Biopharmaceutical Mammalian Cell Culture-Based Manufacturing
A state-of-the-art facility, located in Groningen, The Netherlands, is dedicated to the development, scale-up, and cGMP manufacturing of recombinant proteins and monoclonal antibodies. Proprietary technologies and standard fed batch or perfusion processing are utilized across a bioreactor scale of 50 L, 250 L, 500 L and 1,000 L.
DSM’s proprietary technologies result in a much lower cost of goods, better sustainability by significantly reducing water and energy usage per gram/KG of material produced, and are fully compatible with the flexibility of working with single-use technologies (also for commercial scale), and much more advanced in process control toward a necessary product quality, which is important for new molecules and also for biosimilars.
Examples are: XD® Technology which leads to very high cell densities in the bioreactor, giving significant titer improvement of 5−15 fold compared to standard fed-batch processes. Rhobust® technology, next-generation expanded bed chromatography (EBA), uses cross-linked agarose beads with Tungsten Carbide to increase the particle density. And the Kremer Method™ provides further purification and polishing of proteins streamlined to work as one single unit operation.
Biopharmaceutical and Bio-Industrial Microorganism Fermentation-Based Manufacturing
Customers are offered access to advanced technologies in fermentation-based processes as they are continuously developed and improved for DSM’s in-house production processes. Innovations range from the latest advances in production strain construction and improvement, fermentation process concepts, and product isolation technologies. These innovations fit classical fermentation products as well as modern biotechnology based products, (e.g., recombinant proteins). Additional value lies in the fact that all DSM in-house innovations are focused on applicability in large-scale manufacturing.
Actual examples of innovation include advanced scale compatible expression platforms for protein production, various modes of fermentation process execution, and selected high-performance product isolation and purification operations.
Biochemical Applications for Active Pharmaceutical Ingredients
In 2010, as part of this continued commitment, DSM launched its InnoSyn™ route scouting services in response to the increasing interest of pharmaceutical customers to outsource the development of robust low-cost manufacturing routes. DSM’s route scouting capabilities have proven to lead to significant cost savings and a better environmental footprint by the reduction of synthesis steps or redesign of synthesis routes where true innovation is achieved by integration of different cutting-edge technologies developed by DSM and partners.
DSM’s rapid development trajectory from (bio)catalyst screening to feasibility studies and tech package development proven at pilot-scale provide robust, cost-effective next-generation manufacturing solutions for drug life cycle extension and at a speed to enable supply of clinical trail material based on scalable technology. DSM’s “green chemistry toolbox” includes route scouting with enzymes and the use of micro reactor technologies for commercial-scale production, and the proactive management of learning curves to increase yield and reduce waste. DSM brings down its manufacturing costs through process intensification to offer shorter and more efficient scale-up of pharmaceutical chemicals, speeding up development, better managing manufacturing volumes, and driving down material costs.
Micro Reactor Technology, for example, has been used for commercial-scale pharmaceutical production by DSM, with yields more than 20% higher than in the traditional large vessels, a much lower CO2 footprint and at lower costs.
Aseptic Liquid Filling of Biopharmaceuticals
DSM operates a 1.5 million square foot finished dosage facility in Greenville, North Carolina, U.S., for oral solid dosage, as well as liquid and lyophilized steriles, and holds a range of regulatory approvals including the production of scheduled drugs. DSM offers aseptic liquid filling using a proprietary, flexible, state-of-the-art distributed control system called LiquidAdvantage™. This is used on all filling lines operating under aseptic production methods, and controls SCADA, D3 and electronic cycle run report functions in a single unified solution.
Utilizing a product-specific, recipe-driven single communication interface, all production operations from supply and filling to packaging and warehousing occur with minimal interaction from production staff, which increases sterility assurance. Automated production controls also enhance product quality from the outset. Additionally, sterile clinical trial formulation and filling is also a unique niche served by DSM at Greenville. It meets the needs of global pharmaceutical and biotech companies for projects in post-discovery, cGMP Phases I−II, or ready for commercial manufacturing.
Cytotoxic services are flexible, with complete aseptic liquid filling and lyophilization capabilities, variable batch sizes, options for expanded development and analytical services, and adaptable scheduling. The Greenville facility also received Potent Compound Safety Certification from SafeBridge Consultants. DSM Pharmaceutical Products’ facilities have been approved by the FDA, similar agencies in Europe, the Middle East, Africa, and Japan and many other regulatory agencies. DSM Pharmaceuticals is licensed by the U.S. Drug Enforcement Administration to manufacture scheduled drugs.