20 min read.Updated: 28 Sep 2021, 10:23 AM ISTPriyanka Pulla
The only punishment the regulator meted out in most cases related to substandard drugs was to suspend the firm’s license to manufacture the drug for a few days
Poor training, antiquated record-keeping systems and understaffing also leave drug inspectors ill-equipped to enforce recalls and root-cause analyses
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Monu and Monika could easily pass off as teenagers. The husband and wife are of slight build and they both speak softly, belying the fact that they are in their early twenties. Yet, Monu, a construction worker in the Himachal Pradesh town of Baddi, and Monika, a homemaker, were parents over a year ago. They had a daughter named Radhika. She was two years old when she died, after drinking an adulterated children’s cough syrup.
The couple show me an album of Radhika’s pictures, the diligent work of first-time parents. One photo has Radhika flashing a milk-toothed grin while sitting on a swing; another has her swaddled in woollens and a monkey cap, while yet another shows her posing in what looks like a woman’s dupatta. “She was a very active child," Monika recalls. “She had just begun to walk and would go all the way up to the third floor of this building by herself". If it weren’t for the toxic medicine, Monika is convinced her daughter would have been alive today.
The sequence of events that led to Radhika’s death began in July last year, when the toddler came down with a cold. A local healer prescribed several medicines. Among them was a cough syrup—called Cofset—manufactured by a Himachal Pradesh-based pharmaceutical manufacturer called Digital Vision. As soon as the toddler drank the syrup, she fell ill, vomiting and unable to urinate.
When she was hospitalized at the Post Graduate Institute of Medical Education and Research (PGIMER) in Chandigarh, doctors diagnosed her with acute kidney injury. The cause, the doctors said, was Cofset. Tests at the hospital had revealed that the cough syrup was tainted with a deadly chemical called diethylene glycol.
The child spent nearly a month-and-a-half in the hospital’s intensive care unit (ICU), with little impovement. A photograph from this time shows a very different toddler from the playful one in the earlier album: her eyes are closed, head swaddled in cotton, and tubes and sensors wrapped around her body. Towards the end of this period, the doctors told Radhika’s parents that she was unlikely to improve. So, Radhika was discharged. Within hours of leaving the hospital, Monika says, her daughter passed away.
Radhika was one of the 13 children, all under five years of age, who died in 2020 after drinking the adulterated cough syrup. It was an incident that brought to light how weakly the Indian pharmaceutical industry is regulated. Earlier that year, around a dozen children from Ramnagar village in Jammu had succumbed after drinking another diethylene-glycol-laden tonic, called Coldbest, also manufactured by Digital Vision.
The incident is a case study on the soft stance that Indian drug regulators take towards drug-quality problems, and the deadly consequences of this stance. In a year-long investigation, Mint found that several Indian state drug regulators had ignored dozens of red-flags on Digital Vision’s manufacturing practices for a decade. Publicly available data shows that the company’s medicines had failed to meet quality standards at least 19 times since 2009.
Substandard drugs are not only ineffective, they are also harmful to patients. That’s why an Indian law, called the Drugs and Cosmetics Act 1940, treats their sale as a serious offence. Among its various provisions, this law calls for a jail sentence of a minimum of one year and fines for the manufacturer; for the entire batch of the drug to be recalled from the market; and for the manufacturer to conduct a root-cause analysis into how the faulty drug got made.
These provisions were rarely enforced against Digital Vision, Mint’s investigation found. State drug regulators took the firm to court to push for imprisonment and penalties only four out of the 19 times, while recalls and root-causes analyses frequently didn’t occur at all. The only punishment the regulator meted out in most cases was to suspend the firm’s license to manufacture the substandard drug for a few days—the equivalent of a rap on the knuckles.
The diethylene-glycol poisoning was likely the outcome of this lax attitude. In an inspection it conducted after the incident, the Himachal Pradesh Drugs Control Administration identified many problems with Digital Vision’s manufacturing processes: the firm had fabricated records, hadn’t maintained basic paper trails, and hadn’t procured raw materials for its cough syrup from a licensed dealer. Any of these actions could have led to the lethal chemical entering the cough syrups.
The tragedy is that the regulatory responses to Digital Vision’s offences weren’t unique to the company, but were symptoms of a larger, systemic problem. Faced with chronic understaffing and pressure from the pharmaceutical industry, Indian state and central drug regulators today balk at prosecuting manufacturers of substandard drugs. Meanwhile, poor training, antiquated record-keeping systems and understaffing leave drug inspectors ill-equipped to enforce recalls and root-cause analyses.
