A major pharmaceutical micronizing company needed a mobile, high-containment isolation system suitable for housing 4-, 8-, 12-, or 15-in. micronizing jet-mill systems during the loading, milling, and offloading processes. The company consulted Telstar’s technology center in Dewsbury, United Kingdom, for help with this large project, which involved several engineering challenges.
Milling and micronization operations sometimes involve the size reduction of highly potent active pharmaceutical ingredients (APIs). The company’s system therefore needed to reduce the operator exposure level to less than 1 µg/m3 throughout the operation, and above background levels, with defined sequences of operations (SOPs).
Such containment systems must allow the operator to conduct normal operations successfully using gloves. Operators also must be able to clean the isolator and milling equipment in an enclosed environment while wearing gloves. Ergonomic trials play a major role in ensuring that the final design is the best possible solution for operation and provides a high level of containment.
The company’s micronizing mills varied greatly with regard to size, weight, air consumption, and product usage. The 4-in. mill weighed approximately 10 kg and consumed air at a rate of about 125 m3/h at 120 psi. The 15-in. mill weighed more than 50 kg, and its air consumption was roughly 760 m3/h at 120 psi. In addition, the equipment associated with each mill (e.g., mill support, product feeder, product-feed hopper, air-supply pipes, controls, and outfeed product bag) had to be housed and contained.
Telstar and the company discussed various proposals regarding the containment system’s design and operation, and the final plan was to create a three-chamber mobile isolator with a main chamber that could house any of the mills and associated equipment. The 4-in. mill could operate independently in this isolator. The 8-, 12-, and 15-in. mills, however, required a large, fixed, three-chamber cyclone isolator connected to the mobile isolator to handle the large airflows and product discharges.
The three-chamber mobile micronizing isolator incorporated a transfer chamber, a micronizing chamber, and a discharge chamber. It was designed to provide a high containment barrier for each size of micronizing mill when personnel loaded, micronized or milled, and offloaded APIs. The isolator limited operator and environmental exposure to the API to less than 1 µg/m3 throughout the operation, and above background levels, when defined SOPs were followed. Controls allowed personnel to monitor and adjust the environmental conditions inside the isolator through the various modes of operation.
A drum-docking system was fitted to the transfer chamber and sealed with an inflatable seal to enable personnel to load raw-material drums. A small weigh scale was included within the main chamber for measuring samples, and a safe-change pass-out port also was added so that samples could be passed out safely. A larger weigh scale was fitted in the discharge chamber for weighing the milled product, and a safe-change connection port also was added to enable a safe-change pipe to be connected between the mobile isolator and the cyclone isolator when necessary. Wash guns and spray balls were provided to enable safe cleaning of the isolator after use.
The three-chamber fixed-cyclone isolator consisted of a filter sock–cyclone hopper chamber, a middle rotavalve chamber, and a lower discharge chamber. The fixed-cyclone isolator was designed to provide a high-containment barrier when connected to the mobile micronizing isolator during the offloading of APIs. Operator and environmental exposure was limited to less than 1 µg/m3 throughout the operation, and above background levels, when defined SOPs were followed. Isolator controls let personnel monitor and control the environmental conditions inside the isolator.
A rotary valve was fitted between the cyclone and discharge sections to enable exact amounts of product to be discharged without intervention. A safe-change connection port also was added to the cyclone chamber to enable a safe-change pipe to be connected between the mobile isolator and the cyclone isolator when necessary. Safe-change pass-out ports also were added to the sock chamber and middle chamber so that samples and waste bags could be passed out safely. A large weigh scale was fitted in the discharge chamber for weighing the milled product, and wash guns and spray balls were provided to ensure safe cleaning of the isolator after use. To enable access to all parts of the 18-ft tall cyclone isolator, various access platforms and stairs were integrated into the construction.
A drum lifter tipper was provided to assist the loading of large drums of product into the isolator. The drum lifter tipper lifts the drums and docks them onto the transfer chamber of the mobile isolator through an inflatable seal to prevent operator exposure. Personnel can remove the drum lid from inside the chamber and transfer product safely into the isolator. Some of the mills weighed more than 50 kg and were difficult to lift into the isolator. To overcome this challenge, the drum lifter was given a flat lift bed that enabled the mill to be loaded safely from the floor to the correct height.
The company was pleased with the results of this large, bespoke, and challenging high-containment project. The team proclaimed the effort a huge success.
John Hargreaves is a project engineer in Telstar’s Technology Centre for Containment Systems in the UK (Telstar ACE), [email protected].