Following an inspection by the World Health Organization (WHO), Indian generic manufacturer Hetero Drugs is withdrawing six antiretrovirals from the WHO prequalification list in order to review data on their bioequivalence. The move follows an inspection of contract research organizations used by Hetero to provide bioequivalence data for the products.
The development is yet another blow to the credibility of data submitted by generic drug manufacturers to WHO's prequalification programme, but Dr Lembit Rago, Coordinator of Quality, Safety and Efficacy of Medicines at WHO, said today: "Current WHO procedures are ultimately improving medicines monitoring mechanisms which will, in the long term, ensure better quality treatment for patients. Our findings, and the companies' admission of responsibility by withdrawing their products, show that CRO inspections are necessary".
WHO's practice of contract research organisation inspection for HIV products follows the same principles used by the US Food and Drug Administration: if spot checks reveal problems, a more comprehensive policy of inspection will be pursued with particular sites or particular drug classes.
As in the case of Ranbaxy last week, the company evaluated the contract research organizations (CROs) it had used after receiving a warning letter sent by WHO to all manufacturers earlier this year, and found them non-compliant with international standards of Good Clinical Practice and Good Laboratory Practice. Hetero Drugs has committed to contract different CROs and submit new test results for the bioequivalence of the six medicines as soon as possible.
Ongoing WHO inspections of CROs conducting tests on antiretrovirals are part of the continuing monitoring process and an integral component of the prequalification work, WHO said today.
The current WHO list of prequalified medicines contains 48 antiretrovirals, including a triple fixed dose combination (a three-in-one pill) manufactured by Cipla. However, 19 generic antiretroviral products have been removed from the list since April as a result of contract research organisation inspections, leaving only a handful of generic products on the list. Only one fixed dose combination remains on the list, Cipla's Triomune.
WHO's advice to countries is that, in principle, patients should suspend the use of de-listed medicines and switch to other prequalified products. However, if it is difficult to obtain alternative prequalified products immediately, it is recommended that patients continue the use of de-listed products. The risk of withholding treatment is higher than that of providing medicines whose bioequivalence is not proven but which have demonstrated quality and safety. A switch to non-prequalified products is not recommended, as their quality has not been documented by WHO.