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 Reuters reported last month that the European Medicines Agency (EMA)’s
review of the drug’s safety and efficacy was delayed because a June
10 deadline to submit data on the vaccine's clinical trials was
missed, according to one of those people, who is close to the
agency, and another person familiar with the matter. The EMA is the
European Union’s medicines watchdog.
The hitches go beyond that one deadline, the person close to the
agency said. As of early June, the EMA had received hardly any
manufacturing data, and the clinical data the agency had received
was incomplete, the person said.
Separately, an assessment of Sputnik V by a French delegation of
scientists in advance of the EMA review found that the vaccine
developers were unable to document that the so-called master cell
bank, the initial building block of the vaccine, complied with
specific EU regulation on preventing disease contamination,
according to four people with knowledge of the delegation's
findings.
The EMA, which launched its formal review of the Russian vaccine in
March, had previously been expected to decide in May or June whether
to approve use of the drug in the EU.
The person close to the EMA said notable missing clinical
information during the EMA review included case report forms that
record any adverse effects people experienced after receiving the
jab in trials. It is standard practice for developers to submit such
forms, this person added. It was also not clear how the scientists
working on the vaccine tracked the outcomes of people given a
placebo, the person said.
The watchdog rates such data shortcomings on a scale that goes from
“critical” - the most serious - to “major” to “minor.” The person
said nothing had met the critical threshold, “but there are several
‘majors,’” indicating issues that can be remedied but require much
work. The person added they didn’t expect the review to be completed
until after the summer.
Several people who have interacted with Russia’s Gamaleya Institute,
which developed Sputnik V and oversaw the clinical trials, attribute
the repeated failure to provide some information to lack of
experience in dealing with overseas regulators. "They are not used
to working with a regulatory agency like the EMA," the person close
to the agency said, referring to Gamaleya’s scientists.
Gamaleya is supervised by Russia’s health ministry. Neither Gamaleya
nor the ministry responded to questions for this report. The Kremlin
declined to comment.
Sputnik V is marketed overseas by Russia’s sovereign wealth fund,
called the Russian Direct Investment Fund (RDIF).
RDIF said Reuters’ reporting contained “false and inaccurate
statements” based on anonymous sources who are attempting to harm
Sputnik V as part of a disinformation campaign. RDIF suggested the
vaccine could be under attack by the “Western pharmaceutical lobby,”
without offering evidence of such a campaign.
RDIF added that the vaccine is registered in more than 60 countries
and that studies from places including Argentina, Mexico and Hungary
that are already using the vaccine show it is safe and effective. It
said there had been “no reported serious adverse events.”
On the French delegation’s findings, RDIF said “the Sputnik V cell
bank is fully compliant with all EMA requirements.”
RDIF said it is working closely with the EMA, whose inspectors have
visited Sputnik V production facilities. “From the inspections
already completed we’ve received no major critical comments and none
of the issues raised doubted the safety and efficacy of the
vaccine,” said RDIF.
One of the people with knowledge of European efforts to assess the
drug said they had no reason to doubt that Sputnik is a safe and
effective vaccine. A study by international scientists published in
the Lancet in February found Sputnik to be more than 90% effective.
The EMA, which is headquartered in Amsterdam, declined to comment on
details of the review while it is ongoing. The agency said it
applies the same standards to all applicants and to authorise a
COVID-19 vaccine the EMA requires “detailed information on its
safety, efficacy and quality.”
The delay could allow rival vaccine makers to sew up key markets.
The stumble is one of several for the developers of Sputnik V in
dealing with some overseas drugs watchdogs reviewing the vaccine,
who have identified a lack of data, insufficient documentation of
methodology and non-compliance with what they view as standard
protocol.
Brazilian regulators initially rejected imports of Sputnik V after
technical staff highlighted "inherent risks," citing a lack of data
guaranteeing its safety, quality and effectiveness. Slovakia’s drug
agency said it had insufficient data from Moscow before the
government ultimately gave a limited go-ahead for the vaccine.
Hungary gave emergency approval for the jab despite what several
people with knowledge of the process said were concerns raised by
some specialists working on the review at Hungary’s drug regulator
about insufficient documentation.
Brazilian regulator Anvisa last month gave conditional approval for
imports of Sputnik V. The conditions imposed “seek to overcome the
information gaps in the process and ensure minimum conditions of
vaccine safety and quality,” Anvisa told Reuters. It added that
Sputnik V has not been distributed to people in Brazil.
