Single-Use vs Stainless Steel – Choosing the Best Technology for Your Biomanufacturing Needs

Biopharmaceutical manufacturers continue to face a number of issues amid increased demand for critical therapeutics and pressure to make headway on sustainability goals. While the therapeutics industry has evolved over the last several decades, manufacturers are still looking for ways to scale efficiently and increase production.

With sizeable patient populations and demand for large product volumes, commercial-scale manufacturing via stainless steel bioproduction dominated the market even after the first single-use bioreactors (SUBs) emerged during the late 1990s. Adoption of single-use technology (SUT) was initially slow due to skepticism and concerns regarding sustainability, leachables and extractables, operational equivalence and scale limitations.

However, today’s SUTs offer several advantages in terms of flexibility, capital costs and reduced downtime, and can be quickly scaled up or down, allowing for rapid changes in production volumes. Additionally, disposable elements of SUTs can be quickly assembled and disassembled, reducing the amount of downtime needed for cleaning, sterilization and maintenance, enabling faster turnaround and leading to faster production cycles and greater productivity.

The choice between SUTs and stainless steel bioreactors (SSBs) is dependent on each biomanufacturer’s unique scenario, including molecule type, range of titer, cell density, demand phase (e.g., pre-clinical, early-phase, late-phase clinical, commercial), patient population, single-product versus multi-product facility, the quantity of product, and facility type (e.g., new facility, existing facility, etc.).

As SUTs continue to grow and evolve, biomanufacturers need to better understand how they match up against stainless steel in terms of sustainability, flexibility and scalability, quality and cost, and choose the method that is right for them. Here, the capabilities offered by SUTs and stainless steel systems are outlined and compared, with a focus on the flexibility of implementing SUTs.

Advancing sustainability in biomanufacturing

As companies formulate and formalize their environmental, social and governance (ESG) goals and determine their respective paths toward achieving them, choosing the right manufacturing technology becomes critical.

Liquid and solid waste, in addition to facility footprint – which includes energy and HVAC requirements – assumes high importance.

SUBs have been shown to greatly reduce water consumption and facility energy use when compared to SSBs. However, the disposal of single-use components raises concerns regarding waste generation and potential environmental impacts. Life cycle assessments (LCAs) comparing SUBs and SSBs have shown that the environmental impact of both systems is highly dependent on manufacturing conditions and disposal practices.

Implementing circular economy concepts, such as recycling and reuse of single-use components, can mitigate the negative environmental impact of single-use technology. Tremendous strides are being made in SUT sustainability from materials to packaging to regional manufacturing and distribution.

SUBs have been shown to reduce cost of consumables by 37% when compared to stainless steel. Single-use centrifuges also deliver great benefits in water savings compared to devices that utilize depth filtration, which is a requirement for SSBs (Figure 1). There’s still opportunity to improve the sustainability and recyclability of single-use components, such as bags, used in the process.

Figure 1. Harvest comparison: Water, buffer and NaOH reduction. Credit: Thermo Fisher Scientific.

Achieving goals with flexibility and scalability

Scalability is important as processes are further developed and larger quantities of molecules are required for clinical or commercial manufacturing. Additionally, flexibility is vital for manufacturers that produce an array of products for commercialization.

SUTs bring increased flexibility to biomanufacturers, including shorter set-up times, fewer cleaning requirements and easier customization of reactor size and configuration. This allows for better volume projections, especially for companies focused on research and development, who are not always planning for the commercialization stages.

Because SUTs are modular, they offer a unique way to add flexibility and scalability into the timing for a facility build-out, reducing the time needed to get the facility up and running. This can lead to easier adjustments and adaptation of newer technologies down the line.

Stainless steel is a well-established choice for large and commercial-scale biopharmaceutical production. However, SSBs require substantial upfront investment and, because of challenges in their installation and vast size requirements, it can take a while before a biomanufacturer begins to see a return on their investment.

Overall, SUTs are useful in facilities that produce a multitude of products in different volumes and where flexibility and scalability is top of mind. But for the largest commercial-scale manufacturers, the economic benefits of SSBs outweigh those of SUTs.

Quality process control

Existing quality process controls can be implemented with either SUTs or SSBs depending on each individual manufacturer’s needs.

When using SSBs, the end user is required to control and update their own processes and components, whereas SUT suppliers own the quality and documentation components of their own products, including multisourcing of reactor and single-use components, which removes this burden from the end user.

SUTs bring great advantages in quality, such as a supplier-centered change control, no batch-to-batch production contamination, no soil carry-over and consistent product-contact materials. Though SSBs also offer benefits through existing documentation and processes, end-user-centered change control and consistent product contact materials.

Improving the overall cost

The choice of manufacturing method can have tremendous impact on a biomanufacturer’s spending. Stainless steel technologies have strict sterilization and maintenance guidelines, in addition to needing a separate space for each unit, whereas SUTs allow for more flexibility in cleanroom space requirements and negate the requirement for changing of gowns and other processes required by stainless steel.

SUTs bring more efficiency to the entire workflow, and facilities that utilize SUTs realize better resource utilization and reduced labor costs. Additionally, manufacturers can take advantage of cost savings in consumables compared to utilizing depth filtration (Figure 2). At a scale of 5,000 L, reductions of 37% in consumables costs, and up to 33% in overall costs, can be achieved.

Figure 2. Harvest batch costs comparing the Thermo Scientific DynaSpin Single-Use Centrifuge versus depth filtration at various volumes. Credit: Thermo Fisher Scientific.

Despite SUTs having a lower upfront capital expenditure (CAPEX) because of lower infrastructure requirements compared to SSBs, manufacturers could see increased operating expenditures (OPEX) because of the increased cost of consumables that require disposal.

SSBs have higher upfront costs but could provide more long-term savings because of their well-established durability. However, attendant OPEX is also high due to increased water usage, labor costs, training and other preparation and sanitation requirements.

Many new advances are being made in SUTs to improve their affordability. Next generation technologies are also introducing automation tools that can reduce contamination and improve process control.

The path forward for manufacturers

The choice between using SSBs and SUTs for bioproduction boils down to each biomanufacturer’s needs in terms of economic and environmental considerations.

Stainless steel technologies will remain a viable option for a variety of large-scale manufacturers. However, SUTs have come a long way since their inception to keep up with the changing therapeutic landscape that requires greater process intensification, resulting in higher-yielding production, in smaller volumes and with greater flexibility in manufacturing.

These benefits in flexibility, scalability and performance, coupled with greater sustainability, make SUTs a desirable option for biomanufacturers who are looking for ways to increase yield and improve efficiencies, while also achieving their ESG goals more easily and cost effectively.

About the author:

John P. Puglia, received his PhD in Polymer Science from University of Massachusetts, at Lowell. John is currently senior director of research and development in Thermo Fisher Scientific’s bioprocessing business focusing on single-use technologies. Puglia’s research history includes plastics engineering, composites, cell culture, chromatography, sustainable engineering and high-purity manufacturing.