欧盟atmp批准后变更分类的科学和基于风险的方法

Science and Risk-based Approaches for the Classification ofPost-approval Contents Executive Summary2Background3Introduction: Drivers for Change3Application of a Flexible Regulatory Framework under the Provisions of ICH Q124Case Studies5 1.Plasmid Starting Material Changes.................................................................................................5 1.1.Scope and Background1.2.Submission in Accordance with EU Variation Classification 2.Change of Cell Bank Starting Material..........................................................................................11 2.1.Scope and Background2.2.Submission Strategy in Accordance with EU Variation Classification 3.Addition of Alternative Manufacturing Suites for Cell-based Medicinal Products.......................14 3.1.Scope and Background3.2.Submission Strategy in Accordance with EU Variation Classification 4.Replacement of a Test Method with Improved Analytical Technology for Control of AAV-basedFinished Products.................................................................................................................................17 4.1.Scope and Background4.2.Quantitative PCR and Droplet-Digital PCR4.3.Submission in Accordance with EU Variation Classification ConclusionsReferences Page1of22 Executive Summary Regulatory efficiency, as a prerequisite for a modern regulatory system, is recognised in thePharmaceutical Strategy for Europe and the need to revise the variation framework through changes Due to the unique properties of ATMPs and the rapid evolution of technologies, even with thecurrent revisions, the variation guideline still creates a rigid framework that may block innovation, The European Commission is in the process of revising the variation framework for medicines forhuman use to establish more efficiency during life cycle management and to reduce theadministrative burden for both marketing authorisation holders and the regulatory authorities. Theinitial revisions to the variations guideline has resulted in the reclassification of specific variations The EuropeanCommissionCompetitiveness Compass was launched in January 2025 and wasintended to help manufacturers by simplifying legislation across the EU. ATMP stakeholders(regulators, manufacturers, and patients) would benefit from appropriate use of a risk-basedframework(similar to the thought process shared by the EMA in their investigational ATMPguideline EMA/CAT/22473/2025) supporting the management of life cycle variations of ATMPproducts. The upcomingsecondrevision of the variation regulation is therefore a goodopportunityto simplify the legislation appropriately for the lifecycle of ATMPs. This would include enabling the Background Revision of the Variation Regulation (1234/2008) and the Classification Guideline (C(2013) 2804) isbeing conductedto provide for simplification, efficient life-cycle management (including addressingchallenges relating to the interplay of medicines and devices and for novel and more complextherapies) and to adapt to digitalisation. There is an opportunity here for the EU to play a leading The European Commission isin the process of revising the variation framework for medicines forhuman use to establish more efficiency during life cycle management and to reduce theadministrative burden for both marketing authorisation holders and the regulatory authorities. The Introduction: Drivers for Change The field of ATMPs is still nascent, and the analytical and manufacturing technologies are rapidlyevolving providing opportunity for production processand/or product optimisationsduringdevelopment or post approval.In addition, ATMPs often involve accelerated clinical developmentprogramsand a limited number of batches manufactured during clinical developmentresulting inlimited manufacturing experience and the need forfurtherprocessdevelopmentafter initial MAA Due to the unique properties of ATMPs, and the rapid evolution of technologies, the variationguideline designed for chemical and “traditional” biological medicinal products creates a rigidframework that may block innovation, continuous improvements and potentially patient access.Forinstance, depending on the modality, the cells or plasmids could be considered to be starting In the case of personalised ATMPs (e.g., autologouscell therapies) which are produced for a specificpatient,there areunique changesnon-existent for other modalities,for example,changes to theplasmid starting materials within or outside the gene of interest. Those changes are not categorisedin thecurrent variation guidelinewhich is causing classification constraints and very often increases The European Commission intends to revise the variation regulation to address some issues,includingdatabase entry of Type IA variations and full implementation of ICH Q12, whichcanonly bemade after the revision of the general pharmaceutical legislation (GPL) is completed. There is anopportunity to ensure that the upc