A guide to trending your cleanroom EM program – Natural Self Esteem

April 13, 2022

Institutions set their own rules for data trending and violations. While there is no universally accepted method, there are a number of common factors that need to be considered, as explained by Microgenetics’ Edward Webber

The results of environmental monitoring (EM) should be analyzed regularly to assess whether there are any trends in the data. Routine review of EM data provides confidence in the quality of production areas and surrounding clean environments, and ensures that any adverse trends that may develop are quickly identified.

Identifying trends can reveal potential problems with environmental control systems. A single breach may indicate an isolated problem, but multiple breaches or trends may indicate a loss of control that needs to be addressed.

Consideration must be given to how data will be grouped and analyzed for trending purposes, e.g. B. Evaluation of the results of individual operators

Individual facilities should establish rules for trending, and when these rules are violated, a trend deviation investigation should be conducted.

There is no universally accepted method for defining and identifying trends, but the rules must achieve the goals of the EM program and provide details of how the facility should be governed. According to the 2020 draft of Annex 1: “Trends may include but are not limited to; Increasing number of action or alarm limit violations; Consecutive violations of alarm limits; Regular but isolated exceeding of limit values, which can have a common cause, e.g. B. Individual deviations that always follow a planned preventive maintenance” or “Changes in the type and number of microbial flora and predominance of certain organisms.”

Some examples of trends that can be set within a facility are listed below:

  • Consecutive readings equal or greater than the alarm limits
  • Multiple records of the same organism in multiple locations on the same day or over several days
  • Three or more action-level excursions for a sample type on the same day
  • Three or more field trips for one sample type in one room from four consecutive samplings
  • Increasing contamination recovery rates over a period of time
  • Unusual microorganisms such as B. gram-negative bacteria from arid regions or bacteria forming unusually many endospores, have been recognized

Significant changes in microbial flora should be considered when reviewing the data, and other trends should also be considered when analyzing EM data, such as For example, seasonal trends, trends for an individual, or trends by territory, lot type, or shift.

Setting trend rules

Trends are often viewed as repeated breaches of alarm limits, as this often indicates lower levels of contamination that may not be significant enough to exceed an action limit, but can still indicate a loss of control in an area or facility.

When setting warning limits, it is important to analyze historical data to determine a normal or acceptable level of contamination for samples, and then set limits based on that. Setting limits that reflect normal operating conditions is important to ensure that any deviation from normal operating conditions is detected.

Significant changes in microbial flora should be considered when reviewing the data

Additional trend rules should be established in the EM program and regularly evaluated to ensure they reflect the operating condition of the plant. Consideration must be given to how data will be grouped and analyzed for trending purposes, e.g. B. to evaluate the results of individual operators to demonstrate the performance of each operator.

In addition to evaluating individual operators, trends across all operators can provide useful information about system-level processes such as dressing and should be evaluated together with trends for individual operators.

Stepped areas should also be considered, e.g. e.g., a facility may only use Class C environments for the preparation of reagents to be transferred to production areas and therefore the assessment of all Class C areas as similar units may be appropriate for trending purposes.

In the areas used as background for Class A, the alarm limits should be set lower

However, some facilities may also use Class C areas as the background environment for Class A biological safety cabinets and therefore it would not be appropriate to assess these areas in the same trend analysis as Class C preparation areas. The alarm limits should be set lower in the areas that serve as background for Class A environments, as the impact of field trips is higher in these areas due to the higher potential for contamination of the aseptic areas.

This in turn means that counts in these areas are generally lower due to tighter contamination controls.

Therefore, it is not appropriate to trend these different areas in the same way. These areas and locations should have been defined in the EM plan and identified and qualified during validation of the EM program.

Analysis of your trends

In a busy pharmaceutical manufacturing environment, identifying and analyzing trends can be challenging—many samples are often collected each day and multiple analysts may be reading EM samples at the same time or over multiple days. It can therefore be very difficult to quickly pick up on an emerging trend until all the data has been reviewed, entered into a data storage system and then analyzed for trends.

For example, if a trend is triggered after two consecutive violations of the alarm limit, and a sample point is monitored infrequently, it is easy to miss that trend. If the analysts read hundreds of samples per day, or if two different analysts read the samples on different days, it would be impossible for the analysts to remember that the alert limit was exceeded from a previous sample.

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Situations like this make it very difficult to react immediately to a trend, especially when there are delays in data entry, e.g. B. by waiting for identification results or lack of resources.

SmartControl helps here – data is entered directly into the software and immediately analyzed by the software. Trending rules can be set by the user and if a trending rule is violated, the user will be notified immediately. Even when thousands of samples are entered into SmartControl, the analysis is performed automatically and notifications can be sent to the appropriate managers or supervisors to initiate an immediate investigation.

SmartControl even makes investigating these trend breaks easy – graphical analyzes of personnel, locations or contamination can be generated instantly for inclusion in reports, and these can be generated on a recurring, consistent basis to ensure everyone has the same information.

Trend analysis should be performed regularly and consistently to ensure changes in the facility are identified. SmartControl can help ensure this happens immediately and can also generate periodic trend reports, making reviewing large amounts of data easy for facilities of all sizes.


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