NorthWest Biotherapeutics Inc (NWBO)

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Aha! "Cell-based therapy technology classifications and translational challenges"


http://rstb.royalsocietypublishing.org/content/royptb/370/1680/20150017.full.pdf

Broadly, there are two approaches to yield increase. The more straightforward option is to produce the desired cells more cheaply. This is the path many are currently following, using the tools, technologies and approaches discussed earlier. An alternative option is to not produce more of the same cells, but to produce cells which have an increase in functionality per unit cost. This can be achieved by different methods depending on the product type, but the underlying principle is that potency per cell dose is as high as possible, allowing fewer cells to be given per dose. Broad approaches to increase yield include ex vivo gene modification of cells, increasing the number of desired cells per population through positive or negative selection or representing the tissue niche within the bioreactor to produce cells which are better adapted to survive and elicit efficacious responses within the patient....


....Another common challenge with autologous cell therapies in particular is variability of the starting material from the patient and the limited amount of cells or tissue which can be made available for destructive inprocess, final release and stability testing. The approval of marketing authorizations for four autologous therapies in the EU to date shows that these challenges can be addressed. In this regard, it is important to define the acceptable variability of starting material, which may have a broad range of acceptability separate to the acceptable variability of the manufacturing process itself, which will usually have a more narrow range. It is the control and variability of the manufacturing process itself and the results of product characterization and release testing that facilitate a robust comparability strategy enabling the effects of changes to the manufacturing process or introduction of a new manufacturing site to be assessed without the requirement for costly clinical bridging studies.

As discussed above, developers are increasingly considering GMP compliant cell manufacturing and characterization at an earlier stage in development and working towards common standards to enable an acceleration towards marketing authorization....

Finally, for both autologous and allogeneic therapies, as discussed with respect to clinical trials, relatively low-risk final stage or point of care manufacturing steps may be required. Under the current EU GMP framework, these manufacturing steps for an ATMP are required to be covered under a full manufacturing licence. However, where these steps are well controlled and low risk, such as a final cell expansion and medium exchange step in a closed device, a case can be made for an alternative approach such as satellite licensing under a main licence holder. This would stimulate manufacturing innovation in this area as well as facilitating multiple site clinical trials and future commercial supply where there would otherwise be a need for large numbers of manufacturing licenses to be in place for these relatively simple steps.