Monitoring locations should be risk based
The locations for environmental monitoring should be selected according to a risk assessment. This needs to account for potential hazards.
For example:
- Where do personnel congregate?
- What types of equipment could generate particles?
- What is the flow of people and equipment coming in and waste out?
- Is there a water source?
Such hazards should be evaluated for their respective risks. After any controls have been introduced, higher risk areas become targets for environmental monitoring.
Risk assessment is concerned with the process captured in Figure 1.
Figure 1: Risk flow diagram for environmental monitoring
Sampling
As well as the location for samples, there are other sampling related considerations.
It is useful to have a rationale for each of these:
- What sampling technique will be used?
- When should a sample be taken?
- How often should sampling be performed at each location?
- How long should sampling be for? (e.g. settle plate exposure)
- What is an appropriate sample size? (e.g. active air sampler volume)
Data needs to be trended
Data should not simply be collected - it is important to trend data and assess the direction. Data should be studied below the alert level as this can provide an indication of future excursions.
There are different approaches for data trending, although graphical representations are often clearest.
Individual results are rarely significant
Aside from the assessment of aseptic processing (where any Grade A count is of potential concern), individual results are rarely sufficient to give the true picture. Assembling a series of results at meaningful time intervals for specific locations is invariably necessary for understanding what is happening.
Being able to understand and discuss the overall picture is key.
Alert and action levels are needed
Alert and action levels are necessary to contextualise the data. These should be set with some reference to historical data (a data set of sufficient size to be representative and one that has taken account of seasonality).
Alert and action levels can be numerical or based on some form of contamination frequency interval.
Alert levels indicate a potential drift from the norm. A position will be required as to how many drifts from the norm signal a concern e.g. three consecutive breaches. An action level is a clear breach of acceptable conditions and this normally requires an investigation and some form of remediation.
Alert levels should fluctuate
It is expected that alert levels will vary across time. There are many variables that can affect data. It is sometimes required that a proposal is made to increase the alert level. This can be justified on the basis that:
- The facility remains well controlled
- Action will still be taken when action levels are exceeded
- If it is a non-sterile facility, the products may not support microbial proliferation in relation to the types of microorganisms regularly recovered from the environment
Appropriate alert levels can save resources by removing needless investigations into excursions of limits that have been set too low, enabling resources to be reassigned to higher risk activities.
Statistics
Although statistics can be useful for limit setting and for trending, it is important not to blindly use statistics without understanding what the technique is and what the result means. It is also important not to seek to dilute the extent of any repeating contamination or any contamination in a key area (contamination at Grade A is always a risk no matter how it is expressed).
Microbial species
Environmental monitoring data is not simply about numbers. Regular characterisation of the microbiota is important as this can signal drifts from the norm. This is especially important when the drifts reflect increases with spore forming bacteria or fungi detected. This can signal cleaning and disinfection or item transfer concerns.
Answering questions
Periodic review of the data can aid understanding. Questions could include:
- Are we in control?
- Where we have excursions, was the system able to identify the contamination sources?
- Are we taking appropriate action to reduce the likelihood of contamination occurring?
- Do we need to change any personnel practices?
- Do we need to alter the cleaning or disinfection regime?
- Do we need to make any changes to the monitoring programme
- Do we have sufficient information to understand the effectiveness of any specific actions?
- Should monitoring frequencies be increased or decreased?
In answering such questions, bear in mind that within a pharmaceutical and healthcare facility a level of cleanliness is expected. It is not appropriate to justify poor practices and hygiene. The target should be for continued improvement.
