FAQ - Pharmaceutical/Life Sciences Particle Counting

Question
Is it necessary to monitor for non-viables at the capping station on a batch by batch basis? The product entering the capping station is filled and stoppered. There is a school of thought that the capping station should be monitored as there may be a risk that the stopper may not be fully seated as it enters the capping machine/station. Monitoring at the capping station can be a problem as the capping activity is an inherent particle generating operation.

Answer

The capping station monitoring has had much debate for several years, it first reared it's head at the European 2002 PDA meeting in Basel, where debate ran that give there is no guarantee that a vial is truly stoppered until the cap is crimped it should be maintained in a Class A environment throughout that transitory path. This met with much angst as the viables in the air are not somehow drawn magnetically to stoppered vials and so suitable protection from environmental contaminants should be made.

This has now gone through several iterations and the FDA and the EU have made a stance on requirements, albeit loose ones.

FDA

Require that the environment be suitable for the process based upon risk and that routine samples be taken to show that an ISO5 environment exists where capping is performed, in the at rest state. They recognize that during operations capping is a particle generating process and that these limits may change providing they are monitored to ensure that OOT events are recorded.

EU

The EU is looking at the release of a new clause 93 that covers capping exercises. The basics are though that the air supply should be Grade A quality (ISO5) although the area that capping is performed in is maintained and operated as Class C, remember only the HEPA Air needs to be of a particulate and viable Class A quality and nothing else. They are also pushing for continuous measurement of stopper integrity, stopper seating O2 in the free space etc. That is not yet a direct requirement but watch this space.

1. Containers should be closed by appropriately validated methods. Containers closed by fusion, e.g. glass or plastic ampoules should be subject to 100% integrity testing. Samples of other containers should be checked for integrity according to appropriate procedures. Partially stoppered freeze drying vials should be maintained under Grade A conditions at all times until the stopper is fully inserted.

The container closure system for aseptically filled vials is not fully integral until the aluminium cap has been crimped into place on the stoppered vial.

As the equipment used to crimp vial caps can generate large quantities of non-viable particulates, the equipment should be located at a separate station equipped with adequate air extraction. Vial capping can be undertaken as an aseptic process using sterilised caps or as a clean process outside the aseptic core. Where this latter approach is adopted, vials should be protected by Grade A conditions up to the point of leaving the aseptic processing area, and thereafter stoppered vials should be protected with a Grade A air supply until the cap has been crimped. Vials with missing or displaced stoppers should be rejected prior to capping. Where human intervention is required at the capping station, appropriate technology should be used to prevent direct contact with the vials and to minimise microbial contamination

For more information on cleanroom monitoring, read Particle Monitoring Requirements in Pharmaceutical Cleanrooms.