Transcript Drug Quality Issues in Developing Countries

Quality Control Approaches for Essential
Medicines
“Good Intentions – Bad Drugs”
The World Bank
March 10, 2005
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
Good Quality: Definition
Good quality medicines meet official
standards for identity, strength, purity,
quality, packaging, and labeling.
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).
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
An Early USP Monograph
Isoniazid Monograph
Isoniazid
Dissemination of Standards
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.
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
What drugs are being counterfeited?
Reports of counterfeit drugs by therapeutic class
received by WHO 1999-2002
Analgesics &
antipyretics
Antimalarials 6%
7%
Other (14
therapeutic
categories)
33%
Antiasthma &
anti-allergy
8%
Hormones &
steroids 18%
Antibiotics,
28%
What’s wrong with the drugs?
Failed Anti-tuberculosis and Antimalarial Samples (n=479) in Selected
USAID-assisted Countries
(16 countries represented in 12 reports: 1997-2003)
Other deficiencies, such
24%
as contamination,
weight variation,
unusual appearance,
incorrect labeling
No active
ingredient
8%
68%
Source: Carpenter J P, 2003. Drug quality report matrix of USAID-assisted countries by the USP
DQI Program, www.uspdqi.org
Incorrect amount of
Active ingredient
Availability of poor quality medicines
Fig. 1. Percentage failure - chloroquine tablets (content)
% Failure
100
80
60
40
20
0
Source: Maponga and Ondari. The quality of antimalarials: A study in selected African countries. WHO/EDM/PAR/2003.4
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
Drug Resistance - Malaria
Repeated exposure to sublethal 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
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.
Build local capacity
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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
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.
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.
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 deaths
Source: World Health Organization
MCH clinic in Mozambique
Nancy Blum, M.P.H., M.A.
Director, Global Assistance Initiatives
United States Pharmacopeia
12601 Twinbrook Parkway
Rockville, MD 20852
www.usp.org
www.uspdqi.org
[email protected]