Shifting The Biomanufacturing Paradigm: Intensifying Upstream Processes

By Habib Horry, Ph.D., Jochen Sieck, Ph.D., Tobias Krachtus, and Russell Jones

The first commercial monoclonal antibody (mAb) was approved in 1986 and today, the global market is large and growing. Reports estimate the size of the market to be approximately $100 billion with expectations of it growing to more than $130 billion by 2023, a robust compound annual growth rate of more than 5.5%.

The demand for mAbs and other antibody-based biologics continues to be fueled by a number of factors including:

• A growing elderly population experiencing age-related conditions including cancer, cardiovascular and respiratory diseases
• The opportunity for significant breakthroughs in cancer, diabetes, liver and kidney diseases which continue to have high mortality rates
• The availability of biosimilars and novel modalities including bispecifics and antibody-drug conjugates

While demand increases, so does pressure on the biopharmaceutical industry to accelerate development, improve flexibility and reduce costs all while sustaining or improving drug product quality. New, innovative approaches are needed to address these challenges. In 2017, the BioPhorum Operations Group (BPOG), an industry consortium, published the Biomanufacturing Technology Roadmap in an effort to establish a dynamic and collaborative technology management process to accelerate change. The roadmap is intended to focus the effort of the biomanufacturing community and provide direction by identifying technology and/ or manufacturing targets and prioritizing potential technological solutions.

Adoption of next generation processing and technologies can enable improvements in productivity by streamlining workflows, reducing the manufacturing plant footprint and increasing flexibility. And while the benefits of next generation processes are recognized, there are many options to consider and multiple pathways to success. We are developing technologies and approaches to intensify upstream and downstream processes, delivering both short term improvements as well as game-changing solutions to enable substantial gains over a longer timescale. 

This whitepaper explores several upstream strategies to increase protein titers which can translate into higher throughput, improved flexibility, and compressed timelines. The topics to be covered are:

• Perfusion culture and media
• High cell density cryopreservation
• Modified amino acids
• Cell culture media compaction
• Buffer and media concentrates