FDA panel split on approach to COVID-19 vaccines for younger children

Regulatory NewsRegulatory News | 11 June 2021 |  By 

Members of the US Food and Drug Administration’s (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) disagreed as to whether the agency should grant emergency use authorizations (EUAs) for COVID-19 vaccines for children at a 10 June meeting.
Some said that EUAs were necessary to get the pediatric population vaccinated quickly to achieve herd immunity as the country emerges from the pandemic and that these vaccines should be available soon as the fall and flu season approach and the risk of contracting respiratory infections increases.
The meeting, which was not convened to discuss any specific vaccines, followed FDA’s decision last month to authorize the Pfizer-BioNTech vaccine for adolescents 12 to 15 years of age. (RELATED:  FDA authorizes Pfizer-BioNTech vaccine in children 12-15, Regulatory Focus 10 May). Pfizer recently announced it will begin a late-stage trial of the vaccine in children under 12 years of age and Moderna has requested an EUA for its vaccine in children 12 and up.
Some members of the committee who were wary of EUAs in younger age groups said there was insufficient justification and safety data to support emergency use in this population and were concerned about recent reports from Israel that cited elevated cases of myocarditis, or inflammation of the heart, in males ages 16 to 30 who received both doses of Pfizer-BioNTech’s mRNA-based vaccine Comirnaty.
During the meeting, panelists also heard from the US Centers for Disease Control and Prevention (CDC), which has observed similar elevated rates of myocarditis or pericarditis in males ages 16-24 who received two doses of the Pfizer-BioNTech or Moderna vaccines based on preliminary data from the Vaccine Adverse Event Reporting System (VAERS), though CDC’s Vaccine Safety Datalink (VSD) database did not identify myocarditis/pericarditis as a signal.
FDA asked the committee to discuss circumstances under which an EUA or biologics license application (BLA) should be granted for pediatric age groups and the types of pediatric postmarketing studies they would like to see following the issuance of an EUA or BLA.
In its briefing materials, FDA says it has accepted an overall pediatric safety database in the range of 500 to 3,000 participants exposed to an age-appropriate dose and followed for at least six months after vaccination to support licensure of preventative vaccines for other infectious diseases.
FDA’s Doran Fink, the deputy director of Division of Vaccines and Related Products Applications in the Office of Vaccines Research in the Center for Biologics Evaluation and Research, told the committee that, “These are very complicated issues and we welcome your input.”
FDA’s Dr. Ramachandra Naik, a biologist with the FDA’s Office of Vaccines Research and Review for the Center of Biologics Evaluation and Research, told the panel that, “There is intense interest in pediatric COVID-19 vaccines. There are no approved vaccines for those under 12 years of age.”
Panel has opposing viewpoints on EUAs
Some panel members cited declining COVID-19 cases and hospitalizations and the incidence of severe disease in children as reasons to avoid taking the EUA route.
“We certainly need a pediatric vaccine, that is not the issue of what we are discussing today, the question is at what point will we have sufficient data …There are four hospitalizations per one million children, that is not an emergency and is a very low hospitalization rate,” said Cody Meissner, professor of pediatrics at the Tufts University School of Medicine.
Meissner said that he is also concerned about the potential link between the mRNA vaccines and myocardia in children based on the data from Israel and the CDC.
“I am worried about myocarditis,” Meissner said, adding that it is still unknown whether these cases could cause scarring of the myocardium or a predisposition to arrythmias, though he believes those outcomes are unlikely.
He added that, “Before we start vaccinating millions of adolescents and children it is so important to find out what the consequences are … By not insisting on a full BLA … I do not feel we can justify [an] EUA including children.” Meisner said he would prefer to see the vaccines licensed with at least 12, or potentially 18-24, months of safety follow-up in children and adolescents.
“Once we clarify [the risks] then we definitely want to go ahead with this immunization program,” Meisner added.
“I really am not seeing this as an emergency authorization in children. The EUA just seems like overkill in my opinion,” said Michael Kurilla, director of the division of clinical innovation at the National Center for Advancing Translation Sciences at the National Institutes of Health (NIH).
Pamela McInnes, a retired deputy director of the National Center for Advancing Translational Sciences at NIH, concurred. “I am uncomfortable in granting an EUA for these vaccines. I think there should be full licensure.”
