Regulatory issues, including ICDRAIPC Meeting, 16-17 December 2014.

Washington D.C., United States

Dr Lembit RägoHeadRegulation of Medicines and other Health TechnologiesEssential Medicines and Health ProductsWorld Health OrganizationGeneva, Switzerland E-mail: ragol@who.int

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ContentContent

Restructuring in WHO – one single unit for all health product streams with four specific activity oriented teams

Major landmarks in Global regulatory scenery

Regulators and emergency response

WHA resolutions and ICDRA

Concluding remarks

Disclaimer. The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and not necessarily those of the World Health Organization

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New structure of Department of Essential Medicines & Health Products. RHT unit covers medicines, biologicals including vaccines and blood products,

and medical devices with focus on in vitro diagnostics

New structure of Department of Essential Medicines & Health Products. RHT unit covers medicines, biologicals including vaccines and blood products,

and medical devices with focus on in vitro diagnostics

More at: http://www.who.int/medicines/en/

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WHO Ebola pages health products partWHO Ebola pages health products part

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Globalization and diseasesGlobalization and diseases

Emergencies involving emerging diseases (SARS, MERS, H1N1…, Ebola) is a Global issue.   No geographic area is immune – reduced flying times/better connections brings it to all of us

When crisis is over – could WHO convene a group to look at the lessons from not only Ebola, but also other recent experiences, to see what WHO did and did not do well, what affected NRAs did and did not do well, and what non-immediately affected NRAs did and did not do well …

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How to better respond to challenges like Ebola? How to better respond to challenges like Ebola?

Good news – good cooperation between concerned regulators and WHO (US FDA, EMA, Swissmedic, HC, African regulators from affected countries – AVAREF etc.)

The issue of clinical data confidentiality and study plan confidentiality in light of an epidemic. Companies have been open, the agencies still reluctant …Need for WHO guidance on planning, executing, and transparency of clinical trials/data in epidemic situations as a guide to expected behavior by member states and companies in epidemic situations?

“Emergency listings/approvals” to allow use in the affected countries.  Likely real “learning” about these products will come outside the clinical trials environment. But who’s responsible for that and who is assuring that the necessary structures are there?

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WHO is mandated to “develop, establish and promote international standards with respect to food, biological, pharmaceutical and similar products” (Article 2, WHO Constitution); the work is at large focusing on specific topics not address by other parties and complimentary to other standard setting initiatives

WHO Expert Committee on Specifications for Pharmaceutical Preparations WHO International Working Group on International Nonproprietary Names (also

for biologicals) WHO Expert Committee on Biological Standardization

…

Joint FAO/WHO Expert Committee on Food Additives

Standards and WHOStandards and WHO

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WHO global standards and norms – what are they? http://www.who.int/biologicals/biotherapeutics/en/

Global written standardsGlobal written standards Global Global measurementmeasurement standardsstandards

INNsINNs

Measurement standards: tools for product development, licensing and lot release

A single name for a substance for use globally(more than 8000 names assigned)

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WHO global standards - current portfolio

Pharmaceutical Preparations

approximately 75 written standards

approximately 240 International Chemical Reference Substances

a total of 700 specifications and test requirements in the International Pharmacopeia

Biologicals

approximately 70 written standards

approximately 300 international Biological Reference Substances

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2010 2011 2012

2013

Development of written standards for biologicals

ECBS 2010 - 2014

Cell substrates (TRS 978)YFV (TRS 978) Hep B (TRS 978)Vaccine lot release (TRS 978)

Dengue (TRS 979)BCG (TRS 979)aP (TRS 979)

OPV (TRS 980)D, T + Combos (TRS 980) Malaria (TRS 980)JE LA (TRS 980)

Nonclinical evaluation of adjuvanted vaccines (new) Biologicals derived by rDNA tech (revised)Typhoid conjugate vaccines (new)Strategic plan for blood and blood products (revised)

IPV (revision of TRS 926)Manufacturing Changes (new)Regulatory Risk Assessment(new)

2014

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http://www.who.int/biologicals/biotherapeutics/similar_biotherapeutic_products/en/http://www.who.int/biologicals/biotherapeutics/similar_biotherapeutic_products/en/

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Collaboration in making regulatory guidelines: Good Review Practices

Proposal from APEC to WHO/ECSPP and WHO/ECBS to develop a Guideline on GRevP

Such a guideline would be the first of its kind globally, addressing an important gap

ECSPP/ECBS agreed to collaborate with APEC to develop draft GRevP guidelines

Global consultation process completed in 2014, and guideline adopted by WHO ECSPP

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https://extranet.who.int/sree/Reports?op=vs&path=/WHO_HQ_Reports/G4/PROD/EXT/Design%201.1

http://apps.who.int/prequal/trainingresources/training_EMP_table.htmhttp://apps.who.int/prequal/trainingresources/training_EMP_table_2.htmhttp://www.who.int/medicines/training/qsm_training/en/

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Increased Collaboration: WHO Prequalification inspections' group has increased steadily International

Collaboration

Share the workload and promote avoiding duplicative inspections.

