An environmental monitoring (EM) program is used to monitor the controls designed to minimize the risk of microbial and particulate contamination of a manufacturing facility, its associated processes and ultimately the final medicinal product. EudraLex Volume 4 Annex 1 “Manufacture of Sterile Medicinal Products” [1] and FDA’s Guidance for Industry on Sterile Products Produced by Aseptic Processing [2] provide guidance regarding the EM program and the data it generates. Pharmig, a nonprofit professional organization for individuals involved in microbiology in various sectors, organized two conferences in India [3] focused on having an effective and meaningful . Presentations were given on various topics, including the design and data interpretation of an EM program and how to conduct a structured investigation in case of a data excursion.
The conference included regulatory experiences and observations made by regulatory bodies in relation to EM. The key points presented and discussed include:
- Fundamentals of an Environmental Monitoring program
The speaker who is an industry expert noted that samples are not taken from the right location, the data generated is meaningless. Cleanroom design and process knowledge are keys to designing a program that is based on the principles of Quality Risk Management capable of generating meaningful data in support of batch disposition. EM sampling should provide an overall status of the cleanroom and its processes, where the results of the different sample methods give a total picture. - Environmental Monitoring Methods
In a separate presentation from a different expert it was mentioned that utilized in a company’s EM program should aid in understanding contamination sources and the associated risks. Methods are expected to be qualified using calibrated equipment and clear procedures with instructions to ensure consistent performance and minimize variability associated with sampling. Each sample method has its own characteristics, benefits, and limitations. Annex 1 expectations include that sampling methods are fully understood and the recovery efficiency of the sampling methods selected is supported by data.
Another key takeaway was that using alternative methods can result in faster results but these are often not reported in Colony Forming Units (CFU) and do not always have the ability to identify the micro-organism recovered. This can be a limitation when trying to identify the potential root cause of contamination. - Environmental Monitoring Data
A third presenter with expertise in the field of environmental monitoring emphasized that sampling results are often not meaningful and EM data should not be used as a batch release tool on its own, but rather as supportive data for the overall level of sterility assurance for a manufactured product. Instead of focusing on a single result, trending of EM data is key and data are to be interpreted in a correct manner. Procedures should clearly describe what the company defines as an adverse trend and must include information about the expected level of investigation and actions to be taken when an adverse trend is detected. This is not limited to trending of numerical results, but also includes trends in the type of micro-organisms as part of overall cleanroom performance.
References
- EudraLex Volume 4 Good Manufacturing (GMP) Guidelines – Annex 1, Manufacture of Sterile Medicinal products (2022) . Accessed through: https://health.ec.europa.eu/system/files/2022-08/20220825_gmp-an1_en_0.pdf
- FDA Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice (2004). Accessed through: https://www.fda.gov/media/71026/download
- Pharmig India – Best practices in Environmental Monitoring (2024). Accessed through: https://www.pharmig.org.uk/en/product/pharmig-india-best-practices-in-environmental-monitoring/
