A while back, I heard of a company who withdrew their application to get their assay approved by the FDA. Not knowing the details, I can only speculate – my hunch is the company was overwhelmed by the process and not that their assay was a lost cause.
In fact, I’ve worked for several companies when things looked pretty bleak. That is, after years of development and a careful submission, the letter that comes back from the FDA makes things look hopeless. There are a huge number of findings – some admittedly minor while others seem insurmountable. But all is not lost and it would be a mistake to give up. One needs to understand the situation and then plan what to do. Keep in mind:
- The fact is that virtually all assays should be approved. I have written about this before. Basically, the harm caused by the unavailability of an assay result (due to the assay being rejected) is usually far greater than harm due to a rare, highly incorrect result.
- One reason findings occur is because that is what reviewers do! For example, being a reviewer for journals, I always have findings, even for good papers. Hence, one should plan for a bunch of findings – this is the current environment.
The plan of action should include:
- Ensuring that there are no misunderstandings. Some findings occur because the reviewer has not understood something, for a variety of reasons. The best way to remedy this is with a conference call.
- Managing how the company personnel react to the findings. Typically, the company scientists are experts in the topic compared to the FDA reviewer. If a contested point arises where the company is clearly correct, one needs to be diplomatic. No one likes to be called wrong. Moreover, not all findings are as simple as one view is right and the other wrong. I remember one case where the company was told to redo all of their regressions using a different statistical method. They proposed to argue this rather than simply do this task, which in all likelihood would not have changed any conclusions.
- Reinforce the value of the assay – i.e., the problems with the unavailability of the information should the assay be rejected. This of course must be done carefully. The problem is that the FDA tends to overweight the risk of harm due to wrong results compared to the risk of harm due to the unavailability of results.
- Stand your ground when work is suggested (or required) that is both unnecessary and would delay the assay by too much time.
One thing some companies do is to submit a detailed pre-IDE with a lot of questions. I don’t favor a detailed pre-IDE because it allows for the possibility of arguing over details (e.g., findings) before any actual data has been collected.