Unknowingly, biological drugs have occupied a leading position in the TOP10 list of global best-selling drugs, and Xiu Mei Le has been awarded the title of “Pharmaceutical King” for many years. There is no doubt that the popularity of biological medicine has overshadowed chemical medicine in recent years. With the breakthrough success of tumor immunotherapy in the treatment of advanced cancer and other biological drugs in rare and intractable diseases, the biopharmaceutical industry will continue to maintain rapid development for a long time in the next few years.
With this spring breeze, the global biopharmaceutical outsourcing industry has also ushered in a prosperous scene. This article makes an inventory of major events in the global biopharmaceutical outsourcing industry in 2017 from the four aspects of “technology, facilities, mergers and acquisitions, and cooperation.”
In May 2017, MilliporeSigma developed a new CRISPR genome editing method called proxy-CRISPR. Most of the natural CRISPR systems found in bacteria cannot interact with human cells without in-depth engineering and reengineering. Proxy-CRISPR provides a quick and easy method that can improve its usability without reengineering the natural CRISPR protein. . This technology can remove previously unreached cell sites, making CRISPR more efficient, flexible and specific, providing researchers with more experimental options, and obtaining results faster, thereby accelerating drug development. As of the end of December, proxy-CRISPR technology has been authorized by national and regional patent offices in Australia, Europe, Canada, and Singapore.
In June 2017, Fujifilm Diosynth’s pAVEway™ advanced protein expression system completed its 100th project since it was put on the market in 2007; this system facilitates reliable large-scale GMP production based on the E. coli process; not only can be expressed and Secretory association can effectively control protein expression, and it can also bring higher folding rate through slow expression, and maintain accumulation for several hours through continuous cell growth. This system is particularly suitable for proteins that are toxic to cells and difficult to express, as well as challenges in folding and periplasmic secretion.
In April 2017, EAG Laboratories announced the expansion of biopharmaceutical development capabilities, the construction of a dedicated bioassay laboratory in Columbia, Missouri, the addition of cell culture incubators and testing equipment, and increased production capacity and testing efficiency, thereby supporting the simultaneous development of multiple projects. The laboratory is divided into multiple small units, thereby minimizing the risk of cross-contamination between cell lines. At the same time, the company will increase the biopharmaceutical research team by about 35% to cope with the growing business needs.
In May 2017, Boehringer Ingelheim held the commercial production opening ceremony of Shanghai Zhangjiang Base. The first phase of the base invested more than 70 million euros to engage in the development and production of biopharmaceuticals based on mammalian cell culture technology. Since 2014, BI Zhangjiang Base has started the production of 100L and 500L clinical samples. Now it can also carry out clinical samples and commercial production of 2000L disposable reactors. In the future, 2000L disposable reactors and filling facilities will be flexibly added to meet the growing market demand.
In July 2017, Boehringer Ingelheim announced an investment of US$217 million to upgrade and expand the Fremont production base, while adding 300 jobs. The BIFremont base now has 500 employees, covering the development and production capabilities of biopharmaceuticals from small-scale trials to commercial scale, including raw liquid, filling, packaging and device assembly.
In September 2017, MilliporeSigma’s first BioReliance®End-to-End biological development center in the Asia-Pacific region officially opened in Shanghai, China. The center focuses on providing biopharmaceutical companies with comprehensive process development capabilities and services, including cell line development, upstream and downstream process development, and preclinical sample production. The center aims to meet the specific needs of customers in the Asia-Pacific region, and will provide a complete set of services for biopharmaceutical companies in China and the Asia-Pacific region to help accelerate the development of clinical drugs from molecular to commercial production.
In September 2017, Sartorius Stedim Cellca, a subsidiary of Sartorius, started construction of a cell culture technology center in Ulm, Germany, with a total investment of 30 million euros. Sartorius Stedim Cellca currently has 90 employees, mainly engaged in cell line and protein production process development, authorized protein production technology, and provided cell culture media.
In December 2017, WuXi Biologics announced that the world’s largest biopharmaceutical cGMP production base using disposable reactors, which was expanded in Wuxi, was fully operational, with a total capacity of 30,000 liters, including the two 1000L perfusion production reactors previously put into operation and the newly installed 14 2000L flow-added cell culture reactors. As early as June, WuXi Biologics was successfully listed and traded on the Hong Kong stock market, with a current market value of approximately HK$50 billion.
In January 2017, WuXi AppTec announced the acquisition of Huiyuan Biotechnology, a preclinical drug development outsourcing company. The acquisition will further enhance WuXi AppTec’s drug development capabilities from target verification to lead compound discovery and optimization, and improve and expand WuXi AppTec’s integrated R&D service platform.
