CRED Getting the CMC Dossier Right 2024

28/08/2024

Drug Substance Development – Early Phase IND/IMPD

➢

Limited information provided

➢ Starting materials for GMP steps based on impact to drug substance only (e.g steps that generate impurities specified in DS – Can be a very small number of steps) ➢ Drug substance specification should ensure patient safety and efficacy, but ICH Q3A and Q3C do not apply during clinical development

➢ See Harvey paper http://dx.doi.org/10.1016/j.yrtph.2016.12.011

➢ And recent Kenyon paper : https://doi.org/10.1016/j.yrtph.2024.105644

➢ Mutagenic impurities should be assessed as per ICH M7

➢ Justification of shelf life for the study

The Organisation for Professionals in Regulatory Affairs

9

Drug Substance Development - Late Phase IND/IMPD

➢

Increasing amount of information

➢ If commercial manufacturing process is identified, GMP steps should start at the identified starting materials per ICH Q11 and Q11 Q&A ➢ ICH Q3 guidances still do not apply during development, but unless justified, specifications are expected to converge with ICH Q3 standards

➢ Starting material, IPC and intermediate specifications expected

➢ Mutagenic impurities as per ICH M7

➢ High level discussion of the control strategy

➢ More detailed discussion of stability

The Organisation for Professionals in Regulatory Affairs

10