 "Strong medicine")
AN UNFINISHED AGENDA: MY LIFE IN THE PHARMACEUTICAL INDUSTRY
Author: K Anji Reddy
Publisher: Penguin Books India
Pages: 288
Price: Rs 699
When we set out to make filgrastim, the only recombinant products which were indigenously manufactured were vaccines to prevent disease. But no recombinant therapeutic drug to treat a disease was made in India. In 2001, Wockhardt introduced erythropoietin, a drug to treat anaemia caused by chronic kidney disease. It was the first indigenously manufactured recombinant therapeutic drug. A few months later, Dr Reddy's introduced the generic version of Amgen's Neupogen, perhaps the first therapeutic protein developed from the clone stage in the country, and it kicked up a storm.
Amgen had licensed the product to Hoffmann-La Roche for India. Roche was headquartered in Switzerland and the product was marketed in India by Nicholas Piramal. The company was previously Nicholas Laboratories and the diversified business group of Ajay Piramal acquired the company in 1988 in its first foray into pharmaceuticals. This was followed by the acquisition of the Hoffmann-La Roche subsidiary in India in 1993 along with the exclusive right to market a number of Roche products. This was how Neupogen came to be marketed by Nicholas Piramal.
We branded our product Grastim. We received approval of the Drugs Controller General (India) in June 2001 and introduced our product into the market at half the price of Neupogen. I was told that the doctors using the product were happy with their experience and even happier with the price at which it was being sold. The adviser to the ministry of science and technology in the Department of Biotechnology lauded the launch as 'an important milestone'.
Then came the bombshell.
All medicinal products are required to have an insert along with the medication that provides details of the medicine, the indications for which it can be used, the summary of the evidence from clinical trials, the dosage, adverse effects and so on. Nicholas Piramal filed a complaint in September 2001 against Dr Reddy's before the Monopolies and Restrictive Trade Practices Commission (MRTPC), alleging that the statements in the Grastim insert were false, misleading and tantamount to unfair trade practice. Their main grievance was that the insert would lead people to believe that Grastim had undergone various clinical trials that demonstrated efficacy, whereas it was Neupogen that was used in clinical trials. It is normal practice for generics to have an insert that replicates the one of the innovator, except for the brand name of the innovator. It was never our intention to create an impression that Grastim was used in the clinical trials whose results had been reported, so we promptly made an offer to make the situation clear by making changes in the insert. Nicholas Piramal also objected to certain other information contained in the insert. We agreed to make all the changes demanded and obtained clearance for the new insert from the Drugs Controller. MRTPC dismissed the complaint. The matter should have rested there, but it did not.
There was intensive media coverage of the dispute. Many of the reports were factual, but some were quite surprising in content. These reports said the amino acid sequence of Grastim was not the same as Neupogen. I was aghast and asked for the facts. It turned out that in our sales brochure, the sequence of the 175 amino acids of filgrastim was printed as a design element and there were errors in a few of them. It also turned out that the Neupogen monograph had two printing errors in the sequence and the comparison therefore revealed some differences. I heaved a sigh of relief that Nicholas Piramal's case was based on printer's devils and not actual analysis. We had irrefutable evidence that our sequence was right, not only based on our own analysis but also that of CCMB and IISc.
Fresh salvos followed. Newspapers reported that Nicholas Piramal had analysed samples of Grastim procured from the market and found 'either an impurity or a drug aggregate'. A news report stated that Nicholas Piramal had alerted all the leading haematology and oncology associations in the country about its findings. Another publication quoted an unnamed molecular biologist as saying that bacteria could escape during the purification process and this would be a potential hazard: that impurities could affect immunogenicity or bioavailability, thereby increasing the potential of toxicity. Dr Swati Piramal, director and chief scientific officer of Nicholas Piramal, clarified the position of the company. She was quoted as saying, 'It's not about patents or trademarks. Not about MNCs versus Indian companies. But it's a battle for safe and effective drugs for the patients - to ensure that doctors are not misled and get correct information from pharma companies. And we feel it's our duty to fight to the finish.'
