U.S. Is Suddenly OK With Indian Hydroxychloroquine Maker It Banned For Multiple Violations

The US Food and Drug Administration has lifted a 3 year-long import ban on chloroquine products manufactured by Mumbai-based Ipca Laboratories, a company that it last investigated in August 2019.

NEW DELHI — The United States Food and Drug Administration (FDA) lifted import curbs on hydroxychloroquine produced by a tainted Indian pharma company on the same day that President Donald Trump promoted his controversial theory that the anti-malarial drug could help COVID-19 patients, documents show.

As late as August 2019, the US FDA had censured India’s Ipca Laboratories, a company producing close to 70% of the world’s hydroxychloroquine, for a “cascade of failures”. In one particular case, the FDA said, the firm’s quality control analysts had deviated from standard test procedures, or STPs, “for over twelve (12) years.”

The US FDA’s years-long investigation into Ipca’s manufacturing processes had prompted the Switzerland-based Global Fund to Fight AIDS, Tuberculosis and Malaria to drop Ipca from its list of suppliers of antimalarial drugs in 2016.

But a Trump-inspired global race to stockpile hydroxychloroquine appears to have forced the FDA to overcome its squeamishness in dealing with a drug company the agency has previously accused of a litany of violations including the falsification of clinical data. The FDA volte face reveals the extent nations are willing to go to secure medical supplies in their battle against the global coronavirus pandemic.

On March 21, Ipca informed the Indian stock exchange that a day ago, the FDA had temporarily lifted import curbs on the company’s hydroxychloroquine products “due to the shortage implications and/or medical necessity of certain drugs and finished products.” The exchange filing was reported by news outlets including Bloomberg.

India banned the export of hydroxychloroquine on 25 March, but on 6 April, the government said it would consider allowing limited exports to some countries. Prime Minister Narendra Modi is under fire at home after President Trump suggested India reconsidered its position on hydroxychloroquine exports after he threatened India with “retaliation.”

As late as August 2019, the FDA had issued a scathing assessment of Mumbai-based drug company Ipca Laboratories. An inspection of Ipca’s manufacturing sites in the Indian states of Madhya Pradesh and the Union Territory of Dadra & Nagar Haveli between August 19 and August 23 2019 revealed “a cascade of failure”, the FDA observed.

“Your Quality Unit has not been effective in carrying out its duties of ensuring that drug products are manufactured in accordance with current good manufacturing practices (CGMP) to ensure safety, efficacy, purity and overall quality of drug products manufactured at your firm,” the FDA said.

In one particular case, the FDA said, the firm’s quality control analysts had deviated from standard test procedures, or STPs, “for over twelve (12) years.”

The August 2019 inspection was not the first time the FDA had flagged issues at Ipca’s facilities. In January 2016, the FDA sent Ipca a warning letter, noting that its inspectors had found “systemic data manipulation and other CGMP violations and deviations at three separate sites.”

Then on March 20, 2020, US President Donald Trump enthusiastically promoted his theory that anti-malarial drug hydroxychloroquine was a cure for COVID-19 at a press briefing, and followed it up with a similarly bombastic tweet, the New York Times reported.

The next day, March 21, Ipca Laboratories informed Indian stock exchanges that the USFDA had made a temporary exception on import curbs on Hydroxychloroquine Sulphate and Chloroquine Phosphate APls and Hydroxychloroquine Sulphate Tablets from the very same facilities the agency had castigated for failing quality standards. The FDA’s exception, Ipca said, will be reconsidered if “shortage implications change.”

In their exchange filing, Ipca claimed there were “several credible articles / reports / research papers claiming prophylactic as well as treatment potentials of Chloroquine Phosphate and Hydroxychloroquine Sulphate formulations in managing/treating Coronavirus Disease (Covid-19).”

The World Health Organisation is overseeing one such study, but the results are not yet in. Meanwhile scientists across the world, including the head of the US task force on COVID-19, Dr. Anthony Fauci, have cautioned against using the drug on COVID-19 patients.

Thus far, the only study claiming to show positive results is a largely discredited French study that violated all norms of randomised controlled trials — the gold standard for clinical testing.

Cascade of Failures

On July 15 2019, Ipca Laboratories published its annual report, noting that 2018-19 had been one of its most profitable years. Net profits were up 95%, the company’s cash reserves were healthy, and it was now exporting to 100 countries around the globe. Antimalarial drugs, which include hydroxychloroquine, accounted for 18% of all exports, the company said.

The only glitch in an otherwise sterling report was a US FDA “import alert”, which affected the company’s ability to export its products to the United States. An “import alert”, the US FDA website explains, allows the agency to detain products that appear to violate the agency’s rules and regulations.

Ipca’s troubles with the US FDA had been going on for some time: According to a warning letter dated 29 January 2016, the agency drew attention to a 2014 inspection of three manufacturing facilities, where it found several serious deficiencies including the manipulation and possible falsification of data.

“Our investigators found that your firm routinely re-tested samples without justification, and deleted analytical data. We observed systemic data manipulation across your facility, including actions taken by multiple analysts, on multiple pieces of testing equipment, and for multiple drugs,” the FDA noted at one point.

Elsewhere in the letter, the FDA said, “During the inspection, our investigators spoke with an analyst who reported that “…if we find a failure, we set back the date/time setting and re-integrate to achieve passing results…” The analyst explained that deleting, overwriting, changing integration parameters, and altering PC date and time settings were done for raw materials, in-process testing, and finished API drugs.”

The January 2016 letter warned Ipca to fix these problems, failing which its products could be barred from the United States. On June 16 2017, Mint reported that the FDA had barred the company’s products due to non-compliance.

But Ipca’s 2018-2019 annual report struck an optimistic tone, said the company had implemented “comprehensive remedial measures at all its manufacturing sites to ensure quality and regulatory compliances” and noted that it was awaiting a re-inspection by the US FDA.

“Your management is confident that implementation of remedial measures will ensure that the Company will regain all its regulatory approvals,” Ipca’s annual report said.

The US FDA’s subsequent inspection report suggests Ipca’s optimism was misplaced. The FDA’s inspection report from August 2019 continued to find problems with the way Ipca recorded their data, a failure to review any discrepancies in the data, and finally, issues with the quality control units of Ipca’s manufacturing facilities.

It was only in March 2020 that the FDA lifted curbs on imports of Ipca’s products, albeit temporarily, amidst the global rush for nations to secure stocks of medical supplies in the fight against Covid-19.

HuffPost India has reached out to Ipca Laboratories for comment, and will update this article once they respond.