Presenter: James DeKloe, Solano College, CA

1. Single Use Technologies in
Biomanufacturing
June 8, 2016
Bio-Link Summer Fellows
Funded by the National Science Foundation
Advanced Technological Education grant DUE 1405766

2. Single Use Technology = Disposable (Plastic) Systems
• The use of single use technology in biomanufacturing is widespread
• There are some advantages and disadvantages to single use technologies
• Single Use strategies have been applied to both Upstream and Downstream applications,
but cell culture applications are the most common
• Many companies use hybrid strategies with only a component of the manufacturing
process using SU technology.
• Single-use: systems that consist of fluid path components intended for one time use,
usually to replace reusable stainless steel components. These components are typically
made of plastic and are disposed of after use
• Hybrid: a process that contains both single-use and reusuable (stainless steel) strategies
at different parts of the manufacturing process

3. Process – Cell Culture versus MicrobialProduction Systems
E. coli S cerevisiae Insect cells Hybridomas Mammalian Cells Transgenic Animals
Ferrier-Miralles et al.,
Microbial Cell Factories 8(17) 2009

4. There is a potential to use a Single Use
Application during every manufacturing step
Source: http://www.invite-research.com/en/contentseite/aktuelle-forschungsprojekte/mobidik.html

5. Single Use Components are widespread and
their use is increasing:
According to BioPharm International’s 2015 Manufacturing Trends
Survey:
• 71.4% of respondents currently use hybrid manufacturing systems –
these include single-use systems for at least a part of the product
• 15.9% use all stainless steel systems
• 12.7% use all disposable systems
R. Peters BioPharm International 28(1) 2015

6. Advantages of Single Use Technology
• Reduction or elimination of cleaning, sanitization, and sterilization steps
• This reduces the consumption of water – pure water is extraordinarily
expensive to produce
• This reduces the energy used to produce purified water
• This reduces the consumption of cleaning and sanitizing chemicals (CIP)
• This eliminates the need to sterilize bioreactors (the vendor has done this)
• This eliminates the need to generate clean steam
• This reduces the need for cleaning and sterilization validation (and moves it
to the vendor) – this eases regulatory compliance

7. The Advantages - Continued
• Lower upfront capital costs – this becomes a major advantage for a
small company or a new company wanting to start production quickly
• Again, an advantage in regulatory compliance for a small or new
company
• More rapid, less expensive changeover between campaigns – less fear
of cross-contamination
• Faster cycle times (by eliminating the need for cleaning)
• Lower Risk – lower probability of cross-contamination with another
product or microbial contamination

8. What are the disadvantages? Why isn’t
everything single-use?
• Scale Limitations (only up to 2000 liter cell culture)
(although increasing product titers and cell densities are making this
less important)
• Technical limitations that currently leave some operations without good
single-use options
• Increased reliance on outside vendors – potential supply chain problems
• Concerns over leachables/extractables from the plastics
• Additional consumables cost
• Concerns over the environmental impact – mainly the increase in solid
waste that currently goes to landfill

9. The Most Common Application is Upstream
The Wave Bioreactor was the first
“Rocker” bioreactor design.
This technology was purchased by
GE Life Sciences.
There are now many competitors.
Source: GE Life Science

10. Single Use Bioreactors
Source: Eppendorf

11. Single Use Bioreactors
Source:
ThermoFisher

12. Probes Used in Single Use for Process Control
• Disposable Probes
• pH
• dO2
• Temperature
Source: GE Life Sciences

13. Single-Use Cell Harvesting Options

14. Single Use Purification Options
• Chromatography: Expensive
• Membranes: smaller binding
capacity
• Upstream is ahead of
downstream in single use
Source: Repligen

15. Plastic Bags used for
• Initial Media
• Bulk
• Fill needles
• Single use hypodermic
needles

16. Environmental Impact
• There is the generation of much more solid waste that typically will go to a
landfill (although there might be an incineration and co-generation option)
• The plastics used in single use technologies cannot be recycled
But…
• Major reduction in energy costs associated with sterilization and cleaning –
the production of pure water takes energy
• Major reduction in chemical use associated with cleaning
• Major reduction in waste water
Several studies have calculated, although this is counterintuitive, that there
is a positive effect on the environment with the adoption of single-use
technologies

17. Single Use Technologies
Advantages/Disadvantages Summary
Advantages
• Lower Capital Costs
• Rapid and inexpensive
changeover between products
• Potentially greater productivity
• Reduction of costs for pure
water, steam, and some
chemicals
• Reduced risk of chemical and
microbial contamination
Disadvantages
• Increased consumables cost
• Scale Limitations
• Increased reliance on outside
vendors
• Concern over leachables,
extractables
• Environmental concerns

18. Examples
Genentech
• Antibody production requires a
large scale that Single Use cannot
accommodate
Stainless Steel Bioreactor sizes:
South San Francisco:
8 X 12,000 liter
Vacaville: 12 X 12,000 liter
8 X 25,000 liter
Oceanside: 6 X 15,000 liter
BioMarin
• Orphan drug production
requires a smaller scale
• 200 liter perfusion bioreactor
• Extensive use of single-use
technologies

19. Implications for Teaching About
Biotechnology
• Single-use technologies are widespread in industry, here to stay, and
therefore students should know about them
• SU technologies have advantages for the classroom; especially for
having the students grow cells in mammalian cell culture.
• Contamination prevention is probably easier for students in a SU
system
• For microbial production we will probably stay with glass and stainless
steel bioreactors.