Upstream process development

We deliver scalable and robust GMP-compliant production processes for recombinant proteins.

Upstream process development for mammalian platforms

For small scale, high-throughput productions (microgram to milligram range of proteins), we typically apply our SCOUT^® technology. This system integrates high-throughput cell culture using mini bioreactors (spin tubes; 2 – 20 mL working volume) with high throughput purification technology (spin-traps and spin-tubes) and matching analytical capabilities. Hereto, we have optimized CHO and HEK293 cell growth in our mini-bioreactors and have developed a number of media and medium feeds. For larger scale productions, we deploy a range of bioreactors up to 200 L depending on the development phase of the process. For suspension cultures, typically microwell plates, T-flasks, shake flasks or roller bottles in shake incubators, as well as WAVE Bioreactor™ systems and stirred single-use bioreactors are used, while for adherent cell cultures T-flasks, cell factories in static incubators or microcarriers, iCELLis^® systems or scale-X™ bioreactors in R&D and GMP are used in batch, fed-batch or perfusion culture protocols.

All relevant real time assays are available to monitor pivotal upstream process parameters and to ensure optimal translation of the culture process at a large scale.

Upstream process development for microbial platforms

For small scale, high-throughput productions as well as for optimization of culture conditions (media, time of induction, inducer concentration, harvest time, etc.), we typically apply our SCOUT^® technology. This system allows good aeration and integrates high-throughput cell culture using mini bioreactors (spin tubes; 5 – 10 mL working volume) with high-throughput purification (spin-traps and spin-tubes) and matching analytical capabilities. Hereto, we have optimized E. coli cell growth in our mini-bioreactors and have screened many culture conditions for optimal protein production in shorter periods of time. For intermediate-scale productions we use our Multifors in parallel bioreactors (4 x 0.7 L) that allows us to perform process development at small scale but still controlling important parameters as oxygen, feedings, metabolite consumption and pH. For larger scale productions, we use our 10 L Sartorius bioreactors.

Typically, upstream process parameters are monitored by SDS Page or western blot and/or enzymatic assays to monitor protein production. When desired, other analytical or biological assays can also be implemented.