In April 2017, Sartorius Stedim Biotech acquired Umetrics for USD 72.5 million. The company is headquartered in Malmö, Sweden, with about 50 employees. It is a software supplier that focuses on R&D and production process data analysis, with annual revenues of approximately US$15 million. The two companies have been cooperating to promote Umetrics’ software in the biopharmaceutical industry since the end of 2012. The software is used in key process steps in biopharmaceutical R&D and production, including cell culture and purification. Multi-factor data analysis (MVDA), such as glucose and lactic acid, can show process changes and their causes in real time. Design of Experiments (DoE) can efficiently discover and determine key process parameters, thereby greatly shortening the development cycle.
In May 2017, Thermo Fisher announced the acquisition of Patheon for US$7.2 billion. The company is a pharmaceutical contract development and production organization, with advanced production bases in North America and Europe, with approximately 9,000 employees, and in 2016, the company’s revenue was approximately US$1.9 billion. Through the acquisition of Patheon, Thermo Fisher’s clinical trial services and production technology services will be highly complementary to Patheon’s contract development and production capabilities, making the company a stronger partner for pharmaceutical and biotechnology customers. The acquisition was officially completed at the end of August.
In June 2017, Japan JSR announced the acquisition of SelexisSA, the company focused on the development of mammalian cell lines (CHO-K1). Selexis will be integrated into KBIBiopharma acquired by JSR in 2015 to establish a “gene to GMP” service system. Since 2012, Selexis and KBI have collaborated on a total of 15 different cell lines.
In June 2017, KBIBiopharma announced the acquisition of AllianceProteinLaboratories in San Diego. The company focuses on biopharmaceutical characterization and analysis services, including therapeutic proteins, peptides, nucleic acids and vaccines.
In August 2017, MilliporeSigma announced the acquisition of NatrixSeparations in Ontario, Canada, which is a supplier of disposable chromatography hydrogel filtration membranes. The acquisition will further enhance the company’s biopharmaceutical process technology. Natrix promotes anion and cation exchange membranes at the same time, and is also developing various scale biological purification process products suitable for complete disposable.
In September 2017, 3SBio announced the establishment of a joint venture company with CITIC Industrial Fund, and the acquisition of TherapureBiomanfacturing in Ontario, Canada for US$290 million. Founded in 2008, the company mainly provides a series of services for the development and production of therapeutic proteins, including technology transfer and process development, analysis development and testing, process scale-up and cGMP production, aseptic filling and freeze-drying, etc. The company The pharmaceutical production line of the United States, Canada and the European Union has the cGMP production qualifications for biopharmaceuticals.
In September 2017, Eurofins Scientific acquired EAGLabs, a provider of analytical testing services, with the intention of entering the North American market. Previously in 2015, Evans Analytical Group (EAG) had just acquired Analytical Bio-ChemistryLaboratories (ABCLaboratories), which was renamed EAGLabs in 2016. Headquartered in San Diego, EAGLabs has 21 laboratories in 18 cities around the world. In addition to the biopharmaceutical business sector, it also has materials engineering and agronomy sectors. The company has 1,000 employees and annual revenue of approximately $220 million.
In September 2017, Catalent acquired CookPharmacia, a contract development and production organization based in Indiana, for US$950 million. The company focuses on cell culture, prescription processes, finished product production and packaging, as well as clinical samples and commercial production. The dosage forms include liquid, lyophilized, prefilled needles and cartridge bottles. Cook Pharmacia has 750 employees and annual revenue of approximately US$180 million.
In October 2017, Lonza acquired Shire’s mammalian cell clinical sample production base in Hayward, California, including 1000L and 2000L disposable reactors and related downstream production facilities. The base has been in operation since 1990 and currently has approximately 100 employees.
In November 2017, GE announced the completion of the acquisition of Puridify in the UK, a start-up company focusing on the purification technology FibroSelect, a nanofiber platform for biopharmaceutical production, and currently has 17 employees. The acquisition will strengthen the company’s strength in downstream process resins and chromatography membranes.
In December 2017, JSR announced the acquisition of Sino-US Crown Technology for approximately RMB 2.6 billion. Sino-American Crown is a CRO biological company that provides pre-clinical technical services for the research field of tumor and metabolic diseases. It has high-quality and most complete in vitro and in vivo research models for customers to evaluate and measure the actual efficacy and pharmacological properties of drug candidates before clinical trials. In the future, Sino-American Crown will continue to develop further along the original strategic plan. In addition to the pharmacodynamics currently being done on tumors and metabolic diseases, Crown may develop in the direction of toxicology and production. At the same time, with the help of JSR’s existing large-scale antibody production department, Crown Technology may adjust and deploy the life science and new drug R&D process throughout the company.
