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Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2019 13 means of controlling them, add cost and confu- sion without adding value. At this point, it is not clear what value this classifi- cation would provide. Monitoring is already a com- mon practice that addresses conditions during use. Is there any identified benefit to the adoption of this standard? For these reasons, classifying cleanrooms based upon microbial population is an unnecessary objective. In short, there is a clear distinction between classification and monitoring. Classification using particle counts focuses on the design performance of the cleanroom in the absence of the complicating ac- tivities associated with microbial control. Monitoring confirms the effectiveness of all the functional controls on the environment. It incorporates microbial assess- ments because that is a universal concern in clean- rooms in the healthcare industry. Confusing these very different activities can create a host of problems for the practitioner. For one thing, imposing arbitrary microbial expectations adds no value to an activity where microbial control has yet to be established. In addition, variations in facility design, cleaning, and decontamination regimes and the major variations in usage and operating practices makes the imposition of a 'microbial' çlassification wholly inappropriate. A one-size-fits-all approach to monitoring prac- tices and results is never appropriate, given the diversity of practice. And finally, the use of clas- sification type values as monitoring performance targets does not turn monitoring into classification. It merely establishes a process goal. Ideally, these two activities should be maintained as indepen- dent activities, loosely connected by the non-viable monitoring values used to record the results. References 1. Federal Standard 209E : Airborne Particulate Cleanliness Classes In Cleanrooms and Clean Zones (ISO, September 11, 1992). 2. ISO, ISO 14644-1-2015, Cleanrooms and associated controlled environments Part 1: Classification of air cleanliness by particle concentration (ISO,2015). 3. PDA ,TR #22, Process Simulation for Aseptically Filled Products, 2011 revision (Bethesda, MD, 2001). 4. ISPE, Sterile Product Manufacturing Facilities, Baseline Guide, 2nd Edition (ISPE,2011). 5. FDA, Guideline on Sterile Drug Products Produced by Aseptic Processing (FDA,2004). 6. EMA, Annex 1, Sterile Medicinal Products (EMA,2008). 7. ISO, ISO 14698-Cleanrooms and Associated Controlled Environ- ments Biocontamination Control Part 1: General Principles and Methods (ISO,2003). PT Table I: Comparison of classification and monitoring. HEPA is high efficiency particulate, and RODAC is replicate organism detection and counting. Classification Monitoring Why Confirmation of facility design expectations Confirmation of operating practices: (i.e., cleaning, decontamination, gowning, human activity) Non-viable Viable Non-viable Viable When Static, prior to use Execution prior to introduction of operational controls precludes useful values. Dynamic, during activity Where Random locations Locations of greatest risk What Air Air Air, surface personnel Who Certification firm Facility owner Calibrated device Particle counter Particle Counter Active and passive air samplers, settle plates RODACs, Swabs Calibrated device Yes Yes No Recovery Counts all Counts all Misses most Influenced by Design, air changes, HEPA coverage, return locations Design, air changes, HEPA coverage, air return locations, cleaning, gowning decontamination practices, personnel practice, equipment, components, procedures