NorthWest Biotherapeutics Inc (NWBO)

[Lykiri]

Flipper44,

I think i found more evidence of the use of an optimized DCVAX-L in Germany in the annual reports from Fraunhofer Institute for Cell Therapy and Immunology IZI 2013 and 2015. I also think the HE in Germany requires a more stringent process.

From the annual report 2013.
Interview with the director Prof. Frank Emmrich (P.8)

“As early as spring 2013, we were able to lay the foundation stone for the next structure, the second extension building. Once again, through the fantastic support provided by the
City of Leipzig, the Fraunhofer IZI received a leasehold for a plot of land which has allowed us to build an additional laboratory on Perlickstraße between the main building and the BioCube. This will be almost the same size as the main building and will also be connected to the main building through a number of passages. Besides modern laboratories for GLP and GMP work and a special S3 laboratory for vaccine development, this building is especially distinguished by its ”marriage stations” for joining biomedicine with biotechnology.

Here, the focus will predominantly be on developing automated cell technology devices, which will support the development of new diagnostic and therapeutic procedures. Both the first and ground floors will feature glass showrooms where respective development processes and the application of cell technical device combinations can be observed. This will make the institute more transparent and attractive for visitors, international partners, customers and also advanced training events”
https://www.izi.fraunhofer.de/content/dam/izi/en/documents/Publications/Annual_Report_IZI_2013.pdf

In conversation with Dr. Gerno Schmiedeknecht (P.22)

“What particular challenges did the 2013 reporting year have in store for the department of Cell Engineering and what is the outlook for 2014? The greatest challenge of 2013 came with the commissioning and GMP-compliant qualification of the new clean room facility in the Fraunhofer IZI’s first extension building. Carrying out this work required numerous external service providers to be coordinated, a range of risk analyses to be drafted and checked, validation plans and reports to be written, and the existing quality assurance system to be expanded to include the newly added rooms, equipment and procedures. All of this had to take place during business hours, which meant at the same time as production and quality controls for active clinical trials, which were being conducted on behalf of our customers. As we were unable to bring in additional members of staff for this work, my colleagues found themselves facing an enormous workload. I would like to take this opportunity to thank them once again for all their efforts. Besides this, following complex preparatory work and authorization procedures, a real highlight of 2013 was when we started to manufacture and conduct quality controls for investigational medicinal products with regard to two of our key projects: CVac™ on behalf of Prima BioMed Ltd. and DCVax®-L for Northwest Biotherapeutics Inc. / Cognate BioServices Inc. The next challenge is already in sight for 2014 in the construction and qualification of an additional celltherapy clean room facility in the Fraunhofer IZI’s second extension building”
https://www.izi.fraunhofer.de/content/dam/izi/en/documents/Publications/Annual_Report_IZI_2013.pdf

From annual report 2015:
T. (P.27)
…….” With the second extension building, the department now has access to several special laboratories and devices. For example, a safety level 3 laboratory for experiments involving infectious materials, a core facility for implementing the latest nano-biotechnology methods and a facility for the GMPcompliant production of antibodies were completed and prepared for operation. These expanded instrument-based and lab technology facilities have already provided the basis for several newly acquired projects in the department.”
https://www.izi.fraunhofer.de/content/dam/izi/en/documents/Publications/Annual_Report_IZI_2015.pdf

DR. GERNO SCHMIEDEKNECHT (P.31)

“Highlights and challenges in the 2015 reporting year Thanks to a newly established major project carried out together with an international pharmaceuticals company, the Cell Engineering / GMP Unit increased its capacities to 90 members of staff over a short space of time and significantly rearranged its structure. Quickly integrating so many new members of staff in the existing team and providing them with effective training on the regulations governing our complex quality assurance system and the complicated manufacturing and quality control procedures by far posed the greatest challenge of last year.”
https://www.izi.fraunhofer.de/content/dam/izi/en/documents/Publications/Annual_Report_IZI_2015.pdf

And the following is from the same annual report 2015 and posted by Flipper44 a few days ago(P.35)

“Manufacture of the immunotherapeutic product DCVax®-L for brain tumor patients
Fraunhofer IZI is producing and optimizing an investigational medicinal product in Europe, the efficacy of which is currently being investigated as part of a phase III clinical trial. American biotechnology company Northwest Biotherapeutics Inc. has already successfully used the immunotherapeutic product DCVax®-L in clinical trials in the US. This advanced therapy medicinal product (ATMP) is based on autologous dendritic cells for the treatment of glioblastomas, a particularly aggressive type of brain tumor.
To be able to manufacture DCVax®-L for each individual patient, tumor tissue and a blood product have to be taken from the respective patient. Numerous clinics taking part in the study have undergone an elaborate qualification and auditing process in order to obtain the required authorization for the procurement of tissues in accordance with Section 20b (2) of the German Drug Act (AMG).
Besides monitoring quality standards at the clinics, manufacturing company Cognate BioServices Inc. also established the manufacturing process and related analytic methods in 2011/2012 at Fraunhofer IZI. Following successful validation, manufacturing authorization was granted specifically for DCVax®-L by the Landesdirektion Sachsen (Saxony Land authorities) and the Paul-Ehrlich-Institut (responsible federal pharmaceutical supervisory authority) in accordance with Section 13 AMG.
Furthermore, applications to conduct respective clinical trials were submitted to the responsible authorities in the United Kingdom and Germany and initially authorized in the UK. Consequently, in June 2013, production commenced for the treatment of patients there. Authorization of the trial in
Germany the following year then also gave the green light for the production of batches for German patients, which has been ongoing since August 2014.
Alongside the clinical trial, a special provision pursuant to Section 4b AMG was also granted by the Paul-Ehrlich-Institut (manufacture since October 2014). Treatment pursuant to Section 4b AMG is permitted using advanced therapy medicinal products provided such products are individually prepared for patients who are unable to be enrolled in clinical trials due to strict exclusion criteria.
The capacity increases surrounding the new clean rooms and staff, which have been ongoing since 2013, and the regular updates to the submission documents continued to pose a major challenge to the entire group.
Elaborate manufacturing processes in the clean rooms, quality control and the dispatch of DCVax®-L to be administered to patients will also form the focus of our work in the coming year. During the course of this, involved clinics will be closely supervised and additional clinics will soon be qualified in Germany and the UK.”

Best Wishes.