Uncertainty Estimation Of Antibiotic Reference Standards

Antibiotic reference standards(ARS) is an important class of reference standards for pharmaceutical products, and its quality and specifications will directly affect qualities for antibiotic products. Therefore, high quality for ARS which should ensure accurate characteristic values and traceability, is an important area for ARS research. Characteristic values for ARS have their particularities. Currently, characteristic values for most ARS can not be directly traced to international system of units (SI unit), and they can only be traced to internationally recognized units. To establish ARS with high qualities, this paper will discuss how to ensure accurate characteristic values for ARS to establish ideal value transfer and trace system based on reasonable evaluation of uncertainty for characteristic values of ARS.In this paper, value determination processes for previous batches of ARS in China are firstly reviewed. Based on internationally recognized guides, characteristic values for ARS of each batch and their uncertainties are calculated. Based on actual work experiences, issues in value determination are identified by statistical analysis. Two primary factors affecting accuracy in value determination, including assay method and determination method, are identified. Secondly, uncertainty for Microbiological assay for antibiotics, the specific method used in value determination process is comprehensively evaluated. For methodological principles, value transfer, and standard operation, factors which may affect accuracy in value determination were quantitatively and qualitatively reviewed to identify key factors, which may be controlled to establish accuracy in value determination for ARS. Based on previous2aspects, general principles and statistical methods are established for value determination and uncertainty evaluation. Value determination methods, calculation methods for characteristic values and their uncertainties are explained in detail. Comprehensive technical practices for routine value determination for ARS are provided to ensure accuracy in value transfer. Thirdly, based on summary of uncertainty evaluation of previous ARS, traceability for ARS is studied. Based on whether characteristic values can be traced to international system of units (SI unit), a traceability system for ARS is established. Uninterrupted tracing links for each product are established to ensure the integrality in tracing process.