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The Art and Science of Productive FDA Meetings

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View the presentation to learn key strategies for optimizing meetings with the FDA.

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The Art and Science of Productive FDA Meetings

  1. 1. © 2017 PAREXEL INTERNATIONAL CORP. THE ART AND SCIENCE OF PRODUCTIVE FDA MEETINGS Ronald Farkas, MD, PhD Vice President –Technical PAREXEL® Consulting
  2. 2. © 2017 PAREXEL INTERNATIONAL CORP. / 2 OVERVIEW • Understanding FDA's position; not just what it wants but why • Understanding the dynamics within the FDA • What to agree on now and later; What does agreement mean? • The key to proceed • Flexibility and norms and what they mean • Experts, Patients and Advocates at Meetings • Meeting minutes and follow up
  3. 3. © 2017 PAREXEL INTERNATIONAL CORP. / 3 FDA WANTS TO INNOVATE AND BE REASONABLE “[21st Century] Cures set FDA on a transformative path… modernizing how FDA oversees breakthrough technologies…to advance innovations more efficiently, while maintaining our gold standard for protecting patients” Scott Gottlieb Dec 7, 2017 Use New Scientific Tools & Methods •Qualification of Drug Development Tools (3011) •Targeted Drugs for Rare Diseases (3012) •Novel Clinical Trial Designs (3021) •Real World Evidence (3022) Set Reasonable & Feasible Goals • Patient Experience Data (3001) • Patient-Focused Drug Development (3002-3004) • Expanded Access Policies (3032)
  4. 4. © 2017 PAREXEL INTERNATIONAL CORP. / 4 EVERY SCIENTIFIC ISSUE IS OPEN TO DISCUSSION • FDA defines itself as a “science-based organization” • And prides itself in being open, objective, perceptive and fair • Trust that FDA thinks this of itself, and gently remind it if necessary
  5. 5. © 2017 PAREXEL INTERNATIONAL CORP. / 5 …BUT FDA INNOVATES BEST WHEN “FORCED BY THE OCCASION” What does this mean for you? Your best path often differs from the “previous wisdom” of earlier products To support an innovative approach, show FDA how the broader context “forces the occasion” and requires that some risks be taken “Those who govern, having much business on their hands, do not generally like to take the trouble of considering and carrying into execution new projects. The best public measures are therefore seldom adopted from previous wisdom, but forced by the occasion.” Benjamin Franklin
  6. 6. © 2017 PAREXEL INTERNATIONAL CORP. / 6 YOU NEED TO ANSWER MOST OF YOUR OWN QUESTIONS FDA resources are limited…seek answers…from the multitude of [FDA] resources available… Sponsors also can employ an independent consultant for assistance in conceiving strategic drug development and regulatory plans… …allows both sponsors and FDA to conserve their respective resources to address the more complex and challenging drug development and regulatory science issues. FDA resources are limited…seek answers…from the multitude of [FDA] resources available… Sponsors also can employ an independent consultant for assistance in conceiving strategic drug development and regulatory plans… …allows both sponsors and FDA to conserve their respective resources to address the more complex and challenging drug development and regulatory science issues. December 2017 new FDA Guidance
  7. 7. © 2017 PAREXEL INTERNATIONAL CORP. / 7 THE GOAL IS NOT ALWAYS “AGREEMENT” WITH FDA • Seek agreement mainly to YES/NO questions that you think are non-controversial and likely to be “yes” (or: “do xyz to satisfy requirement”)  Have appropriate nonclinical studies been conducted for “IND May Proceed”?  Have the necessary clinical pharmacology studies been conducted for approval?  Is this NDA appropriate to submit under the 505(b)(2) pathway? • For the “more complex and challenging questions” FDA speaks of, often beneficial for you to push the envelope, gently • Goal is more often that FDA tolerate your approach, not agree with it
  8. 8. © 2017 PAREXEL INTERNATIONAL CORP. / 8 SNATCHING “NO” FROM THE JAWS OF “IT DEPENDS” • When FDA says “No, we do not agree” it does not necessarily mean “we disagree” • It often means “it’s more complicated than that” • FDA will tend to “not agree” if it does not know or if the question is beyond the authority of the person responding • For questions that might elicit “No’” consider instead asking FDA to discuss it’s view of the pro’s and con’s, possibilities, alternatives – what does it depend on?
  9. 9. © 2017 PAREXEL INTERNATIONAL CORP. / 9 ASK FDA TO EXPLAIN IT’S POSITION TO YOU … AND TO THE PATIENTS OR ADVOCATES YOU BRING • If there is disagreement, do explain yourself clearly, but also ask for a detailed explanation from FDA • Not just what FDA wants, but why it wants it • Can be helpful to keep questions open-ended; you may be pleasantly surprised by what you learn from FDA • At the bottom of many disagreements is a value judgment about what is reasonable; stakeholders have a say in this
  10. 10. © 2017 PAREXEL INTERNATIONAL CORP. / 10 Consider modeling complex IND discussions on FDA’s own “Structured Benefit- Risk Assessment for NDA approval
