By Crystal M. Booth, PSC Biotech
Environmental monitoring (EM) trending is an essential component of the EM program and can be used to evaluate the overall health of the facility in terms of microbial control. EM trending should be clearly defined within the company to ensure that the data is evaluated consistently. Part one of this series looked at the regulations and guidelines around EM. This part will discuss tools and best practices for using the trends to ensure that an efficient environmental monitoring program is established.
There are many different methods and tools for performing EM trending. However, different does not mean that it is wrong. For example, trending personnel data can be done by sorting the data either by the individual operator or across all operators performing similar operations or functions. The determination of which data set to use will depend on what information is anticipated to be gained.1
Regarding tools, trending can be performed manually with the use of applications like Microsoft Excel or with electronic systems such as MODA, NOVATEK EM, or laboratory information management systems (LIMS), to name a few. Before implementation, all database applications used should be validated or qualified for specific software applications.2 Graphs, such as histograms, can be generated from these applications in order to provide the data in a pictorial format. Histograms or tables characterized by a number of data points that fall within a common frequency are valuable tools.2 These graphs can be used to easily explain complex EM data to management. The graphs can be useful in proactively identifying potential problematic areas, proactively correcting microbial contamination, and determining if the cleaning and disinfection program is working effectively.
For the EM data to be useful, the data should be grouped and sorted in strategic ways to obtain a clear picture of the microbial state of the facility. Each area (or area type) and accompanying data set must be viewed as distinct.2 For instance, all ISO 7 areas can be grouped together for trending if all the ISO 7 areas are used in a similar fashion for manufacturing.1 When deciding on how to collect and trend EM data, keep in mind that the EM program and subsequent trending of the data should be geared toward the needs of the facility and the information that is sought after in the EM trending.3 Trending data may also be used to monitor the microbial flora of the facility, seasonal trends, and sources of contamination.
Environmental Monitoring Best Practices
Firms must establish alert and action limits with their environmental monitoring data. There are many sources that provide action limits for environmental monitoring. Some of these sources include the Annex 1 of the European Union’s GMP guide, ISO 14464-1, and USP <1116>. Alert levels for new companies are typically established at 50% of the action level until enough data is generated to statistically calculate the alert limits. PDA TR13 provides many different options to statistically calculate alert limits. One popular method is to use a 95% confidence interval where 95% of the samples taken would be expected to pass the established alert limit.
It is important to use historical data to establish the alert levels of the environmental monitoring program so that the limits and excursions obtained will provide a better view of the control of the program and what the system can accomplish. Both alert levels and action limits should be reviewed minimally on an annual basis to ensure that the established limits still reflect the normal operating levels of the facility.1
USP <1116> describes the use of contamination recovery rates (CRRs). The USP states that when optimum operational conditions are achieved within a facility, contamination recovery rate levels typically become relatively stable within a normal range of variability.4 A change in the CRR may be a signal of a change to the state of control of the facility and this must be investigated. USP <1116> provides recommended contamination recovery rates for aseptic environments in which all operators are aseptically gowned. In areas where operators are not aseptically gowned, it may be more appropriate to establish realistic CRRs based on historical EM data.
“Once alert and action levels have been established, the limits should be periodically reviewed, as part of routine trend analysis. The alert and action levels may be revised to reflect improvements, advances in technology, changes in use patterns, or other changes.”2 Meetings should be held with quality management, also known as a quality management review, to evaluate the environmental monitoring trends along with other quality metrics and key performance indicators (KPIs). Any decisions or changes that may need to be made to the EM program or associated programs, such as the cleaning and disinfection program, should be made by experienced and qualified personnel.
Reports should be clearly written and documented in a concise logical manner to describe the EM trends. These reports should list and describe items such as applicable procedures (e.g., EM, material and personnel flow, cleaning, and disinfection), facility maps and room classifications, the EM program and samples that are taken, summary of alert and action levels, contamination recovery rates (if applicable), investigations, facility maintenance, applicable procedural changes, any graphs that were created, and comparisons to previous trends. The quality unit should review the monitoring and trend reports.2 The data needs to be analyzed and any identified discrepancies and adverse trends must be investigated.
Routine review and analysis of environmental monitoring data for trends must occur at appropriate intervals to assess the control of the facility. Management must keep up with trends and the state of operations within the facility and review the quarterly and yearly monitoring reports.2 However, the appropriate interval for trending must allow for a proper statistical evaluation to be performed. Many companies perform trending monthly, quarterly, or yearly. Whether these frequencies are appropriate depends on the amount of collected data.1
As previously mentioned, trends should be clearly defined. In general, they may include a gradual increase or decrease in the overall counts observed over time, or a change in flora or counts on several plates of a particular area on a given day. Three or more consecutive points or drifts may be a pattern or cluster formation that, if above the alert level, signals a trend requires investigation.2
Understanding the potential impact of the results generated during EM is critical to a successful environmental monitoring program.2 EM trending assists in this critical understanding and proper EM program establishment. Properly trended data helps to confirm the following:
- Regulatory compliance
- A state of microbial control
- The ability to be proactive before a problem gets out of hand.
- A graphical representation of the data that is created.
- Any problem areas in the facility can be identified.
- That the cleaning and disinfection program are working as expected.
- The monitoring of the microbial flora of the facility and seasonal trends are performed.
- A simpler means of communication of the EM data to management.
- That the sources of microbial contamination can be identified.
- Alert and action limits are properly established.
There are numerous regulatory guidance documents that describe EM trending. Warning letters and observations have been written regarding EM and trending programs. Regulators want to ensure that the facility is operating in a state of control and will ask to see the trending reports. It is imperative that management is kept informed of environmental trends and that proper decisions are made to keep the facility in a healthy controlled state. Properly established EM programs and trending reports are essential in keeping management informed of the EM data, what the EM data means, if there are any contamination issues, and of the routine microbial flora that is present in the facility.
I would like to thank my PSC Biotech colleagues AyCee Carter and J Alexander Thompson for their review of this article.
- Peacos, Paula and Marc Glogovsky (2020) Points to Consider when Designing an Environmental Monitoring Trending Program. American Pharmaceutical Review. Accessed on 24Mar2021 at https://www.americanpharmaceuticalreview.com/Featured-Articles/569210-Points-to-Consider-When-Designing-an-Environmental-Monitoring-Trending-Program/?catid=25258
- Parenteral Drug Association Technical Report 13 (2014) Fundamentals of an Environmental Monitoring Plan.
- Sutton, Scott, Ph.D. (2015) Trending in the Environmental Monitoring Program. American Pharmaceutical Review. Accessed on 24Mar2021 at https://www.americanpharmaceuticalreview.com/Featured-Articles/179364-Trending-in-the-Environmental-Monitoring-Program/
- United States Pharmacopeia (USP) <1116> Microbiological Control and Monitoring of Aseptic Process Environments. USP 43-NF38.
About the Author:
Crystal M. Booth, M.M., is a regional manager at PSC Biotech and has over 20 years of experience in pharmaceutical microbiology, environmental monitoring, and quality assurance. She obtained her master’s degree in microbiology from North Carolina State University. Crystal is a seasoned award-winning technical writer and author of Method Development and Validation for the Pharmaceutical Microbiologist. During her career, Crystal has worked in microbiology, consulting, quality assurance, CDMOs, R&D, and quality control laboratories. Crystal has developed and validated numerous microbial methods and has worked with many different product types.