New Delhi: Drugs testing positive for a toxin called diethylene glycol (DEG) and their consumption leading to the deaths of children is not uncommon news to read these days.
But now, a curious case has surfaced of a drug that tested positive for DEG in a big government hospital lab but negative in another lab (both labs belong to the Union government).
Not only are the drug and its manufacturer the same, but the products’ batch numbers are also just next to each other.
The drug in question is Cofset-AT, a cough-and-cold syrup. But what was the trigger for testing the drug?
It was the death of Radhika, a two-year-old from Himachal Pradesh’s Baddi district, on September 12, 2020. She died due to kidney failure at the Post Graduate Institution of Medical Education and Research (Chandigarh), also known as PGI-Chandigarh.
Radhika became sick with cold and flu in July 2020. She was taken by her parents to a local doctor, who prescribed her a bottle of Cofset-AT syrup along with other medicines.
Her condition deteriorated. She stopped urinating and started vomiting three to four times a day. Subsequently, she was admitted to a private hospital in Baddi. By now, she was on eight medicines, including Cofset-AT.
But her condition continued to worsen. She was referred to PGI-Chandigarh.
Radhika was admitted on July 22, 2020 to the PGI’s paediatric intensive care unit. She passed away two months later, as her kidneys stopped functioning.
This sequence of events leading to her death is summarised from an order passed by the National Human Rights Commission (NHRC) on July 7 this year.
The PGI doctors did a pharmacological examination in their biochemistry lab of all the eight drugs Radhika was on at the time. Cofset-AT was revealed to be contaminated with DEG. All seven other drugs passed the tests.
A part of the PGIMER campus. Photo: Facebook.
DEG is an industrial solvent used in brake fluids.
According to WHO, it can be fatal even taken in small amounts, and should never be found in medicines.
Dr Bhavneet Bharti, who was a professor of paediatrics at the PGI at that time, had shared the lab results with drug control authorities in Himachal Pradesh on August 4, 2020, and asked for urgent and necessary action to prevent further deaths.
The manufacturer of Cofset-AT was Digital Vision, a Himachal Pradesh-based company. It was in the news around the time Radhika’s death occurred, in September 2020, because another syrup for children that it manufactured had been linked with the deaths of 12 children in Jammu and Kashmir’s Udhampur district. These deaths had taken place between December 2019 and January 2020.
The product they had consumed was another cough syrup, ColdBest-PC. Out of 12 children who died, six were treated at PGI-Chandigarh after they were referred to the apex hospital by the Jammu government.
The presence of DEG in Coldbest-PC was also revealed by the PGI lab, just like in the case of Radhika. Its presence was later reconfirmed through an investigation done by the Jammu drug control department.
When Dr Bharti mailed the test results of Cofset-AT, which Radhika had consumed, to the Himachal authorities, she also shared an important nugget of information. She said, “ColdBest-PC was manufactured and distributed by Digital Vision and Orison Pharmaceuticals respectively – the same entities who manufactured and supplied Cofset-AT which Radhika consumed. And shockingly, the manufacture and expiry date of [the] contaminated ColdBest-PC and Cofset-AT were also identical.”
In fact, the batch number of Cofset-AT that Radhika took was DL5200, and that of ColdBest-PC that the Jammu children consumed was DL5201.
The Jammu case was also heard by the NHRC. Upon taking cognisance of the complaint and the status report filed by the Jammu authorities, the NHRC ordered a compensation of Rs 3 lakh to the kin of the dead children.
Radhika passed away within a span of 10 months of these children dying.
However, in her case, the NHRC dismissed the petition seeking compensation for her parents on the basis of a status report provided by the special secretary of the Himachal Pradesh’s health department, as the latter had denied any impurity in the drug.
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The status report discussed many points. In brief, some of them are as follows:
• The Himachal drug control officials pointed out that during their visit to the premises of the doctor who was claimed to have handed the bottle of Cofset, they did not find the drug there. They went there two days after the email from PGI-Chandigarh landed, i.e., August 6, 2020.
• Radhika’s Cofset-AT had the batch number DL5200. The Himachal Pradesh authorities said they didn’t find this drug bearing this particular batch number in the entire market at Baddi when they went on to investigate on August 6, 2020.
• Therefore, the drug control authorities collected samples of the same drug bearing two other batch numbers – DL5326A and DL4544 – and sent them to the Regional Drug Testing Laboratory (RDTL), Chandigarh. These samples were declared of ‘standard quality’ and negative for DEG contamination.
• The drug control authorities also collected what are known as five bottles of ‘control samples’ or ‘reserve samples’ from the Baddi plant on August 5 and August 6, 2020. These are samples which are preserved by the manufacturer while releasing every batch in the market. They are preserved precisely for any future investigation, if needed.
The control samples were also sent to the RDTL and they were declared, again, of standard quality.
