Particle classification and monitoring of clean rooms

The recent issue of the Annex 1 draft and the update of the ISO 14644 series have finally clarified some aspects concerning the particle classification and monitoring of clean rooms, which have often been the subject of confusion in the pharmaceutical world.

Particle classification

The limit for 5 µm for class ISO 5 (ISO 4.8) has been removed from the document. Precisely, the request to quantify particles of size ≥ 5 μm is only with respect to the limits for the continuous monitoring of non-vital particles, while their determination in the cleanroom qualification phase was removed. The latter are classified according to ISO 14644. Classification must be based on the measurement of airborne particles larger than 0.5 μm, both carried out during system operation and in shutdown conditions (5.25). The table shows the maximum concentration of particles allowed for each class of sterile chamber.

 Table: Maximum permitted airborne particle concentration during classification

Particle monitoring

The qualification (and classification) of clean rooms should be clearly differentiated from process operational environmental monitoring (5.28).

Chapter 9 of Annex 1 is dedicated to environmental and process monitoring and reports the limits allowed for the presence of viable and non-viable particles. Environmental and process monitoring programs must be an integral part of the contamination control strategy aimed at minimizing the risk of microbial or particulate contamination (9.1).

This program is typically comprised of the following elements:

1. Environmental monitoring – non viable.
2. Environmental monitoring – viable.
3. Aseptic process simulation (aseptically manufactured product only).

Table: Recommended limits for airborne particle concentration for the monitoring of non-viable contamination

A robust monitoring program requires a careful risk assessment program.

Abbonati a NCF Notiziario Chimico Farmaceutico