HEPA filters in Pharmaceuticals

1.0 Introduction

• HEPA filters are the high efficiency particulate air filter with a 0.3 µm particles being retained with an efficiency of 99.97%
• HEPA filtered air is supplied to critical areas at a particular velocity in order sweep the particles away from closing or filling area and also to maintain unidirectional airflow during operations.
• Integrity of HEPA filters should be maintained to ensure aseptic conditions. During installation leak tests should be done at regular intervals to identify integrity breaches around sealing gaskets & frames or through different points on filter media in aseptic processing facility
• The filters which are for leak testing are the ones that are installed in a dry heat depryogentaion tunnels & ovens which are commonly used to test HEPA filters
• Aerosol used for HEPA filter should comply with critical physicochemical attributes like viscosity. Leak testing aerosols like poly-alpha-olefin (PAO) & Dioctylphthalate (DOP) are used. Problem encountered in the usage of aerosol is the risk of microbial contamination in the area of testing.

1.1 HEPA filter tests

• Efficiency testing for HEPA filter is done to rate the filter where it has to retain minimum 99.97% of particulates which are greater than 0.3µm in diameter
• Filter leak testing is done to detect leak from filter media or filter frame or seal. Here a polydispersed aerosol is used which consists of particles with the light scattering mean droplet diameter in submicron range of size at 0.3µm. If sufficient upstream challenge of particles is not introduced then it makes the filter inefficient for detecting leaks. In order to ensure accuracy of the aerosol photometer an aerosol upstream concentration should be introduced.
• The test should be done with the filter face scanned on downstream side with photometer probe with sampling rate of one cubic foot per minute
• Downstream leakage is calculated as percent of upstream challenge which is measured by probe
• Scanning should be done on entire filter face & frame and 1-2 inches away from face of the filter. This whole process of scanning should be documented.
• If probe reading is 0.01% of upstream challenge then it indicates leaks & HEPA filter should be replaced or if it is appropriate then should be repaired in limited area.
• The leak tests are insufficient in monitoring performance of the filter. Periodic monitoring should be done of key attributes like uniformity of velocity across the filter. Variation in velocity tends to cause turbulence which increases the risk of contamination.
• Velocity of unidirectional air should be measured from 6 inches away from face of the filter & also at distance proximal to the work surface of HEPA filters. The measurements should be in compliance with range of velocity established at air pattern analysis studies.
• When air velocity is not uniform across an area of filter then HEPA filters should be replaced otherwise the airflow pattern may affected.
• Drug manufacturers should ensure that specifications of equipment’s, test methods & acceptance criteria are defined & the certification activities are conducted properly

1.2 Related Documents

1) http://www.fda.gov/downloads/Drugs/.../Guidances/ucm070342.pdf

Hepa filters, efficiency testing, filter leak testing, air velocity, air flow