“As the industry and regulatory landscape continues to evolve, it’s vital that as an industry, we take a lifecycle approach to risk management –to ensure that we mitigate as much risk as possible all the way from discovery through to commercialization.” - Dr. Dominic Clarke, Global Head of Cell Therapy, HemaCare
Cell and Gene Therapy Insights has just published HemaCare’s white paper on how to manage starting material quality and stability to maximum effect during cell therapy manufacturing.  Quality cell therapies can only be created from quality starting materials, yet paradoxically, starting materials are the single greatest source of variability in the cell therapy manufacturing process. Mitigating risk requires minimizing that variability, and also managing shelf-life limitations and biopreservation logistics. HemaCare’s white paper points out that traditionally, a great deal of focus has been placed on cold chain logistics of the final product, preserving the cellular therapeutic until it reaches the patient. But while this is unquestionably important, stability at the front end of the supply chain is just as important. Donor networks, cell collection, isolation, cryopreservation-all of these parameters affect downstream efficacy of the final product. The optimization of each step that goes into producing quality starting material can be used to limit the variability of the final product, and protect starting material stability until it reaches the manufacturer.
For example, one of the most important decisions a cell therapy manufacturer makes is their choice of starting material supplier. Manufacturers need to make an accurate assessment regarding the quantity of starting material that will be required for process development and manufacturing, and they need to be sure the chosen supplier can consistently source adequate high-quality donor material. A large, diverse, and well-managed donor network can go a long way toward assuring the timely and consistent availability of appropriate starting material.
Alongside donor network management, apheresis staff training and expertise are key factors for ensuring quality. An experienced apheresis nurse knows, for example, how to best serve the needs of their donor, especially when that donor is also a patient. They understand how to navigate the optimal balance between therapeutic cell quantity and purity from one project to the next.
Ensuring Starting Material Stability
Cell therapy starting material is often shipped off-site for preliminary processing, so the manufacturer needs to establish a shipping timeframe that safeguards the optimal viability and therapeutic qualities of the material. This is especially logistically difficult when shipping to multiple international sites.
Not all cell therapy products require cryopreservation, but an optimized cryopreservation protocol lends flexibility to shipping and storage timeframes, as well as treatment regimens. For this reason, many companies choose to freeze or otherwise biopreserve their cell therapy starting materials to protect them from degradation. The optimization of cryopreservation reagents and methods should therefore be worked out as early as possible during cell therapy process development. Extending the shelf-life and improving the quality of cell therapy starting materials enhances the flexibility of product manufacturing protocols, while reducing bottlenecks. It also improves risk management by providing a consistently high-quality product.
Read the full article here.
- Clarke D., and Smith D. Managing Starting Material Stability to Maximize Manufacturing Flexibility and Downstream Efficiency. Cell and Gene Therapy Insights. 303-313. 2019.