Control of the environment and personnel activities is critical in an aseptic processing plant to provide sterility assurance.  Plants are dependent on Engineering Controls, such as HEPA filtration, frequent air changes per hour, laminar air flow, and use of disinfectants to keep counts of non-viable and viable particulates low.  Testing of the environment particulates (viable and non-viable), as well as ensuring personnel monitoring samples have minimal counts, is a vital part of demonstrating control of this environment.   This is necessary because Sterility Testing is a destructive finished product test, where only 20-40 samples are tested.  A high level of contamination would have to be present to find growth.  Low level contamination is not likely to be detected.

The key issue is how to respond to counts found from environmental monitoring (EM) and personnel monitoring (PM), particularly viable ones.  The USP, in earlier versions, indicated that investigations were needed for low counts of even 1 CFU, but in May 2014, Version 37 described that individual counts of 1-10 may not be significant.   Actually a count of 15 is deemed to be of concern, requiring investigation. Also, the search for monthly trends was and is recommended for EM and PM, particularly in Grades A and B areas with a 1 to 3% recovery rate, respectively, and to evaluating risk to product quality in those cases.   Use of the Fishbone methodology is helpful in reviewing possible root causes.  With low numbers of counts, it is sometimes impossible to determine a most probable root cause, and to develop Corrective and Preventive actions (CAPAs).  Therefore, we are frequently left with an assessment of whether the risk to product quality is low, medium or high, and if high the only choice must be to reject the product.