Aseptic Processing: Points to Consider

How often do airflow measurements need to be taken?

Areas that fall under air cleanliness classifications have an obligation to ensure the purity (read: contamination-free existence) of their product. To that end, airflow measurements should be done whenever operational or performance qualification studies are done, which happens whenever changes/adjustments are made to the air handling systems, processing equipment, or HEPA filters in the area that could potentially affect the product and the personnel. Testing on an annual, semi-annual, quarterly, or even monthly basis depends on how important it is to ensure the cleanliness of the room for all concerned. (ISPE, “Baseline Guidelines, Vol. 3”, January 1999)

Where do airflow measurements need to be taken?

Airflows taken six inches from the filter face allow for accurate and reproducible measurements. (Ljungqvist, B. and Reinmuller, B. PDA J. Pharm. Sci. Technol., 1995)

Why perform smoke studies?

Smoke studies help visualize exactly the air movements in a room, which means you can actually see how the air flows over the product under a variety of conditions, and whether or not external airborne contaminants are affecting the product. As such, they should be taken during performance and qualification studies. (ISPE, “Baseline Guidelines, Vol. 3”, January 1999)

Do all airflow velocities measured 6 inches from the filter face have to fall within the range of 72-108 fpm?

No, because the airflow velocities measured from one area to another will vary due to differences in the layouts of the HVAC systems, though the measurements must stay within limits previously defined in baseline studies. (ISPE, “Baseline Guidelines, Vol. 3”, January 1999)

How often do HEPA filters need to be leak-tested?

As airflow measurements are taken at the filter face (see earlier question), it makes sense to check the integrity of each HEPA filter at the same time. Again, an annual check is the longest acceptable time interval between tests. (FDA, “Aseptic Processing Guidelines”, 1987, 2002 (draft))

Can HEPA filters be patched if a leak is detected?

That depends on the size of the patch. A filter given a patch that covers no more than 3% of the area and measures 1.5 inches on its shortest dimension has been found to have no negative effects on the cleanliness of the area. Any filter with leak/s that require larger patches would need to be replaced to ensure that the product is still being adequately protected from airborne contaminants. (IEST-RP-CC006.2, 1997; ISO 14644-3 (draft))

Given all the emphasis on product protection, isn’t protecting the worker equally important?

Protecting the worker is equally as important as protecting the product. Some of the procedures in use at facilities, however, are designed to protect the product and not the worker. It is the therefore the employer’s responsibility to ensure that each worker at the facility has adequate personal protective equipment (PPE) and the knowledge/training to use them correctly at all times. Otherwise, both the worker and the product are placed at risk if the PPE is not properly used. (OSHA, 29 CFR 1910.132-138, 1994)