Punish those guilty of approving Letrozole

Officials in Central Drugs Standard Control Organization (CDSCO) seem to have "colluded with private interests" to get the controversial drug Letrozole approved in India "in a clear violation of laws" for use against infertility.

Now, the parliamentary standing committee on health and family welfare has asked the Union health ministry to take action against those who were involved.

Though globally the drug is used for treatment of breast cancer, in India it was being administered to young infertile women to help them conceive.

The drug's side-effects are believed to have led to severe genetic abnormalities among babies born to infertile women.

Though its use for infertility was banned recently, the standing committee in a scathing report submitted on Tuesday said, "It is a gross violation of laws by the CDSCO. First, in approving the drug for use in case of female infertility. And, thereafter in exhibiting overt resistance in taking timely corrective steps favouring suspension of use of the drug for infertility."

The panel, headed by Brajesh Pathak, says Letrozole, discovered by Novartis, is an anti-cancer drug for use only in postmenopausal women and is contraindicated (not permitted) to be used in women of reproductive age.

If it is to be used for any other indication except breast cancer, the drug is categorized as a New Drug under Indian laws. On April 10, 2007, the Drug Controller General of India approved the use of Letrozole for improving female fertility.

The committee said that the drugs and cosmetic rules require that while approving a drug for use in females of reproductive age, animal studies are to be done in this specific group. Its report said, "No such studies were done in India. The innovator also did not conduct such studies abroad because there was no plan to use Letrozole in women of reproductive age."

"Under Indian rules, Phase II studies should have been conducted before Phase III since such studies were not conducted anywhere. Permission to conduct Phase III studies was given without prior Phase II studies. Phase III clinical trial was conducted on just 55 women by three doctors in private practice while the minimum requirement as per mandatory good clinical practice (GCP) rules is at least 100," it added.

The committee said that after the approval, the sponsor Sun Pharmaceuticals did not submit periodic post-marketing periodic safety update reports (PSURs), or monitoring the safety of a drug or device after it has been released in the market to look for serious side-effects due every six months as required by law.

"No action was taken against the company in such a sensitive case since India is the only country where the drug was permitted to be used for female infertility. Post-marketing data is crucial and critical in detecting adverse effects both in women and babies born to them if they use Letrozole before the onset of pregnancy. Clearly, there was a serious lapse on the part of CDSCO. In the wake of media outcry, in a diversionary move, the DCGI instead of investigating the allegations of regulatory lapse and taking corrective measures referred the matter to clinical experts and the Drug Technical Advisory Board on the restricted issue of safety and efficacy," it added.

The committee also took strong exception to CDSCO's soft corner for "experts" from Delhi. An investigation by the Standing Committee has found that in case of majority of decisions that called for a ban on a drug, the experts were all from Delhi.