Pharmaceutical Biotechnology Innovations in Manufacturing

Challenging conventional process technologies with innovation and forward-looking solutions lead to the next generation of manufacturing processes. With its biotechnology, chemistry, and fine chemistry capability, DSM has an extensive toolbox for developing the most economic and sustainable solutions for customers. DSM’s biotechnology uses microorganisms, enzymes, and mammalian cells to produce novel ingredients and improve existing food ingredients, (bio)pharmaceuticals, plastics, and chemicals.

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-, 250-, 500-, and 1,000-L disposable technology. Commercial production will begin in 2013 in a new Brisbane, Australia, facility.

Examples include

Microorganism Fermentation–Based Manufacturing

Fermentation-based processes are continuously developed and improved for in-house production processes at both the DSM Biotechnology Center in Delft, The Netherlands, and the Capua, Italy commercial-scale facility.

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).

Other examples include advanced-scale compatible expression platforms for protein production, called PlugBug^®, 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 in outsourcing the development of robust, low-cost manufacturing routes. Route-scouting capabilities have led 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.

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 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 microreactor technologies for commercial-scale production, and the proactive management of learning curves to increase yield and reduce waste.

Aseptic Liquid Filling of Biopharmaceuticals

DSM operates a 1.5 million ft² finished dosage facility in Greenville, NC (USA) for oral solid dosage as well as liquid and lyophilized steriles. DSM also holds a range of regulatory approvals including the production of scheduled drugs.

Aproprietary, flexible, state-of-the-art distributed control system called LiquidAdvantage™ is used on all aseptic liquid filling lines operating with aseptic production methods. It 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.

Potent Compound Safety Certification from SafeBridge Consultants, Inc.

Facilities have been approved by the FDA; similar agencies in Europe, the Middle East, Africa, and Japan; and many other regulatory agencies.

About the Author

Author Details
Guy Tiene is at DSM Pharmaceutical Products, 45 Waterview Boulevard, Parsippany, NJ 07054-1298; 1-973-257-8011; [email protected]; www.dsmpharmaceuticalproducts.com. XD^® and Rhobust^® are registered trademarks of DSM. PlugBug^®, Kremer Method™, InnoSyn™, and LiquidAdvantage™ are trademarks of DSM.