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Single-use systems hold key benefits for biomanufacturers, despite certain limitations.
As downstream bioprocessing operations gradually implement single-use, biomanufacturing facilities are also being brought into alignment. What hurdles do biomanufacturers face in converting facilities to accommodate single-use systems (SUS) in downstream processing?
Certain key innovations in technology and equipment have helped to advance the performance of SUS in downstream bioprocessing. Jay Harp, director of Single-Use Product Management at Avantor, notes that the higher product yields and greater cell densities resulting from the increased acceptance of perfusion technology in upstream bioprocessing has put a strain on downstream processes. However, advancements in chromatography and filtration techniques have been implemented to meet these challenges.
“Advancements in sensing technology and the ability for single-use monitoring tools give manufacturers a greater degree of control over their processes,” Harp states. “Tangential flow filtration systems use this advanced process technology to better control flow rates and achieve better process performance.”
Ati Alizadehbirjandi, manager of Manufacturing Science and Technology (MSAT) at Avid Bioservices, notes that continuous processing technology, such as the multi-column chromatography platform (BioSMB) has been a key innovation in biomanufacturing. The development of continuous inline viral inactivation skids (by Pall Sciences), single-pass tangential flow filtration, and other multiple components that have been built all address bottlenecking issues in the downstream, Alizadehbirjandi emphasizes.
Bioprocess skids have the capability to process larger volumes in a shorter period of time, where previously only hard-piped systems could handle such volume, adds Gene Yoshioka, senior director of Manufacturing at Avid Bioservices.
“The rise of multi-modal chromatography allowed for higher precision in purification efficiency. Membrane chromatography was also developed to act as a more size-efficient replacement for high-capacity packed bed resin chromatography,” Alizadehbirjandi says. Furthermore, in-line process analytical technology development will advance performance and minimize bottlenecks to a higher extent by providing instant essential results, she adds.
The implementation of SUS has had its share of challenges, including the stress of high-volume products, high facility cost, and supply chain vulnerability, according to Alizadehbirjandi.
Alizadehbirjandi explains that if a high-volume product used a stainless-steel system for its purification, then it would be costly to switch to SUS, and the manufacturing process for the product would need revision. Moreover, stainless steel is generally more cost-efficient for a high-volume product. In terms of facility cost, companies that have established stainless-steel facilities would also face a high cost for the switch to SUS.
In addition, single-use facilities require a much larger warehouse footprint to store consumables, says Yoshioka, who mentions that managing the supply of consumables becomes critical as the reliance on vendors becomes more prominent.
Another aspect to be wary of is safety concerns regarding extractables and leachables (E&L) from plastic-derived or polymer material, which comprise SUS, adds Alizadehbirjandi. As expected, regulatory concerns for E&L are elevated for SUS systems, vs. transitional stainless-steel production, she says.
Tim Korwan, director of New Product Introduction at Avantor, explains that biomanufacturing facilities differ greatly from those that are fully single use. One of the key differentiators that he notes is the operating expenses and reliability of supply.
“In standard biomanufacturing facilities, the ability to change something in the manufacturing process relies upon the manufacturer to manage through extensive investments (both capital and time). With fully single-use facilities, manufacturing technicians and process engineers need to have a deeper knowledge about new technologies because the supplier is responsible for the managing the supply,” Korwan emphasizes.
Because the supplier is responsible for components in a fully single-use facility, if one component of the manufacturing process isn’t met by the supplier, then the process cannot move forward, cautions Korwan. Coupled with the flexibility inside fully single-use facilities, a biomanufacturer could end up with a stalled manufacturing process that could cause delays to the supply chain.
“To address this challenge, facilities can take a hybrid approach where the standard stainless-steel footprint is used (where appropriate) and is supplemented with single-use products.” Korwan states.
Korwan also explains that there is greater demand placed on the warehouse in a single-use facility, with lead times being a main issue. Because single-use products do not have an infinite lead time, one cannot overstock these products or risk having them expire. “As a result, single-use facilities require robust inventory management and coordination with vendors,” he says.
In terms of advantages, single use offers the greatest degree of flexibility, says Harp, who highlights the fact that biopharma manufacturing is constantly evolving with new processes and modalities. “Scientific advancements would not be capable without the equal advancements of single-use technology and the response of single-use integrators,” he states.
Korwan says that the need for supply chain professionals has never been greater because managing the supply of the entire fluid pathway in biomanufacturing is an extremely rigorous exercise. “As a result,” he explains, “the warehouse infrastructure needed to support this has never been greater.”
Facilities have been moving away from a stainless-steel footprint in recent years. Facilities are transforming into more of a shell-type structure, which is a substantial change for how these buildings have operated in the past, says Korwan.
The former stainless-steel footprint requires mass amounts of infrastructure and immovable piping, Korwan adds. Whereas now, SUS have allowed for the unit of operations to be placed in unclassified rooms, which minimizes the requirement for electrical sterilizing equipment, and thus allowing the ability for flexibility within the suite.
“Coupled with the lack of immovable piping, the facilities are able to flex between different modalities quickly and efficiently without having to change the infrastructure of the building,” Korwan states.
Meanwhile, Alizadehbirjandi points to a quicker turnaround time as being a key advantage of SUS. SUS allows for better time management by avoiding steam-in-place cleaning. This time advantage has resulted in achieving better speed-to-market.
Another benefit is water usage conservation, in which water intake for biomanufacturing facilities has been cut down by >50%, resulting in decreased plumbing, Alizadehbirjandi emphasizes. Other benefits include agile process development, process intensification, as well as better ability to deliver personalized medicine.
Yoshioka adds that for a contract development and manufacturing organization working with multiple products, eliminating the risk of cross-contamination is vital to the safety of the products that are produced. SUS allows for quick changeover while removing the risk of product residuals on product contact equipment surfaces.It has also eliminated the need for equipment cleaning and cleaning validation/verification which in itself is a large resource commitment.
Feliza Mirasol is the science editor for BioPharm International.
Vol. 36, No. 2
When referring to this article, please cite it as Mirasol, F. Benefits of Technologies Facilitate Adoption of Single-use Systems. BioPharm International 2023, 36 (2), 20–21.