Regulatory harmonization of 3Rs in QC testing requirements for biological products - from the viewpoint of users. Iwona Wilk-Zasadna

Transcription

1 Regulatory harmonization of 3Rs in QC testing requirements for biological products - from the viewpoint of users Iwona Wilk-Zasadna

2 Overview 1) Why we are interested in alternatives to animal testing goal and business benefits 2) Current process of changes to licensed products - Stakeholder analysis - Procedure - Regulatory assessment; 3) Harmonization effort (regulatory) hurdles 4) Harmonization effort proposed approaches 5) Take home messages 2

3 Alternatives to animal testing - goals and business benefits Need We want safe and ethical products quickly available for medical needs Drivers More rapid release Reduced costs Better tracking of vaccine consistency Ethical approach Measures QC release lead time QC release lead time adherence Cost of animals Cost of materials Animal maintenance materials Personnel (hrs) Ratio of in vitro/ in vivo tests Number of animals used 3

4 Stakeholder Analysis optimization of QC release testing PROJECT CHAMPION/TEAM QC System RA PLANNING GOAL QA RELEASE FINANCE MANUFA CTURING Animal Centre Positive Influence Negative Influence SIZE Influence Magnitude Involvement

5 Harmonization process - Milestones Area What? Who? Research applicable data Change Control Regulatory Affairs Specifications Licensure Research all pertinent data Contact Product- Steward(s) Identify depts./staff involved Collate all data collected. Change request management Assessment and change submission SOPs review, elimination, creation + TRAINING Decision of relevant authorities Project Champion QC Doc/ various departments RA QC system Compliance and RA Animal Experiments SOP revision + Training Animal Center 3Rs Program and BEST Plan Business Use Only 5

6 Change control Change control change impact assessment Change and risk assessment Impacted sites Impact assessment Impacted documents Impacted equipment/ systems Evaluation actions Milestones Regulatory evaluation actions with timelines 6

7 Good to know - regulatory assessment of change re IMPACT US EU CAN Category Description Category Description Category Description Batch release impact: YES Tell and wait prior approval Prior Approval Supplement (b) Changes (..) that have a substantial potential to have an adverse effect (..) Variation Type II Major variation Level I Supplements changes that have a substantial potential to have an adverse effect Variation Type IB Level II Notifiable Changes changes that have a moderate potential to have an adverse effect Batch release impact: YES Tell, wait and do Changes Being Effective after 30 or 0 days CBE30 CBE (c), changes (..) that have a moderate potential to have an adverse effect (..) Minor variation Batch release impact: NO Do and tell Annual Report (d), changes (..) that have minimal potential to have an adverse effect (..) Variation Type IA Minor variation Submission within 12 Months after implementation Level III Annual Notification changes that have minimal potential to have an adverse effect Batch release impact: NO 7 Not notifiable Level IV Record of Changes changes are (..) not expected to have an adverse effect

8 Level II Notification only EU Canada Mexico Ecuador Peru Argentina Australia Brazil Chile Colombia Egypt Indonesia Israel Jordan Malaysia Saudi Arabia Singapore South Arabia Korea Rep Thailand Iran Vietnam Taiwan New Zeland Harmonization effort example (removal of ATT) Type II Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ Ѵ

9 Criteria for regulatory acceptance of 3R testing approaches 1) Demonstration of method validation. 2) Demonstration that the new or substitute method or testing strategy provides either new data that fill a recognized gap or data that are at least as useful as, and preferably better than those obtained using existing methods. 3) Demonstration of adequate testing of medicinal products under real-life conditions (human and veterinary) which can be generated through the safe harbour process Guideline on regulatory acceptance of 3R (replacement, reduction, refinement) testing approaches; EMA/CHMP/CVMP/JEG-3Rs/450091/2012 9

10 Harmonization effort scientific hurdles There are scientific challenges to develop in vitro strategies to demonstrate efficacy of the product, which correlates with in vivo efficacy The potency attribute contains a collection of tests to ensure product consistency by measurement of Critical Quality Attributes (CQA), which impact immunogenicity The Analytical Target Profile (ATP) is generated to determine the most suitable assay to determine vaccine immunogenicity based on: - Selectivity/specificity - Accuracy - Linearity - Precision - Sensitivity 10

11 Harmonization effort regulatory hurdles Complexity of regulatory changes and different regulatory requirements between regions do not generate strong incentives for industry to develop and implement alternatives to animal testing Prudence of Health Authorities to accept deviations from established guidelines is observed 11

12 Harmonization effort possible future directions Well established vaccines (e.g. Rabies, DT) generic tests, suitable for all products from different producers Classes of (new) vaccines (e.g. conjugated vaccines) harmonized approach assay may be company specific Novel vaccines (e.g. based on reverse vaccinology) product toproduct specific assay 12

13 Take home messages It is beneficial to both, public health and pharmaceutical industry to implement alternatives to animal testing for final batch release Implementation of changes to licensed products is complex, time and resource consuming It is critical to harmonize 3Rs requirements by health authorities worldwide to facilitate development and implementation of alternative testing strategies for batch release We recognize the importance of informed stakeholder debate on harmonization of 3Rs requirements and welcome the opportunity to engage in constructive dialogue 13

14 Thank you very much for your attention!