www.who.int

Medicine Quality and Public Health

Substandard and Falsified Medical Products

• You are a local small pharmaceutical wholesaler who is licensed by the National

Regulatory Authority. You have been licensed for 10 years, but due to a

downturn in the economy your business is under financial pressure.

• You have a large consignment of 1000 packs (28 tablets per pack) of an Anti-

psychotic medicine which you were supplied by a reputable manufacturer at a

reduced price to due short expiry date. It formed part of a larger consignment of

medicines, the rest of which have been sold.

• The shelf life of the medicine is due to expire in 2 months.

How will you seek to sell these medicines without incurring a financial loss.

Examine all options and possibilities

Exercise 1

Democratic Republic of Congo

Remote rural area

Low literacy levels

Poor access to medicines

Civil unrest

3 medical centres and 100 medical staff dealt with over 1000 hospitalizations and at least 11 deaths

Containers labelled Diazepam containing an overdose of anti-psychotic medicine - Haloperidol

Irrational use of Diazepam

Limited Access in the region

Illegal cross border supply

Unethical / Criminal practice by distributors

Little regulatory oversight

FALSIFIED MEDICAL PRODUCT

• The role of WHO

• Member State Mechanism

• Global Surveillance and Monitoring System

• Causes, Consequences and Solutions

• Prevention, Detection and Response

• Ongoing projects

• Challenges

OUTLINE

THE ROLE of WHO

• Member State Mechanism

• Global Surveillance and Monitoring System

WHO MEMBER STATE MECHANISM

World Health Assembly 65.19 ; 2012

Recognised as an unacceptable threat to public

health

MANDATE

• Steering Committee

• 1 Chair (Spain)

• 11 Vice Chairs

• Regional Rotation

GOVERNANCE

International collaboration from a public health

perspective on substandard and falsified medical

products

PURPOSE

Member State Mechanism Steering Committee

African Region

Tanzania Togo

Americas Region

Brazil USA

Eastern Mediterranean Region

Iran Morocco

European Region

Spain (Chair) United Kingdom

South East Asia Region

India Indonesia

Western Pacific Region

China Malaysia

GOVERNANCE

MS MECHANISM WORK PLAN 2018/19

• Develop training material and guidance for Member States

• Expand and maintain the global regulatory focal point

network

• Detection technologies, authentication and track and trace

models

• Identify links between access and SF medical products

• Risk communication and awareness raising campaigns

• Understand and address the supply of medical products via

the internet and social media

9

A common global understanding

WHO DEFINITIONS (World Health Assembly 2017)

SUBSTANDARD

Also called ‘out of specification’, these are authorized medical products that fail to meet either their quality standards or their specifications, or both. e.g. Manufacturing error, expired or degraded

FALSIFIED

Medical products that deliberately/fraudulently misrepresent their identity, composition or source.

UNREGISTERED / UNLICENSED

Medical products that have not undergone evaluation and/or approval by the NRRA for the market in which they are marketed/distributed or used, subject to conditions under national or regional regulation and legislation.

Commissioned by the WHO Member State

mechanism, with objectives focused on:

