F, No. SND-16011(11)/66/2025-eoffice Government of India Directorate General of Health Services Central Drugs Standard Control Organization (Subsequent New Drugs Division)

FDA Bhawan, New Delhi Dated: 15 SEP 2025

Subject: Clarification for regulatory pathway for Cocrystals -Reg.

Representation has been has received seeking clarification for regulatory pathway for the approval of Cocrystals.

Co-crystals are crystalline materials composed of two or more different molecules, typically active pharmaceutical ingredient (API) and co-crystal formers (“coformers’), in the same crystal lattice in a defined stoichiometric ratio associated by nonionic and noncovalent bonds.

Pharmaceutical co-crystals have provided opportunities for engineering solidState 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 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.

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 Cocrystal of already approved active substance may require validation of 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

new drug and Applications of such new drug may be processed considering 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.

Accordingly, applicant should submit application as per the requirement prescribed in the New Drugs and Clinical Trials Rules, 2019.

Yours faithfully, mya <a (Dr. Rajee¥. Sifgh\ Raghuvanshi) Drugs ControllerGeneral (India)

To,

\

1. All States/UTs Drug Controllers.

2. All Zonal/Subzonal/Port Offices of CDSCO.

Copy for information to:

All stakeholders through CDSCO website.