16/17 November 2022
Typically, the room humidity is also regulated and controlled in cleanrooms. For this purpose, the outside air is dehumidified in summer, especially in humid weather conditions (max. RelHumidity 60-70% is common). In winter, especially in dry cold weather, there is a need to humidify the outside air to ensure a minimum humidity in the cleanroom (min. 40% RH is usual).
If the room air is too dry, it can cause irritation of the employees' mucous membranes. Coughing and coughing irritation in the cleanroom are of course problematic and should be avoided. Too dry room air can also lead to increased static charge and thus destroy sensitive electronic components, among other things. Disinfectants can also behave differently in a very dry environment, e.g. evaporate more quickly, which would no longer ensure the required exposure times. So how exactly is the humidification of the room air for GMP-regulated areas carried out? What quality should the evaporated water or its condensate have? These questions are frequently asked and controversially discussed.
For sterile areas (Annex 1 EU GMP guidelines purity classes A, B and partly also C) it is usually steam humidification. Humidification with steam is relatively safe from a microbiological point of view - and the heat supplied is needed in winter anyway to raise the temperature of the outside air.
From the GMP point of view, the only defined steam quality is the Pure Steam quality described in the American Pharmacopoeia. This is defined by the condensate of the steam, which has WFI (Water for Injection) quality. If the steam should come into contact with the product via the room air, this would be the only permissible quality, because only ingredients of the corresponding pharmaceutical quality are allowed to enter pharmaceutical products. In practice, however, this is not the rule, i. e. Pure Steam is not used for humidification in every pharmaceutical production.
A frequently used approach is to judge the quality of the steam used for humidification by the quality of the water used for production. If Purified Water (PW) is used in production, steam of a quality where the condensate corresponds to PW is used. If WFI is used in production, the condensate of the steam is also of WFI quality. A linguistic distinction is often made here between Pure and Clean Steam. However, it should be mentioned that both the EU GMP Annex 1 (draft 15) and the ISPE Guidelines equate Pure Steam and Clean Steam. The risk analysis used to determine and document which steam quality is to be used for humidification is the key to success here. Points to consider here should be: cleanroom class, product handling (open/closed), avoidance of static charge, labour regulations if applicable, packaging materials, microbiological requirements, etc.
Filtered black steam (heating steam) is also sometimes used for class D and areas in production of oral solid dosage forms. For this black steam, however, a food authorisation for the corrosion protection agent used must be available in any case. Its compatibility with the manufactured products and surfaces must be considered in advance in a risk analysis or hazard assessment. Inspectors may wish to view these as well as other documents such as filter maintenance.
Another option is pressurized water humidification for adiabatic humidification with softened or partially treated drinking water, e. g. in storage or black areas. The critical factor with such water injection systems is the - seasonal or weather-related - discontinuous operation. In the event of prolonged standstill in the supplying water systems, considerable contamination can occur - extremely high numbers of pseudomonas and legionella have been reported - which in the worst case can then be carried into the room air. Both pressurised water humidification and all other humidification systems must therefore be operated with special care. VDI 6022 provides important information on how to proceed during maintenance and operation. Here, too, appropriate documentation must be available and one should be prepared for discussion during inspections.
Which method and which media are used for GMP cleanroom air humidification requires careful planning. Humidification with clean steam can cause very high operating costs in factories with a high proportion of fresh air. The quantities required here often correspond to many times the amount of steam that would otherwise be needed to supply the actual production. The entire treatment chain must be adapted accordingly - for the few weeks of winter operation of the ventilation system. Starting with the deionised or purified water system as feed water and continuing with the black steam system to supply the clean steam generator with the necessary heating steam.