Quality Control Approaches for EssentialMedicines

“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

Antibiotics, 28%

Other (14 therapeutic categories)

33%

Analgesics & antipyretics

6%Antimalarials 7%

Antiasthma & anti-allergy

8%

Hormones & steroids 18%

What’s wrong with the drugs?

68%

8%

24%

Failed Anti-tuberculosis and Antimalarial Samples (n=479) in Selected USAID-assisted Countries

(16 countries represented in 12 reports: 1997-2003)

Source: Carpenter J P, 2003. Drug quality report matrix of USAID-assisted countries by the USP DQI Program, www.uspdqi.org

Other deficiencies, such as contamination, weight variation, unusual appearance, incorrect labeling

No active ingredient

Incorrect amount ofActive ingredient

Availability of poor quality medicines

Fig. 1. Percentage failure - chloroquine tablets (content)

0

20

40

60

80

100

Gabon

Ghana

Mali

KenyaM

ozambique

Sudan

Zimbabw

e

% Failure

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

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

Drug Resistance - Malaria

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

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 deathsSource: World Health Organization

MCH clinic in Mozambique

Nancy Blum, M.P.H., M.A.Director, Global Assistance Initiatives

United States Pharmacopeia

12601 Twinbrook ParkwayRockville, MD 20852

www.usp.orgwww.uspdqi.org

nlb@usp.org