Role of Environmental Monitoring and Microbiological Testing during Manufacture of Sterile Drugs and Biologies

摘要

The microbiological quality of drugs and biologies is necessary for their efficacy and patient safety, because microbial contamination of drugs causes immediate adverse effects on patient health in terms of morbidity and mortality, as well as long-term adverse effects, such as cancer, autoimmune, and other diseases. Additionally, microbes can alter the chemistry and pharmacology of drugs, with a potential adverse impact on their effectiveness due to the breakdown of the active ingredients as well as on their safety due to the toxicity of potential degradant products. Therefore, control of microbes in drugs is essential, either by assuring absence of microbes in sterile drugs that are administered parenterally and applied to sensitive tissues or by controlling microbial bioburden to appropriate levels for non-sterile drugs that are administered to regions rich in microbial flora with physical or immunologkal barriers to infections. Table 1 lists major differences between sterile and non-sterile drugs. For sterile drugs, microbes are essentially eliminated by terminal sterilization (heat or irradiation of final containers) or by employing an aseptic manufacturing process where terminal sterilization is not possible, specifically for most biologies. Assurance of the absence of bacterial, yeast, and fungal contaminants is provided by the sterility test for sterile drugs. For non-sterile drugs, bioburden due to aerobic bacteria, yeast, and fungi and absence from objectionable microorganisms, as required, is controlled to appropriate levels based on product attributes, route of administration (oral, intranasal, topical, anal, vaginal, etc) and target patient population (neonates, infants, elderly, immunocompromised, healthy population, etc). Non-sterile drugs are tested for total aerobic bacteria, yeast, and fungi by the bioburden or microbial limit test and for the absence of objectionable organisms, as required (Table 1).