High Efficiency Particulate Air (HEPA) Filters Used in Pharmaceuticals Manufacturing
Biological Safety and High Efficiency Particulate Filters
A filter’s efficiency rating describes the relationship between particles retained or trapped by the filter to the number of particles entering the filter. For example a 99.97% efficient filter indicates that 99.97% of particles entering the filter are removed from the air by the filter. To further describe efficiency, a filter is also rated by the size of particles at which it is most susceptible to particles passing through it, or its weakest point of particle penetration. Filter penetration is defined as the ratio of particles that pass through the filter media without being trapped to the number of particles that actually enter the filter.
A filter that is 99.97% efficient at 0.3 microns is 99.97% effective at trapping particles at its most vulnerable size of 0.3 microns. For particles that either larger or smaller than 0.3 microns, the filter is actually more efficient than 99.97%. In this example, 0.3 microns is considered the filter’s most penetrating particle size (MPPS), in other words, 0.3 microns is the size particle at which penetration of particles through the filter is highest. In biological applications, laboratory personnel regularly work with microorganisms in biological safety cabinets. HEPA filters used in these cabinets must effectively trap hazardous bacterium and viruses to provide personnel protection. Although an individual virus particle ranges in size from 0.005 to 0.1 micron, viruses generally only survive to travel through the air as part of larger particles (0.3 micron or larger), for example, attached to mucous particles. Because it is difficult to disperse or aerosolize single viral particles and because of the particle collection mechanisms of HEPA filters, particles larger and smaller than a filter’s most penetrating size are collected with greater efficiency.
As air passes through a HEPA filter, the air is not simply strained as many presume, rather a number of actions take place. First, as the air comes into contact with the bends and folds of the pleated filter media, the volume of airflow breaks off into numerous smaller air streams as its own velocity and the velocity of the air upstream forces the air through the filter. Some particles become trapped because they are larger than the pores of the filter media, and cannot pass through. This takes place throughout the filter media, not solely at the surface of the filter. For large particles greater than 1.0 micron, the primary collection mechanism is impaction.
Impaction occurs when air traveling through the filter and the particles suspended in it encounter a web of randomly placed fibers in the folded filter media through which it must traverse. Although the air can change direction to weave through the filter fiber maze, the tendency of particles is to continue on the same trajectory and to collide with the filter media, resulting in entrapment. For small particle entrapment in the 1.0 micron or smaller particle size range, diffusion is the primary collection mechanism. Small aerosolized particles behave similarly to gases in that they move from an area of higher concentration to an area of lower concentration.
Particles are removed from the air stream as they settle in areas of low airstream concentration at the fiber surface where other particles are already trapped. The combination of aforementioned collection mechanisms results in effective removal of particles from a HEPA filtered air stream.
Filter Performance and Industry Standards
In the United States, the Heating, Ventilating and Air Conditioning (HVAC) industry uses filter efficiency ratings defined by American Society of Heating, Refrigeration and Air Conditioning Engineers (ASHRAE) 52.2 testing. A Minimum Efficiency Reporting Value or MERV rating is assigned to each filter. A higher MERV value indicates better filtration. MERV ratings are used in home consumer products to give an indicator of the product’s effectiveness.
In Class II biological safety cabinets, the type of filter required is defined by a standards organization. In the North America, the NSF Standard 49 details the construction and performance requirements of Class II biological safety cabinets. To comply with the NSF standard, Class II cabinets must utilize Type C HEPA filters that are 99.99% efficient at 0.3 microns for the supply and exhaust airflow. The types of HEPA filters available are classified by RP types as defined by the IEST RPCC001.3 standard on HEPA and ULPA filters according to the filter’s efficiency and penetration at a specific particle size. Although other types of HEPA filters with different efficiencies are classified by the IEST standard, the Type C filter is the standard for use in biological safety cabinets.
HEPA filters are tested by challenging the filters with an aerosolized product of known size to determine the filter’s efficiency at that specific size. For example, D.O.P or P.A.O. is forced through the filter using an aerosol generator. The filter is then scanned using a photometer, or aerosol detection device, to measure the mass of the particles in the airflow both upstream and downstream of the HEPA filter and to ultimately calculate the efficiency of the filter at the testing particle size.
In addition to HEPA filters, the IEST standard also classifies ULPA (ultra low penetration filters) and Super ULPA filters by type. Generally ULPA filters have a higher efficiency rating from 99.999 to 99.9999% at a smaller micron size (0.1, 0.2 or MPPS). Although it may seem that more is better, ULPA filters are intended for use in industries such as the semiconductor industry where the types of particles that are detrimental to semiconductor manufacturing and development are dispersed at smaller submicron sizes. For biological applications, there is no gain in using an ULPA filter compared to a HEPA filter. As explained previously, microorganisms and viruses are not airborne in single particles, but rather are grouped together in larger particles or are attached to other particles in air. Use of an ULPA filter in a biological safety cabinet creates more resistance in the airflow dynamics of the cabinet, requiring a larger blower motor to maintain proper airflows.
A larger blower motor will add increased noise level to the cabinet, and potentially increase vibration levels.
Additionally, ULPA filters require a different testing protocol with equipment that is generally not maintained by biological safety cabinet certification companies. To test ULPA filters, aerosolized polystyrene latex spheres of specific size are introduced to the air stream. A laser particle counter then measures the size and number of airborne spheres to determine efficiency of the ULPA filter.
In Europe, the EN standard 12469 defines Class II biological safety cabinets and filters that must be used for compliance to the standard. The EN 12469 requires a class H14 HEPA filter as defined by the EN 18221 standard classifying HEPA and ULPA filters. An H14 HEPA filter is 99.995% efficient at its most penetrating particle size (MPPS). A specific particle size is not assigned in the classification of H14 filters. Per EN 18221, to test the filter for its MPPS, airborne particles are forced through the filter at the flow rate in which the filter will ultimately be used. A five channel particle counter reading particles 0.1, 0.2, 0.3, 0.4 or 0.5 microns in size is used to determine which channel allows the most particles through the filter. The MPPS is determined by choosing the particle size which has most frequently penetrated through the filter. As with the IEST standard for filters, the EN 18221 also includes classifications of other types of HEPA and ULPA filters, however, none is required for use in biological safety cabinets.
HEPA Filtration in Biological Safety Cabinets
After discussing particles size, various filter options, particle collection mechanisms and filter performance testing, it is evident why HEPA filters are the industry standard in biological safety cabinets. Particles generated in biological work fall into the spectrum of particles efficiently trapped by HEPA filters. It is a commonmisconception that ULPA filters given their smaller MPPS rating are somehow better than HEPA filters for biological applications. The known behavior of viruses and bacterium and the tendency of microorganisms to be dispersed in air as part of larger particles support use of HEPA filters for biological work. In addition to utilizing HEPA filters, a properly designed BSC must meet performance standards for airflow velocities, structural requirements and proven product containment capabilities to ensure user safety. HEPA filtration, biological safety cabinet design and user technique combined provide occupational safety in the biological laboratory.