Biopharmaceutical manufacturers are evaluating UV to supplement HEPA filters in filtering critical environments and reducing ductwork sanitization
By Samuel E. Speer, P.E. and Dr. Rao S. Chatty
In designing a cleanroom for biopharmaceutical manufacturing, the airflow into and out of the area is one of the critical processes of maintaining the standards of cleanliness. Continuous airflow in desired patterns will purge the “contaminated” air and replenish it with HEPA-filtered air. As such, the capital costs of the HVAC system may be up to 35 percent of the overall project costs.
The HVAC system for a cleanroom brings in tremendous amounts of airflow. Each air change is passed through a series of filters, where the filters retain the viable particulate. The filters are continuously challenged and may leak, or the entrapped microorganisms can grow through the filter media, provided there is a host substrate (dirt, dust, powders, etc.). Also, microorganisms can plate out onto the inner duct surfaces and onto diffuser grilles.
 UV installed in a cleanroom HVAC system can act as a secondary barrier against introduction of bioburden into duct, onto filters and into the cleanroom. |
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There are new and expanding solutions to reduce the amount of bioburden growing on the filters and their housings, as well as the interior walls of the ductwork, with a technology that may already exist in the cleanroom's water production facility—Ultraviolet Light (UV).
Ultraviolet light comes of age
Commercial UV light has been in existence for decades as a germicidal tool. Pioneering experiments in disinfecting air were performed in the 1920s and '30s. In 1940, Dr. William F. Fells studied UV for reducing the spread of measles in schools.
In 1989, Dr. Richard Riley and Dr. Edward Nardell prepared a comprehensive article on applying UV-C to air disinfection.1 By installing ceiling-mount UV fixtures in a room, the authors compared the impact of upper air UV equivalent to 20 air changes per hour (ACH). The rule was that one 30-watt UV fixture equaled 20 ACH in a 200 ft2 room. This installation can significantly reduce the amount of air turned over in a facility, at least from a bioburden perspective.
Low-Pressure (LP) UV-C lamps produce peak output at about 254 nanometers (nm), which is within the “germicidal” band of 240 to 280 nm. At this wavelength, the photons emitted from the lamp penetrate the microorganisms and split their DNA, which prevents replication of the microorganism. At the sufficient UV energy, the microorganisms are inactivated.
With additional energy in the UV-C, B, and A bands, microorganisms suffer from other photobiological effects, such as rupturing and leaking vital elements. The UV output of the LP UV-C lamps is 30 to 40% of their electrical input, or 9 to 26 UV watts per lamp. High-output (HO) LP lamps contain a mercury amalgam that permits a doubling of the UV output, up to 60 UV watts, or more.
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Medium-Pressure (MP), or Broad-Band UV lamps emit a wider spectrum, combining the wavelengths in the UV-A, UV-B, and UV-C ranges. Their UV output is on the order of 100 to 2300 watts. Other photobiological effects from high doses of UV-A and UV-B have been identified and validated by the authors by pilot unit demonstration, adding to the ultimate demise of the microorganism.
Standard quartz UV lamps will generate limiting amounts of ozone. The wavelength cut-off for ozone generation is around 240 nm. LP and MP lamps have standard and ozone-freequartz envelopes, where the latter glass composition filters out the ozone-generating wavelengths (<240 nm).
Depending upon where the installation is arranged, ozone may be tolerated in the duct volume, until it is decomposed before entering a production room.
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Table 1 provides a short listing of UV dose (fluence) required for 99.9 percent inactivation of common bacteria and viruses. It's important to note that the data is extracted from “plate” studies, whereas the disinfection of the same microorganism in an airstream may only require one-quarter of the UV dose.
We had confirmed this rule of thumb during our pilot demonstrations of inactivating bacillus species. Materials such as polished aluminum or certain inorganic coatings will almost double the dose within the UV zone by repeatedly reflecting the photons without adding more lamps.
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The design of a UV system for air disinfection will be based upon the amount and composition of the expected biological contamination, as well as the degree of inactivation.
UV in HVAC systems
As seen in Table 1, the minimum amount of UV dose will vary with biological species to achieve a 99.99 percent inactivation. A general rule of thumb with respect to UV dose is that an additional log change in inactivation (for example, going from 99.9 percent to 99.99 percent) will require a doubling of the UV dose, while design for only a 99.0 percent inactivation will only require one-half of the published UV dose.
To apply the required dose, the allowable volume of duct or air handler space will mainly drive the number and orientation of UV lamps. Table 2 addresses process parameters requiring consideration when calculating the final design UV dose, since they may be a de-rating issue with colder air and higher humidity.
Once the UV dose is determined for in-line disinfection, the number and type of lamps and their respective orientation is initially selected. UV dose is the product of the residence time of exposure and the irradiance (or intensity) of the lamps.
It's difficult to strictly calculate the UV dose manually, since the irradiance decreases with respect to distance from the lamp, both radially and longitudinally. Most UV lamp installations will have the lamp(s) positioned perpendicular to the airflow, traversing the cross-section of a short section of duct to maximize exposure time.
The conservative approach is to integrate the estimated dose product over a distance of 1 meter from the lamp's surface before and after the lamp(s). There may be calculation iterations for UV dose, where lamps may be added or subtracted from the design.
Opto-mechanical software can easily determine the UV dose projected within the ductwork (including light scattering up and downstream). Integration of the UV dose can let the designer optimize the quantity and configuration of the UV lamps to reduce the related energy costs of operation.
