CDSCO India has published a clarification circular on changes to already approved active substance if the active moiety remains unchanged.
Question
If there is a change change to any of the following for an already approved active substance, should it be considered a new drug if the active moiety (Active Pharmaceutical Ingredient-API) remains unchanged?
- a) Polymorphs/crystalline/amorphous/solvates/hydrate etc.
- b) salt
- c) Derivative/analogue/ester etc.
Clarification
Any change in a), b) or c) above for an already approved drug substance may have an influence upon any of the following and may lead to a change in drug specification:
- Physicochemical properties such as particle size, hygroscopicity, solubility, density, flowability and compatibility etc.
- Dissolution, bioavailability and bioequivalence
- Manufacturing of drug substance/drug product
- Stability of drug substance/drug product
This means that any change in a), b) or c) above for an already approved drug substance, in order to demonstrate its safety and efficacy may require:
- validation of the approved manufacturing process,
- stability studies,
- additional clinical and non-clinical studies,
- bioavailability/bioequivalence studies
Therefore, any change in a), b) or c) above for an already approved drug substance is considered a new drug. However, the application of such a new drug may be processed in one of the following ways:
- Where a change in a), b) or c) above of an already approved drug substance significantly affects any of 1 – 4 above, thereby significantly impacting safety and/or efficacy, the new drug will be process as a new active substance and the requirements will be the same as for any new active substance as prescribed in the New Drugs and Clinical Trials Rules 2019.
- Where a change in a), b) or c) above of an already approved drug substance does not significantly affect any of 1 – 4 above, thereby not significantly impacting safety and/or efficacy, the new drug will be processed as subsequent new drug of an already approved new drug and requirements will be the same as for new claim for any already approved new drug as prescribed in the New Drugs and Clinical Trials Rules 2019.
Note: To improve clarity, the text above has some changes from the original circular. Please refer to the text in the original circular at all times when contemplating any changes to the drug substance.
Source: CDSCO website