Promoting an Effective Approach to regulatory Convergence and Cooperation through GRevPs

9th Conference of APEC Network on Pharmaceutical

Regulatory Science

October 15, 2011

Taipei City

Mike Ward

Chair, APEC RHSC

Objectives of GRevP Workshop

October 12-14, 2011

• To establish a common understanding of

good review practices (GRevPs) and why

they are important

• To share best practices and advance

thinking on GRevPs

• To ultimately contribute to regulatory

performance and interagency cooperation

Expected Outputs

• Summary of discussions, ideas and

recommendations

• Outputs will assist in developing more

advanced course, a report and a series of

recommendations

• Recommendations to be considered for

further action

Target Audience

• Officials from regulatory authorities

involved in the review and authorization of

medical products

• Role of industry

– Continuum

– Responsibilities and expectations

Open Forum

October 15, 2011 • Mixture of presentations and summary

reports from GRevP workshop sessions,

ending with panel discussion and closing

remarks

• Includes a presentation on GRevP roadmap

• Opportunity for communicating outcomes

• NB – workshop materials and summary

outcomes to be made publicly available

Context

Some background on APEC to put GRevP

activities into context….

a brief word on why this workshop

is taking place under the APEC

banner…

Overview of APEC • Asia-Pacific Economic Cooperation (APEC) created

in 1989

• Currently comprised of 21 member economies

• Goals: Promote trade, sustainable economic growth and prosperity of member economies through policy alignment and economic and technical cooperation

• APEC agenda and annual work plan developed around SOMs culminating in Leaders declaration

• APEC Chair rotates annually – host economy (Singapore 2009, Japan 2010, US 2011, Russia 2012)

Source: APEC

Life Sciences Innovation Forum

• Created following endorsement by

APEC Leaders in 2002

• Recognized importance of life sciences

innovation in promoting public and

economic health

• From outset, harmonization seen as

prerequisite to fostering innovation

LSIF an enabler of harmonization

Unique in that LSIF doesn’t produce harmonized guidances; rather, promotes use of existing international guidelines:

• Ability to access APEC funds to advance projects

• Voluntary basis for engagement: ensures participation of those economies interested and committed to cooperation

• Linkages to international harmonization initiatives: since 2004 sits on the ICH Global Cooperation Group

• Tripartite structure / complementary roles: government, industry, academia

• To date, sponsored many workshops on ICH and GHTF guidances

Important Developments

June 2009, Seoul:

– Inauguration of the APEC Harmonization

Center (AHC)

– Creation of a Regulatory Harmonization

Steering Committee (RHSC)

APEC Harmonization Center

• APEC-wide resource to enhance and sustain

harmonization and capacity building efforts by:

– conducting research and surveys

– providing educational programs

– publishing and web posting

– establishing networks and exchanges

• Operates under the authority of LSIF, with

direction from RHSC and an international

advisory board

RHSC: Mandate and Goals

To promote a more strategic, effective and sustainable

approach to harmonization by:

– Proactively identifying and prioritizing projects seen

to be of greatest value

– In partnership with AHC, strengthen linkages with

harmonization initiatives, training organizations and

other key players to promote complementary actions

and most effective use of resources

– Products of interest: medical products, notably drugs

and devices

RHSC Members

• Regulators from Canada, China, Chinese

Taipei, Japan, Republic of Korea, Peru,

Thailand and USA with official observers

from Mexico and Singapore

• Industry representatives from drug and

medical device sectors

• Director of APEC Harmonization Center

Strategic Framework Developed

• Framework outlines strategic multi-year approach for achieving greater regulatory convergence by 2020

• Describes guiding principles and general multi-step approach

• Includes appendices for pharmaceuticals and medical devices and suggested indicators of success

• Voluntary action: each economy proceeds at own pace

• Also includes definition of regulatory convergence

Regulatory Convergence

Regulatory convergence, within context of the framework and APEC principles of voluntary action, represents a process whereby regulatory requirements across economies become more similar or aligned over time as a result of the gradual adoption of internationally recognized technical guidance documents, standards and best practices.

Does not represent the harmonization of laws and regulations, which is not necessary to allow for the alignment of technical requirements/approaches and greater regulatory cooperation.

Strategic Framework

Coordinated approach

to promote regulatory convergence

Priority Work Areas

Needs assessment from diagnostic workshops

and a roadmap for promoting best practices

Individual projects are part of strategy & contribute to goals

Move away from Ad Hoc/Individual Proposals

Project Project Project

Higher Level Regulatory Areas of Focus

Good Regulatory Practices

Prospective Harmonization

Product Quality

Supply Chain Integrity -Drug Security & Safety

Post Market Surveillance - Vigilance - Inspection / Auditing

Clinical Trials - MRCT - GCP Inspection

Biosimilars - Develop roadmap depending on objectives and whether

foresee series of activities to effect desired outcomes

Priority Work Areas (PWAs)

• Define priority clusters

• Roadmap to be developed by champion

economy for each PWA

• Champions/PWAs identified to date:

– MRCTs (Japan - roadmap completed)

– Supply chain integrity (US)

– Pharmacovigilance (Republic of Korea)

– Cellular Therapies (Singapore)

Training Approach

• Workshop as diagnostics

• Act upon recommendations from workshop, including true training sessions aimed at acquiring new skill or knowledge

• Events open to non-APEC economies

• Sustainability, including AHC and annual curriculums

• Make use of available technologies and AHC website to maximize access and reuse of information

