Osmolality, a Critical Quality Attribute for Cell Line Development and Cell Therapy

Osmolality, the measurement of dissolved solutes in media, is a well-established critical quality and process control measure within bioproduction of therapeutic antibodies and in cell therapy. Where osmolality is too high, or too low, production yields and cell viability can be affected, or even an entire batch can be lost. Frequent measurement of osmolality is therefore a crucial component to effect process design.

With the advent of easier to use, cheaper and higher throughput methods, assays traditionally only used in later stages of bioproduction are being adopted in the earlier process development stages. Earlier implementation establishes good working practices and can contribute to process control.

Within the cell line development or cell therapy development, process pools of transfected cells are brought back to a single cell (‘clonal’) stage then grown back up into colonies prior to selection based on critical quality attributes (CQA), with the aim of controlling pool heterogeneity and identifying clones with desirable traits. In addition to evidence of clonality, selection of clones to bank commonly use productivity (yield per cell per time), viable cell density and product stability. In addition to these, osmolality measurement prior to seeding and frequent monitoring through cell line development can contribute both as a process control mechanism and a critical quality attribute for selection.

In this presentation, the use of osmolality in bio-production and in earlier process development will be discussed. The case will be made for more frequent, earlier monitoring in cell line development and cell therapy.