A lab technicians holds up a box of remdesivir at a pharmaceutical facility in Cairo, June 25, 2020. Photo: Reuters/Amr Abdallah Dalsh/File Photo
- Remdesivir made by Zydus Cadila triggered life-threatening illnesses in at least 69 COVID-19 patients and led to the death of one, according to Mint.
- The drug regulators of Gujarat, Maharashtra, Rajasthan and Uttar Pradesh failed to uncover the source of the problem or bring Zydus Cadila to book.
- The regulator of Bihar collected samples from one suspected batch and sent them to a better-equipped facility in Kolkata, which revealed the presence of endotoxins.
Bengaluru: Contaminated batches of remdesivir made by Gujarat-based pharmaceutical company Zydus Cadila and sold to five states led to the death of at least one COVID-19 patient while triggering life-threatening illnesses in many others – even as four of the five drug regulators did little to nothing to ensure these batches were taken off the market or Cadila was brought to book.
These findings, uncovered by health journalist Priyanka Pulla in a report for Mint, were based on the effects of remdesivir in Zydus Cadila batches numbered V100153, V100156, V100166, V100167, V100170 and L100148, and around the month of May. According to the report, COVID-19 patients who consumed this remdesivir developed signs of endotoxin poisoning: fever, chills and septic shock, which can be lethal.
May 2021 was when India’s second, and devastating, COVID-19 outbreak peaked. From April 15 to May 24, the country recorded at least two lakh new cases every day.
However, while problems with the remdesivir were reported from Bihar, Gujarat, Maharashtra, Rajasthan, Uttar Pradesh, only the Bihar drug regulator took the trouble to uncover the cause of the illness. Pulla also noted that the Gujarat regulator bore the most blame because it had the most to do, considering Zydus Cadila is located in the state and is answerable to state authorities.
The remdesivir in question was in powdered form, and had to be mixed with sterile water and saline before use. According to health workers quoted in the report, that the remdesivir made by Zydus Cadila was responsible became clear after patients whose breathing had stabilised on supplemental oxygen became worse an hour after taking the drug. Their condition also improved once they were switched to remdesivir made by other manufacturers. But the exact reason for the Cadila remdesivir’s effects were unclear.
Maharashtra reportedly had the intention and wherewithal to test samples from the implicated batches, but didn’t check for endotoxins. This was because its regulator followed the Indian Pharmacopoeia. The Pharmacopoeia is the book that lists what tests different drug classes should be subjected to, but it didn’t include powdered remdesivir because it hadn’t been updated. The Drugs and Cosmetics Act 1940 asks regulators to comply with the Pharmacopoeia’s recommendations, but in the event the Pharmacopoeia doesn’t include the drug, to simply comply with the Pharmacopoeia’s general recommendations for all drugs. This section of the book didn’t include tests to look for endotoxins.
In Rajasthan, remdesivir from batch number L100148 caused severe adverse events among COVID-19 patients in two Jaipur hospitals: the Employees’ State Insurance Corporation Model Hospital and the Rajasthan University for Health Sciences. But while authorities from these facilities reportedly informed the Rajasthan Medical Services Corporation, the corporation didn’t inform the regulator. As a result, the regulator didn’t even test the batches in question.
And in Uttar Pradesh, “multiple hospitals” informed the state drug regulator that they were dealing with bad remdesivir that was making COVID-19 patients sicker. The regulator then tested batches V100153, V100156, V100166 and L100148. But it didn’t have the facilities to check for endotoxins or the purity of the sterile water, nor did it outsource the tests to a better-equipped lab. It simply proceeded to declare the batches to be of “standard quality”.
The drug regulator in Bihar – a state whose healthcare system is often used as an example of dysfunction on this front – collected remdesivir units in the state belonging to batch number V100167 and, realising it didn’t have the necessary tests, send them to the Central Drugs Laboratory in Kolkata.
The Central Drugs Laboratory then asked Zydus Cadila for its test specifications, instead of relying on the Pharmacopoeia’s limited syllabus. These specs included a test for endotoxins, which the lab performed and concluded that the problem was the drug contained this substance (endotoxins are “compounds present in the protective envelopes of bacteria”).
While Bihar did the right thing, the report noted that the state is still hamstrung by the fact that it doesn’t have the tests in-house to check for this aspect of drug quality. This means in turn that while Bihar may have zeroed in on the problem with Cadila’s powdered remdesivir, it may also have missed problems with many other drugs that pass through its lab into the state’s hospitals and pharmacies.
The regulator of the remaining state, Gujarat, reportedly professed ignorance. According to Mint, the joint commissioner of Gujarat’s drug-regulating labs said no sample from any of the implicated batches had arrived for additional tests while the commissioner of the state’s food and drug control administration didn’t respond to questions about failure to test.
Finally, Zydus Cadila itself said through a spokesperson that it denied all reports of severe adverse events due to the consumption of remdesivir made in its facilities and didn’t comment on whether it would recall any of the batches.
When the Rajasthan Medical Services Corporation had asked Cadila to explain the effects of remdesivir in batch number L100148 in May, the company had reportedly said it wasn’t aware of similar issues in other batches. The Mint report called this statement “incorrect” because hospitals in Varanasi and Aurangabad had flagged issues with remdesivir from the same batch at roughly the same time.
But even as it denied all reports of contamination, the company also replaced all unused bottles of batch L100148 in Rajasthan at short notice and at no extra cost.