Low-Risk Lyophilization

By Brian Bucur, Associate Director, Lyophilization & Sterilization and Timothy Smith, Director, Product & Process Development - Ben Venue Laboratories, Inc. Freeze-drying (lyophilization) of pharmaceuticals has been used successfully for many years to provide stable, sterile injectable dosage forms. However, as with any technology, lyophilization continues to evolve. Advances in analytical and process sciences allow pharmaceutical manufacturers to further exploit both chemical and physical phenomena that occur during lyophilization. At the same time, energy conservation, safety and complexity of pharmaceutical formulation chemistry continue to push the science of lyophilization well beyond the limits of basic cryogenic and sublimation equipment. This article presents suggested practices for developing a lyophilization program based upon Ben Venue Laboratories' years of experience and technical expertise. Key points include cycle development for new products, container/closure systems, equipment issues, and risk mitigation. BVL monitors new technologies and strives to remain current with industry and regulatory expectations for optimized development practices based upon Quality by Design (QbD). BVL continues to be a leader in contract lyophilization of investigational and commercial parenteral pharmaceuticals. We have new and long term relationships with many domestic and international clients, a longstanding relationship with the National Cancer Institute and a successful generic division, Bedford Laboratories. Many of the products we manufacture (which include cytotoxins, genotoxins, biologics and diagnostics) require unusually complex production processes. The exterior of Ben Venue's BVL operates twenty-nine production lyophilizers and five development lyophilizers (one of which is a production-scale unit). BVL is currently validating a new cytotoxic/genotoxic facility which houses nine of the twenty-nine production lyophilizers. These will be loaded through the use of laminar flow carts and unloaded into special isolators used to transfer vials to capping equipment. Production chambers range in shelf capacity from 96 square feet to 380 square feet for a total of 7692 square feet.