The Drugs Controller General (India) has said that certain changes in the active substance of an approved drug may lead to change in drug specification and require validation of the manufacturing process.



In a circular, the DCGI has said that his office has received representation seeking clarification on if already approved drugs with change in (a) polymorphs, crystalline, amorphous, solvated or hydrate etc, (b) salt and (c) derivative, analogue, ester etc. are manufactured using the new manufacturing process, will be considered as old drug or new drug.



The circular clarifies that the change in these properties or already approved active substance may lead to change in drugs specification and may influence on the physiochemical properties particle size, hygroscopicity, solubility, density, flow ability and compatibility etc. It will also impact the dissolution, bioavailability and bioequivalence classifications, manufacturing of drug substance/drug product, and stability of drug substance/drug product.



Hence, changes mentioned above in 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, said the drug regulator.



“Therefore, any new (a) (b) & (c) of already approved active substance is considered as a new drug,” added the Circular.