A Bitter Pill to Swallow

Katherine Eban's Bottle of Lies uncovers the egregious practices of generic pharmaceutical companies by following the events that led to the conviction of India's generic drug company Ranbaxy.

Tweet Review (50 words or less)

A hard to put-down thriller with a few powerful villains, mafia groups and greedy bureaucrats that make millions by providing sub-standard drugs to patients with little guilt -- and a handful of heroes who fight the corrupt system. Unfortunately, it is not fiction but based on true events.

Longer Summary

In the movie Matrix, the protagonist is offered two pills. If he takes the blue pill — it would lead him back to a ‘happy’ existence. However, if he takes the red pill — it would let him know the reality which might be harsher and more difficult. Reading Katherine Eban’s Bottle of Lies is like taking the red pill (pun intended). The book felt more like a thriller fiction with rich, powerful villains profiteering by providing low-quality products to poor people, rent-seeking bureaucrats who overlooked glaring mistakes, clunky and outdated regulations, and a handful of courageous individuals who fought the system to expose the malpractices in the generic industry. Unfortunately, it is not fiction. And spoiler alert, there are no happily ever after.

The central theme of the book is the events that ultimately led to exposing of Ranbaxy’s malpractices. However, Katherine Eban also provides commentary on the history of the Pharma Industry, the rise of the generic industry, and regulatory flaws that led (and continues to lead) to such egregious outcomes.

But before I provide the details here are 11 things you should know about the book & the Pharma Industry

1. This book is not about ‘A White American ranting about Indian Pharma.’ When I suggested this book to my Indian friend, he angrily mentioned that Americans should fix their industries instead of bad-mouthing Indian pharma. Obviously, he hadn’t read the book. Katherine Eban’s book is balanced, well-researched, and equally trenchant about the American pharma industry. Don’t judge a book by its color or cover.
2. Almost all drugs will harm you. Only those drugs made in a controlled setting and tested rigorously can be beneficial to you. Others are likely to harm you.
3. Remember one acronym — Active Pharmaceutical Ingredients or APIs. It is a fancy term for ingredients (molecules, compounds) required to create the drug. 
4. Sorry, one more acronym — Food and Drug Administration or FDA. An American Federal agency that is responsible for overseeing and approving all the drugs that are sold in the US. 
5. Sub-standard drugs are different from counterfeit drugs. This book is about the former. Counterfeit drugs are fake but look genuine — like muddy water looks (somewhat) like chai. We are outraged when someone sells fake drugs. But sub-standard drugs are like chai made with spoiled milk. It won’t kill but it can make your life miserable. We should be equally outraged but aren’t. And remember point 2. 
6. Sub-standard drugs are very bad in a long run. Since these drugs have some APIs of the original but not everything, it can make pathogens develop resistance to it. In the long run, even genuine drugs will lose their efficacy. 
7. Big Pharma makes branded drugs and has a monopoly over selling them to consumers for X number of years. Since they spent millions in R&D to develop the drug, the governments give them Intellectual Property (IP) to sell in the market for x number of years to recoup the input costs and make profits.
8. Once the patent expires, the brand-name company gives the recipe to the world, the generic company makes the same drug at a cheaper cost since they don’t need to invest in research and marketing. 
9. Point 8 doesn’t happen. 
10. Instead, the Big Pharma resorts to ‘shenanigans’ to stop generic drugs. They patent the manufacturing process, make small changes to the drug and declare them new, don’t reveal the recipe, and hired a bunch of lawyers to stop companies from manufacturing generic drugs. 
11. The generic industry needs to reverse engineer the branded drug, change the manufacturing process and achieve the same results. If Big Pharma follows 1-2-3-4-5 to create the drug, generic companies need to create the drug following different steps like 4-3-1-2-5. 
12. Generic drug testing is outdated and wrong. They focused on the outcome of the generic drug and not how it achieved it. However, the rate and duration of absorption could be different. Let me give an imaginary situation. Assume the branded drug reduces 10 calories by making the patient’s heartbeat a little faster. The generic drug will be approved if it reduces 10 calories even if it doubles the heartbeat of the patient. What are the side-effects of increased heartbeat? Not tested.
    

Rise of Generic Industry in India

One must credit the rise of the generic industry in India to two (relatively) unknown Indian heroes.

Dr. Khwaja Abdul Hamied, inspired by Gandhi’s message in 1920 to serve Indians, studied chemistry in Cambridge, married a Jewish girl with Communist leanings in Germany -- and later, founded Cipla in 1935. His company supplied anti-malarial drugs and vitamin B12 to the Indian Army during World War 2. Despite facing bureaucratic redtape after India’s independence, he worked relentlessly to make drugs that were accessible and affordable to Indians.  

Yusuf Hamied, son of Dr. Hamied, took the baton from his father and changed the image of India and the generic industry around the world. During the 1990s, AIDS was ravaging across Africa. Big Pharma was selling the drug cocktail that controlled HIV at $12000 a year per patient. Yusuf Hamied promised and provided the generic AIDS drug for less than $1 a day per patient. People were outraged that Big Pharma is charging such high prices when it can be developed at such low cost. Eventually, the attitude of the West changed — from ‘we can’t afford to help’ to ‘we can’t afford not to.’

