Proven strategies for cleanroom and water system qualification success

During the webinar, Navigating Pharmaceutical Environmental Monitoring in a Changing Industry, panelists explored how in pharmaceutical manufacturing, product quality and patient safety rely on a robust framework of controls, designed to prevent contamination at every step of production for sterile products.

An aspect that requires further unpacking is how the foundation of this framework begins with the qualification of cleanrooms and water systems. The qualification serves as documented evidence that the cleanroom and water system are designed, installed and operating in accordance with specifications and meet regulatory standards. Beyond the initial qualifications, both cleanrooms and water systems must be regularly monitored to ensure they remain in a validated state.

Manufacturing qualifications

In recent years, significant emphasis has been placed on robust qualifications of pharmaceutical production systems to ensure reliable and informative ongoing monitoring. Regulations like EU GMP Annex 1 and USP Chapter <797> now require manufacturers to deliver reliable QC data that proves their ability to produce safe, effective products. Cleanroom validations encompass a broad range of activities aimed at verifying and documenting that a cleanroom meets predefined cleanliness and environmental control standards. Qualified water systems must establish comprehensive operation, maintenance and control procedures to monitor system performance, thereby ensuring a resilient and compliant water system. However, qualifications are not a one-and-done activity, as periodic re-qualifications are required to confirm continued compliance, with the frequency driven by risk, regulatory expectations and performance data from microbial monitoring programmes.

Robust qualification of the pharmaceutical production system is a crucial component of the lab’s contamination control strategy (CCS), enabling reliable monitoring programmes and evidence-based approaches to maintain a state of control.

Minimising risk by optimising recovery

When designing an environmental monitoring (EM) programme, one of the most common questions manufacturers ask is: Which incubation scheme is best for my facility? There’s no one-size-fits-all answer – both the dual plate method (two plates incubated separately at different temperatures) and the single plate method (one plate incubated sequentially at two temperatures) are valid. The general regulatory expectation is that either approach is permitted as long as you validate and justify your method. The ultimate goal is to ensure that incubation conditions are optimised to recover a broad spectrum of bacteria, yeast and fungi, thereby reinforcing a robust CCS.

Establishing and optimising sampling sites, intervals, and alert/action thresholds are critical for generating reliable data that reflect the true state of microbial control in a facility.  USP Chapter <1116> emphasises that sampling frequency must be tailored to each unique manufacturing process and supported by rigorous risk assessments. EM programmes should also evolve alongside the manufacturing environment, especially during the introduction of new processes or equipment installation. Previously mentioned webinar panelists highlighted that EM functions are a series of concentric ‘rings of control’ around a product. A breach in any ring, whether due to incubation gaps or poorly positioned sampling, can escalate contamination risks. Experts further emphasised the need for rapid, species-level data and modern technologies, such as real-time microbial ID, AI and LIMS, to shift from reactive to proactive monitoring. Effective contamination control builds on this foundation and depends on unique insights provided by microorganism identification to understand not only which microbes are present, but what risks the microbes may pose.

By combining a validated incubation scheme with a risk-based EM programme and modern microbial identification technologies, manufacturers can establish and sustain a comprehensive CCS that ensures product quality and patient safety.

Actionable microbial data depends on accurate identifications

One of the biggest challenges in microbial monitoring is the variability and unpredictability of microbial contamination. Sampling provides a single point-in-time snapshot, which may not fully represent the overall state of the environment. For this reason, species-level identification provides the manufacturer with insights into potential contamination ingress and risks posed to manufacturing environments, water systems or products. This, along with tracking and trending microbial monitoring results, allows manufacturers to be proactive in the case of a contamination event. Each facility should have a profound understanding of their resident microbiota along with an evaluation of the effectiveness of cleaning and disinfection procedures.

To help manufacturers meet the challenges of internal quality initiatives and increasingly stringent regulatory expectations, working closely with a trusted contamination control partner is crucial. Our nine globally harmonised Accugenix laboratories provide validated species-level identifications with DNA sequencing services (AccuGENX-ID) and MALDI-TOF identification services (AccuPRO-ID) when speed and accuracy are of utmost importance.

Conclusion

Robust cleanroom EMPQs and water system qualifications define the foundation of an effective contamination control strategy and ensure ongoing compliance. Within the Accugenix Customer Web Portal, manufacturers Routine monitoring, combined with species-level identifications and insightful data management tools, helps guide companies toward data-driven approaches that maximise manufacturing uptime and ensure the consistent production of safe and reliable products.

Mirna Vazquez is a Product Manager at Charles River Laboratories