After a tweet by Donald Trump, US drug regulator reverses four-year-old ban on Mumbai’s Ipca Laboratories, one of the world’s largest makers of a medicine that Trump wants to import as a Coronavirus cure. His eagerness should concern India
St Petersburg (USA): First approved 65-years ago for medical use as an antimalarial drug, hydroxychloroquine made news on 21 March 2020, when US President Donald Trump, tweeted that the medicine was a possible cure for COVID-19, if used in combination with the antibiotic azithromycin.
Trump’s announcement should concern India because, after his tweet, his administration reversed a four-year ban on a Mumbai company—one of the world’s largest manufacturers of hydroxychloroquine—that had been caught falsifying regulatory data and violating quality standards.
A reversal of the ban also puts at risk India’s ability to build stocks of hydroxychloroquine, either for the coming malaria season or as a potential salve for the country’s expanding Coronavirus outbreak—if Trump’s claim ever acquires scientific validity.
A cure is what the world needs as the Coronavirus pandemic spreads. If true, Trump's declaration should be the cause of great celebration. But the case for the hydroxychloroquine/azithromycin combination rests on a shaky scientific foundation.
The best evidence for the claim came from a March 2020 clinical study in France. The study appeared to show that the drugs helped patients reduce or even eliminate the COVID-19 virus.
But the French study was criticised because it involved a small number of patients, and almost a quarter of those enrolled in one of the arms of the study were not included in the evaluation, for a number of reasons. Further, the publication of this study was rushed; unlike most clinical studies, it did not receive adequate peer-review before being published. Even if the French team turns out to be right, chloroquine poses significant risk to patients with heart disease and requires diligent patient screening and monitoring.
This is not how drugs are supposed to get to market.
Most modern medicines are required to undergo well-designed clinical studies to demonstrate that they are both safe and effective. These studies typically randomize the patients getting the drug being tested versus a comparator, which in many cases is a placebo or an existing drug. Ideally, neither the doctors administering the treatment nor the patients receiving it are allowed to know whether the patient is receiving the drug or the comparator, so as to eliminate biases.
It is not easy to plan an airtight study in the middle of an epidemic, but the French study was not designed in this manner. At most, the French study provides a promising lead.
Trump’s Hope: A Discredited Indian Drug Manufacturer
Yet, the American President has pinned a nation’s hope on this drug combination, and his administration is taking swift and desperate steps to build a stockpile of these drugs.
This includes lifting an import ban imposed by the United States Food and Drug Administration (USFDA) on Indian manufacturer Ipca Laboratories: one of the largest global manufacturers of hydroxychloroquine, as we said. This means that the USFDA's role in overseeing the safety of the drugs on the market is in danger of being compromised.
Ipca Laboratories was prohibited from exporting its products to the US market in January 2016 because of serious lapses found at three of its manufacturing plants by drug inspectors from the USFDA, including "multiple examples of [Ipca's] backdating and falsifying laboratory data."
More than three years later, USFDA went back to the same facilities to reinspect them. Its inspectors’ “record of the observations” implied nothing much had changed.
FDA inspectors observed what they called “a cascade of failure” in the company’s quality control unit and suggested that the firm had fiddled with the computer system to avoid having to figure out how to remove impurities in their drugs.
The same report suggested that the company was not diligent in chasing down the cause of consumer complaints, such as when a "hair was found embedded in the tablet".
None of these observations is surprising. Most Indian pharmaceutical companies that have faced regulatory action from the USFDA were found guilty of similar violations (here, here, here and here), including Ranbaxy, where, in 2004, I found evidence of widespread fraud.
Indian Drug Companies And The FDA
The USFDA's sudden change in attitude bears explanation. For the past six years, the USFDA has declared that Ipca's drugs were not good enough for the US market. The most recent inspection, less than a year ago, reinforced rather than assuaged the agency's doubts.
Yet, the USFDA has now suddenly lifted its ban on Ipca, making it apparent the regulator is relaxing its standards because of political pressure.
The political whims of a government agency half a world away has profound effects on the Indian pharmaceutical industry because India’s drug industry is deeply entangled with the regulatory framework of the United States.
The USFDA requires US inspectors to visit drug companies in India (and in other countries) to ensure that its standards are met. This is an odd arrangement: The US Federal Aviation Administration does not have its inspectors travel to India to ensure that Air India meets US safety standards when it flies to Newark Airport. It relies on a (multilateral) treaty to ensure that its Indian equivalent, the Directorate General of Civil Aviation, complies with safety standards for its aircraft and crew.
There is no reason why this model cannot work when it comes to our drug supply; Indian regulators should be able to hold Indian drug manufacturers to a standard that would satisfy the world community.
Over the last decade, the Indian government has lacked the political will to address its generic-drug industry’s persistent quality problems, as manufacturer after manufacturer gets caught selling tainted drugs, falsifying tests, and reinforcing the American lack of trust in India's capability for self-regulation.
It seems unlikely that the Indian government will change its attitude during the pandemic, even though the stakes are high. For now, India's regulators must step in to minimize the damage from a politically-driven rush to foist unproven drugs on scared American citizens.
What Does India Need To Do?
First, India should regulate the sale of hydroxychloroquine and azithromycin; already there have been reports (here and here) of healthy people buying up stocks of both drugs in anticipation of getting infected by COVID-19.
Self-medication for hydroxychloroquine should be prevented, not just because its efficacy is doubtful, but also because it has serious side-effects, including potentially affecting the rhythm of the heartbeat.
Already, a US man in his 60s died from the unsupervised consumption of chloroquine phosphate—a chemical used to clean fish tanks—which he mistook for hydroxychloroquine after listening to Trump.
HydroxyChlroquine is a Schedule H drug in India. It should only be dispensed and administered under medical supervision. To remind you, its efficacy to treat coronavirus is not yet established.
Second, the Indian government should take steps to ensure that patients who need these drugs—hydroxychloroquine is used as a treatment primarily for rheumatoid arthritis, lupus and malaria—are not faced with shortages because of the Trump-inspired buying spree.
India should have adequate supplies of these drugs for its citizens who rely on these drugs, before any exports are authorized, for those speculating about its possible use as an antiviral.
We do not know if hydroxychloroquine is of use in combating COVID-19, but we know that it needs to be available to combat any outbreaks of malaria in the coming monsoon season. If the drug is approved to combat the Coronavirus, it would also be a tragedy if India loses its ability to alleviate the suffering of its own people to salve the political ego of a man on a different continent.
(Dinesh Thakur is a public-health activist, based in St Petersburg, Florida. He wishes to acknowledge help from Prashant Reddy, a lawyer based in Bengaluru and Charles Seife, a professor of journalism at New York University, in authoring this piece.)