Single-use technologies (SUT) emerged commercially in the 1990s, when companies such as HyClone Laboratories, a serum and cell culture media provider, pioneered “bio” bags for cell culture media packaging.¹ Today, the term encompasses a range of disposable equipment and materials suited to a variety of scales and applications, from upscale bioprocessing to final formulation and filling. 

SUT have been widely adopted by the industry and their uptake continues to grow. Due to their rapid deployment and flexible response to market demand, the proportion of commercial-scale single-use bioreactors (SUB) grew from 32.5% in 2019 to 43% in 2022,² driven by increased global demand for biologics and vaccines during the COVID-19 pandemic. Many multinational companies, such as Amgen, Eli Lilly and Merck, have invested in accelerating SUT capabilities and capacities in recent years, reflecting the fact that SUT have become the next-generation choice for leading pharmaceutical companies.

Advocates of SUT have highlighted their potential for improved efficiencies, flexibility, lower costs, reduced contamination risks and faster production times. Opponents have been equally vocal in concerns over higher consumable costs and sustainability issues.³ This article uses real-world observations from the application of SUT in more than 300 large batches of biomanufacturing—with over 99% success rate—to answer some of the outstanding questions concerning single-use
versus stainless-steel systems (SSS).

Cost-efficiency 

A key argument in favor of SUT is cost efficiency. Compared with SSS, SUT have a lower up-front capital investment and a shorter construction period. Historical calculations suggest that, ten years ago, building a large-scale monoclonal antibody (mAb) facility with SUB could reduce total capital cost by over $100 million, compared with SSS of equivalent capacity.⁴ Another example from 2015 suggested that, after 10 years of active use, SUB reduced capital cost by 40–50%, operating costs by 20–30%, and time-to-build by 30%.⁵ 

As well as lowering capital costs, use of SUB can reduce indirect costs such as human resources and cleaning costs. It has been estimated that a plant retro-fitted with SUT made annual savings of $250,000 in water for injection (WFI) costs and $60,000 in labor time by avoiding set-up and cleaning of stainless-steel bioreactors (SSB).⁶

Using data from more than 300 large-scale batches, WuXi Biologics can confirm that current manufacturing costs with SUT continue to compare favorably with SSS (Figure 1). The data suggest savings of around 10% for comparable production volumes at a basic level, and further savings when integrating advanced bioprocessing technology platforms. 

Cost of goods (COG) from a single SUT can be reduced by novel processing technologies such as WuXiUI and WuXiUP. For example, WuXiUI, a high-productivity bioprocessing platform launched in 2023, employs an intensified fed-batch approach to greatly enhance the yield and quality of mammalian-based biologics. The platform can achieve a 3–6 fold increase in productivity, while reducing drug substance manufacturing COG by an estimated 60-80% compared with traditional fed-batch processes. This indicates a notable increase in drug substance output by up to 500% at a similar production scale, driving improved manufacturing efficiency and agility for industrial applications.

Another integrated continuous bioprocessing platform, WuXiUP (the WuXi Biologics Ultra-High Productivity platform), combines an intensified continuous cell culture process with excellent scalability and robustness. A continuous or hybrid downstream process and direct product capture column chromatography generate better purification yield than traditional purification processes for biologics. Cell culture productivity can be increased by 5–20 fold compared with traditional fed-batch culture platforms, with high downstream yields of 80–90% and excellent product quality. Its continuous capture reduces the requirements and costs of chromatography resins. The WuXiUP platform is designed to accelerate biologics development and manufacturing, reduce COG, and allow for a smaller facility footprint. 

Manufacturing efficiency and flexibility

In addition to cost-efficiencies, SUT bring process efficiencies as they reduce the time needed for construction, cleaning and maintenance. SUT are seen as supporting flexible cGMP manufacturing, while enabling efficient and rapid adjustment of production schedules and volumes. 

