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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

Is it possible to increase stability of apheresis/leukapheresis cell products?


 
 


With the increased development and regulatory/marketing approvals of cell immunotherapies, there has been greater recognition of the starting material variability, and potential cell product manufacturing impact vulnerability from the starting material quality. The clinical and industry interest on the topic of apheresis/leukapheresis material quality has generated discussions in various circles regarding gaps in the methods, and development of best practices for starting material collection, processing and biopreservation. A representative discussion has been provided by Juliano et al. [1] Promising commercial development of cell therapies from apheresis/leukapheresis starting material, some of which have encountered disappointing post-commercial manufacturing variability issues [2]. This has also increased scrutiny on potential variability stresses in the cell therapy manufacturing workflow from source material to patient administration. With the diseased patient starting material as a major source of variability in autologous cell therapies, and increased time and distance between starting material collection and manufacturing activities, additive workflow stresses that exacerbate that initial variability between collection and culture expansion/activation are only further detrimental.

BioLife Solutions scientists have been engaged with a number of leading cell immunotherapy developers to increase stability, and reduce variability, of source material apheresis/leukapheresis material. For several years, we have raised discussions regarding starting material quality, and were encouraged by early recognition of potential variabilities amongst clinical centers [3]. We have been issued a patent on Whole Blood Collection [4]. The recognition that time and temperature impacted the isolated cells from apheresis and bone marrow further reinforced the recognition of a biopreservation/stability gap that might be improved with Biopreservation Best Practices methods optimization.

In the subsequent development years for commercial cell immunotherapies, several collection service providers and industry partners began evaluating cryopreservation of the apheresis/leukapheresis starting material with CryoStor CS10, as well as non-frozen hypothermic storage with HypoThermosol FRS. Collection service providers HemaCare and Key Biologics have been leaders in working with cell therapy manufacturers, and sharing their knowledge and positive feedback of BioLife’s intracellular-like biopreservation media.

Current methods for cryopreserving apheresis/leukapheresis might involve just adding 100% DMSO and/or using a freezing protocol that had been developed for isolated hematopoietic stem cells for transplant. Current methods for non-frozen apheresis/leukapheresis storage might involve storage as-is, and at temperatures that could be room temperature, variable ambient, or 2-8°C. In contrast, methods modifications with our customers specific to increasing stability of apheresis/leukapheresis starting materials has focused on adding intracellular-like biopreservation media at a 1:1 ratio to the collected cellular product. Those that target a cryopreserved starting material would add CryoStor CS10 (and store/ship frozen), and those that target a non-frozen starting material would add HypoThermosol FRS (and store/ship at 2-8°C).

The cryopreservation method optimization may also entail protocol modifications to pre-freeze handling, controlled rate freezer steps specific to the use model, and thawing methods. We believe biopreservation of starting materials for Regenerative Medicine and patient-derived testing models will continue to gain recognition as a risk point for potential improvement. Our scientific team at BioLife Solutions, Inc. welcomes the opportunity to further this discussion topic.

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References

1. Lou Juliano, George Eastwood, Todd Berard, Aby J. Mathew. The Importance of Collection, Processing and Biopreservation Best Practices in Determining CAR-T Starting Material Quality. Cell Gene Therapy Insights 2018; 4(4), 327-336. doi: 10.18609/cgti.2018.032

2. Pagliarulo, N. In CAR-T, manufacturing a hurdle Novartis has yet to clear. BioPharma Dive. Dec 6, 2018: https://www.biopharmadive.com/news/in-car-t-manufacturing-a-hurdle-novartis-has-yet-to-clear/543624/.

3. Kao, et al. Validation of short-term handling and storage conditions for marrow and peripheral blood stem cell products. Transfusion. 2011 Jan;51(1):137-47. doi: 10.1111/j.1537-2995.2010.02758.x.

4. Nicoud, Clarke, Mathew, Rice. Materials and methods for hypothermic collection of whole blood. USPTO 8,642,255; PCT/US2009/038634.


Affiliation

Aby J Mathew
Senior Vice President &
Chief Technology Officer,
BioLife Solutions Inc

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