Higher volumetric productivity is contributing to smaller scale manufacturing. In addition, noted Whitford, volume demand is decreasing, with emerging products such as personalized medicines with companion diagnostics targeted to screened populations, and cancer vaccines generally required in substantially smaller amounts.
Another trend described by Whitford is “scaling out” instead of scaling up, also known as distributed manufacturing. Instead of running one 10,000 L batch, a company might opt to run five 2,000 L reactors in parallel.
Among values inherent in this flexibility, this minimizes the potential loss if one batch were to become contaminated or unusable for some other reason. Single-use systems also simplify geographic distribution of manufacturing capacity. To duplicate a facility in another location would require only purchase of the same devices and transfer of the process, whether to an adjacent building or another country.
Manufacturers of single-use devices are pursuing R&D to create new, cleaner materials for single-use products and new ways of producing these materials. For example, Paul Killian, Ph.D., senior scientist at EMD Millipore, described research under way on new methods for sterilizing single-use materials that would reduce the amount of leachables created. At present, most single-use systems are gamma-irradiated, a process that generates small oxygenated compounds that contribute to the leachables load.
Raising the ceiling for “large-scale” processing in single-use bioreactors from 1,000 L vessels to the new generation of 2,000 L vessels has expanded the utility of single-use systems for commercial-scale batch production. Sartorius Stedim Biotech plans to introduce a 2,000 L scale single-use bioreactor in 2013. Davy De Wilde, director of marketing for fermentation technologies for the company does not anticipate any volume increase beyond that.
“Improved cell strains, media, and process conditions have led over the past years to a significant increase in product yields per volume,” he says. “This enables the industry today to reach their required product volumes already at 1,000 L or 2,000 L scale, while previously required bioreactor volumes were up to five times higher.”
This is helping to drive uptake of single-use systems overall, according to Alison Rees-Manley, fermentation application specialist at Sartorius Stedim Biotech.
Other factors contributing to the increase in adoption of single-use bioreactors, in De Wilde’s view, are reduced cost of ownership and increased flexibility, thus allowing users to switch more easily between processes and to increase capacity rapidly due to reduced lead times and utility requirements.
User needs are a critical driver of technology and product development, and in response Sartorius Stedim Biotech plans to introduce a point-of-use integrity test for single-use bioreactor bags, beginning with a test for its bioreactors up to the 200 L system by the end of 2012 and shortly followed by tests for bags up to 1,000 L.