Setting threshold limits for the significance of objectionable microorganisms in oral pharmaceutical products.

Due to the increasing number of immuno-compromised patients, increased attention is paid to the quantitation and identification of microorganisms in oral pharmaceutical products; therefore, a systematic approach is required by the manufacturers of non-sterile oral pharmaceuticals to evaluate the significance of microbial isolates other than primary pathogens and/or those in the product specification based on the number of organisms present, the type of dosage form, and the potential hazard to the user. Limits for objectionable microorganisms in oral products intended for use by immuno-compromised patient populations such as pediatric, HIV, cancer, etc., must be tighter than the limits for oral products intended for treating patients with diseases or conditions not affecting their immune systems because patients with deficient immune systems are more at risk of microbial infections. Smaller numbers of opportunistic pathogens become infectious when resistance mechanisms are impaired, either by severe underlying disease, or by use of immunosuppressive drugs. This article proposes a systematic approach for evaluating the significance of microbial isolates other than primary pathogens and/or those in the specification (e.g., Staphylococcus aureus and Pseudomonas aeruginosa) of non-sterile oral pharmaceutical products by setting appropriate threshold limits.