Facilitation of harmonization through joint inspections and sharing of outcomes.

Capacity building of NMRAs inspectors.

Facilitating use of WHO-PQ inspection results in national regulatory environment for information and decision making.

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AVAREF-African Vaccine Regulatory ForumAn informal network approach to regulation of clinical trials in Africa

National RegulatoryAuthority

Ethics Committees

Representation: 19 countries target for CT of HIV, Malaria, TB, meningitis vaccines

Scope

Regulation of medicines

Regulation of vaccines

Regulation of clinical trials

Support from USFDA, Health Canada, European regulators

New vaccines in clinical development presented by sponsors/Vaccine developers

Recognized and supported by donors as an efficient platform

Informal structure allows rapid and dynamic response as per needs identified Currently working on

formalization process

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World Health Assembly 2014 resolution WHA67.21 on biotherapeutic products

World Health Assembly 2014 resolution WHA67.21 on biotherapeutic products

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http://apps.who.int/gb/e/e_wha67.html

WHA67.21 Urges Member States:http://apps.who.int/gb/e/e_wha67.html

WHA67.21 Urges Member States:

(1) to develop or strengthen, as appropriate, national regulatory assessment and authorization frameworks, with a view to meeting the public health needs for biotherapeutic products, including similar biotherapeutic products;

(2) to develop the necessary scientific expertise to facilitate development of solid, scientifically-based regulatory frameworks that promote access to products that are affordable, safe, efficacious and of quality, taking note of the relevant WHO guidelines that may be adapted to the national context and capacity;

(3) to work to ensure that the introduction of new national regulations, where appropriate, does not constitute a barrier to access to quality, safe, efficacious and affordable biotherapeutic products, including

similar biotherapeutic products;

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WHA67.21 REQUESTS the Director-General of WHO: WHA67.21 REQUESTS the Director-General of WHO:

(1) to support Member States in strengthening their capacity in the area of the health regulation of biotherapeutic products, including similar biotherapeutic products;

(2) to support, as appropriate, the development of national regulatory frameworks that promote access to quality, safe, efficacious and affordable biotherapeutic products, including similar biotherapeutic products;

(3) to encourage and promote cooperation and exchange of information, as appropriate, among Member States in relation to biotherapeutic products, including similar biotherapeutic products;

(4) to convene the WHO Expert Committee on Biological Standardization to update the 2009 guidelines, taking into account the technological advances for the characterization of biotherapeutic products and considering national regulatory needs and capacities

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Where we are with medicines regulatory

systems today?

WHO has developed a comprehensiveAssessment Tool for National Regulatory

Authorities with objectives:1. To identify gaps and help

to develop institutional development plans

2. In conjunction with vaccines prequalification: as a pre-condition of prequalification

The attached publication from 2010 is a good example of this work and available also on web site.

Note. Each study published is out of date in certain details and progress has been made since assessments in several countries

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Regulatory system strengthening for medical products WHA67.20

Regulatory system strengthening for medical products WHA67.20

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WHA67.20 Urges Member States, among others:WHA67.20 Urges Member States, among others:

1) to strengthen national regulatory systems, including – as appropriate and voluntarily – by:

(a) undergoing self-evaluations, including with WHO support, to identify the strengths and opportunities for improvement in regulatory system functions, as a first step towards formulating plans for regulatory system strengthening, including through WHO-coordinated institutional development plans; …

(e) developing needed competencies as an integral part of, although not limited to, the health workforce, and encouraging the development of the regulatory field as a profession;

(f) facilitating the use of relevant guidance and science-based outputs of WHO expert committees and good regulatory practices at the national, regional and international levels; …

(2) to engage in global, regional and subregional networks of national regulatory authorities, as appropriate, recognizing the importance of collaboration to pool regulatory capacities to promote greater access to quality, safe, efficacious and affordable medical products;

(3) to promote international cooperation, as appropriate, for collaboration and information sharing, including through electronic platforms; …

(10) to identify the need to strengthen regulatory system capacity, collaboration and cooperation in the technically complex areas where substantial gaps may still exist, such as the regulation of biotherapeutic products, blood products, and in vitro diagnostics;

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WHA67.20 REQUESTS the Director-General of WHO, among others:

WHA67.20 REQUESTS the Director-General of WHO, among others:

(1) to continue to support Member States upon their request in the area of regulatory system strengthening, including, as appropriate, by continuing to:

(a) evaluate national regulatory systems; …

(e) provide technical support to national regulatory authorities and governments;

(2) to continue to develop appropriate norms, standards and guidelines, including taking into account national, regional and international needs and initiatives, in accordance with WHO principles; …