This has created a lenient regulatory environment in which more deaths like Radhika’s are only waiting to happen.
A soft stance
Digital Vision was established in 2009 by two brothers, Parshottam Lal Goyal and Konic Goyal, and has a turnover of ₹45 crore annually, according to the firm’s website. Since its establishment, seven Indian state regulators, including that of Maharashtra, Gujarat and Kerala, have found drugs from the company to be substandard at least 19 times. These drugs included acid-blockers, blood pressure medicines, antibiotics, antidiabetics and vitamins.
A medicine is considered substandard if it doesn’t do what it says on the box. This could mean one of several things: the medicine has less than 90-95% of the amount of active ingredient claimed on the label; lab tests show that the drug doesn’t dissolve or disintegrate as claimed, thus failing to release its active ingredient into the patient’s body; or it contains impurities apart from the active ingredient and excipient listed on the label.
Indian law also defines two more categories: the so-called spurious and adulterated drugs, which it considers far more serious offences than substandard drugs. A spurious drug is one that masquerades as another genuine drug. In practice, several state regulators treat any drug with no active ingredient as spurious. Meanwhile, an adulterated drug is one that contains a poison or other noxious matter.
Digital Vision’s drugs ran almost the entire gamut. Information obtained by Mint under the Right to Information Act reveals that out of 19 of the firm’s substandard drugs, nine had failed dissolution and disintegration tests. In another eight cases, the active ingredient was less than 90% of the labelled amount, while in two cases, there was no active ingredient at all.
Yet, state drug regulators prosecuted Digital Vision only four times. This soft stance wasn’t limited to Digital Vision alone but was a deliberate one adopted by state regulators towards the whole pharmaceutical industry. The key elements of this stance are spelt out in a set of controversial guidelines written by the Drugs Consultative Committee, an advisory body to state regulators. Issued first in 1993 and then in 2010, these guidelines argue that prosecuting every case of substandard drugs would lead to the harassment of manufacturers.
Instead, the committee calls for the weapon of prosecution to be used “sparingly and judiciously". As a first step, it suggests, state drug regulators must only take administrative action—such as a temporary suspension of the license to manufacture the offending drug. Only if this doesn’t bring the firm in line must the regulator prosecute the firm in a court of law, a requirement for punishments such as imprisonment. And before deciding to prosecute, the committee says, the regulator must establish that the manufacturer’s actions amounted to either “gross negligence" or “criminal intent".
The rationale behind these guidelines was to protect an emerging pharma industry, several sources told Mint. According to M.P. George, who retired as head of Kerala’s Drugs Control department in 2010, one reason behind the framing was that it would be hard for manufacturers to prevent substandard drugs in a country such as India, with its hot and humid climate and weak drug-distribution infrastructure. Both can impact drug quality.
And upgrading the distribution infrastructure or medicine packaging to withstand heat and humidity extremes would raise the costs of drugs unacceptably. This meant that prosecuting every single case would throttle India’s emerging pharmaceutical industry, George said. George was an attendee at the Drugs Consultative Committee meeting where the 2010 guidelines were given the green light.
Whatever the motivation behind the guidelines, their net result is that today, state regulators do not prosecute most substandard drugs. In fact, some states have lowered the bar for prosecution so much that they only take spurious and adulterated drugs to court.
Others do prosecute what they deem the worst of substandard drugs, but how they pick these cases is arbitrary. While the Drugs Consultative Committee talks about establishing criminal intent and gross negligence, most states don’t do so. Instead, they pick cases wherein the amount of active ingredient drops below an arbitrarily low number, treating these as major offences. For instance, the Kerala regulator will prosecute any case in which the active ingredient falls below 70%, the department’s current head, K.J. John, told Mint.
Meanwhile, the Maharashtra Food and Drugs Administration will prosecute a manufacturer only if the active ingredient is less than 30% of the labelled amount. Gujarat has the lowest bar of all, and will only prosecute spurious and adulterated drugs.
Finally, none of these states will prosecute dissolution, disintegration or impurity failures because they deem them minor.
This background explains why regulators responded to Digital Vision’s substandard drugs the way they did. Out of the 13 instances that the Maharashtra regulator’s labs identified, the state prosecuted only four. Three had less than a third of the active ingredient, while one was spurious.
But there is a major flaw with this rationale: the distinction it makes between minor and major offences isn’t scientific. A drug with active ingredient less than the mandated 90-95% can, in fact, be as dangerous as a drug with active ingredient less than 30%. For instance, from the point of view of antimicrobial resistance—a major public health scourge today—an antibiotic with 70% active ingredient is more dangerous than one with none at all.
