FDA NDA to ADCOM: Five Tips to Ensure a Smooth Transition
Preparing an FDA New Drug Application (NDA) or Premarket 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 NDA/PMA and ADCOM preparation 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 NDA/PMA preparation with a possible ADCOM in mind.
Conduct a thorough internal review of all data, FDA communications, and relevant precedents. Your submission team must carefully review the data and consider all possible interpretations – especially the most negative interpretations. Reviewing all communications with the FDA as the NDA/PMA is being developed is essential to ensure that any issues or concerns 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 the FDA has reviewed similar products, recent activity within the same or similar indications and relevant safety issues can provide key insights on how to prioritize information in the submission.
Develop key messages around your data and product attributes. The 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. 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 you present data to a potential ADCOM.
Arrange for external experts to review and interpret NDA/PMA data. Engaging the right external experts is crucial to ensuring that the data have undergone an objective and comprehensive review. Individuals with expertise in relevant disease areas, 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 ADCOM trends and precedents are also valuable. Be receptive to unbiased, frank feedback, and recommend strategies to present and address the data.
Test the NDA/PMA content. Once you draft a submission – using the messages developed with internal and external input – 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?
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 you to alter your messages. Keep informed and ready to reinterpret or reposition data in light of new information.
Incorporating these tips EARLY – as the NDA/PMA is being developed – may reduce your risk of having to modify your data interpretation and messages, and may avoid an ADCOM altogether.