I’ve noticed the language regarding regional manufacturing and the mention of Cognate has changed in the 10K’s over the last couple of years. It was necessary to have regional manufacturing during the trial because the PBMC’s collected from leukapheresis were shipped from the hospital fresh (not frozen) to Cognate’s manufacturing facility, but I doubt that this will be feasible for commercial manufacturing, and it may be part of the reason for the language change.
With fresh monocytes, there’s a limited window (24-48 hours) in which manufacturing should take place because cell viability decreases after that time. Therefore, manufacturing timeslots have to be reserved for each patient prior to undergoing leukapheresis. This presents logistical challenges if there are shipping delays, or if sick patients miss their leukapheresis appointment, which can cause cancelled manufacturing slots and rescheduling backlogs. During the trial, there were only a few hundred patients treated over many years, so these issues could be overcome fairly easily. But this becomes a nightmare for commercial manufacturing when hundreds of patients a month from all over the country are being scheduled. The solution is to cryopreserve the leukapheresis material, which not only provides scheduling flexibility, but also allows centralized manufacturing from a greater distance. Unfortunately, this requires comparability studies to show the equivalence of cryopreserved cells to fresh cells. The question is: who will perform the comparability studies, and when? By the way, Kite performed the comparability studies early in the development of Yescarta, and used cryopreserved leukapheresis material during their clinical trials so they were well prepared for commercialization.
I’ve said that I believe manufacturing has been the major hold up, and there are still so many issues that have yet to be worked out for commercialization. How can they sign commercial manufacturing contracts when they haven’t even worked out the commercial process, or know if the automated equipment they intend to use will even function properly?
To me, the talk of fast-track status and rapid Project Orbis approvals seems a bit premature if manufacturing isn’t ready. And yes, I’ve been guilty of it too, but that was before the March 16th reality check. I believe there’s a reason that Northwest Bio is currently projecting not just monthly production of 40-45 patients, but an annual figure based on that number . . .
2017 10-K
Cognate BioServices’ manufacturing facility for clinical-grade cell products is located in Memphis, Tennessee. Cognate BioServices' facility is approximately 80,000 square feet and contains substantial buildout expansion space in addition to the portions currently built out and in use. The current manufacturing facilities are sufficient to produce DCVax for at least several thousand patients per year. The expansion space will allow us to procure significantly increasing capacity when needed for commercial readiness. We are also developing a facility for manufacturing in the U.K. for the European market. It is necessary for us to have manufacturing operations in Europe to meet the logistical requirements for European patients relating to the collection, delivery and processing of the patient’s blood draw containing the immune cells (for which the time window is too limited to reach the US manufacturing facility).
2018 10-K
Cognate BioServices’ manufacturing facility for clinical-grade cell products is located in Memphis, Tennessee. Cognate BioServices' facility is approximately 80,000 square feet and contains substantial buildout expansion space in addition to the portions currently built out and in use. The current manufacturing facilities are sufficient to produce DCVax for at least several thousand patients per year. The expansion space could allow us to procure significantly increasing capacity when needed for commercial readiness. We are also developing facilities for manufacturing in the U.K. for the European market. It is necessary for us to have manufacturing operations in Europe to meet the logistical requirements for European patients relating to the collection, delivery and processing of the patient’s blood draw containing the immune cells (for which the time window is too limited to reach the US manufacturing facility).
Our intention is for the U.K. facility to manufacture DCVax products for the whole European region. With the impending exit of the U.K. from the European Union (Brexit), it is unclear whether it will be feasible for U.K.-based manufacturing to supply DCVax products throughout Europe. It could be years before the full legal and regulatory rules and requirements become clear. We anticipate that the manufacturing facilities in the U.K. will eventually obtain the necessary approvals, and will be able to supply DCVax products, for clinical trials or otherwise, anywhere in Europe; however, this may not turn out to be feasible, for regulatory, operational and/or logistical reasons.
2019 10-K
Our intention is for the U.K. facility to manufacture DCVax products for the whole European region. With the recent exit of the U.K. from the European Union (Brexit), it is unclear whether it will be feasible for U.K.-based manufacturing to supply DCVax products throughout Europe. It could be years before the full legal and regulatory rules and requirements become clear. We anticipate that the manufacturing facilities in the U.K. will eventually obtain the necessary approvals for Europe, and will be able to supply DCVax products, for clinical trials or otherwise, anywhere in Europe; however, this may not turn out to be feasible, for regulatory, operational and/or logistical reasons.
2020 10-K
Our intention is for the U.K. facility to manufacture DCVax products for both the UK and other regions. However, this may not turn out to be feasible, for regulatory, operational and/or logistical reasons. It is also unclear whether or how Brexit will affect or interfere with these plans in regard to Europe.
