Thanks for sharing Lykiri. He was a good person to ask, and I would think he knows about the system and process you were describing but because of the vague way the questions were asked, his answers were more general and less specifically helpful, so this is my two cents:
To the first question: Advent is changing a part of the manufacturing process with the Flaskworks system, so they will need to prepare a Comparability Protocol (CP) which s a comprehensive plan that describes the specific tests and validation studies and acceptable limits to be achieved to demonstrate the lack of adverse effects that the Flaskworks system has on the identity, strength, quality, purity, or potency of the final product. So the Regulatory Authorities will approve the manufacturing process changes using the Flaskworks system rather than actually certifying the system itself. If the current process is for an investigational or clinical product, then then the system will only need to comply with the Good Manufacturing Practices for an investigational product.
To the second question: For the CP, the Regulatory Agencies require data from a minimum of 3 runs (in a row) post process change for comparison, and this is the most common number submitted. However, I would guess that Advent has likely run between 20 to 30 tests prior to the study for Performance Qualification, and to “dial in” the system for Northwest Bio’s product.
To the third question: Often a CP is submitted as part of the MAA or BLA in the CMC section, or later as a post-approval supplement. Irregardless of where Northwest Bio is in the marketing application process, the CP could be submitted on its own, and I believe the Regulatory Agencies have a 60-day window to approve it, but this could be delayed due to Covid backlogs or other more critical issues. The professor raises an issue about the testing of the new EDEN consumables from Saint. Gobain. A comparability study may be required for the new plastic consumables as part of the second Flaskworks’ milestone. This may be why Northwest Bio has not reported the second milestone in the 10-K, as this consumables comparability study may be part of the larger CP, and it would likely be submitted all together, so the second, third, and fourth Flaskworks’ milestones may be recognized together when the CP is approved.
