Challenges for Visual Inspection and Particle Control in Cell Therapy Products

Abstract

Cell therapy products represent a transformative class of advanced medicinal products with unique manufacturing and quality control challenges. Unlike conventional parenteral products, cell therapies consist of living cells—typically delivered as turbid, non-filterable suspensions—which inherently complicates the control and detection of visible (VP) and subvisible particles (SvP). This review outlines the distinctive risks associated with particle generation in autologous and allogeneic cell therapies and highlights limitations of existing pharmacopeial methods for particle testing.

We identify three major sources of particles in cell therapy products: the manufacturing process with often several manual manipulation steps, the single use manufacturing components, and the container closure systems. The complexity of the process is compounded by small batch sizes, short shelf-life, and complex formulations, and thus traditional sampling and visual inspection approaches have limitations in their utility. Therefore, cell therapy products often require tailored inspection strategies and supplemental process simulations.

We review the current global regulatory requirements (USP <790>, Ph. Eur. 2.9.20, JP 6.06), contrast US and EU definitions for particle types, and discusses practical gaps in harmonization. We further evaluate emerging technologies like flow imaging microscopy for SvP characterization and propose optimized visual inspection strategies tailored for turbid cell suspensions. However, preventative or preemptive control, rather than end-stage inspection, is recommended as the most effective strategy. This requires systematic risk assessment, raw material control, process simulations, and supplier collaboration.

The authors advocate for the development of cell therapy-specific inspection standards and call for regulatory alignment to support consistent global development and patient access.