1. History and Importance of Terminology, the Terminology Landscape, and Options for Regulators Institute of Medicine Workshop International Regulatory Harmonization Amid Globalization of Biomedical Research and Medical Product Development Washington DC, February 13-14, 2013 Mike Ward Health Canada

2. The Regulatory Lexicon Regulatory Cooperation Harmoniz(s)ation – Convergence – Alignment – Coherence – Integration Equivalence – Mutual/Unilateral Recognition – Reliance Guides – Guidelines – Standards Laws – Regulations – Directives Conformity Assessment Treaties – Arrangements Bilateral – Plurilateral – Multilateral Adopt – Adapt - Implement

3. Why is this Important? No internationally ‘harmonized’, ‘standardized’ or ‘consensus’ definitions Compounded by increasing number of terms, often used interchangeably, can lead to confusion and set unrealistic or varying expectations in the minds of central agencies, regulators, industry, consumers and other vested stakeholders Effective cooperation begins with a common language: a possible outcome of this workshop?

4. Historical Underpinnings Shaping the Language of Regulation Need for standards driven by the Industrial Revolution Accelerated in the 20 th Century with the rapid expansion of trade, technology and a growing consumer population

5. Notable Post WW2 events 1947: Creation of the International Organization for Standardization (ISO) and the signing of the General Agreement on Tariffs and Trade 1994: Marrakesh Agreement on Establishing the World Trade Agreement (WTO) -> TBT and SPS Agreements particularly important in defining Member obligations, policy and terminology in non-tariff arena Creation of the EEC (1957)-> EC (1967)-> EU(1993)

6. Internationalization of Biomedical Product Regulation Rapid increase and diversity of technical requirements witnessed in 1970s and ‘80s...coupled with globalization, increasing workloads, complexity of products, rising development costs, more informed public, etc. While initially (and still) motivated by trade and commercial considerations, desire to cooperate increasingly driven by regulators and other players

7. World of Harmonization Initiatives

8. Framing the Discussion – Some Important Terms

9. International Regulatory Cooperation (IRC) Inter-country activities carried out with a view to improving national regulatory outcomes and promoting convergence Occurs at all stages of the regulatory lifecycle Includes a wide range of undertakings such as information sharing, collaborative scientific work, developing common or international standards and worksharing - adapted from draft GoC consultative document on IRC, April 2006

10. Harmonization – Some Definitions “Bringing into harmony, agreement, accord” – Common dictionary usage “Yields same result” – Pharmacopeial harmonization “The establishment, recognition and application of common… measures by different members (jurisdictions)” – WTO SPS Agreement

11. Considerations Key enabler for enhanced cooperation May occur at different levels – Technical requirements – Procedures and processes – Laws and regulations Simple in concept…more difficult in execution Gold standard: ICH

12. ICH: Keys to Success Involvement of both regulators and industry Science-based, consensus driven Well managed Limited number of players with comparable regulatory and technical capability Commitment of regulators to implement products of harmonization

13. Adoption…Adaption…Implementation Adoption – Official (administrative) incorporation of a guidance or standard into the regulatory framework “as is” Adaption – Deliberate changes, additions, restrictions; may or may not respect principles of source document Implementation – The true measure of harmonization

14. 14 ICH Product Life Cycle ICH Regulatory Authority ICH Process: Steps 1-3Step 4Step 5 Concept Paper Draft for Comment Adopt Implement Implementation Issues Finalize

15. Implementation Considerations Regulatory implications Collateral policy/guidance work Scope of application Training/competencies Infrastructure/system requirements Inherent complexity of product Readiness of industry Resources 15

16. 16 “Adoption” versus Implementation Finalized guideline or standard Regulatory Framework Implementation Issues Complete integration / implementation Adoption or “Intent to Adopt”

17. PANDRH – Variation on a Theme Pan American Network on Drug Regulatory Harmonization established to promote pharmaceutical regulatory harmonization and capacity building within the Americas From the start, recognized pre-existing asymmetries within the hemisphere 17

18. Characteristics Organized into 5 sub-regional economic blocks Broader mandate More players with greater diversity in capacity and needs 18

19. A Different Definition of Harmonization Harmonization understood to be the search for common ground within the framework of recognized standards, taking into account the existence of different political, economic and health realities among the countries of the region 19

20. Represents process whereby regulatory requirements across economies become more aligned over time as a result of the adoption of internationally recognized technical guidances, standards and best practices Does not require the harmonization of laws and regulations Broader concept than “harmonization” – Example: Good Review Practices Regulatory Convergence 20

21. Equivalence Two or more systems are said to be “equivalent” if, despite differences, they are expected to produce the same outcomes Should be established through objective means and documented Example: Mutual Recognition Agreements relating to conformity assessment of GMPs 21

22. 22 “Regulatory Cooperation – “The Continuum” Development /adoption of same or similar standards and processes Enhanced forms of cooperation: e.g., worksharing, reliance Catalysts: workload, globalization, technology, public expectations Feedback Assess equivalence Convergence: a dynamic process

23. Two New Terms “Pharmacoverging” “Interconnectivity”

24. Pharmacoverging pharma – pertaining to pharmaceuticals co – together, joint, jointly, mutually verging – being on the edge or margin of something – the limit beyond which something begins to happen “If you want to promote change you may need to change the vocabulary” - Capt. Justina Molzon, CDER, US FDA

25. Interconnectivity “WHO should promote the principle of interconnectivity: Information sharing and cooperation between harmonization initiatives and enabling organizations in order to build synergies, leverage capacity and sustain efforts” - Recommendation from 13 th ICDRA

26. A Global Regulatory Village