Some panel members disagreed and were more favorable of making vaccines available for younger age groups. “I think we are going to have to have a highly vaccinated or highly immune population for years — if not decades — it just seems silly to think that we’re not going to have to include children as part of that since they can suffer and be hospitalized and occasionally die from this virus,” said Paul Offit, professor of pediatrics at The Children’s Hospital of Philadelphia.
While acknowledging the potential risks involved with vaccinating pediatric populations, David Kim, director of the Division of Vaccines, Office of Infectious Disease and HIV/AIDS Policy at the Department of Health and Human Services, asked his fellow committee members to consider the risks of not vaccinating children.
“What is the cost of not vaccinating, what is the cost to our children if we do not proceed with a vaccination program? Not only in terms of protecting their health but for the larger public health?” Kim asked.
Eric Rubin, chair of the Department of Immunology and Infectious Diseases at the Harvard TH Chan School of Public Health, pointed out that it would be important to have COVID-19 vaccines for children in our arsenal because it remains to be seen what happens with the pandemic in the fall and winter. “[Just] because we give an EUA to the vaccine doesn’t mean we have to use it,” he said. Rubin also noted that these vaccines have been studied and administered more extensively in adults: “This isn’t a blank slate, we’re not going in with a new vaccine to kids, we’re going in with a gigantic base of experience now in adults, and that experience has suggested that there may be rare side effects.”
“I’d hate to not have the tool because as people have said, when you get back in September and kids are back in school and people are back indoors … who knows what things are going to look like? I would just like to have the ability to use this vaccine if we need it. If now we set preconditions that are not achievable over a reasonable amount of time, we won’t have it,” Rubin said.
Amanda Cohn, chief medical officer at the National Center for Immunizations and Respiratory Diseases at the CDC, said her concern regarding safety follow-up is less about duration than it is the size of the cohort being followed and suggested increasing the size of the cohort for younger age groups. Archana Chatterjee, dean of the Chicago Medical School, agreed with Cohn and added that concomitant use of other vaccines must be carefully considered in the 6 months to 1 year age group.
Oveta Fuller, associate professor of microbiology and immunology at the University of Michigan’s School of Medicine, stressed that, “We are in an emergency situation.”
She added that children have been at home and therefore “protected” from the virus, yet, “We already know that staying home is not viable” and that vaccines should be made available earlier as the risk of respiratory infections increase in the fall and winter seasons.
Mark Sawyer, professor of clinical pediatrics at the University of California School of Medicine in San Diego, said that vaccinating children will be necessary to reach herd immunity. “I do agree with those in general who think we need these vaccines sooner rather than later in children … I’m pretty sure we’re going to need the pediatric component of immunity to create the herd immunity we need given the number of unimmunized adults that are still going to be around.” Sawyer suggested a safety database of 3,000-5,000 children who received the vaccine and that postmarket surveillance systems will be more useful for identifying rare side effects.
Melinda Wharton, director of the Immunization Services Division of the National Center for Immunization and Respiratory Diseases at the CDC, said she is “quite comfortable” with the FDA’s proposed approach to safety follow-up for pediatric populations considering that hundreds of millions of doses of the current vaccines have already been administered. “We’re adding incremental knowledge to already a very large and robust database on safety and efficacy,” she said.
Michael Nelson, chief of the Asthma, Allergy and Immunology Division at the University of Virginia School of Medicine, said he believes that older children should be the priority for rolling out the vaccine based on their risk of contracting COVID-19. “Taking into social considerations of the highest risk category as we enter the fall season, I do believe the 5- to 12-year age group is probably the one we should focus on,” Nelson said.
Committee members offered varying takes on whether more data or more time would be necessary to support full licensure of a COVID-19 vaccine in adolescents ages 12 to 18. Chatterjee said she wasn’t sure how many recipients would need to be followed but said that at least 6 to 12 months follow-up should be required to support licensure. Hayley Gans, professor of pediatrics at Stanford University Medical Center, said she would like to see “enhanced information on the current safety signals” to get to full licensure.
FDA Advisory Committee meeting


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