Asunto(s)
Descubrimiento de Drogas , Preparaciones Farmacéuticas/química , Amidas/química , Compuestos Heterocíclicos de 4 o más Anillos/química , Legislación de Medicamentos , Compuestos Macrocíclicos/química , Modelos Moleculares , Farmacocinética , Estereoisomerismo , Relación Estructura-Actividad , Termodinámica , Estados Unidos , United States Food and Drug AdministrationRESUMEN
PURPOSE: This commentary is intended to provide a scientific perspective on pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs). METHODS: This report proposes recommendations for monitoring and controlling drug substance polymorphs and describes scientific considerations of pharmaceutical solid polymorphism in the determination of drug substance sameness. RESULTS: It presents three decision trees for solid oral dosage forms or liquids containing undissolved drug substances to provide a process for evaluating when and how polymorphs of drug substances are monitored and controlled in ANDA submissions. CONCLUSIONS: It is scientifically concluded that differences in polymorphic composition of drug substances in generic drug products and reference-listed drugs are not directly relevant in the determination of drug substance sameness in ANDAs.