FDA guidance on API-excipient co-crystals unnecessary; Amgen

The comments follow draft co-crystal guidance from the US Food and Drug Administration (FDA). In the December guidance the FDA outlines data needed to support applications for API (active pharmaceutical ingredient) – excipient co-crystals but some in the industry are unimpressed.

“We do not believe that a guidance document on pharmaceutical co-crystals is necessary. Pharmaceutical co-crystals can be classified under existing drug substance, drug product and solid form guidance​”, Matt Peterson, preclinical director at Amgen, wrote to the FDA​.

According to Peterson the wording of the guidance would allow companies to use co-crystals without going through the characterisation process needed for other drug substances, despite having similar characteristics.

“Because pharmaceutical co-crystals can modify the performance of an API, both in vivo and ex vivo, we believe [they] should be subject to the same regulations as other drug substances​”, Peterson wrote.

Amgen wants co-crystals included in a general solid-form guidance document. “Each form has unique properties and the properties critical for drug product performance need to be understood; regardless of what name is given to the form or how it is manufactured​”, Peterson wrote.

A question of class​

AstraZeneca, Lundbeck and others also submitted comments to the FDA but stopped short of calling the guidance unnecessary. Like Amgen, AstraZeneca questions the classification of co-crystals as drug product intermediates, describing the basis for the classification as “unprecedented​”.

Co-crystals are often isolated in the final stage of API synthesis, AstraZeneca wrote​, using the same processes are used as for sales and hydrates. “It would seem logical, therefore, to classify co-crystals as alternative forms of APIs, rather than drug product intermediates”, AstraZeneca wrote.

If it classes co-crystals are drug product intermediates the FDA has questions to answer. “The co-crystal can be manufactured at an API manufacturing facility. Will the API facility be considered a drug product facility and be subject to applicable regulations?​”, Peterson wrote.