FAQ - Pharmaceutical/Life Sciences Particle Counting

Particle Sensors Used for Cleanroom Monitoring

Question
We are filling an opthalmic product under ISO 5 and measuring particle counts every minute. Occasionally. particle counts are going beyond limits (more than 100 particles) .Automatically, it comes down subsequently. Does a rise in particle counts means the system has gone out of control? What should be done to avoid this? How do we address such incidences so that there will not be any 483?

Answer

An event which exceeds operational limits must be deemed to be a point of failure. This is a fairly critical statement and has a first part - how did you define your operational limit? The correct method is to establish a risk assessment based upon acceptable tolerances for product quality. Environmentally, this would mean - what is the acceptable limits for aseptic manufacture your facility will support while still producing sterile product?

The best way to establish this that during the media fill, turn off alarm limits. Run the media fill in accordance with your SOP and perform finished product testing. If the product meets expected tolerances for media fill (EU GMP 1 / 10,000) then whatever the environment and operators were doing during that period would meet requirements.

It is expected that any particle event would not be of any significant duration and of any significant magnitude. Therefore, it would be prudent to set the alarm limit for the 0.5 micron size to allow for 2 events occurring together to create an alarm but a single event would be deemed to be of a risk, so short lived that it can be considered negligible. Of course, to support this, you must have data proving it - and we are back to the media fill.