Expanding aseptically

The equipment installed was selected from various suppliers and designed and built to specifications that achieve the highest standards. The lyophilisers, for example, are driven by liquid nitrogen to enable the extremely precise and aggressive control of process variables needed for freeze-drying biologics. This enables the lyophilisers to execute cycles, which demand fast freezing up to 2°C per minute loaded. The filling area includes a high-speed vial washer and sterilising tunnel, vial filler line, automated stopper delivery system, automated vial loading and unloading system, and three automated lyophilisers.

Flexible control The areas are designed to provide maximum flexibility while maintaining the process and environmental control required to meet US, European and Rest-of-World regulatory guidelines. The design, construction, and installation of the areas were continually scrutinised and, if necessary, modified to comply with cGMP and other relevant standards.

Minimum human interaction System design is focused on minimising human intervention and presence in the aseptic areas. As the potential introduction of human contamination is the greatest risk to an aseptic product, minimising human intervention improves product quality. The manufacturing, filling, stopper delivery and lyophilising equipment are all highly automated and utilise Clean-In-Place and Sterilise-In-Place cycles to enhance aseptic processing procedures by eliminating unnecessary handling of equipment parts.

Maximum efficiency The aseptic suite was designed for maximum manufacturing efficiency. The vial filling line is capable of processing 2ml to 30ml vials at speeds of up to 400 vials per minute and holding those vials on a chilled loading table, for temperature sensitive products, prior to loading of the lyophilisers. The lyophilisers are loaded automatically with a robotic shelf loader through a slot door. After completion of the cycle, unloading occurs automatically via a hinged door in the back. This design makes it possible to simultaneously implement product filling at one unit while a second unit is in a product freeze drying cycle and the third unit in an unloading cycle. In addition, the use of an unloading accumulation buffer for unloading the lyophilisers reduces unloading time from about 10 to 2 hours.

Liquid advantage DPI utilises a proprietary SCADA-D3 system called Liquid Advantage (Supervisory Control and Data Acquisition), designed specifically by DSM engineers to monitor, alarm and store process data for utility systems such as WFI, Pure Steam and HVAC as well as vial filling suite operations. It delivers a recipe-driven user- friendly operator interface that allows the operators to efficiently run the equipment, while allowing the computer system to store and process the data generated during a batch and provide a complete batch record. The lyophilisers are operated using LyoAdvantage, which is a specialised lyophilisation control system designed and developed by DSM Pharmaceuticals. It monitors 150 cycle parameters in real time and provides the flexibility to develop cycles and manufacture products with demanding lyophilisation cycles – allowing a broader range of customer requests and specifications to be satisfied.

Dedicated customer focus Manufacturing and aseptic filling equipment are designed to allow dedication of the product train to a particular customer. This capability is highly desirable when evaluating product surface cleaning procedures and eliminates the risk related to product compatibility between customers. Additionally, this design allows multiple products to be manufactured in the same area without concern of cross-contamination.