FDA Publishes Final Guidance on Classification of Co-Crystals
FDA has published the final Guidance for “Regulatory Classification of Pharmaceutical Co-Crystals”
The guidance document can be accessed here.
The key highlights of the guidance documents are –
- The guidance does not have any retrospective effect
- This guidance finalizes the August 2016 revised draft guidance for industry Regulatory Classification of Pharmaceutical Co- Crystals, which classified co-crystals as a drug product intermediate (or as an in-process material)
- From a physical chemistry and regulatory perspective, co-crystals can be viewed as a special case of solvates and hydrates, wherein the second component, the coformer, is not a solvent (including water), and is typically non-volatile
- Evidence is required to be provided to establish that both the API and the coformer are present in unit cell
- The ΔpKa <1 rule stands unaltered
- Evidence is required to be provided to establish that the API and the coformer are substantially dissociated from the co-crystal before reaching the site of pharmacological activity; and –
- - that the interaction of the API with its coformer is of similar magnitude to the interaction of the API with solvents in solvates; and –
- - in vitro evaluation based on dissolution and/or solubility is generally considered sufficient to demonstrate that the API dissociates from its coformer
- pharmaceutical co-crystal and has a regulatory classification similar to that of a polymorph of the API
- Specifically, it is not regarded as a new API.
- Different co-crystals of a salt API will be treated as a polymorph of that salt
- A co-crystal that is composed of two or more APIs (with or without additional inactive coformers) will be treated as a fixed-dose combination product and not a new single API.
- If you are using a material that the Agency previously considered to be a co-crystal, you may continue to do so.