RESUMEN
The ICH M7 Option 4 control of (potentially) mutagenic impurities is based on the use of scientific principles in lieu of routine analytical testing. This approach can reduce the burden of analytical testing without compromising patient safety, provided a scientifically rigorous approach is taken which is backed up by sufficient theoretical and/or analytical data. This paper introduces a consortium-led initiative and offers a proposal on the supporting evidence that could be presented in regulatory submissions.
Asunto(s)
Contaminación de Medicamentos/prevención & control , Pruebas de Mutagenicidad/normas , Mutágenos/toxicidad , Preparaciones Farmacéuticas/normas , Tecnología Farmacéutica/normas , Simulación por Computador , Humanos , Pruebas de Mutagenicidad/métodos , Preparaciones Farmacéuticas/síntesis química , Guías de Práctica Clínica como Asunto , Control de Calidad , Relación Estructura-Actividad Cuantitativa , Medición de RiesgoRESUMEN
The mutagenicity of arylboronic acids has recently become an important area of research because of their potential to be genotoxic impurities in active pharmaceutical ingredients. There is no known mechanism, so currently all structure-activity relationships have been derived using Ames test data. We present preliminary data supporting a hypothesis that the mutagenicity of arylboronic acids is related to the (11)B NMR chemical shift. This could indicate that the mutagenic activity of the arylboronic acids is related to the reactivity of the boron center.