October Supplement From the Editor

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SAM-straightonGood things come in small packages — like this issue, for example. Each author brings a critical aspect of regenerative medicine development into perspective, highlighting progress and remaining challenges. I am especially pleased to highlight the current stage of gene therapies.

At cell therapy conferences a few years ago, some people insisted to me that quality by design (QbD) would have little to no relevance for these advanced therapies. Speakers were academic and medical researchers or commercial manufacturers of traditional biopharmaceuticals, but few appeared to be working to connect those perspectives. This issue makes an excellent case for the utility of QbD. As cell/gene therapies progress toward large-scale viability, demonstrating process control and managing risk leads logically to approaches that are establishing themselves in the larger biopharmaceutical industry.

In his introductory article, David Orchard-Webb says QbD can help companies “determine the most influential critical process parameters and material attributes.” Cell therapy companies need to begin with their final goals in mind, and new analytical tools enable them to identify necessary process changes early on — when they will incur less risk. The following papers expand on his key points. As Tony Hitchcock explains in his update on plasmid manufacturing, defining and understanding critical quality attributes to monitor as scales increase also draws from quality systems and risk-management initiatives. Supply-chain management is critical as well, given the large numbers of plasmids that may be required as gene therapies progress. Hitchcock discusses the role of good manufacturing practices (GMPs) in generating acceptable cell banks for larger, later-stage trials.

Orjana Terova and her colleagues next explore production of viral vectors. They used affinity chromatography resins for clinical-to-commercial scale-up of adenoassociated virus purification. In collaboration with Généthon, they evaluated ways to simplify the process — again, because of the large amounts of vectors that will be needed to meet future market demands.

Finally, we present an extensive white paper on designing a manufacturing strategy for an allogeneic cell therapy, tying together issues discussed above. The authors also emphasize the increasing importance of a GMP validation package as well as business strategies that factor in scale and cost. They discuss the realities of large lot sizes and challenges of managing quality control for high volumes of cells.

We editors enjoy watching new technologies advance, and each of our cell therapy issues seems to push our understanding to new, more mature (and soberingly realistic) directions. As we continue to explore these topics in 2017, what aspects will you want to see pursued in more depth? As always, we welcome your thoughts.

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