Contained Cytotoxic Installation for in-line Clinical Trial Production

Powder Systems Limited (PSL) supports Helsinn Advanced Synthesis SA’s expansion into the cytotoxic market with their recently installed Clinical Trial Isolator. Helsinn Advanced Synthesis SA (HAS), located in Biasca, Switzerland, is the chemical manufacturing business unit of the Helsinn Group. To meet the demand of anticancer molecules HAS will open a new cytotoxic facility in 2013. The facility will be dedicated to cytotoxic compounds that require safe product handling in a contained area for operator, environment and product protection. PSL worked closely with Helsinn to develop suitable solutions for their cytotoxic facility and is providing a suite of high containment systems including contained agitated nutsche filter dryers, charging gloveboxes with slurry vessels and a Clinical Trial Isolator. Helsinn’s cytotoxic plant comprises a small scale GMP area for the production of reduced quantities of cytotoxic active pharmaceutical ingredients (APIs) for clinical and registration purposes. PSL recently installed the state-of-the-art clinical trial isolator into this small scale GMP area. Numerous operations will be processed inside this high containment isolator with a required operator exposure level (OEL) of less than 50ng/m³ in 8 hours TWA. The Clinical Trial facilities present a total synthesis solution for manufacturing and handling cytotoxic compounds on a small scale. The isolator allows the following operations to be performed in one unit in a completely contained environment: - Transfer and reactor charging - Reaction in glass reactor - Hydrogenation - Filtration - Drying - Discharging - Dispensing, packing and transfer The Clinical Trial Isolator consists of several in-line synthesis processes including reaction or hydrogenation within a glass reactor of 20L, Buchner filtration and drying within PSL’s CakeStand Tray Dryer. This unique vacuum tray dryer overcomes the inherent difficulties with traditional vacuum drying ovens: through its direct tray heating, the CakeStand performs proven heat uniformity up to a maximum temperature variation of 1°C. The tray dryer integrated within the Clinical Trial Isolator has 4 heated shelves, pioneering pivot door and is contained in a PSL isolator ensuring high containment during transfer of the cytotoxic compounds. The full synthesis containment system has HMI/PLC control, washing and clean-in-place capabilities with an OEL of less than 50ng/m³ in 8 hours TWA. The new cytotoxic facility is 3b category and provides full protection for the operator, environment and product when handling cytotoxic compounds throughout PSL high containment systems. Helsinn Advanced Synthesis is hosting an event on Wednesday January 9th, 2013 in San Francisco, California, in conjunction with the JP Morgan Conference to showcase the new cytotoxic facility in Biasca (Switzerland). Gionata Frasca, Head of Scientific Division will give a presentation on working with cytotoxic compounds. Additionally, PSL has been invited to participate at the event. Michelle Frisch, PSL Senior Global Technical Systems Manager, will make a presentation on cytotoxic production.