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.