In a closed system, SUB can save anything from a couple of days to a couple of weeks, thanks to reduced cleaning and validation time, reduced set-up times, and reduced time to operate or oversee equipment.⁷ If contamination occurs in one bioreactor, downtime can be minimized as only the affected unit in the single-use set-up needs to be replaced, with limited loss of product. WuXi Biologics’ experience has demonstrated that production can resume within 24 hours (at the fastest) by replacing a new single-use bag. In contrast, contamination in SSS requires the entire batch to be discarded, incurring costs and time for sterilization and revalidation. 

Previously, SUB volumes were limited by pressure challenges from the weight of the liquid medium, as well as handling issues,⁸ but recent advances have allowed SUB to become commercially available at higher working volumes of up to 6,000L. WuXi Biologics is currently exploring the application of a range of larger volume SUB for scaled-up commercial production, including three 5,000L SUB at the company’s facility in Hangzhou, China.

For situations requiring volumes above the limits of even newer SUB, scaling out (increasing the number of bioreactors used in parallel) can be implemented flexibly.⁹ WuXi Biologics has developed scale-out strategies (with associated cost savings), achieving large-scale production through parallel multiple SUB, with a maximum production scale of 16,000L. For example, the WuXi Biologics MFG7 facility in Ireland houses four 4,000L SUBs, meaning it can realize manufacturing at 4,000L, 8,000L, 12,000L, and 16,000L, for different stages, scales and products. 

This flexibility is important as managing capacity utilization is now one of the main challenges in the biopharmaceutical industry. Oversized production leads to reduced utilization rates and inflated manufacturing costs, while undersized capacity risks drug shortages. Scale-out strategies remove non-linear scale-up risks and enable rapid growth (or reductions) directly in line with demand. This facilitates contractual and financial flexibility, while supporting emergency production and different process types. 

With trends such as on-demand production and personalized medicines for smaller patient groups, the biopharmaceutical industry is no longer suited to the traditional approach of building factories that rely on large-scale SSS. Only 20% of commercial biologics now require a bioreactor of over 10,000L, and a 2,000L bioreactor can produce enough protein over a year to meet the needs of over 50% of marketed biologics.¹⁰ 

Furthermore, as biopharmaceutical production shifts towards more flexible, smaller footprint facilities, many production lines require upgrading. However, production lines of SSS need to be redesigned to optimize processes, as their fixed maximum capacity limits operational flexibility. In contrast, SUT provides greater adaptability through modular design, enabling seamless scalability and efficient adjustments without major infrastructure changes.

Biopharmaceutical companies are transitioning from large-volume, single-product facilities to small-volume, multi-product ones. This aligns with the advantages of SUT—efficiently and quickly increasing or decreasing the number of SUB, achieving industrial-scale production at laboratory scale without facing the challenges of process scale-up¹¹ (Table 1). 

Sustainability 

It may seem paradoxical to claim that SUT can have a smaller environmental footprint than a traditional SSS, but the requirements for sanitization and cleanliness in biological drug manufacture place an extreme environmental burden on the traditional facility. Sanitization and cleaning are chemical, water and energy intensive. As a result, multiple studies have shown that SUT can significantly reduce the overall product carbon footprint (PCF) and minimize the life-cycle environment impact of bioprocessing by consuming less energy, water and cleaning agents.¹² 

Compared with SSS, SUT can save up to 70% of water consumption for the same output. SUT plants are also potentially more energy efficient, as they are reported to achieve process electrical savings of about 30% because of their smaller facility footprints, and about 25% lower CO2 emissions due to the reduced usage of WFI during the stainless-steel cleaning cycle.¹² 

The environmental impact of SUT can be further reduced through the application of advanced technology platforms. The high-productivity bioprocessing platform WuXiUI demonstrates more efficient media consumption, reduced waste generation and downsized facility occupation, reducing the PCF per gram of protein product by 80%, compared with traditional fed-batch SSS (Figure 2). As highlighted in the UN Global Compact’s recent report using WuXi Biologics as an example, SUT reduced water consumption by up to 70% and resource usage by approximately 33%.¹³

Therefore, by several parameters, SUBs can have a smaller environmental footprint than a traditional SSS. The main negative impact of SUBs is their plastic content. Echoing the current global focus on reducing single-use plastics, this is a common argument against SUB. It has been reported that about 880 kg of solid waste per batch is generated,¹⁴ but material recycling is challenging due to GMP regulations. Waste that comes into contact with pharmaceutical liquids must follow disposal protocols, making recycling difficult. Globally, there are no robust solutions, although Merck has achieved some success in the USA by repurposing single-use waste into road construction materials. WuXi Biologics is in the process of replicating this project in Ireland in collaboration with Merck and other companies.

