Cipla Must Resolve Concerns About Duovir

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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

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Duovir has been withdrawn from the market because the MCC has serious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

[ENDS]