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Conformity Decisions Based on Measurement Uncertainty—a Case Study Applied to Agar Diffusion Microbiological Assay

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Abstract

Purpose

Antimicrobial activity of drug products containing antibiotics is often measured using microbiological assays. However, the high values of measurement uncertainty associated with the analytical results obtained from microbiological assays may be an issue to conformity decisions.

Methods

The aim of this work was to estimate the risk of false decisions in conformity assessment due to measurement uncertainty for the potency of apramycin in pharmaceutical drug products. Monte Carlo method (MCM) simulations were performed in order to estimate global consumers’ (Rc) and producers’ (Rp) risks using a Bayesian approach and specific consumers’ (R′c) and producers’ (R′p) risks using a frequentist approach.

Results

Despite of the high value of measurement uncertainty, Rc and Rp were found to be 0.0% and 0.3%, respectively. However, R′c and R′p were found to be high when the analytical result is close to the specification limits. Risk estimation using Bayesian approach is recommended to be applied by manufacturers, while frequentist approach may be an alternative to regulatory and third-party laboratories.

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Funding

This study was funded by FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo (2016/04100-8 and 2017/04539-2) and CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

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Authors and Affiliations

  1. Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Prov. Lineu Prestes, 580, CEP 05508-000, São Paulo, SP, Brazil

    Luciana Separovic, Maria Luiza de Godoy Bertanha, Alessandro Morais Saviano & Felipe Rebello Lourenço

Authors
  1. Luciana Separovic
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  2. Maria Luiza de Godoy Bertanha
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  3. Alessandro Morais Saviano
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  4. Felipe Rebello Lourenço
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Correspondence to Felipe Rebello Lourenço.

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Separovic, L., de Godoy Bertanha, M.L., Saviano, A.M. et al. Conformity Decisions Based on Measurement Uncertainty—a Case Study Applied to Agar Diffusion Microbiological Assay. J Pharm Innov 15, 110–115 (2020). https://doi.org/10.1007/s12247-019-09374-8

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