Industry Yields Increasing
The largest portion of survey respondents (59.7%) now report mammalian cell culture commercial production of monoclonal antibodies (mAbs) at between 0.5 and 2 g/L, with increases in this group observed in the past three years.
Another 26.6% report attaining commercial titers between 2–3 g/L, 20.5% attaining 3–5 g/L, and 8.5% attaining >5 g/L. Nearly half (46%) reported clinical-scale manufacture between 0.5 and 2 g/L, with 30.1% reporting 2–3 g/L, 25.7% reporting 3–5 g/L, and 11.5% reporting ≥5 g/L. In general, higher expression levels are now reported for late-stage compared to commercial manufacturing. This is not unexpected since process improvements generally take place at earlier development stages.
Increasing expression system yields enables use of smaller bioreactors and facilities. Bioprocessing system (bioreactor) sizes for large-scale manufacture are likely to decrease or remain steady in coming years, with companies increasingly adopting single-use 1,000–2,000 L bioreactors for late-stage and commercial manufacturing.
Particularly as single-use bioreactors begin to displace stainless steel for commercial manufacture, those needing higher capacity may begin to use multiple single-use bioreactors operating in parallel to achieve production levels and economies-of-scale now largely restricted to those operating ≥10,000 liter bioreactors.
This is especially true for recombinant mAbs with a large number of new drugs and biosimilar products in development; mAbs have high repeated dosing requirements and large amounts of protein, e.g., 100s of kilograms/year, are needed for a blockbuster product. Also, advances in bioreactor technology, particularly in smaller size perfusion systems, will likely result in overall reduction in bioreactor requirements.