I suspect that management realized early on that the 483 issues are a problem that will cause a delay in approval. However, I also think that they were pleasantly surprised by the panel vote, as we all were, and thus concluded that they will get a minor approvable letter regarding the 483 issues only that could delay marketing till the end of 2007.
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The fly in the ointment here is that the 483 letter may also be the cause why the FDA felt that they could dealy approval until they got further confirmation from 9902b. From the FDA viewpoint, since approval was going to get delayed to 2008 anyway because of the 483 issues, why not delay a bit longer and make sure the data is confirmed.
"a bit longer" would not be something I use to describe the difference between a delay to end of 2007 because of minor CMC issues and a delay to some time in 2009 to wait for the interim data and then resubmit new data. Further, CMC issues are certainly fixable while interim data success is not guaranteed. The weight of CR letter lays squarely on the requirement for new efficacy data and has very little to do with the CMC issues.
I would tend to trust Urdal who said something to the effect that the mention of the CMC issues in the CR letter was just a reminder to get it done. DNDN might or might not have done all the technical work to resolve the issues already. But if they have to resubmit a new set of documents in the second half of 2008, there is little urgency to put together a document on CMC now. If they get it all done by year end, that would be fine. The plant is still producing Provenge for new IMPACT patients so whatever the problems were, they probably had little to do with the manufacturing of Provenge itself.
