Date: 2021-07-23Category: Not ApplicableState: Union GovernmentCountry: India
Clarification if change in a) Polymorphs/crystalline/amorphous/solvates/hydrate etc (b) salt and (c) Derivative/analogue/ester etc of already approved active substance to be considered as new drug if main active moiety (Active Pharmaceutical Ingredient-API) is same?
**Subject: Clarification Regarding Changes to Approved Active Pharmaceutical Ingredients (APIs)**
**Circular No.:** F. No. 120121DCPt15
**Date:** 237 [Date unclear in original text, please refer to original document]
**Source:** Government of India, Directorate General of Health Services, Central Drugs Standard Control Organization (CDSCO), New Drugs Division
**Summary:**
This circular addresses the classification of drug modifications involving changes to approved Active Pharmaceutical Ingredients (APIs), specifically concerning polymorphs (crystalline, amorphous, solvates, hydrates, etc.), salts, and derivatives/analogues/esters, where the main active moiety remains the same.
The CDSCO clarifies that such changes to approved drugs are *not* automatically considered old drugs due to their potential influence on:
* Physicochemical properties (particle size, hygroscopicity, solubility, density, flowability, compatibility, etc.)
* Dissolution, bioavailability, and bioequivalence.
* Manufacturing processes of both drug substance and drug product.
* Stability of both drug substance and drug product.
Therefore, applications for drugs with such modifications must provide adequate data to substantiate safety and efficacy, although bioavailability/bioequivalence studies may not always be required depending on the specific change and justification provided.
However, applications for such drugs will be processed as new active substance and will be assessed similarly as for any new active substance as prescribed in New Drugs and Clinical Trial Rules, 2019.
Key Entities Referenced
Directorate General of Health Services: A department under the Government of India responsible for health services.
Central Drugs Standard Control Organization: National Regulatory Authority (NRA) of India for Pharmaceuticals and Medical Devices
New Drugs Division: A division of the Central Drugs Standard Control Organization responsible for new drugs.
FDA Bhawan, Kotla Road, New Delhi, Delhi: Location of the Central Drugs Standard Control Organization, New Drugs Division.
Active Pharmaceutical Ingredient (API): The biologically active component of a drug product.
New Drugs and Clinical Trials Rules, 2019: The regulatory framework in India governing new drugs and clinical trials.
Bioavailability: The proportion of a drug or other substance that enters the circulation when introduced into the body and so is able to have an active effect.
Bioequivalence studies: Studies conducted to compare the bioavailability of different formulations of the same drug.
F. No. 12-01/21-DC(Pt-15)
Government of india
Directorate General of Health Services
Central Drugs Standard Control Organization
(New Drugs Division)
FDA Bhawan, Kotla Road
New Delhi- 110002
Dated: 23/7/ «|
CIRCULAR
Subject: Clarification if change in a)
polymorphs/crystalline/amorphous/solvates!
hydrate etc (b) Salt and (c) Derivative/analogue/ester etc of already approved
active substance to be considered as new drug if main active moiety (Active
Pharmaceutical Ingredient-API) is same? -Reg.
Representation has been received seeking clarification, if already approved drugs with change in
(a) Polymorphs/crystalline/amorphous/solvates/hydrate etc,
;
Salt, and
be considered To as old adr uGgy o4r Gnsew odfr ucgr.on eros adden sibetance rey land to change in
drugs specification and may influence on;
. Physicochemical properties particle size, hygroscopicity, solubility, density, flowability and
compatibility etc.
* Dissolution, bioavailability and bioequivalence.
e Manufacturing of drug substance/drug product.
¢ Stability of drug substance/drug product.
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Bicavailabilty/Bicequivalence studies, to demonstrate its safety and efficacy.
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However, applications of such new drug may be processed considering following: -
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