In February 2017, Sanofi and Lonza reached a strategic cooperation to establish and operate a large mammalian cell culture base for monoclonal production in Visp, Switzerland. Both parties have equal rights and interests, and the total investment in the first phase is 270 million euros. In September, the joint venture company’s production base started construction.
In March 2017, Seebman announced the signing of a strategic cooperation framework agreement with GE Healthcare. The two parties intend to establish a joint laboratory at Seebman Group’s new site in Zhangjiang, Shanghai, to jointly build an advanced automated and industrialized cell production process system and jointly develop It is suitable for the personalized customization of autologous and allogeneic cells and gene therapy and the advanced supporting production process system that can be multi-recombined. On November 4th, Seebman-GE Healthcare’s joint laboratory in Zhangjiang was officially listed, and Seebman-Thermofei Cell Therapy Innovation and Application Center also ushered in its inauguration.
In April 2017, Thermo Fisher Scientific and Powerway announced the establishment of the “Thermo Fisher Scientific-Powerway Joint Antibody Engineering Technology Exhibition and Service Center”. The center will be equipped with the Asia-Pacific region’s first world-leading Thermo Fisher antibody drug pilot-level smart factory platform SmartFactory. After the center is completed, it will provide a variety of antibody drug contract development and production (CMO) services.
In May 2017, MilliporeSigma and Stelis of India announced the establishment of a joint laboratory to provide preclinical, clinical and commercial scale process development and scale-up production services. The joint laboratory is located in the Stelis Biopharma R&D center and will be equipped with MilliporeSigma’s Mobius® bioprocessing equipment and disposable production devices. In addition, MilliporeSigma will provide process and application support to help establish disposable platform technology.
In October 2017, Catalent and GridTherapeutics signed a long-term agreement to provide development and production services for the latter’s candidate lead antibodies for the treatment of solid tumors. Catalent will use patented GPEx cell line technology to develop cell lines and provide cGMP antibody stock production services.
In November 2017, WuXi Biologics and Pall established a joint laboratory to develop a continuous production process for monoclonal antibodies. The two parties signed a three-year strategic cooperation agreement, planning to gradually transition from a single process point of continuous biopharmaceutical process operation to full process continuous production. The joint laboratory will use the unique Cadence integrated continuous flow biological treatment system of the Pall platform. Through the integration of the continuous production process and the one-time use platform, it will ensure the flexibility of the process, avoid cross-contamination, and help enterprises in less plant space. Realize product production and effectively reduce production costs. The joint laboratory eventually plans to scale up to multiple 1,000 liters and reduce the cost of antibody production to less than $15/g.
In November 2017, MilliporeSigma and Samsung Biologics reached a strategic cooperation to jointly provide process development and clinical sample production services for small biotechnology start-ups. Samsung Biologics is a contract manufacturer, and MilliporeSigma not only provides Mobius® disposable systems to Samsung, but also provides process development and support technical training.
In December 2017, MilliporeSigma announced a collaboration with IPS-IntegratedProjectServices and G-CONManufacturing to provide a 2000L monoclonal antibody facility and disposable process technology platform for the iCON base design platform established by the latter in September.
After surveying the major events in the biopharmaceutical outsourcing industry in 2017, it is not difficult to find that MilliporeSigma is the most active, with its presence on all fronts of technology, facilities, mergers and acquisitions, and cooperation. This is not surprising, after all, the company has a very rich product line in the field of biopharmaceutical services, not only disposable equipment and consumables, but also process development and technical services.
Another company worthy of attention is Japan’s JSR. This company started out with tire rubber, and it matched the biopharmaceutical industry because it later also provided downstream purified resins. In recent years, it has further extended to the industrial chain, acquired KBI Biopharma, Selexis and Sino-American Crown Technology, entered the field of biological drug discovery, development and production services, and quickly established a complete system. In the future, it will also be a supplier that cannot be ignored.
In addition, WuXi Biologics is also a company that has to be said. In 2017, it not only successfully listed and traded on the Hong Kong stock market, but also expanded its production capacity to an astonishing 30,000L. The establishment of a joint laboratory with Pall aims to control the cost below 15 US dollars per gram, which has really won a lot of attention.
Other established companies in the industry, such as Lonza, Thermo Fisher, Boehringer Ingelheim, and Sartorius, also have large-scale operations. It is believed that these players will still play an important role in the days to come, boosting the steady progress of the biopharmaceutical industry.