This is the first in a new series of “Ask the Expert” posts, which feature the wisdom and seasoned insight of Pearl Pathways Advisors and Consultant Advisors. First up is Bob Seevers, PhD, a former FDA reviewer and Consultant Advisor to Pearl Pathways with more than 40 years of experience in pharmaceutical research and development.
If you have any regulatory, quality, or clinical development questions for any of Pearl Pathways’ advisors, forward them to us and we will provide answers in future posts.
Q: Bob, we’ve heard many stories of drug development companies (or “sponsors”) sharing ill-chosen and/or irrelevant information with FDA or simply failing to give the Agency what it needs. Please describe for us what FDA does and does NOT want to hear.
A: What the Agency cares about, above all else, is patient safety. That’s why, when they ask “is the drug safe and efficacious,” “safe” comes first. With that understood, FDA is concerned about whether you know exactly what you are giving the patient. Have you done all your homework?
For example, one former client had a drug that could exist in different crystalized forms depending on how it was manufactured. That variability could lead to a safety issue; therefore, it was imperative to demonstrate to FDA that the potential safety issue was addressed in the sponsor’s development plan.
Something FDA really doesn’t want to see is your slide deck for investors—your “bragging deck.” That has nothing to do with patient safety.
Q: What is something else that FDA does not care about, but sponsors make the mistake of presenting?
A: FDA doesn’t care about a sponsor’s finances. If sponsors try to argue that doing a test or clinical trial in the way FDA is requesting would take too long and/or cost too much, the Agency is not likely to be sympathetic. FDA doesn’t care if what they’re asking for might kill your project. In such cases, say instead, “Here’s another way of getting at the same kind of information that FDA reviewers need to make a good decision.” You don’t have to tell them that your way is faster and/or cheaper.
Q: Something else FDA does care about?
A: FDA is going to focus in on safety and efficacy. FDA doesn’t care about how fast you’re moving, or whether your investors or your board are happy. They care about getting good data, a well-defined study. How many patients? What doses? How do you know that your drug only has one crystalized form? How do you know there isn’t a safety issue? Have you checked for that? Those are things that FDA cares about.
FDA really only asks one question: “What is the risk-benefit ratio?” A risk that would be acceptable in cancer patients, could be completely unacceptable in patients looking for a cure for baldness. A risk that may be acceptable in patients for whom there’s no other treatment, might not be acceptable in patients for whom there are decent alternatives.
Q: Could you share some mistakes that sponsors commonly make?
A: Anyone who doesn’t practice for their meeting with FDA is going to make mistakes. They’re going to say things they shouldn’t, promise things that they don’t need to promise, or argue when it’s not productive.
I don’t pretend to have all the expertise that a sponsor’s team has, but I know who the experts are, so I can say, “Dr. Smith is the person who really knows most about this. Dr. Smith, could you respond to the FDA’s comment?” But if Dr. Smith jumps in by herself, things are not necessarily going to go well. So, we practice. I’ll play the difficult FDA person asking hard questions. I’ll ask questions that I know my clients may consider stupid and/or irrelevant, and when I do, I can see their blood pressure go up. We practice so that we can calmly respond with, “Ah, I’m glad you asked that.” Too often, people will just argue.
Q: Anything else that might make for a poor showing with FDA?
A: FDA has already given a lot of guidance. There’s guidance out there from FDA on thousands of topics. If you want to annoy FDA, ask a question that’s clearly answered in one of those guidances. “How should we design a study for this particular disease?” Well, guess what? If you had looked, you would know that FDA has a guidance out that states how the Agency would like studies done in that disease.
Do you have a question for the next Ask the Expert blog? Forward it to us at contact@pearlpathways.com. We look forward to hearing from you.