Nor are dissolution, disintegration, and impurity failures to be sneezed at. A patient taking a tablet of the enzyme levothyroxine to control hypothyroidism will fall ill if the tablet doesn’t dissolve. Impurities such as arsenic and lead, which can easily creep into drugs, are life-threatening. And an antiplatelet drug that doesn’t disintegrate in one’s body won’t protect a person having a heart attack.
The impact of these failures on patients depends on the situation in which the drug is being prescribed, says Sarika Pardhe, a pharmaceutical quality expert who runs a consulting firm called AblyReg Advisory. “If an emergency drug doesn’t disintegrate in time, it will not save a person’s life. That is not minor."
Yet, Indian regulatory algorithms today dismiss these nuances. Instead, they lump together the vast majority of quality lapses as unimportant, and do not push firms to correct them, something that happened with Digital Vision too. This is against the spirit of Drugs and Cosmetics Act, critics argue.
Mahesh Zagade, who headed the Maharashtra Food and Drugs Administration between 2011 and 2014, has harsh words for the Drug Consultative Committee’s guidelines. “They are designed to protect the industry, not to safeguard the patient," he says.
Prosecuting a firm is, however, not the only way to prevent future substandard drugs. In fact, given India’s notoriously slow legal system which prolongs cases for decades, they are not an effective way to control quality problems either. Three of the four cases against Digital Vision in the last decade are still continuing.
What’s far more important, say pharma quality experts, is for the manufacturer to investigate why a substandard drug occurred in the first place. This is also mandated by the Drugs and Cosmetics Act. Yet, this clause, too, is rarely enforced, several state drug regulators told Mint.
The lack of reflection means that many manufacturers are flying blind. The presumption behind a root-cause analysis is that when a firm makes a substandard drug, it has failed to adhere to a quality control system, called Good Manufacturing Practices. These practices include simple checks and balances, such as testing a raw material before putting it into a drug, buying raw material from a licensed manufacturer, and maintaining clean equipment.
A root cause analysis into a dissolution failure, for instance, could link it to the manufacturer failing to test raw material while making the final drug. Unless such mistakes are pinpointed, the manufacturer cannot correct them, and is likely to keep making defective medicine, says Chaitanya Kumar Koduri, a pharmaceutical quality expert at the United States Pharmacopoeia’s Hyderabad office.
It’s clear today that, for a range of reasons, the Himachal Pradesh regulator rarely pushed Digital Vision to probe its quality failures. Until a couple of years ago, says Garima Sharma, assistant drugs controller in the Himachal Pradesh Drugs Control Administration, manufacturers were not asked to do a root-cause analysis except in the worst cases. Even when completed, these analyses weren’t thorough, Mint found.
In July 2015, Digital Vision manufactured an anti-inflammatory drug called Cerico-SP. It was supposed to contain three molecules: diclofenac, paracetamol and serratiopeptidase. Roughly a year later, a drug inspector from Maharashtra’s Buldhana district picked up samples of Cerico-SP from a local pharmacy. When he sent it for testing, the results showed that it had no serratiopeptidase at all. In other words, it was a spurious drug.
In keeping with the state’s guidelines, the drug inspector prosecuted the firm, while intimating the Himachal Pradesh regulator, since Digital Vision is located in the latter’s jurisdiction. But when the state regulator told the company to do a root-cause analysis, its response wasn’t satisfactory, says Sharma, assistant drugs controller, Himachal Pradesh Drugs Control Administration.
This failure to conduct a proper root-cause analysis didn’t cost Digital Vision much. It did lose its license to manufacture Cerico-SP—after all, it was a spurious drug. But the firm continued to sell its other medicines and got new licenses. This is in sharp contrast with how other stringent global regulators view such laxness. For instance, the United States Food and Drugs Administration is known to frequently follow up drugmakers’ failures to investigate quality issues with warning letters.
Perhaps it was due to its superficial investigation into the Cerico-SP case that, in February 2017, Digital Vision had trouble with serratiopeptidase again. This time, a drug inspector from Maharashtra’s Thane district got another of the company’s anti-inflammatory drugs, Serynim-D, tested. The results revealed that the content of serratiopeptidase was a mere 64.9% of what the label said. As is protocol, the Maharashtra drug regulator claims to have intimated the Himachal Pradesh drug regulator by post. But the state regulator never received the letter, Sharma says. The net result was that Digital Vision was neither asked to recall its faulty drug, nor conduct a root-cause analysis.
This sequence of events—of intimation letters getting misplaced, and of the firm neglecting to probe its failures—played out again and again. Of seven substandard cases, for which Mint sought root-cause analyses reports, none were fully investigated.
