Ann: FDA Notifies Clinical Data Sufficient for Refiling aGVHD BLA, page-304

So the cells that they retained in nitrogen can't be tested using the same process but with better QC? I see no reason that they can't use the same test but using a more reliably produced test on cryopreserved cells. Specifically the reference was one of 5 reagents used in the potency assay was poorly controlled. You seem pretty well informed on the methodologies used. What is the exact process in the potency assays used and what reagents are used in each step?

Share Cafe' video that I posted about at approx the 3 minute mark SI says. ' Second potency assay forgvhd that was in place during the phase III trial but wasn’t shown to fda havenow been given to the fda. Will be discussed in the fda mtg march 2024. msb have analysed the data of the potency assay that was in place during the original trial in a different way that more than provides what the fda have been asking for.'

SI most certainly discussed with a group of people after the AGM that the new potency assay that the FDA accepted (perhaps an in principle acceptance rather than a formal one; I don't know) for use in the adult GvHD study was in his view inferior to one previously used in the trial. He indicated that he believed the new data they had generated would provide the FDA what they asked for. Guess what, he did just that, and the FDA did accept the new data. No clearer indication that I heard him correctly. BTW, as is my practice, I take contemporaneous notes so I don't have to rely on memory.

As for your reference to correlation between each passage it seems that this is not relevant as the Research Report states (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322819/)

'Investigational Agent
Remestemcel-L comprises healthy adult volunteer donor human bone marrow-derived MSCs that have been ex vivo cultured and cryopreserved in Plasma-Lyte A supplemented with human serum albumin and dimethyl sulfoxide. Each remestemcel-L dose was stored in the vapor phase of liquid nitrogen, thawed, and reconstituted in Plasma-Lyte A (Baxter International, Inc. USA) immediately prior to administration.

MSCs are nonhematopoietic cells that express low levels of major histocompatibility complex class I, are negative for major histocompatibility complex class II molecules, and are negative for costimulatory molecules CD40, CD80, and CD86. Remestemcel-L cells are CD105+, CD156+, and CD45−; express tumor necrosis factor receptor 1; and suppress IL-2Rα expression on activated lymphocytes. Remestemcel-L cells are harvested at passage 5 and then cryopreserved as a final product. In this study, 4 donors and multiple product lots were used. Most patients received infusions from more than 1 lot, and some patients were exposed to cells from more than 1 donor.'

Can you please provide detail as to where you saw referenced all the potency assays used to test Potency (included in the original data sent to the FDA and those provided later). I can't seem to find reference to it to further my learning.