EMA/CHMP: Updated Guideline on Active Substances published

In March 2026, the now final "Guideline on the chemistry of active substances" was published on the EMA website. As reported in the news "EMA/CHMP: New Guideline Draft on Active Substances published for Comment", the draft guideline was open for public consultation until the end of January 2025 and has now been adopted by the Quality Working Party (QWP) and approved by the Committee for Medicinal Products for Human Use (CHMP). The guideline is due to come into force on 1 September 2026.

The draft guideline open for comment already contained the following table of contents, which is now final:

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 applies to both existing and new active substances. As already envisaged in the concept paper, the issue of N-nitrosamines was addressed and incorporated, for example, into section 4.3.2. Impurities.

In addition, the topics of "re-processing" and "recovery of materials and solvents" were examined in greater detail and were presented in the final version in a more detailed manner than had been envisaged in the draft guideline (Chapter 4.2.2).

Furthermore, clarifications were made in the final guideline, for example in Chapter 4.2.3 under the section "Active Substance (AS) Starting Material(s)".

Please consult the EMA website for the draft and the final version of the CHMP/EMA's "Guideline on the chemistry of active substances".