From a very pragmatic perspective, the FDA better be damned careful how they step on this manufacturing issue. It's a potential powder keg.
As you note, @Lopez, knocking back Ryoncil on the basis of "unproven batch consistency in manufacturing" could have SERIOUS blowback onto Rem-L and the COVID ARDS and MIS-C trials.
In the end, a rejection for Ryoncil on this basis could end up undercutting any contrary decision they might want to make if the ARDS trials go well and they want to approve Rem-L for those diseases.
Again, you have a country there that does NOT trust big pharma in the slightest, with something like 30% of the population saying they are so suspicious of vaccines and the pharmaceutical industry that they won't take a COVID vaccine, regardless of the process behind its development.
So the FDA being so strict as to refuse to approve Ryoncil, letting under-12s die in the interests of manufacturing concerns...
At its base, that's a damning indictment of MSB's ability to recreate the effect of Ryoncil across a sufficient number of batches to render it truly efficacious. In other words, Ryoncil may be "safe", (thank goodness there are no issues with safety), but overall, it's not sufficiently effective for approval.
That would end up branding Rem-L as similarly uneven in its application and outcome.
Taking any FDA rejection on the grounds of unproven quality/consistency to its logical extreme, it's tantamount to the FDA saying "if you get Rem-L, you MIGHT get an effective batch...but it's just as likely that you might get some (expensive) crappily-manufactured cells that do nothing."
At that point, and if I am a doubting anti-vaxxer...it's really no better than a placebo, is it?
Perfect advertising for MSCs' effectiveness in fighting ARDS, FDA. Thanks for sacrificing the good at the Altar of the Perfect.
The FDA has a trump card here, though - they don't have to decide anything on Ryoncil until the end of September - AFTER the interim ARDS results read out. If those results are stellar, they can simply find that SI and MSB have done enough to satisfy their concerns (even saying they will continue to monitor, take the ODAC's suggestions on this issue into account going forward for a Phase 4, etc.).
The only point this becomes a real Catch-22 for the FDA is if the interim results show clinical benefit, but not to a degree that warrants halting the ARDS trial for overwhelming efficacy, pushing the trial out to wait on further interim results. That would force the FDA to make a decision on Ryoncil by 30 September, uninformed by whether the ARDS trials otherwise warrant approval for ARDS.
Anyway, I am confident that SI's cap raise decision, showing he has the cash to invest in upscaling quality/consistency, and his clear awareness of the FDA's concern on this issue means they are totally prepared to make the best possible case they can to lay the FDA's concerns to rest, or at least to convince the FDA to give them the benefit of the doubt and approve, subject to Phase 4 data supporting claims of quality improvements to ensure batch consistency.
(20min delay)