An interview with Jann Kochel Senior Regulatory Expert with over 30 years of experience. Former regulatory leader with Astra Zeneca and Accenture/Octagon Research
The IND is a critical milestone for companies. Are there some consistent themes between programs that have successful IND’s versus those that do not?
Yes. My going in position is that the sponsor has engaged the right group of scientific experts so they have done the right therapeutic, safety and CMC work to be ready for an IND. Having said that, there are five pretty simple things people can do to ensure success:
Request and participate in a pre-IND meeting.
Ensure you seek regulatory advice in the appropriate current context for your program
If you are referencing a DMF make sure you are fully aware of the contents of the document
Treat your investigator brochure with the care and focus that you would for your label of a marketed product
Be concise, overwhelming reviewers with content will not serve you well.
Tell me more about your comments regarding having a pre-IND meeting.
Believe it or not, many programs decide not to have a pre-IND meeting. I am not sure whether it is due to time or perceived delays but everyone can gain considerable insights from having the meeting.
What is your experience around some of the regulatory advice teams get around IND submissions?
The team must appreciate that each IND is very unique and will be read by the agency in that context. Given that, the regulatory advice is best given by someone with recent experience in the division, indication and perhaps even the mechanism of action. The team should seek out experts to help navigate potential safety concerns by the agency etc. and onboard them well in advance of the agency interactions.
You believe teams should be more diligent in their understanding of referenced DMF details. What are some examples where folks did not do that and what were the results?
It is sometimes difficult for sponsors to get the detailed information contained in a DMF. It is important for the sponsor to press the DMF owner to ensure the sponsor has an understanding of what is and is not in the DMF. For example, is the DMF up to date? Does the DMF contain the necessary and complete CMC information? In a Type V DMF for a chronic, were the right carcinogenicity studies performed? At a minimum the sponsor must audit the DMF owner.
I must admit I was a little surprised by your energy around the importance of the Investigator Brochure. Would you talk more about your thoughts on the IB?
I have seen factions within companies struggle internally with the objective of the Investigator Brochure. There are two schools of thought: One group would like to paint their drug in the best possible light and therefore carefully pick what content to include and the other wants to include every bit of data generated. The Agency requires the IB to include all pertinent information. The thing to remember is the Agency has all the data in the IND and if you do not include the necessary information in the IB you may be put on clinical hold. The IB must be concise but forthcoming about the drug.
Would you talk more about the need for sponsors to be concise while crafting and IND? It seems like there is a significant amount of information that must go into IND and brevity would not serve the sponsors interest.
There is normally and incredible amount of effort expended and therefore data gathered during drug discovery and early development. Sponsors are sometimes compelled to include all of this data in the IND. It feels like they are trying to get credit for all the hard work. For example, rather than include all of the discovery work, just include the key experiments whose data are being used to establish the hope for efficacy and safety.
Another example is summary documents in module 2. Sponsors should work to provide a holistic picture of the performance of the drug. This will include summaries of the studies performed but in addition the sponsor should synthesize the summaries into providing cross study insights for the review team. In addition, it is important to include the seminal papers that are key to an understanding of the content. Other papers that are important but not key should be referenced and but not included.
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