The Indian pharmaceutical industry is in denial over drug-quality charges
Katherine Eban’s new book, “Bottle of Lies,” has focused a very intense spotlight on the mostly ignored transgressions of the Indian generic pharmaceutical industry in the processes they follow — or all too often don’t follow — to make quality products. This industry, which has rarely been subjected to such rigorous journalistic scrutiny, has lashed back at Eban, attacking her integrity and her work.
The latest salvo comes from Kiran Mazumdar Shaw, who calls Eban’s exposé anecdotal, biased, unfair, and unbalanced, and accuses the author of playing up to the poor perceptions of the Indian pharmaceutical industry and the country. Shaw did this in a softball interview she gave to an Indian publication in which she is an investor.
Shaw, who owns Biocon Ltd, a pharmaceutical company that has been cited multiple times by the United States Food and Drug Administration over the last few years for its failure to comply with Current Good Manufacturing Practices, is one of the biggest names in the Indian pharmaceutical industry.
Like many of Eban’s critics, Shaw has tried to wish away the concerns raised in “Bottle of Lies” by claiming that the Ranbaxy case at the heart of the book (I was the whistleblower who brought it to light) was a one-off incident that occurred 15 years ago, and so can’t be used to paint the entire industry in poor light — especially, as Shaw points out, when Indian industry has done its share of good deeds by producing large volumes of affordable medicines for the world.
Her characterization of the problem is unfortunate because it represents a stubborn denial of reality. There are reams upon reams of official documentation showing that the fraud at Ranbaxy was not a one-off event. In the six years since Ranbaxy pled guilty to selling adulterated medicine in the U.S., a number of leading Indian pharmaceutical companies have been cited by the FDA for behavior that is not too different from what is described in the book at Ranbaxy and Wockhardt.
These include companies like Dr. Reddy’s, Aurobindo, Ipca, Emcure, Megafine, Unimark, Claris, and many more. And the violations of good manufacturing practices do not stop. Just this week, the FDA leveled severe allegations against Strides Pharma for shredding its manufacturing quality records in advance of a scheduled U.S. FDA inspection. Two weeks ago, Apotex India withdrew 31abbreviated new drug applications, largely from its facilities in Bangalore and Mumbai, because it couldn’t substantiate the data filed with the FDA supporting the applications to market these drugs in the U.S. These are not 15-year-old incidents, as claimed by Eban’s critics.
The striking aspect of the multiple warnings to Indian pharmaceutical companies is the similarity in the violations cited. The first category of violations involves the lack of cleanliness and sanitary conditions at Indian manufacturing plants which, under the law for finished pharmaceuticals, are required to operate in a hygenic environment. This is an issue that can be fixed with relatively small investments in better training and thorough supervision.
The second category of violations pertains to data integrity: maintaining meticulous and accurate records of all stages of manufacturing and quality testing. “Bottle of Lies” documents how the FDA’s investigators repeatedly discovered falsified records at Indian plants. When a batch would fail testing, rather than destroy the batch or remedy the manufacturing process, the quality control staff at these plants generally manipulated the records to create false data that supported releasing the batch to the market.
The data fabrication processes at these companies were often quite intricate. Some of the most reputed Indian companies were found to have entire laboratories dedicated to generating fake records that were off the books. Fabricating these records is ridiculously easy, especially for facilities that were given advance notice of inspections by FDA inspectors, unlike the usual practice in the U.S. where inspectors turn up unannounced. This gives Indian safety managers plenty of time to stage-manage these inspections.
Shaw makes the point that the facilities in India that make medicine for the U.S. are more advanced and automated than those in the United States. Some of this is true. The Indian pharmaceutical industry has upgraded its facilities. But stainless steel reactors do not produce drugs all by themselves. They need trained operators — and ones who know right from wrong and do not put profits over patients. Evidence collected by FDA inspectors shows this is sorely lacking in overseas manufacturing facilities.
Automation and investment in upgrading facilities is an argument made to distract from the real issue, which was never about capacity, technology or training. It is all about profits, because quality comes at a price. There is a cost to destroying a batch of drugs that doesn’t meet release specifications, and no amount of third-party consultancy or employee retraining will address that issue.
While shiny new stainless steel reactors and automated processes may well be showcased for products made for Americans, the companies that tout them use dilapidated, pest-infested, unsanitary conditions to make medicines for consumption by patients in India and for export to other countries, especially those in Africa and Latin America.
U.S. law requires meticulous record keeping at all FDA-approved plants that make pharmaceutical products for the U.S. market. Not maintaining records is not an option. By covering up failed test results, companies were essentially covering up the sale of adulterated medicine to Americans. If these companies were to maintain accurate records of all the failed tests for products to be sold in the U.S., they would also be required to destroy or recall entire batches of medicine that had failed to pass tests conducted before their release. This would mean lost profits, and that is the simple reason behind the massive efforts these companies have invested in — like undisclosed quality control laboratories — to manipulate and fabricate data, even if it comes at the cost of compromising lives.
The statements made by Shaw and other titans of the Indian pharmaceutical industry demonstrate no will to accept that a problem exists.
The only way Indian companies are going to modify their behavior is through a combined policy of tough penalties and unannounced inspections. Yet in the last decade, despite several Indian pharmaceutical companies being enjoined from exporting drugs to the U.S. because of systemic violations of U.S. regulations, only Ranbaxy was ever brought to justice. It does not help that the FDA, after a brief and highly successful experiment with unannounced inspections, has reverted to giving advance notice of its inspections to overseas pharmaceutical facilities.
As one of those who helped bring Ranbaxy to justice in a U.S. court, I chose to make my disclosures to American regulators rather than Indian regulators because I had no faith in the latter. A few weeks after the U.S. Department of Justice unsealed my case against Ranbaxy in May 2013, India’s Ministry of Commerce and Industry issued a press release claiming that “vested interests” were trying to malign the Indian industry. When I tried approaching Indian courts about making changes in the Indian regulatory system, the Indian regulator publicly questioned my “intentions” and my “nationalism.”
Despite this slander, I have tried engaging with Indian regulatory authorities on multiple occasions, but with only lukewarm results. The one helpful bureaucrat in the Indian Health Ministry who was willing to hear me out was punished with a transfer to a low-key department shortly after he implemented a few of my recommendations.
Things are not getting better and part of the reason is because the generic drug industry is too powerful and influential in India.
If Americans are expecting India, which supplies a significant percentage of the finished drug supply in the U.S., to get its act together to improve the quality of the medicines it makes, I am afraid they will be waiting a long time for that to happen. The only solution is for American lawmakers to enact new regulations focused on holding those who intentionally put public health at risk to account.
Dinesh Thakur, the former director and global head of research information and portfolio management at Ranbaxy Laboratories, was the whistleblower in the Ranbaxy case and is a key source in “Bottle of Lies.” He is now a public health activist focused on improving the quality of affordable medicines.
Source : statnews