The World Health Organisation today announced that it has removed three antiretroviral products manufactured by the Indian company Ranbaxy from its list of prequalified antiretroviral products. Prequalification has been suspended because site visits within the past two weeks to contract research organisations that carried out bioequivalence studies for Ranbaxy revealed non-compliance with international standards of Good Clinical Practices and Good Manufacturing Practices.
The three products are:
- Lamivudine 150mg plus zidovudine 300mg tablet (marketed as Virocomb).
- Lamivudine 150mg plus stavudine 30mg plus nevirapine 200mg tablet (marketed as Viro LNS).
- Lamivudine 150mg plus stavudine 40mg plus nevirapine 200mg tablet (marketed as Viro LNS).
WHO prequalification of antiretrovirals is intended to signpost which products are manufactured to acceptable international standards. Only products that have been prequalified can be purchased by UN agencies, and the prequalification list is intended to serve as a guide for government regulatory agencies.
The withdrawal of prequalification is the second such announcement in two months; in early June WHO withdrew prequalification from two products manufactured by the Indian company Cipla for similar reasons. One of the products, a 150mg lamivudine (3TC) tablet was restored to the prequalification list on July 13 by WHO following submission of new data.
WHO points out that an international requirement to carry out inspections of contract research organisations only came into force in the European Union in May 2004, and that it has been proactive in carrying out such inspections compared with other regulatory authorities.
Daniela Bagnozzi told aidsmap.com: "We are now conducting inspections of the contract research organisations that carry out bioequivalence studies for manufacturers as a matter of course as a result of the two cases of poor practice that have already come to light."
A US Food and Drug Administration spokesman commented that the FDA would also tend to prioritise inspections of contract research organisations on the basis of risk. Organisations that had a previous history of problems would be more likely to undergo inspection when a new product dossier was submitted, he said.
The withdrawal of Virocomb is particularly problematic because this fixed dose triple combination is one of the recommended first-line combinations for use in resource-limited settings. WHO emphasised today that a similar product containing the same drugs manufactured by Cipla, called Triomune, has not been withdrawn. A site inspection of the contract research organisation that carried out bioequivalence studies for Triomune found no irregularities.
Ironically, Ranbaxy announced on Monday that it would file the first applications for approval of its antiretroviral products with the US Food and Drug Administration by the end of 2004 after carrying out bioequivalence studies using contract research organisations in the United States. The FDA announced in May 2004 that it would offer speedy approval for fixed dose combinations, whoever manufactured them, and the US government announced that any products which received FDA approval could be purchased for use by the President's Emergency Plan for AIDS Relief.