An integrated robotic system for high-throughput process development of cell and virus culture conditions: Application to biosafety level 2 live virus vaccines

Live virus vaccines are a critical component of worldwide vaccination strategy for reducing disease burden but often require complex biological production processes that are sensitive to many different factors, both known and often unknown. Prior application of high-throughput process development (HTPD) approaches to these processes has been hampered by a complex design space, low-throughput analytics, and challenges inherent in biosafety level 2 containment and asepsis in laboratory automation. In 2013, we initiated a project with HighRes Biosolutions to design and install an integrated high-throughput screening platform to enable HTPD for biosafety level 2 upstream process development studies. The system incorporates the necessary tools for performing cell and virus culture studies in microplates, as well as advanced analytical capabilities necessary for assessment of cell phenotype, product quality, and antigen yield. To date, we have applied this system to screen optimal media formulations and viral production conditions in support of two viral vaccine programs, with phenotypic assays performed as an integrated part of the workflow. This case study illustrates the power of HTPD in addressing large-scale biological screening challenges by narrowing a vast design space and identifying parameter interactions in live virus production processes.