Meanwhile, manufacturers may be encouraged to participate in programs such as waste-to-energy initiatives. Across WuXi Biologics’ bioprocessing sites, a proactive adoption of energy recovery for waste treatment has resulted in a high implementation rate—at least 80%. 

Final word

While stainless-steel systems have been foundational to the bioprocessing industry, their rigidity clashes with modern, often unpredictable demands for varying quantities of biologics and vaccines. In contrast, single-use bioreactors are modular, rapidly deployable, and scalable. Capable of global implementation within months, SUT align with the agility required for 21st century industry challenges. 

In an era of unprecedented market volatility, smarter manufacturing solutions are essential. SUB offer a tool to navigate complexity while optimizing efficiency. They expand operational flexibility and signal a transformative shift in production routine, driven by evolving technologies and industry needs. To propose that the industry should now revert to SSS would be akin to suggesting we should all surrender our smartphones and use landlines instead. 

The data consistently demonstrate SUT’s potential for improved efficiencies, comparable or even lower costs, and faster production times. With their proven flexibility, reduced contamination risks, and evidence for a smaller environmental footprint, it seems clear that they are the best available technologies to address today’s commercial manufacturing challenges. It is time to embrace the era of the SUT.

References

1. Martin JM. A Brief History of Single-Use Manufacturing. BioPharm Int 2022;8.

2. Bhatkhande S. Single-use bioprocessing technologies enabling more rapid vaccines production. Am Pharm Rev, April 1, 2023.

3. Clapp K. The great debate: stainless steel versus single use. The Medicine Maker, September 21, 2016.

4. BiopPharm. Mab manufacturing today & tomorrow. Press release, May 14, 2014. 

5. Hernandez R. Top trends in biopharmaceutical manufacturing: 2015. Pharmaceut Tech 2015;39.

6. A. Goldstein, O. Molina. Implementation strategies and challenges: single use technologies. PepTalk Presentation, 2016.

7. Editor. Closed Systems in Biomanufacturing Offer a Variety of Benefits. Cell Culture Dish, April 15, 2015.

8. Kai. Single-use technologies enable biologic scaling. Contract Pharma, May 3, 2023.

9. Sargent B. Scale-out biomanufacturing—a paradigm change to scale up. Cell Culture Dish, January 24, 2018. 

10. BPI Editors. Biomanufacturing supply and demand: industry trends and projected impacts. BioProcess Int, July 31, 2024.

11. Jacquemart R et al. A single-use strategy to enable manufacturing of affordable biologics.  Comp Struct Biotech J 2016;14: 309–318.

12. Sinclair A et al. The environmental impact of disposable technologies. BioPharm Int 2008; 201-9. 

13. United Nations Global Compact. 20 case examples for 20 years. 2024. 

14. Walker N. Single-use technology integral to advancing biomanufacturing. Contract Pharma, March 9, 2016.

Dr. Chris Chen is the CEO of WuXi Biologics. Under his leadership, WuXi Biologics is a leading global contract research, development and manufacturing organization (CRDMO) offering end-to-end solutions that enable partners to discover, develop and manufacture biologics. It has built up a world-class open-access integrated platform, enabling over 800 integrated biologics projects. Dr. Chen served on the International Board of Directors for ISPE as the first board member from Asia. He holds Bachelor’s degrees in Chemical Engineering and Automation from Tsinghua University and a PhD in Chemical Engineering from the University of Delaware.

Contributing writers: Dr. Wei Guo, senior vice president, head of global manufacturing; JIAN ZHU, senior director of global manufacturing; Siyuan Tang, director of global development and technical operations; YIXIN ZHANG, associate director of corporate communications and public affairs.