Why AstraZeneca and J & J vaccines used worldwide are still on hold in the United States

This month, the World Health Organization approved the emergency use of the AstraZeneca and Oxford covid-19 vaccines. This follows procedures from the United Kingdom, the European Union, etc., which are already injecting the masses as quickly as possible.

But the United States is still waiting.

As the death toll increases on a daily basis, critics say the Food and Drug Administration is moving too slowly. Meanwhile, new coronaviruses are evolving and new variants are stalking people around the world.

“We are really in the competition, and this competition is a reality. The more we vaccinate people, the weaker the mutated virus will be,” said an infectious disease expert. Dr. Monica Gandhi, a professor of medicine at the university, said. University of California, San Francisco.

There are seven vaccines in the world and clinical trials have been completed, but the United States has approved only two, and Gandhi and others lament.

AstraZeneca states that it has not filed an application in the United States after a global study involving misadministration and must first complete the Phase 3 US study. Simply put, AstraZeneca has not applied for a job in the United States.

The company knows that the FDA does more than just accept the results of tests in other countries. The confusing test results, collected from clinical trials of different designs in Brazil and the United Kingdom, also raised questions about dosage and how well it works for people over the age of 65. Germany and France say they will not give the vaccine to older people, but the World Health Organization says it is okay to give it.

The FDA, one of the oldest drug approval agencies in the world, issued an emergency use authorization for two vaccines manufactured by Moderna and Pfizer-BioNTech at the end of last year. We are considering an application from Johnson & Johnson submitted on February 3, and the Advisory Board will discuss it at a meeting on February 26.

“The FDA is not a villain here,” said Dr. Cody Meissner, a pediatric infectious disease specialist at Tufts University, who belongs to the FDA’s Vaccine Advisory Board.

Drug approval usually takes months after the application is submitted, but urgent approval of the FDA’s covid vaccine is approved within a few weeks. Abigail Capobianco, an FDA spokesperson, said staff are working at night, on weekends and on holidays to prepare for the meeting. It is moving with urgency.

“The FDA staff includes mothers, fathers, grandparents, daughters, sons, sisters, siblings, etc.,” Capo Bianco said. “They and their families are also directly influenced by the work they do.”

Received J & J vaccine $ 1 billion Operation Warp Speed’s development funding uses adenovirus, a vector that causes cold-like symptoms, to provide the genetic code that triggers an immune response in the body.it would be First single dose vaccine Licensed in the United States — Vaccination of more Americans could make you a game changer.

“People are keen to get it approved, and everyone wants it to go faster,” said Dr. Ameshua Darja, a senior scholar at the Johns Hopkins Health and Security Center. It was. European Medicines Agency.

“The problem will be from a policy perspective,” Adalja said. “Does the FDA happily say that what the EMA does is on par with them and that they are completely confident in their decisions?”

Despite the need for speed, the FDA said it wouldn’t cut corners. Until last fall, vaccines usually went through a full licensing process before being distributed to the public. The use of emergency permits to vaccinate millions of healthy people has never been “never done,” said the former director of the FDA’s Vaccine Research and Review Office, which is currently consulting with pharmaceutical companies. Norman Baylor said.

To prepare for J & J’s advisory board, FDA staff and an independent advisory board will discuss whether the benefits of the vaccine outweigh the risks of injecting the vaccine into millions of healthy people. Analyze stuff data points. The FDA does not have to follow panel recommendations, but it usually does.

“We want all vaccines to succeed,” said Meissner, who abstained from voting for the Pfizer-BioNTech vaccine. Everyone on the planet needs vaccinations — billions of people.

“The more manufacturers we can offer vaccines, the better,” Meissner said. “I don’t think anyone opposes other manufacturers.”

At this moment, the FDA’s drug approval process has been honed for decades, as Americans are wondering why more tested vaccines like AstraZeneca and J & J’s vaccines aren’t approved. Shows how independent of other global institutions. Dr. Henry Miller, a senior researcher at the Pacific Institute, who was the founding director of the FDA’s biotechnology office, said it was difficult to compare international vaccine development.

“It’s not like a foot race where everyone starts together,” he said. “There are many variables in each country.”

There can be minor things such as differences in the application process and whether the company has filled out the form properly. Others are more substantive — while many countries rely on scholars on contracts, the United States relies on full-time staff who spend their careers focused on drug development, Miller says. I did.

Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said: In a recent radio interview “The FDA is involved very early in the process, which makes us unique among global agencies.”

FDA staff discussed with several vaccine makers “how they work,” even before the vaccines entered early clinical trials in humans. They keep in touch through various stages of manufacturing, Marks said.

Technically, AstraZeneca and other vaccine makers have submitted applications for so-called “new clinical trial products” to the FDA. This means that companies provide early formulation, stability, and laboratory work details. We also provide results data at the end of each clinical trial phase.

Award-winning AstraZeneca Up to $ 1.2 billion AstraZeneca spokesman Brendan McEvoy said he developed the vaccine through Operation Warp Speed ​​and “maintains close and regular communication” with federal agencies.

There are differences in what each country needs from a vaccine. The AstraZeneca vaccine will be “for a very different population than the Pfizer and Modana vaccines,” said Miller, a former FDA staff member. Pfizer and Modana vaccines are more expensive and require refrigerated infrastructure that is not available in many developing countries.

In addition, Miller said he believes that international organizations are keen to approve AstraZeneca. “The situation suggests that they are willing to accept slightly lower standards. Greater because drugs aimed at treating cancer are in great need and very profitable. Be willing to accept the side effects. It’s all about risks, benefits, and probabilities, “he said.

The overseas acceptance of AstraZeneca is sufficient for some people. “Why wait for another clinical trial to complete?” Asked Dr. Martin McCulley, a professor of surgery and health policy at Johns Hopkins University School of Medicine in Baltimore. “You have a real-life observation that the vaccine is being given to millions of people.”

Gandhi, who is following clinical trials around the world, has expressed greater urgency. “The UK will get herd immunity sooner,” she said. “All of these great things the FDA is doing are taking too long because we are all so impressed.”

In October, the FDA released Corporate guidance “The design needed for the study and the FDA’s expectations for the data are fairly clear,” said Dr. Jesse Goodman, former director of the FDA’s Center for Biologics Evaluation and Research, which regulates vaccines. He was also the FDA’s Chief Scientist from 2009 to 2014 and led the response to the 2009 H1N1 pandemic.

Authorities sought evidence that the benefits of the vaccine outweigh the risks, based on data from at least one well-designed Phase 3 clinical trial. To pass a rally, at least 50% of vaccinated people need to prevent or reduce the severity of the disease. Both the Moderna and Pfizer-BioNTech vaccines are well above that threshold. 94.5% And 95% Respectively.

Dr. Stanley Plotkin, a scientist and vaccine developer, said the Pfizer and Moderna vaccines came to the fore after a large US trial with “very clear results and high efficacy.” One of AstraZeneca’s challenges is data variability. That is, different trials with different doses and population numbers.In clinical trials, the effectiveness of the vaccine 82.4% When two doses are given at 12 week intervals.

The FDA will delve into the incoming study numbers to determine how well each vaccine works at different doses and schedules. They question whether to prevent serious or mild illness, taking into account the different age groups of the study population, including a subset that is likely to get sick. Other aspects to be analyzed are immunogenicity, or antibody response, and safety data.

“Ask questions and request more data is exactly what they are supposed to do,” said Plotkin, an emeritus professor at the University of Pennsylvania and consulting with Moderna and others. Mr. says.

Also, as multiple vaccine studies are underway, FDA staff may review data from different applications and ask questions that are not clear to researchers at companies working on individual projects. Said Goodman, a former vaccine regulator who is now a professor at Georgetown University. ..

The FDA’s staff work in excess and often perform “in-depth research and validation of plants” where vaccines are produced, virologists and former unit chief of the Federal Department of Advanced Biomedical Research and Development. Kevin Gilligan said. “We want to make sure that there are no pathogens left there and that all the equipment in use is completely clean and reassessed,” Gilligan said.

Novabax, which received $ 1.6 billion through Operation Warp Speed ​​in July, is developing a two-shot protein-based vaccine.After dealing with FDA question, Novavax has stepped up its full-scale manufacturing operations. Novavax spokesman Silvia Taylor said the company “is in constant contact with the FDA and is” beginning to submit various parts of its application and data to government officials. ” It expects the first results of its US Phase 3 trial before the summer.

According to Taylor, Novabax has already “locked” a large manufacturing process and is ready to sell in the United States as soon as emergency use is approved.

KHN Editor Arthur Allen contributed to this report.