The significant differences in business models between contract manufacturing organizations (CMOs) and biotherapeutic developers translates to very divergent reasons for their increased use of disposable, single-use biomanufacturing devices, according to results from our 9th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production[1]. The CMO business model, which is built around a pipeline of multiple projects, needs smaller footprint requirements to generate higher revenue. Faster turnaround times and cleaning between campaigns are major factors in decision making for CMOs, as well.
In our study this year we surveyed 325 global biomanufacturers in 30 countries regarding areas of biomanufacturing including trends, budgets, downstream processing, quality, hiring and single-use, disposable device usage.
One of the factors regarding usage of single-use devices that we measured were the factors driving increasing adoption. This year we measured 24 critical factors and found that the largest gap between CMO respondents and biotherapeutic developers related to "Reduced space requirements" where 58.8% of CMOs cited the factor as a ‘very important’ reason to increase their use of disposables. This was almost triple the proportion of developers (22.2%) who cited that attribute. Other major gaps existed in areas like "Improved scheduling ability" (44% vs. 23%), "Faster campaign turnaround time" (53% vs. 36%), and "Increasing total annual capacity at the facility" (38% vs. 18%) are all cited as key factors by a greater proportion of CMOs than developers.
This gap is relevant in understanding the differences between these two market segments. However, both drug innovators and CMOs cite the factor: "Reducing capital investment in facility and equipment" at or near the top as the most critical attribute (CMOs, by 77%, drug innovators by 36%). This is the leading CMO factor and the fourth leading biotherapeutic developer factor.
Many of the common reasons for increased use of disposables are shared among the 325 developers and CMOs we surveyed, including decreased risk of contamination, and reducing time to get the facility up and running. Yet in nearly every category, CMOs see the factors we identified as substantially more important than their drug innovator counterparts, with the largest discrepancies among factors that are most germane to their business model.
Factors Restricting Use of Disposables
Strong differences in perception between CMOs and developers show up in factors that restrict the industry’s use of disposables,as well.
Factors that more CMOs than developers say (agree and/or strongly agree) inhibit their use include:
- High cost of non-disposable equipment (housing, controllers, etc.)
- High cost of disposables (consumables)
- Incompatible controllers & data management systems that don't work with existing systems
- We do not want to become vendor dependent(single-source issues)
Factors that CMOs are less concerned about include:
- Breakage of bags and loss of production material is a concern
- We have already invested in equipment for current system
- Leachables and extractables are a concern
It is interesting to note that CMOs’ concerns regarding leachables and extractables are dramatically lower than biotherapeutic developers’ concerns. This may be due to CMOs greater familiarity with these devices. As bio-developers’ experience increases, their concerns over L&E/regulatory issues may also diminish.
Not unexpectedly, some of the areas where CMOs display a measurably greater concern relative to developers are cost related. Although CMOs can often pass much, or all of the cost for operational items such as SUS equipment, high-priced devices can increase overall costs of CMO services. For instance, the high cost of disposables (consumables) is a much greater hindrance to CMOs than developers (78.6% of CMOs vs 58.1% of developers). Notably, it appears that these cost constraints are specific to the disposable space: just 29% of CMOs said that general budgetary constraints were a significant factor reducing their use of single-use devices, compared to 26% of developers.
Critical Decision Factors for Disposables Remain Constant
Data on the ‘most critical reason’ for increasing disposables has been fairly consistent for the past few years. When asked to indicate
the single most critical reason for using disposable technologies in 2012, participants (developers and CMOs combined) said that ‘reduce capital investment in facility and equipment’ was the most important (17.1% of respondents). The same reason was in the #1 spot for 2011, cited by 21%, and in 2010, indicated by 16.8%. ‘Eliminating cleaning requirements’ (presumably the associated costs, as well) remained in the second spot in 2012, up from 12.6% of respondents in 2011 to 14.3% 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.
When asked to indicate the most critical reason for not increasing the use of disposable technologies, we also found consistent results in 2012 from 2011 data. This year, the top 2 reasons were the same as in 2012, although they switched positions. ‘Leachables and extractables are a concern’ took the top spot this year, noted by 14.4% of respondents, up from 12.9% in 2011 and 12.3% in 2010. 13.3% of respondents said, ‘we have already invested in equipment for current system’ (this compares with 13.6% in 2011). This year the ‘high cost of disposables’ was cited by only 6.7% of respondents, taking the fourth spot, after being third in 2011 (with 10.6%) and 2010 (with 11.0%).
Leachables and Extractables Still an Issue
One of the most challenging factors inhibiting the acceptance of single-use devices is the attitudes and concerns among decision-makers and regulators regarding leachables and extractables (L&E)in disposable systems. This factor was cited as a critical hindrance by the greatest proportion of biotherapeutic developers and CMOs combined (74.2% agree or strongly agree).
To evaluate changes in perception over time, we ask respondents (CMOs and developers) whether they "agree" or "strongly agree" with several statements. For the past 4 years, the L&E issue has continued to stand out. For example, this year, 79% of respondents "agreed" or "strongly agreed" that ‘Vendors should generate and validate L&E data,’ While this was a decrease from 90% in 2011, it still represents the concerns of the great majority of biomanufacturers and CMOs. This result is consistent with response rates from 2008-2010, when they hovered around 82%. This suggests that end-users remain convinced that vendors need to do more regarding testing and analysis of the materials used in their devices.
We note, however, that this number declined in relation to later stages of manufacturing, where 51.4% said they ‘Expect to generate L&E data myself for Phase III or commercial applications.’ This likely reflects biomanufacturers’ need to reduce regulatory risks associated with leachables and extractables at later stages of production. At earlier stages of production (Phase I/II), the percent of manufacturers expecting to generate L&E data themselves drops to 27.6%, although this is an increase from 17.4% last year.
Increased Adoption Ahead?
It is possible that respondents’ concern regarding acquisition of L&E data may be tied to their expectation of near-term disposables adoption, and as such are increasingly considering how L&E testing will be done, and who will do it (vendor as part of a quality/validation package, outsourced, or in-house). The top factors restricting adoption of disposables (especially existing investments in equipment and L&E concerns), we expect that penetration of SUS devices will become more widespread, especially as CMO experience translates to greater adoption by biotherapeutic developers. Once current installed equipment is depreciated or wears out, and when L&E regulatory issues are addressed, it is likely that cost effectiveness will become a bigger obstacle to adoption. And, as our data shows, even this barrier seems to be falling.
Author's Note
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.
References
1. 9th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, Preliminary Data, Release April 2012, www.bioplanassociates.com.
Eric S. Langer is president and managing partner at BioPlan Associates, Inc., a biotechnology and life sciences marketing research and publishing firm established in Rockville, MD in 1989. He is editor of numerous studies, including "Biopharmaceutical Technology in China," "Advances in Large-scale Biopharmaceutical Manufacturing," and many other industry reports. [email protected] 301-921-5979. www.bioplanassociates.com