132 Good Design Practices for GMP Pharmaceutical Facilities TABLE ISO and U.S. Federal Standard 209E so EU —_US.Federal Standard Common Application in Recommended Air (Standard) Grade 2096 (Reference Only) Pharm Industry (Change per Hour - NA NA 1 NA NA 0 NA NA A 100 Bielvaeitenle operations 00 B 1.000 Bio/vaclsteile operations 35 ¢ 1,000 Blo/vaceiepar operations 2 D 100,000 Bio/aeiteielp haem opeations 15 ot applicable ITF (20°C-25°C) with a maximum mean kinetic temperature (MKT) of 77°F (25°C). However, individual products may require a more stringently controlled environment. Product temperature monitoring may be performed as an alternative to room temperature moni- toring. Room temperature can be monitored by return or exhaust duct-mounted sensors or wall ‘mounted sensors that relay information to the BAS or separate sensors connected to an independent environmental monitoring system (EMS). Typically, a relatively ight control range is specified (i.e. (68°F-72°F), with an excursion alert occurring when a wider range is exceeded (ie, 65°F-75°F), and ‘a further excursion alarm occurring when a maximum range is exceeded (62°F-78°F). All values ‘must be well inside the USP excursion limits. ‘Allowable space and system conttol tolerances must also be identified, as well as the impact of these tolerance requirements on the systems design. Proper outdoor ambient design conditions must ’be determined in order to select the air conditioning equipment. If outdoor conditions are chosen too conservatively the equipment will be oversized, costing more than required and requiring more ‘energy for operation. Conversely, if the selection does take variation of ambient conditions into consideration, the facility or process conditions may not be met under certain circumstances. An assessment must be made of the possible risks of not meeting space or process condition require ‘ments and the effects on productivity Air Cleanliness ‘The level of acceptable airborne contamination within the space must be identified, whether required for product quality or employee safety. Environmental cleanliness is determined by sev- cral factors, including the quality and quantity of air introduced into the space, the effectiveness of air distribution through the space, and the effectiveness of the removal of the air contaminants, Removal of the contaminant as close to its source as possible is always the most effective method ‘of contamination control—whether itis central filtration at an air handling unit before supply to the facility or dust collection at a point source of contamination within a space. ‘Clean room design takes contamination control to its highest level. Federal Standard 209 histori- cally was the document governing clean room design, Ths standard has been replaced by the TSO 14644 and 14698 global clean room standards, Cleanliness is categorized by cleanliness classes, which are qualified by the quantity of 0.5 micron oF larger particles per cubic foot of air within a specific area, Standard categories of cleanliness used in the pharmaceutical industry are ISO 5, 7, and 8 (Classes 100, 10,000, and 100,000 per U.S, Federal Standard 2098, which was replaced by the ISO standard), See Table 5.