Environmentally friendly disinfection of a pharmaceutical cleanroom

With the growing need for microbiological clean environments, room disinfection is becoming ever more critical.

Many pharmaceutical, biotech, cosmetic and other microbiology-sensitive industries are dependent on microbiologically clean areas for both production and R&D. Microbiologically clean environments are essential for a variety of purposes: manufacturing, employee safety in research environments, patient safety in hospitals and contamination control. Additionally, some industries are governed by regulatory bodies that impose standards for microbiological cleanliness and set requirements for regular, certified biodecontamination of certain areas.

Typical biodecontamination procedures include:

• annual shutdown biodecontamination
• commissioning biodecontamination
• decommissioning biodecontamination of areas used for pathogen work
• eradication of problematic microorganisms from production lines and laboratory areas
• emergency biodecontamination for accidental release or spillage of microorganisms
• regular cleanroom biodecontamination
• isolator and pass-through biodecontamination

A large pharmaceutical plant in the US Midwest wanted to achieve a higher level of system automation and integrity as well as improve its spore-kill level during disinfection. The plant had used two different types of disinfection, H₂O₂ (hydrogen peroxide) and formaldehyde, and was not satisfied with either approach. Operating personnel decided to explore alternatives in order to achieve their requirements more effectively.

Dry fog technology

After researching the available alternatives, the plant decided to investigate a dry fogging approach. The technology selected - the Minncare Dry Fog (DF) System - produces very fine droplets of disinfectant that are dispersed throughout a room. The disinfectant used by this system is a proprietary cold sterilant solution consisting of a stable mixture of peracetic acid and H₂O₂ that is bactericidal, fungicidal, virucidal and sporicidal.

Biocides	Gram - bacteria	Gram + bacteria	Myco- bacteria	Spores	Moulds	Yeasts	Virus
Peracetic acid	+++	+++		++	++	++	++
Alcohols	++	++		0	++	++	+
Alcohol 70%	++	++	0	+	+	++	+
Glutaraldehyde	+++	+++	++		+++	++	++
Quaternary ammonium	+++	+	0		+	+	+
Hydrogen peroxide	+++	+++			+	+	0
Chlorine	+++	+++	++		++	++	++

Table 1 compares the activity levels of peracetic acid, H₂O₂ and other biocides in treating common contaminants. (Guyader 1996.)   

During the DF process, the humidity level of the room to be treated is first raised to 80%. Then the dry fog solution is evenly and completely dispersed in the room. A single DF unit can disinfect rooms up to 1000 m³. Figure 1 shows a sample DF system set up for a 240 m³ room.

Figure 1: Dry fog room layout example.

The disinfectant droplets are only 7.5 µm in diameter, so they bounce off solid surfaces and resist the excessive condensation, possible corrosion and surface wetting commonly associated with other fogging or manual cleaning procedures. The droplets eventually evaporate and the vapour penetrates normally inaccessible areas resulting in a more thorough disinfection process. The chemical is fully biodegradable, requires an extremely short process time and is much less corrosive than aldehyde-based materials.

Autosan room test

The immediate area of concern for the pharmaceutical plant was the autosan (automatic sanitisation) room, a staging area for disinfection of non-product contact parts and large equipment heading into the cleanroom. The plant was using a solution of H₂O₂ sprayed via wet/fogging nozzles for sanitisation in the autosan room. The solution feed was set up in the staging chamber just outside the room with a line penetrating the wall to the nozzle. While the system was consistently achieving a 3-log or greater reduction of bacterial spores with the H₂O₂ method, having to wet all of the surfaces led to concerns over the potential for corrosion and material compatibility issues. Also, handling the low-pH active H₂O₂ required extensive safety precautions and the overall method’s efficiency in terms of total dispense, exposure and exhaust timing was less than desirable. A test procedure was arranged for the autosan room, which was 27 m³ in size. Two sets of tests were run using two different levels of DF exposure time. The goal of the plan was to demonstrate a point at which the DF achieved a 4- to 6-log reduction on biologic indicator (BI) spore strips. The use of bacterial endospores, typically Geobacillus stearothermophilus, as a BI to measure the success of decontamination is a common standard. Overall results of testing showed that regardless of the concentration of the dry fog disinfectant and in as low as 15 minutes of contact time, a >6-log reduction was achieved on all BI indicators. Further, even with a reduced exhaust time versus the pre-existing process, issues with corrosion and residual clean-up were eliminated.

API production area test

Based on the results of the DF test in the autosan room, the plant decided to investigate using it in active pharmaceutical ingredient (API) production areas. Previously, these areas were being disinfected - when returned to an aseptic state after facility shutdown - using a formaldehyde fog/spray. The procedure involved evacuating the building, remotely initiating spraying and quarantining the building for several hours. Afterwards, ventilation would be reintroduced and an additional one to two days were required to bring the formaldehyde concentrations back to the very low levels required by procedure, finally allowing re-entry.

Furthermore, after the building was deemed safe for re-entry, extensive personnel protective equipment and significant monitoring were required to ensure that operators were not exposed to detectable levels of formaldehyde during subsequent manual cleaning and sanitisation activities. The test procedure with dry fog consisted of disinfecting a two-storey area of the building that included a stairwell and elevator shaft. The dry fogging unit was positioned on the floor near the centre of the room. Twelve 3-log BIs and twelve 6-log BIs were placed around the room and on the ceiling. After a standard diffusion time and a hold time of 1 hour the HVAC was reintroduced.

The disinfectant level dropped to a safe re-entry point in less than 15 minutes, saving one to two days that would have been lost using formaldehyde treatment. Subsequent BI results showed an overall spore reduction of six logs at the monitored locations, a level of sanitisation which easily surpassed the protocol requirements.

Conclusion

As a result of the demonstrations, the plant decided to use the DF technology for disinfection procedures. Some of the benefits noted by the company were:

• More reliable and better efficacy (6-log reduction)
• Replacement of a hazardous chemical previously used (formaldehyde)
• Reduced downtime during the treatment procedure (typically 3 hours or less)
• Greatly reduced downtime for venting (compared to formaldehyde)
• Reduced procedure costs (compared to either H₂O₂ or formaldehyde)
• Significantly reduced corrosion
• Fewer material compatibility issues
• Elimination of sanitisation agent residue
• Elimination of post-sanitisation manual clean-up

Those benefits ultimately translated into a better, faster, safer and more environmentally friendly process that reduced labour and lowered operational costs.