Where should airflow velocity measurements be taken, with respect to a filling line or other aseptic processing areas?

 

Recommendation

Airflow velocity measurements should be taken at locations where meaningful and reproducible results can be obtained. This typically at a distance of 15-30 cm from the filter face.

Rationale for Recommendation

The primary reason for airflow velocity measurements in unidirectional airflow areas (e.g, area where products , product contact packaging components, and product contact surfaces are exposed) is to ensure adequate airflow to protect the materials from external airborne contamination and to verify continued compliance with qualified conditions. The adequacy of the environment can be determined, in part, from airflow velocity and air flow pattern studies, and from particulate matter monitoring (at the working position).

Accurate measurements can be taken ad changes over the detected when air flow velocity are evaluated at a predetermined distance from filter surface, which is sufficiently close to the filter surface to be reproducible to detect changes in the performance of the filter.

The airflow velocity depends on the design of the filling line, room design, and air-handling system. Once velocity is determined, it is important to ensure that the velocity stays within the specific parameters. Routine air velocity measurements should be taken at the same locations used during the initial airflow studies to ensure consistency.

Reference Guidance:

EudraLex; The Rules Governing Medicinal Products in the European Union

Volume 4; EU Guidelines to Good Manufacturing Practice; Medicinal Products for Human and Veterinary Use; Annex 1; Manufacture of Sterile Medicinal Products (corrected version)

Laminar air flow systems should provide a homogeneous air speed in a range of 0.36 – 0.54 m/s (guidance value) at the working position in open clean room applications. The maintenance of laminarity should be demonstrated and validated. A uni-directional air flow and lower velocities may be used in closed isolators and glove boxes.

Reference Guidance:

USFDA Sterile guidance document http://www.fda.gov/downloads/Drugs/.../Guidance/ucm070342.pdf (accessed o 09-08-2015)

A velocity of 0.45 meters/second (90 feet per minute) has generally been established, with a range of plus or minus 20 percent around the set point. Higher velocities may be appropriate in operations generating high levels of particulates.  

It is important to conduct periodic monitoring of filter attributes such as uniformity of velocity across the filter (and relative to adjacent filters). Variations in velocity can cause turbulence that increases the possibility of contamination. 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.

Reference Guidance:

WHO 961 annex 6

The local zone for high-risk operations, e.g. filling and making aseptic connections. Normally such conditions are achieved by using a unidirectional airflow workstation. 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.

The uniformity and effectiveness of the unidirectional airflow should be demonstrated by undertaking airflow visualization tests.

Reference Guidance:

Schedule M

For Grade A laminar air flow work stations, the air flow rate shall be 0.3 meter per second ± 20% (for vertical flows) and 0.45 meter per second ± 20% (for horizontal flows).