There is a common industry misconception that 1 m³ particle monitoring should be performed. This is not stated anywhere. Unfortunately, the original EU GMP text for particle counters was confusing and frequently misinterpreted.

The guide is for continuous particle monitoring in Grade A and immediate Grade B areas using an insitu particle counter, such as the Airnet® or IsoAir® PLUS particle sensors. This is because the risk of contamination of finished product is very high and the greatest risk, the operator, is in close proximity. The operator is not only the greatest risk posed to product but also a random generator of those particles. These are not all inert particles; some will be viable, which poses an even greater risk to the finished product. Since we cannot control the risk, we must measure it. If it is in excess of proven acceptable limits, then the particle counter system must alert the users. How quickly the facility monitoring system alarm should alert the users, is dependant upon the risk.

Analysis of risk can be considered as how resilient the filling operation is to potential particle contamination events while still able to protect product. If the system is very robust (Isolator, RABS) then an event has a relatively low risk of contamination. If it is an ampoule line with curtain protection then small deviations could have a greater impact. No particle counter solution will fit all applications as all risk is variable; considerations such as what gowns are used, what under garments are supplied, air changes / hour rate, number of personnel in room…..etc. are all important factors.

Particle Measuring Systems' Recommended Particle Counter System Set up for a Grade A Zone

(Download the pdf for images walking you through these steps.)

Step 1: Set all values in the facility monitoring system to m³

Step 2: Set the 0.5 µm particle counter alarm channels (1 = alert, 3 = alarm) to 1625 and 3250 n/m³. (These values are temporary until the real values are discovered from the process.)

Step 3: Set the particle counter alarm level 1 (alert 0.5 µm) to react on a frequency of 2:2 events. So two consecutive events will trigger an alert = Orange light.

Step 4: Set the particle counter alarm level 3 (alarm 0.5 µm) to react on a frequency of 3:3 events. So three consecutive events will trigger an alarm = Red light.

Step 5: Set the 5.0 µm particle counter alarm channels (0 = alert, 2 = alarm) to 71 and 35 n/m3. (These are identical, but we will use a different frequency to determine risk.)

Step 6: Set the particle counter alarm level 0 (alert 0.5 µm) to react on a frequency of 2:2 events. So two consecutive events will trigger an alert = Orange light

Step 7: Set the particle counter alarm level 2 (alarm 5.0 µm) to react on a frequency of 3:10 events. So three consecutive events will trigger an alarm = Red light.

This rationale allows you to respond quickly to 0.5 µm particle events but not receive particle counter alerts for nuisances - very short lived events that may exceed the alarm limit, while posing little threat. It also allows you to look at the 5.0 µm particle counter alarm as an event-based approach rather than one of number of particles. ISO14644-1 gives a demonstration that as 5.0 µm levels rise, a corresponding 0.5 µm will happen [(0.1 / D) ^2.08]. Therefore, if it is of environmental importance you will know as it will also trigger the 0.5 µm channel. If it is of microbial importance it will trigger the 5.0 µm channel.

After three to six months of using this method, you should look back through the finished product quality records, viable sampling records, and the number of particle counter alarm events and again apply the guidance for the particle counter system against these findings.

It should be noted that the that 1m³ value is to be used for certification purposes only using a portable particle counter, such as the Lasair® II or Lasair III particle counters, which have been designed specifically for the purpose of routine testing.

Author Mark Hallworth
Pharmaceutical Business Manager
Particle Measuring Systems

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