Amid Soaring Demand and Tightening Trade Restrictions, Where Is the Single-Use Bioreactor Industry Headed?

On the second day of work in the Year of the Tiger, domestic pharmaceutical investors were truly startled.

WuXi Biologics, a leading biologics CDMO in China ranked among the top nationwide in production capacity, has been added to the U.S. Department of Commerce’s Unverified List (UVL). Although there is no explicit cutoff in supply for single-use bioreactors—a core consumable in manufacturing tools—import scrutiny has become more complex. Chinese manufacturers have long relied heavily on imports for single-use bioreactors. When addressing domestic substitution for controlled products, WuXi Biologics expressed hesitation, noting, “If imported products can achieve a score of 90, current domestic offerings only reach a level of 60.” Amid global shortages of COVID-19 vaccines, this portion of production capacity has begun shifting toward foreign manufacturers, extending lead times for domestic suppliers awaiting deliveries. Under stricter import regulations, the shortage of single-use bioreactors is clearly set to intensify.

Of course, for secondary market investors, the greater panic is that more key raw materials for biopharmaceuticals are being choked.Therefore, even though WuXi Biologics responded with confidence at the earliest opportunity, it failed to prevent a low opening for stocks in the WuXi group. WuXi AppTec was inadvertently dragged down, plunging to its daily limit down shortly after opening significantly lower. Meanwhile, WuXi Biologics’ H-shares dropped by more than 30% at their lowest point, leading to a trading halt by midday and wiping out over HK$100 billion in market capitalization for the day. This negative sentiment persisted into subsequent trading sessions.

However, looking at the other side of the coin, this situation presents an excellent opportunity for the long-delayed domestic substitution of single-use bioreactors.

In recent days, domestic manufacturers of biopharmaceutical consumables have witnessed a consecutive surge in their stock prices. Tofflon, whose product portfolio covers core biopharmaceutical processes ranging from liquid nitrogen storage to cell culture media handling, saw its stock price rise by 8.03% on the day the UVL news broke, followed by another 6.41% increase the next day. Similarly, the share price of Truking Technology, a leading Chinese pharmaceutical equipment enterprise, climbed by 8.49% and 6.64% respectively. In fact, these two companies emerged as the biggest hidden winners during the COVID-19 pandemic, with their market capitalizations frequently doubling as stock prices soared from single digits to tens of yuan, while their net profits successively surpassed the RMB 100 million mark, gradually positioning them as leading upstream players in the biopharmaceutical industry. Meanwhile, star projects in the single-use bioreactor sector—such as Jinyi Shengshi, LePure Biology, and Duoning Biology—which have completed multiple rounds of financing since the outbreak of COVID-19, have continued to expand production capacity and intensify R&D efforts, becoming vital links in the industrial chain. The current tightening of import channels has undoubtedly injected stronger momentum into their growth and expansion.

In recent years, upstream biopharmaceutical tools have rapidly come into the spotlight for entrepreneurs and investors. High-quality projects in niche sectors such as petri dishes and chromatography systems have sequentially become market favorites, leaving single-use bioreactors appearing to lag behind. The underlying reason is that the higher technical barriers of single-use bioreactors have prevented most domestic teams from engaging in independent research and development. What they can do is more limited to accumulating knowledge through reverse engineering and exploring the inflection points of innovative technologies, which is precisely a critical step in the inevitable growth path of this cell culture technology.

Single-use bioreactors, commonly referred to as such, are cell culture systems composed of regulatory agency-certified plastic materials (such as polyethylene, ethylene-vinyl acetate, polycarbonate, and polystyrene), along with associated controllers and adjustment software. Characterized by their ready-to-use, non-reusable nature, they provide optimal conditions for cell growth and product formation. Although this cell culture tool first appeared in the laboratories of American biologists in the 1960s, it did not enter large-scale application until nearly 40 years later, when Wave Biotech launched the WAVE Bioreactor™ 20, the first wave-mixed single-use bioreactor designed for commercial production.

