The specification limits for bioburden should be NMT 10 CFU/100 ml, in line with the human and veterinary notes for guidance on manufacture of the finished dosage form (CPMP/QWP/486/95 and EMEA/CVMP/126/95).
When a prefilter is installed, unless otherwise justified, a bioburden limit of 10 CFUs/100 ml before first filtration is achievable in principle and is strongly recommended a GMP point of view. Higher bioburden limits should not be justified by the high capacity of two consecutive bacteria retaining filters.
However, when appropriate justification is submitted (processes involving fermentation or other biological or herbal components, use of purified water for ophthalmic preparations, etc.), a bioburden limit of higher than 10 CFUs/100 ml before prefiltration may be acceptable. In such cases, it should be demonstrated that the first filter has the capability to achieve a bioburden prior to the last filtration of NMT 10 CFUs/100 ml, in line with the notes for guidance on manufacture of the finished dosage form (CPMP/QWP/486/95 and EMEA/CVMP/126/95).
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