By Eric Langer, president and managing partner, BioPlan Associates, Inc.
Over the past six years, single-use systems and devices for biopharmaceutical manufacturing have emerged as an important change agent. Today, single-use products have pushed beyond early-stage applications and are emerging into the much larger GMP commercial-scale operations. However, to reach large GMP commercial operations, according to BioPlan Associates, Inc.’s 2011 eighth annual report and survey of biopharmaceutical manufacturing capacity and production, single-use devices still need to address a number of problems. Topping the list are safety issues associated with leachables and extractables, and comparability with existing processes (stainless steel). Once achieved, we will likely see more rapid adoption.
Acceptance of single-use products in R&D and scale-up production has been driven by their effectiveness in reduced risks of contamination, faster changeovers, and advantages in cleaning and validation. Now, more effective, standardized single-use equipment is being demanded. Improvement is most strongly demanded in “extractables and leachables,” which leads the list in “Reasons for Restricting Use of Single-Use Devices” and was cited by 74% of 2011 respondents (up from 68% in 2010) to our survey. Innovation is needed to improve single-use devices in a number of areas. Survey respondents indicated dozens of key areas of concern, such as simplifying change-over and cleaning operations, reducing overall capital investments, and reducing risks of product cross-contamination.
Along with innovation will be the need for standardization of current designs and devices. “We believe the future of single-use technologies will include higher levels of integrity and quality, supply chain security, faster delivery to customers, and global material and specification standards for faster implementation,” says Doug Neugold, CEO, ATMI. To get to the next level of growth and efficiency will likely require a more plug-and-play-device approach guiding product design and innovation. This kind of standardization will also permit greater efficiency and lower costs. These innovations will help make bioproduction easier for facilities with fewer skilled staff and for those in developing regions.
Key Factors Restricting Adoption
A few of the reasons cited in 2011 by survey respondents as holding up the use of disposables include:
Leachables and extractables (L&E): 71.4% of respondents (This compares with 67.6% of respondents in 2010, and 64.2% in 2009).
Breakage of bags and loss of production material: 63%
High cost of disposables (consumables): 57.8%
In 2010 the number one concern was high cost, but that has now moved to the number three spot possibly due to easing of budgetary issues. But cost also likely has been supplanted because, with the greater acceptance of and knowledge of disposables’ options, the spotlight is now on practical implementation issues related to L&E.
Our 2011 Survey queried participants on a total of 26 single-use device-related factors. The number of factors under consideration is extensive — indicating the serious attention being given all facets related to single-use devices. When asked the question another way — which is your MOST important reason for not increasing use of disposable technologies — our 2011 respondents’ answers made up a long list (22) of factors (see figure 1).
CMOs Vs. Biotherapeutic Developers
We compared responses between CMOs and Biotherapeutic developers regarding the primary reasons they might not expand their use of disposables. CMOs were generally much less concerned about factors associated with implementation of disposables. Among both CMOs and biotherapeutic developers, “leachables and extractables concerns” and “breakage of bags and loss of product” remain the top concerns for both groups. However, biotherapeutic developers are more sensitive regarding these top issues, as well as cost factors. We found some very significant differences when comparing therapeutic developers’ single most important reason for restricting disposables with CMOs. The most striking was lack of ‘lifetime operating cost data,’ yet 8.7% of CMOs vs. 1.9% of biotherapeutic developers indicated this as the top reason for restricting usage.
Scalability was a concern for CMOs, where 8.7% of CMOs cited “limited scalability over a broad range” compared to only 3.7% for biotherapeutic developers. CMOs also found the “leachables and extractables” to be the most objectionable factor more often than developers (17.4% vs. 11.1%). Interestingly, CMOs were less concerned about cost this year (11.1% vs. 8.7% of CMOs). Last year, CMOs found the high cost most objectionable and rated it twice as high, as the primary reason to restrict disposable use. Although CMOs purchase a wider variety of disposables, and most pass such direct costs on to the client, expensive disposables may affect the ability to attract clients and overall profitability.