An Example: MRCTs

• June 09 and Sept. 10 workshops in Seoul

served as a diagnostic of challenges, issues,

opportunities

• Led to a series of recommendations on

addressing challenges to MRCT

• Recommendations considered by RHSC in

developing project proposals leading to

concrete, directed actions as part of proposed

MRCT roadmap

Workplan 2011-13

• Global Drug Integrity and Supply Chain (US)

• MRCTs – MHLW/PMDA

• Good Clinical Practice Inspection (Thai FDA)

• Good Review Practices (TFDA)

• Biosimilars

• Pharmacovigilance (AHC/KFDA)

• Combination Products

• Projects completed: – ICH Q8/9/10

– Stem Cell QC/QA Workshop (Thailand)

– Implementation of GHTF Documents (MHLW/PMDA)

– AHC/DIA/IFPMA Asia Regulatory Conference (AHC)

Conclusion

• Developments within APEC that have implications beyond the region in advancing regulatory harmonization in a more strategic, sustainable and effective manner

• Directed towards concrete, complementary actions

• Key role as an enabler: building a better global regulatory convergence model

• Developments to be posted on AHC website in near future (www.apec-ahc.org)

• GRevP project an important part of this overall strategy

Why are Good Review Practices important?

Regulators on Critical Path

• The extent to which regulatory authorities fulfill

their mandate in a timely, effective and consistent

manner can have significant impact on access to

medical products, public health, product

development costs and promoting conducive

environment for research and innovation

• At issue: the contribution of Good Review

Practices (GRevPs) to a well-functioning

regulatory review system and to inter-agency

cooperation

What is required from a regulatory review system?

Predictability Quality Review

Consistency

Transparency

Timeliness

Efficiency

Effectiveness

Tangible elements of a quality review

Right format; scientifically sound; legally and

scientifically consistent; procedurally predictable

and within time targets

Source: CIRS

Good Review Guiding Principles

• A good product review is an independent,

objective, scientific and timely analysis of

information relevant to a marketing application

• Considers context (proposed conditions of use)

and regulatory framework within which

assessments and decisions made

• Documents in clear and consistent manner all

evidence and considerations taken into account in

reaching conclusions, recommendations and

decisions

The Case for GRevPs

• Review highly complex undertaking

• Forms scientific basis for regulatory

decisions, consequences of which highly

significant

• Can’t clone experienced reviewers

• Essential to promoting consistency,

transparency and performance

GRevPs not a panacea, but..

• Good Review Practices can’t and perhaps shouldn’t take the ‘art’ out of review, but should provide those involved in review and decision-making process the best possible support and tools for ensuring consistent, science-based assessments that comply with legal requirements

Advantages of

Good Review Practices System

• Enhanced review system

• Increased interaction between reviewers and

industry

• Enables more effective training

• Minimizes the risk of critical omissions

• Enhanced clarity regarding assessment and

ultimate decisions

GxP and QMS

GAP

GMP

GDP

GCP

GPhVP

..etc

Industry Regulators

Good Regulatory Practices

Good Review Practices

Good Guidance Practices

Good Communication Practices

Common Objectives: Consistent, high quality product

QMS

QMS

Common Elements

While no single definition of GRevP exists, common elements include:

– Principles, procedures and templates related to the review process, including its management, peer review, use of internal/external advisory and interactions with sponsors

– Orientation and training for staff and management linked to defined competencies

– Information repositories

Part of continual improvement process

– Conducting internal quality audit

– Self-assessments

– Analyses of feedback from stakeholders

– Post-approval analysis with other authorities and industry

– Management reviews, and

– Using the results to take corrective action or introduce improvements to the review process and decision-making

Role of GRevP in promoting trust and confidence

The belief:

– Implementation of good review practices,

combined with adoption of common, science

based standards and guidelines that define

regulatory expectations for establishing the

safety, efficacy and quality of medicinal

products, are essential in building trust and

confidence in regulatory systems

Role of GRevP in promoting trust and confidence

• GRevPs should then be important not only within domestic context but also in building trust and confidence among regulatory authorities which, in turn, important for inter-agency exchange and optimal use of regulatory information

• GRevPs help ensure that review reports are well structured, comprehensive, clear and consistent - key considerations in potential use by other authorities

• Should also influence selection of partners for joint reviews or other forms of ‘real time’ collaboration and dialogue

Presumptions in looking ahead

• The contribution of GRevPs to interagency

cooperation has not been fully realized

• The evolution and implementation of GRevPs

within agencies coupled with the increasing

need to leverage one another’s resources and

work will become increasingly important

Further Considerations

• Doesn’t mean that decisions of different agencies will be the same: need to distinguish assessment of quality, safety and efficacy from broader benefit-risk considerations specific to a particular country and health care systems

• Also doesn’t mean that one size or approach to GRevP fits all agencies: different approaches and best practices more likely

• Equivalence rather than harmonization

• EU experience: glimpse of things to come? (interestingly, not a recognized term under centralized procedure)

Outcomes of Workshop

• Forged a common understanding of GRevPs, their importance and an appreciation for this topic as a recognized discipline

• Realization that many agencies have some or many of the elements of GRevPs, even if no prior, formal designation as such

• Different approaches to reach the same end: a better functioning agency, no matter how well resourced you are and what functions you undertake

Outcomes of Workshop

• Adopt a pragmatic approach, appropriate to

local realities and resource

• Advanced discussions on GRevPs

• People engaged

Next Steps

• Findings from surveys

• Advanced course -> annual curriculum

• Develop a best practices document on GRevPs – Definition

– Elements

– Suggested approaches to implement or enhance

– Metrics and assessment

• Pilot and possible framework on the exchange and use of regulatory information

• Roadmap on GRevPs

Thank you for your attention