CRED Managing Variations Effectively

Extensions - Fundamental changes to MAA  Extensions are classified as per Annex I of EU Regulation (1234/2008) 1. Significant changes to the Active Substance that do not lead to significant differences in safety/efficacy:  Different salt/ester  Replacement by different isomer(s), or mixture vs single isomers  Biological with slightly different molecular structure  New master cell bank  New ligand for Radiopharmaceuticals 2. Changes to the strength, pharmaceutical form and route of administration, causing changes in:  Bioavailability  Pharmacokinetics  New strength  New form  New route of administration