WHO Essential Drugs Strategy

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Safe quality medicines
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• Counterfeiting of drugs and the necessity of
  quality systems in developing countries

Sabine Kopp, PhD Quality Assurance and Safety
Medicines Department of Medicines Policy and
Standards
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Main points addressed

• Need for standards for medicines
• Examples counterfeits and DEG et al.
• WHO's measures and new developments

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Usual perceptions may not help in Making
judgements about medicines
Taste
Smell
Appearance
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Why stringent standards for medicines?

• " drugs are a public good and not simply just
  another commodity first for their high social
  value, and then because consumers and prescribers
  are unable to assess their quality, safety and
  efficacy"
• (Dr Gro Harlem Brundtland, former Director
  General of the World Health Organization)
• ? medicines belong to one of the most regulated
  group of products

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What Standards for Medicines?

• Medicines must meet quality, safety and efficacy
  criteria.
• These three sets of requirements are
  complementary to each other and each product has
  to be of good quality, safe and efficacious.
• It is possible that a product is of good quality,
  but may not necessarily be effective or safe
• It is possible that a product is effective, but
  may not necessarily be of good quality or safe
• It is possible that a product is safe but may not
  be of good quality or effective

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Problem Counterfeiting medicines is a major
public health concern
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What is a counterfeit medicine?

• Different definitions in different countries!!!

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WHO Definition of a counterfeit medicine

• A product that is
• deliberately and fraudulently mis-labelled with
  respect to source and/or identity.
• Counterfeiting can apply to both
• generic and branded products.

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WHO Definition of a counterfeit medicine

• Counterfeit products may include
• products with the correct ingredients
• with the wrong ingredients
• without ingredients
• with incorrect quantities of active ingredients
• with fake packaging

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Counterfeiting increasingly sophisticated
business
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Counterfeiting increasingly sophisticated
business
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Counterfeiting increasingly sophisticated
business
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Counterfeit Lipitor (20mg tablets)

• Text should
• be facing
• downwards
• as above

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Substandard medicines a big problem -
antibiotics, antimalarials, antituberculosis
drugs included
Percentage breakdown of data on 325 cases of
substandard drugs - including antibiotics,
antimalarials and antituberculosis drugs -
reported from around the world to WHO database
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Poor illegal manufacturing facility
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Poor control of distribution and sale
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In case of medicines they all look nice, mostly
do not have any smell, some may have bad
tasteand are increasingly marketed even through
internet (see example below, note that selling
medicines via internet may be illegal and
products may be counterfeit or substandard)
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What is the problem?

• Counterfeiting medicines is a lucrative
  "business" and seems emerging, affecting both
  developing and developed countries
• The real magnitude of the problem is unknown
• Existing data not comprehensive
• All parties concerned reluctant to make data
  AVAILABLE or REPORT

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Is there a health risk ?

• Under treatment or non-treatment
• Public health risk ineffective medicines
• Intoxication harmful ingredients
• No quality control
• Adverse reactions not monitored an effective
  product recall not possible
• Erosion of public confidence in medical care
• Waste of money
• .

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Main factors encouraging counterfeiting of drugs
globally? (I)

• Social value of medicines not given priority
  consideration when defining national drug
  policies
• Manufacturing without GMP compliance
• Poor storage and distribution condition

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Main factors encouraging counterfeiting of drugs
globally? (II)

• Lack of government commitment to create strong
  drug regulation
• Weak legislation,
• National medicines authorities weak in terms of
  resources, expertise, and enforcement
• Presence of unregulated markets, manufacturing
  distribution outlets

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Main factors encouraging counterfeiting of drugs
globally? (III)

• High prices and price differentials, health care
  providers and patients looking for cheaper
  sources
• In developing countries scarcity or erratic
  supply of drugs
• Lack of respect for trademark and other
  international agreements
• Corruption

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Main factors encouraging counterfeiting of
drugs globally? (IV)

• "Denial" of existence of problem by governments,
  industries, regulators, etc.
• International aspect of manufacture and supply of
  pharmaceuticals -gt difficult to control ?
  multi-jurisdictional
• New trade arrangements
• opening of boarders for trade
• trade through free ports
• trade through several intermediaries
• promotion and trade through Internet

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WHOs work in combating counterfeit medicines
Three strategies

• 1. Providing tools, international norms,
  standards and guidelines to assist that drugs
  circulating in national and international
  commerce are safe, efficacious and of good
  quality
• 2. Providing support to Member States to build
  national regulatory capacity
• 3. Developing global activities to combat
  counterfeit medicines

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a WHO initiative to combat counterfeit medical
products
Dr V. Reggi World Health Organization
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Who is in IMPACT ?
Who is in IMPACT ?
IMPACT All 193 WHO Member States and major
international stakeholders, such as
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IMPACT approach collaboration among all
those concerned is essential
FAKE MEDICAL PRODUCTS
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Quality of medicines remains a problem in many
countries tragedy in Panama in 2006

• The medical nightmare of Lucia Cruz, a
  74-year-old grandmother, began in mid-September
  2006 when she realized that she had not urinated
  in two days. She was sent to the hospital but her
  condition went from bad to worse. Nausea and
  vomiting came first. Then she could not breathe.
  Her kidneys continued to fail, her arms and legs
  got swollen and eventually she died. When she
  died, her physician told the family to cremate
  the body in case she carried a mysterious disease
  that might spread.