(5) to promote the greater participation of Member States in existing international and regional initiatives for collaboration and cooperation in accordance with WHO principles and guidelines; …

(10) to increase support and guidance for strengthening the capacity to regulate increasingly complex biological products with the focus on biotherapeutic products, blood products and associated in vitro diagnostics, and, where appropriate, on new medicines for human use based on gene therapy, somatic-cell therapy and tissue engineering;

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Harmonization and convergence of regulatory requirements: creating basis for regulatory cooperation

• Objective of drug regulation: TO IMPROVE AND PROMOTE PUBLIC HEALTH

• Harmonization/convergence is aimed to diminish

duplicative efforts, creates "common language", can facilitate cooperation and access to medicines

• In case of harmonization/convergence of regulations the main objective should be: – MEASURABLE PUBLIC HEALTH GAINS

• There may be other gains, but these should be in the centre

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Harmonization and convergence initiativesHarmonization and convergence initiatives

Inter-regional, regional and sub-regional – ICH, IPRF, APEC, Pan American Network for Drug Regulatory Harmonization (PANDRH), ASEAN, SADC, EAC (part of AMRHI), Gulf Cooperation Council, IGDRP etc.

Not harmonized! – Good Harmonization Practice (GHP) needed?– Different organization – with or without strong secretariat– Different involvement of industries and other parties– Different in terms of implementation – some focused on

implementation, others rather focused on convergence of regulatory thinking and eduction

– Different focus technical areas/products

– …

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Key elements of success (1) Key elements of success (1)

Enabling environment and foundation

– Good Governance principles implemented

– Modern legal systems allowing certain flexibilities

Political will and shared common vision

Similar socioeconomic development of participating countries

Participants functional regulatory authorities with necessary capacity and resources available

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Key elements of success (2) Key elements of success (2)

Willingness to invest into harmonization and convergence

Effective governance and secretariat

Willingness to cooperate and compromise

Commitment for implementation and updating/revision

Commitment for applying Good Regulatory/Review Practice principles when implementing

…

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Timely access to better (hopefully) medicines ladder.Where the cooperation and reliance on work done by other regulators fits in?

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Regulatory co-operationRegulatory co-operation

In nowadays complex and interlinked World with rapidly advancing science not a single regulator can operate in isolation, or cope with all the work to be done

– Regulators have ONE common thing across small and big – all complain about lack of resources

Cooperation can be passive/receiving and active/contributing

Cooperation can be institutionalized and legally mandated or voluntary

Whatever the option/s cooperation enables saving resources and making more QUALITY DECISIONS

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Experiences of successExperiences of success

EU experiences – few regulators from 28 MS take the active lead but all benefit (harmonization and legal framework major enabling factor)

EAC and ZaZiBoNa in AfricaJoint reviews of clinical trial applications/products across

borders– AVAREF

– Medicines Prequalification Programme jointly with EAC regulators

Promoting international harmonized standards and good review by staff exchange

– Medicines prequalification has a 3 months rotational fellow position for quality assessors has lead to local subregional activities of cooperation; SA 1st API rotation, Inspectors rotation - China

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Collaboration and cooperation in ICDRACollaboration and cooperation in ICDRA

14th ICDRA recommendations in 2010 for Medicines Regulatory Authorities in Singapore:

Take account of one another’s work with a view to improving the efficiency of the global regulatory system.

Commit resources to form cooperative networks based on uniformity of standards and inspection systems.

Engage with regional and international initiatives promoting harmonization, information sharing and use of data generated by other regulators as a tool for improving timely access to medicines and medical products.

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Collaboration is a necessity, not nicessety. Next ICDRA will be hosted by an African country in 2016!

Collaboration is a necessity, not nicessety. Next ICDRA will be hosted by an African country in 2016!

http://www.anvisa.gov.br/hotsite/icdra/index.html#

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http://www.who.int/medicines/areas/quality_safety/regulation_legislation/icdra/en/

http://www.who.int/medicines/areas/quality_safety/regulation_legislation/icdra/en/

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16th ICDRA sessions16th ICDRA sessions

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Plenary 4Strengthening regulatory systems for

medical products

Plenary 4Strengthening regulatory systems for

medical products Recognize that effective regulatory systems are an essential component of

health system strengthening that contribute to better public health outcomes; that regulators are an essential part of the health workforce; and that inefficient regulatory systems themselves can be a barrier to access safe, effective and quality medical products.

Strengthen WHO’s role in strengthening regulatory systems for medical products from a public health perspective, and in supporting national drug regulatory authorities and relevant regional bodies in this area, and in particular in developing countries.

Support the development and strengthening of national regulatory systems through the assessment of regulatory functions and system performance with WHO support, and the development and implementation of institutional development plans that will protect and promote health at the national level, and will pool and leverage regulatory capacity regionally and globally to promote access to quality, safe and efficacious and affordable medical products

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Concluding remarks