Emer Cooke – WHO – Copenhagen, 26 Sept 2018

Regulatory forum for manufacturers

WHO Activities on Regulation of Medicines and other Health Technologies

Emer Cooke Director

Regulation of Medicines and other Health

Technologies

WHO Technical Briefing Seminar

02 October 2018

Key Themes of WHO’s 13th General Programme of Work

2019-2023

Mission Promote Health - Keep the World Safe - Serve the Vulnerable

Strategic Priorities

Health Coverage: 1 billion more people with health coverage Health Emergencies: 1 billion more people made safer Health Priorities: 1 billion lives improved

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WHO GENERAL PROGRAMME OF WORK - GPW 13

HEALTH EMERGENCIES 1 billion more people better protected from health emergencies

HEALTHIER POPULATION 1 billion more people enjoying better health & well-being

UNIVERSAL HEALTH COVERAGE 1 billion more people benefiting from health coverage

• Diagnostics • Biotherapeutics • Medical devices • Medicines • Vaccines • Vector control

products

Safe, Quality, Effective and Affordable health

products play key roles in achieving 3 billion goals

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“Access to Medicines, Vaccines and Pharmaceuticals (MVP)” Assistant Director General: Dr. Mariângela Batista Galvão Simão

Department of Essential Medicines and Health Products (EMP) Director: Sue Hill

Technologies Standards and Norms (TSN)

Regulatory Systems Strengthening (RSS)

Prequalification Programme (PQT)

Safety and Vigilance (SAV)

Regulation of Medicines and other Health Technologies (RHT)

Director: Emer Cooke

Innovation, Access and Use Coordinator: Sarah Garner

• Innovation, research & development • Intellectual property •Evidence-based selection of Model List of Essential Medicines

•Pricing, Health technology assessment (HTA) •Procurement and supply chain management • Improved use of medicines and health products

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Regulation of Medicines and other Health Technologies (RHT) Director: Emer Cooke

Technologies Standards and Norms (TSN)

Coordinator: François-X Lery

Prequalification Team (PQT)

Coordinator: Deus Mubangizi

Safety and Vigilance (SAV)

Coordinator: Clive Ondari

Regulatory Systems Strengthening (RSS) Coordinator: Mike Ward

• Antimicrobial resistance • Antivenom listing • Coalition of interested partners • Collaborative registration • Data integrity

• Global Benchmarking Tools • Emergency preparedness • Environmental issues • Local production • Non-communicable diseases

Cross Cutting Activities • Paediatric medicines • Shortages • Substandard & falsified

• Establish/maintain international norms and standards: (biologicals, blood and blood products, pharmaceuticals, GXPs*)

• Promote unified standards, as well as a global nomenclature

• Strengthen NRAs** for capacity building to increase efficiencies

• Promote reliance, harmonization, best practices & integrate framework for new products

• Assure quality, safety, efficacy/performance of health products:

(in vitro diagnostics, vaccines, medicines, medical devices, cold chain equipment, vector control products, pilot on biotherapeutics/biosimilar)

• Respond to and minimize health risks from medical products by improving product safety and vigilance through proactive, end-to-end, actionable, smart safety surveillance

*GXPs: good (clinical, laboratory, manufacturing, etc.) practices / ** NRAs: national regulatory authorities 5

“Towards Access 2030”

To Increase Access to Essential, High-Quality, Safe, Effective and Affordable Medical Products

Two strategic roles

http://www.who.int/medicines/publications/towards_access2030/en/

Supporting needs-based innovation and reinforcing health product

selection, use, procurement and supply systems to increase access

Strengthening regulatory capacity and practices to ensure the

quality, safety and efficacy of products and improve the

efficiency of regulatory system to secure health gains

Facilitator Guardian

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3

requires an integrated approach

across all regulatory activities

Access to quality medicines and other health technologies

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SAV

• Increased knowledge of real life adverse events

• Coordinated actions taken against adverse events

• Protection against substandard / falsified products

• Containing antimicrobial resistance

TSN

• Global norms and standards

• Common understanding on regulatory requirements by authority and manufacturer

• Standardized approach used by quality control laboratories

• Decreased work for authorities and manufacturers

RSS

• Collaborative & harmonized regulatory approaches in LMICs

• Faster/smoother registration

• Increased confidence in product quality, safety and efficacy

• Decreased cost & time of regulatory activities

• Local Production

PQT

• Qualify assured medicines, vaccines, medical devices, cold chain equipment, vector control products and more accurate diagnostics for use in LMICs

• Increased competition to shape the market

• patients to access quality medical products

Reduced mortality and morbidity

Decreased regulatory burden

Decreased cost of regulation

Reduced time for regulation

Increased regulatory capacity in LMIC

Strengthening regulatory capacity to ensure quality, safety and efficacy of medicines and health technologies – focusing on Outcomes

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Technical report series

WHO NORMS AND STANDARDS Technologies Standards and Norms (TSN):

MEDICINES QUALITY ASSURANCE GUIDELINES

VACCINES AND BIOTHERAPEUTIC PRODUCTS GUIDELINES OR RECOMMENDATIONS

90 93

International Pharmacopoeia

> 500 SPECIFICATIONS

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Setting international norms and standards for medical products, including:

• medicines • in vitro diagnostics • vaccines • biotherapeutics • blood products

Guidelines cover areas such as:

• Development • Production • Distribution • Inspection • Quality control and • other regulatory issues

Development Inspection

Production Other regulatory guidelines

Quality control Distribution

WHO NORMS AND STANDARDS Technologies Standards and Norms (TSN):

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Expert Committees:

• Specification for Pharmaceutical Products

• Biological Standardization

International Nonproprietary Names (INN)

The International Pharmacopoeia

Blood Regulators Network

Technologies Standards and Norms (TSN): How are the outputs achieved?

