22.01.2019 | LOGFILE Feature 03/2019

Excerpt from the GMP Compliance AdviserChapter 10.E


Microbiological Monitoring: Actions when levels are exceeded

5 min. reading time | by Hanfried Seyfarth


Actions to be taken when levels are exceeded and the related responsibilities should be described in detail in a separate SOP. The Monitoring SOP should include a reference to this SOP.

If levels are exceeded, documenting the results is not enough. It is necessary to determine the reasons why the levels were exceeded, to evaluate the impact on the quality of the medicinal product and take appropriate actions based on these findings. All of the activities carried out during this investigation must be documented. An investigation plan should be put in place and an investigation report created when the investigation is complete.

Investigation plan

The following should be checked during the investigation:

  • results
  • scope of the problem
  • impact on the medicinal product
  • necessity of quarantine measures
  • follow-up investigation

After the investigation, the following should be carried out:

  • notification and involvement of QA
  • determination of the cause, e.g. a sampling error
  • determination and implementation of corrective and/or preventive measures (CAPAs)
  • evaluation of the effectiveness of the actions (efficiency review)

It must first of all be clarified whether the deviation was caused by a lack of production hygiene or whether an error was made in the laboratory.

If an error was not made in the laboratory, the effect of the deviation on the product quality is extremely important. Deviations in the personnel lock, for example, are generally not relevant to the medicinal product. If a deviation does affect the medicinal product, the product should be placed in quarantine. If the deviation is relevant to the medicinal product, testing must also be carried out to clarify whether the product quality is in fact being negatively affected.

The PDA Technical Report 13 (Revised): Fundamentals of an Environmental Monitoring Program (2014) contains a useful summary of actions to be taken when deviations occur (see Figure 1). Although it applies primarily to sterile working environments, the approach taken can also be used in facilities where non-sterile preparations are manufactured and filled.


Figure 1: Corrective actions if levels are exceeded (PDA 2014)

It also makes sense to create a checklist for detecting the causes of errors as suggested by Gingsbury1 to ensure that nothing is forgotten during the process.

If necessary, additional testing should be carried out to discover the source of the microorganisms. If the action level is exceeded, the microorganisms definitely need to be identified. This normally provides information about the source of the microorganisms. When the corrective actions have been taken, appropriate examinations should be carried out to show that the actions taken have been successful and the area and/or process is once again under control.


Investigation report

When the investigation has been completed, an investigation report must be created that documents the following:

  • tests carried out and their results
  • cause of level being exceeded
  • corrective actions
  • management review
  • notification and, if applicable, refresher training for affected personnel
  • preventive actions, if applicable

  1. Gingsbury, K., Environmental Monitoring Investigations in: Moldenhauer J. (ed.)
    Environmental Monitoring – A Comprehensive Handbook, vol. 2, pp. 137–231, PDA Bethesda, Davis Healthcare International Publishing River Grove (2005)

This text is an excerpt from the GMP Compliance AdviserChapter 10.E.

Hanfried Seyfarth


Hanfried Seyfarth, PhD
E-Mail: seyfarth-bc@t-online.de

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