The son of a Gandhi-inspired Muslim freedom fighter and communist jew radically transformed the pharmaceutical industry from profit-driven to care-driven. (I hope a biopic is made about him but I fear it won’t since Muslims and communists are both pariahs in Bollywood).

Rise of Ranbaxy and Fall(ing) of Generic Industry in India

Taking advantage of India’s positive image on the generic industry, Ranbaxy — under the leadership of Maninder Singh — focused on selling generic drugs to the US and other lucrative markets. However, the company focused primarily on profits rather than patients.

It was later found that Ranbaxy was hardly testing drugs — few drugs that were created and sold in India were properly tested. They would either fabricate data or show results from branded drugs while filing their applications. If any drug was rejected in the US, it was usually sold in India or worse, shipped to Africa because — as one Ranbaxy executive put it — ‘who cares about the Blacks.”

But how did they get away with sub-standard drugs?

Lax regulatory policies, political pressure, insufficient capacity

The FDA, which approves drugs sold in the US, visits and inspects manufacturing sites unannounced for assessing quality and standards. With the advent of globalization and the boom in generic industries, most manufacturing sites moved outside of the US. By the mid-2000s, the number of manufacturing sites outside the US was greater compared to within the US. Unlike in the US, FDA had to take formal appointments outside the US — often months in advance — before inspecting the sites. So, you can imagine, generic companies like Ranbaxy had sufficient time to create a facade of high standard when the reality was completely different.

Further, there were only a few FDA officials were willing to visit India. So, some manufacturing sites would be visited once every couple of years.

There was also political pressure to approve generic drugs. Since generic drugs cost a lot less than their original counterparts, the politicians would insist FDA should approve applications faster to make them accessible to millions of Americans. Thus, the FDA was hesitant to deny any application even if they found something suspicious.

Uncovering the Mountain of Lies

The book follows the life of Dinesh Thakur — a US-educated Indian engineer— who returned to India to join Ranbaxy as he was convinced that the generic drug industry can be a force of good worldwide. Initially, he was impressed by Ranbaxy’s style of work with its start-up-like attitude of aggressively testing and filing new drug applications. While there were several red flags like lack of proper data and documentation, Thakur contended this was due to differences in working culture between the US and India.

But things took turn for worse in 2005 when WHO’s Olivier LeBlaye identified and reported fraudulent data on Ranbaxy’s antiretroviral drugs to its AIDS-ravaged population in South Africa. The report concluded that testing data was fabricated. Raj Kumar — Thakur’s boss who recently joined as Director at Ranbaxy — directed Thakur to investigate and uncover the cause of the problem.

However, this was a rabbit hole as more Thakur investigated, more he became concerned with Ranbaxy’s lack of compliance and systematic fraudulent practices. After assiduously documenting all the malpractices, Raj Kumar presented this report called ‘the SAR (Self-Assessment Report) to the top executives. Instead of acting upon this, the executives told Kumar to destroy the report. This report, later, became the key evidence to convict Ranbaxy.

Soon, Kumar resigned while Thakur was threatened before he was unceremoniously fired. Thakur started sending emails to the FDA exposing Ranbaxy’s malpractices as the US was their biggest market. Initially, FDA was slow to respond as they didn’t trust Thakur. Over time, the FDA started investigating further after Thakur shared several damning pieces of evidence of fabricated data by Ranbaxy.

Justice delayed is justice denied

Thakur had thought that once he gives all the evidence to the FDA, his role will be over. But he was embroiled in this investigation for several years. With limited sources of income, he was asked to come to the US, meet state attorneys and submit his evidence. Later, they asked Thakur to get a lawyer to defend himself. (Lawyers in the US are expensive and Thakur was unemployed).
Imagine, you are walking down the street and see a murder. And the murderer is your employer. You capture it on your phone. What should you do?

The right thing to do: Report the incident to the police and share the evidence with them. The police don’t believe initially. After years of conversations and meetings, the police finally write the FIR. But the police ask you to get a lawyer by paying crores to ensure you don’t get sued by the murderer. Meanwhile, the employer (aka murderer) threatens you and your family, fires you from the job with no other sources of income.

You will ask yourself, was this the right thing to do?

Thakur must have asked this question to himself several times. One can imagine the anguish, frustration, and anxiety faced by Thakur and his family throughout this journey.

Arc of the moral universe is long, but it bends toward justice.

Long story short. In May 2013, Ranbaxy pleaded guilty to multiple criminal felonies and agreed to pay $500 million to resolve criminal and civil allegations of falsified drug data and systemic manufacturing violations resulting in substandard and unapproved drugs. But no criminal charges were held against the executives. In other words, the murderer got bail.

Thakur was awarded $48 million as part of the False Claims Act in the US — which awards some percent of the settlement money to whistleblowers to incentivize them to report fraud — for his role in exposing Ranbaxy. But this came at the cost of mental trauma, loss of job, no financial support, family problems for six years. Was this worth it?

All’s Well That Ends Well?

After the conviction of Ranbaxy, one would have imagined that things would have changed for the better. However, Ranbaxy was a symptom of a larger problem — lack of regulatory oversight and capacity by FDA to monitor generic industrial sites outside the US coupled with Big Pharma monopolizing branded drugs. The patients are left with Hobson’s choice — either buy expensive Branded drugs or cheap substandard generic drugs. Either way, the patient pays a heavy price.