Because the Sputnik V vaccine does not convince the EMA
European efforts to evaluate the Russian Sputnik V vaccine are hampered by data gaps. Reuters in-depth analysis
Developers of the Russian Sputnik V coronavirus vaccine have repeatedly failed to provide data that regulators believe to be standard requirements of the drug approval process, according to five people with knowledge of European efforts to evaluate the drug, providing new insight into the country's struggle. to gain foreign acceptance of its product.
Reuters reported last month that the review of the drug's safety and efficacy by the European Medicines Agency (EMA) was delayed because a June 10 deadline for submitting data on clinical trials of the vaccine was not met. , according to one of these people, who is close to the agency, and another person familiar with the matter. EMA is the medicines control body of the European Union.
The hitches go beyond that deadline, the person close to the agency said. By early June, the EMA had received almost no production data, and the clinical data the agency had received was incomplete, the person said.
Separately, an evaluation of Sputnik V by a French delegation of scientists prior to the EMA review found that the vaccine developers were unable to document that the so-called master cell bank, the initial vaccine block, was compliant. the specific EU regulation on the prevention of disease contamination, according to four people familiar with the results of the delegation.
EMA, which launched its formal review of the Russian vaccine in March, was previously expected to decide in May or June whether to approve the drug's use in the EU.
The person close to the EMA said the clinical information missing during the EMA review included case report forms that record the adverse effects people experienced after receiving the vaccine in trials. It is standard practice for developers to submit such modules, this person added. It was also unclear how scientists working on the vaccine tracked the results of people who received a placebo, the person said.
The regulator evaluates these data gaps on a scale ranging from "critical" – the most severe – to "major" to "minor". The person said that nothing met the critical threshold, “but there are several 'majors',” indicating problems that can be solved but require a lot of work. The person added that he doesn't expect the review to be completed until after the summer.
Several people who interacted with the Gamaleya Institute of Russia, which developed Sputnik V and oversaw clinical trials, attribute the repeated failure to provide some information to a lack of experience in dealing with foreign regulators. "They are not used to working with a regulatory agency like EMA," said the person close to the agency, referring to the Gamaleya scientists.
Gamaleya is supervised by the Russian health ministry. Neither Gamaleya nor the ministry answered questions for this report. The Kremlin refused to comment.
Sputnik V is marketed overseas by the Russian sovereign fund, called the Russian Direct Investment Fund (RDIF).
RDIF said the Reuters report contained "false and inaccurate statements" based on anonymous sources that are trying to harm Sputnik V as part of a disinformation campaign.
RDIF has suggested that the vaccine may 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 like Argentina, Mexico and Hungary that are already using the vaccine show that it is safe and effective. He said no "serious adverse events" were reported.
On the results of the French delegation, RDIF said that "the Sputnik V cell bank is fully compliant with all EMA requirements".
RDIF said it is working closely with EMA, whose inspectors have visited the production facilities of Sputnik V. "We have received no major critical comments from the inspections already completed and none of the issues raised questioned safety. and vaccine efficacy, ”the RDIF said.
One of the people familiar with European efforts to evaluate the drug said he has 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 Amsterdam-based EMA declined to comment on the details of the review while it is underway. The agency said it applies the same standards to all applicants and to authorize a COVID-19 vaccine the EMA requires "detailed information on its safety, efficacy and quality".
The delay could allow rival vaccine manufacturers to conquer key markets. The stumbling block is one of many for Sputnik V developers dealing with some overseas drug watchdogs reviewing the vaccine, who identified a lack of data, insufficient documentation of methodology, and non-compliance with what see it as a standard protocol.
Brazilian regulators initially rejected imports of Sputnik V after technical staff highlighted "inherent risks," citing a lack of data to guarantee its safety, quality and efficacy. Slovakia's pharmaceutical agency said it had insufficient data from Moscow before the government eventually gave a limited go-ahead for the vaccine. Hungary gave emergency approval for the vaccine despite what several people with knowledge of the process said were concerns raised by some specialists working on the review at the Hungarian drug regulator about insufficient documentation.