The deaths in January
It was in this context of repeated instances of substandard drugs getting into the market that the deaths in Jammu occurred.
In January 2020, several children in a hilly hamlet of Jammu, called Ramnagar, fell mysteriously ill. The children, most under five years of age, had similar symptoms: vomiting, being unable to urinate, and mental confusion. Some of them were shifted to Jammu’s Shri Maharaja Gulab Singh Hospital. But as they failed to improve, they were referred to the much larger PGIMER in Chandigarh.
At Chandigarh, a team led by pediatrician Bhavneet Bharti decided to investigate the cluster of illnesses. They travelled to Ramnagar, and collected samples of food, water, medicine and soil from the children’s homes. These were brought back and tested for viruses, bacteria and toxins.
The tests threw up a shocker. One of the medicines, which a local pharmacy owner had prescribed to all the children, contained diethylene glycol. The name of the adulterated brand was Coldbest PC, and it was manufactured by Digital Vision.
Dr. Bharti’s team immediately informed drug regulatory authorities, triggering an inspection of Digital Vision’s manufacturing facilities by the Himachal Pradesh regulator. This inspection, which occurred on 17 February 2020, uncovered glaring violations of Good Manufacturing Practices. Among them, the firm had purchased one of the raw materials for Coldbest PC—a solvent called propylene glycol—from a dealer that had no pharmaceutical license. Also, even though the firm claimed to have sent the propylene glycol for quality testing to an external lab, it had no records of having dispatched the test samples.
That wasn’t all. Batch manufacturing records were missing, testing records were a mess, and samples were confusingly numbered. These are serious violations and raise questions about integrity of the firm’s data, says Lalit Tripathi, a quality expert at a Mumbai pharmaceutical firm.
These findings could explain how the cough syrup came to be adulterated. Diethylene glycol, a sweet and syrupy liquid, looks a lot like the pharmaceutical solvents such as propylene glycol and glycerine. Because it is difficult to tell the solvent and the poison apart, and because the poison is cheaper, unethical dealers often mix both.
Historically, such adulteration has had disastrous consequences. In one of the worst such tragedies, in 1986, fourteen patients died after treatment with diethylene-glycol tainted glycerine in Mumbai’s Jamshetjee Jejeebhoy Hospital. The ensuing investigations brought to light several Good Manufacturing Practices violations: the supplier to the hospital had sold the hospital industrial glycerine instead of medical-grade one, and had failed to detect its blunder because it hadn’t tested the glycerine before packaging it.
The high risk of adulteration for propylene glycol and glycerine is why Indian law—specifically a book of quality standards called the Indian Pharmacopoeia—requires these chemicals to be tested for diethylene glycol before use by drugmakers. It is in this context that Digital Vision’s violations become telling.
The gravity of these lapses also raises questions about why the state regulator didn’t pre-empt them. After all, the law requires that the regulator inspect every manufacturer at least once a year, so that such negligence can be caught before it hurts patients. “What was the regulator doing all this time?" asks Zagade, the former head of the Maharashtra Food and Drugs Administration.
Asked this question during an interview in November 2020, Sunny Kaushal, assistant drugs controller at the Himachal Pradesh Drugs Control Administration, who was overseeing the Digital Vision case that year, dismissed the violations as minor. Follow-up questions from Mint on how frequently the firm was inspected in the last decade went unanswered.
Parshottam Goyal, the founder of Digital Vision, also denied that the firm’s Good Manufacturing Practices failures were serious. He claimed that the firm had satisfactorily responded to all the concerns pointed out by the state regulator. In response to a specific question about why the firm had purchased propylene glycol from an unlicensed dealer, Goyal claimed the dealer had misled him about his license.
Not a unique story
The willingness of drug regulators to brush aside Digital Vision’s repeated transgressions over the last decade is not a unique phenomenon. Lax enforcement of Good Manufacturing Practices and the resulting substandard drugs are a widespread problem in the country, experts told Mint. “Regulation is in very bad shape in India today, and nobody is taking cognizance of that," says Kundan Lal Sharma, who was joint secretary to the Union ministry of health and family welfare between 2014 and 2017.
In his recently published book titled Healing the Pharmacy of the World, Sharma pinpoints multiple problems with the Indian regulatory system, themes that also played out in the Digital Vision case. State regulators don’t talk to each other, apply the law non-uniformly, and most worryingly, overlook quality in their eagerness to encourage the pharmaceutical industry.
