Cleanroom Technology in the Pharmaceutical Industry

Principle of the Flow Box

Cleanroom cell with two laminar flow modules

Typical Laminar Flow Hood

CleanRoom Station "CleanBoy"

For approximately 25 years, the company Spetec Gesellschaft für Labor- und Reinraumtechnik mbH in Erding has been involved in the design and construction of cleanrooms of various sizes, which can be set up flexibly and manufactured according to applications or customer wishes. They are used, for example, in pharmaceutical production and packaging when working in a purest atmosphere is necessary or recommended.

The typical design feature is the connection of a confined space with a module equipped with a high-quality fan and a filtration system consisting of a pre-filter and a high-efficiency filter (H14). The filter designation H14 means that this filter is capable of retaining 99.995% of all particles with a diameter ≥ 0.5 µm.

(Image 1: Principle of the Flow Box) For larger cleanrooms, called cleanroom modules, multiple modules can also be used side by side. Modern modules are characterized today by quiet operation and feature a filter change indicator.

Generally, two different concepts of cleanroom layout can be realized in the pharmaceutical industry. One is an almost enclosed room or workspace, which is called a laminar flow box or cleanroom module depending on size. These can be constructed so that objects behind them are enclosed from the outside, devices can be operated, or, if large enough, the cleanroom module filled with purest air can be entered. In the latter case, the hall itself would be the cleanroom, meaning that the periphery and possibly also production and packaging can be carried out within the cleanroom.

According to the Spetec cleanroom system, such enclosures (Image 2: Cleanroom module with two laminar flow modules) can be built. The support frame of a cleanroom module consists of aluminum or stainless steel profiles, and the side walls can optionally be made of acrylic or composite glass or PVC strip curtains. Materials for door elements, windows, or ceilings are freely selectable. Two modules provide, in the example shown, laminar clean air supply. If equipment is installed inside, a low-turbulence clean air flow is recommended to ensure the most complete air exchange possible. These cleanroom modules are an economical alternative to complete cleanrooms. As with these, large cleanroom modules can also be equipped with pass-throughs, changing rooms, or entrance airlocks.

The second concept involves the encapsulation of various machine parts. For example, production can be encapsulated using FFUs, whereby a finished product, for example, transported via an attached conveyor system into an adjacent cleanroom for further processing. The benefit of this concept is obvious. Only as much technology as necessary is kept inside the cleanroom. Additionally, maintenance and service activities do not cause contamination, as these activities can be carried out in a separated area.

To meet these requirements, for example, laminar flow modules from Spetec can be used, which are available in various sizes. This ensures a perfect adaptation to different workstation sizes or layouts.

Both concepts mentioned are implemented by the company SPETEC. From the complete cleanroom module, which can be built up to a size of 350 m², to customized solutions with individual laminar flow modules. Thanks to its own project planning department and metal fabrication, precise functional solutions for enclosing individual machine areas can be developed, which can be easily implemented and assembled using the company's profile technology.

In addition to cleanroom modules and customized enclosures, there are small portable solutions such as a laminar flow box (Image 3: Typical laminar flow box), which allows creating a clean workspace within a normal production environment, suitable for tasks such as assembly or packaging. This workspace can have a size ranging from 0.24 to 1.12 m² depending on the model variant. Also worth mentioning is the mobile cleanroom station CleanBoy (Image 4: CleanRoom station "CleanBoy"), which allows bringing cleanliness exactly where it is needed. The CleanBoy is easy to transport and can therefore be used at multiple different workstations as needed.

The properties and quality classes of cleanrooms are defined in standards such as DIN EN ISO 14644, Part 1 (Classes 1 – 9), DIN EN ISO 14698, Parts 1-3, and VDI 2083, Sheets 1-18 (Classes 0 – 7); US Fed. Std. 209E (Classes 1 – 100,000), or in the EU GMP guidelines (Classes A – D). The latter correspond to the ISO classes 5–8 mentioned here.

By filtering the air with the H14 filter, depending on the purity of the ambient air, ISO classes 5–8 can be achieved, meaning between one thousand and one million particles per cubic meter with a diameter of 0.5 µm. The isolation factor of the laminar flow box is 10³. If this box were placed in a very good complete cleanroom of ISO class 6, then at most 10 particles per cubic meter would remain, which would be practically undetectable in the box.

The environment air and humans have the greatest influence on the cleanliness of objects. In addition, contamination of cleanrooms occurs due to particle transport through the air, the introduction of particles on technical surfaces, and particle generation by devices, personnel, and ongoing processes. Just through skin and clothing, more than 600 million particles (> 0.5 µm diameter) are released per person per cubic meter in a class 8 cleanroom. This, along with measurements of particle emission of the same diameter during personnel movements in protective clothing (sitting with slight arm movement: 20,000; standing up: 50,000; slow walking: 80,000 particles per person), is based on data from the Fraunhofer Institute for Process Engineering and Automation (IPA) in Stuttgart.

The use of variable cleanrooms as an addition or cost-effective alternative to expensive complete cleanrooms has led to the construction of increasingly larger cleanroom modules, where workbenches or packaging systems for food, manufacturing machines in the plastics industry, as well as filling systems for pharmaceutical products and other high-quality equipment can operate protected. The demand for customized solutions, such as enclosures for various machines, is also steadily increasing, allowing Spetec to draw on extensive experience. Since not all customers are familiar with cleanroom technology, Spetec offers support in planning and commissioning, as well as quality assurance and GMP compliance.

These few examples demonstrate that cleanroom technology and the resulting structures are already important tools in various fields and that further applications will inevitably follow.