Brazilian regulator Anvisa last month gave conditional approval for imports of Sputnik V. The conditions imposed "seek to overcome information gaps in the process and ensure minimum conditions of safety and vaccine quality," Anvisa told Reuters . He added that Sputnik V was not distributed to people in Brazil.
The Hungarian regulator, when it approved Sputnik V in January, publicly acknowledged that there may be conflicting views during an authorization process and that it had received reassuring answers to its questions about the vaccine. The Slovak government this month said it sold most of its Sputnik V 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 give legitimacy to the vaccine, which initially faced skepticism from some Western scientists and politicians, and accelerate its availability in Europe.
Moscow's efforts to gain EU approval ran into obstacles before submitting its application.
In November 2020, the French government sent a team of scientists to Moscow to help Paris decide whether to use Sputnik V and produce the drug on French soil, if EMA approved.
The four people familiar with the delegation's findings said the papers the scientists reviewed showed that fetal bovine serum was used in culture to feed the master cell bank, and that the developers did not document the serum's origin. .
Fetal bovine serum is commonly used throughout the world in vaccine development. But since the outbreak of mad cow disease in the 1980s, European and North American regulators have required vaccine developers to document that it comes from a safe source.
One of four people familiar with the delegation's work is French scientist Cecil Czerkinsky, a member of an international advisory committee set up by the RDIF and who was separately briefed on the delegation's concerns about the master cell bank. The French team felt "frustration" with the responses they received when they asked vaccine developers about the matter, Czerkinsky told Reuters.
The French delegation informally shared its findings – including questions regarding the parent cell – with the EMA, one of the people said.
RDIF told Reuters that the Gamaleya Institute "has never used 'untraceable bovine serum' for the preparation of the cell bank." He added that the Sputnik V cell bank has been independently tested for not containing prions – the proteins associated with conditions such as mad cow disease. RDIF did not 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 arrives. But the drug's developers did not submit the first data until a month later, delaying the process in the early stages, a French government official briefed on the matter said.
The French ministries of health and research, which sponsored the delegation in Moscow, did not respond to a request for comment on the delegation's findings.
BRAZILIAN CAUTION
Brazilian regulator Anvisa's refusal of Sputnik V imports in April sparked an irritating public exchange with RDIF, which threatened to sue the Brazilian agency for defamation.
A crucial issue for Anvisa concerned adenovirus, the virus that causes the common cold and which is used in Sputnik V to carry information into the body that triggers an immune response. Anvisa has publicly said there was a risk that the adenovirus in Sputnik V could replicate itself, potentially causing a negative reaction in recipients. Anvisa's manager for drugs and biologics called this possibility a "serious" defect. The Russians said there was no replication evidence and Anvisa had misinterpreted the documentation.
Sergio Rezende, a former science minister who advises Brazilian state governors who are trying to import the Russian vaccine, said that in discussions with Gamaleya, the Russians appeared not to know the expectations of Brazilian regulators. Rezende told Reuters he urged the Russians to rework their question, which he initially resisted, but ultimately did.
Anvisa told Reuters that its requirements "are aligned with the regulations of other reference agencies around the world."
On the possibility of the adenovirus reproducing, Anvisa said the studies and papers provided by Gamaleya indicated the "occurrence of adenoviruses that replicate" and lacked an adequate assessment of the relationship between this and the safety of the vaccine. Anvisa added that the conditions it imposed include the demonstration of the absence of replication in all batches sent to Brazil.
RDIF, in its responses to Reuters, said Gamaleya "confirmed that no replication compatible adenovirus (RCA) was ever found in any of the batches of the Sputnik V vaccine that were produced."
This is a machine translation from Italian language of a post published on Start Magazine at the URL https://www.startmag.it/mondo/vaccino-sputnik-v-ema/ on Sat, 17 Jul 2021 06:03:29 +0000.