VACCINES CONSISTENCY APPROACH PROJECT

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1 VACCINES CONSISTENCY APPROACH PROJECT Dr Ian Ragan Project Co-ordinator EPAA Annual Meeting Brussels 13 th November 2013

2 The European Vaccines Industry Vaccines for human use Most of world production is in Europe 50% of world vaccine R&D is in Europe 2-3 million lives saved per annum Vaccines for veterinary use Protection of livestock & companion animals and prevention of zoonotic disease Market smaller and highly fragmented by species and disease Higher burden of animal use and cost

3 The Consistency Approach Vaccine quality is a consequence of Quality systems (QA, GMP) Quality of starting material Consistent production process Every vaccine consistently manufactured will lead to lots (batches) with similar in vivo properties Safe and effective This approach is already applied to modern vaccines

4 Vaccines and Animal Use LICENSING RESEARCH CLINICAL TESTING PRODUCTION QUALITY CONTROL LOT RELEASE (20%) (80%) 15% of all animal use for biomedical research and testing in Europe 80% of this is for statutory QC of lot release Animal use for vaccine QC is extensive, and pain and distress can be severe.

5 Quality Models Current Approach QC TESTING STARTING MATERIAL PRODUCTION INACTIVATION FORMULATION FINAL PRODUCT LOT RELEASE IN-PROCESS CONTROLS Extensive use of animals for QC testing of final product

6 Quality Models Current Approach QC TESTING STARTING MATERIAL PRODUCTION INACTIVATION FORMULATION FINAL PRODUCT LOT RELEASE Consistency Approach CONSISTENCY TESTING STARTING MATERIAL PRODUCTION INACTIVATION FORMULATION FINAL PRODUCT LOT RELEASE

7 Impact of the Consistency Approach The consistency approach combines rigorous manufacturing quality with non-animal tests to assure safety and potency Many alternatives to current standard tests already exist BUT: Not all the alternatives avoid use of animals completely Validated alternatives are not universally used Assurance of the potency of the final lot remains a challenge The consistency approach does not aim at one-to-one replacement of animal tests by non-animal methods but is a quality framework in which non-animal methods provide improved assurance of safety and potency

8 Consistency Approach: What makes it Attractive? Quality is linked to a well characterised clinical/historical lot (scientific benefit) Quality control is quicker (a few days instead of 2 months) (economic benefit) NO further animal use is required for lot release testing (animal welfare benefit)

9 Aims of the Project Priorities from both vet and human vaccines Gaps in data needed to remove animal tests Funding for further research Validation by EURL ECVAM* and EDQM** Communication to increase uptake * EU Reference Laboratory for Alternatives to Animal Testing (EC) ** European Directorate for the Quality of Medicines and HealthCare

10 EPAA Vaccine Project - Organisation December 2010 September 2011 Vaccine Project Committee Manufacturers Intravacc EURL ECVAM EDQM Launch Meeting April 2011 Technical Committee VPC OMCLs EMA International Observers February 2012 Expert Working Groups Human Rabies Vet Rabies DTaP* Clostridials EWG workshops 2012 onwards *Diphtheria, tetanus and acellular pertussis

11 EPAA Vaccine Project - Workstreams Expert Working Groups Human Rabies Vet Rabies DTaP* Clostridials Workshop October 2012 Replacement of In Vivo Human Rabies Vaccine Potency Testing (the NIH test) by In Vitro Glycoprotein G Quantitation Pre-validation study International working group to select the best assay Collaboration between Europe, US, Canada, Brazil, India and China Workshop to discuss findings March 2014 Submission of proposal for Collaborative Study to EDQM Biological Standardisation Programme

12 EPAA Vaccine Project - Workstreams Expert Working Groups Human Rabies Vet Rabies DTaP* Clostridials Workshop November 2012 Implementation Strategies of the Consistency Approach for Veterinary Inactivated Vaccines Agreement on use of ELISA for Glycoprotein G quantitation as replacement for challenge test Single test format unlikely because of manufacturer-specific processes and formulation Adjuvants present additional issues for final product testing Manufacturers will pursue individual approaches to switching from challenge tests and profit from human rabies experience (joint workshop in 2014)

13 EPAA Vaccine Project - Workstreams Expert Working Groups Human Rabies Vet Rabies DTaP* Clostridials Workshop August 2012 Consistency Testing of DTaP Vaccines: A Road Map for Implementation Discussion of current progress and identification of gaps for safety and potency testing Three main themes to emerge Replacement of challenge tests with serological or in vitro antigen quantitation tests Replacement of in vivo tests for toxoid toxicity (e.g. BINACLE) Opportunities for waiving of toxicity tests for D&T toxoids based on manufacturing consistency

14 EPAA Vaccine Project - Workstreams Expert Working Groups Human Rabies Vet Rabies DTaP* Clostridials Workshops March and September 2013 Validation of In Vitro Alternatives for Inprocess Control of Veterinary Clostridial Vaccines Planning an EDQM Collaborative Study to validate cell-based alternatives to current tests in mice for toxin/toxoid toxicity and toxoid antigenicity (Cl.septicum) Study involves USA, New Zealand, Turkey, Spain, Hungary, Germany, Switzerland, France and UK Workshop to discuss findings in June 2014

15 Future Needs Research funding to fill the scientific gaps Regulatory involvement for validation and approval of the consistency approach Harmonisation of global regulatory requirements Global campaigns to encourage adoption of the consistency approach