Cipla Readies Avian Flu Drug

Cipla, an Indian producer of generic drugs, is preparing to become an alternative producer of oseltamivir phosphate, an antiviral drug better known by the brand name Tamiflu. The drug, so far exclusively produced by patent holder Roche, has gained attention as one of the few medications that may be effective in fighting avian flu.

But Cipla has neither produced the drug in large quantities nor is able to predict whether its price will be much lower than Roche’s. “You must understand one thing: Our synthesis starts from shikimic acid, and it’s not native to India, so we must get it from outside,” Cipla Chairman and Managing Director Yusuf K. Hamied says.

(–)-Shikimic acid, a natural product, is available in bulk quantities from China at $200 to $250 per kg, according to Hamied; but at higher levels of purity, the price can easily exceed $50 per g. Roche has developed a fermentation route to (–)-shikimic acid, something that Cipla is still exploring. Hamied says his company only started working on Tamiflu a few months ago.

Cipla plans to offer Tamiflu in the Indian market and in 49 less-developed countries where the company already sells AIDS treatments, Hamied says. The legality of the introduction in India, where pharmaceutical patents started to be recognized this year, is uncertain.

Hamied says he will withdraw Tamiflu from the Indian market if Roche’s patent is recognized. But he speculates that Roche’s claim may be declared invalid in India because the pharmaceutical was initially invented by Gilead, an American biopharmaceutical company that licensed it to Roche.

Even without making (–)-shikimic acid, producing Tamiflu is a challenging undertaking requiring 10 major steps (C&EN, Aug. 29, page 22). Hamied notes that the process involves a potentially explosive step when sodium azide is used to introduce nitrogen into the molecule. But he says a similar step is required to produce AZT, an AIDS drug Cipla has made since 1991.