Scientific considerations of pharmaceutical solid polymorphism in Abbreviated New Drug Applications

This commentary is intended to provide a scientific perspective on pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs). 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. 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. 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.