Developing stable and high-producing cell lines to manufacture biologics is complex, multi-stage, and time-consuming, often resulting in development timelines that exceed six months when using classical techniques. This represents a frustrating bottleneck in biotherapeutic development, a market where speed-to-clinic is a priority. Louis Boon and Olivia Hughes at Sphere Fluidics present some of the latest strategies to optimise product concentrations and productivities, and high-throughput automated methods to accelerate screening while reducing manufacturing costs.

Extract:

‘Innovations in Cell Line Development to Optimise Biotherapeutic Development’

Developing stable and high-producing cell lines to manufacture biologics is complex, multi-stage, and time-consuming, often resulting in development timelines that exceed six months when using classical techniques. This represents a frustrating bottleneck in biotherapeutic development, a market where speed-to-clinic is a priority.

The challenges to overcome these limitations and meet the increasing demand for novel biologics encourages constant innovation in the manufacturing processes. This article presents some of the latest strategies to optimise product concentrations and productivities, and high-throughput automated methods to accelerate screening, while reducing manufacturing costs.

Biologics represent the fastest growing sector of the pharmaceutical industry, and this constant growth has been complemented with significant improvements in upstream process development. Many biopharmaceutical companies are acting upon new insights and experimenting with ways to accelerate traditional cell line development timelines. Three novel advancements that have has a significant impact on these processes are as follows: 1) a novel method to influence the charge profiles of biologic to improve cell-specific productivity, 2) a technique developed to precisely modify the critical quality attributes of biologic to optimise effector functions, and 3) an automates, high-throughput approach to search and select the optimum high-yielding proven monoclonal cell line.

Harnessing Citrulline for Improved Cell Culture Productivity

Advances in cell culture systems, focused on improving process efficiency by increasing volumetric productivity, can be applied to facilitate process optimisation. Conventional cell culture strategies generally focus on improving the viable cell density (VCD) during upstream processing to increase volumetric productivity. However, while a high VCD results in higher product titres, such changes often lead to difficulties downstream due to the increased complexity of clarification and the requirement for larger filter surfaces. A higher VCD is also associated with a higher concentration of host -cell-related impurities, which researchers must remove during the downstream processing phase, thereby increasing the overall cost of production.

Recent studies to increase specific productivity show that the use of citrulline is a promising alternative.

Click the download button below to read the complete version of ‘Innovations in Cell Line Development to Optimise Biotherapeutic Development’ by Louis Boon and Olivia Hughes at Sphere Fluidics