Contributed by Ron Gara| 21 November, 2004 16:58 GMT
The irregularities found during the CRO inspections do not undermine the proven pharmaceutical quality of the medicines -- including their purity and stability.
An India-based manufacturer of generic drugs used for the treatment of AIDS has taken six products off the World Health Organization's approved list. Following a WHO inspection, the company admitted that its testing for bioequivalence -- the ability of the generic drugs to act on the body in the same way as their brand-name counterparts -- was carried out at centers that did not meet "current standards."Hetero Drugs Limited, in Hyderbad, India, acknowledged that there were "deficiencies in the data submitted … for the studies done at these centres."
The Hetero products withdrawn are Stavudine 40 mg capsule; Stavudine 30 mg capsule; Lamivudine 150 mg plus Zidovudine 300 mg tablet; Indinavir 400 mg capsule; Lamivudine 150 mg tablet;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.
Response to Warning Letter
According to WHO, Hetero 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.
"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."
Ongoing WHO inspections of CROs conducting tests on antiretrovirals are part of the continuing monitoring process and an integral component of the prequalification work, states WHO. That work reflects WHO's responsibility to assist countries in promoting quality medicines and improving their quality assurance mechanisms.
De-Listed Products May Be Effective
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, explains WHO.
Bioequivalence tests are conducted in volunteers whose blood is tested after receiving treatment with the medicine, to determine whether the blood concentration of the generic drug is similar to that of the originator product.
The current WHO list of prequalified medicines contains 48 antiretrovirals, including a triple fixed dose combination (a three-in-one pill) manufactured by Cipla.
Principle versus Practice
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.
More detailed information on the practical implications of the withdrawal of the above-mentioned products from the list of prequalified products for treatment programmes can be accessed on the WHO Prequalification project web page, where the list of alternative products prequalified by WHO may also be found. |
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