FDA NDA to ADCOM: Five Tips to Ensure a Smooth Transition

Preparing an FDA New Drug Application (NDA) or Pre-Market Approval (PMA) is one of the most arduous tasks regulatory teams have to face – and thinking about a possible Advisory Committee (ADCOM) meeting at the same time may seem impossible.  But approaching FDA NDA/PMA preparation with the possibility of an Advisory Committee meeting in mind not only improves a Sponsor’s chances at an ADCOM – it could prevent one from ever happening.

That’s because considering how issues will play out at a very public ADCOM is a good test for: developing a clear storyline that resonates; identifying data gaps; and predicting how those gaps could be interpreted or misinterpreted by regulators. Importantly, it can ultimately put some potential ADCOM issues to rest.

Here are some tips on how to approach FDA NDA/PMA preparation with a possible ADCOM in mind.

  1. Conduct a thorough internal review of all data, FDA communications and relevant precedents. The Sponsor’s submission team must carefully review the data and consider all possible interpretations of the data – especially the most negative interpretations. Reviewing all of the communications between the FDA and the sponsor as the NDA/PMA is being developed is essential to ensure that any issues or concerns raised by the FDA are addressed in the submission. It’s also critical to understand the FDA’s perspective by reviewing relevant FDA guidance documents, and the current regulatory and healthcare environment. Seeing how FDA has reviewed similar products, recent activity within the same or similar indications, and relevant safety issues, can provide key insights as to how to prioritize information in the submission.
  2. Develop key messages around your data and product attributes. Once a sponsor understands the regulatory environment as it pertains to their submission, it’s time to take control of the story. The FDA NDA/PMA should tell a cogent story—not just dump data that leaves it up to the reviewer to draw conclusions. Ideally, this storyline should carry through all communications with the FDA, with the external scientific and medical communities, with media, and ultimately with an ADCOM panel. Sponsors should explicitly develop an overall message for the program; key messages for efficacy/effectiveness, safety, and need; and messages related to all key findings in the development program. These messages will guide how the NDA/PMA is written and guide how a Sponsor presents the data to a potential ADCOM.
  3. Arrange for external experts to review and interpret FDA NDA/PMA data. Engaging the right external experts is crucial to ensuring that the data have undergone comprehensive review, and that the interpretation is objective. Individuals with expertise in relevant disease area(s), safety areas of potential concern, and in some cases trial design and statistical analysis, should review and critically assess the data and the interpretation. Experts in FDA division trends and relevant advisory committee trends and precedents are also valuable. Sponsors should be receptive to unbiased, frank feedback, and to recommended strategies to present and address the data.
  4. Test the FDA NDA/PMA content. Once a Sponsor has drafted the submission—using the messages that the team developed using internal and external input—they should arrange internal and external expert reviews of key NDA/PMA sections. Does the submission tell a consistent, objective, and credible story? Do the messages consistently carry through? Have all potential concerns been adequately addressed?
  5. Stay current and flexible. There will always be unexpected and unavoidable speed bumps between the NDA/PMA submission and a potential ADCOM.  New FDA regulations or precedents, new scientific information, data from other drug development programs, or new data from the NDA program may force a Sponsor to alter the messages developed for the NDA. Keep informed and ready to reinterpret or reposition data in light of new information.

Incorporating these tips EARLY – as the FDA NDA/PMA is being developed – may reduce a Sponsor’s risk of having to modify their data interpretation and messages, and may avoid an ADCOM altogether.

 

ABOUT THE AUTHOR

Christen Anderson, MD, PhD, FTOS, is a biotechnology/pharmaceutical consultant with over 25 years of experience in all phases of drug development. With a background in endocrinology and metabolism, Dr. Anderson assists 3D’s clients with pre-submission strategic planning and post-submission Advisory Committee preparation. She also assists clients with clinical development strategy, trial design and interpretation and data analyses. Throughout her academic and biotech careers, she has published extensively in peer-reviewed journals. Connect with Dr. Anderson on LinkedIn.