India taps own trees for raw material shikimic acid to make swine flu drug oseltamivir

Shikimic acid, which is extracted from a Chinese tree, is in short supply as demand for oseltamivir skyrockets.

India is set to tap its own trees looking for the key ingredient to make swine flu drug oseltamivir, as a severe shortage of  shikimic acid grips Tamiflu manufacturing due to increasing stock-piling of the drug.

Shikimic acid, the basic raw material for making oseltamivir has been found in atleast in 7 plants species across the Western Ghats. This discovery has prompted the authorities to send a team to workout ways to exploit the resource to the full, as the ingredient is very much in demand not only in India but the world over.

Currently, drug makers procure shikimic acid from China. China is  the lead supplier of shikimic acid in the world. Shikimic acid is extracted from the fruits of the Chinese star anise tree, that contains up to 5% of the acid. Star anise tree take a minimum of 6 years to reach its 10-metre seed bearing height to begin yielding shikimic acid.

Obviously,  growing star anise trees do not look a good proposition to meet the rising demand at the moment.

“A few promising species whose leaves yielded shikimic acid level higher than 1%”, a team member form the University of Agricultural Sciences, Bangalore, was quoted as saying.

The trees discovered have yielded 1%-5.02% of the acid, with a plant species called Araucaria Excelsa yielding almost 5.02% of shikimic acid.

A major advantage of the Indian tress which are identified as source shikimic acid is that this ingredient can be isolated from the leaves themselves — an easier process compared to fruits in star anise tree. Star anise fruits contain 2 % – 7 % of shikimic acid, the highest reported estimate from plants.

“Only 7 of the 193 angiosperm species yielded shikimic acid in excess of 1% while the rest yielded no or low shikimic acid. The most promising species were Calophyllum Apetalum (4.10% shikimic acid). All the 17 gymnosperms had detectable levels of shikimic acid with six species accumulating greater than 1%. Among these, Araucaria Excelsa yielding almost 5.02% of shikimic acid,” the scientists said reporting their finding in the latest issue of the medical journal ‘Current Science’.

“The leads presented here appear more promising than most others. In few of these species, the estimates are comparable to those reported from star anise. Because the estimates are from leaves, the sheer volume of the biomass offered by the leaves would render it economically feasible. This finding of the new source of shikimic acid can potentially be used to meet the emerging needs of both the domestic and international markets.”

At present the demand for shikimic acid grew manifold leaving China to impose rationing of its supplies. Last week, Guilin Layn Natural Ingredients Corp., a Chinese supplier of shikimic acid, said the Chinese government has issued orders requiring them to take prior approval before releasing any information regarding the natural extract’s stock position to public.

Nearly two-thirds of the requirement of shikimic acid is being sourced from plants while the remaining one-third is obtained from genetically engineered E Coli,it is estimated. 

Getting the raw material to make Tamiflu in India has been our biggest hurdle. At present, it is found only in China and Germany, health ministry sources said.

Such a situation demands the need for identifying newer sources of shikimic acid.

The health ministry has already assigned a team of researchers to study the modalities for extracting shikimic acid from Indian plants, it is learnt.

The huge market demand also pushed the prices of shikimic acid to sky high. Shikimic acid, which used to cost $40 a kg earlier, now costs around $1,000 per kilogram, pharma companies in India said.

Short supply and exhorbitant costs of shikimic acid have put the Indian manufacturers of oseltmavir in a tight spot. Hetero, Cipla, Roche India, Ranbaxy, Strides and Natco Pharma are some of the leading suppliers of oseltmivir from India.

Hetero, which has got orders for supplying 20 million doses of oseltamivir, said its stock of shikimic acid was sufficient for making 25 million doses. However, Hetero is not taking any fresh orders as it want to reserve some 5 million doses for any emergency situation in India.

Hetero is reportedly negotiating with Chinese suppliers of shikimic acid, to procure 12-13 tonnes of the ingredient.

Roche, which holds the global marketing rights for oseltamivir, has licensed Hetero to manufacture the antiviral in India.

Cipla too has “enough shikimic acid for 1.5 million doses,” company sources said. If the companies want to procure beyond 1.5 million then they will have to pay more, as the Chinese government was putting restrictions on the supply of shikimic acid.