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,  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?

What’s wrong with the drugs? Source: Carpenter J P, Drug quality report matrix of USAID-assisted countries by the USP DQI Program, Other deficiencies, such as contamination, weight variation, unusual appearance, incorrect labeling No active ingredient Incorrect amount of Active ingredient

Availability of poor quality medicines Fig. 1. Percentage failure - chloroquine tablets (content) Gabon Ghana Mali Kenya Mozambique Sudan Zimbabwe % 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 CountryContent failureDissolution failure Gabon18%97% Ghana45%78% Kenya10%55% Mozambique7%70% Zimbabwe5%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 deaths Source: World Health Organization

MCH clinic in Mozambique

Nancy Blum, M.P.H., M.A. Director, Global Assistance Initiatives United States Pharmacopeia Twinbrook Parkway Rockville, MD