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Three AIDS medicines will be removed from prequalification list this week

As part of the continuous effort to rigorously monitor the quality of medicines, the World Health Organization (WHO) is carrying out systematic inspections of contract research organizations which have done bioequivalence studies for prequalified medicines, starting with products for priority diseases.

During the most recent inspection a contracted laboratory which had done bioequivalence studies for three AIDS medicines has been found non-compliant with international standards of good clinical and laboratory practices. As a result, the three antiretrovirals, which are manufactured by Ranbaxy, will be removed from the list until such a time as Ranbaxy can submit data of new studies providing unequivocal evidence of the products' bioequivalence with the originator medicines.

Although it is not standard procedure for prequalification assessments to include the inspection of laboratories where bioequivalence studies are done (in Europe, Directive 2001/10/EC, asking that countries carry out such inspections, came into force only on 1 May 2004), WHO is committed to ensuring that the medicines it prequalifies for procurement in developing countries are of the highest standard.

The antiretrovirals in question are the triple fixed-dose combination pill containing lamivudine, stavudine and nevirapine in two different strengths and a lamivudine plus zidovudine tablet.

The recent inspections follow another inspection which took place in late May when similar non-compliance was found at a laboratory contracted by CIPLA to do bioequivalence studies of two AIDS medicines. However, another WHO inspection of a contract research organization has found that the bioequivalence tests for triple fixed-dose combination lamivudine, stavudine and nevirapine tablet manufactured by CIPLA were carried out properly in compliance with requested standards. This product will therefore continue to be included in the list of WHO prequalified products.

While the three Ranbaxy products to be removed from the list meet quality specifications, proof of bioequivalence is missing in view of non-compliance with good clinical and laboratory practices as well as data handling requirements found in the contracted laboratory. This effectively means that the medicines may or may not offer the same therapeutic benefits as the originals on which they are based. (Bioequivalence tests are conducted in volunteers whose blood is tested after receiving the test medicines, to determine whether the concentration of the test medicine (generic medicine) is similar to that of the innovator or patented medicine).

Ranbaxy has undertaken to resubmit the products in question to a different laboratory for proof of bioequivalence. If and when those products and the laboratories are found to meet the specified requirements, WHO will reinstate them in its list of prequalified products.

WHO will provide advice to countries, UN partners and the NGO community involved in the procurement of medicines as to the best ways to proceed.

In addition to good clinical and laboratory practices inspections, WHO assesses the quality of antiretrovirals through: evaluation of data in the product dossiers for quality as well as bioequivalence; inspection of manufacturing sites for compliance with good manufacturing practices; and testing of product samples at independent laboratories for compliance with product specifications.

The following products have been removed from the list of prequalified products to date:

Lamivudine 150mg plus Zidovudine 300mg tablet by Ranbaxy Laboratories Ltd Dewas, India. 60's and 100's

Lamivudine 150mg plus Stavudine 30mg plus Nevirapine 200mg tablet by Ranbaxy Laboratories Ltd Dewas India. Al strip of 10, 60 per box

Lamivudine 150mg plus Stavudine 40mg plus Nevirapine 200mg tablet by Ranbaxy Laboratories Ltd Dewas, India. Al strip of 10, 60 per box

Lamivudine 150mg tablet by Cipla Ltd, Kurkumbh, India. Blister 10.

Lamivudine 150mg plus Zidovudine 300mg tablet by Cipla Ltd, Vikhroli, India. Blister 10.

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For more information contact:

Ms Daniela Bagozzi
Telephone: +41 22 791 4544
Mobile phone: +41 79 4755490
E-mail: bagozzid@who.int

André van Zyl
Telephone: +41 22 791 35 98
Mobile phone: +41 79 475 55 27
E-mail: vanzyla@who.int