Cocrystals of Approved APIs to Be Treated as New Drugs, Clarifies CDSCO
New Delhi: The Central Drugs Standard Control Organization (CDSCO), under the Directorate General of Health Services, has issued a clarification regarding the regulatory pathway for approval of pharmaceutical cocrystals.
Co-crystals are crystalline materials composed of two or more different molecules, typically an active pharmaceutical ingredient (API) and co-crystal formers ("coformers"), in the same crystal lattice in a defined stoichiometric ratio associated with nonionic and noncovalent bonds.
Pharmaceutical co-crystals have provided opportunities for engineering solid-state forms beyond conventional solid-state forms of an API, such as salts and polymorphs. Cocrystals can be tailored to enhance drug product bioavailability and stability and to enhance the processability of APIs during drug product manufacture. Another advantage of co-crystals is that they generate a diverse array of solid-state forms for APIs that lack ionizable functional groups, which is a prerequisite for salt formation.
The regulator emphasized that the applicant must show that the physicochemical (in vitro) and or pharmacokinetic (in vivo) properties of the multicomponent co-crystals/solid state form are superior to that of the Physical mixture of the same Chemical components.
Furthermore, it added, "If the solid state structure and properties as Cocrystals are fulfilled by diffraction methods not limited to Single crystal XRD, Powder XRD, Electron diffraction, Total Scattering pair distribution function analysis as applicable, and Spectroscopic analysis of the solid state co crystals not limited to IR, Raman, near IR, NMR, then it will be defined as a Pharmaceutical Cocrystal /supramolecular complex drug else the combination will be treated as FDC/ mixture of APIs."
In addition to the above, it stated that a cocrystal of an already approved active substance may require validation of the manufacturing process, stability studies, additional clinical and non-clinical studies, Bioavailability/Bioequivalence studies, to demonstrate its safety and efficacy.
Therefore, Cocrystal of already approved active substance is considered as a new drug, and Applications of such a new drug may be processed considering the following:
"Cocrystal of already approved active substance is will be processed as new active substance and requirements will be same as for any new active substance as prescribed in New Drugs and Clinical Trials Rules, 2019." the order clarified.
