Containment hits new heights

As modern active pharmaceutical ingredients (APIs) become increasingly potent, more stringent operator exposure levels are being enforced and the need for containment is of growing importance. Where typically, five to 10 years ago, manufacturers of containment equipment were being requested to provide equipment to operator exposure levels (OELs) of <100mg/m³, today's OELs are more frequently in the range of <50ng/m³.

These factors have influenced one major unnamed API manufacturer to include high containment of <30ng/m³ in its new state-of-the-art manufacturing plant in Mexico. The design brief incorporated containment equipment for use throughout the facility, including during packing from dryers at intermediate and final steps in production, consolidation and sub-division of material, and milling and micronising of finished powder together with associated packing and finishing. Hosokawa Containment, a division of Hosokawa Micron, in conjunction with sister companies Hosokawa Micron Powder Systems (HMPS) in the US and Hosokawa Alpine AG (HAAG) in Germany, were awarded the contract in April 2005, with the delivery of equipment phased in line with the site building and fitting requirements. Designed, engineered and project-managed in the UK, this installation has been the result of a strong partnership between all companies involved. Phase 1 incorporated a total of six dryer pack-off isolators, five of which are identical static units permanently sited below the associated dryer, each incorporating a high-containment removable discharge duct. The sixth unit is mobile, allowing the isolator to be moved while the dryer is rotated during processing. These units have been successfully completed and delivered on time for immediate installation. A central consideration in the initial design of the dryer pack-off isolator was the incorporation of the client's preferred method of materials handling. It was important that material packed from the dryers could then be further processed in both the consolidation and milling or micronising isolators. This was achieved using Rapid Transfer Ports (RTPs) throughout the project. Each dryer pack-off isolator, whether static or mobile, had to be designed in such a way that it would enable an operator to fill a suitably sized RTP canister in a contained, safe manner and provide assistance with docking and undocking. Material from the dryer was to be dosed vertically into each isolator and a means of dosing control was also to be included. Primary containment was envisaged as using a continuous liner, with secondary containment provided by a once-through negative pressure isolator. An additional RTP was also required for the movement of accessories. In order to better understand and visualise final operability, the concept design was developed using 3D software. This allowed the opportunity for operators and other personnel to assess the design at a very early stage in the project. The use of simple viewing software also allowed the client to review the model in 3D on its own screens, which proved invaluable during tele-conferences in the early stages of design.

Safe handling Addressing the primary requirements quickly led the Hosokawa Containment engineers to a basic concept. The alpha port of the 350mm diameter RTP was to be fitted in the base of the isolator; this would allow the support legs to be further utilised for a drum-lifting device (Figure 1). Dosing of the material would be via a star valve mounted directly under the dryer outlet valve and control would be from a local operator panel, mounted onto the isolator. With the single inlet and double extract HEPA filters positioned for optimum flow across the packing head, enough space for a smaller 190mm dia RTP was available on a side wall. Once the basic design had been agreed, the next stage was to create a wooden mock-up in order to physically assess the ergonomic impact of the design (Figure 2). Protocols were prepared in conjunction with the client to ensure all aspects of operation would be tested. Both the glove port carrier and filling chute were designed to be fully adjustable to achieve the optimum working position during assessment. Hinged plywood covers were included to simulate both the 350mm and 190mm dia RTPs. Although these were lighter than the actual units, they provided a good idea of the arc of operation that would be needed via the glove ports and the viewing area available to the operator during the operation. After final positioning of the main items it was then possible to determine the ideal position for ancillary items such as the CIP spray devices and hand lance. The use of wooden mock-ups for all aspects of the project was so successful that the client is using them to train operators prior to the arrival of the actual equipment. From the findings of the ergonomic assessment the final designs were developed. These developments included incorporating the extract fan, process instrumentation and pneumatic controls for the drum lifter in a GMP technical area cabinet directly under the local operator panel. This design reduced the associated piping and wiring and allowed Hosokawa Containment to bring all terminations to a central point, resulting in a neat and compact unit that requires minimum installation. The local operator panel was manufactured by HMPS in the US and fully conforms to the hazardous area ratings required, even though each panel contains not only control equipment, but the extract fan variable speed drive and system PLC. This was achieved by positively purging the panel at all times when the equipment was live. Control of the entire packing procedure is by PLC via an operator interface which is also mounted on the front of the local operator panel. Start-up and shutdown sequences are fully controlled by the PLC, ensuring that the pack-off system operates in a controlled and defined manner. The system is fully interlocked with the dryer controls and alarms or warnings are available both visually, at the operator interface and by flashing beacon, and audibly via a warning siren. The drum lift system is entirely pneumatic and is operated via pushbuttons mounted to the front of each technical area panel. The drum is manually inserted into the shaped carrier, which automatically positions it for docking. Using pneumatic cylinders of a defined length, the drum is raised to the required height. Docking into the alpha port then requires only a simple twist of the drum by the operator. Once the drum is filled the system operates in reverse, ensuring that the cylinders and not the operator take the weight, fully complying with manual handling regulations. Removal of the drum is a straightforward slide out onto a pallet.

Easy cleaning The isolator has an internal arrangement for cleaning-in-place (CIP). A further consideration in the design was to ensure that solvents used in the cleaning of the dryer could be safely discharged. This was achieved by incorporating a washdown plate (Figure 3) that is connected to a drain nozzle inside the isolator. This nozzle passes through the wall of the isolator to the client's solvent drainage system. When not in use, the washdown plate can be safely removed using the 350mm dia RTP canister. Cleaning of the isolator itself is undertaken either using the spray balls mounted on the rear wall, which rotate to give improved impact and cleaning, or with a small hand lance which is tucked neatly away at the top of the isolator. The feed chute is also shown with the continuous liner cage fitted. During production, the cage is prepared with the required quantity of liner and installed using the 350mm dia RTP canister, further maintaining the required OEL. Once the canister is docked to the alpha port and the cover opened, the cage is easily removed and simply hooked onto the packing head chute. Smaller items such as the "O" ring seals can be introduced into the isolator via the 190mm dia RTP. The packing head features internal filters, which both purify the incoming nitrogen gas during inserting of the liner and prevent migration of powder during extraction of the liner. These filters are automatically cleaned using reverse jetting of incoming nitrogen. Both inlet and extract filters are of a safe change design and can be capped off inside the isolator prior to removal. Before despatch each isolator was tested to strict protocols developed in conjunction with the client. Testing included negative and positive pressure decay tests, which each unit passed with an average decay for all units of only 13 Pascals over a five minute period. All six isolators shown in Figure 4 had successfully completed the tests and were awaiting packing and despatch. The second phase of the equipment contract, which incorporates the consolidation and sub-division isolator, milling and micronising system and isolator, product collection filter and mobile pack-off isolator, is currently under manufacture and due for delivery in March 2006.