Already approved drugs with changes in active substance may be considered as new drug: DCGI

New Delhi: The apex drug regulatory body, the Central Drugs Standard Control Organization (CDSCO), has clarified that any changes in polymorphs/crystalline/amorphous/solvates/hydrates, salt, and derivatives/analogues/esters etc. of an already approved active substance will be considered a new drug even though the primary active moiety (Active Pharmaceutical Ingredient, or API) of an already approved active substance remains the same.

This comes in response to the representation received seeking clarification, if already approved drugs with changes in 

(a) Polymorphs/crystalline/amorphous/solvates/hydrates

(b) Salt, and

(c) Derivative/analogue/ester etc. are manufactured using the new manufacturing process will be considered as old drugs or new drugs.

Clarifying the above, the Drugs Controller General of India (DCGI) stated,

"It is clarified that changes in (a) (b) and (c) of already approved active substances may lead to changes in drug specifications and may influence on :

• Physicochemical properties, particle size, hygroscopicity, solubility, density, flowability and compatibility etc.

• Dissolution, bioavailability, and bioequivalence.

• Manufacturing of drug substances/drug products.

• Stability of drug substance/drug product "

In addition to this, DCGI also mentioned that changes in the above mentioned properties of already approved active substances may require validation of the manufacturing process, stability studies, additional clinical and non-clinical studies, and bioavailability/bioequivalence studies to demonstrate their safety and efficacy.

As a result, any change to a previously approved active substance's polymorphs/crystalline/amorphous/solvates/hydrates, salt, and derivatives/analogues/esters, etc. is considered a new drug.

Accordingly, it is also specified that applications for such a new medication may be processed based on the following:

i. In case (a) (b) & (c) of already approved active substances significantly affect physicochemical properties, manufacturing process, stability, safety, efficacy, and bioavailability/bioequivalence etc., the new drug will be processed as a new active substance and requirements will be the same as for any new active substance as prescribed in the New Drugs and Clinical Trials Rules, 2019.

ii. In the case of any (a) (b) & (c) of already approved active substances, if there is no significant effect on properties, manufacturing process, stability, safety, efficacy, and bioavailability/bioequivalence etc., the new drug will be processed as a subsequent new drug of an already approved new drug and the requirements will be the same as for any new claim for any already approved new drug, as prescribed in the New Drugs and Clinical Trials Rules, 2019.

In continuation, it is also specified that the applicant should submit an application as per the requirements prescribed in the New Drugs and Cinical Trials Rules, 2019.

To view the official notice, click the link below:

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