December 1, 2011 (Vol. 31, No. 21)
Eric S. S. Langer President and Managing Partner BioPlan Associates
Downstream purification has been a well-known cause of capacity headaches for biomanufacturers everywhere, with over half the industry recognizing this as an on-going pinch point. Both end-users and suppliers know that solving this will permit other improvements, including shortening product release cycles and allowing implementation of new upstream innovations, perfusion bioreactor applications, single-use devices, and even fully modular single-use operations.
One way the industry is addressing the bottleneck is by incrementally optimizing the overall downstream purification process. This year, according to BioPlan’s 8th Annual Report and Survey of Biopharmaceutical Manufacturing, 37.8% of the industry is actively “optimizing systems to improve downstream performance”. This includes many small approaches to streamline and reduce the total number of processing steps involved.
To get there, end-users and vendors are working on new approaches both small and large. Because it is unlikely that changes will occur in approved processes, most companies focus on new processes, incremental changes, reductions in the number of steps, and the use of new, more efficient devices and processes. These small steps may yield the biggest overall improvement in the short term.
However, in the long term, technologies are being developed like new mixed-mode chromatography sorbents, which are being implemented in new product processes. Prepacked and disposable columns at smaller scale are the fastest growing area where new downstream processing solutions are being introduced.
In our study, we evaluated which new downstream technologies respondents are considering currently, and compared this to last year’s responses. Although we find a strong interest in high-capacity resins and in-line buffer dilution systems, the most rapid growth has been in single-use prepacked columns, which grew from 1% last year to 31.6% this year.
In our study, depth filtration was seen as creating “moderate” or greater capacity constraint by 25.2% of respondents (compared to last year’s 32.7%). The number of respondents who felt that ultrafiltration steps were creating at least moderate capacity constraints fell to 26%.
Geographically, Western European respondents reported somewhat greater capacity filtration-associated bioprocessing constraints than U.S. respondents. Significant depth filtration constraints were cited by 6.9% of U.S. vs. 11% of European respondents, and ultrafiltration by 6.7% of U.S. vs. 8.2% of European respondents.
Filters are the most commonly used types of single-use (disposable) bioprocessing equipment. The near universal use of cartridge filters is the result of filters being used throughout bioprocessing. Even where not explicitly required, it is common practice to include in-line filters in fluid flow paths. Filters can be of all types and sizes, with external diameters, and pore sizes ranging from coarse stainless steel to nano-scale pore sized ceramic-based filters.
Filters constitute a large part of the total bioprocessing equipment markets. Our global industry analysis of biomanufacturing facilities indicates that there are fewer than 1,200 biopharmaceutical manufacturing facilities worldwide. Bioprocessing facilities typically use multiple filter types, and depending on market definitions, the biopharmaceutical industry use of filters and filter assemblies is $15–20 billion/year.
Fixed systems, e.g., stainless steel bioreactor-anchored systems, including those used for commercial-scale manufacturing, still dominate the bioprocessing equipment market, on the order of 90% in terms of revenue. In this context, the market for filters used in single-use-based systems is significantly smaller than the total, for the time being.
From our annual study, among major purchases planned in 2011, tangential flow filtration devices and disposable filter cartridges are a top item. The average budget reported for these TFF devices was $154,758/facility. This was followed by $144,183 budgeting for disposable filter cartridges and depth filters. The average amount budgeted for filter cartridges and depth filters has been found to vary from year to year, but has been increasing steadily since 2009.
Not unexpectedly, contract manufacturing organizations report even higher average spending on disposable filter cartridges and depth filters, $276,938, and for tangential flow filtration devices, $289,423.
Bioprocessing professionals are rather uniformly dissatisfied with many of their current downstream processing systems. With the large market for single-use filtration products and the high level of interest in improved downstream systems, it is not surprising that equipment suppliers and vendors are working hard to improve their product portfolios.
Eric S. Langer ([email protected]) is president and managing partner at BioPlan Associates.