FDA Guidance Document: ANDAs: Pharmaceutical Solid Polymorphism — Chemistry, Manufacturing, And Controls Information

Chemistry, manufacturing, and controls (CMC) information must be submitted to support the approval of an abbreviated new drug application (ANDA). This guidance is intended to assist applicants with the submission of ANDAs when a drug substance exists in polymorphic forms. Specifically, this guidance provides:

• FDA recommendations on assessing sameness when the drug substance exists in polymorphic forms.
• Decision trees that provide recommendations on monitoring and controlling polymorphs in drug substances and/or drug products.

FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.

DEFINITION OF TERMS: POLYMORPHIC FORMS AND POLYMORPHISM

We recommend that ANDA applicants investigate whether the drug substance in question can exist in polymorphic forms. Polymorphic forms in the context of this guidance refer to crystalline and amorphous forms as well as solvate and hydrate forms, which are described below.

• Crystalline forms have different arrangements and/or conformations of the molecules in the crystal lattice.
• Amorphous forms consist of disordered arrangements of molecules that do not possess a distinguishable crystal lattice.
• Solvates are crystal forms containing either stoichiometric or nonstoichiometric amounts of a solvent. If the incorporated solvent is water, the solvate is commonly known as a hydrate.

When a drug substance exists in polymorphic forms, it is said to exhibit polymorphism.