- Guest blog by Andrea J. Simon, PhD -
This blog by Andrea Simon, PhD, a corporate anthropologist, is one in a series that ParagonRx has initiated to help our readers better understand some of the trends taking place in the field of Risk Evaluation and Mitigation Strategies (REMS) and risk management under the FDA draft guidance. We know you will find them of value and encourage you to comment on them.
In April, ParagonRx is hosting its Wednesday FoREMS webinar on the topic of organizing to effectively manage Risk Evaluation and Mitigation Strategies (REMS). And, in May, the Wednesday FoREMS will host a panel of industry leaders discussing how their organizations are building REMS capabilities and resourcing them in their product development and commercialization functions. In preparation for these upcoming webinars, I thought I would share with you some of my observations from the field and encourage you to share your own company’s perspectives on how you are reorganizing to create and effectively manage REMS.
For the past year I have been conducting interviews with industry leaders in pharmaceutical and biotech companies who are reorganizing their risk management, safety and other functions in response to new expectations of the FDA and REMS requirements. As we have found this to be a quickly evolving process, we have also found that perceptions and attitudes towards risk and risk communications in the product commercialization process are changing as well.
Early Observations
Permit me to share with you some of the early observations from my interviews and discussions. During the early developmental phase as REMS emerged, there was a time of chaos and confusion as safety, risk management, and branding managers all had to deal with the ambiguity of this new thing called REMS. The lack of clarity and the stress of change characterized everything taking place in what appeared to be a process vacuum. Some of the questions that arose were:
- What does the FDA really expect from us?
- How do we match the product to the right risk mitigation strategy to get approvals without compromising the appropriate use of the drug?
- Who is responsible for and accountable to the FDA within an organization?
- We usually wait until the product is in its late stages before we address the risk communications. Should we start earlier?
- Should we outsource or quickly ramp up to do REMS in-house?
And, most importantly,
- How will REMS impact costs and commercial success?
When the FDA published draft guidance this past September, the industry went into fast-forward action trying to get prepared for anticipated requirements.
REMS is changing Risk Management
There are over 100 drugs with REMS that have been completed in the two years since the FDAAA legislation. Already there is a sense that REMS is going to play a central role in future product development and the commercialization process, and will impact drugs already approved and on the market. This is particularly the case in response to the complex requirements of Elements to Assure Safe Use (ETASU) that require on-going management of communication plans, registries, and extensive risk mitigation processes. Commercial success is becoming, it appears, far more dependent upon how a manufacturer organizes for REMS and manages what is becoming the life-cycle of a product with REMS.
Cross-functional Teams are Keys to Success
It is becoming clearly apparent that in order to get a REMS product approved, manufacturers need to have the right cross-functional team(s) in place to draw from the experiences of the commercial, safety, regulatory, and legal departments. And, just as important, they need the right resourcing, capacity, and skill sets for the upfront REMS planning and contingency plans; and later, after approval, the implementation and assessment plans. There do seem to be different ways to achieve this on an organizational basis even though there are few “best practices” to follow, as yet.
To their credit, industry leaders began to fill the REMS vacuum with some highly innovative solutions. They were also quickly recognizing that the process was much bigger than just getting the product approved. Post-approval REMS implementation plans and ongoing responses to the key observations from REMS effectiveness assessments were clearly as important as the REMS approval process itself. In addition, some manufacturers were developing the mind-set and the capabilities to build risk management plans into the product development cycle even before it might be mandated by the FDA.
Determining how a REMS would or could be designed with in-house staff or if it should be outsourced to a vendor became equally important as manufacturers found themselves not yet set up to manage the more complex components emerging from the FDA requirements—from registries to databases.
Three Organizational Trends worth Watching
At this juncture, I’m already seeing at least three important organizational trends emerging for effectively managing REMS. They offer different solutions and reflect the culture of each type of company. All three, however, clearly recognize the cross-functionality of REMS, its place in the product life cycle, the importance of ongoing assessments and quality controls, and how to integrate REMS into their particular organization. They reflect an understanding of the high level of importance that REMS is going to play in the future of product development and commercial success. These are the three that are clearly emerging:
- The REMS Project Management Office or Core Team
Creating a central team to manage REMS, often with outsourced support, is what we see happening when there is no department, as yet, for REMS inside a company. Creating a centralized team is one solution to situations where no one person and/or department have the expertise and excess capacity to become the REMS expert. Marketing wants Safety to own it, and Safety wants it to be in someone else’s shop. The Core Team can be comprised of internal employees sourced from the cross-functional teams, outsourced, or a combination of both.
Some of the functionalities and activities that can be best solved in this manner include:
- Defining reporting structures and governance that assures appropriate accountability
- Defining the new communications processes across all the relevant disciplines
- Developing the essential implementation plan in a collaborative process
- Forming REMS implementation teams, steering committees, and/or designated work streams
- Conducting REMS readiness audits
- Preparing Contingencies for those FDA questions that ultimately arise
2. Changing the Product Development Process
While it may seem that those very same functions need to be done in all organizations, there are other ways of getting them up and operational. The second pattern developing is in situations where the company uses the REMS-focus on mitigating risks to change the research and clinical development processes throughout the entire life-cycle of a drug. In one particular company we interviewed, the response to REMS was to rethink risk mitigation in the drug’s life cycle from development and clinical trials through commercialization. The entire organization was being educated on REMS and systems were being put into place to better understand how key signals would be captured early, where risks could be identified and evaluated before a product was in its late stage development and how to mitigate those risks before it is time to go for approvals.
3. Risk Management “Czar”
The third is where an individual is identified to lead the REMS and risk management processes across the organization. They are continuously creating their jobs as I write. They are beginning to put together their scope and roles and establishing the foundation on which they will play them. They must develop the buy-in that is necessary for everyone in the organization to see REMS and risk/benefit communications in a new light. These communications go far beyond a PPI or Med-guide, rather, they are a comprehensive and effective approach to education, communication, and impactful transformation of prescriber behavior and patient compliance.
In Summary
Regardless of how you organize the REMS team, assembling the right team of players at the table is critical for both initial approvals and effective, ongoing REMS management. Whatever approaches a manufacturer pursues, organizations are fast-forwarding the training and development of the talent pool, recognizing the need for sufficient staffing, bringing together the cross-functional teams, and resourcing them so they can lead the REMS process through commercial success. To turn REMS into a smooth operation will require the appropriation of sufficient resources, an appreciation of the stage of development that REMS is in today, the opportunity to explore innovative solutions, and the skillful use of in-house and out-sourced expertise.
As I continue to conduct discussions, culture probes, and interviews, I will be drafting white papers on this new emerging world of REMS and the impact it is having on the development and commercialization of pharmaceutical and biotech products.