Testing of Pharmaceutical Cleanrooms to Orange Guide Requirements

Medsafe are auditing pharmaceutical manufacturers to the British-European "Rules and Guidelines for Pharmaceutical Manufacturers and Distributors 1997" (known as the Orange Guide.)  So we are offering testing to demonstrate compliance with Orange Guide requirements.

The Orange Guide defines four grades of cleanrooms for manufacture of sterile medicinal products according to air quality in both the 'at rest' and 'in operation' states.

Orange Guide Grade	At rest		In operation		Max permitted viable micro-organisms /m3
	Max particles /m3 equal to or larger than:
	0.5mm	5mm	0.5mm	5mm
A	3 500	0	3 500	0	<1
B	3 500	0	350 000	2 000	10
C	350 000	2 000	3 500 000	20 000	100
D	3 500 000	20 000	Not defined		200

Aseptic filling operations must be done in a Grade A environment with a Grade B background.  The Grade A environment is generally provided in the form of a laminar flow cabinet or class II biological safety cabinet.  The Grade B environment is usually a cleanroom with HEPA-filtered air supply.

Changing rooms should be designed as airlocks and the final stage of the changing room should, in the at rest state, be the same as the area into which it leads.  Thus for a change room leading to a Grade B room (e.g. a cleanroom in which aseptic filling is performed) the change room must also achieve Grade B air quality in the at rest state.  Not all existing facilities comply with this requirement!  A HEPA-filtered supply in the gowning room is generally required to achieve compliance. 

Testing is also more involved (and a little more expensive) as we have to measure air quality in both the 'at rest' and operational states.  This normally means testing (air quality) while the process is running as usual, evicting all the occupants and re-testing.

Also, measurement of air quality in the laminar flow cabinets and/or class II biological safety cabinets is now required and this is time-consuming as a large sample volume is required for statistically valid results.