Estimated prevalence of SF medical products

globally

Estimated economic impact of SF medical

products

Advocacy document for increased Political will

and investment

PUBLIC HEALTH AND SOCIO-ECONOMIC IMPACT OF SF MEDICAL PRODUCTS

www.who.int/medicines/regulation/ssffc/publications/se-study-sf/en/

METHODOLOGY

Expert technical group representing all regions convened

1. Need for Evidence Literature review covering 10-years of

publications

100 publications that matched inclusion

criteria

2. Assess the Extent of the Problem

Over 48,000 samples analysed

Quality surveys in 88 countries

Aggregation of observed failure rates

3. Making the Case for Attention and Investment

Multiplier method to estimate spending based

on country pharmaceutical sales

Results grouped by income level of World

Bank country classification

WHO ESTIMATES 2017

Observed failure rate of analysed medical product samples from low

and middle-income countries

10.5%

US$ 30.5 Billion Estimated spending on SF medical products in low

and middle-income countries based on un-weighted

estimates of pharmaceutical sales

SOCIO ECONOMIC STUDY – IMPACT MODELS

Estimated deaths caused by SF antibiotics

used by children under 5 with childhood

pneumonia*

72,430-169,271 Deaths

31,000 -116,000 Deaths

US$ 38.5 Million

Estimated deaths caused by SF products

used by patients suffering from malaria in

sub-Saharan Africa**

Estimated spending on SF anti-malarials

in sub-Saharan Africa

* University of Edinburgh

** London School of Hygiene and Tropical Medicine

SOCIO ECONOMIC STUDY - LIMITATIONS

Variation across studies

Definitions

Sample sizes

Sampling & testing methodologies

Uneven Distribution

Geographic representation

Therapeutic categories

Available pharmaceutical sales data

GLOBAL SURVEILLANCE and MONITORING SYSTEM

• Systematic reporting and search portal

• Photograph library of SF medical products

• Launched in West Africa in 2013

• Expanded to 150 Countries

• Global Regulatory Network of Focal Points

• 2000 Medical Products Reported from 110

countries

SURVEILLANCE AND ALERT NETWORKS

Global

Regional

National National risk based post

market surveillance and

reporting systems

Regional Rapid Alert Systems

WHO Global Surveillance and

monitoring system for

substandard and falsified

medical products

GLOBALIZATION = INCREASED VIGILANCE

December 2012, Pakistan

50 deaths

September 2013, Paraguay

46 patients hospitalised

WHO International Alert

WHO International Alert

Colombia and Peru

trace the API

Global Impact

8 Countries

4 Continents

0 50 100 150 200 250 300 350

Sensory organs

Dermatologicals

Systemic hormonal preparations

Blood and blood forming organs

Respiratory system

Various

Cardiovascular system

Musculo-skeletal system

Antineoplastics and immunomodulators

Genito-urinary

Alimentary tract and metabolism

Nervous system

Antiparasitics

Antiinfectives

WHO GSMS data; 2013-2017

MEDICAL PRODUCTS REPORTED BY THERAPEUTIC CATEGORY

Importance of sub- regional networks

African Customs Seizure Angola

Coartem – Anti malarial

1.383,528 packs

Postinor 2 – Emergency Contraceptive

4930 packs

Vermox – Worming treatment

1534 packs

Clomid – Fertility treatment

36,550 packs

Clamoxyl - Antibiotic

744 packs

* WHO Essential Medicines List Data extracted 11 January 2018

ANTI-MICROBIAL RESISTANCE*

First or second choice

antibiotics

Should be widely

available, affordable

and quality-assured

Most frequently reported

API: amoxicillin, penicillin,

sulfamethoxazole,

cloxacillin…

77% of antibiotics in the

database are Key Access

antibiotics

Key Access

Have higher resistance

potential

Key targets of

stewardship programs

and monitoring

Most frequently reported

API: ciprofloxacin,

ceftriaxone,

clarithromycin,

ceftazidime…

18% of antibiotics in the

database are on the Watch

Group

Watch Group

Should be treated as

“last resort” options

Tailored to highly

specific patients and

settings, when all

alternatives have failed

Reported products:

Linezolid

2 reports in the GSMS

database of reserve group

antibiotics

Reserve

Source: National Ministries of Health Alerts and Govt Press releases

Falsified vaccines around the world

2010 Cameroon

Meningitis

High prices

Stock Shortage

2016 Indonesia

Hepatitis B, Tuberculosis,

Polio, Tetanus

23 Arrests

2015-2017

Meningitis

Shortage

Public Supply

1995 Niger

Meningitis

2500 Deaths

2013-2016

Tetanus

Rabies

Vaccine Clinics

2009 Philippines

Influenza

2013

Rabies

10,800 Doses

17 Arrests

2010 China

Rabies

1 Death

8 Arrests

2016 Bangladesh

Yellow Fever

Public procurement

Falsified Yellow Fever Vaccine

Falsified vaccines discovered in Bangladesh

Local wholesaler supplied by a bogus employee pretending to work for the genuine manufacturer

