Donkey number two chimes in. Are you his cyber body guard? Did you go to schttoopd skool together? You donkeys don't even understand the question let alone the answer.
The facts are that the FDA frequently allows changes to the mfg process. It is routine. You donkeys say they don't allow changes. You are wrong. Additionally, NWBO can and did change the mfg process as I said. The consequence is not what you donkeys keep braying about. The ISSUE as I stated from the outset, was that changes in the mfg process raise the probability that NWBO will have to do comparative or confirmatory studies to establish that the mfg. changes did not meaningfully alter the end product. So it is well within NWBO's discretion to alter the time it matures the DC's (and the processes it uses) to make the vaccine. It MAY have to undertake additional time and a grey deal of money and to establish that those changes did not materially alter the end product. That changes the risk reward calc substantially. And that donkey is the issue. At the end of the day you shouldn't make bets without knowing all the relevant inputs. and you apparently do not.
Manufacturers3 of biotechnological/biological products FREQUENTLY make changes to manufacturing processes4 of products5 both during development and after approval. Reasons for such changes include 1) improving the manufacturing process, 2) increasing scale, 3) improving product stability, 4) and complying with changes in regulatory requirements. When changes are made to the manufacturing process, the manufacturer generally evaluates the relevant quality attributes of the product to demonstrate that modifications did not occur that would adversely impact6 the safety and efficacy of the drug product. Such an evaluation should indicate whether or not confirmatory nonclinical or clinical studies are appropriate.
While ICH documents have not specifically addressed considerations for demonstrating comparability between prechange and postchange product, several ICH documents have provided guidance for technical information and data to be submitted in marketing applications that can also be useful for assessing manufacturing process changes (see section IV (4.0) References). This document builds upon the previous ICH guidances and provides additional direction regarding approaches to:
• Comparing postchange product to prechange product following manufacturing process changes; and
• Assessing the impact of observed differences in the quality attributes caused by the manufacturing process change for a given product as it relates to safety and efficacy of the product.
First, you do NOT freeze/thaw DC. You freeze/thaw TUMOR CELLS/LYSATE. Why? Because you are trying to kill them all! LOL. Doing that to DC would be terribly stupid . Wellthey do freeze DC's donkey.
FROM NWBO ASCO PRESENTATION Activated, or partially matured, DC have been exposed to maturation agents, and have been arrested in the maturation process by cryopreservation. " Please explain donkey?? I guess you know more than NWBO.
"Cryopreserving the vaccine at the end of manufacturing is something altogether different,(very astute donkey) and extensive studies on the process have shown potency of vaccine is maintained.Next your idea that NWBO could in the MIDDLE of a pivotal trial change process to a theoretically "better" on in manufacturing vaccine is impossible. It would confound the entire trial! You can't just throw in various manufacturing practices along the way. This is the problem here, NW Bio is STUCK using the same exact manufacturing protocol as when this trial began. And the process was licensed around 2003. -- "
The idea the Cognate has to use 12 year old mfg methods and ignore process improvements is laughable. COGNATE obtains any process validations for mfg improvements DURING THE TRIAL from the FDA and then implements them. This is not "changing the trial protocols" you donkey but does increase the risk of equivalency trials being required. Make today the day you learn something donkey. --- http://www.biopharma-reporter.com/Downstream-Processing/NW-Bio-raises-32m-to-expand-capacity-for-personalised-brain-cancer-treat