High-throughput screening for best clone manufacturing using scale-down models

The timelines for cell line development and early-stage process development are decreasing, but simultaneously there has been an increase in the amount of associated data. New methods in molecular and cell biology, new analytical methods, including the application of Process Analytical Techniques (PATs) and other methods to assess product quality early on, as well as new trends in process miniaturization and automation, increase the throughput in cell line and early-stage process development and the amount of data needed to be analyzed and reviewed. Thus, data structuring and curation represents a serious bottleneck to proper data analysis and valid decision making. We have designed a highly integrated data management and workflow system, which supports automated clone and manufacturing process development workflows, and provides the foundation to increase throughput in cell line and process development. The system is designed to continuously capture, in a highly structured manner, the heterogeneous data during the course of process development campaigns. It supports the whole process from expression, construct generation via transfection, cell seeding, selection, passaging, and cryo-conservation to cell culture and product quality analytics. This includes repeated passaging for clone stability assessments as well as (micro-) bioreactor runs for clone selection and process optimization. It can handle molecule, cell line, sample and process information as well as analytical test results. The system tracks the full history of all clones - from initial transfection all the way to their master cell banking and beyond - and provides lineage information for all samples handled during a campaign. Here, we present concrete use cases to demonstrate how the platform supports miniaturized screening approaches in scale-down models such as microtiter plate and micro-bioreactor based clone and process screening by capturing, processing, aggregating, and visualizing online and offline data and integrating them with product quality and molecule data to enable holistic process development for any type of biologics molecules (IgGs, novel antibody formats, novel scaffold, fusion proteins, enzymes, etc.)