Main menu


How the U.S Could Launch a COVID-19 Vaccine Before Elections and Why That Scared Some

When President Donald Trump accepted his party's nomination for another term at the Republican National Convention last night, he vowed that pushing his administration's Warp Speed ​​process to deliver a COVID-19 vaccine would work "before the end of the year, or so. even before. "

This promise worries many vaccine veterans. They are concerned that political forces (the November 3 US presidential election, national pride in "winning" the race, and the need to revive economies) could lead to dangerous early approvals under mechanisms such as the Emergency Use Authorization (US ), a path they use. The US Food and Drug Administration (FDA) to allow rapid access to diagnostics, treatments, and vaccines. It has long been a bulwark of regulatory rigor that many other countries look to for guidance, and the Food and Drug Administration has come under fire for issuing the US for two COVID-19 treatments, convalescent plasma and hydroxychloroquine, based on scant data. and apparent political pressure. (Hydroxychloroquine USA has since been canceled). Paul Offit,

China and Russia have already agreed to limited use of COVID-19 vaccines outside of clinical trials, which presents puzzling reasons and strong criticism. In the United States, Operation Warp Speed, as the name suggests, hopes to drive vaccine candidates faster than ever. It has invested more than $ 10 billion in developing eight different vaccines for COVID-19, and much of that money was previously purchased for hundreds of millions of doses, so it will be ready if it gets FDA approval. Three vaccine-backed Warp Speed ​​trials have become effective and one manufacturer has pledged to start delivering the first 300 million doses starting in October, although someone close to Operation Warp Speed ​​says: "There won't be enough vaccine in October". To create something more than news. "

Food and Drug Administration officials insisted they have "firm regulatory safeguards" and will not take shortcuts. "The acceleration has to do with financial risk [in terms of] the development process," FDA Commissioner Stephen Hahn said at a US House of Representatives committee hearing on the country's response to COVID. June 19. "We will rely on data and science when it comes to this decision on the USA."

Peter Marks, who heads the division of the Food and Drug Administration that oversees the approval of the vaccine, vowed he would resign if the Trump administration paid for a vaccine that was clearly not safe and effective. He insists that the FDA will consult with the Vaccines and Related Biologicals Advisory Committee (VRBPAC), on which OFIT is located, to openly discuss the data on any consent requests. Marx says, "Consent should be something we can make transparent, and doing anything less than that is really bad for people." The next VRBPAC meeting is scheduled for October 22, 12 days before the presidential and congressional elections.

 Science spoke with a group of researchers and regulators about how to accelerate the approval of a COVID-19 vaccine and the possible consequences.

What is the traditional approval route for a vaccine?

After initial laboratory and animal testing, the vaccines enter the first phase of human testing that typically involves about 20 to 100 people and primarily looks at safety and immune responses. Phase II studies are larger versions of phase I trials. Phase 3 studies try to determine if the vaccine works by comparing people who receive it with those who received a placebo injection, and over a period of several months or years, finding out how many infected people were in each group. For COVID-19 vaccines, these trials involve between 10,000 and 60,000 people and will require a total of about 150 cases of illness to determine whether the filter is working or not. Once the experimental endpoints are met, a vaccine developer seeking FDA approval submits a biological materials license application; The VRBPAC will review the data in a public meeting and then vote on whether a vaccine should get approval, a recommendation generally followed by the Food and Drug Administration. The approval process, which includes inspection of vaccine manufacturing plants, typically takes one year.

How does EUA work?

The EUA in the United States, and similar regulatory pathways in many countries, allow the use of an unlicensed vaccine outside of a clinical trial. The EUA may foresee the use of the vaccine in a limited number of residents, for example, healthcare workers or the elderly. Or it could be for the general public. The EUA offers liability protection to vaccine manufacturers, and remains in effect as long as there is a public health, military, or national security emergency. When the state of emergency ends, so does consent.

What evidence of safety and efficacy would the FDA require before an EUA is issued?

The United States Food and Drug Administration (FDA) released "industry guidelines" in June saying that any emergency decision about a COVID-19 vaccine will depend on factors such as "target populations, product characteristics, and data from preclinical and human clinical studies ". The directive specifies that the FDA will only approve a vaccine in the US that is at least 50% effective. But the efficacy estimates have error bars of some kind. For the COVID-19 vaccine, the Food and Drug Administration wants 95% confidence that the effectiveness is at least 30%. The decision to consider the USA application will likely be based on data that is reviewed by independent boards, created by vaccine sponsors or clinical trial researchers, who monitor safety and efficacy throughout the study. (The Financial Times quoted the story on Aug. 30, quoting Han as saying that the EUA could be issued before the Phase III study was completed. A senior official with the Department of Health and Human Services confirms that Hahn was referring to a possible US request driven by early and routine reviews of Phase III data by independent councils in charge of safety oversight).

What harm could the EUA do?

The group Public Citizen, a public advocacy group, has argued that regardless of whether the COVID-19 vaccine is effective, the US could fuel current doubts about the vaccine. "The logic of" saving several months through the fastest but most dangerous route in the US will certainly be diminished by a loss of public confidence in the vaccine, accompanied by a decrease in the desire for vaccination, "warned Public Citizen in a letter from Aug. 6 to Marks and superiors Recruit people for clinical trials of this vaccine and others, because participants may not want to risk receiving a placebo when they can receive an injection of an approved product.

