Microbial,Monitoring,Pharmaceu education Microbial Monitoring in Pharmaceutical Sterile Areas


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Microbiological monitoring limits should be established based on the relationship of the sampled location to the operation.  The limits should be based on the need to maintain adequate microbiological control throughout the entire sterile manufacturing facility.  One should also consider environmental monitoring data from historical databases, media fills, cleanroom qualification, and sanitization procedure studies in developing monitoring limits.Microbiological environmental monitoring should include both alert and action limits.  Each individual sample result should be evaluated for its significance by comparing to the alert or action limits.  Averaging of results can mask unacceptable localized conditions.  A result at the alert limit urges attention to the approaching action conditions.  A result at the action level should prompt a more thorough investigation.  Written procedures should be established, detailing data review frequency, identification of contaminants, and actions to be taken.  The quality control unit should provide routine oversight of near term (e.g., daily, weekly, monthly, quarterly) and long term trends in environmental and personnel monitoring data.Trend reports should include data generated by location, shift, lot, room, operator, or other search parameters.  The quality control unit is responsible for producing specialized data reports (e.g., a search on a particular atypical isolate over a year period) in order to investigate results beyond established limits and identify any appropriate follow-up actions.  In addition to microbial counts beyond alert and action limits, the presence of any atypical microorganisms in the cleanroom environment should be investigated, with any appropriate corrective action promptly implemented.   Written procedures should define the system whereby the most responsible managers are regularly informed and updated on trends and investigations.Environmental monitoring methods do not always recover microorganisms present in the sampled area.  In particular, low level contamination can be particularly difficult to detect.  Because of the likelihood of false negatives, consecutive growth results are only one type of adverse trend.  Increased incidence of contamination over a given period in comparison to that normally detected is an equally significant trend to be tracked. All environmental monitoring locations should be described in SOPs with sufficient detail to allow for reproducible sampling of a given location surveyed.  Written SOPs should also address areas such as: (1) frequency of sampling; (2) when the samples are taken (i.e., during or at the conclusion of operations); (3) duration of sampling; (4) sample size (e.g., surface area, air volume); (5) specific sampling equipment and techniques; (6) alert and action limits; and (7) appropriate response to deviations from alert or action limits.

Microbial,Monitoring,Pharmaceu

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