Filters, associated hardware, filter installation, and the process itself may all pose risks of particulate contamination to the product. Therefore, particulate control for these materials and processes should be evaluated and verified.
Suppliers typically flush filters and sample the flush solution to test for particulates smaller than 10 microns and larger than 25 microns. The test results should comply with the particulate matter standards for injections specified in the pharmacopoeia. These same standards should also be used to confirm that the filter is free from fiber shedding.
In addition to particulates, filters may also be sources of other contaminants, such as endotoxins, organic carbon, or oxidizable substances. Potential sources may include surfactants, wetting agents, additives used in the manufacture of plastic components, debris generated during production, and component materials.
Pre-flushing filters can reduce the levels of particulates and contaminants and may be performed as part of the wetting process prior to integrity testing. However, the operability of pre-flushing must also be considered; for example, the removal of the flush solution must not affect product concentration or other quality parameters. If pre-flushing is performed post-sterilization and pre-use, the collection and disposal of the flush solution must be managed so as not to compromise the sterility of the downstream system. The flushing method should be validated. During normal operation, the flush volume should not be less than the validated minimum flush volume.
When using single-use filtration systems that require pre-flushing before use, additional design considerations are necessary, including: the pressure rating of upstream tubing, maintenance of downstream sterility, and provision of sufficient downstream volume (e.g., installation of a sterilizing-grade barrier filter or a sterile bag of appropriate volume) for venting and drainage.