The World Health Organisation will remove three antiretrovirals manufactured by Ranbaxy from the prequalification list after an inspection found that the bioequivalence studies conducted by a contract research laboratory on these drugs failed to comply with international norms. The antiretrovirals in question are the triple fixed-dose combination pill containing lamivudine, stavudine and nevirapine in two different strengths and a lamivudine plus zidovudine tablet.
Since the contracted laboratory was found non-compliant with international standards of good clinical and laboratory practices, Ranbaxy will have to submit afresh bioequivalence data of new studies providing unequivocal evidence of the products' bioequivalence with the originator medicines.
While the three Ranbaxy products to be removed from the list meet quality specifications, proof of bioequivalence is missing in view of non-compliance with good clinical and laboratory practices as well as data handling requirements found in the contracted laboratory. This effectively means that the medicines may or may not offer the same therapeutic benefits as the originals on which they are based. (Bioequivalence tests are conducted in volunteers whose blood is tested after receiving the test medicines, to determine whether the concentration of the test medicine (generic medicine) is similar to that of the innovator or patented medicine).
"Ranbaxy has undertaken to resubmit the products in question to a different laboratory for proof of bioequivalence. If and when those products and the laboratories are found to meet the specified requirements, WHO will reinstate them in its list of pre-qualified products", a WHO release said.
WHO will provide advice to countries, UN partners and the NGO community involved in the procurement of medicines as to the best ways to proceed.
Responding to the WHO decision, Ranbaxy stated that it has already initiated work on new bio-equivalence studies on these three products. It has suspended all outsourcing work with the CRO in question and has begun investigating into the anomalies.
Ranbaxy confirms its products are manufactured at the Company ' s world class facilities that are routinely inspected and approved by WHO-Geneva for compliance to Good Manufacturing Practices (GMP) and meet all required quality standards and specifications. The Company's ARVs have been used as mainstays in various large treatment programmes, both National and NGO/Institutional," stated a Ranbaxy release.
The recent inspections follow another inspection which took place in late May when similar non-compliance was found at a laboratory contracted by Cipla to do bioequivalence studies of two AIDS medicines. However, another WHO inspection of a contract research organization has found that the bioequivalence tests for triple fixed-dose combination lamivudine, stavudine and nevirapine tablet manufactured by Cipla were carried out properly in compliance with requested standards. This product will therefore continue to be included in the list of WHO pre-qualified products.
The products currently removed from the list of pre-qualified products are Lamivudine 150mg plus Zidovudine 300mg tablet (Ranbaxy Laboratories Ltd, Dewas, India. 60's and 100's), Lamivudine 150mg plus Stavudine 30mg plus Nevirapine 200mg tablet (Ranbaxy Laboratories Ltd Dewas India. Al strip of 10, 60 per box), Lamivudine 150mg plus Stavudine 40mg plus Nevirapine 200mg tablet (Ranbaxy Laboratories Ltd Dewas, India. Al strip of 10,60 per box), Lamivudine 150mg tablet (Cipla Ltd, Kurkumbh, India. Blister 10) and Lamivudine 150mg plus Zidovudine 300mg tablet (Cipla Ltd, Vikhroli, India. Blister10).