Hi biosectinvestor, I thought the same last year about testing the original version of the Flaskworks device, however, my thinking has changed as time has passed. I speculate that Advent’s initial testing and validation of the Flaskworks device, which as you say can be conducted with commercially available leukopheresis products, occurred prior to the acquisition. Then, based on Advent’s evaluation and feedback for their commercial requirements, the Flaskworks technical team had nearly a year to develop the clinical device into a prototype commercial system. The May, 2021 PR stated that “a prototype of the Flaskworks system has been delivered to the Sawston facility.” And you’re right, the Flaskworks MicroDEN device was commercially available at the time of the acquisition, so using the word prototype indicates to me that the Flaskworks system delivered to the Sawston facility is probably not that original clinical version.
I’m not suggesting that Advent fitted out the Sawston facility for the automated process using the Flaskworks system. Of course the testing of the Flaskworks system and commercial process development, will be conducted in the research and development labs, while the primary cleanroom space is devoted to compassionate use production. The recent articles about the Sawston facility basically confirmed this: “The facilities include GMP clean rooms for the production of human cell products, research and process development laboratories, and a large cryo-storage facility.”
I’m also not suggesting that dozens of patients will be required, probably only a few. The comparability protocol will pre-specify how many runs will be conducted, and I believe the minimum number required is three. If the results of those tests show inconsistency, then they may have to make adjustments, and run another study, but I doubt they would even begin the study until they were confident that the system was dialed in.
I agree that automating/mechanizing a manual procedure seems pretty straight forward, and what you say may be true with some processes like fill and finish; however, the cell culturing process is far more complex, and changes there can have a far greater impact. For example, did you know that the dendritic cells produced with the MicroDEN system at Northeastern University had different physical characteristics (they were smaller) than cells produced manually in well plates? That alone is a fundamental difference, (does not show comparability) and could indicate other more significant differences. Regulators expect comparability testing to highlight some differences, but it will need to be clearly demonstrated that those differences do not have a negative impact on safety and efficacy, and that the critical quality attributes have not been affected by the manufacturing changes.
Perhaps I exaggerated a bit with words like “phonebook sized” and “monumental,” but it’s an extremely detailed and extensive process to make multiple changes to the manufacturing protocols. The regulatory approved detailed manual process protocols are known as established conditions. Any changes to the established conditions must be reported to the regulators. There’s several categories for these changes; the FDA classifies them as minor, moderate, and major, while the EU/UK use something like type Ia, Ib and II. The addition of a new supplier for media, or re-agents would be considered a minor change, and can be reported in the annual report. However, any process changes to the established conditions are considered major, and each change, must have it’s own detailed risk assessment, and comparability study. Advent can’t simply compare the old manual process final batch releases to the new final batch releases of the new automated process. I’m not aware of any FDA rules which expedite this process as you describe, but I would appreciate any enlightenment.
I appreciate hearing other posters perspectives, there’s really a wealth and wide-range of experience on this board. Sometimes though, I regret making a post because it often requires multiple follow-up posts, which I don’t often have time for. Plus, I’m west of California, so it seems I’m always far behind most conversations.