Currently, single-use bioreactors are widely employed for seed train expansion, ranging from small-scale to pilot-scale cultures of mammalian, plant, and insect cells. They have become the mainstream production platform for monoclonal antibodies, vaccines, recombinant proteins, and other biologics. However, the industry has long been challenged by limitations in reactor scale-up and potential issues arising from extractables and leachables associated with the disposable materials.

Specifically, on one hand, as previously mentioned, single-use materials struggle to withstand sustained high pressure, thereby limiting the further scale-up of single-use bioreactors. On the other hand, single-use plastic bags used for cell culture may release leachables upon contact with the culture; once these leachables enter the culture medium, they can inhibit cell growth. Currently, there is no standardized test method applicable for detecting leachables from different membranes. Optimizing these underlying technologies is undoubtedly a process that requires long-term accumulation of experience and repeated trial and error.

Internationally, the development of single-use bioreactors has been a process of multiple iterations., giving rise to mainstream types across different eras, such as wave-mixed, stirred-tank, and orbital shaking bioreactors. These single-use bioreactors, developed based on distinct principles, cater to varied cell culture requirements and maximum working volumes.

Three years after the launch of the WAVE Bioreactor 20, orbital shaking single-use bioreactors achieved their first complete operational run in laboratory settings. In 2004, Hyclone introduced the first stirred-tank single-use bioreactor, with a maximum working volume of 250 L. Among these, wave-mixed single-use bioreactors have been widely used for seed cell expansion and the culture of shear-sensitive mammalian cells. The development of orbital shaking single-use bioreactors has been relatively slower; they are primarily employed for culturing animal and plant cells with lower oxygen demands, mainly limited to laboratory-scale applications. They are mostly used for the cultivation of animal cells, microalgae, insect cells, plant cells, and microorganisms.

Stirred-tank single-use bioreactors emerged relatively late but have developed at an extremely rapid pace, becoming the most widely used type to date. Major companies such as Thermo Fisher Scientific, GE, Sartorius, Merck, and Pall have successively launched stirred-tank single-use bioreactors with larger working volumes. Among these, Thermo Fisher Scientific’s HyPerforma series offers a maximum working volume of 2,000 L and is primarily used for the culture of animal and insect cells. Meanwhile, the 2,000 L stirred-tank single-use bioreactors Xcellerex XDR (from GE) and BIOSTAT STR (from Sartorius) are mainly employed for the culture of CHO cells, mammalian cells, and other cell types. The introduction of 2,000 L systems marked a significant milestone in the development of stirred-tank single-use bioreactors. Subsequently, industrial giants such as AVEC and Thermo Fisher Scientific rapidly developed stirred-tank single-use bioreactors with working volumes ranging from 3,000 L to 6,000 L.

During this process, the supply side of single-use bioreactors experienced highly active industry mergers and acquisitions. For instance, Fenwal, a developer of plastic plasma bags, was acquired by Fresenius Kabi; Nunc, the developer of CellFactory, changed hands several times before ultimately becoming part of Thermo Fisher Scientific; the pioneer WAVE was acquired by GE, and later became part of Danaher after GE sold its life sciences division to Danaher; and Hyclone was first acquired by Thermo Fisher Scientific, then transferred to GE, and is currently under Danaher.

At present, the global single-use bioreactor market is predominantly dominated by overseas giants such as Cytiva, ABEC, and Sartorius. Although Chinese companies like Tofflon, Truking Technology, Donning Biotech, LePure Biotech, and Kingyi Shengshi have made early strategic entries, their competitive advantages remain largely confined to related peripheral consumables. For instance, LePure Biotech’s single-use reaction, storage, and mixing bags already account for 20–30% of the domestic market in China.

An investor who has long followed the biopharmaceutical sector told VCBeat that, at the level of foundational technology, domestic single-use bioreactor teams still lag significantly behind overseas giants. “Many core teams at Chinese manufacturers have professional experience in R&D and management roles at these major foreign companies. They place a high priority on technological R&D and have a relatively accurate grasp of strategic direction. In a sense, the anxiety spurred by WuXi Biologics’ inclusion on the U.S. Unverified List (UVL) will serve as a positive incentive for their technology development.”

It is undeniable that single-use bioreactors became one of the most active subsectors for investment and financing activities in 2021.