Advancements in UV Design
One of the chief advancements in UV is the evolution of ballasts—components that take line voltage and convert it into a useable form for the UV lamp. Magnetic ballasts are bulky, yet durable; while newer, electronic ballasts, are smaller and lighter, especially for MP UV lamps.
Electronic ballasts provide flexibility in UV operations. Airflow sensors can tie into a programmable logic controller (PLC) or computer, and dial in the appropriate UV output based on operating parameters, such as airflow, temperature and relative humidity. The PLC can dim the lamps during low airflow or room servicing situations, saving on energy costs.
UV irradiance (intensity) sensors are installed in the housing or duct to trend UV performance and provide indication of low irradiance and lamp failures. The PLC can also annunciate alarm conditions to a central security facility for timely response.
Air purification enhancement
Advanced oxidation is the accelerated oxidation of a material, whether an inorganic or organic compound—including natural organic matter (NOM). Advanced oxidation processes (AOPs) may include UV to initiate the reactions to generate hydroxyl radicals (OH∑). The OH∑ is among the strongest oxidizing species used in environmental remediation, and considered thousands of times stronger than chlorine.
Photocatalytic Oxidation (PCO) is an AOP that has been used for various air purification applications, from reducing volatile organics from groundwater stripping to oxidizing floral ripening gases in large orchid displays.
A ceramic or metallic filter media is impregnated with a thin film of a photocatalytic compound, such as titanium dioxide (TiO2). As UV illuminates the filter surface, its energy activates the photocatalytic coating, initiating several surface reactions that adsorb organic compounds and microorganisms, and mineralize them to carbon dioxide (CO2).
Researchers have even noted that the endotoxins from E. Coli may be de-toxified under photocatalytic oxidation.3 Figure 1 is a simplified depiction of a photocatalytic particle under UV illumination and its reactions.
PCO “air reactors” are typically designed to treat organic loadings to reduce them to regulatory or administrative standards for improved Indoor Air Quality (IAQ). Oxidation kinetics and reaction engineering are applied to target-specific organic compounds to optimize the size of the reactor, catalyst loading and UV intensity. For the purpose of this article, we will simply demonstrate the application of a PCO filter as another barrier against viable microorganisms in biopharmaceutical applications.
For the purposes of retaining and oxidizing viable particulate, a filter with arresting capability of particles in the 1 to 5 micron range would be sufficient for retaining a large percentage of spores and bacteria that carry through the ventilation system before the terminal HEPA filters.
A reduced UV intensity (about 3 milliwatts/cm2 at the surface), or about one hundred times less dose for a typical single-pass inactivation of bacteria, can be used to activate the photocatalytic coating to retain and oxidize the cells (and possibly the endotoxins).
Validation of UV and PCO filters
Since UV can be used in United States Pharmacopeia (USP) water production, validation protocols have been established for testing its performance. Based on our design and field experience, testing objectives for the PCO filters will be highlighted.
In addition to establishing that the UV performs as designed and installed, the unit itself should be tested with the existing HVAC system as a whole. For the purposes of this article, we will focus on the UV/PCO process and how it may affect the performance of the overall HVAC system to which it now becomes an integral part.
Generally, validation of a process unit involves three parts: Installation Qualification (IQ); Operational Qualification (OQ); and Performance Qualification (PQ). The objectives are typical for UV systems and may not include the manufacturer's other objectives—such as a reduction in bioburden plated out onto ductwork captured on filters, reduction in the sterile rooms, etc.
Conclusions
UV installed in a cleanroom HVAC system can act as a secondary barrier against the introduction of bioburden into duct, onto filters, and into the cleanroom. UV is safe, does not alter the air characteristics, and can possibly reduce the periodic sanitization of duct, HEPA filter housings, and diffuser grills.
By applying the design principles of UV disinfection, a designer can estimate the type and number of lamps required for single-pass disinfection in a HVAC system, where the lamps are installed in either the duct or in the air handler.
Software is available to optimize the design of UV systems. Electronic UV ballasts, combined with the use of PLCs, can control UV output and provide alarm functions to conserve energy, and to warn building personnel of failures, respectively.
Photocatalytic oxidation (PCO) filters have the capability of completely oxidizing microorganisms and possibly their endotoxins, prior to reaching the HEPA filters. This oxidation capability depends upon the filter particulate-arresting characteristics.
Validation protocols for UV water purification systems have been established for references. The validation of a HVAC UV installation should involve the unit process itself and its impact on the HVAC system, such as changes in airflow or air pressure differentials.
Samuel E. Speer is vice president of engineering at Catalyx Technologies, a process engineering firm specializing in UV and photocatalytic oxidation systems for water and air purification. He is responsible for the development and commercialization of advanced UV technologies for bioburden control in cleanroom facilities. He can be reached at: [email protected] Dr. Rao S. Chatty is senior consultant and managing director of Schleiden/Eifel, Germany-based M/s C&C Consult—a consulting and technology marketing company specializing in environment protection technologies, such as muncipal and hazardous waste and waste gas treatment. He can be reached at: [email protected]
References
1. Riley R.L. and Nardell E.A., “Clearing the Air —The Theory and Application of Ultraviolet Air Disinfection”, Am Rev Respir Dis 1989; 139:1286-1294
2. Data extracted from Table 1 of Technical Bulletin #97, Ultradynamics Corporation, Hackensack, NJ
3. Fujishima, A., Hashimoto, K., Wantanabe, T., “TiO2 Photocatalysis—Fundamentals and Applications,” May 1999, BKG, Inc.