Better process development is creating industry benchmarks for bioprocessing.
By Eric Langer
Biomanufacturing efficiency is on everyone’s minds, being the single most important area of focus for global bioprocessing. And contract manufacturing organizations (CMOs) are on the leading edge as they implement performance improvements. CMOs must remain efficient if they are to be competitive--so this is no surprise. Results from BioPlan Associates’ 12th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production (1) offer some clues as to what CMOs are doing to remain competitive.
CMOs’ love affair with single-use devices has been well documented. Indeed, single-use implementation and integration is a much larger focus for CMOs than it is for biotherapeutic developers. And as the results in Figure 1 indicate, it’s easy to see why: nine out of 10 CMOs agree that biomanufacturing improvements over the past year are coming from the use of disposable and single-use devices.
Given that CMOs have long been at the forefront of single-use adoption, it’s perhaps more interesting to look at factors that are rising in importance for CMOs. One such factor is better process development, cited by 81.8% of CMO respondents as contributing to improved biomanufacturing performance, up from two-thirds of respondents in 2014.
This is a notable result, as process development outsourcing has been on the rise in recent years. Separately, 43% of industry respondents reported outsourcing at least some upstream process development activities to some degree, up from just 17.1% back in 2010. Additionally, 41% reported at least some outsourcing downstream process development activities to some degree. Improvements in process development, therefore, are an encouraging sign for CMOs as this becomes a growing business opportunity.
A similar pattern plays out in validation services. This is also a growing area of opportunity for CMOs, with validation services a more popular outsourcing activity than process development. In the 2015 survey, for example, almost three-quarters (73%) of industry respondents reported outsourcing at least some validation services, up from less than two-thirds in 2010.
Another area to which more CMOs attribute internal performance improvements is upstream production operations. In the 2015 survey, 64% of respondents said that these improvements contributed to better overall performance, up from 56% in 2014. In fact, CMOs were almost as likely to credit upstream improvements as downstream improvements with better biomanufacturing performance. That may partly be due to the current bottlenecks being experienced in purification and separation operations. And CMOs’ experience with multiple products and campaigns provide them expertise that in-house manufacturers may not have.
Upstream biomanufacturing operations outsourcing has been growing more rapidly than downstream operations, according to BioPlan’s data. In the space of five years, the percentage of industry respondents outsourcing upstream operations has doubled, from 21% in 2010 to 42% in 2015. While outsourcing of downstream operations has been on the rise, it hasn’t had quite the same growth trajectory, up from 28% in 2010 to 39% of respondents in 2015.
Upstream operational improvements are less of an industry focus for both CMOs and in-house manufacturers. Indeed, when BioPlan surveyed the industry on the single most important area or operational focus in 2015, not a single CMO pointed to upstream processing advances as the top area; because downstream production (DSP) operations issues remain strong. A worrisome 64% of CMOs said that downstream processing is impacting capacity and overall production by causing at least some bottleneck problems (noted by 64%). In fact, only a quarter of respondents are currently enjoying no bottlenecks in their downstream processing.
CMOs spending to offset potential capacity crunch
Not surprisingly, CMOs are seeing more problems than biotherapeutic companies due to downstream processing, and are experiencing more significant production capacity constraints, too. The BioPlan study indicated they will likely continue to invest in better DSP technologies as a way out of these problems, for example.
Facility constraints are the most common factor CMOs cite as creating capacity crunches at their facilities over the next five years (cited by more than two-thirds). Probably by no coincidence, 7 in 10 CMOs plan to increase their spending on new facility construction this year, by an average amount of 11.3%.
The next biggest culprit in projected capacity constraints is downstream purification capacity. Spending plans for CMOs are positive: almost three-quarters would be increasing their capital equipment budgets, with an average increase of 11.7%.
Expected budget hikes—for capital equipment (11.7%) and new facility construction (11.3%)—were the largest of all areas tracked. To grow their businesses, CMOs are dedicating funds to offset potential capacity constraints in the future.
Not surprisingly, better downstream purification technologies are also on the agenda. CMOs note that downstream innovation is the leading way to avoid future capacity constraints. Spending projections aren’t quite as buoyant for downstream innovation, though they are solid. In 2015, 6 in 10 will increase spending on new technologies to improve efficiencies and costs for downstream production, for an average budget increase of 6.1%. This is likely due to new technologies providing more incremental increases in efficiencies as opposed to new equipment that can quickly provide access to more capacity and avoid crunches.
Single-use equipment is helping CMOs achieve performance improvements, both for downstream purification and for manufacturing productivity overall. But CMOs are taking numerous other factors into account as they improve efficiencies and lower costs. These range from better analytical testing and product release services to better operations staff training, optimized media and improved existing quality management systems. Better process development is also a growing area of interest for CMOs as they take on more process development work--both upstream and downstream—for clients.
Nevertheless, one of the main routes to overall productivity improvements for CMOs will be better downstream operations. Besides the use of disposable equipment, a majority of CMOs are developing downstream processes with fewer process steps. Many are also using or evaluating a number of technologies, including:
• Membrane-based filtration technologies
• Ion-exchange membrane technologies
• Ion-exchange technologies with higher capacity.Biotherapeutic developers might keep a close eye on these activities. CMOs, with their broad experience, multiple product lines, and need for rapid changeovers, are often at the forefront of innovation. Though their requirements clearly differ from those of biotherapeutic developers, the process improvements sparked by innovations and adopted by CMOs can provide a recipe for the industry as a whole. As such, it will be interesting to monitor the activities and technologies that CMOs adopt to improve downstream production operations and overall biomanufacturing productivity.
1. BioPlan Associates, 12th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production (Rockville, MD, April 2015).