EMA/CHMP: New Guideline Draft on Active Substances published for Comment

As reported, the 'Concept paper on the revision of the guideline on the chemistry of active substances' of the Quality Working Party (QWP) was published for comment in 2022. This document was intended to explain and clarify the need to revise and update the 'Guideline on the chemistry of active substances (EMA/454576/2016)' and to outline the procedure for the revision. The results and insights gained from this were incorporated into the revision of the guideline, with the result that the draft of Revision 1 of the 'Guideline on the chemistry of active substances' was published in July 2024. This draft is now open for public comment until the end of January 2025.

The updated guideline will replace the guidelines 'Note for guidance on chemistry of new active substances (CPMP/QWP/130/96, Rev 1)' and 'Chemistry of active substances (3AQ5a)', and is divided into the following chapters:

Executive summary
1. Introduction (background)
2. Scope
3. Legal basis
4. Body of Data
 4.1. General Information 3.2.S.1 
 4.1.1. Nomenclature 3.2.S.1.1 
 4.1.2. Structure 3.2.S.1.2 
 4.1.3. General Properties 3.2.S.1.3
 4.2. Manufacture 3.2.S.2 
 4.2.1. Manufacturer(s) 3.2.S.2.1 
 4.2.2. Description of Manufacturing Process and Process Controls 3.2.S.2.2 
 4.2.3. Control of Materials 3.2.S.2.3 
 4.2.4. Control of Critical Steps and Intermediates 3.2.S.2.4 
 4.2.5. Process Validation and/or Evaluation 3.2.S.2.5 
 4.2.6. Manufacturing Process Development 3.2.S.2.6 
 4.3. Characterisation 3.2.S.3 
 4.3.1. Elucidation of Structure and other Characteristics 3.2.S.3.1 
 4.3.2. Impurities 3.2.S.3.2
 4.4. Control of the Active Substance 3.2.S.4 
 4.4.1. Specification 3.2.S.4.1 
 4.4.2. Analytical Procedures 3.2.S.4.2 
 4.4.3. Validation of Analytical Procedures 3.2.S.4.3 
 4.4.4. Batch Analyses 3.2.S.4.4 
 4.4.5. Justification of Specification 3.2.S.4.5
 4.5. Reference Standards or Materials 3.2.S.5
 4.6. Container Closure System 3.2.S.6
 4.7. Stability 3.2.S.7 
 4.7.1. Stability Summary and Conclusions 3.2.S.7.1 
 4.7.2. Post-approval Stability Protocol and Stability Commitment 3.2.S.7.2 
 4.7.3. Stability Data 3.2.S.7.3
References

The updated guideline is applicable to both existing and new active substances. As already envisaged in the concept paper, the N-nitrosamine topic was considered and integrated into chapter 4.3.2 Impurities, for example.

Here you can find the draft of the 'Guideline on the chemistry of active substances' of the CHMP/the EMA.