No antigens present

Global WHO Alert Issued

Immunization Programme Indonesia

Diptheria

Pertussis

Tetanus

Polio

HIB Vaccine

Hep B

Snake Venom

Sera

TB diagnostic

Test kit

08/10/2018 26

GLOBAL SURVEILLANCE and MONITORING SYSTEM (November 2017)

www.who.int/medicines/regulation/ssffc/publications/gsms-report-sf/en/

• Data from the GSMS

• Case Studies

• Evidence v Anecdote

• Medicines most at risk

• Weaknesses in Health

Systems

• Vulnerabilities in

supply chains

SF Medical Products

Constrained access to

medicines

Weak

Technical

Capacity practices

Poor governance

SF Medical Products

Availability Affordability Acceptability

Poor oversight Lack of resources Limited awareness

Poor procurement Unethical practice Corruption

CAUSES

Lost Income

Lost Productivity

Lack of

Social Mobility

Economic Loss

Wasted Resources

Increased

Out-of-pocket Spending

Higher Disease

Prevalence

Progression of

Antimicrobial Resistance

Increased Mortality and

Morbidity (Adverse Effects)

Loss of Confidence

SUBSTANDARD

AND

FALSIFIED

PRODUCTS

Increased Poverty

CONSEQUENCES

SOLUTIONS

PREVENTION, DETECTION, RESPONSE

• Medicine Quality Surveys

24 Countries over 4years

• Smartphone Application for Healthcare

professional reporting

2 Pilot studies underway in Africa and South East Asia

• Pharmacy School Curriculum

4 African Pharmacy schools (2 Francophone, 2 Anglophone)

• Insight Studies on Communication campaigns

4 African Countries

WHO PROJECTS

• Risk Based Post Market Surveillance concept

3 Countries

• Upgrade of WHO Global Surveillance and

Monitoring System

Increased languages and functionality, linking to other systems

• Upgraded systems and database for Medicine

Quality surveys

• Streamlined collection protocol, tracking of samples and linking to

laboratory results

WHO PROJECTS

• Political will and leadership

• Transparency

• Investment in National Medicine Regulatory Agency

• Access to accredited laboratories and field detection technology

• Implementation of risk based post market surveillance

• Laboratory methods to differentiate between poor manufacturing and poor

distribution

• Better knowledge of degradation of products

• Links between SF medical products and anti microbial resistance

• More effective education and awareness campaigns, patient behaviours

CHALLENGES

Prevalence of SF medical products, including:

Product type

Geographic distribution

Level of active ingredient

Burden of Disease and health service

utilization

Geographic distribution

Effect of sub-therapeutic dosing, including:

Morbidity

Mortality

Antimicrobial resistance

Improved analytical techniques

Better data on stability of medicines

Differentiate between poor

manufacture and degradation

Reliable and affordable field detection

equipment

Out-of-pocket and health system spending

on health care:

Disaggregated by disease and

geographic region

Income lost, due to:

Death

Increased morbidity

Economic impact of increased antimicrobial

resistance on health systems

Costs to regulators and industry:

Product recalls

Other expenses

Health Impact Estimation Economic Impact Estimation

WHAT DO WE NEED TO KNOW?

KEY MESSAGESNeeds

POLITICAL WILL is required to translate policy agreed at the global level to SUSTAINABLE ACTIONS on the ground with APPROPRIATE FINANCIAL AND HUMAN RESOURCES

From global policy to local

impact

STRENGTHENING REGULATORY CAPACITY AND SYSTEMS is a key step and SOUND INVESTMENT to safeguard the manufacture, distribution and supply of medical products

Sound investment strategies

Improved REPORTING SYSTEMS and greater TRANSPARENCY within and between countries is required, together with wide and EFFECTIVE MULTI STAKEHOLDER ENGAGEMENT

Cooperation and

coordination

Thank you

08/10/2018 35

Michael Deats

WHO Group Lead SF Medical Products

deatsm@who.int

rapidalert@who.int