If we were to intercept an asteroid on its icy, lonely trek through space and take samples from its surface, would we expect to isolate viable cells on warming the samples?
Maybe, maybe not – yet we expect that to happen routinely when we thaw cells from liquid nitrogen here on Earth.
But it is abundantly clear that many cells are deeply affected by such traumatic transitions in temperature. Some die, some change, and often you don’t realize this until it’s too late due to late onset apoptosis pathways and chromosomal rearrangements.
Some cells die, and others mutate!
Thawing cryopreserved products impairs cell functionality, potentially affecting product quality, efficacy and patient safety. It is well known that T-cells and MSC exhibit different functionalities upon thawing. It’s also known that they can regain their normal vitality after being returned to culture for 24-48 hours. So that’s OK, right?
The question is: where should this restoration of function be carried out?
Thawing your frozen cell therapy at the clinic and returning it to culture there before administering it to the patient, turns the clinic into a cGMP manufacturing site. And that’s true for each clinic or hospital, or each doctor’s office, where that process is carried out, with ALL the regulatory challenges that come with it.
We propose a better way, by using our room temperature encapsulation approach:
- Store the cells frozen in your cell bank for as long as you need to
- Thaw them at your processing site and remove the noxious cryoprotectants
- Return to culture to regain full functionality and therapeutic efficacy
- Encapsulate the cells in alginate and ship them “as fresh”
- Dissolve the gel at the bedside and administer to the patient
Combine the benefits of cell banking with better logistics for addressing those “final miles”
When should I start worrying about this?
The short answer is: “as soon as possible”.
The slightly longer answer is: “as soon as possible in planning your clinical development pathway”.
As a therapy progresses through clinical stages it becomes increasingly difficult, complicated and expensive to make changes to elements in the Chemistry, Manufacturing and Controls (CMC) section of your filings. Changing processes, components, container/closures and storage methods can all affect patient safety and the efficacy of the therapy, and there is a clear need to think and plan ahead.
One of my favourite questions to someone just about to enter their experimental treatment into a Phase I trial is “have you thought about how to get the cells from and to the patient?”
The typical answer is “oh, that’s OK – all the patients will be treated here at this clinic so there’s no need to move the cells anywhere.”
“Mmm….that’s fine for the dozen or so patients in your Phase I trial, but what about when you need to open more clinical sites to enroll more patients in your Phase II or even Phase III trials?”
(Slowly dawning look of realisation) “Oh, I see – well, we’ll just change the……oh! I see!”
The short answer to the question is: “As soon as possible”