Ardmac Pharma Solutions Oct 2023

The Challenge and Danger of Classification at 5 Micron Particle Size and Greater in Annex 1 The presence of 5 micron and greater particles in Cleanrooms and in particular ISO 5 UDAF environments has been a source of much discussion and contention over many decades. Essentially the arguments have been over the significance and importance of the measurement of 5 micron particles as indicators of unwanted and adverse microbiological contamination, affecting product quality and ultimately patient safety. In a nutshell this blog will bring out the subtle but important differences between “Classification” and “Monitoring”. Hopefully this will give you the clarity and justification to avoid getting caught out by the law of unintended consequences and follow good science from ISO/TC 209 and the ISO 14644 family of cleanroom standards, referred to in the new Annex 1.

The bottom line is the ISO/TC 209 based scientific guidance is that 5 micron particle size measurements should not be used for formal Classification at ISO 5. Why? because it does not comply with ISO 14644- 1. However, we should not ignore the 5 micron particle size during qualification. We should use the information in an appropriate way during testing, both At Rest and in Simulated Operations. Why? Because the 5 micron particle size is required for measurement and assessment during real-time Monitoring and continuously for ISO 5 and Grade A. Of even more importance is the “Law of Unintended consequences”! In attempting to classify at 5 micron size and greater the danger is you get hooked on Clause 5.9 dealing with

airborne particle counters, where the simplistic guidance is tube lengths should typically be less than 1m (unless justified) and the number of bends should be minimised. So, if you choose to classify at 5 micron size channel size, then “This is the rock you perish upon” Why? because in ISO 5 UDAF environments (e.g. RABS and Isolators) it is not possible to meet Clause 5.9 in every respect, and at every sampling location. There is a new TR (Technical Report) coming from ISO/TC 209 and expected in 2023, that gives best practice guidance on this subject and the correct application of ISO 14644-1 for classification when measuring larger particles, i.e. 5 microns and greater, and when monitoring applying ISO 14644- 2.

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