One recognized method of testing the integrity of HEPA filters is use of a dioctylphthalate (DOP) aerosol challenge. However, alternative aerosols may be acceptable. Poly-alpha-olefin can also be used, provided it meets specifications for critical physicochemical attributes such as viscosity. Some alternative aerosols are problematic because they pose a risk of microbial contamination of the environment being tested. Firms should ensure that any alternative does not promote microbial growth.
An intact HEPA filter is capable of retaining at least 99.97 percent of particulates greater than 0.3 micron in diameter. It is important to ensure that the aerosol used for the challenge has a sufficient number of particles of this size range. Performing an integrity test without introducing particles of known size upstream of the filter is ineffective for detecting leaks. The DOP challenge should introduce the aerosol upstream of the filter in a concentration of 80 to l00 micrograms/liter of air at the filter’s designed airflow rating. The downstream side of the filter is then scanned with an appropriate photometer probe at a sampling rate of at least one cubic foot per minute. Scanning should be conducted on the entire filter face and frame at a position about one to two inches from the face of the filter. This comprehensive scanning of HEPA filters should be fully documented. While vendors often provide these services, the drug manufacturer is responsible for ensuring that these essential certification activities are conducted satisfactorily. A single probe reading equivalent to 0.01 percent of the upstream challenge should be considered as indicative of a significant leak and should result in replacement of the HEPA filter or perhaps repair in a limited area. A subsequent confirmatory re-test should be performed in the area of any repair.