Conformity assessment of medicines containing antibiotics - A multivariate assessment

Pharmaceutical products must meet quality requirements to ensure the efficacy and safety of pharmacological treatment. Non-compliance of medicines can cause economic losses and compromise the patient's health. In this work, the risks of false compliance/non-compliance decisions for parenteral antibiotics (cephalothin, ciprofloxacin and metronidazole) were evaluated on the basis of analytical results, measurement uncertainties and specification limits. Physicochemical and biological quality assays were performed according to pharmacopeial procedures. Measurement uncertainties were determined using the bottom-up approach or the probability of false-positive/false-negative results. The risks of false compliance/non-compliance decisions were estimated using the frequentist approach and Monte Carlo simulations. Guard-bands were determined through a validated spreadsheet for calculating univariate and multivariate acceptance limits. All risk values (particular risks and total risk, consumer's or producer's risk) were below the maximum permissible risk value. The univariate and multivariate guard-bands defined more restrictive specification values, reducing the risks of false compliance/non-compliance decisions. One antibiotic presented unsatisfactory results regarding the drug content and was classified as out of specification product. The application of risk management tools in the pharmaceutical area contributes to improving the quality and safety of products and supports decision-making.