the country is a major global medicine sup-
plier. The World Health Organization has
“prequalified” 54 vaccines produced in India
for use elsewhere, and WHO relies on CDSCO
to oversee the manufacturers.
CDSCO didn’t respond to questions from
Science about the criticism. In May 2020, In-
dia’s health ministry appointed a committee
to advise it on how to restructure India’s drug
regulatory system in line with global best
practices, but that committee’s recommen-
dations haven’t been published. It’s unclear
whether they will address vaccine regulation.
CDSCO has a decent reputation: Based on
an extensive assessment, WHO concluded in
2017 that it was a “functional” drug regula-
tor, a distinction only 30% of its counterparts
around the world enjoy. (It ranks a step be-
low 11 agencies WHO credits with a “high
level of performance,” however, including the
U.S. Food and Drug Administration and the
European Medicines Agency.)
But the pandemic has been challenging
for CDSCO, says Gagandeep Kang, a public
health microbiologist at Christian Medical
College, Vellore. For the first time, Indian
manufacturers developed new vaccines
rather than me-too versions of shots ap-
proved elsewhere, and the agency lacked
some types of expertise, Kang says, such
as the ability to reanalyze data from key
studies. Others suspect CDSCO’s decisions
have been skewed by political pressure to
quickly approve made-in-India vaccines,
which have been a point of pride for the
ruling Bharatiya Janata Party. “The gov-
ernment has a keenness of publicity, and
that has certainly created pressure,” says T.Sundararaman, an independent public
health analyst based in Puducherry.
In January 2021, for example, the agency
greenlit Covaxin, an inactivated-virus vaccine
produced by Bharat Biotech, without data
from large-scale efficacy trials—only phase
2 data about the immune response gener-
ated by the vaccine. By the time the company
published data showing 78% efficacy against
symptomatic COVID-19, 6 months later, mil-
lions of Indians had already received the shot.
NTAGI also differed with CDSCO’s as-
sessment when the regulator approved a
COVID-19 vaccine named ZyCoV-D for use
in both adults and adolescents in August- Produced by Zydus Cadila in Gujarat
state, ZyCoV-D is the first DNA vaccine ap-
proved by any country for use in humans.
CDSCO based its decision on results of a trial
in about 28,000 participants over 12 years of
age, which found the vaccine 67% efficacious
at preventing symptomatic COVID-19.
NTAGI, which does not typically make
its advice public, opposed the use in ado-
lescents, Muliyil says; it felt a completely
new vaccine platform should only be used
in adults at first. Moreover, the phase 3 trial
had a single efficacy estimate for all ages,
says another NTAGI member who asked not
to be identified, even though efficacy can
differ by age group. (In Western countries,
COVID-19 vaccines for adolescents and chil-
dren were authorized after separate trials in
those age groups.)
In March, CDSCO’s reputation took an-
other hit when a WHO inspection of the Co-
vaxin manufacturing facility in Hyderabad
found quality control deficiencies, whose
nature WHO has not disclosed. WHO rec-
ommended that member countries stop
using the vaccine, and Bharat voluntarily
halted exports. But the company has down-
played the problems and says it will keep
selling Covaxin in India. CDSCO did not re-
spond to questions from Science about the
problems or why it failed to spot them. “It
concerns me that CDSCO, the custodian of
public health as India’s national drug regu-
lator, haven’t issued any statements yet on
this issue,” says Jayanthi Vuppala, an in-
dependent expert on good manufacturing
practice based in Hyderabad.
Last month’s approval of Corbevax—
which by now has been given to 30 million
adolescents—raised more questions. CDSCO
authorized the vaccine for 12- to 18-year-olds
based on interim data from a 312-participant
study that showed the vaccine triggered a rise
in neutralizing antibodies. But NTAGI wasn’t
convinced the vaccine was entirely respon-
sible for the rise, Muliyil says. Data from the
unvaccinated placebo group could have shed
light on whether CO VID-19 infections were
also contributing, but as a preprint posted on
26 April shows, the trial did not assess anti-
bodies in the placebo group. Biological E did
not respond to a question about the data.
Since then Botswana has also licensed Cor-
bevax. And on 21 April, an expert committee
advising CDSCO recommended the shot’s ap-
proval for 5- to 12-year-olds in India.
Critics applaud the fact that Corbevax is
free from patents, but they worry its approval
signals a double standard. “[Would] this vac-
cine be acceptable for pediatric populations
in a high-income country with the data we
currently have in the public domain?” asks
Boghuma Kabisen Titanji, an infectious dis-
ease specialist at Emory University.
Corbevax co-developer Peter Hotez, who
leads the Texas Children’s Hospital Center
for Vaccine Development, says Indian com-
panies have a strong track record for pro-
ducing WHO-prequalified vaccines. “I’m not
aware they apply lower bars and standards,”
Hotez says. “It would be unfair to think so
and in fact it reflects colonial attitudes.”
But the controversy has led some Indian
pediatricians to not recommend the vac-
cine. And hasty vaccine approvals, espe-
cially for children and adolescents, pose a
risk that goes beyond the individual vac-
cine, Titanji cautions: “It sets a dangerous
precedent which could be very damaging
for vaccine confidence and uptake down
the road.” jPriyanka Pulla is a science journalist
PHOTO: SUKHOMOY SEN/EYEPIX GROUP/FUTURE PUBLISHING/GETTY IMAGES in Bengaluru, India.
SCIENCE science.org 29 APRIL 2022 • VOL 376 ISSUE 6592 443A girl in Kolkata receives a dose of Corbevax, which
India began to use in 12- to 14-year-olds in March.