Economic, Environmental, and Process Robustness Evaluations
We carried out an economic analysis in which we considered factors such as the upstream and downstream process, the capital
investment, utility requirements, labor time, raw materials, waste management, and maintenance. To do this, we evaluated available
process modeling tools on the market and selected BioSolve, from Biopharm Services Ltd. We were able to run multiple scenarios
very rapidly in BioSolve, comparing the completely stainless-steel based process (scenario 1) with the fully disposable process
(scenario 2) and a third option, which was a hybrid solution involving both disposable and stainless steel equipment (scenario
3).
Figure 1. Cost comparison for three set ups for a bioprocess based on a bioreactor with a 1000-L working volume. Scenario
1: completely stainless-steel process; scenario 2: a fully disposable process; and scenario 3: a hybrid solution.
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Economic Comparison.
The results left no doubt as to which solution was the most economically attractive. Through full disposables implementation
in upstream and downstream processes, we decreased the capital charge by 30% (Figure 1). The implementation of disposables
for each step also meant a 90% decrease in pure water requirements and a 50% reduction in water for injection needs.
Figure 2. Comparison of the energy requirements for a stainless-steel process to a disposables-based process.
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Environmental Impact.
On the environmental impact front, we carried out an energy requirement assessment. Our evaluation showed that the disposable
process (including gamma irradiation, sterilization, manufacturing of tubing, and so on) decreases energy requirements by
35 to 45% compared with a traditional stainless-steel process (Figure 2).
The question of disposable waste is more complex, particularly when you look at the available options. Recycling is not really
feasible. It requires waste segregation and sometimes specific treatment. Landfill, although low cost, has a potentially high
impact on the environment in terms of noise, odor, and visual aspect. Incineration without energy recovery is better than
landfill; modern incinerators allow for carbon dioxide capture. We use incineration.
Process Robustness.
There is improved process robustness when disposable closed systems are implemented for sampling, decontamination, and waste
elimination. This improved process robustness results in better regulatory compliance and significant time and money savings.
These savings apply both to existing facilities for cGMP manufacturing and for new facilities.
SUMMARY
As part of the Sanofi Pasteur Knowledge & Innovation for Technology Excellence (KITE) initiative, we have been able to demonstrate
the feasibility of large-scale Vero cell culture in disposable bioreactors up to the 500-L scale. This included successful
integration of the disposable process from seed to large-scale cell expansion and infection, including cell thawing and expansion
directly in the disposable Nucleo 20 (a closed system for sampling, decontamination, and waste elimination) up to a 500-L
working volume. Good virus yield and productivity were obtained in 20-, 200-, and 500-L scale disposable bioreactors.
By using a validated BioSolve process modeling platform, we were able to identify where significant time and money savings
could be achieved by implementing disposables. Sanofi intends to continue the scale-up program and will move to disposable
industrial integration wherever disposables demonstrate benefits in line with the criteria defined in the KITE program. In
the future, based on KITE program criteria, Sanofi Pasteur will in some cases consider hybrid processes involving a mixture
of stainless steel and disposable technologies to solve ergonomic and large equipment decontamination issues.
ACKNOWLEDGEMENTS
We would like to thank our colleagues who participated actively in the KITE disposables initiative and helped prepare the
scale-up case study.
Andrew Sinclair is the managing director and Miriam Monge is the vice president of marketing and disposables implementation, both at Biopharm Services, Chesham, Bucks, UK, +44 1494
793 243, disposables@biopharmservices.com
Miriam is also the European chair of ISPE's Community of Practice for Disposable Technologies.
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