Subject: Joint Statement by TAC and MSF: Cipla Must Resolve Concerns About Duovir
From: TAC News Service
Date: Wed, 11 Aug 2004 18:16:38 +0200

Cipla Must Resolve Concerns About Duovir

Joint Statement by the Treatment Action Campaign and Medecins Sans Frontieres (South Africa)

Released: 11 August 2004, 16H30 GMT

The Treatment Action Campaign (TAC) and Medecins Sans Frontieres (MSF) note with concern that the Medicines Control Council (MCC) has had to use its powers to declare the use of the antiretroviral Duovir "undesirable" and to enforce a recall of all stocks of this medicine currently on the market.  Duovir is the name of the product marketed by Cipla-Medpro that combines the antiretroviral medicines zidovudine (AZT) and lamivudine in a single tablet.  The TAC and MSF call on Cipla-Medpro and its parent company based in India, Cipla, speedily and publicly to address the concerns of the MCC.  
Generally, for a generic medicine such as Duovir to be registered, it must be demonstrated that it is bioequivalent to the original medicine on which it is based, in this case Combivir manufactured by GlaxoSmithKline (GSK).  Bioequivalence tests are conducted in volunteers whose blood is tested after receiving the test medicines to determine whether the concentration of the generic medicine in question is similar to that of the patented medicine, which is already registered. The purpose of a bioequivalence test is thus to demonstrate that a generic medicine has the same therapeutic benefit as the original product, but it does not challenge its safety.

Duovir has been withdrawn from the market because the MCC has serious concerns regarding the quality of the bioequivalence studies that formed the basis of the medicine's registration. The problems around these bioequivalence studies do not imply that Duovir is not bioequivalent, but the onus is on Cipla to prove bioequivalence in order for the MCC in order to continue registering Duovir.

The MCC's concerns arise from the recent removal of certain antiretroviral medicines from the World Health Organization (WHO) list of prequalified medicines.  Pre-qualification means that a product has been found by the WHO to be safe, effective and of acceptable quality for procurement by United Nations agencies.  In particular, a WHO inspection in late May found a laboratory contracted by Cipla to do the bioequivalence studies of two antiretroviral medicines to be non-compliant with international standards of good clinical and laboratory practices.  The two antiretrovirals have been removed from the WHO list until such a time as Cipla can submit data of new studies providing unequivocal evidence of the products' bioequivalence with the original medicines.

It is important to note that another WHO inspection found that the bioequivalence tests for Cipla's Triomune, which combines lamivudine, stavudine and nevirapine in a single tablet, were carried out properly in compliance with requested standards.  Triomune therefore continues to be included in the list of WHO prequalified products.  It is used by quite a number of patients in South Africa under special authorisation from the MCC because it is not yet registered here.  Its use should be continued where such authorisation has been granted.

In terms of the MCC's decision that was published in the Government Gazette on Friday 6 August 2004, Cipla-Medpro has 30 days to submit documentation explaining what, if anything, is wrong with the bioequivalence studies that formed the basis of Duovir's registration by the MCC.  It is critical that Cipla provides the MCC with this information before the deadline.

In the meanwhile, people with HIV taking Duovir should switch as soon as possible to an alternative equivalent medicine. MSF and the TAC Treatment Project have resolved to shift their patients on Duovir to another brand and keep the stock of Duovir on hold pending the outcome of the deadline given by the MCC to Cipla.

People taking Duovir should know that there are other alternatives to this drug available in South Africa. In addition to Duovir, three other versions of the AZT/lamivudine combination have been registered by the MCC: GSK's Combivir, Ranbaxy's Avocomb and Aspen Pharmacare's Lamzid.  Aspen's product has yet to be placed on the market, while Ranbaxy must co-operate fully with the MCC to ensure their  product does not follow the same fate as Duovir as it has also been removed from the WHO list of prequalified drugs.

In addition, the MCC has also registered four versions of each of the individual antiretroviral drugs AZT and lamivudine: GSK's original patented products Retrovir and 3TC, Ranbaxy's Zidaid and Lamaid, Aspen's Aspen Zidovudine and Aspen Lamivudine, and Cipla-Medpro's Cipla-Zidovudine and Cipla-Lamivudine.  Once again, Aspen's products have yet to be placed on the market and Cipla must resolve the problems which lead to the WHO removing it from its list of prequalified drugs.

The recent steps taken by the WHO and MCC show that the quality, safety and efficacy of our medicines cannot and will not be compromised. These decisions demonstrate that the WHO and MCC have established effective processes of quality assurance which are able to detect and react to irregularities. While the TAC and MSF have in recent months been concerned by the MCC's problematic communication of important information on antiretroviral medicines, we support this decision of the MCC, which is rational, reasonable and in the public interest.  We urge and expect Cipla-Medpro and Ranbaxy to offer their full co-operation.

The MCC's decision also highlights the importance of having a number of drug suppliers for ensuring sustainability of supply and lower prices.  We call on Cipla to use the next few weeks to meet the MCC's requirements to avoid the deregistration of Duovir. If Cipla can unequivocally demonstrate that Duovir is bioequivalent, it will continue to be an important antiretroviral used to treat AIDS. We also call on GSK to comply with the commitments it made last year regarding the licensing of four generic manufacturers to produce and/or import generic AZT and lamivudine products.  It would be unethical of GSK to exploit the temporary reduction in competition to increase its prices on Retrovir, 3TC and Combivir, and we expect that it will not do so.  We also call on Aspen Pharmacare to ensure that its registered products are placed on the market with urgency.