NorthWest Biotherapeutics Inc (NWBO)

[Rkmatters]

Can you tell me what slide 39 states on DCVax-L manufacturing process?

http://www.nwbio.com/NWBT_corp_overview_(SMiconf)_9-16-15.pdf

I see DCVax-L manufacturing confirmed as 8 days.

I repeat 8 days.

Moving on:

http://www.prnewswire.com/news-releases/northwest-biotherapeutics-receives-approval-of-us-patent-for-cost-saving-automation-of-high-concentration-dcvaxr-manufacturing-78507867.html

Can you tell me what the the 2009 press release on batch manufacturing states?

I see 10 days manufacturing in 2009.

You argued that they did not change manufacturing during this trial. I supplied proof. You told me I was wrong. Clearly they did. The TFF is in use. Those are the facts. The same way I have pointed out to you that you are wrong, "as no additional" does not mean one to which was proprietary was not in use. You make assumptions of what methods they use in the absence of being told what proprietary methods are used. The issue of accepting burden of proof as fact is yours, not mine. I do not need to confirm what is in the SEC documents to appease your needing more evidence. You can continue to maintain your skewed perception of how you see this study. I'm happy with the SEC facts. :)

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For others reading this post. A more potent vaccine comes from a 8 day TFF process, which will equate to a both a higher quality and higher reliability DCVax-L personalized product for 3-5 years. Enjoy. :)

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In 2009, they reveal it is already cleared Batch Manufacturing (to 10 day) for their IND and in use, as we learn with long-tail follow-up data:

http://www.prnewswire.com/news-releases/northwest-biotherapeutics-receives-approval-of-us-patent-for-cost-saving-automation-of-high-concentration-dcvaxr-manufacturing-78507867.html

All within the release:

“Use of NWBT's automated system has already been cleared by FDA for human clinical trials. The INDs (Investigational New Drug applications) which have been cleared by the FDA for five different cancers include use of the automated system in the manufacturing process for DCVax®. “

Dr. Marnix Bosch, Chief Technology Officer of NWBT. "NWBT has already achieved significant cost efficiencies by pioneering a unique batch manufacturing process. These efficiencies will be further enhanced by the automated system we have developed, and it is very gratifying to receive the allowance of this important US patent on our automated device."

“The batch manufacturing process takes only 10 days. The shelf life and potency of the frozen DCVax® product have been validated.”


And we know they incorporated the Batch manufacturing change into their technology, as their 2009 Long Tail Follow-up Data confirms the manufacturing went down to 10 day process.


http://www.biospace.com/News/northwest-biotherapeutics-release-long-term-data/159857

The 10-day manufacturing process produces several years of personalized vaccine for a patient, making DCVax®-Brain an "off-the-shelf" product for that patient throughout the treatment period. In addition, NWBT is developing automation of its manufacturing processes to further streamline them, enhance the economics and enable scale-up. NWBT's contract manufacturer, Cognate BioServices, recently moved its DCVax® operations from Sunnyvale, California, to Memphis, Tennessee, reducing the costs and increasing the manufacturing capacity for DCVax®. — October 2009

And the “in addition, NWBT is developing automation of its manufacturing to further streamline”, I understood that to be the TFF. Specifically I interpreted it as a follow-on to this SEC statement:

From SEC 10K released in 2008:

We intend to commence use of the TFF-Cell Separation System in an upcoming DCVax® Phase I clinical trials. The TFF-Cell Separation System is also targeted to be implemented into the DCVax®-Brain product after bioequivalence studies have been completed. Since the product economics are favorable even with the existing first generation manufacturing process, the Company intends to only implement the TFF-Cell Separation System at a time and in a manner that does not interfere with the pivotal Phase II clinical trial for DCVax®-Brain, or product approval or launch.

https://www.sec.gov/Archives/edgar/data/1072379/000089102008000094/v37359e10vk.htm


And they since they told us in 2008 that they intend to incorporate TFF patent, which was cleared in 2008 for use, I do conclude that they again made the change in 2014, once that patent was cleared in 2013:

http://www.nwbio.com/nw-bios-patent-portfolio-further-expanded-with-manufacturing-automation-patent/


And then I found this on the SEC reports, and they did disclose manufacturing changed, early-on (again Batch) and that (TFF patent has been cleared for their clinical trials):


Recent Developments

On September 10, 2013, we announced that we had been issued another U.S. patent (#8,518,636) covering a next-generation process for manufacturing lower cost human dendritic cells of both a higher quality and higher reliability. This next generation system has already been cleared by the FDA for use in the manufacturing of dendritic cells for our clinical trials. These systems are now in use producing the vaccines which have already been injected into the tumors of DCVax-Direct patients.


Changes in manufacturing methods for DCVax-L could require us to conduct equivalency studies and/or additional clinical trials.

With biologics products, “the process is the product”: i.e., the manufacturing process is considered to be as integral to the product as is the composition of the product itself. If any changes are made in the manufacturing process, and such changes are considered material by the regulatory authorities, the company sponsor may be required to conduct equivalency studies to show that the product is equivalent under the changed manufacturing processes as under the original manufacturing processes, and/or the company sponsor may be required to conduct additional clinical trials. Our manufacturing processes have undergone some changes during the early clinical trials. Accordingly, we may be required to conduct equivalency studies, and/or additional clinical trials, before we can obtain product approval, unless the regulatory authorities are satisfied that the changes in processes do not affect the quality, efficacy or safety of the product.


http://www.nasdaq.com/markets/spos/filing.ashx?filingid=9193123


Nothing changed about the treatment protocol, dosing, randomization of patients or other such aspects; but I imagine manufacturing to incorporate the TFF patent was made in 2014, and we were informed in 2008, of the pursuit, in 2013, of it’s allowance into the trial, and then finally in 2014 portion of their PR below, accounting for skew on the data and "other requirements in the trial" (my interpretation the "procedure" that needed changing is manufacturing (to account for low WBC, which will also be statistically addressed in the final trial analysis):


"The Company has been blinded at all times, with no access to any data in the Phase III trial, and will remain fully blinded until the trial is completed.  The changes relate to the statistical analyses that will be done at the end of the trial, and do not affect the treatment protocol, dosing, randomization of patients or other such aspects.  The changes were driven solely by external factors — particularly research reports about a newly discovered variable which has been found to significantly affect GBM patients’ survival times, and which the Company recognized could significantly skew the clinical trial results if the trial’s statistical analyses did not control for it. The Company’s Phase III trial design and statistical analyses already controlled for key variables known at the time when the trial was designed, such as a particular genetic factor (referred to as MGMT methylation), the extent of tumor removal, and others.

The trial enhancements will also have to go through Institutional Review Board (IRB) review and approval at each of the clinical trial sites.  There are currently over 50 trial sites in operation in the US and a number of sites in operation in the UK and Germany.  There will also be certain other requirements for implementation of the changes, modified documentation and procedures."