Safeguarding both product and operators is paramount when designing systems for the processing of highly potent active pharmaceutical ingredients (HAPI), but ensuring that the systems are designed with maximum flexibility in mind is of growing importance too.
Hosokawa Micron recently helped a leading pharmaceutical manufacturer to address these extremely stringent production demands when designing its R&D batch milling and pack-off system used to process HAPI materials of a specific particle size. The system design was made more complex by the dimensional constraints of the existing facility and the need to achieve the most ergonomic working environment for all operatives across multi-shift operations. Hosokawa Micron engineers used their extensive experience to design a two-storey, contained system that allowed considerable production flexibility – enabling the processing of small R&D batches right through to operation as a continuous manufacturing system.
Ergonomic design
First, Hosokawa’s engineers integrated into the client’s engineering team and carried out extensive on-site ergonomic assessments in consultation with multiple shift operators, all of whom collaborated to achieve the optimum design outcome. The resulting ergonomic system design delivers optimum flexibility in terms of the range of particle size and shape production and various filling and weighing options required.
The combined batch milling and packing system features an upper tier, high containment isolator with integrated pharmaceutical hammer mill. This feeds directly into the flexible, continuous liner, filling and weighing system contained within a lower tier laminar flow booth, complete with human machine interface (HMI) screens. The system offers containment to occupational exposure banding (OEB) Level 4, achieves containment between 1–10µg/m3 and can handle batches up to 500 L from the dryer above.
Designed to be located in hazardous areas, the system meets hazardous area classification of Zone 1 and 21 IIB T4. If required, it can be operated under an inert atmosphere by purging all internal areas with nitrogen, offering further flexibility should the products be hygroscopic or explosive.
The milling isolator provides a fully contained environment during active product handling, giving total barrier isolation. The isolator is integrated into an existing product flow from a dryer positioned above the unit. HAPI material is fed from the dryer through hygienic rotary valves at a controlled rate into the hammer mill. The mill can run at speeds of up to 6000rpm, dependent on the particle size required. It also has a series of interchangeable meshes to give variable particle size and shapes that add increased operational flexibility to the system, and is easy to dismantle for cleaning or mesh changing.
Specifically designed for isolator integration, the mill has components that are easily removable and in most cases eliminate the requirement for the operator to handle and lift large, heavy components. All motors are housed within the technical area to the rear of the processing area. The hammer mill delivers a wide range of particle sizes, typically less than 50µm with low quantities of ultrafines. Temperature monitoring at the hammer mill ensures that material stays within temperature tolerances to prevent degradation of the product. Contained sampling from the milling isolator can be undertaken via a 270 RTP. This allows particle size measurements and other QC end product tests to ensure product is maintained within specification.
Small footprint
The filling and weighing system is integrated within a laminar flow booth directly below the milling isolator, giving direct material discharge to the filling packing head and maintaining the benefits of the compact, small footprint within the space limitations. Milled material is gravity fed into continuous liner, single liners or 23 L charge bottles, located on the fill/weigh platform, via a 100mm charge point valve to deliver low containment product transfer.
A containment screen located at the compact inward sealer offers additional barrier protection to operatives from the potential risk of airborne particles within the laminar flow booth by increasing the laminar flow booth face velocity during the pack-off process.
The system is designed for minimal operator intervention or material handling. It is fully wash-in-place with integrated spray guns positioned to ensure efficient cleandown. It also incorporates a free-standing extraction fan complete with safe change filter housing with double H14 HEPA filtration for additional operational safety and reduced contamination risk to surrounding areas. Hosokawa Micron also worked with the customer to develop Standard Operating Principles for the system.
