Good points @stockrock, thanks. I raised a while previously on...

Good points @stockrock, thanks.

I raised a while previously on HC the COVID travel impact on facility inspection with Lonza Singapore since February 2020, and uncertain impact on FDA's perception of the cold storage chain of Form 483s issued re Lonza's Walkerville facility in the US. I've also raised these points at the other conversation place across the pond. So far, I haven't seen any information on whether a new additional facility inspection has been required or even confirmation that OTAT had a satisfactory (or any) facility inspection during the rolling BLA prior to the ODAC meeting. I noted that CBER's Bauer & Puri simply quoted & then commented on MSB's own potency release testing during the 'Inquisition' (see e.g. Slide 7: https://www.fda.gov/media/141130/download referencing Sn 5.1 of MSB's briefing doc on CMC matters).

But if additional assay(s) are to be run now on TNFR1, IL2R or some other CQA - say, on PhIII trial product lots in cryo storage - it would be reasonable to think implementation of any additional assay(s) as product release assays from the Singapore facility would warrant at least a remote FDA facility inspection (if that were to be considered acceptable by CBER). I say that but don't really think 'remote' is what FDA are looking for with cellular therapies, especially MSB as the 1st-in-class one.

The issue would then affect whether the resubmission could even be decided by the CBER Regulatory Project Manager (RPM) to be dealt with under a 2-month Class 1 type, or must be taken as a 6-month Class 2 review process. I initially thought CEO Itescu was talking to this point when he mentioned '.6 months' resubmission review, and then corrected himself with '.up to 6 months.' in that most recent conference call/ update. But on reflection I fell back to the Class 2 review window being 'within 6 months' was most likely informing his choice of words i.e. MSB having accepted that the RPM would inevitably decide it was a Class 2 resubmission. Of course, the RPM could decide to do that just on new data quantity alone, but it got me thinking about any other 'outstanding' items & I just don't see any good reason for that timeframe to shorten as yet.

So I agree with your comment on not getting too far ahead, but from a slightly different angle. We don't know yet if any outstanding inspection was even raised in the CRL, much less how much other implementation info and data it will take for the RPM to sign off on the resubmission portfolio as being complete enough for consideration.

I'm hoping CEO Itescu does have sufficient new data to address the relevance of the revisited immunomodulatory activity on the treatment effect in the successful Phase III trial. Our friends across the pond think he has a mountain of it. All eyes will be on that. GLTAH.