Slow and opaque decisions during Covid-19 crisis put the spotlight on India’s drug regulator

On April 3, the Bengaluru-based biotech startup Bione Ventures Private Limited issued a press statement announcing the launch of its “breakthrough…simple point-of-care home screening kit”. These rapid antibody kits, the company said, had been sourced from “worldwide” partners and had received approval from the “requisite regulatory authorities”.

With the Indian Council of Medical Research’s test kits starting to run scarce and testing having recently opened up to the private sector, the announcement invoked a considerable amount of media interest. News reports hailed these “first of its kind in India” kits that “display accurate results within minutes”. Some even amplified Bione’s false claim that its kits had been approved by the ICMR, the research body spearheading India’s response to the pandemic.

However, India’s drug activists did not greet Bione’s announcement with the same amount of excitement. Their scepticism was not unfounded: rapid tests, which look for disease-fighting antibodies as opposed to the virus itself, could give misleading results and are not reliable diagnostic kits as the company seemed to be marketing them as.

But more disconcertingly, India’s drug regulator, the Central Drugs Standard Control Organisation, was yet to release the list of 18 diagnostic kits manufactured by private companies it had approved the sale of in the last week of March. The organisation repeatedly stonewalled queries about the approved kits by journalists.

In the absence of such a list, activists worried that it was likely for people to mistake Bione as an approved diagnostic kit and develop a false sense of security.

On April 4, the All India Drug Action Network, a watchdog organisation, shot off a letter – its second in less than a week – to the Drugs Controller General of India who heads the Central Drugs Standard Control Organisation, articulating these concerns. The letter referred to Bione’s claims of being approved by the “requisite regulatory authorities”. “In the absence of a public list of all COVID-19 test kits approved by CDSCO, it is impossible for us to verify such claims,” the network pointed out.

The strongly-worded letter urged the regulator to “make publicly available a regularly updated list of all COVID-19 kits…that have been approved by CDSCO” along with their prices and approval pathways.

The drugs controller appeared to have taken cognisance of the letter. The next day, on April 5, the regulator issued a press statement clarifying that it had not licensed the “aforementioned diagnostic kit by Bione” as had been “widely publicised in the media.”

Soon after, the Central Drugs Standard Control Organisation finally uploaded the list of approved kits on its website, which it has routinely updated ever since.

Responding to an email by Scroll.in, the Drugs Controller General of India VG Somani flatly denied there was a delay. “Kits were made known to public in time,” he said.

A not-so-glorious past

The Central Drugs Standard Control Organisation, which operates under the Union health ministry, is responsible for all things related to “safety, efficacy and quality” of medical products manufactured, imported and sold in India. Which means it also oversees and sets safety standards for clinical trial of drugs in the country.

According to its website, the organisation is “constantly thriving upon to bring out transparency, accountability and uniformity in its services” [sic].

Yet, few observers of India’s health regime seem to associate these virtues with the Central Drugs Standard Control Organisation. Its seeming reluctance to share information about the diagnostic kits voluntarily and proactively was not an isolated lapse – but is of a well-documented pattern.

In May, the Central Information Commission came down heavily on the regulatory body for not having made a report of an independent committee probing into irregularities in its functioning public. The organisation had refused to share the report with a person who had sought it under the Right to Information Act, saying it had gone “missing”.

The “missing” report, it turned out, revealed irregularities in how the regulator had approved four drugs (unrelated to Covid-19).

In 2008, a parliamentary standing committee had made scathing remarks about the regulator’s opaque functioning: how it operated in connivance with pharmaceutical companies approving drugs without clinical trials. The report did lead to some reforms, but observers say that the regulator had failed to live up to its mandate yet again in the current pandemic, its biggest test since.

Missing in action

“One thing that has come out very strongly in the last three months is that the CDSCO which is the main regulator for medical devices and is supposed to set the standards for different kinds of tests and therapies is almost nowhere to be seen,” said Amar Jesani, editor of the Indian Journal of Medical Ethics and a public health activist. “It seems it has abdicated all its responsibilities to the ICMR as if it is not answerable to the people of India and has no accountability.”

Public health experts say that a strong and proactive regulatory body in these times is indispensable. “With off-label and compassionate usage of drugs becoming quite common, one needs to have a strong approach to ensure you are looking at adverse events and side effects carefully,” said Anant Bhan, a health researcher at Yenepoya University in Mangalore. “All of that is an important regulatory function in most parts.”

It was, therefore, Bhan said, important to interrogate what role India’s drug regulator was really playing. “If they are not at the forefront and playing a supporting role instead, we need some clarity on that too – otherwise it just creates confusion,” he said.

Little voluntary information

But clarity seems to be hard to come by. The Central Drugs Standard Control Organisation has disclosed little information voluntarily on its website. There is nothing by the way of communication on committees formed, meetings held, and decisions arrived upon.

The regulator’s official Twitter handle has tweeted once on its own since the disease outbreak – to plug a podcast featuring a senior State Bank of India functionary (on June 7, it replied with the two thumbs up emoticons to a tweet sharing a podcast highlighting the Bollywood actor Sonu Sood’s efforts to repatriate stranded workers).