“There is a competition between states to outbid each other," Sharma told Mint. “And this means they are not bothered about the quality of the products being sold in the country. They issue manufacturing licenses to all and sundry without looking into whether Good Manufacturing Practices and other requirements are being followed."
In fact, the problem with Digital Vision likely began much before it manufactured its first substandard drug, says Zagade. The primary goal of the Drugs and Cosmetics Act, he argues, is not to respond to substandard drugs retrospectively, but to prevent them altogether. “Drugs and food are two commodities where taking action after the illegality has occurred is meaningless. Because the damage to the patient cannot be undone."
But the prevention of substandard drugs is tougher than reacting to them later. It requires drug inspectors to inspect manufacturing facilities thoroughly before handing out licenses, and to keep a sharp eye on them post-licensure.
Such inspections are infrequent across Indian states, and not just in Himachal Pradesh, says Zagade. “The ecosystem doesn’t exist," he says. And pressure from the industry is not the only reason for this leniency. Even if drug regulators wanted to improve oversight, they lack the manpower and the training. Himachal Pradesh, for instance, has roughly 550 manufacturing units and 7,300 sales outlets. This would need a minimum of 11 drug inspectors to oversee manufacturing units and 36 to oversee sales facilities, a total of 47. Instead, the entire state has only 26 inspectors today.
The diethylene-glycol tragedy was probably the most serious offence in Digital Vision’s twelve-year history. After all, it had manufactured an adulterated drug, and the drug had caused at least thirteen deaths. In fact, given India’s poor adverse effect reporting system, it is impossible to know if more children died after consuming the same medicine, says Bhavneet Bharti, who has now moved from the PGIMER to the B.R. Ambedkar State Institute of Medical Sciences in Mohali, Punjab. What’s more, the Chandigarh hospital’s finding of diethylene glycol was later confirmed by tests on other Coldbest bottles from the same batch.
Yet, the Himachal Pradesh regulator’s response continued to be lackadaisical. For one thing, they did not ensure that Digital Vision recalled all the medicines potentially tainted with the diethylene glycol.
Given that the contaminated component of the cough syrup was most likely to be propylene glycol, the recall should have included all of Digital Vision’s products that included this solvent, including Cofset. Navneet Marwaha, the Himachal Pradesh state drug controller, says that his office did order Digital Vision to do precisely that. But despite the claim, Cofset remained in the possession of pharmacies, as well as a local healer in Baddi, who then sold it to Radhika’s parents in July 2020.
Asked how Cofset remained in the market despite his orders, Marwaha says it’s hard to tell. He explains that it was the responsibility of Digital Vision and other state regulators to complete the recall across the country. “We have to rely on them when they say they have done the recall. If they tell us they did it, and they didn’t, what can we do?" he asks.
Marwaha’s team had a way to cross-check, however. In their updates to the Himachal Pradesh regulator, Digital Vision and other state regulators only spoke about recalling Coldbest. This ought to have been a red flag for the Himachal Pradesh regulator, who knew the firm was making dozens of other medicines containing propylene glycol. If they realized this, they didn’t act on it.
Meanwhile, there’s little urgency to complete the investigation into how the tragedy occurred. When the Himachal Pradesh regulator sent a sample of Cofset for testing to the Regional Drugs Testing Laboratory in Chandigarh, the results didn’t come back for months. Several questions remain unanswered. A Himachal Pradesh drug inspector told Mint that he wasn’t aware of the results of an inquiry into whether the Delhi drug lab, which claims to have tested Digital Vision’s propylene glycol, had been fabricated.
All this means that more than a year and nine months after the children died in Ramnagar, the Himachal Pradesh administration has still not prosecuted the firm. Moreover, Digital Vision continues to manufacture its full complement of drugs, except medicines containing propylene glycol. In Baddi, Monu and Monika are continuing with their lives. They are still grieving the loss of their first child, but they are also in debt. Monika says she footed bills of over ₹1.5 lakh for her daughter’s lengthy treatment. “I had to borrow money from everywhere. I had nothing left at the end of it," she told Mint.
The Drugs and Cosmetics Act has provisions to compensate the families of victims of adulteration like Monika. It calls for the penalty extracted from a convicted manufacturer to be given to such families. But yet again, in keeping with the overall theme of Indian drug regulation, the law is unlikely to work like it is supposed to. With the state regulator yet to prosecute Digital Vision, and the case likely to stretch for years, Monu and Monika probably won’t get paid for years. The hope for them is dim.
Priyanka Pulla is a Bangalore-based reporter covering health. Her reporting on covid-19 is supported by a grant from the Thakur Family Foundation. The Foundation exerts no editorial influence on her work.
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