The breadth and potential efficacy of cell and gene therapies promise a new range of treatments, but there’s one big problem—particulates. These can include protein aggregates, beads used in a manufacturing process, or even polymer fibers from filtration steps. As Samuel A. Molina, PhD, of the International Society for Cell & Gene Therapy Process Development, Manufacturing, and Analytics Committee in Vancouver, Canada, and his colleagues wrote: “When considering particle separation and product purification strategies, these diverse and complex product types pose new manufacturing challenges compared with their biologic (monoclonal antibodies and recombinant proteins) and small-molecule predecessors.”

Much of the challenge arises from the diverse types of particulates and their wide range of sizes. Smaller particles—25 micrometers or less in diameter—create the biggest problem. For one thing, such small particles can actually harm a patient by, for example, clogging capillaries. In addition, the therapy itself might lie in this particle-size range. Particulates can even impact the efficacy of a cell or gene therapy.

When asked to pick the top two pressing concerns regarding particulates in cell and gene therapies, Molina says that they are: “how to effectively remove particulates generated in closed single-use system manufacturing processes, and how single-use manufacturers, therapy developers, and regulators should seek common ground on particulate safety in CGT products.”

Despite the challenges, Molina and his colleagues do suggest some solutions. As one example, they point out: “Running a process cycle with purified water or buffer alone can aid in the determination of sources of particulates released during processing, and single-use systems may benefit from flushing prior to application, especially components like filter cartridges.”

Addressing the wide range of particulate challenges, though, will require the development of new standards for cell and gene therapies. To best address these concerns, Molina says, “It’s time to revisit injectable particulate risk in human health for modern medicines.”

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