  11. 11. © 2017 PAREXEL INTERNATIONAL CORP. / 11 WHAT TO SEEK AGREEMENT ON NOW VS. LATER • Internally, you must map your path precisely: what is your value proposition; what nonclinical and phase 1, 2, and 3 studies are needed; what are the “gaps” in your program? • But at FDA meetings, focus on key issues for your next step, or perhaps next two steps, in your development program – initial data often changes future steps  e.g. You should know at the Pre-IND meeting what wording you’re aiming for in prescribing information, but FDA rarely willing to speculate • Asking too many questions to FDA is counterproductive
  12. 12. © 2017 PAREXEL INTERNATIONAL CORP. / 12
  13. 13. © 2017 PAREXEL INTERNATIONAL CORP. / 13 SEEK SEQUENTIAL AGREEMENTS • FDA can, in essence “throw out the baby with the bath water”, reject something that is good to eliminate something that it sees as bad • Agree upon what can be agreed upon first, then work on areas of disagreements • The first agreement can smooth the way for later agreements
  14. 14. © 2017 PAREXEL INTERNATIONAL CORP. / 14 FDA RESPONDS TO FEASIBILITY ISSUES • FDA tries not to ask for what is infeasible • But “infeasible” needs to be defined to be persuasive • Explain the facts, realistically and honestly, about the hurdles you face and where the limits of feasibility might be drawn
  15. 15. © 2017 PAREXEL INTERNATIONAL CORP. / 15 FDA DOESN’T BELIEVE YOU, AND THAT’S OK • Recognize that the FDA is very skeptical and thinks you are over- optimistic (or over-pessimistic if claiming infeasibility!) • You can’t argue with them about their skepticism • Give their skepticism consideration, they will appreciate and remember
  16. 16. © 2017 PAREXEL INTERNATIONAL CORP. / 16 FDA MEETING MINUTES CAN BE LESS THAN CLEAR “…shall, must, required, or requirement to convey a statutory or regulatory requirement” “…words to communicate advice (e.g., on trial design), comments, or current thinking: advisable, critical, important, may be appropriate, should, consider, discourage, encourage, prefer, recommend, suggest, or urge” “…shall, must, required, or requirement to convey a statutory or regulatory requirement” “…words to communicate advice (e.g., on trial design), comments, or current thinking: advisable, critical, important, may be appropriate, should, consider, discourage, encourage, prefer, recommend, suggest, or urge”
  17. 17. © 2017 PAREXEL INTERNATIONAL CORP. / 17 Should, sometimes, in fact, means must Example* from Pre-IND meeting response A 3-month nonclinical general toxicology study in a relevant animal species should be conducted to support expanded or long-duration clinical studies and marketing of the drug Sometimes FDA’s wording is not precise – you must understand the intention and context to avoid misinterpreting Example* from Partial Clinical Hold Letter To support doses in humans anticipated to result in plasma exposures that exceed the hold limits, you will need to further investigate the toxicity in animals, in order to better understand relevance to humans or to identify a monitoring strategy so that similar toxicity may be avoided in humans *modified to assure confidentiality
  18. 18. © 2017 PAREXEL INTERNATIONAL CORP. / 18 FDA’S “VAGUE LANGUAGE” IS NOT (USUALLY) ACCIDENTAL • It conveys degrees of risk, uncertainty, and flexibility • FDA might seem sure of themselves, but they’re not • Regulations have multiple complex interpretations • Often there is more disagreement within FDA than between FDA and the sponsor • Just like FDA Guidance, meeting minutes reflect FDA’s current thinking • Lack of certainty now (bad) can allow greater FDA flexibility later (good)
  19. 19. © 2017 PAREXEL INTERNATIONAL CORP. / 19 AGREEMENT AND FLEXIBILITY ARE “OIL-AND-WATER” • Flexibility reflects departure from norms • Agreement is based on FDA norms • Agreement on flexibility would set a new norm, so would no longer represent flexibility • Flexibility is often “11th hour” by nature; after other options haven’t worked
  20. 20. © 2017 PAREXEL INTERNATIONAL CORP. / 20 PATIENTS AND ADVOCATES AT MEETINGS • You will be helping FDA reach it’s goal of incorporating the “patient voice” • Works well across all stages of development • Even when difficult issues arise often benefit from “outside witness” • Patient Experts are, simply, the future
  21. 21. © 2017 PAREXEL INTERNATIONAL CORP. / 21 • Expert clinicians can be invaluable, but there are many ways they can undermine productive meetings and favorable outcomes • Ego is a risk; saying too much is more common than not saying enough • Invest in discussions between you and your consultants prior to the meeting LEAD YOUR EXPERTS
  22. 22. © 2017 PAREXEL INTERNATIONAL CORP. / 22 RESTATE THE DISCUSSION POINTS • Surprisingly often there is lively and productive discussion with FDA but implications are unclear • Tell FDA at the meeting how you think the discussion should be summarized in the minutes • Explain if there is specific wording for the minutes that would help or hinder
  23. 23. © 2017 PAREXEL INTERNATIONAL CORP. / 23 CONCLUSIONS • Scientific interactions with FDA may be best viewed as parts of an ongoing negotiation… • …ongoing in part because evolving data over the course of development may change your plan and FDA’s advice • Think carefully ahead of time how much reassurance you really need from FDA, and how much confidence you have in your own plan
  24. 24. © 2017 PAREXEL INTERNATIONAL CORP. / 24 THANK YOU © 2017 PAREXEL INTERNATIONAL CORP. / 24

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