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Prequalification team (PQT):

• Provide United Nations agencies and WHO Member States with guidance on the acceptability and standards of quality, safety and efficacy or performance of health products for procurement

• Set up initially for vaccines in 1987, PQT now covers a spectrum of health products, including: o medicines (FPPs and APIs), quality control laboratories o in vitro diagnostics (IVDs), male circumcision devices o vaccines, immunization devices & cold chain equipment, o vector control products (since January 2017)

• The current PQ structure is the result of 5-year consolidation of quality assessment processes from across WHO

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Prequalification Achievements: broadening product types

Diagnostics In vitro diagnostics

(IVD) & male circumcision device

(MCD)

Medicines Finished pharmaceutical

product (FPP), active pharm ingredient (API), quality control lab (QCL)

Vaccines Vaccines (Vx),

Immunization device (ImD) & cold chain equipment (CCE)

Vector Control

VC Products (VCP) (VCPs: FPPs & APIs)

Larvicides Long-lasting

insecticidal nets Indoor residual

spraying products Space spraying

products

24 priority diseases, covering vaccines required for routine immunization Eligibility criteria for

evaluation includes NRA functionality & programmatic suitability

HIV/AIDS Malaria Tuberculosis Diarrhoea Influenza Reproductive

Health Neglected tropical

diseases (NTDs)

HIV/AIDS Hep B Hep C HPV Malaria G6PD Cholera Syphilis

80 IVD 2 MCD 612FPP 129 API

44 QCL

148 Vx (327 Vx*) 400 ImDs/CCE 71 VCP

(Cumulative numbers of PQed products: August 2018)

Hep B Hep C

NEW: as of Jan 2017

Vx*: covering all dosage forms 13

Risk assessment: snake antivenom / Ebola vaccines

Emergency listing: IVDs for Ebola / Zika

Prequalification updates and challenges:

• All product streams involve screening, assessment, inspection, laboratory testing (to a greater or lesser degree)

• Abridged procedures for all product streams

• Current focus on Malaria, TB, HIV, Reproductive Health and Neglected Tropical diseases

o Can model be used for non-communicable disease treatments

o e.g Pilot on similar Biosimilars

o Impact of prequalification on time to market in countries

o How to be more integrated and facilitate an end-to end approach

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Pilot procedure for prequalification of rituximab and trastuzumab:

• Pilot project of biotherapeutic products (BTP) or their corresponding similar biotherapeutic products (SBP) using either Full Assessment or Abridged Assessment pathways o Full assessment on SBP that have already been registered by non-SRAs, using SRA-

approved Reference biotherapeutic products as comparator, and marketed (in the authorized country)

o Abridged assessment on innovator products or SBPs for rituximab and trastuzumab that are approved by SRA

• Potential applicants so far: o Austria, China, India, Iran, Korea

• Nominations for assessors and inspectors received from 6 NRAs o Argentina, Denmark, Italy, Korea, Spain, UK

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• Listed in the EML + WHO technical guidance for evaluation • Some SRAs - extensive experience in evaluating these products • Multiple Manufacturers– potential for competition – increased access • Commitment to pursue collaborative registration in participating countries

How do we get the needed quality products to these patients faster, and more efficiently?

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Accelerated registration through Collaborative Registration Procedure (CRP)

Objectives: • to facilitate the assessment and accelerate national registration of PQ products • to accelerate registration of health products that have already received approval from a

“stringent regulatory authority”

Principles: • Voluntary for manufacturers and NRAs • Sovereignty –does not interfere with national decision making processes or regulatory

fees schemes • Identicality - ensures that the details of the nationally registered products are the same

as prequalified or approved • Co-operation between manufacturers, NRAs and WHO to overcome confidentiality

issues and ensuring information flow and product identity • Reliance – sharing detailed outcomes of assessment and inspections to support Yes- or

No- decision making in exchange for accelerated registration process (less than 90 days) • Maintenance “Harmonized product status' monitored and maintained

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CRP: Country registrations & therapeutic area

Total registrations: 353 (As at 5 July 2018)

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36

61

81

124

36

6 12 15 16 20 8 0

20

40

60

80

100

120

140

2013 2014 2015 2016 2017 2018

Registrations Countries

197 74

40

32

6 2

1 1

Therapeutic categories of registered medicines

HA

TB

MA

RH

NT

DI

HP

IN

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CRP: Median time to registration

