Don’t rely on this but my understanding is that they reverted to...

Don’t rely on this but my understanding is that they reverted to an “old” (referred to as the “second”) potency assay that the company was at pains to point out, had existed at the time of the trial (presumably the one that the company took ~ 18 months to track down the problematic reagent for, ie. not in time for them to use in the resubmission last year) and apparently it worked “perfectly” in the backtesting of inventory used in the trial. (The company had previously mentioned that the cells were stable but the potency assay was not stable enough.) Logic tells me that as long as this “second” potency assay (1) yields the same assurance power (to discriminate between products that are good to go and degraded ones on retained samples from the trial) as the enhanced (matrix) potency assay which the company spent a considerable amount of money developing during the Covid years and then tested on the commercial inventory, and (2) it yields the same or consistent result on the commercial inventory ready to be released for the adult aGVHD trial, then it should have done the things that the company until recently had said were necessary to show what the FDA had wanted them to demonstrate (not of course, how to do it because the trial data are proprietary). I think the company has also added a third thing in the last couple of public releases that the backtested data are able to show, in terms of why Ryoncil worked better than what they now call “early generation product” in Promchymal (which was never used in Trial 001 but of which questions did get asked). Maybe the last point was not something the company had wanted to disclose until they had complete confidence that they could deliver the data for - I don’t think they did anything wrong by initially stating the purpose of the data work but only gradually disclosing what they had achieved towards that purpose.

When all these are put together alongside the fact that manufacturing process had not changed since the start of the trial (with some enhancement having been done before), then the data should, in my view, prove that the product has been standardised or, was “similar enough” in Dr. Krause’s earlier iteration of explaining the FDA’s requirements at the end of August. This is something that is required for product approval. I mentioned before how this requirement is even more important than for small molecule products because Ryoncil is a donor product, therefore a bit more variability is to be expected but there has to be some limit and enough standardisation. , For commercial release, common sense, a reading of the FDA guidance on product assurance strategies for cellular products and the FDA townhall series that Dr. Matthew Klinker took part in tells me that such products must have things like acceptance ranges in the manufacturing process and a robust potency assay. The data, if indeed they can be looked at this way, should provide a complete picture of the product development and evolution. This is NOT financial advice, just an educated guess - do your own research.