The challenge of raw material variability and strategies for standardization

The advancement of cell therapies depends on the success of industry-wide efforts to reduce variability in source materials, manufacturing processes, and analytical strategies. A newly-published paper in Regenerative Engineering and Translational Medicine identifies several sources of variability throughout the cell therapy supply chain, manufacturing process, and release testing, and identifies standardization efforts, automation strategies, and changes to source materials that are enabling more uniform therapies.

In this paper, co-authors Carl J. Burke, PhD. (Century Therapeutics) and Claudia Zylberberg, PhD. (Akron Biotech) acknowledge that variability in the apheresis product – both due to donor-to-donor variability and due to variability in collection and processing – limit our ability to define release criteria and standardize manufacturing, at least in the case of autologous therapies. Efforts are underway to standardize the collection process to minimize center-to-center variability. Increased interest in allogeneic therapies is welcome from the standpoint of process control, as it enables greater characterization and ultimately, consistency in the final product.

Furthermore, variability in the ancillary materials used to produce a cell therapy can lead to variability in the final product. Regulatory standards for these materials are lacking. As such, terms like good manufacturing practices (GMP) are used widely to signal a certain quality threshold. However, GMPs can look different from one manufacturer to the next, and developers have limited means to benchmark and ensure that the materials used to generate their therapies are suitable. Standardization efforts led by organizations such as the Standards Coordinating Body (SCB) and the International Organization for Standardization (ISO) are underway. However, suppliers must do more to ensure greater transparency – we need to speak the same language.

Analytical development is another area where limited standardization coupled with the difficulties inherent in characterizing advanced therapies leads to challenges in clinical development and commercialization. To address the challenges of potency assay development, for example, a strategy should incorporate phase appropriate strategies to ensure pragmatic characterization early in development with the goal of incorporating learnings as well as refining assays and acceptance criteria as development progresses to later phases. Although there are significant challenges early in development, mapping the analytical strategy early will be helpful in guiding and prioritizing aspects of assay development and identifying CQAs and CPPs.

In addition to these themes, the authors delve into automation strategies and their effect on process consistency, efforts to increase standardization in the transportation of cells and cell therapies, and the need to keep costs of goods manageable to enable the continued development and successful commercialization of these life-saving therapies. To read the full article, entitled “Sources of Variability in Manufacturing of Cell Therapeutics,” please click here.