Module 9 2021

19/03/2021

Consensus on timing of Change

• Changes during Phase 3 should be avoided  To avoid comparability issues confounding the interpretation of Phase 3 data • However, some manufacturers have incorporated components of the Ph 3 study to compare the PK and clinical attributes of their product • Implementation of changes post Phase 3 and prior to approval is ill advised.

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ICH Q5E has Established the Scientific Principles ICH Q5E: Comparability of Biotech/Biological Products Subject to Changes in their Manufacturing Process  Objectives – Principles for product comparability and guidance on design and conduct of studies to collect data – Ensuring Quality, Safety and Efficacy – Harmonise regional approaches and data packages  Scope – Proteins/polypeptides and their derivatives – predominantly those from recombinant/non-recombinant cell culture expression systems – All manufacturing operations executed by the authorised manufacturer or other approved parties – Products where process changes are made in development or for which a marketing authorisation has been granted – Products where changes are made by a single manufacturer who can directly compare results from analysis of pre-and post-change products – ie this is not intended for biosimilar comparability which is subject to separate guidance  Follows the general principle – Hierarchical approach to comparability assessment

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