The 'fight' was taken to the Drugs Controller, the ministry of health and even some members of Parliament. Every 'development' somehow found its way to the newspapers. Nicholas Piramal asked that Grastim be withdrawn and an expert from Roche was also said to have met the Drugs Controller.
An expert group was formed by the Drugs Controller. It was headed by Prof N K Ganguly, director general of the Indian Council of Medical Research, with Dr Nitya Anand, the legendary former director of the Central Drug Research Institute, and Dr Amit Ghosh, the serving director of the Institute of Microbial Technology. They obtained samples of Grastim and Neupogen from the market and analysed it. The drama finally ended in January 2003. There was complete transparency as the expert group presented its findings to the Drugs Controller in a meeting where both Dr Reddy's and Nicholas Piramal were present. Contrary to all the news that had been published, the expert group found that there was no difference between Neupogen and Grastim. Nicholas Piramal asked for, and obtained, a copy of the test reports, but apparently had nothing further to say. Nicholas Piramal had indeed fought the 'fight' to its logical conclusion.
The expert group recommended that we change our brand name to something else as it was not desirable to have a brand name that corresponded so closely to the generic name. We pointed out that it was the practice in India as there were so many brands and a brand name that incorporated part of the generic name made it easy for the doctors to remember it. There was no legal compulsion for us to change the name, but we did so nevertheless. Dr Reddy's filgrastim was rebranded Grafeel.
Dr Reddy's filgrastim had overtaken Neupogen in volume soon after its launch in 2001. Volumes, however, dropped in the next two years as doctors hesitated to prescribe the product. A doctor in Mumbai's Tata Memorial Centre told a newspaper he did not know whether Grastim was as good as Neupogen or not but would not risk prescribing Grastim. If I were in his place, I would have done the same. No wonder Dr Reddy's sales suffered. By 2005, however, we regained our lead and have been ahead of Neupogen ever since, though the price of the latter has dropped to match ours in the last three years.
Author: K Anji Reddy
Publisher: Penguin Books India
Pages: 288
Price: Rs 699
When we set out to make filgrastim, the only recombinant products which were indigenously manufactured were vaccines to prevent disease. But no recombinant therapeutic drug to treat a disease was made in India. In 2001, Wockhardt introduced erythropoietin, a drug to treat anaemia caused by chronic kidney disease. It was the first indigenously manufactured recombinant therapeutic drug. A few months later, Dr Reddy's introduced the generic version of Amgen's Neupogen, perhaps the first therapeutic protein developed from the clone stage in the country, and it kicked up a storm.
Amgen had licensed the product to Hoffmann-La Roche for India. Roche was headquartered in Switzerland and the product was marketed in India by Nicholas Piramal. The company was previously Nicholas Laboratories and the diversified business group of Ajay Piramal acquired the company in 1988 in its first foray into pharmaceuticals. This was followed by the acquisition of the Hoffmann-La Roche subsidiary in India in 1993 along with the exclusive right to market a number of Roche products. This was how Neupogen came to be marketed by Nicholas Piramal.
We branded our product Grastim. We received approval of the Drugs Controller General (India) in June 2001 and introduced our product into the market at half the price of Neupogen. I was told that the doctors using the product were happy with their experience and even happier with the price at which it was being sold. The adviser to the ministry of science and technology in the Department of Biotechnology lauded the launch as 'an important milestone'.
Then came the bombshell.
