Avid Bioservices, Inc. (NASDAQ: CDMO), was an early adopter of cutting-edge single-use technologies (SUT). The commercial biologics contract development and manufacturing organization (CDMO) took its first step into large-scale single-use technology in 2007 with a 1000L single-use bioreactor (SUB).
 
“At that time the decision was based on our limited, but very positive, experience with single-use product storage bio-containers or filters operations like membrane chromatography. Bringing the technology to the manufacturing scale served as a proof of concept and only further demonstrated the benefits of time savings, reduced system maintenance, and process flexibility,” explains Ryan MacDonald, senior engineer, manufacturing sciences and technology at Avid Bioservices.“It was these benefits that led us to build Avid’s Myford North facility that was designed to exclusively use SUT, and was completed in 2016.”
 
Today, the company utilizes single-use technology for buffer and media preparation and storage, bioreactors, filtration and chromatography membranes, transfer assemblies, downstream flow-kits, and intermediate product storage. Avid has also recently been utilizing more pre-packed columns, and is interested in the growing number of improved single-use solutions for harvest clarification.
 
Avid’s two manufacturing facilities have a large upstream capacity with multiple 2,000L, 1000L, and 200L SUBs between them. That experience, combined with its excess and expanding manufacturing capacity, puts Avid in a unique position to serve its existing and future clients.
 
Why Make the Switch to SUTs?
 
More and more companies are adopting single-use technologies in the manufacturing process. MacDonald attributes the change in the biopharmaceutical industry toward single-use bioprocessing systems to the combination of improvements in SUT capabilities, and the increased awareness about the benefits of the technology.
 
“Single-use bioreactors are now capable of facilitating high titer processes at large scale volumes, with some vendors developing systems up to 5000L,” he says. “Additionally, vendor research and development has led to more reliable products, reducing concerns about bio-container leaks or maintaining material sterility. Manufacturers who have not adopted single-use are now seeing early adopters clearly benefitting from the quick product turnarounds, decreased development times, and simplified operations and equipment. With the improvements in the technology, the benefits become harder and harder to ignore.”
 
SUTs also offer significant advantages over stainless steel from both a business perspective and production perspective.
 
MacDonald explains: “From a production perspective, I think the most obvious benefit of single-use is the time savings. The setup time for each process is also reduced with bag setups taking one to two hours whereas stainless setups can take multiple days.
 
“Daily operations are also faster and simpler when quick welds or line connectors replace line sterilization. System Maintenance is substantially easier as well with no annual cleaning, sterilization validations, and fewer systems and pieces of equipment that need to be monitored and maintained.
 
All of the advantages in production also benefit Avid from a business perspective. “However,” MacDonald says, “single-use technologies allow us to also offer our prospective clients faster process development with vendor provided scale down models, reduced risk of product cross contamination, and simplified and often shorter investigations as a result of inherently less complex systems.”

Challenges
 
The greatest challenge Avid has faced with single-use systems is the required reliance on vendors.
 
“In single-use processes, all materials are considered critical and manufacturers are dependent on vendors to provide a sufficient supply,” MacDonald remarks. “This can be mitigated with a strong supply chain and frequent communication with vendors, but even the largest vendors can be greatly impacted by natural disasters like hurricanes or our current pandemic.”
 
Materials can also be changed by vendors due to updates in manufacturing methods, no longer supporting a technology, or company acquisitions. “Vendors provide change notifications, often with comparability packages,” says MacDonald. “However, sometimes these comparability packages do not provide sufficient data to justify low process risk. This can require additional, and often costly, studies to assess the impact of the changes.”
 
The most common concern about SUTs that Avid hears from clients is about consumables supply to ensure production plans remain on schedule. This is one of the reasons Avid looks for SUT vendors that are willing to work closely together to address issues with lead times and failure rates. COVID-19 has also highlighted Avid’s desire to work with vendors that have manufacturing redundancy, raw material dual sourcing, and adequate crisis plans.
 
SUTs for The Future
 
Despite its challenges, Avid views single-use technology as the way forward.
 
“When 5000L vessels are readily available, single-use bioreactor sizes will be able to support the vast majority of biologic products on the market and in development, with some global blockbusters as exceptions,” says MacDonald.
 
To stay up-to-date and prepare for the future, Avid completed the expansion of its process development laboratory space in 2019 that now supports 30 small-scale benchtop bioreactors and pilot-scale SUBs.
 
The company also recently began the expansion of its Myford North facility with the addition of a second downstream processing suite that will be completed in the first calendar quarter of 2022. Avid is planning to follow that expansion by building a third manufacturing facility capable of running six 2000L single-use bioreactors.
 
“Future improvements such as larger-diameter pre-packed chromatography columns and more efficient membrane filtration systems for harvest clarification would significantly reduce processing and preparation time,” MacDonald says. “Downstream purification can often be the largest process bottleneck and with these technology advancements, manufacturers could see a dramatic increase in their product generating capacity.”
 
The future of single-use technology is bright and Avid is well-prepared to take advantage of it and share the benefits with its clients.

Learn more about Avid Bioservices >>>>>