• On further investigation, the drug control authorities found that Cofset-AT’s lot bearing DL5200 as its batch number was supplied by the manufacturer to one Shiva Medical Hall at Ambala Cantonment. They picked up samples from there and sent it to the RDTL. Again, they were of standard quality, as no DEG contamination was found.
Keeping these points in mind, the NHRC dismissed the petition of Radhika’s father, who was seeking compensation, as the drug was declared to be kosher by the Himachal Pradesh government.
The Wire discussed the 37-page-status report of the Himachal Pradesh drug authorities with a Hyderabad-based ‘good manufacturing practice’ expert and independent auditor for pharmaceutical firms. The auditor has 18 years of experience in the pharma industry. Their name has been withheld as per their request, as they apprehended reprisal by Digital Vision.
The auditor said that the first points regarding the drug bearing the batch number in question not being found in the Baddi market, or at the premises of the doctor, are “irrelevant and useless details … for the drug might have been consumed or simply withdrawn from the market almost overnight to avoid an adverse investigation”.
However, the fact that the control samples as well as the samples of the batch in question which were collected from Ambala also tested negative for DEG, was intriguing in the backdrop of the PGI biochemistry lab report, as the government’s and the PGI’s investigations had given contradictory results.
Also Read: Why India’s Pharma Industry Needs to Act Now to Win Back the Trust It Lost
Meanwhile, The Wire reached out to the PGI’s Dr Bharti, who had shared the biochemistry lab report with the Himachal Pradesh government.
“Notwithstanding what the Himachal Pradesh government’s report says, we stand by our report,” she said on September 5, 2023.
So the situation stood like this. The PGI’s biochemistry lab confirmed the presence of DEG in Cofset-AT made by Digital Vision bearing the batch number DL5200. The Himachal Pradesh drug control authorities, on getting the control samples and the samples of the same batch marketed in Ambala, found them not to contain DEG, and of standard quality.
The said and unsaid of the government’s report
While this seems a strange sequence of events to deal with, the status report submitted by the Himachal Pradesh drug authorities itself has such details, especially about propylene glycol (PG), which can potentially unravel this intriguing set of circumstances.
Before looking into those details, it is important to note here what PG is. It is a raw material added to syrups to make them soluble. However, either due to oversight or to cut costs, pharmaceutical companies may end up putting DEG-contaminated PG in syrups. In most cases of DEG mass contamination reported worldwide, PG’s role has been very important.
Now, Digital Vision had procured PG from two different sellers for making the DL5200 batch of Cofset-AT.
The other important details in the report are as follows:
First, every pharma firm has to test PG for any potential impurity before putting it in a drug. Digital Vision did not have an in-house testing facility for PG. Therefore, it sent its PG to a lab called Shree Sai Test House in New Delhi.
Digital Vision was able to show Sai Test House’s report (or what is known as ‘certificate of analysis’) to the drug inspectors. It had said the PG was of standard quality.
However, Digital Vision “failed to produce the evidence of sent samples like postal details [of order being sent] etc. but stated that samples are collected by a representative of a testing firm,” the Himachal government’s report noted.
“This is a big loophole,” the auditor said. “The pharma company needs to have a written contract in place if a third-party lab is involved in PG testing. The work order raised, the specifications of testing, the amount of PG to be tested, and many other such details are to be mentioned.”
“Without these details, how do I be sure that the particular pharma company had … sent the samples and not someone else? If there are no records to trace this back, it is as good as not having a PG test being conducted in the first place,” the auditor explained.
Second, the firm had two different suppliers of PG to make the same batch of Cofset-AT. They were located in Himachal Pradesh’s Sirmaur district and Haryana’s Ambala district. The government’s status report said the individual quantities of the two sets of PG used for making the drug are not mentioned in the record-keeping of the firm.
In other words, there was no way the drug inspectors could have known how much of the total PG used came from one supplier and how much from the other.
The auditor called this “shocking”. They explained that every batch of a drug produced has a what is called a ‘bill of materials’ – which says what ingredient was used, how much of it was used, its material ID and many such details.
“If there are five different raw materials that have gone into any drug, then there has to be complete traceability of each one of them. This is like the ABCs of drug manufacturing,” the auditor added.
Third, and most important, the status report mentions that out of the two sets of PG used in making the batch of CofSet-AT that Radhika consumed, one was identical to a set that went into making the drug that the Jammu children consumed and died.
In other words, one of the two sets of raw material used in making Cofset-AT was the same as one used for Coldbest-PC. (The report is mum which is this one supplier of the two).
However, a rider here is that despite this fact, the control samples which were picked up from the company’s plant tested negative for any toxin. It’s not known which set of PG out of the two – the Sirmaur and Ambala sets – was used in the control samples.
