The South African Medicines Control Council (MCC) has told doctors in South Africa that the use of Cipla’s Duovir formulation of zidovudine (AZT) and lamivudine (3TC) is `undesirable` until Cipla can explain problems with product bioequivalence data highlighted by the World Health Organization (WHO) in June 2004.
All stocks of the drug have been recalled and doctors have been advised to switch patients to equivalent products manufactured by Glaxo SmithKline (Combivir) and Ranbaxy/Thembalami (Avocomb). Each contains the same drugs as Duovir. A third product called Lamzid, manufactured by Aspen Pharmacare, has yet to be registered by the MCC.The number of patients affected by the announcement is unknown.
The MCC is the first regulatory agency in Africa to act upon WHO’s announcement that it had removed two Cipla products from its list of prequalified antiretrovirals. (The registration status of Cipla products in other African countries could not be confirmed).
WHO took the decision as a result of a spot check on a contract research organisation that had carried out the original bioequivalence studies, which found that guidelines on good clinical practice were not being followed. This called into doubt all data produced by the laboratory, said WHO, including the bioequivalence studies conducted by that contract research organisation and submitted to WHO to gain prequalification.
Nic De Jongh of Cipla-Medpro (Cipla’s South African subsidiary) said that new bioequivalence tests are already being carried out at a new laboratory in South Africa.
The Treatment Action Campaign (TAC) and Médecins sans Frontières (MSF) welcomed the decision and called on Cipla to publicly address the concerns as quickly as possible.
They also called on Ranbaxy to supply the MCC and the public with information about the bioequivalence of Avocomb, which is manufactured in South Africa from active ingredients imported from India.
Last week the WHO announced that Virocomb, a zidovudine/lamivudine fixed dose tablet manufactured by Ranbaxy in India, had been removed from the prequalification list owing to failure to follow good clinical practice at a second contract research organisation in India. This organisation carried out studies on three Ranbaxy products, all of which were removed from the prequalification list until further data could be produced.
The decision is a further blow to international confidence in generic versions of branded antiretrovirals, which had been bolstered by the publication of a study in The Lancet showing good results of treatment after 24 weeks of use of Triomune, a fixed dose combination of stavudine, lamivudine and nevirapine.
However TAC and MSF stressed in a joint statement: "The problems around
these bioequivalence studies do not imply that Duovir is not bioequivalent, but the onus is on Cipla to prove bioequivalence ."