Why a trial?, page-29

the working assumption is that the FDA were completely unconvinced by the resubmission and have not budged one inch from their “at least one additional randomised controlled trial” position.

Respectfully Southoz, you've used that quoted phrase a couple of times now. I don't recall ever seeing it in exactly that form. Do you have a source or are your paraphrasing perhaps?

I've used the phrase "at least one adequate and well controlled trial" which comes from an FDA guidance note on substantial evidence and probably comes from a piece of legislature or a regulation - but that is not exactly the same thing as what you are saying - its possible to have an adequate and well controlled trial without it being randomised in my opinion. Though randomising certainly wouldn't hurt.

Unrelatedly, this is a second point, like you I haven't particularly focussed on MSBs financial situation as that isn't really what interested me, however, I do recall that there was supposed to be about 30 million dollars worth of inventory that would become an asset if the FDA deemed the potency assay was valid (I might be expressing that poorly) but the flip side is if the FDA isn't convinced the potency assay is measuring the product that is the inventory then that could be a big problem.

I think MSB will have measured the lots of product to confirm conformity with TNFR1 levels and with IL2alpha levels (and chosen above the mean values), BUT they have never said that they will also verify that no lots of MSCs increase INF gamma levels in vitro when they are added. And if any did - irrespective of what happens with the other two potency assay items - I think that would be a cause for concern - and MSB have themselves posted at least one example where INF alpha levels did increase after a batch of MSCs were added to a mix.

INF gamma - once called macrophage activating factor - would be something Matt Klinker would be inclined to look for. He has seen it used to prime MSCs and has used it that way himself.

In a recent post pfeifer1982 included referring to the Japanese Temcell stuff - INF gamma was on the data sheet.