Looking to the future

As health and safety concerns increase and environmental issues grow, the trend continues for process industries to develop and utilise isolator technology to protect products from microbiological and particulate contamination and for operator protection from toxic or hazardous components. The awareness of contamination control and personnel safety now extends beyond the confines of the pharmaceutical industry. Industries, such as food and beverage and more recently bio-engineering and nano-technology, have been focusing on isolators to overcome issues of potent product containment. Traditional methods of process containment and operator protection use a low-tech combination of cleanroom and personal protective equipment (PPE). Isolation technology offers enhanced product handling capabilities without constrictive gowning regimes and minimises potential for human error through incorrect procedures. Considering these performance advantages the potential for innovative isolator development in these 'new' industries becomes apparent.

Isolator status-quo Established isolator technologies exist for (among others): subdivision of bulk powders, drum or process vessel charging, product dispensing, sampling, milling, filling and weighing as well as liquid decanting. These offer acceptable, achievable, validatable control of potent substance handling with measurable protection levels for people and environments. However, where once glove boxes or isolation chambers were built around a single 'process', the trend is now for the integrated design of complete contained systems. These often now incorporate unique, integrated processing equipment such as dryers and mills within isolators. Leading process equipment integrators Hosokawa Micron has led the field in such bespoke engineering work, creating partnerships with blue chip pharmaceutical manufacturers to pioneer innovative equipment designs. Hosokawa Micron's unique position as one of the world's largest powder-process and containment equipment manufacturers has meant that customers are assured of bespoke engineering solutions to their specific contained process needs. For example, a totally contained, space saving micronising system, developed in conjunction with AstraZeneca, involved the redesign of the mill to fit into an isolator. This was also of an innovative design to take into consideration the noise and vibration resulting from the high classifier rotor speeds within a confined space as well as the overall 600kg weight of the monobloc designed mill.

Catalysts for design change As isolator technology and contained processing becomes more commonplace across a range of industries, design changes will be needed. Catalysts for design change include: 1. Increased potency/value of products 2. Increased demands for operator protection 3. Exacting standards of validation for processes and containment levels 4. Single line multi-processing requirements 5. Biotechnology development.

Increased product potency The increase in potency of active ingredients in pharmaceuticals is already pushing the boundaries of system design for the protection of the product, the protection of the person and the total recovery of expensive ingredients. Fully contained systems achieving 8 hour TWA OELs below 0.01mg/m3 with purpose-designed processing equipment will continue to be developed with increasing use of monobloc and crevice free mill designs which facilitate complete product discharge. Easy clean CIP/SIP systems will also become the standard. As less and less human intervention is deemed appropriate, design and production protocols will focus on automatic and remote operation and cleaning options.

Health and safety issues While production issues will remain of key importance the health and safety of personnel and protection of the environment will become a catalyst for change in the design of the waste handling and component maintenance covering the complete process. As demands for lower and lower OELs grow so too will the focus on other health and safety issues including lifting and workstation ergonomics leading to developments in automated or semi-automated internal transport and transfer systems.

Demand for validation The demand from manufacturers for validated processes and guaranteed operator exposure levels will greatly influence future isolator technology. Investigation and interrogation of process protocols and operator procedures will determine strict operational parameters. There will be design integration of semi automated systems alleviating the potential for human error. Improvements in in-line sampling and real time analysis display may also be incorporated into isolator design. Single line multi-processing The majority of pharmaceutical manufacturing systems are moving away from dedicated single product facilities, which are now often regarded as a luxury. The ideal is now considered to be a highly flexible multi-purpose plant, which can process several high value products in one fully validated production unit. It is with this design criteria in mind that Hosokawa Micron has collaborated with a world-leader in pharmaceutical manufacturing to produce a highly flexible ultra fine grinding/micronising suite with high containment isolation. This suite has been tested and validated to meet all their current and also their predicted, future micronising needs. The brief was to design a fine grinding system to mill pharmaceutical products while maintaining a philosophy of no reliance upon PPE (personal protective equipment) within the processing area . The ultra fine grinding system consists of an enclosed drum tipping section for the unloading of the primary coarse product, a state of the art classifier milling unit and a final fill/weigh packing system for the end milled product. No special protective clothing is required during product processing and there are full CIP (clean in place) systems to ensure cleanliness between batches. Working closely with the client engineers, Hosokawa Micron designed an integrated milling system with high containment Stott isolator units situated in a multi storey process area. System controls were integrated into existing control systems at the client's site, enabling monitoring of all critical process parameters for historic trend analysis. The containment philosophy attains operator exposure levels of 10 microgrammes/m3 and full isolation achieving containment levels below 5 microgrammes/m3.

Bio-technology development The growth in this industry sector will undoubtably be the catalyst for change in modular design isolators., across a range of processing applications. The Stott Flexible Isolator has been developed in response to R&D and bio-technology client demands for a low-cost, lightweight compact isolator but still offers the same high levels of product and personnel protection. It comprises of a 'standard' stainless steel base section, suitable for bench mounting (or with an optional baseframe). To this base can be fitted a range of upper sections c/w gloveports. These include an FDA compliant flexible anti static polyethylene canopy or a rigid perspex cover or even a stainless steel canopy complete with windows. This design philosophy ensures these units can be offered at extremely cost-effective prices. By offering the same high level protection and performance levels as larger and more expensive isolators they are ideal for companies looking for the flexibility of a contained small-scale R&D unit who may wish to do trial batches before scaling up to full production facilities. Clearly the future of isolator technology lies in partnership interaction between the customer and specialist containment engineering companies with the facilities and expertise to develop bespoke solutions for specific production, environmental and safety parameters. Design protocols will then be available for some standardisation of engineering and operating procedures for cost-effective production solutions.