Efforts to evaluate the Russian Sputnik V vaccine exclusively in Europe are blocked by data gap Reuters

Authors: Michel Rose, Polina Ivanova and Emilio Parodi

Paris (Reuters)-According to five people with knowledge of the work in Europe to evaluate the drug, the developers of the Russian satellite V-coronavirus vaccine have repeatedly failed to provide data that regulators consider to be required by the drug approval process standards. New insights The country strives to win foreign acceptance of its products.

Reuters reported last month that the European Medicines Agency (EMA)’s review of the drug’s safety and effectiveness was postponed because it missed the June 10 deadline for submitting vaccine clinical trial data. One person familiar with the matter Say. The agency and another person familiar with the matter. EMA is the European Union’s drug regulatory agency.

People close to the agency said the problem exceeded that deadline. The person familiar with the matter said that as of early June, EMA had received almost no manufacturing data, and the clinical data received by the agency was incomplete.

In addition, the evaluation of Sputnik V by the French delegation of scientists before the EMA review found that the vaccine developer was unable to prove that the so-called master cell bank (the initial building block of the vaccine) complied with specific EU regulations. According to four people who understood the delegation’s findings Said about the prevention of disease pollution.

EMA initiated a formal review of the Russian vaccine in March, and was expected to decide whether to approve the drug in the European Union in May or June.

People close to EMA said that the clinical information that was apparently missing during the EMA review included case report forms, which documented any adverse reactions that people experienced after receiving injections in the trial. The person added that it is standard practice for developers to submit such forms. The person familiar with the matter said that it is unclear how the vaccine scientists track the results of people taking placebos.

Regulators rate such data deficiencies on a scale from “severe” (most serious) to “major” to “minor”. The person said that nothing reached the critical threshold, “but there are a few’main'”, indicating that the problem can be remedied, but a lot of work is required. The person added that they expected to complete the review after the summer.

Several people who interacted with the Gamaleya Institute in Russia, which developed Sputnik V and oversaw clinical trials, blamed the lack of experience in dealing with overseas regulators for the repeated failure to provide some information. “They are not used to cooperating with regulatory agencies like EMA,” said a person close to the agency, referring to Gamaleya scientists.

Gamaleya is supervised by the Russian Ministry of Health. Neither Gamaleya nor the Ministry responded to questions in this report. The Kremlin declined to comment.

Sputnik V is marketed overseas by the Russian sovereign wealth fund, known as the Russian Direct Investment Fund (RDIF).

RDIF stated that the Reuters report contained “false and inaccurate statements” based on anonymous sources that tried to harm Sputnik V as part of a false information campaign. RDIF stated that the vaccine may be attacked by “Western pharmaceutical lobby groups,” but did not provide evidence of such activities.

RDIF added that the vaccine has been registered in more than 60 countries/regions, and studies from Argentina, Mexico and Hungary where the vaccine is already being used have shown that the vaccine is safe and effective. It said that “no serious adverse events have been reported.”

Regarding the survey results of the French delegation, RDIF stated that “Sputnik V cell bank fully complies with all EMA requirements.”

RDIF stated that it is working closely with EMA, and EMA inspectors have visited Sputnik V’s production facility. RDIF said: “From the inspections that have been completed, we have not received any major criticisms, and the questions raised did not cast doubt on the safety and effectiveness of the vaccine.”

A person familiar with Europe’s efforts to evaluate the drug said that they have no reason to suspect that artificial satellites are a safe and effective vaccine. A study published by international scientists in The Lancet in February found that the effectiveness of artificial satellites exceeds 90%.

Amsterdam-based EMA declined to comment on the details of the ongoing review. The agency stated that it applies the same standards to all applicants and that to approve the COVID-19 vaccine, EMA needs “detailed information about its safety, effectiveness, and quality.”

The delay may allow rival vaccine manufacturers to open up key markets. The developers of Sputnik V encountered some mistakes when dealing with some overseas drug regulatory agencies reviewing vaccines. They found lack of data, insufficient methodological documentation, and non-compliance with what they believed to be standard protocols.

After the technicians emphasized the “inherent risk”, the Brazilian regulatory agency initially refused to import Sputnik V on the grounds that it lacked data to ensure its safety, quality and effectiveness. Slovakia’s drug agency said it had insufficient data from Moscow until the government finally granted limited approval for the vaccine. Although some people familiar with the process stated that some experts from the Hungarian Drug Regulatory Agency raised concerns about the inadequate review of the documentation, Hungary urgently approved the jab.

