The Drug Controller of India has demanded that the Serum Institute of India (SII), Pune, which is conducting Phase-3 trials on people in India involving U.K.-based AstraZeneca’s COVID-19 vaccine candidate, explain why tests have not been paused in India too until safety has been established.
AstraZeneca on late Tuesday put global trials on hold after reports emerged of “ severe adverse reaction ” in a volunteer being injected with the vaccine, probably in the United Kingdom. The nature of the event was not known.
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This pause would prevail, pending a review by a data safety monitoring board, AstraZeneca said in a statement in response to medical news website, Stat News.
Pune-based SII, which is testing a COVID-19 vaccine, said on Wednesday that so far there had been “no issues” with its trials.
“It has been widely reported in the national and international media that sponsor of the aforesaid vaccine, M/s AstraZeneca has paused the ongoing trial as a volunteer developed an unexplained illness....Serum has not informed the Central Licensing Authority regarding pausing the clinical trial and also not submitted causality analysis of the reported severe adverse event,” said a letter signed by Dr.V.G. Somani, Drug Controller General (India), “I [Somani] give you an opportunity to showcause why permission granted to you should not be suspended till patient safety established.”
The Hindu has viewed this letter.
Last month, SII began Phase-2/Phase-3 trials to compare the safety and immunogenicity of its vaccine candidate COVISHIELD (SII-ChAdOx1), with the Oxford vaccine (Oxford/AZ-ChAdOx1).
Both vaccines are similar in structure and the early-human-trial data of Oxford/AZ-ChAdOx1 from studies in the United Kingdom was used to approve Phase-2 and Phase-3 trials in India, Renu Swarup, Secretary, Department of Biotechnology told The Hindu .
According to information on India’s clinical trial registry, where all human trials of vaccine and drugs must be registered, 1,600 adults would be enrolled in the study. Of these, 400 participants will be part of an immunogenicity cohort and will be randomly assigned either COVISHIELD or Oxford/AZ-ChAdOx1 nCoV-19, respectively. The remaining 1,200 participants from the safety cohort will be randomly assigned in a 3:1 ratio to receive either COVISHIELD or a placebo, respectively. Immunogenicity is to test if a vaccine can coax the immune system to launch a protective response that can shield against future infection.
Regarding the show-cause notice issued by the DCGI, SII, told The Hindu , “We are going by the DCGI’s direction and, so far, were not told to pause the trials. If the DCGI has any safety concerns, we will follow their instructions and abide by the standard protocols.”
Earlier in the day, the SII tweeted that Indian trials were continuing and the company “faced no issues at all”.
SII last month announced a partnership with Gavi, the Vaccine Alliance, and the Bill & Melinda Gates Foundation, to accelerate the manufacture and delivery of up to 100 million doses of the vaccine to India and other Low and Medium Income countries.
“Adverse events in the process of vaccine development are not an unexpected outcome. There doesn’t seem to be complete information on what exactly is the adverse event. Probably, the regulator might take a call, if need be, on whether this requires to be paused in India. So far, the DBT does not have any additional information,” Dr. Swarup had added.
AstraZeneca is testing the candidate vaccine in the United Kingdom, Brazil and South Africa. It announced plans on August 31 to begin recruiting 30,000 volunteers across the United States.
The vaccine candidate has been developed on a chimpanzee adenovirus vector platform, which is still experimental in that it has not been used in a commercial human vaccine for any disease.
Other potential vaccines being tested in India are ones by Bharath Biotech, which is based on an inactivated virus from the Indian Council of Medical Research’s National Institute of Virology, and one by Zydus Cadilla, which is testing a DNA-based vaccine. Both are in smaller human trials testing for safety and immunogenicity.
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In July, AstraZeneca had reported results of early Phase-1/2 trials in the peer-reviewed journal The Lancet of acceptable safety and immunogenicity basis, with which it was proceeding to larger Phase-3 trials. It reported that 60% of volunteers reported some kind of reaction such as a fever, headache and muscle pain, which were deemed to be minor reactions that are routine in vaccine inoculations.