Development and manufacturing of biopharmaceutical medicines from mammalian cell culture

The Heritage of our Business

Biopharmaceutical medicines from mammalian cell cultures have a long tradition at Boehringer Ingelheim BioXcellence™. With a track record of currently 22 launched products, a global network with a commercial bioreactor capacity of more than 280,000 L and a broad variety of cell lines and molecules, we are the preferred partner of our customers  for virtually all their needs in cell line development, process development and clinical and commercial supply.

Global Network of Mammalian Cell Culture Experts

Our global production network gives us great flexibility in transferring processes from our customers to our sites, between sites and between scales. In addition, the combination of our stainless-steel bioreactors (capacity from 2,000 L to 15,000 L each) and our fully disposable single-use bioreactor system (capacity from 100 L to 2,000 L) allows us to work at any scale our customers may need. The disposable system is fully integrated into our manufacturing processes and implemented globally at our cell culture sites in Biberach (Germany), Fremont, CA (USA) and Shanghai (China). We also constantly add to our capacity, with the investment in a new large-scale cell culture facility in Vienna, Austria as the next milestone. 

For mammalian cell line development, we take advantage of our High Expression Technology (BI-HEX® CHO-K1), an established high expression technology platform that ensures fast-track development of high-quality, high-titer processes. We use multiple high expression CHO cell lines to produce several mammalian molecule formats and our experience reaches well beyond standard monoclonal antibody (mAb) formats, for example in recombinant proteins and enzymes or multi-specific mAbs. Whether it is formulation, upstream or downstream development:

We have the technology and experience for your cell culture project.

Mammalian Cell Culture at a Glance

  • Experience with Fab fragments, Fc fusion proteins, TandAb, Ig DART, and further complex biologics like bi- or multispecific mAbs
  • Proven experience for all commercially available single-use bioreactor systems including fully disposable downstream
  • cGMP compliant manufacturing
  • Seamless process transfers from our customers and within our network
Proven experience in biopharmaceutical medicines from mammalian cell cultures

Value Added: Cell Culture Innovation

  • Accelerated development timelines using highly-automated laboratory equipment (e.g. Ambr® 15, Ambr® 250, in-house developed robotics)
  • Tailored product quality tool box to deliver desired molecule efficacy, stability and safety
  • Improved development workflow by using Design of Experiments (DoE), Multivariate Aata Analysis (MVDA), mechanistic modelling and machine learning approaches supported by our dedicated data science department
  • Process monitoring using Process Analytical Technologies (PAT) with the latest online, inline and at-line sensors
  • Computational Fluid Dynamics (CFD) modelling utilized for scale-up and optimal process definition allowing for evaluation of integral parameters including energy input, mixing time, shear forces and mass transfer coefficient (kLa)
  • 15,000 L acrylic bioreactor model built in cooperation with TUHH (Hamburg University of Technology) provides opportunities to validate simulation results and improve scale-up
  • State-of-the-art technologies including Next Generation Sequencing (NGS)
  • Application of sophisticated mathematical models supporting process analysis, de-risking scale-up and facility adaptations as well as identifying improvement options
Left: 15,000 L acrylic glass reactor with streamlines for velocity I Right: CFD simulation from a 12,000 L stainless steel bioreactor

BI-HEX® CHO-K1

Take advantage of our established high-expression technology platform BI-HEX® CHO-K1 to ensure fast-track development of high-quality and high-titer processes.

Take advantage of our established high-expression technology platform BI-HEX® CHO-K1 to ensure fast-track development of high-quality and high-titer processes.

  • Boehringer Ingelheim’s BI-HEX® platform enables accelerated process development
  • Based on our proprietary platform BI-HEX® CHO-K1 cell line
  • Optimized expression vectors with proprietary genetic elements
  • Automated high-throughput screening and miniaturization platforms for cell line development
  • Toxicology material supply available five months post-transfection using a clone tested for stability, biosafety and BI-HEX® platform fit
  • Seamless transfer to Boehringer Ingelheim’s clinical supply facilities for Phase I/II clinical trial material supply
  • Successful completion of more than ninety BI-HEX® cell line development programs

 

Cell Culture Media

Boehringer Ingelheim’s proprietary media ensure reliable and reproducible process platform suitability.

Boehringer Ingelheim’s proprietary media ensure reliable and reproducible process platform suitability.

  • Our proprietary chemically defined media and feed platform meet the demand of cells during expansion and production in single-use or stainless steel bioreactors
  • Designed for high performance in fed-batch and perfusion processes with high product quality
  • Our proprietary media platform has proven adaptability with various cell lines

 

Process

Boehringer Ingelheim provides fast-track development, which facilitates seamless transfer to production facilities and scale-up of our high-titer processes.

Boehringer Ingelheim provides fast-track development, which facilitates seamless transfer to production facilities and scale-up of our high-titer processes.

  • Fast-track process development using fed-batch and process intensification
  • Flexible and well-characterized bioreactor scales from cell thaw to harvest based on Computational Fluid Dynamics (CFD) studies
  • Use of N-1 perfusion and ultra-high seeding density approaches for process intensification e.g. development of 2nd generation processes
  • Strong track record filing IND/IMPD, CTA, BLA/MAA by focusing on all requirements from project start to finish

 

 

Concepts

Learn more about Boehringer Ingelheim BioXcellence™ concepts in mammalian cell culture:

Learn more about Boehringer Ingelheim BioXcellence™ concepts in mammalian cell culture:

CMC I – Smart to Clinic

CMC II – Commercial Process Development

PVS I – Process Validation Stage