Scott Burger, MD
This is part four of a four-part series from Scott Burger, MD, Principal, Advanced Cell & Gene Therapy, LLC.
IV. NEW REAGENTS, NEW METHODS – EFFECTIVE PROCESS MODIFICATION
Changing to a new biopreservation solution, like any manufacturing process modification, raises questions about unintended effects on the product.
These can be addressed by a validation study incorporating rigorous characterization testing to compare products manufactured using the original and modified biopreservation processes. Testing should include product purity and identity characterization parameters, as well as the relevant biological function, i.e., potency.
Introducing and validating a new reagent or process step does not invalidate the original process. In fact, the opposite is true.
Successful validation indicates the modified process is as capable of producing the desired product as the original method. A cell banking operation with an established, validated cryopreservation process could, for example, change to a different cryoprotectant, cryopreservation method, or product container, provided the new process could be validated. Cells banked using the original process would be no less valid than they were prior to introduction of the modified process.
During clinical development, it is preferable to introduce manufacturing process modifications, including new reagents, during the intervals between clinical trials. Changes made early in development are the simplest to implement.
Regulatory requirements become increasingly stringent and rigorous as clinical development progresses, necessitating more extensive validation and documentation.
- As one would expect, barriers to change are greatest after product approval (BLA) has been attained.
- Even in Phase 4, manufacturing process and analytical modifications are possible, if difficult.
- Stability-enhancing modifications ideally would be introduced at the earliest opportunity in clinical development.
- 3-D cell systems, such as mesh constructs (left panel) and Hydrogels (including Hydrogel-mesh constructs, right panel), present new challenges for biopreservation of cells and tissues.
The benefits of extended cell stability (shelf-life) may be realized at any stage, and the cost-benefit potential of improved biopreservation can be viewed as an aspect of the cell therapy process worthy of consideration throughout development and commercialization.
See:
Biopreservation Stability (Part 1): Impact of Stability
Biopreservation Stability (Part 2): Enhancing Stability – Cryopreservation
Biopreservation Stability (Part 3): Enhancing Stability – Hypothermic Storage