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 Hungary’s regulator, at the
time it approved Sputnik V in January, publicly
acknowledged that there can be conflicting
opinions during an authorization process and
that it had received reassuring answers to its
questions regarding the vaccine. The Slovakian
government this month said it sold most of its
Sputnik V back to Russia, citing low interest.
CELL CULTURE
Sputnik V is named after the Soviet-era
satellite that triggered the space race, in a
nod to the project’s geopolitical importance for
Russian President Vladimir Putin. EMA approval
would lend legitimacy to the vaccine, which
initially faced scepticism by some Western
scientists and politicians, and speed up its
availability in Europe. Moscow's
efforts to obtain EU approval hit obstacles before it submitted its
application.
In November 2020, the French government dispatched a team of
scientists to Moscow to help Paris decide if it should use Sputnik V
and manufacture the drug on French soil, in the event of EMA
approval.
The four people with knowledge of the delegation’s findings said
that the paperwork the scientists reviewed showed that fetal bovine
serum had been used in the culture to nurture the master cell bank
and that the developers hadn’t documented the serum’s origin.
Fetal bovine serum is commonly used around the world in vaccine
development. But since the outbreak of mad cow disease in the 1980s,
European and North American regulators have required that vaccine
developers document it is from a safe source.
One of the four people familiar with the delegation’s work is French
scientist Cecil Czerkinsky, a member of an international advisory
board set up by RDIF and who was separately briefed on the
delegation’s concerns about the master cell bank. The French team
felt “frustration” with the answers they received when they asked
the vaccine developers about the issue, Czerkinsky told Reuters.
The French delegation informally shared their conclusions --
including their questions regarding the master cell -- with the EMA,
one of the people said.
 RDIF told Reuters the
Gamaleya Institute “never used ‘non-traceable bovine serum’ for cell
bank preparation.” It added that the Sputnik V cell bank has been
independently verified not to contain prions - the proteins
associated with conditions like mad cow disease. RDIF didn’t
identify who conducted the independent verification.
The EMA in early March announced the launch of a "rolling review" of
Sputnik V, a faster process that checks data as it lands. But the
drug’s developers did not submit the first data until a month later,
delaying the process at the earliest stages, said an official in the
French government briefed on the matter.
France's ministries for health and research, which sponsored the
delegation to Moscow, did not respond to a request for comment on
the delegation’s findings. BRAZILIAN CAUTION
Brazilian regulator Anvisa’s rejection in April of Sputnik V imports
kicked off a testy public exchange with RDIF, which threatened to
sue the Brazilian agency for defamation.
A crucial issue for Anvisa related to the adenovirus, the virus that
causes the common cold and which is used in Sputnik V to carry into
the body information that triggers an immune response. Anvisa
publicly said there was a risk the adenovirus in Sputnik V could
replicate, potentially causing a negative reaction in recipients.
Anvisa’s manager for medicines and biological products called this
possibility a “serious” defect. The Russians said there was no
evidence of replication and Anvisa had misinterpreted the
documentation.
Sergio Rezende, a former science minister advising Brazilian state
governors who are looking to import the Russian vaccine, said that
in discussions with Gamaleya, the Russians appeared unfamiliar with
the expectations of Brazilian regulators. Rezende told Reuters he
urged the Russians to rework their application, which they initially
resisted but ultimately did.
Anvisa told Reuters its requirements “are aligned with the
regulations of other agencies of reference around the world.”
On the possibility of the adenovirus reproducing, Anvisa said
studies and documents supplied by Gamaleya indicated the “occurrence
of replicating adenoviruses” and lacked adequate assessment of the
relationship between that and the vaccine’s safety. Anvisa added
that the conditions it imposed included demonstrating the absence of
replication in all batches sent to Brazil.
RDIF, in its responses to Reuters, said Gamaleya “has confirmed that
no replication-competent adenoviruses (RCA) were ever found in any
of the Sputnik V vaccine batches that have been produced.”
(Reporting by Michel Rose in Paris, Polina Ivanova in Moscow and
Emilio Parodi in Rome; Additional reporting by Matthias Blamont in
Paris, Lisandra Paraguassu in Brasilia, Stephen Eisenhammer in Sao
Paulo and Marton Dunai in Budapest; Writing by Christian Lowe;
Editing by Cassell Bryan-Low)
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