NorthWest Biotherapeutics Inc (NWBO)

[hyperopia]

Interesting. So ex quietly concedes that DCVax will be in commercial production. So now it’s not that it won’t be, but simply WHEN. I think that WHEN, is likely to be considerably less than two years, but it’s still speculation. As usual though, I think you have mischaracterized the process. As iwasadiver suggests, Northwest Bio has already developed assays to identify and demonstrate the critical quality attributes of DCVax. Yes, they will need to fine tune and document the process to produce Northwest’s product to specification, but the only signing off by RA’s is done during the approval process. I understand the OP was discussing Sawston and the UK, but in the US, Cognate has had a couple years to fine tune the process, and I’m pretty sure that they are more than ready for commercial production.

Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)
Guidance for Industry JANUARY 2020

https://www.fda.gov/media/113760/download

Some relevant sections here:

It may be crucial to establish CQAs as early as possible particularly when you plan to make manufacturing changes during product development because well-established CQAs are generally necessary for demonstrating product comparability by analytical methods. For additional information regarding establishing CQAs, please see FDA’s Guidance for Industry: “Q8(R2) Pharmaceutical Development” (Ref. 6), and “Q11 Development and Manufacture of Drug Substances” (Ref. 8). Information to support a CQA and results from specific studies or published literature may be included in Module 3 of the CTD in the “Manufacturing Process Development (3.2.S.2.6)” section or the “Pharmaceutical Development (3.2.P.2)” section (see Ref. 1) depending on whether the attribute pertains to a DS or a DP. Information may also be linked to the relevant nonclinical or clinical sections of the application in the CTD.

f. Manufacturing Process Development (3.2.S.2.6)
You should provide a description and discussion of the developmental history of the manufacturing process as described in the “Description of Manufacturing Process and Process Controls (3.2.S.2.2)” section of the CTD.
For early stage INDs, there may be differences between the manufacturing and testing of the toxicology lots and the material you plan to use in the clinical studies. For later stage INDs, there may be changes to the manufacturing process as part of process development, optimization, or under certain conditions there may be reprocessing step(s). In both situations, we recommend that you describe how manufacturing differences are expected to impact product safety and activity and to provide batch analysis information in the “Batch Analysis (3.2.S.4.4)” section of the CTD.
If you make significant manufacturing changes, then comparability studies may be necessary to determine the impact of these changes on the identity, purity, potency, and safety of the product. The extent of comparability testing would depend on the manufacturing change, the ability of analytical methods to detect changes in the product, and the stage of clinical development. For first-in-human studies, any differences between toxicology lots and clinical lots should be assessed for their impact on product safety. For later phase studies, especially those designed to measure product efficacy, differences in clinical lots should be assessed for their impact on product safety and activity.
Please note that it is important to retain samples of the DS and manufacturing intermediates, when possible, in the event that comparability studies are requested during future product development or after licensure of the investigational DP.

d. Batch Analysis (3.2.S.4.4)
You should include a table with test results for batches (or lots) of the DS that you have manufactured. For early stage INDs, this may include toxicology lots, developmental batches, engineering runs, or a single manufacturing run for clinical grade material. We recommend that you gain adequate experience with a new clinical manufacturing processes prior to making clinical material. This is especially critical following technology transfer to a new manufacturing facility, when manufacturing changes occur during development, and when multiple manufacturing facilities will be utilized. Please note that batches manufactured in different ways should be clearly identified in the submission. Information regarding process development of these materials should be outlined in the “Manufacturing Process Development (3.2.S.2.6)” section of the CTD. We recommend that you annually update this section of your IND as new batches are produced. You should indicate any batches that fail to meet release specifications and any action taken to investigate the failure according to your Quality Unit procedures (for Quality Unit information please see section V.C.1., “Appendices – Facilities and Equipment (3.2.A.1),” of this guidance). We recommend that you retain samples of production lots for use in future assay development, validation, or comparability studies.