Pharmaceutical Technology - May 2019

Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2019 11 defined in the ISO 14644 series. Classification does not consider viable contamination, which is supposed to be controlled by the facility owner during building use. Much of this control occurs at the process level. Related aspects of cleanroom operations are outside the control of cleanroom engineers, ventilation engineers, facility designers, construction firms, and certifying firms. Monitoring Monitoring provides information about contamination generated by processes and operators and other work- ers within the facility. The means for assessment are adapted to the specifics of the cleanroom's use. An aseptic environment is expected to meet more strin- gent controls than an environment where materials are yet to be sterilized. The presence of contamination is influenced by many factors: activity levels; cleaning and decontamination practices; gowning materials; numbers of personnel; and material entry procedures. As a consequence, microbial populations and process-generated non-viable particu- late do not correlate directly to ISO class. Monitoring should include areas of limited activ- ity (i.e., those that pose minimal risk to product) such as corridors and storage areas to ensure that these are maintained in the desired state. While these areas may appear in 'as-built' condition, they are subject to the same operating influences as the rest of the facility. ISO 14644 indicates that classification can be performed in the operational state; however, this is restricted to non-viables. The healthcare sector routinely considers the levels of particles present during use, thus the ISO classes can be to used to designate the expected level of performance while equipment operates and person- nel are present. This must be recognized as monitoring, however, because the operational controls will dictate the conditions observed. Classification or monitoring? Perhaps the most important reason for standards of any type is to facilitate communication between and across organizations regarding the system upon which the standard is focused. Classified environments, due to their complexity and rigorous but varied performance expectations, are no exception. The following summa- rizes the typical activities of classification and monitor- ing employed for a new cleanroom (4). Owner. The firm using the cleanroom will identify the environmental performance required by the facility to minimize contamination potential during 'operational' use. This will consider the regulatory expectations for the intended use. Designer. The operational expectations will be trans- lated into a suitable design considering the budget, per- formance expectations, and internal activities that might contribute to contamination. Routinely, the intended design will result in a system that substantially exceeds the owner's operational expectations when tested in the 'as-built' state. There are multiple reasons for this: • The uncertainty of measurement • The need to provide a margin of confidence in meeting the 'operational 'performance target • The need to accommodate internal particle gener- ation expected when the facility is in operation. Although this practice is not defined in ISO 14644 (2015), it represents good engineering practice across the cleanroom community (2). Builder. The builder will execute the design to fulfill the owner's needs and designer's vision, then handle cleaning in preparation for certification. Classification contractor. Using defined methods from the ISO 14644 series confirms that the completed fa- cility meets the standard in the 'as-built' state. This is a formal process with documented reports certifying the

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