NorthWest Biotherapeutics Inc (NWBO)

[hyperopia]

Thanks for your thoughts and comments dmb. I understand what you’re saying, and agree that the MAA could include Flaskworks, and if it was in fact included, then that could be a reason the MAA application has taken so long. However, my thinking is that Northwest Bio only needs the Flaskworks system for commercial scale up, but not necessarily to gain marketing approval, so they may not want to include the Flaskworks process, which could potentially complicate and/or delay receiving marking approval, which could also delay other (financial?) plans. I think a less risky and preferred approach, (even if it takes a bit longer) would be to add the Comparability Protocol (CP) for the Flaskworks’ process after the marketing application has been approved, as a Post Approval Supplement (PAS). I’ve always maintained that this was a possibility, and now I think it may be likely, given what we know.

I agree with your validation concerns. Shashi Murthy commented at the ASCO presentation in June, that more validation work needed to be done, and that language “integrating technology for monitoring cell culture to ensure reliability” sounds like validation work, so this is why I believe that Flaskworks’ Eden was left out of the initial commercial licensing process, and likely, the final MAA as well.

It makes sense (to me) that Advent would do it step by step; file a CP for the initial change to a semi-automated manufacturing process (which had all been validated) for the general commercial license, excluding the Flaskworks system; so basically automated cell selection, manual culturing, and automated fill & finish. The idea is to get the initial commercial manufacturing license approved, and then use that approved semi-automated commercial manufacturing method in the marketing application without further complication.

Meanwhile, in the intervening period since the ASCO presentation, the Flaskworks’ team has been working to get the Eden system fully validated including in-process controls. Then, once validation has been completed, Advent will plug the Flaskworks system into that established approved process, run the comparability study using the Flaskworks automated process to show equivalence to the established semi-automated process, and then submit the CP to regulators as a PAS . . . and hopefully within 60 days, it will be approved. Simple as that!

By the way, I’m not trying to convince anyone of this, or even saying that this is correct, but just saying that this is what makes the most sense to me at the moment.