process.