Bulletin of the World Health Organization

Developing countries take a creative approach to R&D

A few low- to middle-income countries have developed new drugs to address their pubic health needs while other developing countries have found innovative ways to be more active in the global multibillion dollar R&D pharmaceuticals business which is concentrated in industrialized countries.

29 December 2004

In the late 1970s, a small Croatian pharmaceuticals company called Pliva developed an original antibiotic called azythromycin. In early trials, it proved to be effective and able to stay longer in the body tissue of animals than similar antibiotics.

Researchers in Brazil developing antimalarial medicines.

At the time, the company lacked the capital to market and distribute the product worldwide. In 1981, Pliva patented the product globally and this led to a licensing agreement under which Pfizer Inc. of the United States bought the rights to sell azythromycin worldwide while Pliva continued to sell it in Central and Eastern Europe.

Today Zithromax — Pfizer’s version of azythromycin — is one of the biggest selling branded antibiotics in the United States.

Producing a blockbuster drug— with more than US$ 1 billion annual sales — came true for Croatia but remains a distant dream for most middle- and low-income countries.

It’s not easy with limited funds, weak infrastructure and little or no hi-tech equipment and even when researchers in developing countries find a promising product, regulatory bodies often lack the staff and expertise needed to ensure that clinical trials are ethical and new drugs are safe.

Yet despite the challenges some developing countries including Brazil, India, Indonesia and South Africa have over the last decades built up expertise in producing generic copies of R&D products to address public health needs.

Spurred by national pride and potential economic rewards a few, notably Croatia, Cuba and India, have produced original R&D medicines too.

Of some US$ 105.9 billion annually spent on global health research, only a fraction — 4% — or a roundedoff US$ 4.3 billion, is spent by middle and low-income countries, according to the Global Forum for Health Research.

Most of that— 2.4% or US$ 2.5 billion — is public sector-funded. The remaining amount rounded off to US$ 1.8 billion is private sector funding. The Global Forum said this includes: US$ 1.35 billion from foreign and domestic pharmaceuticals, US$ 80 million from domestic private funds and US$ 300 million from the private non-profit sector.

Some public health experts question whether the US$ 4.3 billion would not be better spent on good value drug procurement deals.

Indeed, many developing countries still find it cheaper to import rather than to produce drugs. But since patented R&D products are prohibitively expensive for some, smaller developing countries are importing drugs from regional economic powers: such as Brazil, India and South Africa.

Cuba is one of the few developing countries to be successful in biotech research. The Centre for Genetic Engineering and Biotechnology in Havana has produced several recombinant molecules such as interferons (proteins to fight viral infections), a hepatitis B vaccine, streptokinase (an agent used in medicines for heart disease), epidermal growth factor (a protein used in cancer medicines), and other products.

These help address public health needs in Cuba and attract revenues with exports to more than 50 countries.

The Republic of Korea’s R&D in pharmaceuticals has also played a role in the country’s spectacular rise from a low-income developing country in the 1950s to a major economic power.

South Africa, where about 10% of the population is HIV positive, is developing a promising vaccine tailored to its specific health needs. Most HIV vaccines being developed are for virus subtype B, the dominant strain in the United States and Europe, but there is no certainty these would be effective against subtype C of the AIDS virus which accounts for more than 90% of HIV infections in southern Africa.

The project has state and private sector funding and aims to produce a vaccine for subtype C. It was initiated by South Africa’s Medical Research Council. Phase I trials started in 2003.

India’s generic drugs industry has pioneered fixed-dose combination antiretroviral medicines. These are not only more affordable for poor countries with high HIV infection rates, but these two- or three-in-one pills and blister packs make it easier for patients to follow treatment.

By copying and combining two or three drugs, each originally developed by a different R&D company, Indian companies Cipla and Ranbaxy have have come up with competitive products unmatched by R&D originators like multinational, GlaxoSmithKline.

That success underscores one of the greatest challenges to drug production in developing countries: ensuring that medicines meet international criteria for quality, safety and efficacy.

Spurred by national pride and potential economic rewards a few, notably Croatia, Cuba and India, have produced original R&D medicines.