Regarding the internationalization of new drugs in China, more discussion has focused on clinical research and supervision, and the issue of production has not received enough attention. In fact, production is also a barrier to internationalization, especially for small and medium-sized innovative companies that develop biological drugs.
International CDMO
The internationalization of domestic new drug research and development shows different characteristics from Europe and the United States. European and American leading pharmaceutical companies have mature experience in the internationalization of innovative drugs, and small and medium-sized biotechnology companies can work with them to achieve product internationalization. The domestic is more small and medium-sized biotechnology companies layout innovative drug international research and development, such companies have strong independent research and development capabilities, but lack of production and registration and other aspects of the software and hardware support.
According to the statistics of R&D customers, there are more than 50 enterprises in the domestic layout of international development of biological drugs, but only a very few companies such as Henlius and Cinda Biologics have international GMP certification of biological drug production bases. Many companies believe that it is extremely difficult to sell domestically produced biological drugs to the European and American markets, so the overseas rights and interests of many products are directly transferred to European and American enterprises.
There are also some companies that have taken inspiration from the MAH system and chosen product internationalization to cooperate with CDMO (Contract Research and Development and Production Organization) companies.
Wang Bin, General Manager of Boehringer Ingelheim China Biopharmaceuticals (hereinafter referred to as BI Biopharmaceuticals), said: "If SMEs plan to adopt the strategy of independent international development of products or even simultaneous listing and sales at home and abroad, choosing to cooperate with CDMO is a shortcut to achieve global supply of products. ”
Wang Bin spoke at the Shanghai International Biomedical Industry Week Summit Forum on October 14.
Companies such as Lijin Bio and Anritsu Xirong are among the representatives. Lijin Bio focuses on the research and development of tumor immuno-agonist antibodies, and its products LVGN6051 and LVGN7409 are carrying out clinical research in China and the United States. Anritsu Xirong's antibody product EI-001 for chronic hepatitis B has also submitted a clinical research application to begin Phase I research in Australia. Both companies are currently handing over clinical samples to BI Biopharmaceuticals for production.
Wang Bin believes that in such cooperation, product development companies are most interested in the protection of intellectual property rights and product quality by CDMO.
"In terms of intellectual property protection, we will strictly keep it confidential, on the other hand, BI Biopharmaceuticals takes the initiative to set limits on its own behavior and does not undertake similar product business of potential competitors; secondly, the company adheres to the high quality of products, including establishing a good quality system, providing excellent quality drugs, and complete data."
In addition, the international advantages of BI biopharmaceuticals are also an important engine for promoting cooperation. It is one of Boehringer Ingelheim's three business modules, with four CDMO production sites in the United States, Germany, Austria and Shanghai, and four factories using the same standards in hardware design, construction and management systems. At the first Shanghai International Biomedical Industry Week held not long ago, BI Biopharmaceuticals became a co-construction partner of Shanghai's world-class biomedical industry cluster.
At the same time, the company has rich experience in drug registration in major markets around the world, including the United States, Europe, Japan, Australia, etc., and the quality system meets the regulatory standards of major markets, and has been audited by more than 40 national regulatory agencies.
In the past 35 years, BI Biopharmaceuticals has successfully brought 40 biological drugs to the market, which makes Wang Bin very proud. In June, Nature published a review mentioning that 100 ANTIBODY drugs have been approved by the FDA. Comparing the numbers 40 and 100, it can be seen that a large part of the world's marketed biopharmaceuticals are produced by BI biopharmaceuticals.
Many of these orders also come from multinational pharmaceutical companies. Some domestic biotechnology companies specifically mentioned that if local enterprises have plans to carry out product combination drug research with multinational companies and choose BI biopharmaceuticals for sample production, they can also provide certain convenience for cooperation, and their production standards are widely recognized. Rebbe's LVGN6051 is conducting a combination study with Merck's Keytruda.
Partnered with Baekje to provide samples for MAH
BI Biopharmaceutical has also been operating in China for 6 years, and its development in China complements the implementation of the domestic MAH system. Wang Bin is the "No. 1 employee" of BI Biopharmaceuticals in China, and he still remembers the early pictures of the company's establishment.
He mentioned that 10 years ago, Boehringer Ingelheim headquarters was hesitant to invest in the establishment of CDMO departments in China, fearing that development in China would be constrained by policies and market demand. Therefore, the initial test was very careful, and the first investment in 2014 was to build a pilot plant with a production scale of 500 liters in China alone, Biolab.
BeiGene is Biolab's first partnership. At that time, BeiGene had just been established, and the company's products were ready to start clinical research, and in view of time, funds and other reasons, they had not yet established their own production facilities, and urgently needed to find CDMO cooperation.
When the cooperation agreement was signed, BeiGene CEO Ou Lei Qiang had the same concerns about regulations, and he also mentioned that because the policy barriers had not yet been fully broken, the initial cooperation was only for the production of samples in the clinical trial stage, but he predicted that this beginning would bring greater development in the future.
In fact, the cooperation has also become a lever to leverage the implementation of the domestic MAH system.
Wang Bin said: "At that time, the domestic experience in this area was still in a blank space, the first attempt of the two companies in China provided a valuable sample for the implementation of the MAH system, and BI Biopharmaceuticals also repeatedly communicated with the regulatory authorities to expound the internal logic system and risk control points of the MAH system. ”
Shortly thereafter, the MAH system began a pilot in China, and bi biopharmaceuticals that smelled the opportunity immediately expanded the scale of production lines. The headquarters invested 75 million euros in the construction of the Oasis production site for suppliers of industry-scale products, equipped with a 2,000-litre single-use production line.
China's first product approved to be listed under the contract production model, BeiGene's PD-1 inhibitor terelizumab, was officially born on this production line at the end of 2019, and the strength of BI Biopharmaceutical in clinical research and commercial CDMO services has also been proven, and its success has created two precedents in the field of MAH in China.
Nowadays, many domestic products have been commissioned to produce in the FORM of MAH, and the innovative vitality of a large number of small and medium-sized biotechnology companies has also been released. The Shanghai Municipal Food and Drug Administration has counted a set of data, and since the pilot of the MAH system, 27 production licenses have been issued to new drug research and development enterprises without independent production capacity.
BI Biopharmaceuticals also continue to steadily improve their service capabilities. Not long ago, the company expanded its commercial production capacity from the original 2,000 liters of one production line to the fermentation scale of 6,000 liters of three production lines. The business scope covers all aspects from process development, process transfer, raw solution production to preparation filling and product release.
"CDMO transforms the original manufacturing bottleneck of the biomedical industry chain into a service platform, allowing R&D companies to focus on product innovation, which is also the original intention of BI Biopharmaceutical to open operations in China." Wang Bin said, "In the future, BI Biopharmaceuticals will continue to work together with China's new drug research and development industry to support Chinese innovative drugs to achieve 'local innovation and global application'." ”
Editor| Yao Jia layout| Zhang Yue
Issue 1432
