Microbiological environmental monitoring of Pharmaceutical Clean Rooms

In principal British NHS manufacturing and aseptic units follow the guidance given in the EU Guidance on Good Manufacturing Practice1 (“The Orange Guide”). A further reference is the Quality Assurance of Aseptic Preparation Services2 which is widely used within the NHS. However the interpretation of this guidance as it applies to a very diverse range of facilities from large scale manufacturing units to small aseptic preparation laboratories does present challenges.

The range of microbiological monitoring includes the following;

1. Settle plates left open for a session up to 4 hours or the results normalised for a four hour exposure period.
2. Contact plates.
3. Surface swabs.
4. Finger dabs.
5. Airborne monitoring using commercially available sampling pumps and the results normalised to cfu/m3.
6. Validation of materials transfer, particularly in aseptic units.
7. Speciation of microorganisms recovered from plates etc.

Monitoring frequencies can vary, but a rough guide is given below;

1. Each working session for critical work zones (EU Class A)

• Settle plates
• Finger dabs

2. Weekly;

• Clean room settle plates
• Clean room contact plates
• Clean room swabs

3. Monthly/3 monthly more intensive monitoring with;

• Settle plates, contact plates and swabs.

4. Active air sampling

• Practice varies widely from weekly use in critical work-zones and clean rooms to 3 monthly monitoring of these areas.
• Monitoring of particular validation exercises e.g. broth fills.

Interpretation of results

In general the limits given in the Annex 1 to the Orange Guide are followed. In addition MHRA inspection guidance has indicated that an overall microbial contamination level in aseptic units should be less than 5% of all samples from critical work-zones (good units should certainly be achieving 1-2% or less). Trending of low levels of microbial contamination presents particular challenges and there is currently no specific guidance on how this is to be managed.