Single-Use Systems Enable Commercial-Scale CGT Manufacturing

Single-use systems (SUS) are essential in cell and gene therapy (CGT) manufacturing. Because the product flow-path components are supplied pre-sterilized and then disposed of rather than cleaned and sterilized between products, SUS reduce cleaning validation burden and enable quick changeover, which is particularly beneficial in multiproduct facilities and for the small batch sizes of personalized medicine.

“Single-use systems have become integral to CGT manufacturing, with technologies applied across most process steps for cell therapies and gene therapies, as well as plasmid production. Common applications include general assemblies, filling operations, homogenizing, and cryobags for cryopreservation,” says Ania Payne, chief strategy and marketing officer at Single Use Support. “[SUS offer] simplified compliance with good manufacturing practice (GMP) requirements via pre-validated assemblies [and] scalability for small volumes, perfectly suited for CGTs’ low-volume, high-value production needs.”

“Single-use technologies (SUTs) are widely adopted in CGT manufacturing because they deliver sterility, flexibility, and process efficiency,” adds Emmanuelle Cameau, scientific director, Genomic Medicines, at Cytiva. She notes that the majority of CGT manufacturing processes are fully single use, with a few exceptions, such as specific technologies with volumes larger than 3000 L.

As clinical and commercial manufacturing for the CGT sector ramps up, one challenge is ensuring a stable supply chain for consumables. Another challenge is how to create enough CGT manufacturing capacity by scaling up or scaling out; in either approach, automation is seen as crucial (1). 

How do SUS facilitate industrial-scale manufacturing?

“[SUS] favor scale-out strategies, where demand is met by parallel small units rather than scaling a single large vessel, a model well suited to autologous therapies and distributed manufacturing,” says Wayne Bowen, consultant at TTP, which combines single-use consumables with modular, automated instruments to address specific manufacturing needs. “Overall, SUS deliver faster, more flexible, and lower risk manufacturing paths for CGT when paired with closed automation.”

“[The industry has] spent 20 or more years translating the production of these living medicines out of flasks and tubes and into closed, single-use systems, [and manufacturers are now] challenged with how to automate the handling and operation of SUS that were designed and developed for human hands and eyes into more industrialized systems,” says Jason Jones, vice-president of Cellular Origins, a TTP company, which has developed an automated platform for clinical and commercial cell therapy manufacturing using mobile robots and the company’s proprietary sterile fluid transfer technology.

Bringing CGT manufacturing methods and systems to commercial scale will require automation that goes beyond merely aiding human operation, adds Jones, but he cautions that changes to the process or to product-contact materials should be minimal to avoid changes that would affect regulatory approval or require costly comparability studies. “Automating operation for scale requires innovation in robotic handling and connection of these very specific, approved, designed-for-human SUS to multiply efficiencies and standardization for scale but maintain the processes.Mobile robotics, full digital integration and full process connection are the platform we apply around these SUS,” he explains.  

Cameau says the diversity of process types and the use of manual workflows in today’s CGT manufacturing adds complexity to scaling manufacturing, but SUTs and modular platforms that provide flexibility can help. “The recently launched Cytiva Sefia platform combines modular automation with single-use kits to standardize complex steps like cell isolation, processing and expansion, helping customers move from manual processes to industrialized solutions that improve consistency and accelerate access to therapies,” she explains.

In January 2025, Cytiva and Cellular Origins announced a collaboration to combine Cytiva’s automated cell therapy manufacturing platform with Cellular Origins’ automated robotic platform (2). Cameau says that such collaborations will help advance robotic automation and modular designs, which can enable industrialization.

How does standardization support industrialization and reduces supply risk?

Standardized systems could facilitate industrialization and increase process flexibility, suggests Payne. “The absence of industry-wide standards for connectors, materials, and validation protocols creates interoperability challenges and slows adoption,” she says. “We believe that to overcome these obstacles, biomanufacturers will increasingly rely on modular and vendor-independent solutions.”

“Pandemic-era disruptions highlighted one key issue: the industry lacked standardized methods to qualify interchangeable single-use components, putting supply chains, production continuity, and compliance at risk,” adds Sade Mokuolu, Regional Business Development Manager of Life Sciences at Watson-Marlow Fluid Technology Solutions. “The SUS supply chain faces challenges around component interchangeability, particularly in CGT manufacturing, where small-batch, customized assemblies are common. A single unavailable component can halt production.”

Mokuolu says that solutions such as Watson-Marlow’s WMArchitect Interchangeable Parts help mitigate risks. “Qualifying entire fluid paths containing interchangeable components ultimately increases manufacturing agility while supporting regulatory compliance and faster patient access without compromising performance or compliance,” she explains.

How can supply chain challenges be addressed?

