Development of robust upstream and downstream sequences with subsequent upscaling

Upstream: Mammalian cell culture

Services

  • 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

Upstream: Microbial cultivation

Services

  • Development and scale-up of batch and fed-batch cultivation processes
  • Optimization of cultivation process parameters
  • Evaluation of critical process parameters
  • In-process control analysis for media parameters
  • Analytical tools for product and impurity quantification
  • Development of processes for preparation of inclusion bodies
  • Reaction kinetics
  • Model development
  • Simulation of stationary and dynamic biological systems

Methods and hardware

  • Cultivation systems: stainless-steel stirred tank bioreactors from small scale (10 l) to 400 l, single-use bioreactors (Wave system), parallel laboratory-scale bioreactor systems for screening purposes
  • Filtration systems: microfiltration, ultrafiltration, and sterile filtration
  • Centrifugation systems: steam-sterilizable solid-ejecting centrifuges (CSA8, CSH30-hycon technology), tubular centrifuges (CEPA)
  • Cell disruption systems: high-pressure homogenizer, chemical/enzymatic tools

Downstream

Services

  • Development and scale-up of downstream processing sequences
  • Optimization of downstream processing sequences by multifactorial (DoE) approaches
  • High-throughput process development
  • Development of protein renaturation processes
  • Validation of critical process parameters
  • Development and verification of cleaning procedures for reusable equipment parts that are in direct contact with the process stream
  • Processing of technical (non-GMP) batches

 

Methods and hardware

  • Protein refolding up to 1000-l scale
  • Protein extraction with aqueous two-phase systems
  • Preparative precipitation
  • Solid/liquid separation by centrifugation, cross-flow micro- and ultrafiltration (membrane area up to 6 m²), and dead-end filtration
  • Preparative process chromatography; modes: IEX, HIC, TAC, affinity, GPC
  • Chromatography hardware: ÄKTAexplorers 10 and 100, ÄKTAavant, ÄKTApilot, BioProcess, columns with diameters up to 30 cm
  • Preparative HPLC

Contact

Corinna Lüer

Contact Press / Media

Dr. Corinna Lüer

Fraunhofer-Institut für Toxikologie und Experimentelle Medizin
Inhoffenstr. 7
38124 Braunschweig

Phone +49 531 6181-6402