Zone concept and clean room classes

The kitchen is not used in the same way as a bathroom or bedroom. The rooms are also furnished differently. There are smooth surfaces in the kitchen and bathroom which can be cleaned easily with a wet cloth, whereas the living room and bedrooms are often fitted with carpets and textiles. A vacuum cleaner normally gets the job done without the use of water.

The situation in a pharmaceutical company is similar. Here, too, there is a practical division of the rooms into defined areas (hygiene zones, cleanliness zones) based on their function and hygiene status – the zone concept. Manufacturing and packaging rooms usually have a higher cleanliness class than storage rooms, quality control rooms, ancillary areas and offices.

Hygiene zones

The different types of hygiene zones differ in the following areas:

• Type of furnishings: In rooms with a higher cleanliness class, there is a minimum amount of furnishings and everything must be smooth and free of gaps to avoid an accumulation of dirt.
• Type of ventilation: In rooms with a higher cleanliness class, the air is filtered using special filters and monitored. The air pressure and air exchange rate are also different than in other rooms. It is important to ensure that unfiltered air from neighbouring rooms cannot enter the room in an uncontrolled manner.
• Type of use: The higher the cleanliness class, the less cluttered the room should be. Only the actual materials required should be kept in the room. Waste must be packaged immediately and removed from the room as soon as possible.
• Type of cleaning: Rooms with a higher cleanliness class often have to be cleaned and disinfected more thoroughly and more often.
• Personnel: Only specially trained personnel are allowed to enter these rooms (access authorisation). As few persons as possible should be present in clean rooms.
• Clothing: Special hygiene clothing must be prescribed for every zone (trousers, lab coats, coveralls, shoes, headgear, face masks, beard covers, gloves) (clothing concept). The higher the cleanliness class, the greater the amount of skin and hair that must be covered.
  All members of staff must follow the clothing instructions exactly. Even if an individual enters or leaves the hygiene zone for a short time, the required clothing must be put on or taken off in the lock. This also applies to managers, employees of third-party companies and visitors (e.g. customers, inspectors):

Open products require clothing that provides greater protection. Always wear all of the required hygiene clothing and wear it correctly.

Clean rooms

Particularly strict requirements apply to sterile or aseptic manufacturing processes for medicinal products. Even the slightest contamination of these dosage forms can threaten the lives of patients. For this reason, these medicinal products may only be manufactured in special clean rooms.

The individual manufacturing steps for these products must be carried out and monitored in clean rooms with a clearly defined cleanliness class. The number and size of dust particles and microorganisms in the room air and on surfaces is determined when classifying a clean room. Different names are used for all four clean room classes.

The FDA uses numbers (classes 100000, 10000, 1000 and 100), whereas the EU guidelines use the letters D, C, B and A. Class D rooms are used, for example, to prepare solutions that can be sterilised at a later stage, whereas class A or class 100 rooms (the highest clean room class) are used when particularly sensitive products are filled: members of staff are not allowed to be present during the process. This clean room class can be achieved using isolators. Isolators are chambers that isolate filling systems completely from the environment. The filling systems can only be accessed from outside using grippers, integrated gloves (glove-box systems) or half suits. Because these systems offer optimum protection for both product and operating personnel, they are also suitable for highly potent active ingredients (extremely small amounts of these substances put employees at risk).

If complete isolation of the system is not required or not possible, the components of the system used to fill an open product are protected by blowing specially filtered air across them (laminar flow, i.e. an airflow that does not create eddies). In the case of so-called RABS concepts (restricted access barrier system), the filling system is not isolated completely from the environment, but there is an extremely low risk of contamination caused by personnel because the system can only be accessed using integrated sleeve/glove systems.

Special cabinets are used for manual tasks that have to be carried out under clean room conditions. Laminar flow air is drawn into the cabinet through a high-performance filter. Clean benches or LF benches are used if the focus is on product protection. Biosafety cabinets have to be used when the protection of personnel is also necessary, e.g. when processing cytostatics or highly active substances.

Locks

Adjacent hygiene zones must be protected by locks to ensure that dirt, dust and bacteria cannot be transferred into clean rooms by materials or personnel entering or leaving the hygiene zone. Locks are closed rooms with at least two doors, located between rooms of different clean room classes. They are used to prevent contamination.

However, locks only function if all persons change their clothing and wash or disinfect their hands every time they move from one zone to another. This also applies to technicians, external service personnel, managers, visitors and inspectors.

To ensure that the hygiene clothing does not get dirty when dressing, e.g. because it comes in contact with the floor or with street clothes, gowning must be trained, practised and carried out exactly as described in the relevant SOP. The sequence for putting on clothing, shoes, hair covers or head cover hoods, washing and disinfecting hands and putting on gloves must be followed exactly. Clean room clothing should never be worn outside the clean room.

Interlocking systems (often with indicator lights or acoustic signals) prevent the doors of the lock being used simultaneously and ensure that contaminated air cannot enter a room with a higher cleanliness class.

Containers and packaging of equipment, materials and tools must be cleaned from dust and dirt in material locks. If required, outer packaging (cardboard or foil) even must be be removed or disinfected. Products are often transferred from wooden pallets to pallets made of plastic, aluminium or stainless steel. All materials that are transferred into clean rooms with a B/A class undergo sterilisation, sterile filtration or disinfection, at least.

Locks are used to block as many dust particles and microorganisms as possible.

This text is an excerpt from the step-by-step guide GMP Fundamentals