Single-use technologies are often suggested as an option to introduce flexibility and reduce costs in biomanufacturing. Although true, benefits can vary between upstream and downstream processing.
Supplementing conventional biomanufacturing with single-use technologies
With more than 8000 drug candidates in development (1), the biopharmaceutical industry is highly competitive. Possibilities to keep development and manufacturing costs to a minimum is therefore of great interest to gain competitiveness in this market space. Single-use technologies are commonly used as alternative to conventional reusable technologies to reduce costs and shorten time to market. However, a truly single-use facility is not necessarily a requirement to achieve efficiency. “In reality, claimed single-use manufacturing is in fact hybrid bioprocessing”, says Andrew Sinclair, President and Founder of Biopharm Services.
Biopharm Services supports the biopharmaceutical industry with solutions to address strategic challenges faced in biomanufacturing. The company is the developer of BioSolve™ bioprocess analysis tools that enable biopharma innovators to reduce manufacturing costs and make informed process decisions to improve profitability and ultimately patient access.
“Hybrid bioprocessing is not a very precise term”, Andrew says. “In my view, its where the manufacturing process uses a combination of single-use and reusable components in contact with the process material and associated fluids, such as piping, housings, containers, and vessels. If we look at the key benefits that are attributed to what are described as single-use facilities, but are in fact hybrid, they have lower costs, smaller footprints, and less support infrastructure, but they still have some reusable equipment. The key benefits are derived from the decoupling of process equipment from building, that is, having no interstitial piping other than provision of basic service utilities. Removing cleaning-in-place (CIP) and sanitization-in-place (SIP) from the equipment are the primary drivers for simplification, the reduction in the size of vessels, so that everything fits into a single-floor facility. With the improvements and the rise of single-use equipment, such as bioreactors, containers, and physical transfer, a lot of the complexity is removed and, even with some reusable equipment in the downstream area, we can still achieve the facility simplification. A good example is the chromatography unit. A well-designed stainless steel chromatography column can be cleaned in situ and is effectively standalone and, hence, has many of the attributes of a single-use chromatography unit in terms of facility simplification.”
Process economic impact of single-use technologies in upstream and downstream operations
“There is a definite difference between upstream and downstream”, says Andrew Sinclair. “In most cases, upstream operations are managing the largest volumes, and bioreactors tend to be very complex when incorporating CIP and SIP. Single-use bioreactors address this complexity by removing the supporting infrastructure requirements. By limiting working volumes to 2000 L, the manufacturing area is contained to one level and, hence, it often makes good operational sense to scale out single-use bioreactors rather than go to stainless-steel bioreactors. Volumes reduce significantly in downstream operations after harvest and, hence, the scale of the equipment reduces”, Andrew continues. “Once supporting infrastructure such as hold vessels for buffers are converted to single-use, a lot CIP and SIP complexity is removed. Therefore, it is not as important to convert to single-use in downstream processing. Instead, staying in a reusable stainless steel format can often be cheaper.”
Reducing support infrastructure by introducing continuous processing
Continuous bioprocessing is getting a lot of attention to further reduce support infrastructure related to hold vessels for buffers and such. Also in this area, the term hybrid bioprocessing is discussed.
“In the upstream arena, people often refer to perfusion as a variant of continuous. Perfusion culturing is a mature technology and the economics are well understood. Where the productivity of the cell line is equivalent in fed batch and perfusion, the balance favors fed batch based on efficient medium utilization and easier process development. Perfusion has potential, but so does fed batch. The bias is towards fed batch with membrane techniques being used to increase cell density. The situation in downstream is different. Although the technology is at the early stages of implementation, continuous downstream processing has the potential for a step change in our approach to purification. In my view, it will require innovative thinking around, automation, PAT, and online release to realize its full potential”, Andrew concludes.
Sign up for future post on hybrid bioprocessing that will discuss the following topics:
- Solutions for large-scale buffer management.
- Single-use versus re-use equipment in downstream bioprocessing.
- Batch versus continuous bioprocessing.
1. EvaluatePharma® World Preview 2017, Outlook to 2022. Evaluate Ltd, 10th Edition, June (2017).