Cleanrooms are engineered to maintain strict environmental controls to shield sensitive biopharmaceutical processes from microbial threats. This includes control and monitoring of airflow, temperature, humidity and levels of viable and non-viable particles. Yet, even the most rigorously maintained facilities are vulnerable to forces beyond their control. Environmental issues can occur at a moment's notice - such as flooding, HVAC failures, power cuts or other infrastructure breakdowns that can rapidly compromise cleanroom integrity, introduce the risk of contaminants and breach critical thresholds.

This article explores how such events can impact cleanroom integrity and highlights a real-world example of how being well prepared led one pharmaceutical manufacturer to a swift, science-driven restoration to operational safety by performing a bio-decontamination of their facility following an environmental disaster.

Environmental issues which can impact cleanroom integrity:

1. HVAC System Failures
   HVAC systems are the backbone of cleanroom environmental control. They regulate airflow, maintain pressure differentials and filter particulates and microbes. A failure is often unpredictable, whether due to power outage, mechanical breakdown, or filter compromise. This can lead to:
   • Loss of positive pressure, allowing unfiltered air to enter from surrounding areas.
   • Increased humidity, fostering mould and bacterial growth.
   • Recirculation of contaminated air if ductwork or filters are compromised.
2. Flooding and Water Intrusion
   Water is a potent vector for microbial contamination. Flooding from storms, pipe bursts or drainage failures can introduce:
   • Waterborne pathogens such as Pseudomonas, Legionella and fecal coliforms.
   • Organic debris that supports microbial growth.
   • Moisture retention hidden in walls, floors and equipment, creating long-term contamination risks.
3. Equipment Failures
   Malfunctioning incubators, autoclaves, or cleanroom machinery can:
   • Create stagnant zones with poor airflow.
   • Allow temperature or humidity to drift outside validated ranges.
   • Harbor microbial growth in inaccessible or unmonitored areas.
4. Structural Breaches
   Cracks, leaks or damaged seals in walls, ceilings or doors can compromise the cleanroom envelope. These breaches may:
   • Allow ingress of unfiltered external air.
   • Introduce particulates and spores from adjacent uncontrolled environments.
   • Disrupt airflow patterns critical to contamination control.
5. Human Error During Emergency Response
   In the chaos following a disaster, emergency repairs or cleanup efforts may inadvertently:
   • Bypass contamination control protocols.
   • Introduce non-sterile tools or materials into a controlled environment. Fail to properly isolate contaminated zones, leading to cross-contamination.

These risks highlight the importance of rapid assessment and intervention following any environmental disruption.

Case Study: Implementing Bio-Decontamination for Flood Recovery in a Pharmaceutical Facility

A severe storm surge struck the northeast coast of the UK, flooding a large pharmaceutical production facility. The floodwaters included both seawater and "black water" from the sewer system, posing a significant contamination risk.While upper-level cleanrooms thankfully remained unaffected by the flooding, their operational viability depended on transit routes through the flooded lower levels. Without intervention, the risk of cross-contamination was inevitable.

Microbiological Risk Assessment

The presence of black water introduced a high bioburden risk through opportunistic pathogens. The challenge was not just surface cleaning but ensuring the elimination of invisible microorganisms throughout the facility, including difficult to reach areas such as elevator shafts and tall ceilings. All voids where microbes could linger needed attention.

Bio-Decontamination Strategy

After water removal, a full dehumidification and manual clean of the facility was performed. This was followed by engaging Ecolab’s Bioquell RBDS (Rapid Bio-Decontamination Service) team to perform a rapid, comprehensive bio-decontamination using Hydrogen Peroxide Vapor (HPV) to deliver a 6-log sporicidal kill on exposed surfaces¹.

A plan was devised in which the facility was segregated and critical areas subsequently prioritized for bio-decontamination to ensure that contaminants from the water were eliminated from especially hard to reach areas like elevator shafts and trapped voids of air. Following bio-decontamination to grant clean access to unaffected areas, the remainder of the affected facility was bio-decontaminated following a strategy that allowed other remediation works to continue immediately outside the areas being treated. Some specialist warehousing areas were also included in the scope and in total, an area with a volume of 20,000m³ was bio-decontaminated.

Given the scale of the project and the need to get biological contamination under control, Ecolab’s RBDS team was able to offer advice on all aspects of the project to:

• Prevent further unwanted spread of contamination.
• Ensure that the manual cleaning processes optimised the facility for bio-decontamination.
• Ensure the efficient use of Bioquell’s HPV technology while reducing the risk of cross- (or re-) contamination.

As time pressures were extremely important, Ecolab placed a team on the customer's site so that as each area became available, the bio-decontamination could start immediately. A large cache of equipment was also transported to site so that everything from small rooms to large warehouses could be treated with little notice.

After bio-decontaminating a large warehouse area (5000m³ with a 12m ceiling height) the focus was switched to the bio-decontamination of the elevator shafts to allow materials access to the upper, clean floors. The RBDS technicians placed the HPV generators in the base of the lift shaft, completely sealed the shafts and, using directional ‘nozzles’ and powerful fans, ensured that hydrogen peroxide vapor was distributed around the whole shaft (both below and above the elevator car). This was demonstrated by achieving 6-log deactivation on all Geobacillus stearothermophilus biological indicators and chemical indicators placed inside the area. Following the successful bio-decontamination of the elevator shaft, the elevator car was reactivated and decontaminated as a separate enclosure.

With access granted, and the elevator back into operation (without the risk of cross contamination), focus switched to large production areas which were now dried and cleaned to a stage where it would be appropriate to use Bioquel’s HPV process. This final production area consisted of a single zone 6,000m³ in volume which was bio-decontaminated as one discrete area within 20 hours.

Results and Recovery

Within 10 days of the flood, the production facility was back within its operational guidelines for permitted contamination levels – measured by air sampling and surface swabbing. From the moment of initial contact until facility recovery, the entire process took only 8 days and covered 20,000m³ in 15 separate zones. Despite working in recently flooded areas with numerous other contractors nearby, all bio-decontamination cycles were conducted safely and achieved a validated 6-log bioburden reduction of Geobacillus stearothermophilus biological indicators.

Lessons Learned: Proactive Preparedness and Rapid Response

This case underscores several key microbiological principles:

1. Environmental thresholds matter: Cleanrooms are vulnerable when humidity, airflow, or pressure differentials are disrupted.
2. Contamination is not always visible: Microbes can persist in air voids, ductwork, and behind surfaces.
3. Rapid intervention is critical and requires preparation: Delays in tackling the contamination increase the risk of microbial spread and product compromise. Without having an emergency action plan in place, turnaround time could have increased dramatically for this pharmaceutical manufacturer, delaying production even further.
4. Validated bio-decontamination can provide relief: HPV offers proven efficacy, detailed reporting and validated results while reaching spaces manual disinfection may not.

Conclusion: Building Resilience in Cleanroom Operations

Environmental disasters are unpredictable, but their impact on cleanroom integrity can be mitigated with science-based bio-decontamination strategies. Microbiologists play a vital role in assessing risk, guiding remediation and validating bio-decontamination efforts.

Facilities should incorporate disaster response protocols into their contamination control plans, including partnerships with bio-decontamination experts and suppliers, and should perform routine risk mapping of vulnerable zones. As this case demonstrates, with the right tools and expertise, even the most severe breaches can be resolved – restoring microbiological control and safeguarding production.

1. Bioquell HPV-AQ 35% hydrogen peroxide approval written into European law – Biocidal Products Regulation (BPR, Regulation (EU) 528/2012))↵