by Lisa Jenkins VanLuvanee, Ph.D.
For small biotech and medical device companies without internal regulatory experts, knowing whether you’re getting the right advice can be a real challenge. In this interview, Dr. Lisa Jenkins VanLuvanee, Chief Operating Officer and Vice President of Research and Development at Facet Life Sciences, gives tips on how to evaluate the quality of regulatory guidance. Drawing on her dual perspective as a regulatory consultant and a runner, she offers a clear and memorable way to think about the difference between good advice and guesswork.
Evaluating Regulatory Guidance Without Internal Experts
How do I determine if I am getting good regulatory guidance especially when it is outside my area of expertise and there are no regulatory experts internal to my company?
I’d like to answer this with one of my favorite fitness activities as a metaphor.
Running has long been my favorite fitness activity. Although I run for the sheer joy of it most of the time, I occasionally run “competitively” in mud races and in 5K outings. I’ve read countless books, magazines, and articles on the right shoes, the proper running techniques, the necessity of sleep, and of course, proper nutrition.
Many “experts” provide recommendations on how to enhance performance and perhaps not surprisingly, there are lots of contradictory opinions. In a recent example, one “expert” stated that stretching isn’t necessary and that one can best stretch while warming up during the first kilometer of a run whereas another “expert” said that stretching is the most crucial activity that a runner can do to enhance performance and avoid injury. So, which expert (if any) should I believe?
This is a situation that many small pharmaceutical companies are faced with on a routine basis. How do I decide what to do when I get different and sometimes even contradictory regulatory opinions from expert consultants?
What I am about to tell you may sound simple, but I think it’s worth putting it all in black and white. Let’s return back to the fitness example because I think it provides a nice parallel. What do I listen for when I get fitness advice:
How to Identify Real Regulatory Expertise
Is the expert truly an expert in the field?
Recommendations from a YouTube or TikTok celebrity are likely to be less influential to me than advice from my physical therapist or my physician who is also a runner. Expertise matters and expertise that has been currently used or applied is particularly influential in my decision-making.
This is the same for small organizations receiving regulatory guidance. Timely, expert feedback from consultants who have recently “been there and done that” successfully should be weighed more heavily than feedback from consultants (be they ex-FDA or otherwise) who have never done it, haven’t done it in a long time, or have only seen it done. The regulatory landscape changes so quickly that current experience matters. Finally, having small company experience also matters – effective, best practices for large companies are dramatically different than those for small companies.
Scientific Support Is the Foundation of Strong FDA Regulatory Guidance
Did the expert provide a scientifically supported, sound rationale for why I should listen to their guidance?
A recommendation that has no justification or has a weak justification such as “I told you so” or “I’ve heard this works,” I tend to view with skepticism. Instead, I look for guidance grounded in good science. I’d be much more likely to believe an expert who says, “I recommend stretching because in a controlled study (Turki et al., 2012), highly trained male athletes who performed 1–2 sets of 20 minutes of active dynamic stretches in a warm-up showed enhanced 20-meter sprint performance.” It’s important to understand why your regulatory strategist is making the recommendations that they are. If their assumptions align with yours and their recommendations are grounded in real data and experience, that’s typically a recipe for success!
The best regulatory experts provide innovative, customized regulatory and development strategies and detailed justifications to support those strategies. A solid justification includes, but is not limited to, support based on international and local regulation, guidance documents, regulatory precedent, medical practice, sound scientific principles, and the company’s goals, objectives, and financial considerations.
Matching Regulatory Guidance to Your Product and Business Goals
Can the guidance and rationale be applied to me and my specific situation?
Going back to the running example, it’s all fine and good that a study has shown that elite male athletes benefit from stretching, but what about older female athletes, such as myself? Even if it does apply, I am not a sprinter. Are the gains in sprint performance even applicable to a distance runner? I also need to consider the guidance in the context of my running. Perhaps stretching is great for racing, but I don’t race often. I run for fun – would it really make a difference?
Same too for regulatory guidance. Just because it worked for a big pharma company does not mean that it will work for a small company. In fact, small companies usually are championing novel and innovative products under different timelines, budgets, and exit plans than larger ones. Telling a small company that they must conduct 60+ nonclinical studies prior to filing their IND is more than likely a nonstarter.
Similarly, regulatory strategies are optimal when they are formulated in the context of the company’s corporate goals and objectives. A regulatory strategy SHOULD differ depending on whether a company wants to move a product from phase 1 to phase 2 and then divest the product or if they want to develop a product through to approval and go on to market that product in the US. With so much diversity in products, people, companies, and health authorities, no two regulatory strategies should ever be alike!
Understanding the Risks of Ignoring FDA Regulatory Guidance
Has a sound rationale been provided for why not following the recommendation is problematic or could be problematic?
Rosenbaum and Hennig (1995) showed that achilles tendon reflex activity was significantly reduced in subjects who did not warm-up as compared with those who either did static stretching or a 10-minute warm-up run. This would suggest that even if the performance gains are less applicable to me, I’m less likely to get hurt if I stretch.
When providing regulatory strategies and guidance, it is just as important to explain why alternatives are likely to be suboptimal. If there is regulatory uncertainty and/or risk, it is the strategist’s responsibility to identify and quantify the risk as well as provide several possible mitigations so that you can make the most informed decisions for your company about your product. Practical considerations are also important: significant differences in timelines and/or costs can lead to one regulatory scenario over another.
Resilience and Adaptability in Regulatory Strategy
Does your regulatory partner adjust successfully to unanticipated events?
In sum, good regulatory guidance is provided by experts who have deep, recent experience and a proven track record of success with regulators. Their regulatory strategies should be sound, scientifically supported, and aligned with your objectives for your product and company. They should also include evaluations of risk, risk minimization, and why alternative strategies are suboptimal. Finally, your regulatory strategy and guidance needs to evolve in the face of unanticipated events, surprising data, changing regulations/guidances, and evolving business situations.
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