FDA Releases Guidance on Co-Crystal Classification

FDA published draft guidance on August 16, 2016 that provides information on the appropriate classification of co-crystal solid-state forms and the data needed to support the classification. The guidance is directed at those submitting new drug applications (NDAs) and abbreviated new drug applications (ANDAs). The recommendations in the guidance apply to those materials the agency has not previously determined to be pharmaceutical co-crystals.

According to FDA, co-crystals, which are composed of two or more different molecules in the same crystal lattice, offer opportunities for engineering of solid-state forms of APIs. They can be tailored to enhance bioavailability and stability. They also generate an array of solid-state forms for APIs that lack ionizable functional groups.

The guidance states that NDA and ANDA applicants should submit data that supports a “conclusion that the component drug and coformer exist in their neutral states in the co-crystal and interact nonionically.” Applicants should also supply assurance that “substantial dissociation of the API from its co-crystal form occurs before reaching the site of pharmacological activity.”