In terms of official communication, it was the department of biotechnology which on March 20 announced the formation of a joint empowered committee with the Central Drugs Standard Control Organisation to examine and facilitate regulatory requirements related to “development of diagnostics, prophylactics and therapeutics for COVID-19”. It was to be co-chaired by the drug controller general and the chairman of the department of biotechnology’s Review Committee on Genetic Manipulation.

There has been no news on the joint empowered committee ever since. There is no mention of the committee on the Central Drugs Standard Control Organisation website at all.

Responding to Scroll.in’s query about the committee, Somani said, “CDSCO is working in hand to hand with DBT and its committee is working regularly for clearance.” The official did not respond to supplementary queries about how many times the joint committee had met and how the two organisations coordinated.

Of Remdesivir and emergency use

Apart from transparency, there have also been allegations that red tape within the organisation has held up important clearances. First, it pertained to testing kits. Now, it concerns the alleged delay in issuing production approvals to Indian drug makers to manufacture the antiviral drug Remdesivir.

However, independent experts say the Remdesevir story was more complex and it was unfair to corner the Central Drugs Standard Control Organisation over it.

On June 13, the health ministry greenlighted the use of Remdesevir for mild cases of Covid-19 thorough an emergency authorisation route (to be only used under monitoring).

Gilead Sciences, a United States-based company, has a patent on the drug. Indian manufacturers who have voluntary licences from Gilead to manufacture a generic version of the drug have been asked by the Central Drugs Standard Control Organisation to furnish some quality and safety data before they start manufacturing.

The Indian companies, though, have said that the regulator ought to waive off some of the usual data requirements as it was preventing them from manufacturing the drug “despite the know-how, resulting in shortage and unavailability”.

Somani said the regulator was following due process and working closely in tandem with the companies, “doing daily hand-holding for manufacturer to make their product, get it tested, prove the stability etc. so that this critical injection of robust quality is made available to public at earliest”.

A lawyer working on access to medicine said that the regulator’s cautious approach was understandable to a certain extent since Remdesevir was an injectable formulation and that called for greater safety measures. “Whether they want to waive off some data requirement to fast track the availability of the drug is a decision that the CDSCO has to take, but it is not a simple decision to make,” said the lawyer who did not want to be identified.

The lawyer, however, did not completely let the regulator off the hook. She said the regulator’s failure to formulate rules till date concerning emergency usage of drugs in crisis situations was likely to dilute the whole whole idea of “emergency use” .

“There is going to be a massive wave of patients coming in with moderate to severe disease,” said the lawyer. “Once the generic is available and hospitals receive a cut from the pharma companies, emergency use is going to become regular use and the hospitals would profiteer.”

In the absence of a regulatory regime governing emergency use, there was nothing to prevent hospitals, the lawyer said. “Our criteria right now for emergency use is pharmacovigilance combined with informed consent from the patient,” she pointed out. “But emergency use is much more than that: it involves a scientific and ethics committee to look into every patient who needs the drug. We don’t have any such committees. What we have is a government decision.”

On June 5, the health ministry published draft rules for the “compassionate use” of unapproved drugs on the Central Drugs Standard Control Organisation website for public comments. While these rules are meant to provide the regulatory framework for a situation like this, the carelessness in the drafting of the new rules – it uses the word “compassionate” while the ministry’s clinical management guidelines refer to “emergency” use – could mean hospitals would easily circumvent the regulations, said the lawyer.

More complaints

There have been more complaints about the Central Drugs Standard Control’s conduct during the pandemic. One pertains to its handling of clinical trials of the antiviral medication Favipiravir, which has been used in the past against influenza, for Covid-19 treatment.

According to the clinical trial registry of India website, two companies are currently conducting trials for the drug: Glenmark and Cipla. According to news reports, a third company, Strides, has also received approval from the Central Drugs Standard Control Organisation to conduct trials.

Critics said the regulatory body should have insisted on all the companies getting together and doing a “bigger” clinical trial instead of handing out clearances to multiple companies. “Then you would have better data,” said Amit Ranjan, who runs a pharmaceutical consultancy firm in Mumbai. “What purpose does separate trials serve in a situation like this except commercial interests the company?”

Jesani tended to agree. When the outcome is the same, it made sense to club trials, he said. “When there are multiple institutions doing these trials with the same clinical design, the CDSCO can ensure that they are done under one umbrella,” he said. “That way the trial takes a shorter time and in an emergency, we need information as early as possible.”

Somani, for his part, said the regulator was doing what it could to protect consumer interest. He said, “Favipiravir data generation in India depends on applicant and at times, they due to their business act separately, however, we have full watch to make this outcome available in interest of patient.”

But for those who closely track the drug regulation regime in India seems, the regulatory body’s lack of transparency during the current pandemic has been no surprise. It has operated in the last three months as it always has, said S Srinivasan, co-convenor of the All India Drug Action Network. Hoping for its conduct to change during the pandemic would be akin to expecting “the CDSO to have a character and personality it never had”, Srinivasan said.

This reporting was supported by a grant from the Thakur Family Foundation. Thakur Family Foundation has not exercised any editorial control over the contents of this article.