Screening to Small-Scale GMP Biomanufacture: Exploring a Simple, Unified Platform Strategy for Handling a Range of Cell-Culture Needs

The cell-line development process starts with in silico procedures combining codon-optimization algorithms, a secretion signal toolbox, flexible expression vector configurations, and high-productivity CHO-K1 cell lines. Machine learning combined with in vitro screening is used to consider the end product and final process from the onset of the project. Process development can be done in parallel with clone development, thus reducing the number of steps and shortening the overall project time. Screening is performed using 96-well plates in an automated platform and either transient HEK cells or stable CHO cells. Multitron Pro incubation shakers configured for 96-well plates are used (3 mm orbit/1,000 rpm mixing). The shakers control all critical running parameters (agitation, temperature, CO2) and have active humidification to minimize evaporative losses. This ensures a consistent and reproducible growth environment from 1-mL volumes in 96-well plates to 5-L flasks. Each shaker has a capacity of up to 80 plates (7,680 wells). This makes it possible to test large numbers of clones and running conditions in triplicates, and to generate statistically significant data in every screening pass.