Anyone else buy in after todays dip/crash?, page-129

actually the mechanism of action does not have to be demonstrated. I believe it is simply the FDA's job to raise all and any questions. They even brought up the question about single armed trial..even though it has been discussed before with the company and that it is clear you can get approved with the right single armed trial design.

my source - same document, couple of paragraphs down.
"Development of adequate potency assays, however, can be particularly challenging for MSCbased products. ......

Despite these challenges, FDA has suggested that developers of cell-based products may
progress in two relevant ways. The first is that potency assays based on reasonable hypotheses
about mechanisms of action rather than a clearly demonstrated mechanism of action may be
adequate in some circumstances. FDA has provided guidance on potency assay development that
allows a matrix approach for complex biological products, including cell therapies. This matrix
approach relies on at least one quantitative bioassay and one qualitative bioassay, which together
are sufficiently related to the proposed mechanisms of action. As for other assays for quality
attributes, potency assays used under these conditions must be sufficiently robust in terms of
reproducibility and as indicators of product quality and product stability.

The second approach is to use clinical performance to demonstrate potency. For instance, if a
product meets the primary clinical outcomes, has been extensively characterized during product
development, and is produced by a well-controlled manufacturing process, these clinical data
may be considered to demonstrate potency even if the mechanism of action is not completely
understood. In this scenario, assays purporting to measure product attributes thought to be related
to product potency must be sufficiently robust in terms of reproducibility and as indicators of
product quality and stability. This approach can allow novel therapies with clearly demonstrated
efficacy and well-controlled manufacturing processes to progress to licensure even if the
mechanism of action and its relationship to the relevant potency assay are not completely
understood."