Upstream: Mammalian cell culture

Fraunhofer ITEM develops robust and reliable suspension culture processes in both single-use and multiple-use cultivation systems. A focus is on scalability from laboratory to technical scale, and on evaluation and validation of process parameters.


Screening of cell clones and cell lines for production feasibility parameters (stability, productivity, glycosylation patterns)

Cell line adaptation from adherent to suspension culture and from serum-free to protein-free media

Development of batch, fed-batch, and perfusion cultivation regimes

Optimization of process parameters by multifactorial (i.e. DoE) approaches

In-process control analysis for media parameters such as glucose, lactate, ammonia, amino acids, and several ions

Cell analysis by cell cytometry

HPLC-based analytics for product and impurity quantification (RP, SEC, IEC)

Scale-up of batch/fed-batch cultures up to 400 l and perfusion cultures up to 50 l

Tailoring of culture media components for fed-batch and perfusion

Evaluation of critical process parameters


Methods and hardware

Cell cultivation systems: culture flasks, spinner flasks, shake flasks, single-use wave-bioreactor systems up to 30 l, multi- and single-use stirred-tank bioreactor systems from 2 to 400 l

Cell retention systems: spin filter, alternate tangential flow (ATF) system, acoustic settler (BioSep), gravitational settler, and centrifuge

Culturing strategies: batch, repeated batch, fed-batch, perfusion, repeated perfusion

Cell lines such as CHO, BHK, HEK, hybridoma, HL60, human amniocyte cells (CAP), and insect cells (Hi-5 and SF9)

Depth filtration for subsequent downstream applications