As at 5 July 2018

*Including regulatory time and applicant time (without CRP, average time for registration is 2 – 10 years)

Days 81.0

93.0 78.0 75.0

93.0 78.0

85.0

0.010.020.030.040.050.060.070.080.090.0

100.0

Day

s*

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• Requires basic functionality of National Regulatory Authorities (NRAs)

• Investment in regulatory systems strengthening essential

• Increased focus on pharmacovigilance and post-marketing surveillance competences

But to build collaborative procedures,

CRP: What is needed to do more

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World Health Assembly Resolution 67.20 requests WHO to support Member States upon their request in the area of regulatory system strengthening, including, as appropriate, by continuing to:

Evaluate national regulatory systems

Apply WHO evaluation tools

Generate and analyze evidence of regulatory system performance

Facilitate the formulation and implementation of Institutional Development Plans (IDPs)

Provide technical support to national regulatory authorities and governments

Regulatory system strengthening (RSS)

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• Global Benchmarking Tool (GBT) to assess NRA capacity and identify gaps, followed by Institutional Development Plan (IDP)

• Moving from the concept of “Stringent Regulatory Authority” to “WHO Listed Authorities” based on the GBT

• Promoting reliance and facilitated market authorization pathways, including joint assessment and Collaborative Registration Procedure (CRP)

• Supporting convergence and harmonisation, regulatory networks such as AVAREF, EAC, CRS, SEARN

• Coalition of Interested Partners

• Pharmacovigilance preparedness

Regulatory system strengthening (RSS) What we work on:

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How can we get help to achieve this goal? Coalition of Interested Partners (CIP)

• More effective use of overall resources

• Better outcomes and impact through coordinated action at regional and/or country level

• Wealth of expertise available across the member organizations

• Greater capacity and sustainability

• Sharing and adoption of best practices

Build a framework to achieve better coordination, efficiency and outcomes in regulatory strengthening activities in the same target Member States or regions to achieve better public health outcomes

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Dealing with Emergencies: Some of the Gaps in Regulatory Preparedness

• Lack of coordinated emergency regulatory processes o Link regulatory processes with overall national preparedness planning

for public health emergencies

• Weakness of drug regulatory systems and lack of capacity o Strengthen regulatory collaboration and capacity

• Limited capacity and experience in stakeholder communication o Need for guidance in communicating with the media and public

• Poor engagement of product developers with affected regulators

• Weakness in regulation of supply chains o Need to minimize entry of substandard and falsified products in supply

chains

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Emergency Use Assessment and Listing (EUAL)

Following 2014 Ebola outbreaks in Africa, WHO introduced EUAL procedures to expedite the availability of medical products needed in PHEIC Procedures for candidate Vaccines, Diagnostics and Therapeutics published 2015

1. Intended to be used for UN procurement decision-making and to support highly impacted countries in their regulatory decision-making

2. EUAL is not prequalification, but a time limited procedure 3. Rolling review based on review of data by external experts 4. Listing under EUAL is based on eligibility criteria, a set of quality, safety and

efficacy data and benefit-risk assessment 5. Inclusion in the EUAL should not compromise the clinical development of the

product EUAL status as of June 2018

9 diagnostics evaluated (7 Ebola, 2 Zika) 3 applications for vaccines (Ebola) No therapeutics defined as eligible

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EBOLA RESPONSE What we supported as regulatory activities

• Support to member states on the review of Clinical trials of Ebola vaccines through AVAREF and collaboration from relevant Regulatory agencies and ethics committees – Nov 2017

• Development of WHO guidelines and reference standards • Development of EUAL procedures for IVD, pharmaceuticals and

vaccines – meeting with African countries and AVAREF – June 2018 • Expert review panel for Lassa diagnostics • Development of Public Health Emergency roadmap • CEPI Regulatory working group • WHO Blueprint • Pharmacovigilance preparedness, including vaccine safety monitoring

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Key Messages

• WHO is committed to contribute to access to safe, effective and quality medical products for every patient

• This can only be achieved with stakeholders and member states

• WHO encourages collaboration at regional and global level between member states for efficient use of resources

• Needs to adapt to a changing world – countries at the centre

• Pre-market safety assessment and post market surveillance are equally important

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• Strong Regulatory systems are on the critical path to innovation and access to safe, effective, quality and affordable medical products

• Opportunities to consider more modern and intelligent models of regulation that consider resource constraints, increasingly complex technologies, globalization and public expectations

• Good regulatory practices, flexible regulatory frameworks, and increasing focus on reliance and networking can help the challenges of an increasingly complex global regulatory environment

• Collaboration not Competition- the new reality to enable patient access

A Shared Responsibility for Improving Global Health

Dr Tedros Aghanom Ghebreyesus

“No family should endure financial hardship for out-of pocket payments for the purchase of medicines to treat their loved ones, and no man, woman or child should die simply because they cannot access the life-saving medicines they need.”

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RHT is there to help achieve WHO Vision!

A world where every child, man and woman has access to the quality essential medicines, vaccines and other health products they need to lead a healthy and productive life.

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