Editor’s Note: For a broad overview of BioPlan’s Survey, read “Biopharma Faces the Future.”
Disposable process equipment is on its way to becoming an industry standard, with 30% demand growth projected over the past few years . Stepwise acceptance of single-use disposable components has allowed the technology to progress from simple fluid handling applications involving storage bags and tubing to complex bioprocessing.
Today, we see a growing number of commercially viable, up- and down-scalable bioreactors being developed, and we will likely see fully integrated, up- and downstream disposable technologies being adopted in the not-too-distant future.
At this point, though, disposable systems are not fully accepted in the industry. BioPlan’s sixth and latest Annual Report and Survey of Biopharmaceutical Manufacturing (see Pharmaceutical Manufacturing, April 2009, p. 16), examined disposables along with nine other critical areas associated with biopharmaceutical production, eliciting responses from 446 production executives at drug developers and CMOs in 35 countries. Survey results identify key user technical concerns as:
- Leachables and extractables
- Scale of operation for bioreactors
- Costs of chromatography
Regulatory concerns about L&E have diminished slightly. Where 17% of respondents considered this a top issue last year, only 10% did this year (Figure 1). Similarly, “lack of disposable equipment that meets process requirements,” the primary user concern last year, has drifted into a lower priority status.
Budget Concerns Increasingly Critical
In fact, in this year’s survey, three of the top four issues were cost-related, rather than technical. The top concern, “We have already invested in equipment,” suggests that decision makers are not convinced that, for their applications, they need to change to disposable systems.
Single-use products are being adopted in new areas of biomanufacturing at an increasing rate, especially for the more technically advanced disposables. For example, production bioreactors were newly introduced to 39% of respondents’ facilities over the past 12 months (Figure 2).
Reasons for Increasing Use
We identified 25 reasons that respondents considered to be factors in deciding on the use of single-use technologies. This year, the top reason continues to be to “Eliminate cleaning requirements,” noted by 88% as being “Important” or “Very important.” Following were “Decrease risk of product cross-contamination.” Then, “Reduce time to get facility up and running” (79% this year, 74% last), and “Reduce capital investment in facility & equipment” (78% this year, 73% last year). (See Figure 3.)
What’s Holding Disposables Adoption Back?
We identified 26 possible reasons that manufacturers may be restricting their use of disposables. The primary reason biopharmaceutical manufacturers and CMOs might not expand their use of disposables this year, as in previous years, was concern over L&E. This year a total of 64.2% of respondents “Agree” or “Strongly agree” that L&E issues are restricting their use (Figure 4).
This compares with 75.4% of respondents last year. Part of this is likely the result of the increased use of disposables, which has, in turn, increased awareness and regulators’ interest.
The second greatest concern this year regarding the use of disposables was “Breakage of bags and loss of production materials” (which grew to 62.5% from 54.9% last year). Following these factors were concerns about cost of disposables (60.8%), and “Becoming vendor-dependent (single-source issues),” and “Material incompatibility with process fluids.” (51.1%)
The top three factors cited this year:
- Leachables and extractables are a concern (cited by 64.2% of our respondents)
- Breakage of bags and loss of production material is a concern (62.5%)
- High cost of disposables (consumables) (60.8%)
Pointing out the potential risk of E&L to patients during clinical trials, Ingrid Markovic, PhD, an Expert Review Scientist for FDA CDER, has emphasized the need to develop appropriate detection and continuous monitoring systems for these compounds and to establish acceptable limits . She suggests that every biologic protein product and its accompanying packaging system be evaluated on an individual basis using common scientific principles.
Who Should Perform L&E Analysis?