What if the vaccine does not work well or causes harm?

Vaccines go to healthy people, so using them before a full benefit-risk assessment is a bigger gamble than the US version of an experimental treatment for someone who is already sick. If the hastily approved COVID-19 vaccine is shown to be ineffective or has serious side effects, confidence may wane in what many see as the best hope for ending the pandemic. The World Health Organization (WHO) Expert Group on Vaccine Solidarity Trials said in an editorial published yesterday in The Lancet that a weakly effective vaccine can worsen an epidemic if it causes authorities to relax control measures, such as wearing a mask, or if people who get vaccinated think they are immune and increase their risky behavior.

Has the EUA ever been used for a vaccine?

Yes. In 2005, the US Food and Drug Administration issued the anthrax vaccine to people who were determined by the military to be at high risk for an attack with anthrax used as a biological weapon. The incident sparked lawsuits alleging that there was no evidence that the vaccine, which the army ordered from soldiers, was working against the type of inhalation anthrax used in biological weapons. The judge ruled in favor of the plaintiffs, but by then the vaccine had become voluntary.

What is the difference between the FDA and US Extended Access Program?

Generally, extended access, also called compassionate use, covers treatments but not vaccines in the United States. For people with a life-threatening condition for which there are no alternatives or for small groups of patients when the treatment has promising evidence but its effectiveness has not yet been proven. Anyone receiving an experimental drug signs an informed consent form, and the organizations that provide it must obtain permission from the Food and Drug Administration, submit a protocol, report adverse events, and continuously monitor safety. The EUA removes these requirements. The US Food and Drug Administration allowed nearly 100,000 people to receive convalescent plasma by expanding access, an unusually large example of compassionate use, but last week it granted a US agreement that supporters say would reduce the paperwork. The Democratic Republic of the Congo used its expanded access list to allow more than 300,

If the Food and Drug Administration decides not to grant the EUA or extended access to COVID-19, are there other avenues of approval?

Yes. The Department of Health and Human Services, the parent of the Food and Drug Administration, or the President of the United States can override the FDA's denial of a US application. Although the episode did not include the US agreement, in 2011 the Secretary of HHS reversed the FDA commissioner's decision to allow the sale of contraceptives without a prescription without age restrictions. The viewpoint on regulatory decisions for the COVID 19 vaccine of August 31, the Journal of the American Medical Association, cites this precedent when discussing the ways in which the US rejection could be reversed. The opinion also demonstrates that the FDA's "accelerated approval" process could lead to approval of a vaccine based on an alternative marker rather than clinical efficacy. A vaccine manufacturer could argue, for example, that its filter produces high enough levels of certain types of antibodies to protect a person from COVID-19. Alternative markers are often accepted by the FDA to evaluate experimental treatments and are sometimes used to reformulate approved and approved vaccines, such as the seasonal influenza vaccine. If a small number of COVID-19 vaccines show adequate protection against the disease to meet the FDA threshold of effectiveness, their experiences may also reveal "protective links," and subsequent candidates may receive rapid approvals based on those markers. alternative.

Does Europe have similar emergency approval procedures?

The European Medicines Agency (EMA) can issue a "conditional approval" for a vaccine during a pandemic. As part of the ongoing review process, companies continue to provide data as soon as it is available. The UK, which will leave the EMA in power due to Brexit, today issued a public comment query on how its regulatory agency is issuing an interim mandate for its unlicensed COVID-19 vaccine.

How quickly did China and Russia pass COVID-19 vaccines?

On June 25, China granted CanSino a one-year approval for the use of the COVID-19 vaccine in the Chinese military, although there is no evidence other than statements by company officials that anyone has received it. On July 22, China also allowed Sinopharm's China National Biotec Group to administer the COVID-19 vaccine to healthcare workers, customs officials and others in "high-risk" occupations. Both vaccines are still in phase III efficacy trials. CanSino is also reported to be in talks with regulators in Pakistan and unidentified Latin American countries about early approval of its vaccine.

The Russian Institute for Aesthetic Research of Epidemiology and Microbiology in Moscow received a "certificate of registration" on August 11 to award the COVID-19 vaccine for what a spokesperson for the Ministry of Health described as "a small number of citizens at risk." . Including medical workers and the elderly. The product is called Sputnik V, in clear reference to the space race between the United States and the Soviet Union, and has been described as "the first registered vaccine for COVID-19." The recording says that it cannot be used on a large scale even after January 1, 2021, but President Vladimir Putin said: "I hope we can start a mass launch of this vaccine soon."

Many countries do not have strong regulatory agencies. How do they decide to use the COVID-19 vaccine without a license?

The World Health Organization has what it calls its emergency use list, which many low- and middle-income countries have relied on in the past. "We can decide on the benefits / risks of the product and determine the conditions in which it should be used," says Emer Cooke, Director of Regulation of Medicines and Other Health Technologies at the World Health Organization. "We work as a regulatory body, but we are not a regulatory body." Cook, who was recently elected to chair the EMA later this year, says his jobs are particularly challenging now due to the influx of COVID-19 vaccine candidates and intense pressure to find a safe and effective vaccine. "I think we are seeing more political influences now than we usually see," he says.