The auditor explained it thus: “Control samples may contain both sets of PG or either – once it goes into the final product, it is not possible to differentiate unless there is a proper documentation done before.”
The auditor drew the analogy of curry to simplify. “While making a curry, you may use the same ingredient from two different sources. But once you have put them in, and the curry is ready, there is no way that you can know which of the two sources of the same ingredient is present in a particular serving.”
The only way to know, in the case of a drug, is through documentation done before and during the manufacture of the drug – and not after the final product is made.
Even the status report notes that the overall record-keeping of Digital Vision was poor and hence a show-cause notice was issued. “The documents and records are not satisfactorily maintained for the tracing of the manufacturing and testing of the impugned product,” the report reads.
Fourth, the status report goes on to say that there is another key detail missing.
As many as 40 different batches of Cofset-AT were made by Digital Vision using PG from two different suppliers. The drugmaker could furnish the sale details to drug inspectors of 21 batches which were produced using PG from the Ambala supplier.
The remaining 19 were made using PG procured from the supplier in Sirmaur. The sale details of these 19 batches couldn’t be produced.
In other words, the drug inspectors could not find the sale records of batches of Cofset-AT which were made using PG that came from Sirmaur.
Add this missing detail with another one pointed out previously, and then one is left wondering: Did the sale details of those 19 batches of Cofset-AT (drug linked to Radhika’s death), which went missing, contain the same PG as ColdBest PC (drug linked with Jammu’s children’s deaths).
The Himachal Pradesh government’s status report is silent on this.
Despite these important questions being left unanswered, the status report of the Himachal Pradesh drug authorities cleared the name of Digital Vision in the case of Radhika. Whether the NHRC looked into these details is not clear from its final order.
N. Sai Vinod, the lawyer for Radhika’s case at the NHRC, said he could not put forward his rebuttal against the status report submitted by the Himachal government authorities.
“I got an SMS from the NHRC saying the case has been disposed of. When I checked the NHRC portal, I learnt that the state government had submitted the report after which the petition was dismissed,” he told The Wire. He added he got a copy of the government report only after giving a written request to the NHRC, after the dismissal of his petition.
Radhika and the Jammu children: Similar history
While the jury is out on whether the drug Radhika consumed was poisonous, there exist stark similarities between the sequence of events that led to her death and that of the children in Jammu.
The documentation from PGI-Chandigarh states Radhika had stopped urinating at one point before her death. She had to undergo dialysis because of renal failure and be put on ventilation too. She had suffered from encephalopathy (injury in the brain) due to the DEG that entered her body. She had no past history of any significant illnesses.
The 12 children from Jammu who died due to consumption of DEG-contaminated Coldbest-PC also showed symptoms like decreased or no urine output, had to undergo dialysis and had brain injuries. Out of these 12, six were treated at the PGI.
Last year, 70 children died in The Gambia. The WHO and the Gambian government blamed the deaths on four cough and cold syrups made by another Indian manufacturer, Maiden Pharmaceuticals. The WHO lab report had established the presence of DEG in the said products and the investigation by the Gambian authorities established acute kidney injuries in those children.
However, when the Indian government tested the control samples of the four products, they were found to be alright. The Indian government never made its report public.
Meanwhile, PGI’s Dr Bharti, while speaking to The Wire, made one more revelation. She said, another child who had consumed the same batch of Cofset-AT as Radhika, had died in Chandigarh in 2020 – the same year that Radhika died.
That child didn’t die at the PGI, but at the Government Medical College and Hospital (GMCH) located in Chandigarh’s Sector 32. So, Dr Bharti could not give a history of their symptoms.
Asked if the PGI lab had tested the other child’s drug too, she replied in the negative.
“Since the child did not land with us, we didn’t. Moreover, what I can say definitely is that the batch number of syrups that Radhika and the other child consumed was the same [and there wasn’t need for a separate lab investigation, therefore].”
It could not be immediately known whether this second death was investigated or not.
Her information could be corroborated through a Tribune report published on March 1, 2020. It read, “The reported case of an infant patient in Chandigarh’s Sector 32 GMCH from Patiala – with similar symptoms [displayed by the Jammu children] and probably ill under the same circumstances – points to the challenge at hand.”
The newspaper hadn’t mentioned the infant’s death, which Dr Bharti confirmed.
Meanwhile, Monu, Radhika’s father, doesn’t have much hope for what he calls ‘justice’, he said while speaking to The Wire. The 26-year-old, who goes by only one name, is a migrant labourer and works in Baddi. He has two more children.
The Wire had reached out to Himachal Pradesh’s drug controller Navneet Marwaha multiple times through phone calls and text messages for comments. He didn’t respond. The state’s health secretary M. Sudha Devi also didn’t respond. The Wire also wrote to Digital Vision, which did not reply.
If any of them respond, their response(s) will be added to this article.