Close on the heels of Ranbaxy withdrawing its anti-retrovirals from WHO pre-qualification list, Hyderabad-based Hetero Drugs has also informed WHO to follow suit with regard to six of its pre-qualified drugs. The reason given being the same, the incompatibility of bioequivalence studies data. The Hetero products withdrawn are Stavudine 40 mg capsule; Stavudine 30 mg capsule; Lamivudine 150 mg plus Zidovudine 300 mg tablet; Indinavir 400 mg capsule; Lamivudine 150 mg tablet; Zidovudine 300 mg tablet.
The company has told WHO, it recognized that the "centres" it had used for studies of bioequivalence "were incompatible with the current standards" and that there were "deficiencies in the data submitted for the studies done at these centres." 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 also committed to contract different CROs and submit new test results for the bioequivalence of the six medicines as soon as possible.
"Our findings, and the companies' admission of responsibility by withdrawing their products, show that CRO inspections are necessary," said Dr Lembit Rago, coordinator of Quality, Safety and Efficacy of Medicines at WHO. "Current WHO procedures are ultimately improving medicines monitoring mechanisms which will, in the long term, ensure better quality treatment for patients," he stated.
The 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 states that the work reflects WHO's responsibility to assist countries in promoting quality medicines and improving their quality assurance mechanisms.
The irregularities found during the CRO inspections do not undermine the proven pharmaceutical quality of the medicines- including their purity and stability -but show that not all CROs can be relied upon as a source of evidence on the medicines' bioequivalence with their originator products, WHO says in the release.
The current WHO list of prequalified medicines contains 48 antiretrovirals, including a triple fixed dose combination (a three-in-one pill) manufactured by Cipla.