Many cell culture experts will argue that improvements in media and feed have been more responsible than any other factor in raising production titers for therapeutic proteins. While the “nature vs. nurture” argument is far from settled, culture media is at worst the partner of cell-line development in the quest for productivity, safety, and efficacy.
Media selection supports every stage of development and manufacturing, from clone selection to process development, scale-up, and commercial manufacturing. Absent the optimization of cell culture media, meeting biomanufacturing challenges such as scalability, process robustness, time to market, supply chain reliability, and cost of goods becomes impossible.
According to Achim Quandt, cell culture media and consumables business leader at GE Healthcare, scalability, especially for monoclonal antibody production, has improved through platform processes that allow using the same host cell line and culture medium for whole families of products.
“A robust process provides manufacturers with a relatively large design space where product quality remains unaltered. Once validated, platform processes provide huge advantages during scale-up, as wider acceptable ranges for the process parameters can be used.”
One company’s platform may differ significantly from another’s, particularly with respect to media and feed. Yet media manufacturers need to stay ahead of the curve(s). “For media manufacturers, the challenge is to offer a wide portfolio that reflects the needs of the most common cell culture platforms,” notes Pascal Lefebvre, media product manager at Sartorius Stedim Biotech.
Supply chain reliability is a key factor in modern bioprocessing that employs specialized equipment and raw material from a multitude of vendors. “Manufacturers strive for improved control of their supply situation by careful selection of vendors, conducting of supplier audits, and requirements for safety stocks where applicable,” says Quandt.
Cell culture media and media development are significant contributors to cost of goods, but when executed perfectly can greatly shorten time-to-market, Lefebvre notes. “As competition becomes more intense, fast-tracking to the commercial phase becomes critical.”
Related manufacturing issues include process robustness, reproducibility for both upstream and downstream processing, “quick-and-clean” processing, technical and regulatory support, and matching titers for optimal upstream and downstream operations. “You can’t run purification identically for 1 g/L and 6 g/L processes.”
The bioprocessing landscape is not quite settled in terms of culture type: fed-batch (including variants) or perfusion. “We’re seeing hybrid approaches—quasi-continuous processing—employing feeding strategies that do not involve complete media exchanges as you’d see with perfusion,” notes Shawn Smith, senior director, upstream bioprocess technologies at Pall Life Sciences.
The trend toward continuous manufacturing as a cost-saving measure will create additional challenges to media manufacturers and end-users. Right now this is an open-ended area for vendor and customer alike, since broad experience in this manufacturing mode does not yet exist. Top media vendors tell us, however, that they will be prepared when the dust settles.