Since 2008, downstream purification issues have become progressively more acute problems for biomanufacturers. But that’s begun to change this year, according to results from BioPlan Associates’ 9th Annual Report and Survey of Biopharmaceutical Manufacturers.
In our study of 302 global biomanufacturers, we found that there are now fewer downstream processing “acute” problems (typically, capacity bottlenecks in chromatography and ultrafiltration steps), and more “chronic” ones associated with general operational inefficiencies. Facility budgets are funding downstream purification solutions that reduce the number of steps, improve performance, and lower costs.
Compared to prior years, we are seeing a notable decrease in the percentage of global biomanufacturers that expect to move away from Protein A purification. For example, the industry’s interest in alternatives to Protein A for existing production units dropped from 27.1% in 2009 to 15.5% this year (Figure).
Although a majority of respondents are still interested in improving their downstream processing, and Protein A chromatography, they display less conviction about actually doing so. From our report, 21.1% of respondents said they had investigated alternatives to Protein A to improve downstream purification operations (down from 31.1% in 2011), but just 11.8% had actually switched to alternatives.
Some of this may be attributable to a gradual lessening of impact of downstream chromatography on capacity levels. This year, 17.5% of respondents said that chromatography steps create “significant” or “severe” capacity constraints at their facilities. That’s a slight increase from 14% last year, but is lower than in prior years (2010: 18.9%; 2009: 21.6%; 2008: 20.2%).
Disposable UF Systems
There appear not to be any major advances on the immediate horizon for capacity improvements in chromatography. This may be affecting the extent to which respondents are considering alternatives. When we asked respondents which downstream purification technologies they are considering, we found that disposable ultrafiltration systems are in the most demand, by 47.1% of respondents, followed by buffer dilution systems/skids, use of high capacity resins, in-line buffer dilution systems, and single-use disposable TFF membranes. We also found that 23.5% are considering the use of filters instead of resin chromatography.
Perhaps in response to a lessening demand for chromatography alternatives, our study shows that vendors are placing significantly more emphasis on new product development in disposable/single-use devices, and less on chromatography alternatives. Of 35 broad areas of new product development, the top new downstream areas that vendors are currently working on include:
1) Disposable/single-use filtration
2) Chromatography, disposables
3) Chromatography, alternatives to Protein A
The impact of downstream chromatography steps are leveling off and becoming more of a chronic vs. acute problem. This is the result of step-wise improvements in downstream operations.
Development of new, innovative technologies in purification continues to be funded by vendors (although not at the level seen in recent years), and downstream innovation is being actively sought by end-users. So within five years it is quite likely that single-use, simplified, and/or continuous-process purification may emerge that will change the way biologics are purified.