When Single-Use Technology Becomes An Economic Imperative

A conversation with Dawn Ecker, BDO

The transition from stainless steel to single-use technology (SUT) — or vice versa, from SUT to stainless — might be one of the most significant financial and strategic decisions made by any bioprocessor.

With dozens of factors to consider, we asked single-use pro Dawn Ecker, a director at BDO USA’s BioProcess Technology Group who oversees the group’s database for biopharmaceutical manufacturing capacity, to answer some questions.

Here’s what she told us.

You have called the transition to single-use technology an economic imperative. What are the specific constraints or cost pressures on the stainless-steel side that have driven that shift? Are those pressures new or long-standing?

While the transition to SUT is not an economic imperative for every biopharmaceutical product, it often provides a distinct economic advantage when a product is well-suited to this approach. Most industry professionals recognize that biopharmaceutical manufacturing is not a one-size-fits-all process; some products are ideally manufactured using SUT, while others are better suited to stainless steel systems.

The evolution of SUT¹ since the introduction of the wave of SUT bioreactors in the late 1990s has been gradual but significant. In 2002, less than 10% of installed bioreactors were SUT; by 2012, this figure had risen to nearly 25%. By 2023, approximately half of all bioreactors were SUT, and projections indicate that by 2029, 55% of installed reactors will utilize SUT. The drivers behind this shift are rooted not in the limitations of stainless steel but in industry changes that increasingly favor SUT for many products.

Regulatory agencies have embraced SUT as a viable option, with VPRIV becoming the first approved product in 2010. The industry’s ongoing pursuit of higher titers and process yields has enabled more product to be manufactured in smaller volumes, making the use of smaller, single-use bioreactors feasible. Additionally, the growing trend toward outsourcing has made SUT even more attractive, as it allows for faster equipment turnaround times due to minimal or no cleaning and sterilization requirements, alongside the development of larger SUT systems.

While questions often arise regarding the constraints or cost pressures associated with stainless steel, I think it is clear that the advantages offered by SUT have been the primary drivers of its adoption.

For clinical-stage antibody developers, what key signals or thresholds should trigger a shift from single-use to stainless systems, especially when preparing for commercialization?

This is exactly the type of question the bioTRAK team has been working to model: understanding when and how the industry determines that scaling out has reached its practical limits and it’s time to scale up. In other words, we are working to identify the volumetric breakpoint. While we have established some basic parameters, we are collaborating with our process economic modeling team to gain deeper insight into the financial breakpoint, where scaling up becomes more economically advantageous than scaling out.

For product developers, projected volumetric demand is likely the most significant factor influencing a potential shift from SUT to stainless steel. This refers to the total bioreactor capacity required to meet anticipated patient needs. For some products, the decision is straightforward; for others, it falls into a gray area.

For example, consider three products: one estimated to require 8 kL per year, another requiring 25 kL per year, and a third needing 400 kL per year. Suppose the company operates multiple 2 kL and 5 kL bioreactors (four of each) and prefers not to manufacture a product just once per year, nor exceed six bioreactor runs annually. How can these products be manufactured efficiently?

The 8 kL product is best suited for the 2 kL scale — either four bioreactor runs in a single bioreactor or two runs in two bioreactors.

The 400 kL product would require a bioreactor larger than 5 kL, as running 50 bioreactor runs with four 2 kL bioreactors or 20 bioreactor runs with four 5 kL bioreactors is simply impractical.

The 25 kL product presents a more nuanced scenario. It could be manufactured using three 2 kL bioreactors over six runs or a single 5 kL bioreactor with five runs.

For products in this gray area, the decision may also be influenced by factors such as the product’s future potential in additional indications, which could increase demand and favor scaling up. Conversely, concerns about product quality — such as changes in gas exchange, mixing, or shear stress at larger scales — might favor scaling out. Ultimately, there are many considerations in developing a commercial manufacturing strategy, and the choice between scaling out and scaling up is just one of them.

