3.5 Microbiological Attributes:
3.2.P.2.5 Where appropriate the microbiological attributes of the dosage form should be discussed, including, for example, the rationale for not performing microbial limits testing for non-sterile products and the selection and effectiveness of preservative systems in products containing antimicrobial preservatives. For sterile products the integrity of the container-closure system to prevent microbial
contamination should be addressed.
Where an antimicrobial preservative is included in the formulation the amount used needs to be justified by submission of results of studies of the product formulated with different concentrations of the preservative(s) to demonstrate the lowest necessary but still effective concentration. The effectiveness of the agent needs to be justified and verified by appropriate studies (e.g. national, regional or international pharmacopoeial general chapters on antimicrobial preservatives) using a batch of the FPP. If the lower limit for the proposed acceptance criterion for the assay of the preservative is less than 90.0%, the effectiveness of the agent has to be established with a batch of the FPP containing a concentration of the antimicrobial preservative corresponding to the lower proposed acceptance criteria.
As outlined in the WHO guidelines on Stability testing of active pharmaceutical ingredients and finished pharmaceutical products (23), a single primary stability batch of the FPP should be tested for effectiveness of the antimicrobial preservative (in addition to preservative content) for the duration
of the proposed shelf-life for verification purposes, regardless of whether there is a difference between the release and shelf-life acceptance criteria for preservative content.
Pharmaceutical Development of Multi source (generic) Finished Pharmaceutical Products – points to consider, (Annex 3, WHO Technical Report Series 970, 2012)
