Air Flow in Class Air Areas per ANNEX 1
MANUFACTURE OF STERILE MEDICINAL PRODUCTS

Grade A Air speed must be in the range of 0.36 to 0.54 m/s.

In order to have an equilibrium pressure, the amount of air leaving the room and entering the room must be the same. However, unless the return duct areas are similarly sized to the HEPA inlet areas, the flow through the returns will be different (and probably faster) than the flow through the HEPA's. Indeed, for the room pressure to be positive, the return air must be slightly restricted.

Since the air is laminar and starts at the ceiling and goes to the returns, the volume of air changes, per unit time, is only dependent on the air speed.

Thus the number of air changes per hour will be between 470 and 710. Further, what makes the difference in the number of air changes used is the ceiling height ! Lower ceilings, require greater air changes per hour!

Grade D Air must be at least 20 changes/hr according to FDA "Sterile Drug Products Produced by Aseptic Processing" (page 7, line 36). The EU cGMP Annex 1 states "The particulate conditions given in the table for the 'at rest' state should be achieved after a short 'clean up' period of 15-20 minutes in an unmanned state after completion of operations." Although very precise, the HVAC design requirement is too easily met if applied to Grade B Air.

<= Air changes/min

<= Air Changes needed to move from ISO Class 7 to ISO Class 5 in 15 minutes.

This calculation assumes a well mixed room, which is of course the worst case.

Grade C: Recommend 50 to 90 Air Changes per Hour
Grade B: Recommend 100 to 200 air changes per Hour.

The table above is from an article in Feb 2002 in Clean Room Technology. These numbers were reported as 'typical' by the author, Sheila Sadaghiani.