Georg Klima, Executive Director, Process Science Austria, Biopharmaceuticals Division, Boehringer Ingelheim is a featured presenter at the Eighth Annual Applying Expression Platforms conference at the PEGS Europe Summit in Lisbon, Portugal. Below, he discusses his work with microbial systems, initial process development that enables scale-up and diversification of molecule formats.
Microbial Expression Systems, Scale-Up and Future Considerations
Why have you chosen to apply microbial systems for your protein expression work at Boehringer Ingelheim?
Microbial expression systems pioneered recombinant protein production and continues to play a key role in today’s biopharmaceutical industry. Our choice of microbial systems for protein expression is based on 20 years of know-how and successful development, production and commercialisation of biopharmaceuticals. In particular for novel, finicky biotherapeutics, microbial host systems such as E. coli and P. pastoris offer a wide range of expression options for efficient manufacturing, be it intracellular soluble, insoluble or secreted expression. To fully exploit these options, high-throughput development utilising miniaturisation and automation are key to success.
What considerations come into play when scaling up your processes from the lab to clinical manufacturing of novel biotherapeutics?
For non-platform molecules such as novel biotherapeutics, gaining sufficient process and product understanding during initial process development is essential and lays the foundation for successful scale-up. Still, development efforts need to be carefully balanced and frontloading needs to be avoided considering early phase attrition rates. Time to Phase I enabling GLP-Tox is typically on the critical path for product development. However, process development needs to also take into consideration large-scale equipment capabilities, utility capacities and regulatory requirements to name a few. A well-structured process scale-up and transfer scheme is crucial to achieve successful scale-up.
What areas of interest will earn the most attention over the next few years across the protein expression field?
A significant diversification in molecule formats beside replacement proteins and monoclonal antibodies can be observed, such as bi- and multispecifics scaffolds addressing multi-causal disease pathways or acquiring immune cells to fight cancer. A number of therapies is still in early clinical stages and future success in late-stage trials will further fuel the field. However, also alternative approaches utilising nucleotide-based therapeutics such as RNA are also gaining momentum. Overall it’s quite exciting times!
Georg Klima is Executive Director of Process Science in the Biopharmaceuticals Division at Boehringer Ingelheim RCV in Vienna, Austria. His current responsibilities include host engineering, upstream, downstream, analytical and technology development. Prior to this, he served in various roles in Quality, Validation and Regulatory Affairs. During his time at BI RCV, Georg contributed to the development and registration of 10 biopharmaceuticals. Georg graduated in biotechnology at the University of Applied Life Sciences in Vienna, Austria.
Featured Presentation: Thursday, 5 November in the Applying Expression Platforms conference: