As cell culture goes, so goes biomanufacturing. The slow, downward evolution in manufacturing scale, while at some level lessening demand for cell culture media, nevertheless creates opportunities for more specialized media products and services.
Several factors are responsible for the shift from mega-cultures to more manageable production batches. Most prominent are ongoing improvements in protein titers for CHO and other cell lines, advances in personalized medicine and cell-based therapies, the emergence of nonantibody protein drugs and biosimilars, and vaccine development.
“As a result of interest in personalized medicine and titer improvements, vendors must fill the need for smaller volumes of media in disposable formats,” says Laurie Donahue-Hjelle, Ph.D., director of cell culture product development at Life Technologies. Personalization of biotherapies creates opportunities, she says, to test products for multiple indications.
The one-drug-fits-all model, of which blockbuster drugs are one manifestation, may be fading. Under this scenario multiple products, manufactured in smaller batches, will replace one or two big sellers for leading indications. Every such product will require smaller quantities of highly specialized media.
The emergence of nonmonoclonal antibody products (e.g., blood factors, replacement enzymes) is another factor contributing to bioprocesses shrinking in size. MAbs are typically high-dose drugs produced in large batches. The manufacture of lower-dose replacement proteins, cytokines, and enzymes, for example, is expected to take less production volume.
Cell-based therapies, another facet of personalized medicine, will require media that support the growth of human stem, progenitor, and primary cells used in human therapy. Media for primary cells differs from CHO media in the supplements and the required attachment substrates, although many of the processing lessons learned in protein therapeutics can be directly applied.
Biosimilars are still nowhere near as important as generic small molecule drugs, but Dr. Donahue-Hjelle and colleague Trent Carrier, Ph.D., believe that the eventual success of generic biopharmaceuticals will further change the types and quantities of cell culture media customers demand. “Supporting customers in these emerging markets is a new area for cell culture media companies,” Dr. Carrier says. “These new business models are no longer based on 20,000-liter processes. Media companies have to figure out how to manufacture, inventory, and manage the delivery logistics to support these new models and their novel dynamics and usage trends.”
Meeting the changing demands for cell culture media will require vendors to adapt and modify not just their product offerings, but the approach to producing and distributing media and nutrients.
To better integrate molecular and cell culture needs, Life Technologies is creating a series of kits that combine vectors, GMP-banked host cells, and cell culture media into streamlined workflows for biotherapeutic developers. The first of these kits, the OptiCHO™ Protein Express Kit, was launched earlier this year. Offerings in 2010 include a kit, based on Invitrogen’s CHO-S cell line, that will link transient expression and stable cell-line workflows together.
Concern over the H1N1 influenza strain has led to fears of border closings and large pockets of humanity being cut off from life-saving vaccines. Thankfully that situation has not materialized, but it has spurred interest in local or regional small-scale vaccine manufacture, and with it the need for platform media that is easily created and shipped to distant production sites.
Thermo Fisher Scientific has been active in this area, developing media products optimized for production at 1,000–2,000 L volumes. “We have been building out our infrastructure around the world, and now have field-based experts who can go onsite to demonstrate how media products can be used and to support setup of these processes,” says Brandon Pence, associate director of market management.
Related to the “agile vaccine” idea is the trend toward ready-to-use products, says Ken Lydersen, CSO at Irvine Scientific. “This creates opportunities for suppliers to provide value-added products and services like cell-line and media optimization.”
Irvine, which currently produces more than 1,000 tons per year of powdered media, will double its capacity with the addition of a second cGMP manufacturing site in Tokyo. The plant is expected to come online early in 2011. The company specializes in rapid turnaround of prototype media formulas through its Express Media Service, reports Lydersen.