Single-use bioprocessing equipment has made considerable progress in the past 10 years. An estimated 10% of current total worldwide bioprocessing capacity, or about 1.7 million liters, involves primarily single-use system (SUS) process lines. The market has grown from a few legacy products, such as plastic serum and media storage bags, tubing, and filter membranes, to the current situation where single-use technologies represent the majority of non-commercial applications in bioprocessing. This includes a wide variety of products and novel technologies currently available and in development.
BioPlan’s 15th Annual Report and Survey of Biopharmaceutical Manufacturing, 2018,1 which included responses from 222 biopharmaceutical manufacturers and CMOs in 22 countries and 130 bioprocessing suppliers or vendors, shows that single-use equipment is dominating small- and mid-scale bioprocessing and is being adopted for larger-scale commercial manufacturing.
With advancing technology, knowledge, and experience, future progress and market expansion are expected. In addition, the expansions and adaptations now being implemented in mainstream biologics production are also being seen in adjacent sectors, including cell and gene therapy, and even in the production of cosmetics and food derived from plant cell and tissue cultures, which are now being produced at manufacturing scales.
Single-use equipment is generally made of plastic parts that are sterilized by gamma irradiation, then used once and discarded. More than a decade of combined industry experience has shown the benefits of single-use versus fixed stainless steel, including lower capital investment and operational costs, as well as flexibility. SUS enable rapid setup of bioprocessing and progressive manufacture of multiple products at multiple scales in the same areas. Single-use product lines have expanded from basic storage bags to complex bioreactors. Now, essentially all bioprocessing, particularly upstream, can be done with single-use systems.
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from American Pharmaceutical Review – all delivered right to your inbox! Sign up now!
Less than 20 years ago, just a few single-use systems were available, generally limited in size to 100 liters. Now single-use bioreactors and mixers are available at ≤2,000 L scale. Due to engineering limitations, systems above 2,000 L are generally not practical or cost-effective. Currently, 1,000 L bioreactors are on track to be become the industry standard for new product large-scale and much commercial-scale manufacturing, with a growing number of companies offering an increasing range of product options.
In terms of revenue, stainless steel facilities currently account for ~85% of the market and single-use ~15%. This is projected to change in 5 to 10 years to about 70-75% stainless and 25-30% single-use. This includes growth in the SUS market of up to 300% and market share growing to ~25-30%. These data reflect downstream applications remaining limited over the next 5 years, with some increased adoption of SUS continuous chromatography and increased use for commercial manufacturing. These projections also reflect likely market growth from many new players entering bioprocessing, including in developing countries and biosimilar developers.
Market for Single-Use Equipment
The most dramatic growth will be for commercial-scale GMP manufacturing. The single-use market for commercial applications is projected to grow to over $1 billion/year in the next five years. This will be driven by products currently in development using single-use systems receiving approval and graduating to commercial-scale manufacturing. New products will continue to mostly be monoclonal antibodies, which will generally continue to require manufacture of 100 kilograms or more. This will increasingly involve parallel tracks, continuous bioprocessing, and/or multiple facilities worldwide anchored by 500-2,000 L SUS bioreactors. But even with this growth, fixed stainless steel systems will still dominate GMP/commercial and thus the overall market.
The BioPlan annual survey and other sources confirm that among the facilities surveyed, mostly in the U.S. and Europe, average purchases of single-use equipment are over $1 million/year. Bioprocessing professionals realize that SUS has improved bioprocessing. Over two-thirds (68.8%) of survey respondents cited SUS as providing “some” or “significant” improvement in their bioprocessing within the past year.
But end users recognize that they are often using first-generation or other less than optimal equipment. Our survey indicates that over the past five years, end users have continued to express a desire for improved single-use systems. As with most emerging technology, once new and better products and systems are introduced and become the norm, demand for further improvement continues until a general level of satisfaction is reached. In the bioprocessing industry, end users are apparently concerned that innovation in single-use bioprocessing supplies has been slow in coming. This is fully expected and normal in such a highly regulated environment, and demand for better products continues.
Single-use products with the highest rate of use at any stage/scale are shown in Figure 1. The most commonly used products are simpler devices, such as bags and connectors. But it is significant that more than 70% of facilities use major bioprocessing systems, including bioreactors, mixers, and tangential fl ow filtration, and are more likely to be fully dedicated to using SUS.
