Shriya Bhatkhande- Research Associate, BioPlan Associates
32% jump in use of disposables at the commercial scale since the beginning of COVID-19
Introduction
As the world races towards a post-pandemic future, the surge in demand for single-use systems (SUS) and devices is revolutionizing the production of biologics and vaccines. In BioPlan’s 19th Annual Report and Survey of Biopharmaceutical Manufacturing,1 we found that the use of commercial-scale SUS bioreactors in particular has grown appreciably during COVID, increasing from 32.5% in 2019 to 43% in 2022 (Figure 1). This 32% increase is partly due to the demand for flexibility and rapid deployment of bioproduction during the pandemic crisis. However, the pandemic only accelerated the adoption of SUS devices, which has seen rapid growth since 2006 when we first began measuring the deployment of disposables in bioproduction.
This growth at the commercial scale has been predicted by the industry for many years. For example, back in 2017, we asked industry respondents if they expected to see a “100% fully SUS/disposable facility within five years (by 2023)”. Even then, before COVID-19, there was an anticipation of these shifts. Back then, over two-thirds of respondents, 67.4% in the US “Agreed” or “Strongly Agreed” that such was a likelihood.
The COVID-19 pandemic has increased demand for more flexible and quickly deployable biomanufacturing strategies. Bioplan has estimated that over 85% of pre-commercial manufacturing is now being done using SUS. At a larger commercial scale, stainless steel is often considered a more economical manufacturing strategy.
The growth in SUS usage starts at earlier stages in the development process. R&D and Process Development typically see more rapid use or adoption of novel technologies. From there, we see growing usage at GMP clinical scale, assuming these SUS approaches can be scaled up to larger commercial applications.
For example, we can see in Figure 2 that 17 years ago in 2006, there began a relatively rapid uptake of disposable SUS bioreactors, from 21% in 2006 to 87% in 2022. Other SUS devices show similar growth, but complex bioreactors can be used as a leading-edge indicator of adoption of the technology because they require a facility to make a more significant shift in their manufacturing strategy than with, for example, tubing or simple storage or buffer bags.
The need for rapid vaccine production during the pandemic shifted the trend toward the adoption of flexible technologies that could be implemented quickly. The trend towards the use of SUS in commercial manufacturing continues post-pandemic.
COVID-19 has been a primary factor in accelerating the use of SUS devices. However, this rising tide of SUS usage has floated more than just COVID-19-related therapies. The growth at the clinical scale is less due to COVID-19 than to other long-term factors such as the flexibility and other advantages delivered by SUS. For example, cellular therapies, are produced at small scales, and virtually all require SUS bioreactors, tubing, and manifolds. These ensure yet another steady market for SUS suppliers.
Reasons For Expanding the Use of Single-Use Systems
SUS continues to enable more rapid, cost-efficient bioprocessing as it provides multiple other advantages. Most of these benefits have been clearly demonstrated over the past 15-20 years. So when the COVID-19 pandemic arrived, SUS technologies had been used in human therapeutics for many years…long enough to ensure rapid deployment for the production of related vaccines and biotherapeutics.
Typical advantages of SUS compared to stainless steel-based facilities include:
- Shortens processing times.
- Cuts operational costs related to reducing times to market.
- Production capacities can be adapted in response to changes in market needs.
- Reduces the risk of cross-contamination which allows the manufacturing of multiple products in the same facility.
- Contamination control due to SUS reduces related quality and regulatory concerns, testing, and documentation which can boost productivity and enable rapid bioprocessing of vaccines.
- SUS can reduce facility costs and size, can be more easily implemented, require fewer validation requirements, and provide faster changeovers in bioprocessing.
SUS is currently being used for almost every bioprocessing application, including upstream expression, harvesting, filtration, purification, storage, mixing, formulation, fill-finish, etc. of biopharmaceuticals. The cost of non-blockbuster scale commercial manufacturing using a SUS is now compared to, and many claim it is less expensive than, stainless-steel systems.
Benefits of Single-Use Systems for Bioprocessing
Single-Use Systems in bioprocessing enhance speed and efficiency, allowing for rapid bioprocessing setup and progressive manufacturing of multiple products at various scales within the same facility. The flexibility of SUS enables more adaptability, allowing for seamless transitions from R&D to full-scale production or for the manufacturing of different products. This results in improved throughput and scalability, enabling developers and manufacturers to bring products to market more quickly.
In the past, SUS usage had been constrained by the physical properties of the plastics and bags typically to 1000-2000L. This was insufficient to meet demands for commercial production scales. However, in recent years, with increased upstream productivity and newer products frequently requiring lower or less frequent dosing, the production requirements have increasingly been met using equipment with a tenth of the capacity compared to just a decade or two ago (e.g., a 2,000 L bioreactor can do the job previously done by two x 10,000 L bioreactors).
