Environmental monitoring in pharmaceutical cleanrooms is an essential component to ensure product purity and compliance with stringent regulations.
A robust monitoring program allows control of viable and non-viable particulate contamination levels, identifying any deviations that may compromise product quality and process integrity.
Table of Contents
Non-viable Particulate Matter Sampling Strategies
The control of non-viable particles is essential, since they can act as vectors of microbiological contamination and directly affect the sterility of the products. Monitoring should be carried out both at rest and in operation. Sampling points should be based on a formal risk analysis, considering critical areas and those most likely to generate or accumulate particles.
In A and B classification zones, continuous particulate monitoring is required during critical processes. For C and D zones, the frequency of monitoring in operation will depend on the nature of the activities, but the cleaning recovery time, generally around 15-20 minutes, should always be verified.
Airborne particle counters are used to assess air quality and determine the quantity of particles according to their size. In pharmaceutical environments, these instruments are crucial to ensure compliance with the limits specified in regulations such as ISO 14644 and EU-GMP.
- Serial selection systems or dedicated remote counters are recommended.
- Highly sensitive portable counters can locate sources of particulate emissions.
Viable Particulate Sampling Strategies
Viable particle monitoring complements non-viable particle monitoring by focusing on the detection and quantification of microorganisms present in the environment. In aseptic production, frequent microbiological monitoring is essential.
Various sampling techniques are used, among which the following stand out:
- Volumetric air sampling: Sucks a known volume of air through an impactor or filter, retaining viable particles that are then cultured.
- Sedimentation plates: Nutrient agar plates exposed for a certain time to collect viable particles by gravity.
- Contact plates: Pressed onto equipment surfaces or personnel clothing.
- Gloves: Finger impressions are made on agar plates to monitor hand hygiene.
The frequency and location of sampling should be justified by risk analysis and be representative of the working conditions. Recommended limits for microbial contamination in operation are specified in standards.
Management of Alarms for Limit Exceedances
It is essential to establish warning and action limits for particles and microorganisms, based on historical data and regulatory requirements according to the degree of classification.
When an alert limit is exceeded:
- Investigate possible causes.
- Implement corrective measures to avoid future deviations.
When an action limit is exceeded:
- Exhaustive research.
- Implement immediate corrective and preventive actions.
- Repeat cleaning and disinfection.
- Review operating procedures.
- Check the HVAC system.
- Evaluate the impact on product quality.
Detailed documentation of all deviations and actions taken is crucial to meet regulatory requirements and demonstrate environmental control.
Conclusion
Effective cleanroom environmental monitoring is a continuous and dynamic process that requires strategic planning, appropriate methods and equipment, and rigorous alarm management.
By implementing sound strategies for the control of viable and non-viable particles, and acting proactively in the face of deviations, the pharmaceutical industry can ensure the production of safe and effective drugs.
A thorough understanding of monitoring principles and regulatory compliance are pillars for maintaining cleanroom integrity and pharmaceutical product quality.
