HEPA filtration and integrity testing

A HEPA filter is a "high efficiency particulate air filter specified in accordance with a relevant international standard" (Annex 1, glossary). In a sterile facility the terminal filter, in the ceiling or in a unidirectional airflow unit, is the last barrier between the air handling system and the room.

A filter that met its class at the factory can be damaged in handling, installation or use, or leak at its seal. Annex 1 defines the filter integrity test as one that confirms a filter has kept its retentive properties and "not been damaged during handling, installation or processing" (glossary), and asks for it in qualification (4.25) and in every requalification (4.32).

Where it sits: In the supply air of every classified room, in unidirectional airflow units over grade A, inside isolators and RABS, and in the air supply of depyrogenation tunnels and dry heat ovens.

• —Cleanroom ceilings and terminal housings
• —Unidirectional airflow units and laminar airflow cabinets
• —Isolators and RABS
• —Depyrogenation tunnels and dry heat ovens (Annex 1, 8.67, 8.70)

In the reference facility: Plant utilities, HVAC & energy centre, Processing & formulation suite, Aseptic filling & isolator line

Not covered on this page: Sterilising-grade liquid and gas filters, which have their own integrity tests; Filter class specifications, which belong to EN 1822 and ISO 29463.

• 01Filter media pack. Captures particles; pleated glass-fibre or membrane media.
• 02Frame and seal (gasket or gel). Joins the filter to its housing; a seal leak bypasses good media.
• 03Terminal housing or ceiling grid. Holds the filter and provides the upstream challenge and sampling ports.
• 04Diffuser or protective screen. Spreads or protects the airflow below the filter face.
• 05Pressure-drop gauge across the filter. Shows loading over time; it does not show a leak.

Connects to: Air handling unit and pre-filters upstream; Room or unidirectional airflow zone downstream; Maintenance and filter change procedures; Change control.

• 01Aerosol photometer (with aerosol generator). Installed leakage across the filter face and seal, against the upstream challenge. Watch for: upstream challenge not measured or not uniform.
• 02Optical particle counter. An alternative leak scan by discrete counting, and room classification downstream. Watch for: sample tubing long or bent enough to lose large particles.
• 03Differential pressure transmitter. Pressure drop across the filter, for loading and change decisions. Watch for: ports connected the wrong way round, reversing the sign.
• 04Airflow velocity probe (anemometer). Face velocity and uniformity below the filter. Watch for: readings taken at a different height from the one qualified.

• 01Installed filter leakage (limit, % of upstream challenge). Scanned across the face and seal of each installed filter, against the acceptance criterion in the site’s qualified test method.
• 02Supply airflow volume (measured, m³/h). At each filter, part of qualification and requalification (Annex 1, 4.25, 4.32).
• 03Airflow velocity (measured, m/s). Below the filter face in unidirectional airflow, at the location justified in the qualification protocol (Annex 1, 4.30).
• 04Pressure differential (measured, Pa). Across the filter; a rising value shows loading, and the change point is set by the site.

SPEQ publishes no universal alarm or acceptance values: they depend on the process, the product and the site’s own qualification.

• 01Procedure: Integrity test of final filters at requalification. At most every 6 months for grade A and B areas and every 12 months for C and D (Annex 1, 4.32).
• 02Procedure: Tunnel and oven filter tests. Air supplied to a depyrogenation tunnel passes through at least a HEPA filter, with integrity tests at least twice a year (Annex 1, 8.67).
• 03Procedure: Change control on filter replacement. A change of final filters is an example of special maintenance that calls for requalification (Annex 1, 4.32).

An alarm asks for a response; an interlock stops an action; a safety function protects people and has its own risk basis.

• 01Supply. Filter class and factory test certificate for each filter.
• 02Installation and qualification (Annex 1, 4.25). Installed filter system leakage and integrity test; Airflow volume and velocity; Downstream classification.
• 03Requalification (Annex 1, 4.32). Integrity test of final filters; Airflow volume measurement; Air velocity or recovery, as the grade requires.
• 04Change. Requalification after a final filter change or other special maintenance.

• 01EU GMP Annex 1: Manufacture of Sterile Medicinal Products — European Commission (EudraLex Volume 4), 2022 revision, in operation 25 August 2023. EU / EEA; revised jointly with the PIC/S Committee; in force. Supports: HEPA and filter integrity test definitions (glossary); installed filter leakage in qualification (4.25); final filter integrity and filter changes in requalification (4.32); tunnel filter tests (8.67).
• 02ISO 14644-3: Cleanrooms and associated controlled environments — Part 3: Test methods — ISO (TC 209), 2019 (Edition 2). International; consensus standard. Supports: Installed filter leak test methods.
• 03EN 1822-1: High efficiency air filters (EPA, HEPA and ULPA) — Classification, performance testing, marking — CEN, 2019 (replaced the 2009 edition). Europe; consensus standard. Supports: European classification and factory testing of HEPA and ULPA filters.
• 04ISO 29463-1: High efficiency filters and filter media for removing particles in air — Part 1: Classification, performance, testing and marking — ISO (TC 142), 2024 (Edition 3). International; consensus standard. Supports: International classification and factory testing of high-efficiency filters.