In July 2021, Jinyi Shengshi, a provider of single-use systems for biopharmaceuticals, completed two major rounds of financing within six months, with each round amounting to hundreds of millions of RMB. Six months later, Huatai International Private Equity Fund led the company’s Series B+ financing round, which raised tens of millions of US dollars. Founded in 2014, Jinyi Shengshi became the first company in China to localize the technology for single-use bioreactors and single-use consumables in biopharmaceutical manufacturing processes. After introducing top-tier investors such as Matrix Partners China, Huarui Investment, and Jiayuan Capital during its Series A financing, the company secured further support from institutions including CMB International Capital, Sherpa Capital, CITIC Medical Fund, and C&D Emerging Investments in its Series B round.

In late 2021, Lepu Biotech and Duoning Biotech successively announced the completion of their Series C and Series B+ financing rounds, respectively, with total amounts exceeding RMB 1 billion.

Among them, Lepu Biopharma, a provider of single-use technologies and integrated solutions for biopharmaceutical manufacturing, completed a B+ round of financing worth hundreds of millions of U.S. dollars in the first half of the year. This round followed its Series B financing, which was led by two funds under Junlian Capital and participated by Shanghai Gaoling Chenjun Equity Investment Partnership (affiliated with Hillhouse Venture Capital), and saw the addition of several well-known institutions. Meanwhile, Duoning Bio, which focuses on product development in the fields of serum-free media, single-use products, and bioreactors for the biopharmaceutical industry, secured continued additional investment from existing shareholders such as Sequoia China and Qingchi Capital in its Series C financing, while also introducing renowned professional investment institutions including DeFu Capital and Huitianfu.

In fact, the surge of capital investment has brought abundant liquidity, enabling domestic manufacturers of single-use bioreactors to devote greater resources to the development of more complex technologies and products.For example, Lepu Biopharma’s team has been dedicated to the development of single-use consumables and equipment for biopharmaceuticals for over a decade. Recently, it began establishing an R&D center in the United States, integrating the upstream industrial chain, securing its supply chain, and expanding its R&D and market operations teams both domestically and internationally, thereby formally entering the global competition for key technologies.

For another example, Duoning Biologics, which initially built its business on CHO cell culture media, accelerated its M&A pace in the past two years after acquiring a 40% stake in Lepu Biotech in 2016. It has brought companies such as Guangzhou Qizhi, Lianghei Technology, Jinke Filtration, Shanghai Ximai, and ATS Antuos under its umbrella. Building upon its existing platforms for domestically produced serum-free culture media and novel single-use consumables, the company has continuously expanded into new business areas, extending its reach across the upstream and downstream supply chain of biopharmaceuticals.

Among them, Guangzhou Qizhi specializes in laboratory-scale cell bioreactors, pilot- and production-scale cell bioreactors, laboratory-scale microbial fermenters, and pilot- and production-scale microbial fermenters, with technical capabilities comparable to imported counterparts. Lianghei Technology provides professional, customized technical solutions for liquid transfer, instrument connection, fluid storage, and system assembly in biopharmaceutical manufacturing. It supplies GMP-grade pharmaceutical hoses, tubing assemblies, and compatible single-use connectors and sensors for R&D, small-scale trials, pilot studies, and scaled-up production. Following the acquisition, these efforts will help Duoning Biology reduce the cost of single-use products and enhance the quality of domestically produced single-use products.

Entering 2022, investment and financing enthusiasm for single-use bioreactors remained strong. Jin Yi Sheng Shi announced its latest funding round just before the Spring Festival of the Year of the Tiger, while many other investors hit the ground running, visiting projects related to single-use bioreactors as soon as work resumed. An investor confided to VCBeat that although the market size for single-use bioreactors—and indeed for most upstream biopharmaceutical projects—is not particularly large, with industry ceilings generally below RMB 10 billion, they remain an indispensable component in the investment portfolios of specialized biomedical institutions. “In fact, we do not wish to see excessive heat in this sector,” the investor noted. Nevertheless, amid surging demand, single-use bioreactors, as a critical link in biopharmaceutical manufacturing, have inevitably become a hot spot.