Brazilian regulator Anvisa granted conditional approval to the import of Sputnik V last month. Anvisa told Reuters that these conditions “are designed to overcome the information gap in the process and ensure the minimum conditions for vaccine safety and quality.” It added that Sputnik V has not been distributed to the Brazilian people.

When the Hungarian regulatory agency approved Sputnik V in January, it publicly acknowledged that there may be conflicting opinions in the authorization process and has received reassuring answers to the vaccine question. The Slovak government said this month that it sold most of the satellite V back to Russia on the grounds of low interest rates.

Cell culture

Sputnik V is named after the Soviet-era satellite that triggered the space race to recognize the geopolitical importance of the project to Russian President Vladimir Putin. EMA’s approval will provide legality for the vaccine, which was initially suspected by some Western scientists and politicians, and will accelerate its availability in Europe.

Moscow’s efforts to obtain EU approval before submitting its application have encountered obstacles.

In November 2020, the French government sent a team of scientists to Moscow to help Paris decide whether Sputnik V should be used and manufacture the drug on French soil with EMA’s approval.

Four people familiar with the findings of the delegation said that the documents reviewed by the scientists indicated that fetal bovine serum had been used to cultivate the master cell bank, and the developers did not record the source of the serum.

After the story was published, RDIF said in a statement that the assertion was “false,” but did not elaborate.

Fetal bovine serum is widely used in vaccine development worldwide. But since the outbreak of mad cow disease in the 1980s, European and North American regulators have required vaccine developers to prove that it came from a safe source.

One of the four people familiar with the delegation’s work is the French scientist Cecil Czerkinsky, who is a member of the international advisory committee established by RDIF and listened to the delegation’s concerns about the main cell bank. Cherkinski told Reuters that when the French team asked the vaccine developers this question, they were “disheartened” by the answers they received.

After the report was published, Cherkinski said in an email that since his last social conversation with Reuters in May, “scientific refutation” has been “scientifically refuted” that there are potential problems with the main cells of the satellite vaccine and fetal bovine serum. . He did not answer a follow-up question from Reuters, asking who refuted this.

He also stated in the post-published email that “the harmlessness of artificial satellite vaccines is difficult to argue about after being vaccinated to the general public in many countries.”

One of the people familiar with the matter said that the French delegation informally shared their conclusions with EMA-including their questions about master cells.

RDIF told Reuters that the Gamaleya Institute “has never used’untraceable bovine serum’ to prepare a cell bank.” It added that the Sputnik V cell bank has been independently verified and does not contain prions-related to diseases such as mad cow disease. protein. RDIF did not specify who conducted the independent verification.

In early March, EMA announced the launch of a “rolling review” of Sputnik V, which is a faster process that can be checked when the data is landed. But the developers of the drug did not submit the first data until a month later, delaying the earliest stages of the process, a French government official said.

The French Ministry of Health and Research, which sponsored the delegation to Moscow, did not respond to requests for comment on the delegation’s findings.

Brazil warning

Brazilian regulator Anvisa’s refusal to import Sputnik V in April triggered a fierce public exchange with RDIF, which threatened to sue Brazilian institutions for defamation.

One of Anvisa’s key problems is related to adenovirus, which is the virus that causes the common cold. It is used in Sputnik V to bring information into the body to trigger an immune response. Anvisa publicly stated that the adenovirus in Sputnik V has a risk of replication, which may cause a negative reaction from the recipient. Anvisa’s drug and biologics manager called this possibility a “serious” defect. The Russian said that there was no evidence of copying and Anvisa misunderstood the document.

Sergio Rezende, the former Minister of Science who advises Brazilian governors who want to import Russian vaccines, said that in discussions with Gamaliya, Russians seemed unfamiliar with the expectations of Brazilian regulators. Rezende told Reuters that he urged the Russians to revise their application, which they initially refused but eventually did.

Anvisa told Reuters that its requirements “are consistent with the regulations of other reference agencies around the world.”

Regarding the possibility of adenovirus replication, Anvisa said that the research and documents provided by Gamaleya indicate “the occurrence of replicating adenovirus” and lacked a sufficient assessment of the relationship between this and vaccine safety. Anvisa added that the conditions it imposed included proof that all batches sent to Brazil were free of copies.

In its response to Reuters, RDIF stated that Gamaleya “has confirmed that no replication-competent adenovirus (RCA) has been found in any batch of Sputnik V vaccine that has been produced.”