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 WardHealth Canada

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

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?

Historical Underpinnings Shaping the Language of Regulation

• Need for standards driven by the Industrial Revolution

• Accelerated in the 20th Century with the rapid expansion of trade, technology and a growing consumer population

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)

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

World of Harmonization Initiatives

Framing the Discussion – Some Important Terms

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

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

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

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

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

ICH Product Life Cycle

ICH Regulatory Authority

ICH Process:

Steps 1-3 Step 4 Step 5

Concept Paper

Draft for Comment

Adopt Implement

Implementation Issues

Finalize

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

“Adoption” versus Implementation

Finalized guidelineor standard

Regulatory Framework

Implementation Issues

Complete integration /implementation

Adoption or “Intent to Adopt”

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

Characteristics

• Organized into 5 sub-regional economic blocks

• Broader mandate• More players with greater diversity in

capacity and needs

18

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

• 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

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

“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

Two New Terms

• “Pharmacoverging”

• “Interconnectivity”

Pharmacoverging

pharma – pertaining to pharmaceuticalsco – together, joint, jointly, mutuallyverging – 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

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 13th ICDRA

A Global Regulatory Village