Concise Review: Process Development Considerations for Cell Therapy

Abstract

The development of robust and well-characterized methods of production of cell therapies has become increasingly important as therapies advance through clinical trials toward approval. A successful cell therapy will be a consistent, safe, and effective cell product, regardless of the cell type or application. Process development strategies can be developed to gain efficiency while maintaining or improving safety and quality profiles. This review presents an introduction to the process development challenges of cell therapies and describes some of the tools available to address production issues. This article will provide a summary of what should be considered to efficiently advance a cellular therapy from the research stage through clinical trials and finally toward commercialization. The identification of the basic questions that affect process development is summarized in the target product profile, and considerations for process optimization are discussed. The goal is to identify potential manufacturing concerns early in the process so they may be addressed effectively and thus increase the probability that a therapy will be successful. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1155-1163 SIGNIFICANCEThe present study contributes to the field of cell therapy by providing a resource for those transitioning a potential therapy from the research stage to clinical and commercial applications. It provides the necessary steps that, when followed, can result in successful therapies from both a clinical and commercial perspective.

Subvisible Particulate Contamination in Cell Therapy Products—Can We Distinguish?

“…1 The specific nature of cellbased products, for example, short shelf life or hold times or their sensitivity to many stress factors, pose new challenges for the development and manufacturing of these products compared to other biologics. 2,3 Nevertheless, cell therapy products need to fulfill critical quality requirements to assure patient safety. [4][5][6][7][8][9][10] Cell therapy products must be parenterally administered, that is, typically by injection or infusion into the human body.…”

Bioprocess decision support tool for scalable manufacture of extracellular vesicles

“…Process and product become tightly intertwined; the bioprocess should be kept as consistent as possible during scale-up to generate EV fractions with reproducible performance. This is already seen in the manufacturing of cell therapies (Campbell et al, 2015;Davie & Brindley, 2012) and Currently, most clinical trials investigating EV therapy are in Phase I (Fais et al, 2016;György et al, 2015), and as such, the effective dose range of EVs is unclear. We also recognize that dose will likely vary between disease applications.…”

Regenerative Medicine Build-Out

“…The challenges inherent in translating a research‐grade method to a reproducible and robust manufacturing process suitable for routine production are significant [17, 18]. Scalability, automation, raw material supply, intermediate and product stability, grade of clean room, process control and general process robustness/failure rate, and the cost of goods all exemplify pertinent issues [19].…”