Contract manufacturing organizations (CMOs) are constantly looking for technologies that can reduce production and scale-up costs. This year they are finding those answers in single-use technology.
According to our 9th Annual Report and Survey of Biopharmaceutical Manufacturing,1, single use technologies make up 4 of the top 5 new products and services CMOs want their suppliers to focus development efforts on. From our study, we tested 21 different new product and technology areas, and ‘Disposable product: bioreactors’ heads the list this year, cited by 56% of respondents, a huge increase from just one-quarter last year. ‘Disposable products: bags, connectors’ is second on the list, with 48% of CMOs indicating they would like to see new developments in this area, up from 32.1% last year. Tied for third, with 40% of respondents, are ‘Disposable product: probes, sensors, etc.’, and ‘Disposable product: purification’.
After the top 5, there is a significant drop-off to the next tier of products and services CMOs are interested in. These second tier products include single-use chromatography products and process development. The lower interest in chromatography products may be due to the high costs of these devices.
Differences in CMO and Drug Developers
CMOs need flexibility and rapid change-overs, including cleaning/validation between campaigns. Disposable devices offer these advantages better than stainless steel options. Thus, the significant differences between CMO responses and those of drug developers are not surprising. However, when looking at how CMO responses stack up against biotherapeutic developers/innovators, we find a similar interest in some disposable products, but also some keen differences. For the second year running, drug innovators show the most interest in ‘disposable products, bags connectors etc.’ (38.7% this year compared to 37.4% in 2011), while this year ‘disposable product: probes, sensors, etc.’ takes the second spot with 35.5% of developers, up marginally from 34.2% last year, when it was in the third spot.
After these top 2 areas of new product development, though, on which both CMOs and developers are in relative agreement on ranking, opinions start to diverge. For example, developers are more interested than CMOs in ‘chromatography products’ (32.9% vs. 28%), ‘process development services for formulation’ (19.4% vs. 4%), ‘process development (downstream) services’ (27.7% vs. 24%), and ‘analytical assays’ (25.8% vs. 12%).
We also found that CMOs are far more interested in ‘cell line services’ (40% vs. 11%) and ‘disposable product: bioreactors’ (56% vs. 27.7%), which is a change from last year when developers and CMOs were eye to eye on ‘cell line services’ and CMOs indicated lower interest in disposable bioreactors.
Can Vendors Deliver Innovation?
With single use technologies atop the minds of developers and CMOs alike, the question becomes whether current bioprocessing vendors can deliver innovations in the near term. The predominant single-use paradigm remains adding multi-layer plastic laminate bags/ liners to what are essentially classic-design stainless steel bioreactors, mixers and other fluid containers. Most major vendors are committed to this approach, with some having invested in costly bag-making manufacturing facilities in the past couple of years. These companies will be committed to current product lines and this paradigm for at least the next few years.
Also, the nature of the bag-in-a-stainless-steel-bioreactor and many other current single-use equipment designs restricts opportunities for innovation and new product introductions. Current vendors are restrained by their customers from significantly upgrading existing product lines once they are introduced. Incremental product upgrades risk distressing their current customer base, particularly if current products are phased out. Any bioprocessing product change requires considerable expense and work, including making sure new devices work in specific applications; modification of regulatory filings, SOPs and training; and perhaps requiring costly validation testing. Innovations in single-use equipment may be more likely to come from small companies or from new corporate entrants.
What is particularly needed is the development of new materials, new and improved plastics and variations of current plastics that might enable major design innovations. Possible innovations might include single-piece molded plastic bioreactors that improved performance and safety, and reduced costs.
How Much Does Cost Figure In?
Many respondents’ desires for improved single-use equipment may actually involve desire for decreases in the cost of this equipment and improvements in productivity. In fact, as we found when we asked developers and CMOs their reasons for increasing use of disposables, cost factors are very much germane to the equation, particularly for CMOs.
Indeed, 83.3% of CMOs said that ‘reducing capital investment in facility and equipment’ is an either very important (72.2%) or very important (11.1%) reason for them to increase their use of disposables, compared to 66.4% of developers. This ranked ahead of other disposable attributes CMOs indicated as very important, such as ‘reduced space requirements’ and ‘faster campaign turnaround time’, all of which are relevant to the CMO business model that needs smaller footprint requirements to generate higher revenue.
When asked to indicate the single most critical reason for using disposable technologies in 2012, participants said that ‘reduce capital investment in facility and equipment’ was the most important. The same reason was in the #1 spot for 2011. ‘Eliminating cleaning requirements’ remained in the second spot in 2011, up slightly again this year. CMOs and developers seem to be viewing disposable options from a perspective that is tuned to a greater organizational focus on productivity, efficiency, and short-term cost savings.
In fact, particularly for CMOs, cost inhibits greater adoption of disposables, too. The ‘high cost of disposables’ is a much greater hindrance to CMOs than developers, with 78.6% of CMOs either agreeing or strongly agreeing this restricts their use, compared to just over half of developers. Not unexpectedly, CMOs also show a greater concern for the ‘high cost of non-disposable equipment,’ at almost double the rate of developers. Notably, though, it appears that these cost constraints are specific to the disposable space.
This year’s data shows that the industry continues to explore new technologies, modern expression systems, bioprocesses, bioreactors and purification equipment, and single-use equipment/disposables. And although direct, short-term cost considerations certainly play into the equation when looking at single-use technologies, the elimination of cleaning and sterilization validation of biomanufacturing equipment can offer major cost savings over the conventional stainless steel approach and reduce concerns for cross contamination. Our expectation is that in as short as a decade, single-use based systems will make up the majority of new commercial biopharma manufacturing systems.
1. 9th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production: A Survey of Biotherapeutic Developers and Contract Manufacturing Organizations, BioPlan Associates.
Survey Methodology: The 2012 Ninth Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production in the series of annual evaluations by BioPlan Associates, Inc. yields a composite view and trend analysis from 325 responsible individuals at biopharmaceutical manufacturers and contract manufacturing organizations (CMOs) in 30 countries. The methodology also included over 150 direct suppliers of materials, services and equipment to this industry. This year’s survey covers such issues as: new product needs, facility budget changes, current capacity, future capacity constraints, expansions, use of disposables, trends and budgets in disposables, trends in downstream purification, quality management and control, hiring issues, and employment. The quantitative trend analysis provides details and comparisons of production by biotherapeutic developers and CMOs. It also evaluates trends over time, and assesses differences in the world’s major markets in the U.S. and Europe.