Building better barriers

Barrier technology utilising isolators and glove boxes is now accepted, not only throughout the pharmaceutical sector but increasingly across the broader spectrum of chemical, food and metals industries as the obvious solution for process containment.

Initial health and safety-led requirements to safeguard operators from toxic or hazardous components and the need to protect products from microbiological and particulate contamination are now ranked alongside the economic desire for in-process cleaning and maintenance and the protection of processing suites from airborne particle migration to facilitate less arduous cleaning regimes. This is the case particularly in areas where high potency compounds are processed and where multi-processing of a variety of different compounds take place.

Constricting regimes As traditional methods of process containment and operator protection involving the use of personal protective equipment (PPE) are being replaced by barrier technologies, it is easy to see why a return to the use of PPE with its constricting gowning regimes for cleaning, maintenance and product changeover are seen - certainly by the operators - as a retrograde step. From the manufacturers' perspective, anything that decreases production downtime, potential for product contamination and product migration is crucial in maintaining quality, optimising production efficiencies and reducing the time needed to get products to market. Working in partnership with some of the worldÕs leading pharmaceutical manufacturers to meet increasing containment demands, Hosokawa Micron has developed isolation technology that integrates not only the process equipment within the isolator, but also integrates the isolator within the processing suite as well as integrating the services to the process. Designing a complete installation in the broadest sense, to achieve total isolator integration, has meant extending working partnerships to include facilities management, end user designers and operators. Hosokawa Micron has led the field in bespoke engineering of innovative and unique equipment and processing lines, extending this expertise into the design and manufacture of special equipment for incorporation into integrated isolated systems. Innovative interpretations of proven industry standard size reduction and drying equipment best illustrate the engineering technology essential within total isolator integration. To meet the stringent industry standards for cGMP design, many of the Hosokawa machines are manufactured in line with a Monobloc philosophy. Solid billets of metal are used, from which the components are carefully machined. This provides guaranteed surface finishes and ensures tight tolerances are maintained for the high speed rotating equipment. Equipment within the workspace of the isolator is kept to a minimum. All the service points, valves, motors and instrumentation are marshalled within a separate enclosure adjacent to the main workspace. This allows for complete integration of the equipment while still retaining the flexibility to gain access to the service enclosure without compromising the containment mid batch. Consequently, there is less disruption to production and the potential for either product contamination or operator exposure is minimised, as is the need for additional cleaning. The utilisation of quick access tri-clamp type connections is vital in a restricted access workspace such as an isolator. This ensures that key equipment such as mills, classifiers, feeders and valves, which are constructed in several component parts for cleaning assessibility, can be opened and closed easily despite the inherent restrictions of glove ports.

Handling problems As the safe weight for internal glovebox handling is considered to be 5kg, problems may be experienced with any manual actions undertaken at arms length involving equipment exceeding this weight. Construction in lightweight materials may resolve some of these problems but this may not always be appropriate for process equipment such as mills or rotary valves, which may have to be pressure rated. The mock-up stage of design is often the first indicator of potential difficulties in this area. Resolution of this weight-associated problem has resulted in Hosokawa Micron completely redesigning a UPZ impact mill in one recent installation, with the rotor and grinding track being independently supported on articulated arms. Where machines from other manufacturers have been specified, Hosokawa Micron has even worked in partnership to redesign its equipment. One example of this was a collaboration with rotary valve manufacturer RotaVal where the valve was adapted to give full access for cleaning. The valve opens fully inside the isolator, with its considerable weight supported along sliding arms and an extending (and removeable) drive shaft to permit the motor to reside in the service enclosure. As all tooling remains inside the isolator, its design incorporates brackets for safe-keeping of tools and shelves on which tools and dismantled component parts can be placed while procedures are carried out. Often specially designed tools can make it easier for operators to undertake tasks with restricted movement. These requirements can be determined at the mock-up stage. In the early stages of discussion, when only an outline of a basic user requirement specification (URS) exists, the integrated solution can start to be defined through a series of conceptual sketches. Progression using standard engineering design tools such as 3D autocad drawings and computer-generated animations enables refinement of the basic design of a fully integrated system to continue in the most cost-effective and expedient way prior to the manufacture of the mock-ups.

System evaluation Initial testing and ergonomic trials of the system are carried out on wooden mock-ups with the internal equipment mocked up as well as the isolator. These mock-ups enable all the practicalities of the system to be evaluated and operational questions addressed. Some examples are given below: • Will the operators be able to reach far enough into the booth ? • What tools will be required within the isolator? • Is it possible to carry out certain actions with the restrictions of gloves and reduced finger sensitivity? • Is it possible to pass maintenance tools from one hand to another while reaching through the gloveports? • Where will the discarded drum lid be placed ? • Is there enough light for the operator to see? • What are the best routes for the cables and pneumatics?

Visualisation on a computer screen is no guarantee that practical manoeuvres can be carried out by operators, quite literally at arms length. Combine this with the added complication of equipment operators of differing heights or when complicated procedures are carried out and the true realisation dawns of the real practicalities involved in carrying out daily functions and how they may be impeded by less than conscientious design detail. Trial documentation at this stage helps build procedure protocols crucial within later Factory Acceptance Testing (FAT) of the stainless steel production versions of integrated systems and their component parts. The planned management, segregation and integration of the services at the design stage can alleviate problems in installation, commissioning and maintenance later on as well as day to day operational problems. Segregated services such as low voltage power, high voltage power, compressed air/nitrogen, CIP and analogue and digital controls are labelled and cross-referenced on PID diagrams and equipment drawings. This facilitates Installation Qualification (IQ) and is a crucial factor to consider when working with different engineering partners. Consideration of the complete installation involves, quite literally, taking a wider view of things. The impact that the isolator has on the design of the process facility as well as the impact that the design of the facility may have on the overall design of the isolated system can be significant.

Accessibility is crucial As operability, maintenance and cleanability are paramount in the URS, consideration for all round accessibility is crucial. Often architectural restrictions determine to some point the end design; for example, low ceiling heights may restrict the opening of isolator doors, likewise height restrictions may preclude top entry servicing. Height restrictions at a recent installation by Hosokawa Micron meant that a new design for the light assembly was incorporated when the usual top access for light replacement was restricted. This meant that the isolator ceiling mounted lights could now be accessed and replaced by simply pulling out a drawer. This design feature has been so successful that it has been used on other installations, even where no height restrictions exist. Neat management and segregation of services may be achieved utilising a single service enclosure, typically a large polished stainless steel conduit that carries all the services to bulkheads and junction boxes in the isolator. Anotated cable trays and other service carriers identify the services, alleviating problems for main contractors on installation and facilitating IQ. Isolation technology, which fully integrates the process equipment, the isolator, the facility and the services to the process, offers manufacturers increasing production benefits and opportunities to increase processing potential while maintaining product and personnel protection. In time, the types of processes integrated in this way will inevitably be increased and even greater flexibility of operation introduced with an escalating impact on the design of process equipment. As a leader in the design and manufacture of powder and particle processing equipment, Hosokawa Micron will continue to be at the forefront of this engineering innovation.