Premises clean rooms

All persons entering production areas should wear protective garments appropriate to the processes being carried out The garments should be regularly and frequently cleaned and not worn outside the factory premises. Changing Rooms should be provided. 

For the design of premises reference is made to Sect. 27.2, including aseptic processes and the pressure conflicts that may occur when product safety as well as persoimel safety have to be dealt with. A typical radiopharmacy department consists of one or more clean rooms, a quality control room and adjacent rooms such as locks for people and goods, a room for admin-istration/storage, a room for cleaning materials and a waste disposal room [1,2,21]. Often the radiopharmacy department is called hot lab, while this term originally refers to the room(s) where radioactive materials are handled. 

The premises for the most critical preparatirai steps (e.g. filling) must be built as a clean room (see Sect. 27.3) and require a controllable air conditioning installation. 

What should be attended to in the assessment of the DS In premises intended for sterile and aseptic preparations (clean rooms) the most severe requirements apply to the walls, doors, floors, ceilings, heating and furniture, see further subsections. Premises which are only intended for non-sterile preparations can do with less far-reaching demands. Nevertheless in practice it might be wise to apply the requirements for sterile premises also for non-sterile premises if both are at stake. In the first place in a new building the itemisation of methods and materials between premises meant for sterile preparation and for non-sterile preparation usually doesn t yield much cost reduction. Additionally many of the starting points for the requirements for sterile preparations more or less apply to non-sterile . 

A requirement for premises for sterile preparations (clean rooms) is that walls are free from any ledges and seams to enable effective cleaning and disinfection. The provisimi of ample glazing for supervision and well-being of personnel should be considered. The ledge free and seamless mounting of windows and doors into walls is known as flush fitting . 

Doors in clean rooms must be flush mounted, smooth, clean-able, if necessary disinfectable and as far as possible seamless. This especially goes for doors in GMP classified premises as indicated in Sect. 27.4.2. Points of special interest are ... 

During the execution phase of newly built or rebuilt pharmaceutical premises (including clean rooms) the building control department should take a few particularities into account. The ISO 146 - standard [4] specifies those particularities for clean rooms. 

In March, 2000, a thunderstorm struck the Philips semiconductor plant at Albuquerque in New Mexico, which made silicon chips for products like cellphones. Damage at first seemed minor, and fire fighters soon left the premises. At first. Philips told major customers like Nokia and Ericsson that the delay to production would only be one week. But damage to some of the clean areas in the plant - created by smoke and water - was actually going to take months to remedy. Clean rooms in semiconductor plants must be spotless, and particles of more than 0.5g are filtered out. 

Attention should be paid to classification of clean area requirements taking into account the possible high degree of initial microbial contamination of herbal materials. Classification of premises as applied to sites for the production of other pharmaceutical substances may not be applicable to processing of herbal materials. Specific and detailed requirements should be developed to cover microbial contamination of equipment, air, surfaces and personnel, and also for rest rooms, utilities, ancillary and supporting systems (e.g. water and compressed air). 

The required apparatus and utensils, the preparation processes they are used for and the required provisions such as air conditioning, clean water, electricity, compressed air and gasses. For extremely hazardous preparations (antineoplastics, radiopharmaceuticals, see Sect 26.3.5) and for sterile preparations separate premises may be required to protect products and operators adequately, as is also laid down in GMP. Scaling up of the processes may lead to partitioning of the rooms into areas for dedicated functions. 

Refrigerators and freezers within the preparation premise are unwanted for several reasons such as that the expansion radiator at their backside cannot be cleaned. If a refrigerator or freezer in the preparation premise is indispensable it should be airtight separated from the room, e.g. by means of a flat shaft of sheets up to the ceiling or a throughput through the wall. 

For all major premises or equipment instruments and devices which may have critical influence on the preparation or analytical processes, a logbook should be kept. The logbook is the history of a piece of equipment or a facility and it aims at traceability and verification. The investigation of any deviation may use the logbook as a vital source of information to enable the root cause to be traced. In addition, the logbook will include records as to whether equipment is maintained on time, if rooms are cleaned on time etcetera. 

A good working discipline is essential to prevent cross contamination. This requires careful planning, but a system for identification as well. In stock preparations the identity of the product in operation must be fixed to premises, equipment and vessels. For this purpose labels can be used, or a form that is part of the preparation record. Logbooks can also play an important role in the securing of the history of use of rooms and equipment (see Sect. 33.7). If a room or equipment has been cleaned according to the applicable procedure, the status indicatimi clean has to be applied. 

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