NorthWest Biotherapeutics Inc (NWBO)

[dennisdave]

You have that from Biosec I assume? Well he is wrong, thats Biosec just making stuff up without sources.

A sponsor canNOT switch the way they are Manufacturing Mid-Review and Still Expect Approval on the Old Process. People keep repeating the myth that “manual Grade B is enough for approval even if NWBO changed manufacturing midway.” That is not how MHRA regulation works, and the MHRA’s own rulebook makes this very clear. Below I have quoted an overview of MHRA regulation as to why.

1. MHRA performs product-related GMP inspections for every MAA of the actual process in the dossier.
MHRA itself states: “The MHRA conducts product-related GMP inspections when assessing an application for a UK marketing authorisation. This inspection checks if the manufacturer complies with GMP.” source https://www.gov.uk/guidance/good-manufacturing-practice-and-good-distribution-practice
Meaning: If NWBO changes the commercial process (manual => Flaskworks/Grade C), the MHRA must inspect that process, not the obsolete one.
You cannot get an MA based on a process you no longer intend to use.

2. The MAA must contain the actual manufacturing method and facilities for the product being approved.
MHRA requires: Products must “meet the requirements of the marketing authorisation.”
sources https://www.gov.uk/guidance/good-manufacturing-practice-and-good-distribution-practice

And: the MAA must include “all information required to demonstrate the safety, quality and efficacy of the product.”
MHRA National Assessment Procedure https://www.gov.uk/guidance/national-assessment-procedure-for-medicines
Meaning: If Flaskworks in Grade C is the commercial pathway, that pathway must be:
* in the dossier
* GMP-inspected
* assessed for consistency and comparability
You cannot describe one process (manual) and commercialize another.

3. The Manufacturer’s Licence (MIA) must match the current production route including automation.
MHRA: “Manufacturers need a manufacturer’s licence from the MHRA to manufacture ATMPs.”
source https://www.gov.uk/guidance/advanced-therapy-medicinal-products-regulation-and-licensing
The licence must cover:
* the actual equipment
* the actual cleanrooms
* the actual process
* the actual automation
If Flaskworks is part of the commercial process, the MIA must be updated and reinspected before that process can be approved in the MAA.
A process not yet licensed under the MIA cannot be approved under the MAA.

4. MHRA requires full proof of consistent manufacturing ability before authorization.
MHRA explicitly states: “The MHRA requires you to fully demonstrate your ability to consistently and correctly manufacture your product in order to grant an authorisation.” source https://www.gov.uk/guidance/good-manufacturing-practice-and-good-distribution-practice
Manual Grade B IS NOT automated Grade C with Flaskworks.
These are different processes with different risks, controls, and validation requirements.
If the commercial process uses Flaskworks, that is what MHRA needs to see demonstrated.

5. MHRA requires the MA to be varied if the manufacturing process changes.
MHRA (Specials/ATMP context):
“This would require a manufacturer’s licence and the Marketing Authorisation will have to be varied accordingly.”
source https://www.gov.uk/guidance/advanced-therapy-medicinal-products-regulation-and-licensing

Meaning: If NWBO updated the manufacturing route mid-review (manual => Flaskworks/C-suite),
The MA must be complemented with the new production process. MHRA then evaluates the new CMC package before granting approval.
This is exactly why the regulatory clock stops, perfectly normal for ATMPs.

If NWBO indeed added Flaskworks/C-suite automation into the commercial CMC package during the review, which their own yesterdays PR language stated,
then the MHRA rulebook requires:
* Inspection of the new process
* Inclusion of the new process in the MAA
* Updating the MIA to cover it
* Comparability and validation of the new process
Only then is approval in play.

This is not an interpretation. This is exactly what MHRA’s own regulations require.

6. If NWBO were still pursuing commercial approval only for the old manual Grade B process, then:

* manual is already licensed,
* manual is already GMP-compliant,
* manual is already validated,
* manual is already inspected,
* manual is already used for Specials clinical supply,
* manual requires no new CMC expansion.

In that scenario, approval would have been issued long ago. There would be no justification for two years of clock-stops,
and Parliament would not have said the application is “not affected by any backlogs.” it would, in that case, be backlogged.

7. The only scenario that fits MHRA rules + NWBO’s own PRs + the timing is:
NWBO voluntarily upgraded the CMC pathway mid-review
=> MHRA paused the clock
=> waiting for automated Grade C + Flaskworks validation and inspection.

Everything else collapses under MHRA’s own regulations.

To be quite honest Im really disappointed in most of you to think that changing the way the sponsor produces the medication would have zero effect on MAA timeline and could just pass without review. It kinda matters HOW a cancer medication will commercially be produced, doesn't it for the MAA if you think about it more than 10 seconds. Strange I even have to explain this here