SUS bioreactors and other equipment are now fully viable and cost-effective options, for capacities of 2,000 L or larger. Entirely SUS processes capable of supporting cost-competitive larger commercial-scale manufacturing have become a reality, including scaling out by running multiple SUS in parallel, such as those anchored by 1,000- 2,000 L bioreactors. As a result, more companies are focusing on cost-effective downstream SUS innovations, which continue to be a need.
CMOs and product developers/manufacturers continue to integrate SUS into most or all of their bioprocesses. This is determined by economics, risk mitigation, and speed. Furthermore, as new regions, such as China and India, continue to produce vaccines, and biosimilars, even if only for domestic markets, the need for consistent quality and GMP compliance may necessitate the increased use of SUS as it can be implemented more efficiently, and quickly.
As new biologics enter the pipeline, SUS has become an integral part of developers’ manufacturing strategies. SUS can assist smaller and newer organizations, as well as those in less developed regions, in becoming more effective and competitive.
Percentage of Unit Operations That Are Single-Use
In 2022, we gauged the relative adoption rate of single-use devices by asking respondents to provide an estimate for what percent of your biomanufacturing systems (e.g., # of major components/ devices) would you describe as “single-use” or disposable? (Figure 3). We averaged respondents’ percentages of SUS usage at various scales. While this method does not provide a comprehensive industry analysis of actual SUS penetration, over time it shows the growth and rate of change for this penetration.
Changes from last year include:
- 62.9% for Upstream Clinical Production (up from 45.0% in 2021)
- 76.3% for Downstream Clinical Production (up from 66.1% in 2021)
- 82.5% for Upstream Commercial Production (up from 65.0% in 2021)
- 52.8% for Downstream Commercial Production (up from 38.7% in 2021)
Respondents were not asked to quantify the percentage of equipment by “value,” or number of units. Thus, these estimates are primarily useful over time to better understand trends in single-use adoption rates. These increases in use reflect the trends discussed in other sections of this report indicating a shift toward single-use devices, particularly at commercial scales, with 14.1% growth in downstream applications from 2012 to 2022.
SUS penetration in downstream processing (DSP) at the commercial scale took a big leap, from 17.3% in 2014 to 52.8% in 2022. Innovating downstream disposable technologies is challenging. Aside from filtration steps, these DSP processes tend to involve chromatography resins, which are generally reusable, expensive, and not disposable. However, there are several innovators already developing commercially viable alternatives to costly Protein A resins and other media. DSP has been historically slow to adopt SUS unit operations for commercial chromatography steps. Our data suggest that as clinical biotherapeutics work their way through the development pipeline, they will ultimately scale up using the same SUS technologies to commercial scale, over time.
The usage trend around all upstream SUS (including bioreactors, media and storage bags, tubing, and manifolds) at a commercial scale started in 2020 at 34.7% average penetration. It climbed to 65% in 2021 and 82.5% in 2022. A similar growth trend can be seen in the downstream commercial scale growing from 22.6% average utilization to 52.8% in 2022.
Clinical scale usage of SUS showed similar pre-and and post-COVID-19 growth, but not as dramatic since clinical scales have generally already been a relatively strong SUS domain for at least 10 years.
Conclusion
The COVID-19 pandemic is reaching an endpoint in many communities, but the impact the crisis has had on bioproduction over the past three years has been indelible. Disruptions in supply chains for virtually all equipment, consumables, and services in bioprocessing have stressed the system more than anyone could have predicted. Accelerating the adoption of SUS devices is only one of COVID-19’s many vestigial legacies. However, SUS was already on track for a dominant role in the industry even without the pandemic’s prodding.
More facilities will continue to adopt SUS technologies and both new and old technologies from cellular/gene therapies to biosimilars are likely to continue to accelerate. However, with the SUS market becoming largely saturated at scale-up and clinical manufacturing, much of the growth will be at larger commercial scales as products progress through development and continue to use SUS for commercial manufacturing.
The COVID-19 pandemic has led to a significant increase in demand for biologics and vaccines. Single-use systems have become essential in ensuring the safe and efficient production of these products. With the ability to rapidly deploy flex capacity and reduce the risk of cross-contamination while increasing production speed, single-use systems have become a vital part of the biopharmaceutical industry. This trend is expected to continue in the future as the demand for biologics and vaccines remains high and as new products and platforms are developed, further driving the demand for single-use systems at a commercial scale.
Reference
- Langer, E.S., et al., Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, 19th annual edition, BioPlan Associates, Rockville, MD, April 2022, 490+ pages.
About the Author
Shriya Bhatkhande holds a Master’s in Biotechnology and Business from University College, Dublin, and a Masters graduate in Food Science and Technology. Her background includes strategy and business development for Cambridge Life Sciences, UK, and Inflection Biosciences, Dublin. She’s done extensive research and industrial analysis on a range of products from the design phase through product.
sbhatkhande@bioplanassociates, www.bioplanassociates.com
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