Improved expression systemsBiosimilars manufacturers will need to increase expression-system yields to enable use of smaller bioreactors and lower cost facilities. New expression-system technologies, along with large single-use bioreactors for late-stage and commercial manufacturing, may begin to displace stainless steel for commercial manufacture. This shift is particularly true for recombinant monoclonal antibodies (mAbs), where a large number of biosimilar products are in development. mAbs have high repeated dosing requirements, and large amounts of protein in the magnitude of hundreds of kilograms per year often are needed.
New platforms (i.e., new host cells/organisms) and genetic-engineering advances applied to traditional platforms also can offer advantages in product yield, product quality, lower operating, purification, and infrastructure costs (2). Some newer technologies offer shorter times required to go from gene to transformed host cell line/organism to commercial-scale manufacture. Currently, there are just a few major players promoting new expression-system technologies, but there are many advances ready for adoption, adaptation, and further development.
Higher titers to reduce capacity requirements
The next generation of commercial products will have an even greater average yield. For late-stage clinical manufacture, the overall average in 2011 is 2.68 g/L, up from 1.96 g/L in 2008. Although protein yields over 30 g/L are being reported by expression system developers and early adopters, these yields are the exception, and yields for commercial manufacture in the 5–10 g/L range are more likely in coming years (1).