If we further analyze the reasons behind the recent surge in popularity of single-use bioreactors, beyond the shortage of imported supplies caused by the COVID-19 pandemic mentioned at the beginning of this article, it is undoubtedly driven by the R&D and clinical implementation demands resulting from the continued prosperity of the innovative drug ecosystem.

This demand is primarily reflected in the continuous growth in the number of clinical trials.In November 2021, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) released the Annual Report on the Status of Clinical Trials for New Drug Registration in China (2020). The data showed that a total of 2,602 clinical trials were registered in 2020, representing an overall increase of 9.1% compared to 2019 (2,386 trials). Among the clinical trials completed in 2020, Phase I trials were the most prevalent, followed by Phase II trials, while only five Phase III trials were completed.

Conducting a vast number of clinical trials for a large pipeline of innovative drugs may be the most dynamic scene in China’s pharmaceutical ecosystem in the short term.Typically, the number of patients required for enrollment in drug clinical trials increases from Phase I to Phase III, leading to a corresponding rise in demand for investigational medicinal products. As clinical trials advance to later stages, manufacturing capacity for these investigational drugs inevitably comes under pressure.

Under pressure, innovative pharmaceutical companies are expanding their production capacity, driving huge demand for bioreactors.In the first half of 2021, four domestically produced PD-1 inhibitors were in a critical phase of post-reimbursement market expansion, with varying degrees of capacity expansion underway. Antibody and antibody-drug conjugate (ADC) candidates in Phase III clinical trials or with marketing applications submitted also began preparing for capacity building. WuXi Biologics, a biological drug CDMO, led capacity expansion efforts across China. According to first-half 2021 financial reports, capacity construction by Chinese pharmaceutical companies primarily relied on single-use bioreactors, mostly at a production scale of 2,000 liters. Meanwhile, BeiGene and Innovent Biologics have begun shifting toward the construction of stainless steel bioreactor production lines, which will further reduce the production costs of biologics and enhance their competitive advantage in scaling up output.

Furthermore, for biotech companies that lack the conditions to establish in-house manufacturing capacity, the outsourced demand generated by advancing their R&D pipelines into clinical stages has placed higher demands on CDMOs’ production capacity, prompting them to continuously expand their facilities. For instance, financial reports indicate that WuXi Biologics further expanded its capacity construction in the first half of 2021, with plans to increase its total capacity to 430,000 liters. Domestically, WuXi Biologics’ production bases now cover Hangzhou, Chengdu, Shanghai, and Wuxi, while internationally, it has expanded into the United States, Ireland, and Germany.

A previous study showed that more than 50 monoclonal antibody (mAb) candidates or projects worldwide have adopted single-use bioreactors, and nearly 77% of pharmaceutical companies and contract development and manufacturing organizations (CDMOs) globally use single-use bioreactors for the development of related products. For example, WuXi AppTec established 2,000-L single-use bioreactor capacity as early as 2013, successfully replicating cell culture processes from traditional stainless-steel bioreactors, and completed pilot production of the first batch of ibalizumab, a monoclonal antibody drug for HIV treatment, by culturing NS0 mouse myeloma cells. Furthermore, more than 20 companies in China, including Henlius, have adopted single-use bioreactors for the production of monoclonal antibody products.

It is worth noting that, due to the greater flexibility in capacity configuration offered by single-use bioreactors compared to traditional stainless steel tanks, their compatibility with the outsourcing nature of CDMOs, their ability to prevent cross-contamination between different production tasks, and their improvement of operational efficiency, biological CDMOs are increasingly adopting single-use reactor technology during capacity expansion. For instance, WuXi Biologics extensively employs single-use bioreactors in its production lines; one of its facilities houses China’s first 4,000L single-use bioreactor, while another facility is the world’s largest cGMP biologics manufacturing plant utilizing single-use bioreactors, featuring two complete production lines with a total capacity of 60,000L.

As the international trade environment becomes increasingly challenging, the aforementioned demand for single-use bioreactors has, to some extent, turned into an opportunity for domestic manufacturers. Coupled with the momentum generated by ample liquidity, this industry is being propelled onto a new fast track of development. Whether this process will give rise to world-class, platform-based enterprises remains to be seen.