US FDA’s co-crystal final guidance to reduce cGMP burden

By Flora Southey contact

- Last updated on GMT


Related tags: New drug application, Food and drug administration

In response to stakeholder feedback, the US FDA has issued a final guidance detailing changes to the regulatory classification of co-crystals, from intermediate to API.

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.

Pharma co-crystals

“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.”

Stakeholder feedback

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.

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