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Duovir has been withdrawn from the market because the MCC has serious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
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
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.