Among the reasons for adopting single use described as “very important,” 46.2% of respondents said it decreases the risk of cross-product contamination, 41.2% said it eliminates cleaning requirements, 44.1% said it reduces the time to get a facility up and running, and 40.4% said it reduces capital investments in facilities and equipment. With regard to concerns or potential problems, five were mentioned by more than 50% of respondents: “Breakage of bags and loss of production material,” 75.0%; “Leachables and extractables,” 73.3%; “High cost of disposables,” 68.8%; and “Material incompatibility with process fluids” and “We do not want to become vendor-dependent (single-source issues),” 56.7% (tie).
Concerns Over SUS
As use of SUS increases, concerns about cost can be expected to increase, particularly as more bioprocessing professionals only familiar with stainless steel equipment purchase SUS. However, from other survey research, we found that price is not a primary concern among purchasers of any bioprocessing equipment. End users prefer to purchase the best equipment they can get and are willing to pay more, as long as the premium is not excessive.
Single-use systems manufacturing will advance and continue to proliferate, with more diverse technologies and products becoming available. However, in terms of capacity, most of the largest facilities are likely to remain in use. New capacity will be added at smaller scales, with most new commercial manufacturing facilities still using stainless steel. As such, stainless steel will continue to dominate bioprocessing in terms of capacity and number of large-scale and commercial facilities.
A number of individualized biologics and personalized medicines are in active development, including patient-specific cellular and gene therapies, cultured tissues and organs, and cancer and other therapeutic vaccines. With their one-off nature and need for sterility, these products can be expected to be manufactured using single-use equipment. BioPlan has projected significant growth in cellular and gene therapy capacity and facilities, despite a current shortage that will become an actual capacity crunch in coming years.
We are already seeing another trend: modular facilities, with processes housed in connectable, portable clean rooms or isolator units, and whole portable manufacturing facilities that can be constructed and operational in a matter of months or even weeks. With modular systems using SUS equipment and providing much the same advantages as single-use, the market is expected to grow dramatically. This includes “plug-and-play” factories, with whole production lines and facilities fully clonable. With an increasing demand for domestic biopharmaceutical manufacture, modular facilities will become more common in developing countries, particularly China and India, in the next decade.
Besides inherent conservatism in this highly regulated industry, an issue restricting progress in the expansion of single-use systems is vendors’ hesitancy and end users’ distress over incremental improvements and other changes in established product lines. This is because any changes in bioprocessing products already in use can require extensive validation studies, more regulatory filings, costly testing, new SOPs, etc. Innovations in single-use equipment will more likely originate from small companies or new major suppliers and developers less attached to aging technologies. New technologies in this industry are generally implemented by totally new facilities and process lines, not retrofitting.
Fastest Growing Areas of SUS Development
The fastest growing segment of the single-use equipment market will be upstream bioprocessing at large and commercial scales as products now in development using SUS move up to commercial manufacturing. As demonstrated by the annual BioPlan survey and confirmed by many other sources, adoption of single-use systems, generally in place of fixed stainless steel systems, will continue. Modular systems may be the next technology to experience such increased and rapid adoption over the next decade. And as cellular and gene therapies emerge, we will likely see SUS technologies created and adapted explicitly for these personalized applications.
Most of the growth in SUS will be in developed countries, but developing countries will see much faster growth rates. For example, many of the new bioprocessing facilities expected to be constructed in China to meet both domestic demand and its desire to become an exporter of biopharmaceuticals will be primarily SUS facilities.2 The future for SUS technologies remains defined by the expanding global need for better, cheaper, and faster biologics production.
References
- Langer, E.S., et al, 15th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, BioPlan Associates, Rockville, MD, USA April 2018.
- Directory of Top 60 Biopharmaceutical Manufacturers in China, 2nd edition, BioPlan Associates, Feb. 2017, 357 pages (also online database).
About the Author
Ilene Roizman is communications manager at BioPlan Associates, Inc. She is a skilled writer and medical communicator, able to distill highly technical information in medicine and science. Her medical expertise includes editing of textbooks, as well as research papers for international science and medical journals. + 1 301-921-5979, www.bioplanassociates.com
Survey Methodology: The 2018 Fifteenth Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production yields a composite view and trend analysis from 222 responsible individuals at biopharmaceutical manufacturers and contract manufacturing organizations (CMOs) in 22 countries. The methodology also included over 130 direct suppliers of materials, services, and equipment to this industry. This year’s study covers such issues as: new product needs, facility budget changes, current capacity, future capacity constraints, expansions, use of disposables, trends and budgets in disposables, trends in downstream purification, quality management and control, hiring issues, and employment. The quantitative trend analysis provides details and comparisons of production by biotherapeutic developers and CMOs. It also evaluates trends over time and assesses differences in the major markets in the U.S. and Europe.