Continuous monitoring is required in Grade A/B environments, where aseptic product is manufactured.
The monitoring plan should include the monitoring of viable and non viable particulates. In order to meet this requirement point of use particle counters and air samplers should be used.
The position of the sample probes must be validated against a formal risk analysis assessment. This helps to identify the locations where the Product is most likely to be at risk to contamination.
Grade A Environments
If we look at a filling machine line the locations that must be monitored are identified as:
- Sterilisation tunnel - where the sterile vials exit from
- The fill head area - location where product is filled into vial
- The stopper area - where stoppers are placed onto vial
- The capping area - where the crimping or capping occurs
New requirements also state that the transfer of stoppered vials to freeze driers must be maintained under a Grade A environment and the capping/crimping zone should also be maintained in a Grade A environment these add at least 2 more locations.
When we look at Grade B locations this could add another 3 locations or more depending on the size of the filling room and capping room.
Grade B Environments
Grade B environments are also required to be monitored. Although the frequency can be reduced the best option is to use point of use sample probes similar to that of the filling machine.
The image on the left illustrates the location of an ISP to monitor non viable particles and a sample head to monitor viable particles. The particle counter is positioned as close as possible to the ISP and is housed in the stainless steel wall cabinet.
The FDA recommend a height of around 1.3m or chest height for the position of the probes. As with the filling machine the concept is to capture the incoming air from the HEPA filters and verify the air is clean enough to maintain the cleanliness of the cleanroom.
For example PE-009-08 requires that a Grade A cleanroom have no more than 3520 particles at 0.5um and 20 at 5um per cubic meter of air sampled for both At Rest and In Operation condi- tions.
For Grade B At rest 3520 at 0.5 and 29 at 5.0um and In Operation 352000 at 0.5um and 29000 at 5.0um. For viable particles the limits are >1 CFU for Grade A and 10 CFU for Grade B per cubic meter of air sampled.