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Quality of medicines remains a problem in many
countries tragedy in Panama in 2006

• As it turned out the cause of death of more than
  30 other persons was more simple. The cough
  syrup and potentially other medicines produced in
  the governmental pharmaceutical factory were
  contaminated.

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Quality of medicines remains a problem in many
countries tragedy in Panama in 2006

• The death were likely caused by diethylene glycol
  (DEG) found in medicines. DEG is a chemical
  cousin of antifreeze and used widely by various
  industries. It is toxic to the kidneys and can
  cause deadly renal failure.
• Pictures. 1. Waiting for answer.
• 2. A popular medicine in Panama that turned to be
  a killer.
• 3. Medicines traced down and removed from supply
  chain

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Examples of incidents with DEG

• What happened?
• Contamination of glycerol with diethylene glycol
• Mix-up/substitution of propylene glycol with
  diethylene glycol
• Wrong labels
• Diethylene glycol instead of propylene
  glycol
• ? Diagnosis after several days? deaths

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Examples of incidents with DEG

• Why?
• Financial reasons
• Lax regulatory safeguards
• Lack of quality assurance, lack of GMP
  implementation, lack of quality control
• Lack of inspection
• Lack of certification of composition/origin
• ...

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Examples of incidents with DEG

• Where?
• Manufacturing of
• starting materials,
• intermediate or bulk product
• finished drug product
• International trade, distribution and supply
• Importation/distribution/supply of one of the
  above
• packaging and/or repackaging
• shipping

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Challenges past and present

• Past
• Manufacture direct from API -gt finished product
• Manufacture of API in sites close to or same as
  product
• Experience and long-standing knowledge of
  production, product and manufacture of parties
  involved
• Few intermediates in sales chain
• Usually stable trade and sales connections

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Challenges past and present

• Present
• Rationalization of drug production
• Contracting-out of many steps in manufacture
• Many intermediates in trade and sales chain
• Trade, shipping, long distances involved
• Increase of risks
• Increase of requirements and documentation
• Increase of national control mechanisms

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National regulatory and inspection systems

• --gt approx. 1/3 of WHO Member States have well
  developed regulatory systems, approx.. 1/3 have
  none
• In developed countries
• well organized, controlling national market
• dossiers evaluation and inspections
• different approaches used, few MRA
• In developing countries
• often difficulties of resources
• capacity?
• application of national and international
  guidelines
• --gt or non-existent .

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National Medicines Policy

• Need for common framework to coordinate many
  different actors in the pharmaceutical field
• These include - regulators (quality, safety and
  efficacy), - producers (local international), -
  users (prescribers consumers), - health
  planners managers, - health finance authorities
  and researchers
• Each have valid interests in the field which may
  be contradictory or supportive
• Involves both public private sectors

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WHOs global guidelines and strategies

• Requirements for drug registration and model
  legislation
• Networking - among and with regulatory
  authorities
• International alerts
• Counterfeit network
• Global norms and standards in
• - quality control, - production, - inspection, -
  related regulatory standards, - distribution and
  - nomenclature

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Scope of WHO Expert Committee on Specifications
for Pharmaceutical Preparations

• Cover medicines
• Production
• Quality Control
• Quality related regulatory guidelines
• Inspection
• Distribution
• ? from manufacture to delivery to patient

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When does the WHO Expert Committee start
development of a guideline/guidance?

• Based on recommendations by
• World Health Assembly resolutions (e.g. WHA
  20.34, GMP - Good manufacturing practices)
• Executive Board resolutions (e.g. EB37.R9
  delegating certain functions of INN Programme to
  DG based on advice from Experts)
• International Conference of Drug Regulatory
  Authorities (e.g. 10th 11th ICDRA FDC
  guidelines Certification Scheme for
  pharmaceutical starting materials moving into
  international commerce)
• Other WHO programmes and clusters (e.g. necessity
  for quality control specifications for specific
  medicines of major public health interest)
• Expert Committee (e.g. revision of general
  methods included in The International
  Pharmacopoeia)

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World Health Assembly resolution 52.19 May
1999 WHOs Revised Drug Strategy

• Concerned about the situation in which
• (a) one-third of the worlds population has no
  guaranteed access to essential drugs, and
• (b) poor quality pharmaceutical raw materials
  and finished products continue to move in
  international trade
• ... Taking note of concerns of many Member States
  about the impact of relevant international
  agreements, including trade agreements, on local
  manufacturing capacity and on access to and
  prices of pharmaceuticals in developing and least
  developed countries

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WHO efforts

• ? aim to improve access to quality medicines
• Provide standards and norms in area of quality
  assurance of medicines
• Pre-qualification project for UN procurement
• Provide assistance in regulatory area
• Promote logical order of actions
• Priority setting (ABC first )
• Capacity building
• Collaboration and co-operation

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WHO international guidelines, standards and norms
in the area of medicines quality
assurance?http//www.who.int/medicines/areas/qual
ity_safety/quality_assurance
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Safe quality medicines