In terms of cleanliness, the manufacturing space was design to meet ISO 7 classification in at rest condition. Entry and exit points were specified at air changes per hour that met ISO 7 requirements for this non-sterile drug product. The air change rate in the gowning rooms was set higher to promote particle capture at entry and exit points. The corridors were clean but not classified or CNC. A transition zone occurred inside the gowning room to take into account the movement between the CNC space and the ISO 7 area, as depicted in the image below. This transitional zone was physically demarked by a step-over bench that separated the clean side from the dirty side. Gowning at the entry point was downed at a level that was prescribed by the user as part of the administrative protocols to minimize both introduction of particles and cross contamination of the API from external sources. For this facility, people entering the manufacturing area from the CNC corridor downed a second layer of gowning (the first layer was downed at the entrance to the CNC space). People moving from one production suite to the next needed to follow gowning protocols at each entry and exit point.
Cleanliness plan
The API processed in the critical space was not particularly sensitive to temperature but was to the space relative humidity. Temperature was set in the range of 64 to 68 degrees Fahrenheit primarily in response to human comfort and to reduce sweating of the gowned personnel, who would introduce particles in the space. Humidification was added to the supply air to maintain the space relative humidity within allowable range. Doors between rooms were interlocked to prevent cross contamination and reduce safety issues. Visual and audible aids were placed in the critical areas to inform the user of excursions from normal operation conditions. This was a requirement given the validated nature of the facility and the hazardous material used in manufacturing the drug product.
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