NorthWest Biotherapeutics Inc (NWBO)

[antihama]

While the inspections are completed, my gut tells me the action items from those inspections are still in review where there may be a continued back and forth w the inspectors on the corrections NWBO consultants have come up with. Also, it probably has nothing to do w GMP manufacturing at Advent since they recently received a new manufacturing certificate. And I don't think it has to do w the clinical results since 70something doctors gave it the seal of approval. What I see as possibly problematic is 1) having in hand old data going back more than 10 plus yrs where they have to dust off every cob web in every nook and cranny to find it and probably kept in some clinicians/hospital file cabinet who took it home w them when they retired. From the June 2020 PR:

NW Bio Provides Update On Projected Timing For Data Lock For Phase 3 Trial of DCVax®-L for Glioblastoma Brain Cancer

Data Completion Process Nearing Finish Line
BETHESDA, Md., June 2, 2020 /PRNewswire/ -- Northwest Biotherapeutics (OTCQB: NWBO)("NW Bio"), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today reported progress toward data lock for the Phase 3 trial of DCVax®-L for Glioblastoma brain cancer.
The Company reported that the final data collection process has been progressing steadily despite ongoing difficulties due to coronavirus-related limitations on operations and restrictions at trial sites. The coronavirus-related difficulties have impacted most aspects of the process, including review processes at sites and even logistical matters such as the shipping of tissue slides.
The completion process includes final data collection, identification and resolution of queries, data checking and confirmation, and site sign-offs. All of these functions are performed by independent service firms (not by the Company), with oversight by the Company. The service firms have completed the final monitoring visits to the trial sites (including a number of them virtually). The service firms are in the process of resolving the queries from those final monitoring visits (each monitoring visit can generate new queries), and the firms have completed most of the data confirmations. After the query resolution and data confirmation are finished for a trial site, the site's investigator needs to sign off on the data before it can be locked.
In light of the current status of the completion process, and the experience over recent months, the Company currently anticipates that the process may be completed by about mid-June or shortly thereafter – i.e., within a couple of weeks after the Company's anticipated schedule at the time of the Annual Meeting in April.
If some of the information that currently remains outstanding cannot be obtained by mid-June, the Company may consider proceeding with a "soft lock" of the data at that time, if arrangements can be made for the rest of the data to be included when it is obtained later. The Company plans to obtain advice from its regulatory counsel, its Scientific Advisory Board and the Steering Committee of the trial in regard to such possibilities.

and

Northwest Biotherapeutics Announces Completion of Phase 3 Trial Sites' Databases
BETHESDA, Md., July 24, 2020 /PRNewswire/ -- Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today announced that the data collection from all of the clinical trial sites for the Company's Phase 3 trial of DCVax®-L for Glioblastoma brain cancer (the "Trial") has been completed and all of the sites have signed off on the locking of their data.

As noted in the Company's prior reports, in order to reach overall data lock for the Trial, each site's data must go through final collection, review, checking for queries, resolution of queries preparatory steps for locking the site and finally personal sign-off by the lead investigator at each site for that site's data. For that purpose, the lead investigator must undergo training on the system, review the site data, personally complete the confirmation and deliver it to the independent contract research organization (CRO) managing the Trial.
Reaching these personal sign-offs by each lead investigator at each of the Trial sites has been a key focus of activity towards data lock for the last couple of months, especially during June and July. At the time of the Company's last report near the end of June, about 30 Trial sites were in varying stages of progress towards sign-off, and about half a dozen Trial sites had not yet completed the preparatory steps necessary to begin the process towards such sign-off.
All of the Trial sites are now finished. The independent CRO has obtained all of the investigator sign-offs for their site's data lock. The sites' data includes all of the clinical data gathered in the Case Report Forms throughout the Trial, and now sit in a signed off, locked position with the CRO.
These datasets from each of the Trial sites (hospitals) are the largest component of the overall dataset for the Trial and contain most of the data. The remaining information for the overall Trial dataset includes some analyses from specialized service providers who are separate from the Trial site hospitals. Such analyses include, for example, genetic profiles such as IDH mutations. For some of these analyses, it has been necessary to go back and obtain additional material due to the age of the samples. For other analyses, it has been necessary to have the analyses done by two separate experts as a cross-check.
This process continues to be impacted by the effects of COVID-19, especially with the resurgence of COVID cases in many areas. For example, key experts at certain specialized service providers have been unavailable for periods of time due to illness in their family. Other experts have gone on extended leave due to restrictions on operations. However, the CRO and the Company are working intensively with these vendors on a continuous basis to move as quickly as possible.

The other thing that plays in my mind is the actual manufacturing from when the 1st patient was dosed to the last and if so providing a qualification assuring they are one and the same. Again, I don't think it has anything to do w the external data since the MHRA validated the application. External data may have been a reason that they didn't go to the FDA 1st but I don't think it is an issue w the MHRA. Just my 2c worth of guesses.