Airflow velocity measurement for an Unidirectional airflow device

GOOD VALIDATION PRACTICE (cGVP)
1

I have to perform operational qualification for an unidirectional airflow device (formerly referred as laminar work bench). Within our organization, some controversial exist.

Some people said the airflow velocity must be measured at working position AND 6 inches from the filter face. The guidance value (0.36 ~ 0.45 m/s) must be maintained at the working position, not filter face. The data from the filter face is just for informational purpose. In my humble guess, if the guidance velocity is achieved at the working position the velocity from 6 inches from the filter face will be much higher, which will create negative impact on the airflow pattern at the working position due to high supplying air velocity. But not sure. Eventually airflow pattern test will tell me the everything for this approach. Also there is a chance that high face velocity will result in the leaks in HEPA filter media and frame.

But others believe that the guidance value must be maintained at 6 inches away from the filter face. This is historically used for many years in the pharmaceutical industry. But in order to comply GMP, the velocity data at the working position is also important. As you know the measurement of the velocity at the working position would be highly variable due to the equipment size and configuration within the unidirectional airflow device. Proper airflow pattern at the working position is more important than achieving the specified airflow velocity at the working position. So velocity measurement at the working position will be information purpose but can be helpful in understanding the observed airflow pattern.

I’m very frustrated which approach is right interpretation. Especially, this plant should comply EU GMP, rather than US FDA. EU GMP Annex 1 states that “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”. For EU GMP compliance, the former interpretation will be correct. But practical and historic point of view, the latter interpretation will be correct.

Does anyone have the experience on this case for complying EU GMP? Also I’d like to listen the current industry interpretation (practice) for US FDA compliance.

Thanks in advance.

HJ.Kwon

2

Dear Kwon,

Please looks these documents:
IEST-RP-CC002.3–This is the velocity testing method.

EUAnnex 1 or as well as PIC/S Annex 1.

[COLOR=“darkorange”]

“FDA Guidance for Industry - Sterile Drug Products Produced by Aseptic Processing - CGMP”–Airflow velocity in critical area should be around 0.45m/s +/- 20%.

Health Canada -GMP, regulation C.02.029: "Unidirectional airflow systems provide an homogeneous air speed of 0.45 m/s +/- 20% (guidance value)at the working position in open clean room applications IN CRITICAL AREAS. [/color]
Regards

3

Dear colleagues,

I would like to develop the topic and ask you about such situation. Normally in grade A the continuous monitoring systems are used, including air velocity sensors. During production, for example, in a case of vials filling machine there is a laminar doors opening is required due to jams or another kind of technological action on the machine. In this case the air velocity temporary drops below the 0,36 m/s. What do you think, how long and to which value this temporary air velocity drops are permissible with an appropriate reflection on the trends as an “exclusion situation”, that shouldn’t be estimated as a deviation?

4

The guidance value is 0.45 m/s +/- 20%.

If it falls below 15% of the guidance value you must take the immediate action.

Interventions on the vial machine do cause some turbulence in the systems.But this does not account in falling of airvelocity. This is very crtitical in this area.

The worst case value is specified after opening the doors on laminar flow bench. Normally these doors are made with polycarbonate.Even when you open such doors you should have the required value.

I think the CFM works here. You must calculate the proper CFM value above your filling machine and install the Laminar flow bench.

Multiple parameters must be considered during the construction of this point.All worst case scenarios must be worked out so that air velocity does not drop below the guidance limits.

The continuous monitoring sensor is mounted about 15 to 30cm from the LAF at the filling and bunging zones.The velocity does not drastically fall even when door is opened completely or partially for technical interventions.