CRED Getting the CMC Dossier Right 2024

28/08/2024

Specification – Key Guidelines

● Eudralex - Notice to Applicants

● Chemistry of New Active Substances (CPMP/QWP/130/96)

● ICH (Q6A & Q6B): Test Procedure/Acceptance Criteria for New DS and New DP

● ICH (Q3A): Impurities in New DS

● ICH (Q3C): Impurities – Guideline for Residual Solvents

● ICH (Q3D): Elemental impurities

● ICH (Q4B): Annexes (harmonised methods -USP/EP/JP)

• ICH (M7) plus addendum : Assessment and control of DNA reactive (Mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk.

● Pharmacopoeial monograph

● In-house manufacturing and development data

ICH M7 supersedes European guidelines; EMEA/CHMP/QWP/251344/2006 & Q&A EMEA/CHMP/SWP/431994/2007 Ph.Eur Substances for Pharmaceutical use, Monograph No 2034 (Cross references ICH M7) FDA Genotoxic and Carcinogenic Impurities in Drug Substances and Products (2008) - withdrawn

The Organisation for Professionals in Regulatory Affairs

35

Carcinogenicity Potency Categorisation approach

➢ Represented in a series of questions in a flowchart ➢ All to do with number of hydrogens in alpha position – see later as to relationship to potency AND ➢ Other structural features – activating and deactivating

The Organisation for Professionals in Regulatory Affairs

36

18