All medicinal products are required to have an insert along with the medication that provides details of the medicine, the indications for which it can be used, the summary of the evidence from clinical trials, the dosage, adverse effects and so on. Nicholas Piramal filed a complaint in September 2001 against Dr Reddy's before the Monopolies and Restrictive Trade Practices Commission (MRTPC), alleging that the statements in the Grastim insert were false, misleading and tantamount to unfair trade practice. Their main grievance was that the insert would lead people to believe that Grastim had undergone various clinical trials that demonstrated efficacy, whereas it was Neupogen that was used in clinical trials. It is normal practice for generics to have an insert that replicates the one of the innovator, except for the brand name of the innovator. It was never our intention to create an impression that Grastim was used in the clinical trials whose results had been reported, so we promptly made an offer to make the situation clear by making changes in the insert. Nicholas Piramal also objected to certain other information contained in the insert. We agreed to make all the changes demanded and obtained clearance for the new insert from the Drugs Controller. MRTPC dismissed the complaint. The matter should have rested there, but it did not.
There was intensive media coverage of the dispute. Many of the reports were factual, but some were quite surprising in content. These reports said the amino acid sequence of Grastim was not the same as Neupogen. I was aghast and asked for the facts. It turned out that in our sales brochure, the sequence of the 175 amino acids of filgrastim was printed as a design element and there were errors in a few of them. It also turned out that the Neupogen monograph had two printing errors in the sequence and the comparison therefore revealed some differences. I heaved a sigh of relief that Nicholas Piramal's case was based on printer's devils and not actual analysis. We had irrefutable evidence that our sequence was right, not only based on our own analysis but also that of CCMB and IISc.
Fresh salvos followed. Newspapers reported that Nicholas Piramal had analysed samples of Grastim procured from the market and found 'either an impurity or a drug aggregate'. A news report stated that Nicholas Piramal had alerted all the leading haematology and oncology associations in the country about its findings. Another publication quoted an unnamed molecular biologist as saying that bacteria could escape during the purification process and this would be a potential hazard: that impurities could affect immunogenicity or bioavailability, thereby increasing the potential of toxicity. Dr Swati Piramal, director and chief scientific officer of Nicholas Piramal, clarified the position of the company. She was quoted as saying, 'It's not about patents or trademarks. Not about MNCs versus Indian companies. But it's a battle for safe and effective drugs for the patients - to ensure that doctors are not misled and get correct information from pharma companies. And we feel it's our duty to fight to the finish.'
The 'fight' was taken to the Drugs Controller, the ministry of health and even some members of Parliament. Every 'development' somehow found its way to the newspapers. Nicholas Piramal asked that Grastim be withdrawn and an expert from Roche was also said to have met the Drugs Controller.
An expert group was formed by the Drugs Controller. It was headed by Prof N K Ganguly, director general of the Indian Council of Medical Research, with Dr Nitya Anand, the legendary former director of the Central Drug Research Institute, and Dr Amit Ghosh, the serving director of the Institute of Microbial Technology. They obtained samples of Grastim and Neupogen from the market and analysed it. The drama finally ended in January 2003. There was complete transparency as the expert group presented its findings to the Drugs Controller in a meeting where both Dr Reddy's and Nicholas Piramal were present. Contrary to all the news that had been published, the expert group found that there was no difference between Neupogen and Grastim. Nicholas Piramal asked for, and obtained, a copy of the test reports, but apparently had nothing further to say. Nicholas Piramal had indeed fought the 'fight' to its logical conclusion.
The expert group recommended that we change our brand name to something else as it was not desirable to have a brand name that corresponded so closely to the generic name. We pointed out that it was the practice in India as there were so many brands and a brand name that incorporated part of the generic name made it easy for the doctors to remember it. There was no legal compulsion for us to change the name, but we did so nevertheless. Dr Reddy's filgrastim was rebranded Grafeel.
Dr Reddy's filgrastim had overtaken Neupogen in volume soon after its launch in 2001. Volumes, however, dropped in the next two years as doctors hesitated to prescribe the product. A doctor in Mumbai's Tata Memorial Centre told a newspaper he did not know whether Grastim was as good as Neupogen or not but would not risk prescribing Grastim. If I were in his place, I would have done the same. No wonder Dr Reddy's sales suffered. By 2005, however, we regained our lead and have been ahead of Neupogen ever since, though the price of the latter has dropped to match ours in the last three years.
Published with permission from Penguin Books India