Periodic environmental monitoring is integral to maintenance of a controlled environment area (CEA) and is often a requirement, depending on the standards to which compliance is claimed. In the medical device manufacturing industry, periodic monitoring typically includes measurement of airborne microbial contamination. In the business of cleanroom certification, results of this type of testing are presented to the customer, who will then compare against internal specifications with defined alert and action limits. In a perfect world, testing results are found to be within allowable limits and filed away for future reference. However, no customer is immune to the possibility that they will eventually receive results outside these limits.
So, what approach might be taken to investigate in the event an out of tolerance result is obtained? This question may come from operators of smallscale cleanrooms, or those owned by Fortune 500 companies. In either instance, quality personnel should begin this process by evaluating test results, evaluating the environment from which the results originated, and comparing results to other relevant data sets.
The first step in investigating out of tolerance viable airborne sampling is to evaluate the actual test results. There are numerous potential sources of error involved with the microbial sampling process, and error in any area may render the results invalid. Sampling, incubation, and analysis may be done in-house or through local vendors. In either case, the appropriate party should be contacted and the results examined. First, it is worth verifying that no transcriptional errors were made during reporting of results. Other laboratory errors that may have a negative impact include incorrect media type or use of media outside the stated expiry date. Instrumentation used during sample collection, including air sampling devices and incubators, should be in current calibration traceable to NIST standards. In addition to verification of equipment and materials, the methodology by which sampling was completed should be examined. Quality personnel will want to verify the responsible technicians were properly gowned, wearing appropriate masks/gloves, and that they followed relevant procedures for instrument use, sample collection, and incubation. While not meant to be a completely exhaustive list, these checks and verifications should provide quality data to help determine whether or not systemic contamination may be present.
Another means by which to investigate results is to evaluate the local environment that the out of tolerance sample was obtained from. While, at this point, it’s not possible to observe the cleanroom at the instant any given sample was taken, a lot of relevant information can be obtained by interviewing operators who were present at that time. These operators should be able to give reasonable accounts of any abnormal activity that may have been going on while testing took place. There may have been personnel present that were not properly gowned, or even visibly sick. There may have been cleaning or maintenance work being performed or potentially rearrangement of equipment.
Some facilities may log temperature and humidity data, which can be checked for any excursions that may have occurred. In addition to investigating the state of the cleanroom at the time of testing, a review of the present state of the suspect area should be completed. Is there any visible contamination present? Are the HEPA filters operating at normal capacity? Are cleaning supplies within expiry? Any changes or differences from what would be considered “normal operation” should be noted. I was recently contacted by a concerned customer who had received environmental monitoring results significantly higher than those reported previously. After having received a list of items to investigate, the concerned party had come to find a major process change had taken place since the last successful test series. At the time of the change, a preliminary check of contamination levels had been completed. The contamination levels present following the change were found to be consistent with the results that were initially the cause for concern. This instance served as a reminder for the customer that changes to processes or equipment may impact results of environmental monitoring. This scenario touches on another valuable approach for investigation of results, which is comparison to other relevant data sets.
One of the benefits of environmental monitoring, apart from the fact it will show compliance with quality and regulatory standards, is that it provides data points that can be trended for evaluation of performance over time. When monitoring results differ from what was expected, data can be compared against historical values. Quality personnel may find that specific areas trend higher than others, and consistent contamination issues in an area may be indicative of a systemic problem. If data trending shows no adverse results for a location, the contamination may be a localized, isolated incident. When investigating out of tolerance results, it is also valuable to compare the data point to results obtained at neighboring points in the sampling plan on the same day. Contamination at only one test point may suggest a localized event or sampling error occurred, while regions of high contamination may suggest a more widespread procedural or process related issue is the cause.
At this point in the investigation, a large amount of supporting data has been collected that should allow for reasonable conclusions to be drawn. The findings related to the investigation steps outlined above should be documented, as well as the decision-making process for determining follow-up actions. Follow-up may include retesting, decontaminating the cleanroom, reevaluating testing frequency, changing procedures, or other corrective actions. Thoroughly investigating test results, the sampling environment, and comparing with other data sets will provide invaluable support to any corrective action and promote continued, satisfactory cleanroom operation.
Brian Hill is the Validation Engineering Manager at Gerbig Engineering Co. Gerbig Engineering has been designing, manufacturing, installing, and certifying cleanrooms since 1985. www.gerbig.com
This article appeared in the May/June 2015 issue of Controlled Environments.