Module 9 2024

03/09/2024

Timing

• In early development impact to CQAs is assessed against the preclinical batch used in toxicological studies (usually a pilot/engineering batch) • Later in development impact to CQAs is assessed against any previous clinical batches as well as the toxicological study batch • Major changes (those that have a risk of impacting CQAs) 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 Phase 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

• Clinical supply manufacture

• Post approval commitments • Launch and supply

• Clinical supply manufacture • Stability • Process trending • Process/meth od optimisation

• Commercial supply planning • Process/meth od validation • Stability

• Clinical supply manufacture

• Stability • Process

• Proof of concept • Phase I enabling studies

Pre clinical

Clinical phase I

Clinical phase II

Clincial Phase III

Approval Filing

Post Approval

• Stability • Process

enabling changes

characterisati on • Process/meth od optimisation

consistency

• Other

required changes

Comprehensive comparability evaluation

Comparability

Minimal comparability evaluation

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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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