Quality Control Approaches for Essential Medicines

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Quality Control Approaches for EssentialMedicines

• Good Intentions Bad Drugs
• The World Bank
• March 10, 2005

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United States Pharmacopeia

• Private, not-for-profit organization since 1820
• Establishes official manufacturing standards
  enforceable by the U.S. FDA and many other
  countries
• Publishes USP/NF annually
• Distributes chemical reference substances used to
  carry out tests for product identity, strength,
  quality, and purity
• 400 member organizations
• 650 volunteer experts, www.usp.org/volunteers
• Global Assistance Initiatives, Patient Safety,
  Dietary Supplements Verification

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Good Quality Definition

• Good quality medicines meet official standards
  for identity, strength, purity, quality,
  packaging, and labeling.

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Legal basis United States

• A drug or device shall be deemed to be
  adulterated if it purports to be or is
  represented as a drug the name of which is
  recognized in an official compendium, and its
  strength differs from, or its quality or purity
  falls below, the standards set forth in such
  compendium (Section 501(b) of the Federal Food,
  Drug, and Cosmetic Act).

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Standards for drug quality

• Internationally recognized pharmacopoeias -
  e.g., IP, USP, EP, JP, and BP
• Official national pharmacopeias
• Standards and analytical methods developed by the
  manufacturer
• Public standards needed for new products with
  high public health importance, e.g.,
  antiretrovirals, artemisinin-derived

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An Early USP Monograph
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Isoniazid Monograph
Isoniazid
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Dissemination of Standards
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Poor quality products

• Fake/counterfeit deliberately mislabeled for
  identity and/or source. (Usually no active
  ingredient or a different active ingredient than
  on the label)
• Substandard legally registered innovator or
  generic product, but does not meet official
  standards for identity, quality, purity,
  strength, packaging and labeling.

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Why be concerned about drug quality?

• Because counterfeit and substandard drugs are
  prevalent worldwide
• People living in countries with limited
  regulatory capacity and resources are most
  affected
• Substandard drugs may be ineffective or toxic
• Undermines trust in national disease programs
• Waste of limited financial resources
• Can lead to drug resistance and loss of
  life-saving therapies

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What drugs are being counterfeited?
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Whats wrong with the drugs?
Other deficiencies, such as contamination, weight
variation, unusual appearance, incorrect labeling
No active ingredient
Incorrect amount of Active ingredient
Source Carpenter J P, 2003. Drug quality report
matrix of USAID-assisted countries by the USP DQI
Program, www.uspdqi.org
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Availability of poor quality medicines

Source Maponga and Ondari. The quality of
antimalarials A study in selected African
countries. WHO/EDM/PAR/2003.4
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Poor quality SP in Africa
Country Content failure Dissolution failure
Gabon 18 97
Ghana 45 78
Kenya 10 55
Mozambique 7 70
Zimbabwe 5 79
WHO Annual Report 2001
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Drug Resistance - Malaria

• Repeated exposure to sub-lethal doses allows
  parasite to adapt
• Chloroquine-resistant P. falciparum malaria is
  now widespread in Africa.
• Increasing drug resistance in Southeast Asia,
  Africa, and South America

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Antibiotics

• Substandard antibiotics can increase global
  problem of antimicrobial resistance
• Poor response to substandard narrow-spectrum
  antibiotics may lead to unnecessary prescription
  of newer and more expensive broad-spectrum
  antibiotics.
• Wider exposure to these drugs creates opportunity
  for more kinds of bacteria to develop resistance.

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Build local capacity

• Drug regulatory authorities- evaluate and approve
  drugs legally in the country
• Drug Quality control laboratories test products
  at registration and postmarketing surveillance
• Local industry improve compliance to good
  manufacturing practices
• Storage and distribution ensure facilities and
  systems preserve stability and purity
• Law enforcement confiscate counterfeits, work
  with DRA, MOH, customs, inspectors

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Opportunities

• Countries should share data on substandard and
  counterfeit products
• USP working with USAID and others to increase
  regional surveillance and information sharing in
  Mekong region
• Collaborations/partnerships are important
• Research authoritative data on drug quality
  problems can put pressure on governments to do
  more.

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Tools development

• Operational Guide for Drug Quality Assurance in
  Resource-limited Settings
• In development in collaboration with
• WHO
• RPM Plus
• PATH
• Drug Regulatory Authorities of Zimbabwe,
  Malaysia, Vietnam and Uganda.

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Counterfeit Drugs are dangerous

• Substandard and counterfeit drugs can kill
• Substandard e.g., diethylene glycol
• US 1938 120 died
• Nigeria 1990 109 children died
• Bangladesh 1992 223 children died
• Argentina 1992 23 patients died
• Haiti 1995/1996 89 children died
• Counterfeit e.g., meningitis vaccine with no
  antigen
• Niger 1995 around 2500 deathsSource World
  Health Organization

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MCH clinic in Mozambique
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Nancy Blum, M.P.H., M.A.Director, Global
Assistance InitiativesUnited States
Pharmacopeia

• 12601 Twinbrook Parkway
• Rockville, MD 20852
• www.usp.orgwww.uspdqi.orgnlb_at_usp.org