Chemistry of active substances (chemistry of new active substances) - Scientific guideline

This document describes the type of information required for the manufacture and control of active substances (existing or new chemical entities) used in a medicinal product.

Keywords: Active substance, chemistry, dossier, manufacture, quality control, impurities, specification

Current effective version

Guideline on the chemistry of active substances

Adopted Reference Number: EMA/CHMP/QWP/49484/2026 Summary:

Guideline concerning the application of Directive 2001/83/EC with a view to the granting of a marketing authorisation for a medicinal product. This guideline replaced the ‘Note for guidance on chemistry of new active substances’ (CPMP/QWP/130/96, Rev 1) and ‘Chemistry of active substances’ (3AQ5a) in 2016. It was revised in 2026 to include further recommendations on cohort of concern impurities, principally N-nitrosamines, and expand the sections covering starting materials, recovery and re-processing.

Document history

Draft guideline on the chemistry of active substances - Revision 1

Draft: consultation closed Consultation dates: 25/07/2024 to 31/01/2025 Reference Number: EMA/321776/2024 Summary:

Guideline concerning the application of Directive 2001/83/EC with a view to the granting of a marketing authorisation for a medicinal product. This guideline replaces the ‘Note for guidance on chemistry of new active substances’ (CPMP/QWP/130/96, Rev 1) and ‘Chemistry of active substances’ (3AQ5a). It has been revised to cover new and existing active substances in one guideline.

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Concept paper on the revision of the guideline on the chemistry of active substances - Revision 1

Draft: consultation closed Consultation dates: 26/07/2022 to 31/10/2022 Reference Number: EMA/CHMP/600383/2022

Guideline on the chemistry of active substances - First version

Adopted Reference Number: EMA/454576/2016 Legal effective date: 21/01/2017 Summary:

Guideline concerning the application of Directive 2001/83/EC with a view to the granting of a marketing authorisation for a medicinal product. This guideline replaces the ‘Note for guidance on chemistry of new active substances’ (CPMP/QWP/130/96, Rev 1) and ‘Chemistry of active substances’ (3AQ5a). It has been revised to cover new and existing active substances in one guideline.

Overview of comments received on 'Draft guideline on the chemistry of active substances’ (EMA/CHMP/QWP/96664/2015) - First version

Reference Number: EMA/454577/2016 Summary:

Overview of comments received on 'Draft guideline on the chemistry of active substances’ (EMA/CHMP/QWP/96664/2015)

Draft guideline on the chemistry of active substances (human) - First version

Draft: consultation closed Consultation dates: 24/04/2015 to 24/10/2015 Reference Number: EMA/CHMP/QWP/96664/2015 Summary:

This guideline replaces the ‘Note for guidance on chemistry of new active substances’ (CPMP/QWP/130/96, Rev 1) and ‘Chemistry of active substances’ (3AQ5a). It has been revised to cover new and existing active substances in one guideline.

Concept paper on the need for a single note for guidance on the chemistry of active substances - First version

Draft: consultation closed Consultation dates: 10/02/2014 to 10/08/2014 Reference Number: EMA/CHMP/QWP/752676/2013

Chemistry of active substances - Superseded document

Adopted Reference Number: 3AQ5A Legal effective date: 01/10/2015

Chemistry of new active substances - Superseded document

Adopted Reference Number: CPMP/QWP/130/96 Rev. 1 Legal effective date: 01/02/2004