The US Food and Drug Administration (FDA) released the Regulatory classification of pharmaceutical co-crystals guidance this month, following its introduction in April 2013, and a revised draft in August 2016.
In the final guidance, the Agency advises new drug application (NDA) and abbreviated new drug application (ANDA) applicants that a co-crystal API meeting the guidance criteria will no longer be considered a drug product intermediate, but 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,” said the FDA.
Pharmaceutical co-crystals are composed of two or more different molecules, typically an active pharmaceutical ingredient (API) and an excipient.
In theory, the non-API component of a co-crystal can be modified to enhance drug process-ability, stability or bioavailability.
According to the FDA, “Pharmaceutical co-crystals have provided opportunities for engineering solid-state forms beyond conventional solid-state forms of an API, such as salts and polymorphs.
“Another advantage of co-crystals is that they generate a diverse array of solid-state forms for APIs that lack ionisable functional groups, which is a prerequisite for salt formation.”
The reclassification responds to stakeholder feedback, requesting the Agency clarify the appropriate classification of co-crystals and the regulatory consequences of such classifications.
In August, 2016 in-PharmaTechnologist reported drugmakers were reluctant to work with pharmaceutical co-crystals due to their classification as ‘intermediates’ – which require stricter manufacturing practices in the drug making process than solvates.
“In a commercial setting, co-crystals are typically manufactured in drug substance facilities. However, when classified as a drug product intermediate, additional current good manufacturing practice requirements (cGMPs) apply to co-crystals,” said the FDA at the time.