The difference between ISO standards and EU GMP Annex 1 regarding airflow velocity measurement points is a common source of confusion in qualifying HEPA filter velocity is measured in both cleanrooms and laminar airflow (LAF) especially in Grade A areas.
Air velocity is crucial to maintain cleanliness and prevent contamination at clean room but for Grade A zones working 0.36 to 0.54 m/s (or 0.45 m/s +/- 20%), helps to create a unidirectional airflow that sweeps away particles and prevents them from settling on critical surfaces. Hence the requirement are completely different
✅ ISO Standards vs. EU GMP Annex 1 – Key Differences
| Aspect | ISO Standards | EU GMP Annex 1 |
|---|---|---|
| Definition | International standards for quality management systems | A specific EU guideline for sterile medicinal product manufacturing under GMP |
| Issued by | International Organization for Standardization (ISO) | European Commission (EMA / EC) under EU GMP |
| Examples | ISO 9001 (Quality), ISO 13485 (Medical Devices), ISO 14644 (Cleanrooms) | EU GMP Annex 1: “Manufacture of Sterile Medicinal Products” |
| Scope | Generalized and industry-independent (applies to all sectors) | Pharmaceutical manufacturing, especially sterile products |
| Regulatory Status | Voluntary compliance, unless required by clients or contracts | Legally binding for EU/EEA manufacturers and MA holders |
| Focus | Quality Management System (QMS) and process consistency | GMP compliance with a focus on aseptic processing, contamination control, and cleanrooms |
| Cleanroom Standards | Uses ISO 14644 for cleanroom classifications | References ISO 14644, but adds detailed GMP controls and expectations |
| Application | Broad industries (pharma, electronics, food, etc.) | Sterile pharmaceutical manufacturing only |
| Validation Requirements | Encouraged but not specific | Detailed requirements for process validation, CCS, environmental monitoring, etc. |
| Contamination Control | Basic cleanliness and environmental standards (e.g., ISO 14644) | Emphasizes Contamination Control Strategy (CCS), environmental monitoring, gowning, etc. |
| Auditing | External certification bodies (e.g., ISO 9001 certifier) | Regulatory agencies (EMA, national inspectors) |
| Updates | Reviewed every ~5 years | Revised periodically (last update: August 2022) |
What do regulators expect?
EU/EMA (Europe): Annex 1 compliance is mandatory.
Expect proof of unidirectional airflow at working height (typically ~0.36–0.54 m/s).
Also expect testing at filter face level during initial qualification (per ISO 14644-3), but ongoing monitoring focuses on performance at the critical zone.
FDA (US): Follows ISO 14644 guidance but leans heavily on actual risk to product.
Will accept either, but expects justification—if you only measure at filter face, you must show airflow reaches and protects working zone.
“Velocities of unidirectional air should be measured 6 inches from the filter face and at a defined distance proximal to the work surface for HEPA filters in the critical area.” – FDA 2004 Guidance
WHO/Other PIC/S countries: Generally aligned with Annex 1.
Expect velocity measurements at the working height as part of routine monitoring and risk-based qualification.
“Unidirectional airflow systems should provide a homogeneous air speed of 0.36–0.54 m/s (guidance value) at a defined test position 15–30 cm below the terminal filter or air distributor system. The velocity at working level should not be less than 0.36 m/s. ” – WHO 961, Annex 6
