BioPlan Associates just reported results of its 8th annual Survey of Biopharmaceutical Manufacturing Capacity and Production -- a summary of which appeared in July's GEN Vol. 31 No. 13, page 1. The number one issue cited by the 352 respondents as needing more attention was bottlenecks in downstream processing.
Due to the rapid increases in titer being achieved in upstream processes -- through improved expression systems, better cell lines, more optimized media/feeds, and more efficient bioreactors -- many are producing more product than the downstream processes were designed to handle. A total of 68.5% of respondents said that their facility was experiencing at least some bottleneck due to downstream issues -- with a historic survey high of 11.8% characterizing these as serious (up from 4.6% in 2008). Respondents further indicated they were goign to spend more money to try to solve the issues with budgets for downstream work projected to increase by 6.4% in 2011.
Technologies that were identified as important to downstream improvements included high-capacity resins, in-line buffer dilution systems, single use filters, and disposable UF systems. Additionally, several platform level technological improvements were identified by companies as areas they were investigating, including:
- simulated moving bed chromatography
- improved resins that were cheaper, faster-flowing, more selective, and have higher bindng capacities
- novel separation methods like chromatography monoliths
- alternatives to protein A
- disposable protein A columns for mAb purification
- improved depth filters, ultrafiltration and membrane filters to replace columns
- more product-customized affinity purification media
- improved modeling of separation at the molecular and process level
The burden of improvement has clearly shifted downstream for the next phase of biopharmaceutical production optimization. Downstream is now challenged to meet the improvements achieved upstream over the past 5-10 years to bring the system more into balance.
Posted by Bruce Lehr July 5th 2011.