Regulatory considerations of pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs).

A sponsor of an Abbreviated New Drug Application (ANDA) must have information to show that the proposed generic product and the innovator product are both pharmaceutically equivalent and bioequivalent, and therefore, therapeutically equivalent. Many pharmaceutical solids exist in several crystalline forms and thus exhibit polymorphism. Polymorphism may result in differences in the physico-chemical properties of the active ingredient and variations in these properties may render a generic drug product to be bioinequivalent to the innovator brand.

Scientific considerations of pharmaceutical solid polymorphism in abbreviated new drug applications.

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.