Manufacture of Sterile Products — Annex 1 Particle Counting Considerations

August 25, 2023 is the deadline to comply with the newly published update to EU GMP Annex 1. Having increased from 16 pages to 58, there is obviously a lot for pharmaceutical manufacturing facilities to consider and address in a short amount of time — including particle counting for both classification and monitoring in cleanrooms.

Classification in Pharma Cleanrooms

The limits for particles that are 5 µm or larger have been updated to match those stated in the ISO 14644-1 cleanroom standard. This includes no longer specifying limits in Grade A, neither at rest nor in operation, and Grade B at rest. However, it does note: “Classification including 5 µm particles may be considered where indicated by the CCS or historical trends.” Many facilities will likely consider doing this since the monitoring of 5 µm particles remains a requirement. The limit for Grade A has been changed however, from 20 per cubic meter to 29 per cubic meter. The impact of this, based on the equation in ISO 14644-1, is that the minimum sample volume is reduced from 1 cubic meter to 0.7 cubic meters. This could prove to be a significant time savings when sampling Grade A areas with numerous sampling locations.

Particle Monitoring in Pharma Cleanrooms

Besides the changes to the 5 µm particle limits described for classification, there are some additional changes for total particle monitoring. It is now clearly stated that Grade A areas are to be monitored continuously with a suitable sample flow rate of at least 28 liters per minute. Previously, the requirement was vaguely stated as frequently, with the option to use a manifold system. 

Sample Tubing for Particle Counting in Pharma Cleanrooms

Whereas the previous version of EU GMP Annex 1 stated that tubing length and radii of bends should be considered for particle loss, the new version now states that the tubing should be qualified. Guidance provided states: “Tube length should typically be no longer than 1 meter unless justified and the number of bends should be minimized.” It also declares: “Portable particle counters with a short length of sample tubing should be used for classification purposes.”

Portable Particle Counters Engineered for Annex 1 are Key

The TSI AeroTrak^™+ Portable Particle Counter A100 Series is engineered to meet the requirements of the new Annex 1, and to make particle counting easy. The new updated limits have been included, with the ability for the user to define Grade A and Grade B at rest limits. The portable particle counters can generate classification reports that automatically determines that all of the Annex 1 sampling requirements have been met. The TSI AeroTrak+ Portable Particle Counter A100 Series is capable of continuous monitoring in pharma cleanrooms, either as a stand-alone instrument, or as a fully integrated remote particle counter when used with TSI Facility Monitoring Software (FMS). Any concerns with particle loss in tubing can be eliminated by using the direct mount isokinetic sampling probe. Whether for pharmaceutical cleanroom classification or monitoring, the TSI AeroTrak+ Portable Particle Counter A100 Series makes Annex 1 compliance easy.

Learn More

Watch video to learn more about the Annex 1 ready AeroTrak+ A100 Portable Particle Counter.

Content Contributor
Mike Dingle, Product Specialist, TSI Contamination Control