FDA has issued a final guidance for industry, Regulatory Classification of Pharmaceutical Co-Crystals. Co-crystals are crystalline materials composed of two or more different molecules, typically an active pharmaceutical ingredient (API) and a co-crystal former ("coformers"), in the same crystal lattice. Pharmaceutical co-crystals have provided opportunities for engineering solid-state forms beyond conventional solid-state forms of an API, such as salts and polymorphs. This guidance provides applicants planning to submit new drug applications and abbreviated new drug applications with information on the appropriate regulatory classification of pharmaceutical co-crystal solid-state forms.
The guidance document was originally finalized in April 2013; however, after receiving feedback from stakeholders, FDA issued a revised draft guidance in August 2016. In response to the stakeholder feedback, FDA has clarified the appropriate classification of co-crystals and the regulatory implications of such classifications. Applicants should be aware that a co-crystal API that meets the criteria in the guidance is no longer considered to be a drug product intermediate. As described in this revision, a co-crystal that meets the criteria in the guidance will be classified as an API; in other words, the co-crystal form is considered in the same way as would any other morphic form of the API such as a polymorph, solvate or hydrate.