【Development history and trends of China’s bioreactor market】
If we look at the reactor market from a global perspective, domestic biopharmaceuticals, especially antibody drugs, have only truly moved from research and development to the commercialization stage in the past ten years, while the construction of the first round of commercial production capacity in the European and American markets has essentially It started around 2000. The first batch of antibody industrialization construction by Roche/Genentech, Eli Lilly, Bristol-Myers Squibb, Merck Serono and other companies have greatly stimulated the outbreak of the domestic antibody industry, and the domestic understanding of large-scale cell culture reactors After that, we started to delve deeper. In order to reflect the market changes in these years, we divided the history of more than 10 years into 4 stages.
Ⅰ 2005-2010: R&D and early pilot phase
At this stage, after a certain period of R&D accumulation and stimulated by the rapid growth in sales of antibody products that were recently launched, European and American giant pharmaceutical companies have begun to build commercial production lines. At this time, the market demand is still in the development stage. The cell protein expression level in the industry is generally around 1g/L or lower, and the general scale of reactors is 5000L-10000L. At the same time, the first domestic companies to invest in this round of antibody drug development have already started, such as CITIC Guojian, Biotech, etc., have already launched research and development and pilot projects. At this time, the domestic reactor market is mostly dominated by glass benchtop reactors used for research and development or pilot reactors of about 100L-500L, and almost all rely on imports. Only a few domestic companies have started manufacturing cell reactors, but they mainly imitate adherent cell culture reactors, with a scale of about 50L. They are mainly used for R&D and pilot trials, and are bioreactors used for macromolecule cell culture. Accounting for less than 10%.
Ⅱ2011-2015: Pipeline early start stage
In the following five years, the continued R&D and clinical development in the European and American markets, especially the rapid development of drug sales, inspired major pharmaceutical companies and their CDMO companies to build commercial production lines of scale, such as 4×16000L, 4×20000L, 6×12000L, etc., and began to build production capacity in non-Europe and the United States, represented by South Korea and Singapore. At this stage, the pipelines of many domestic pharmaceutical companies and innovative biotechnology companies have also begun to gradually enter the clinical stage, and they are rushing to build early pilot production lines and GMP production lines to complete clinical trials ahead of competitors. The more representative ones are In the 500L-2000L scale, a few companies have built 3000L and 5000L scale production lines. In the past five years, the largest share of the bioreactor market has been disposable reactors, whose large-scale marketing began around 2011. Nearly all of the major biotech suppliers have launched their own single-use reactors and liquid management systems with significant success. Disposable equipment has several salient features: short construction period, easy cleaning and verification, low construction difficulty, and small initial investment. These features are very suitable for start-up biotechnology companies and biopharmaceutical products with uncertain prospects as the first initial investment. production lines to quickly establish the supply of clinical products. During this period, Junshi Biotech was the first in China to build a cell culture production line that uses disposable processes both upstream and downstream. By 2015, not many one-time production lines had been built, and there were about 5-7 production lines built nationwide.
Ⅲ 2016-2019: Construction of the first batch of commercial production lines
From the international market, the product pipeline of biopharmaceuticals continues to expand. From monoclonal antibodies to ADCs to bisAbs, more and more drugs are entering the commercialization stage, and sales continue to grow rapidly. The global market structure has greatly stimulated the influx of domestic and foreign capital into the domestic biopharmaceutical market. It coincides with the first wave of domestic companies’ products entering the third phase of clinical trials. Many pharmaceutical companies and biotechnology companies have sufficient funds to start construction. Started its own GMP production line. Most of the production lines at this stage are the first GMP production lines of many companies, mainly 2000L and 3000L. Disposable or stainless steel lines are chosen as the first commercial production lines. At this scale and capacity, the proportion of disposable systems is higher than that of stainless steel systems. Most companies still choose to import all equipment, but some pharmaceutical companies have begun to actively seek local reactor manufacturers to replace imports and prepare for future cost competition. A very few large reactors have been manufactured domestically.
Ⅳ2020-2021: Production capacity explosion, price war, trade war
Due to factors such as the accumulation of industry R&D investment in the past few years, the sales stimulation of pre-commercial products, the encouragement of national policies, the vision of corporate globalization, and the cost pressure brought by national centralized procurement, biopharmaceutical companies have begun to build large-capacity stainless steel System commercial production lines, such as 3×10000L, 4×10000L, 4×20000L, 6×12000L, 8×15000L and other commercial production line projects have started construction one after another. Under further guidance from the market, the industry has gradually formed a consensus that commercial GMP production lines, especially those with large sales, are more suitable for stainless steel reactors because they can ensure better process conditions, lower operating costs, and higher automation, and also lays the foundation for smart manufacturing. At this stage, the external environment also brought urgency to localized manufacturing. The occurrence of the Sino-US trade war has brought vigilance, and the US government has begun to restrict the export of biotechnology-related products and technologies; the biopharmaceutical industry is an industry that the country encourages the development of, and various policies have been introduced to encourage domestic development of core production and manufacturing process equipment. Capability; the high degree of cost competition brought about by centralized procurement requires the support of relatively low-cost domestic manufacturing equipment; due to the uncertainty in the supply chain caused by the epidemic and the cost pressure of imported consumables, many pharmaceutical companies have also begun to consider one-time responses to local manufacturing Bags and reactors, many domestic companies have launched corresponding products.
At present, many localized manufacturing companies have emerged in China based on the digestion of imported equipment and technology, and have been applied in some large-scale projects. The capacity of large-scale stainless steel production lines under planning or construction in China is nearly 2 million liters. Among them, the ratio of imported brands, imported brands designed overseas and domestically manufactured, and completely domestically manufactured is about 30:20:50. The proportion of domestic manufacturing has increased significantly.
【Future Outlook of the Bioreactor Market】
After years of development, in the field of bioreactor manufacturing, my country has evolved from complete imports to partial domestic substitution and localized manufacturing of imported brands, and has initially formed the manufacturing capacity of high-level bioreactor production lines. However, compared with foreign levels, there is still considerable room for improvement in reactor design, module design, automatic control strategies, and manufacturing quality. In terms of automatic control units and instruments, it is still not possible to completely get rid of dependence on imported products. With the advent of the era of digital transformation in the manufacturing industry, it can be expected that the integration of bioreactor technology and artificial intelligence will be the development direction of digital twin technology. As the core process equipment on which biopharmaceuticals rely, bioreactors will surely further develop in line with the exact needs of biopharmaceutical companies, not only in terms of quantity growth, but also in terms of quality. The pursuit of higher cell density, higher unit output, and higher degree of automation will be the direction and goals pursued by pharmaceutical companies.
