No abstract

In the biopharmaceutical industry, well‐executed process development and characterization studies ensure robust manufacturing processes. In conventional chromatography, these studies are carried out in series with ≥10 mL bed volumes, thus requiring large quantities of feed material and operator oversight. For that reason, the screening of large process spaces becomes very expensive and has the potential to negatively impact other projects in a company's portfolio competing for similar resources. In this study, we evaluated the ability of the three high‐throughput process development formats 96‐well filter plates, pipette tips, and mini columns to reduce resources in a late‐phase process characterization Protein A capture step. The study used a Protein A capture step with a single experimental design, mAb feed material, and analytical package. The evaluation was based on how identical batch and dynamic process parameters impacted the quality and process performance attributes of monomer purity, host cell protein levels, and yield. All formats were able to provide similar models for product yield and monomer purity. Except for practical limitations of PreDictor plates, all formats could identify significant factors for host cell protein levels. RoboColumn units enabled dynamic factor evaluation and the results were the most comparable to conventional chromatography.

Bioprocess development is a relatively new field for the application of high‐throughput technologies (HTT). Similar to historical applications in drug discovery, these new tools are generally being applied to increase throughput and efficiency to either enable improved performance by testing a larger experimental design space or improve speed for development for biological pipelines. In surveying the general application of these technologies in the biotechnology industry, it becomes clear that HTT have targeted a few key steps within upstream and downstream process development workflows (also called HTPD i.e. high‐throughput process development). The primary focus for upstream HTT has been cell line selection and cell culture development, whereas downstream HTT has centered on the chromatography unit operation. The successful implementation of these technologies has come with many lessons learned on technology selection, workflow validation, and study execution. Furthermore towards improving the application of HTT, analytical techniques in combination with experimental design strategies have been developed that enable larger and more complete scientific investigation of experimental conditions. The complete set of tools, techniques, and design strategies have yielded tangible benefits for early adopters, particularly where capacity and timeline restrictions create workflow bottlenecks. Applied properly, high‐throughput technologies can be an important tool in meeting the bioprocess challenges of today and tomorrow.