Glatt Ingenieurtechnik GmbH

An imperative when planning the clean room design for blood plasma fractionations is to think the overall concept through from the outset to the end.

Blood plasma products are the basis of many life-saving therapies. The fractionation and preparation of blood plasma into albumin, IgG immunoglobulin, factor VIII, factor IX and other products is done using highly specialised processes and production technologies in cleanrooms. As the requirements for contamination-free production can only be met in a controlled environment, pharmaceutical companies should rely on experienced specialists when planning cleanrooms. Some important aspects of their construction are outlined below.

Glatt has planned and completed various projects in Germany and abroad for blood plasma fractionation facilities. This includes many high ISO level cleanrooms of more than 1000 m² on several floors and the implementation of well thought-through material and personnel flow layouts (including sophisticated airlock solutions). Optimised washing/CIP stations and equipment such as filter presses and separators have also been integrated when required. From process, utilities, civil/building, HVAC to electrical engineering and automation, a critical part of any project is to co-ordinate and schedule — from an early stage — the work of all the trades and service providers involved. With this in mind, here are a few basic considerations.

When planning a cleanroom, those in charge should work as closely as possible with all suppliers and contractors as there are many aspects that contribute to the successful completion of such a project — including the selection of suitable walls, ceilings and floors, as well as airlock equipment and cleanroom furniture. Communication, organisation and consultation is critical. Equally important is an open exchange with the suppliers of the equipment and systems to be installed in the cleanroom or associated with it. It is therefore best if cleanroom planners are familiar with the process equipment, the technologies and the systems involved — and/or even plan these themselves.

Correct assembly: as clean as possible

Before starting any cleanroom installation, such as fitting out a pharmaceutical interior, the structural infrastructure must be completed as fully as possible. This means that the building shell should be finished, swept clean and be as particle-free as feasible. This might be done by vacuuming and, if necessary, by sealing the surfaces of the building shell. Doing this minimises the introduction of particles from the building structure into the to-be-constructed cleanroom from the outset. The actual cleanroom must fulfil the following requirements regarding all surfaces. They must be

• smooth and non-porous
• easy to clean
• impermeable and crack-free
• effectively and repeatedly cleaned and disinfected
• resistant to light
• have a low joint content
• have no horizontal and/or vertical deposit areas.

In addition, every element must be resistant to all the cleaning agents and disinfectants used. To fulfil these criteria for cleanroom walls, either double-skin systems can be selected for the interior and single-skin ones for the exterior, or monoblock elements with a sandwich structure can be used. The most common wall systems consist of metal elements of two types: stud constructions with suspended wall elements (one-sided or two-sided) and monoblocks. The final design of the cleanroom interior determines the preferred choice. Depending on the supplier, the wall elements can be manufactured up to six metres high without horizontal joints. A double-shell wall system provides flexible assembly with optimum installation options. Plus, adapting the grid elements of these walls — to accommodate small-diameter pipes and cables — can easily be done in the intermediate area.

Interlocks and doors for safe material and personnel flow

During the design phase, the planning team must meticulously analyse all the work and production processes to be done in the cleanroom. This is the only way to determine where airlocks and clean/dirty corridors are required to ensure effective operation and prevent contamination of the end product. As cleanroom elements are generally quite sensitive, it is advisable to use generous amounts of “ram and scrape” protection in transfer areas. And even though these elements might protrude, they are easy to clean.

The selection of the most practical and economical door systems depends on the spatial conditions on site and the frequency of use. Roller shutters, swing doors and sliding doors are widely incorporated. Single- or double-leaf hinged doors are the preferred option owing to their simplicity and should be installed flush with the partition walls whenever possible.

Sliding cleanroom doors are more expensive and can be challenging to clean and maintain, but offer clear advantages when space and handling conditions are limited. Automatic, cleanroom-compatible roller shutter doors are a very good alternative to sliding doors, especially if they have to be opened and closed frequently. In addition to cleanroom-compatible surfaces and reliable mechanics, airlocks and doors in cleanrooms also need a robust and high-quality sealing solution to ensure that they remain hermetically sealed in the long-term.

Sealing is an aspect that is mandatory for all cable ducts, installations and equipment such as filter presses or separators in cleanrooms. To achieve an appropriate ISO status, cleanrooms must be sealed from the outside to prevent diffusion and/or particle ingress. Pharmaceutical machinery may also span several cleanroom classes; as such, wall, floor or ceiling connections (covers or seals) must be as flush as possible. When necessary, they should be implemented by the relevant service provider — in consultation with the expert team — in a cleanroom-compatible manner.

What to consider when designing cleanroom ceilings

With cleanroom ceiling systems, there are three main categories: supporting grid, clamping cassette and panelled versions. They are generally used in cleanrooms of Class ISO 8 or GMP D upwards. As with wall systems, the aim here is to ensure tightness with a minimum number of joints using standardised grid divisions. Thanks to integrated profiles, even large-format elements can easily be attached to the ceiling itself or the steel substructure. Retrofitting fixtures is also often possible with minimal effort. Whether the ceilings should be accessible or non-accessible is another important consideration. With panelled and grid ceilings, accessibility is possible on request. This means that there is no need for additional gangways or other construction. However, the load-bearing capacity is limited for all systems.

Supporting grid ceilings usually consist of a manufacturer-specific flexible grid system with extruded profiles. The widths of the bars vary depending on the supplier, whereby installations such as pressure sensors can be easily integrated from a width of 80 mm. The ceiling panels are available in different sizes so that cleanroom lights and air outlets can also be installed without additional joints. Clamp-on cassette ceilings are suspended metal ceilings that cannot be walked on and are more suitable for lower ISO cleanroom classes.

Similar to the cleanroom walls, the joints in the ceiling can be sealed with cleanroom-compatible silicone, but dry seals can also be used. The intervals at which the cleanroom ceilings need to be opened, for example, should be agreed with the client in advance. A silicone seal must be replaced every time it’s breached, whereas the dry seal is laid above the joints and does not need to be replaced when the ceiling is opened.

Cleanroom height: provide sufficient space in the plenum

A very important part of the preliminary planning of a new building is the shell height of the individual floors. Often, it’s only during the construction phase of the cleanroom and the installation of pipework, ventilation, electrics and sprinkler systems, for example, that it’s realised that the plenum is very tight and this causes that additional engineering (extra work) is required. This is why a precise estimate of the installation parameters and the sizes of air outlets or pipe routes, for instance, must be made in advance.

Convenient maintenance options at every necessary point are a must and should be considered accordingly, especially when it comes to safety relevant components such as sprinkler lines. Fire protection equipment cannot be installed arbitrarily but is subject to strict regulations. If both the plenum and the cleanroom have to be fitted with sprinklers, the amount of space and installation work required increases significantly. A co-ordinated and constantly updated 3D CAD/BIM model provides a remedy and planning security.

The cleanroom specifications, which should be designed to be smooth and flush, also play an important role regarding these fixtures. This is less of a problem with light fixtures and ventilation outlets, as most cleanroom manufacturers offer these as flush-mounted components for their ceiling systems. If possible, sensors should be installed in the grid profiles to have full freedom for the ceiling elements. Not all sensors can be flush-mounted, but there are plenty of cleanroom-compatible sensors and other suitable components on the market.

Cleanroom light fittings can be inspected either from below or from above. With accessible-from-below versions, defective light sources are easily replaced without revoking the cleanroom status, which is a major advantage.

The basic consideration for every cleanroom project also applies to lighting planning: the client should be involved from the outset to agree the best option for the construction project.

Ideally, all the planning services should be co-ordinated and come from a single source.