Pharma firms plan awareness drive to battle cancer scare in antacid

Around four months earlier, the US drugs regulator said it had found a cancer-causing impurity in some products containing ranitidine, a popular prescription for acidity.
 
That has meant a major quake within the Indian pharmaceutical industry, since a number of its prominent members sell versions of this drug. India also happens to be the largest supplier of ranitidine's active pharmaceutical ingredient (API) to the world, with monthly  production capacity of 5,000 tonnes.
 
Both bulk drug and formulation players have been altering their manufacturing processes. The domestic market size for the formulation has since shrunk by at least 20 per cent -- a key player such as GlaxoSmithKline Pharma (GSK), for instance, pulled out its marquee brand, Zinetac.
 
Indian companies have also been hit in their global business. The European Medicines Agency has implemented stringent criteria for permissible limits of the suspected ingredient, Nitrosodimethylamine (NDMA), now considered a probable carcinogen.
 
Armed with laboratory test results, Indian players say they're now gearing up to re-woo domestic patients and restart supplies to their global clients.
 
Rescue ops
 
Pranabh Mody, president at JB Chemicals and Pharmaceuticals, the maker of popular brand Rantac, says they've gone back to the drawing board. They started with the API suppliers. Two of the key ranitidine API makers, Hyderabad-based SMS Lifesciences and Saraca Laboratories, have stated the NDMA in their bulk drug is within permissible limits. "We noticed that any heating can cause production of NDMA. We brought down the temperature in the manufacturing process," Mody said, with several tests to prove NDMA does not rise during the latter sequence.
 
Rantac is an important product for the company in India — of its Rs 700 crore domestic annual turnover, around Rs 190 crore comes from Rantac. "We have seen a 15 per cent drop in average monthly sales," Mody said.
 
 It is now approaching doctors with certificates of quality and wants to reach out to the consumer who is now largely shying away from the product.
 
Earlier this month, a group of doctors met journalists in Mumbai to speak on safety and efficacy of the drug. Rajiv Karnik, cardiologist at Fortis Hospital in Mulund, said: “Cardiologists prescribe ranitidine to counter acid formation in patients as a side-effect of other medicines that are given for different heart conditions. Ranitidine is the safest bet for controlling acid refluxes. The US FDA (the sector regulator there) has also confirmed that ranitidine does not lead to NDMA formation in typical stomach conditions, through their tests.”
 
Mody's company is waiting for all clearances in place from the FDA before exporting to that country.
 
As for GSK's withdrawal of Zinetac from the Indian market, that was part of a global recall in September. Re-introduction here would again be part of a global decision. Afte Zinetac was withdrawn, Aciloc, the category brand from Ahmedabad-based  Cadila Pharmaceuticals is market leader, with JB Chemicals' Rantac in second position. Aciloc sales had increased in October but came down in November, according to data from AIOCD AWACS.
 
The Indian market for ranitidine has been Rs 650-700 crore a year. Monthly sales fell from around Rs 60 crore in September to Rs 47 crore in November. It is a cheap drug, priced at Rs 23 for a pack of 30 tablets.
 
A senior official of a drug firm said if the market shifted to the next available alternative, proton pump inhibitors (PPI, priced higher at Rs 90-110 for 15-tablet strips), the market size would swell. The ranitidine market volume is about a billion tablets per month.
 
Ahead
 
API makers, however, say things will start looking up in the next three to four months. Rajkot-based Orchev Pharma, a single product company, was supplying almost its entire 50-tonne monthly output to Europe. Vasant Bhalodia, managing director, said the company stopped production of the API around September for two months, for a detailed testing on NDMA's presence in the bulk drug. "We made necessary tweaks in the production process after that and now our capacity of ranitidine API is 35-40 tonnes per month. We are now in talks to supply to Indian pharma players. There is also significant demand from the South Asian market and we are exploring it," he added.

 
Bhalodia claims the level of NDMA in its ranitidine API is 0.05 ppm, well within the permissible limits prescribed by the FDA (0.32 ppm) and European authority (0.16 ppm). "There is huge pent-up demand in the European market. However, the European agency has sought stability data on the API -- that is, if there any NDMA creation during storage (shelf life). Once we have that data, which is going to take another two to three months, we can look at restarting supplies," he explained. 
 
Drug makers' lobby groups have met the Indian sector regulator. "The Drugs Controller General of India is looking into the matter but has not yet come out with any guidelines around NDMA," said an official from one such firm. Regulatory staff is reportedly visiting the manufacturing facilities to collect samples for testing.