Clean room classification

Room Description Work Areas Encompassed in Description Clean Room Classification... 

Clearly there are issues here that the pharmaceutical industry needs to address. Particles of the smaller sizes specilied for measurement in the Clean Room Standards are not of direct concern to particulate contamination issues facing manufacturers of sterile pharmaceuticals. Furthermore, it is the quality of clean room technology that is the factor of greatest importance to the pharmaceutical industry, of which the attainment of clean room classification is merely an indirect index. In these circumstances a major increase in the amount of testing required to claim compliance with a particular classification offers no benefit to the industry, and may indeed unnecessarily increase testing costs, downtime, etc. 

Classes for clean rooms Many national standards are in use for the classification of clean rooms. It is recommended that the standard of the country in which they are to be installed be referred to. 

ISO 14644-1. Clean rooms and Associated Controlled Environments, Classification of Air Cleanliness,... 

The clean room or clean zone is deemed to have met the specified air cleanliness classification if the averages of the particle concentrations measured at each of the locations and, when applicable, the 95% upper confidence limit, do not exceed the concentration limits required [13,15,19],... 

A cleanliness classification in accordance with the latest revision of ISO 14644 is generally inadequate by itself to describe a facility used for pharmaceutical processes. The presence of viable particles (living organisms) within the particle count achieved by applying methods described in the standard may affect the product within the facility. A measure of both viable and nonviable particles is required to provide sufficient information upon which to base a decision regarding the suitability of the clean room for its intended purpose. 

In the absence of other guidance governing the cleanliness classification and acceptable levels of microbial contamination of the clean room, the values presented in Table 1 may be used. The room grades presented are from most critical (A) to least critical (E). The definition of criticality is left to the clean-room user organization. 

Room classification tests in the at-rest condition should be carried out with the equipment operating where relevant, but without any operators. Because of the amounts of dust usually generated in a solid dosage facility most clean area classifications are rated for the at-rest condition,... 

Table 1. Recommended Classification of Clean Rooms and Clean Zones for Aseptic Processing Pharmacopeial Forum, Sept.-Oct. 1991, pp. 2399-2404.)...

Clean Room Standards and Room Classification Clean room technology is the most typical feature of aseptic manufacture. The major regulatory sources of guidance to appropriate technology and air standards for aseptic filling [2,3,4]... 

The two Clean Room Standards FS 209 and BS 5295 are referenced in the regulatory documents governing aseptic filling. Table 1 compares the air classifications recommended or required for aseptic filling clean rooms in these pharmaceutical regulatory documents and references the particular Standards cited in support. Strictly speaking, the only options for room classification are the 1976 revision of BS 5295 and the 1973 and 1988 revisions of FS 209. 

Classification and monitoring to the Clean Room Standards requires that particular numbers of samples of air be taken per unit floor area, that samples be taken in specified locations, and that samples be taken at appropriate frequencies. Table 2 summarizes these requirements. It is evident that the evolution of the US standard from FS 209B to FS 2WE. both for validation and for routine monitoring, is toward the as otherwise specific" condition, which bounces the onus for decision-making back to the user and his customer. This is not the case for the British Standard. To validate a clean room, the British Standard BS 5295.1989 asks for more locations and more replicate testing at each location than BS 5295.1976 or either revision of the U.S. standard.. 

Overall, the standards being adopted worldwide for classification of aseptic pharmaceutical filling rooms are those of FS 209. This is because of the practical flexibility of this standard. The British Standard has diverged from strict equivalence with its introduction of levels of testing activity that may be more appropriate to the electronics industry. The availability of Clean Room Standards has been important to the development and responsible control of... 

In some instances the terminology of room classification may be used where it is neither specifically necessary nor specifically correct. The FDA Guideline (2) refers to a "per-cubic-foot particle count of no more than 1(X) in a size range of 0.5 fim and larger (Class 1(X)) when measured not more than one foot away from the worksite and upstream of the air flow. The sampling requirements of the Clean Room Standards may be omitted when superfluous to the purposes of aseptic manufacture. 

White areas (Class 100 clean rooms) should clean up to their classification within 20 min of starting up air handling systems unless theie is some major particle generator present in the room or leaks in the ducting. 

The classification of the clean room for preparation of radiopharmaceuticals should be the outcome of a risk assessment and could be class B, C or D [11, 16, 17]. The risk assessment should take into account the use of closed systems, the time between preparation and use and the namre of the product. The critical working zone should be class A and can be realised with a radiopharmacy safety cabinet, an isolator or a hot cell (see Sect. 15.6.4). A compromise to respond to these demands could be an extra airlock between the clean room clothing area (first lock) and the preparation clean room [21]. The first lock has an overpressure of 10-15 Pa to the outside world for keeping out particulate matter (product protection). The second lock has an extra underpressure of — 10 to —15 Pa relative to the clean room to realise a deep underpressure (the so-called sink) for radioprotection and GMP-overpressure of 10 to 15 Pa between the clean room and this extra lock. See also Fig. 27.1. 

---