On that note, the idea of revalidating can be an immediate turnoff, but in the long term, it could reward the investment with efficiency and reliability. What factors, such supply chain security risks, outweigh or justify the investment?

The need to revalidate a process when transitioning from SUT to stainless steel is often viewed as a significant hurdle. However, two major factors can justify — and even outweigh — the investment and effort required for revalidation.

First, a substantial increase in capacity to meet patient demand can make the economies of scale offered by stainless steel highly attractive, particularly when production volumes are stable and the product is expected to have a long life cycle. Over time, a meaningful reduction in the product’s cost of goods can make the transition financially viable, even if the initial effort seems daunting.

Second, reducing the risk of supply chain disruptions is a compelling reason to consider the switch from SUT to stainless. Recent years have exposed vulnerabilities in global supply chains due to pandemics, trade wars, and other geopolitical events. While it is impossible to predict exactly when or how these disruptions will occur, moving to stainless steel could significantly mitigate these risks.

Regardless of whether a company chooses to transition to stainless steel or remain with SUT, maintaining comprehensive end-to-end visibility of its supply chain is essential. This includes mapping the supplier network, identifying secondary and tertiary suppliers, and understanding the geographic origins of all critical components to avoid overreliance on a single vendor or region.

Proactive inventory management is also crucial. Companies should work closely with suppliers to communicate and anticipate changes in component demand, as well as to understand and plan for supply constraints and historical lead times. Increasing inventory levels for high-risk components, and those with long lead times or sourced from vulnerable regions, can help ensure uninterrupted manufacturing, even in the face of supply chain disruptions.

Increasingly, we talk about alternative expression systems replacing CHO, but SUT doesn’t do higher titers, higher particulates, and wider pH ranges as well as stainless. Can you talk about workarounds? Is SUT a viable option for non-mammalian systems?

For as long as I have been monitoring the supply and demand for recombinant biopharmaceuticals, there has been ongoing discussion about the eventual replacement of CHO cells with alternative expression systems for recombinant therapeutics. Despite these predictions, CHO cells continue to dominate mammalian-based processes, and the industry is still awaiting a major shift.

While alternative systems can achieve higher titers, they often introduce additional challenges, such as increased particulates, more viscous cultures, and the need for a broader pH range. These attributes can lead to mass transfer limitations (such as hindered oxygen transfer), mechanical stress due to viscosity (potentially compromising bag integrity), and heat transfer issues, all of which can negatively impact both product quality and cell viability.

SUT can be a viable option for non-mammalian systems, and several CDMOs are successfully leveraging single-use fermenters (SUFs) at the 1 kL scale. However, implementing SUT with non-mammalian systems requires careful consideration. This includes selecting single-use systems with more robust mixing capabilities supported by more powerful drives and stronger impellers, as well as bags that are resistant to pH and heat-related degradation and are reinforced or specially designed for demanding applications.

Workarounds to enable SUT use for non-mammalian systems in the upstream might include shorter growth times to limit viscosity and associated issues, while for downstream processes, extensive filtration or centrifugation prior to further processing can alleviate membrane fouling.

Reference:

1. Ecker DM. Nearly 20 Years of Supply & Demand Trends – What Trends are Shaping the Next 5? Presented at AGC Biologics CMO Summit 2025; Jan 27-30, 2025; Seattle, WA.

About The Expert:

Dawn M. Ecker is a managing director with the BioProcess Technology Group at BDO USA and leads the bioTRAK Database Services Team, focusing on providing data-driven market intelligence to the biopharmaceutical industry. She began her career in several small companies, gaining experience in many areas including anti-infective drug discovery and in vivo modeling, manufacture and purification of recombinant proteins and biopolymers, xenotransplantation, and the population genetics of parasitic infectious diseases. She specializes in forecasting the supply and demand of biopharmaceuticals and developing methodologies and models to uniquely quantify and forecast drug substance and drug product demand. She has experience in understanding the nuances and dynamics of the supply and demand landscapes for a wide variety of modalities, including mAbs, recombinant proteins, gene therapies, mRNA, and modified cell therapies.