Although interchangeable components are one solution, the industry is adopting a wide variety of approaches to reduce supply-chain vulnerability.

“CGT supply chains are complex due to patient-specific timelines and specialized components. Delays can impact treatment schedules,” highlights Cameau. “Best practices include implementing single use across workflows, thorough risk assessments, and strong supplier collaborations. Cytiva strengthens resilience through dual sourcing, strategic inventory planning, and modular manufacturing strategies—helping customers deliver therapies reliably and at scale.”

“Shortages of proprietary components can delay batches, so manufacturers mitigate risk by qualifying multiple suppliers, holding excess stock, and strengthening contracts,” adds Bowen. “Cross industry collaboration, supplier innovation, and proactive risk management are essential to make SUS robust for clinical and commercial CGT manufacturing and patient access.”

“Our customers increasingly demand shorter lead times and greater flexibility to accommodate changes in products and quantities at short notice,” says Payne. “To address this, we are investing in strategic stockpiling of critical components and fostering close supplier relationships to identify risks or bottlenecks early enough to respond effectively. In addition, we are expanding our capacities to meet higher demand and fulfill expectations for shortened lead times.”

Sterilization is a crucial part of the supply chain for SU consumables, and the industry has recently focused on ensuring capacity for sterilization by qualifying alternatives to gamma irradiation methods (3). To support these efforts, BioPhorum published a protocol to provide guidance for performing a side-by-side study of SUS irradiated by gamma and X-ray (4). According to the group, data indicate that the two methods are equivalent.

Injection-molded system enables distributed manufacturing

Trenchant BioSystems is developing a system for point-of-care manufacturing of autologous cell therapies with a different SUS approach that could address some of the capacity and supply-chain challenges of existing systems. Jon Ellis, CEO of Trenchant BioSystems, says that the automated, digitalized platform would address an urgent need for patients, because manufacturing time and cost limit CGT availability and affordability. “Therapies are successful clinically, but making them takes too long,” says Ellis. “Our manufacturing platform can reduce manufacturing time from weeks to three days as well as reduce manufacturing costs by more than 80%.”

Trenchant BioSystems' process takes place in single-use cassettes. Rather than moving the cells from one unit operation to the next through tubing into bags, this system brings reagents and buffers to the cells, which stay in the cassettes. Ellis says that the cassettes, which are injection-molded from polycarbonate, solve many of the supply-chain challenges associated with more conventional SUS by avoiding the need for sourcing many different pieces.

“The simplicity of our design enables high quality and reduces assembly, which reduces cost,” says Ellis. “Operators do not have to perform any complex installations; there is no threading or welding where error could cause leaks. Very little training is needed.”

Trenchant Biosystems has developed protocols for chimeric antigen receptor t-cell (CAR-T) and gene modified CD34+ cells and is working with partners to test the prototypes. The prototype SUS are made with United States Pharmacopeia (USP) Class VI polycarbonate so that the same materials of construction can be used when the systems move into GMP manufacturing. Because polycarbonate is already widely used in injection molding processes in cleanrooms, GMP manufacturing capability for the SUS equipment is accessible, says Ellis. The ability for easy manufacturing of the SUS will avoid the problems associated with single-sourcing and will enable distributed manufacturing.

Regionalization to secure the supply chain

Localizing supply with multiple manufacturing sites in different regions is seen as a way to reduce supply-chain risk (5). Regionalization can also help CGT manufacturers meet evolving regulatory expectations.

“CGT modalities are advancing faster than global regulatory frameworks can fully keep pace,” says Mokuolu. “Developers are increasingly expected to define critical quality attributes early, involve regulators sooner, and implement robust process control strategies that ensure consistent quality across sites and regions. Regionalization of supply chains helps manufacturers meet differing regional regulatory expectations, reduce dependency on single-source components, and simplify change control under accelerated approval timelines.”

Mokuolu concludes that it is important to design SUS that are resilient and reliable and to enable processes that support scalable, sustainable CGT manufacturing.

References

1. Bio-Process Systems Alliance. Automation of Single-Use Unit Operations in Bioprocessing: Traps, Tips and Trends. White Paper. December 2025.
2. Cytiva. Cellular Origins and Cytiva are Collaborating to Deliver Automated Robotic Manufacturing Capabilities for Cell and Gene Therapies. Press Release. Jan. 16, 2025.
3. Challener, C.A. Sterilization Trends for Single-Use Consumables | BioPharm International, BioPharm International 2024 37 (7).
4. Mitchell, L. Confirming the Equivalency of Gamma and X-ray Irradiation, Jan. 30, 2025.
5. Mangal, A. Building Robust Biomanufacturing Networks for the Next Wave of Therapies, BioPharm International, Dec. 31, 2025.

About the author

Jennifer Markarian is a contributing author to PharmTech and previously manufacturing editor for PharmTech.