(582ay) HEK 293 Platform Bioprocess Development for Second Generation Programs Leveraging Knowledge From First Generation Processes and An Existing In-House CHO Platform Process

A proprietary, chemically defined platform bioprocess was developed for an HEK 293 expression system through the adaptation of existing CHO based platform bioprocesses.  Expedited development timelines and partner programs originally demanded the use of vendor medium dependent processes for two glycoprotein producing HEK cell lines.  This later led to difficulty identifying causes of variability in metabolite concentration, process control, and raw material quality.  Implementation of proprietary, chemically defined medium and feeds during the second generation process development allowed for easier process optimization.  The effect of an existing platform for CHO cell expression systems was initially tested on a single HEK cell line.  The process was then adjusted and tested on a second HEK cell line to determine applicability and subsequently adjusted further.  This development work revealed issues including metabolic differences from existing CHO programs as well as cellular aggregation, shear sensitivity, sensitivity to dissolved gas concentrations, and metal ion dependency.