Replies to post #799276 on NorthWest Biotherapeutics Inc (NWBO)

[dennisdave]

You’re making two assumptions that are simply not true under MHRA rules:

1. “Manual Grade B can be approved now and Flaskworks added later.” => wrong.

A Type II Variation after approval is only possible if the originally approved process remains viable for commercial supply.
That is not the case here. Why?

Because NWBO themselves stated in the Nov-20 PR that: Flaskworks/Eden is required to enable commercial-scale manufacturing, Grade C is “central to large scale-up,” and Eden/Flaskworks is the intended commercial route. If your intended commercial process is not the manual process in the original dossier, then the MHRA cannot approve an MA that does not reflect the manufacturing process intended for commercial use.

You cannot approve “A” when the company intends to sell product made by “B.”
That violates the MHRA’s own MAA rule: “The MHRA require you to fully demonstrate your ability to consistently and correctly manufacture your product in order to grant an authorisation.” MHRA GMP inspectorate guidance

Commercial ability IS NOT manual pilot-scale B-suites. So no, you don’t get approval first and fix your manufacturing later. The MA must match the commercial plan.

2. "Your MHRA contact" ;) gave you general variation guidance not ATMP-specific CMC rules.
Companies file Type II variations “all the time” for formulation tweaks, packaging, scaling adjustments, documentation clarifications, etc.
But here is MHRA’s own rule on manufacturing-process changes in an ATMP:
"A change in manufacturing process that impacts quality attributes requires updating the MA and demonstrating comparability and consistent manufacture before approval." = MHRA ATMP regulation guidance

Flaskworks => Grade C automation => totally different unit operations => different sterility assurance => different critical process parameters => different batch comparability.

That is not a post-approval variation. That is a different process.
MHRA will not approve the MA until:
the intended commercial route,
the intended facilities
the intended cleanroom grade
the intended automation
the intended validation

are all part of the active review and inspected. That's ATMP law, not an opinion.

But hey, whatever makes you sleep at night