Book Explains How Generic Drugs Manufacturers Ignored Security and Fraud: Shots

Generic drugs are supposed to work as well as their brand counterparts.

Once the patent is lifted, generic manufacturers find alternative ways to make a drug that should work without distinction from the branded version. In a world of rising prescription drug prices, cheaper generics have been a crucial counterweight.

But in Bottle of liesKatherine Eban, an investigative journalist and author, exposes the dangerous dark side of some generics. His narrative survey on propulsive story retraces the history of the generic drug boom, revealing how intense demand for cheaper drugs opens up a dangerous gap between regulations imposed on drug companies and the behavior of some of these companies. She also explains how the FDA has struggled to fill these security gaps and address the remaining challenges.

Between detailed stories about the evolution of the FDA and the rise of Indian pharmaceutical companies, factory workers fleeing FDA inspectors with garbage bags filled with fraudulent recordings, and a company that monitors the chambers of regulators in the process of planning a factory inspection. Eban paints a complete and disturbing picture that anyone concerned with the pharmaceutical industry should read.

The generic drug boom began in the mid-1980s, when pharmaceutical giants such as Pfizer dominated the market. In response to rising costs and complaints about the influence of "big pharma," Congress unanimously passed the Hatch-Waxman Act in 1984, which created a new regulatory pathway for generic drugs. As long as generic drug companies could prove that their drugs were bioequivalent to brand name drugs, which meant that they acted the same way in the body, they could be approved. It was a boon for generic drug manufacturers, and in principle for the American public, to allow the market competition to produce cheaper but equivalent drugs.

But according to Eban, some parts of the law drove speed to quality. Its "first-to-file" rule grants the company filing its application to the FDA the exclusive right to sell its version of the generic drug for six months, at prices close to those of the mark, before competitors can enter the market. According to Eban reports, this created a "Wild West" environment where it was more important to be first than to succeed.

"In theory, all companies had to follow the same rigid set of good manufacturing practices," she wrote. "But for companies that were inclined to favor profits over quality, there were many opportunities for improvisation and shortcuts."

The bulk of the book is devoted to the Indian company Ranbaxy, the largest overseas manufacturer to sell generic drugs in the United States and one of the largest generics suppliers in the world. In 2013, Ranbaxy's US subsidiary Ranbaxy USA pleaded guilty – and paid a $ 500 million fine – to several charges related to the sale of adulterated drugs and lying to the FDA on the subject.

Eban's story about the dubious practices of Ranbaxy begins in the early 2000s, but it would take years for the FDA to inquire about the offense, and even longer for the regulator to act. Eban's stories tell this story backed by interviews with more than 240 people, including FDA inspectors and Dinesh Thakur, a former chemical engineer and Ranbaxy's whistleblower.

Before working for Ranbaxy, Mr. Thakur spent about a decade at Bristol-Myers Squibb, where he learned how a well-known brand-name pharmaceutical company was managing and documenting mass drug production in accordance with FDA regulations. When billions of pills are produced each year, maintaining and documenting good manufacturing practices is the only way to ensure – and to demonstrate to regulators – the quality of the drugs.

But in Ranbaxy, Thakur has encountered a systematic fraud ring. The company often used substandard ingredients to save money, manipulate quality control data, or make figures from scratch. (These details were cited in the 2013 trial that the Justice Department ultimately brought against Ranbaxy USA.) As a result, as the case was alleged, the company was selling drugs of dubious purity, thus potentially the safety of patients at risk.

In court documents, the Justice Department alleged that Ranbaxy knew the extent of their problems, but had not done anything to improve their manufacturing processes, or that it was not confessed with the FDA.

Eban writes that, in response to this fraud, Thakur has resigned. In 2005, he contacted the FDA about Ranbaxy practices. But it would take almost a decade before his concerns lead to meaningful action. This prolonged test illustrates how badly the FDA was equipped to regulate foreign manufacturers.

In the United States, FDA inspectors can go to a factory at any time, which encourages companies to always stay in compliance, lest they be caught off guard by an inspection. But the globalization of the pharmaceutical industry has complicated this practice. In order to minimize diplomatic tensions, the FDA notified the plants months before the visits. This delay gave foreign companies enough time to prepare for inspections. Eban describes company accounts that hastily cleaned up workspaces, shredded files and made documents, or even destroyed visibly contaminated drugs.

The evidence provided by Thakur to the FDA has not resulted in swift and radical action. Some Ranbaxy plants have received minor restrictions from the FDA. Others squirted during regulatory inspections, such as the plant that manufactured the generic Lipitor, the most successful cholesterol-lowering drug. Less than a year after the plant passed an inspection in 2012, Ranbaxy admitted that some of the millions of generic Lipitor pills already distributed in the United States were inundated with tiny pieces of blue glass.

Internal divisions and congressional pressures have also limited the FDA's response to violations abroad. In the US, the demand for cheaper generic drugs was huge – delays in launching a generic version of Lipitor could cost Americans up to $ 18 million a day, according to a 2011 group letter of US Senators addressed to the Commissioner of the FDA. Eban reports that a number of FDA officials have estimated that "senior officials" downplayed the scale of the problem.

People outside the FDA have also noticed problems with generic drugs. Eban documents increasing skepticism towards certain generics among American and African doctors. After many cases in which patients had problems after switching from branded drugs to generic drugs, many health professionals began to avoid prescribing some generic drugs.

Some patients who have opted for a generic version of Wellbutrin, an antidepressant, have complained of headaches, nausea, irritability and even suicidal thoughts. There were reports of pills that literally smelled like "fish". It took the FDA five years to verify that the generic pills produced by the Israeli manufacturer Teva were not equivalent to the Wellbutrin brand.

The situation was even worse in Africa, where many manufacturers shipped substandard drugs. Some were completely counterfeit, with independent laboratory tests showing no active ingredients. Those who had active ingredients often had not enough, and doctors should prescribe between two and ten times the usual dose to get an effect, according to Eban.

Eventually, Ranbaxy, as a company, was brought to justice. But none of the responsible persons has been prosecuted. Many Ranbaxy executives simply brought their expertise to other major generic drug companies, where the fraud would continue, as Eban describes later in his book.

Eban points out that when generics work, and many do, they play a vital role in public health. But his work has highlighted the profound challenges of regulating a globalized pharmaceutical industry. She ends the book on a maddening note. Despite a brief stint of unannounced overseas inspections from 2014 to 2016, the FDA is currently informing factories of routine inspections well in advance.

Jonathan Lambert is an independent science journalist based in Washington, DC. You can follow him on Twitter: @evolambert.