South Florida Sun-Sentinel (Sunday)
FDA allows Moderna to increase vaccine in vials
Whether to resume in-person classes at center of debate
WASHINGTON — The Food and Drug Administration has informed the drugmaker Moderna that it can put up to 40% more coronavirus vaccine into each of its vials, a simple and potentially rapid way to bolster strained supplies, according to people familiar with the company’s operations.
While federal officials want Moderna to submit more data showing the switch would not compromise vaccine quality, the continuing discussions are a hopeful sign that the nation’s vaccine stock could increase faster than expected, simply by allowing the company to load up to 14 doses in each vial instead of 10.
Moderna currently supplies about half of the nation’s vaccine stock. A 14-dose vial load could increase the nation’s vaccine supply by as much as 20% at a time when governors are clamoring for more vaccine and more contagious variants of the coronavirus are believed to be spreading quickly.
Two people familiar with Moderna’s manufacturing, who spoke on the condition of anonymity, said retooling the company’s production lines to accommodate the change could conceivably be done in fewer than 10 weeks. That is because while the amount of liquid in each vial would change, the vials themselves would remain the same size, so the production process would not drastically change.
“It would be a great step forward,” said Dr. Moncef Slaoui, who served as the scientific leader of the Trump administration’s vaccine development program.
Last month, Moderna asked for permission to increase the number of doses in its vials to as much as 15 from the industry standard of 10. The change would cut down on the time required for the final manufacturing phase when millions of tiny bottles are filled, capped and labeled, a longtime bottleneck in injectable drug manufacturing.
The company is also asking regulators to approve changes in how its vaccine is stored and to allow health practitioners more time to use up the doses in a vial once the rubber coating is punctured, all steps to increase the flow into arms.
Slaoui cautioned that Moderna might still have to gear up its drug production so it had more vaccine to fill the vials. “Whether it will be 40% increase immediately or a 20% increase at first” is unclear, he said. Another outside expert said the FDA might require an on site inspection of the company’s manufacturing process if it changes.
In a recent email response to questions about the company’s discussions with regulators, Stephane Bancel, the chief executive officer of Moderna, wrote, “No comment.” Ray Jordan, the company’s spokesman, said talks with federal officials were continuing.
On Thursday, President Joe Biden announced that the federal government had locked in a total of 600 million doses of vaccine from Moderna and Pfizer, which developed its drug with a German partner, BioNTech. Because each vaccine requires two doses, spaced three to four weeks apart, that would be enough to cover 300 million Americans.
But getting vaccine shipments out faster remains a top priority. The Centers for Disease Control and Prevention has warned that by next month, a significantly more contagious variant of the virus could become dominant. Another variant that appears to weaken the protection of existing vaccines has also shown up in the United States.
Biden said that the nation would not be able to vaccinate all Americans by the end of the summer, citing “gigantic” logistical challenges. He blamed the Trump administration for not creating a better system to administer shots. But that argument will wear thinner as his time in office continues.
So far, about 10% of Americans have received at least one dose of vaccine. Pfizer has delivered about 52% of the nation’s supply while Moderna has delivered 48%, according to the CDC While both companies are accelerating production, fuller vials from Moderna, if approved, could push it into the lead.
Pfizer’s manufacturing is geared to six-dose vials, but Moderna’s vials have enough free space to accommodate extra doses. Still, there are limits to how much vaccine can be crammed into them.
Too much could lead to cracks in a vial. Each vial must also contain enough room to ensure enough remains to extract the final dose.
The regulations now specify that once punctured, Moderna’s entire vial must be emptied within six hours, so fuller vials could lead to more waste if pharmacists struggle to extract more doses in that time frame.
The industry standard was set at 10 doses partly because the more times a vial’s rubber coating is punctured with a needle, the more risk of contamination. But Slaoui said those standards were not written for a pandemic that had now claimed the lives of more than 480,000 Americans.
The precise number of doses that can be extracted per vial has become a highly fraught issue. Regulators allowed Pfizer to relabel its vials as containing six doses instead of five, so Pfizer is getting credit for delivering more doses than before, though the amount has not changed.
As adults at high risk for
COVID-19 line up to be immunized against the coronavirus, many parents want to know: When will my child get a vaccine?
The short answer: Not before late summer.
Pfizer and Moderna have enrolled children 12 and older in clinical trials of their vaccines and hope to have results by the summer. Depending on how the vaccines perform in that age group, the companies may then test them in younger children. The Food and Drug Administration usually takes a few weeks to review data from a clinical trial and authorize a vaccine.
Two other companies — Johnson & Johnson and Novavax — also plan to test their vaccines in children, but are further behind.
Meanwhile, the University of Oxford announced Saturday that it plans to test its vaccine in children, according to The Associated Press. The trial seeks to recruit
300 volunteers between the ages of 6 and 17, with up to
240 receiving the COVID-19 vaccine and the remainder a control meningitis vaccine.
The Oxford vaccine is being produced and distributed by AstraZeneca.
When researchers test drugs or vaccines in adults first, they typically then move down the age brackets, watching for any changes in the effective dose and for unexpected side effects.
“It would be pretty unusual to start going down into children at an early stage,” said Dr. Emily Erbelding, an infectious diseases physician at the National Institutes of Health who oversees testing of COVID-19 vaccines in special populations.
Some vaccines — those that protect against pneumococcal or meningococcal bacteria or rotavirus, for example — were tested in children first because they prevent pediatric diseases.
But it made sense for coronavirus vaccines to be first tested in and authorized for adults because the risk of severe illness and death from
COVID-19 increases sharply with age, said Paul Offit, a professor at the University of Pennsylvania and a member of the FDA’s vaccine advisory panel.
“We’re trying to save lives, keep people out of the ICU, keep them from dying,” Offit said. That means prioritizing vaccines for the oldest people and for those with underlying conditions.
People younger than 21 account for about one-quarter of the population in the U.S., but they make up less than 1% of deaths from
COVID-19. Still, about 2% of children who get COVID19 require hospital care, and at least 227 children in the country have died of the disease.
Children will also need to be vaccinated in order for the U.S. to approach herd immunity
— that long-promised goal at which the pandemic slows to a halt because the virus runs out of people to infect. Scientists have estimated that 70% to 90% of the population might need to be immunized against the coronavirus to reach herd immunity, especially with more contagious variants expected to circulate widely in the country.
“Not all adults can get the vaccine because there’s some reluctance, or there’s maybe even some vulnerable immune systems that just don’t respond,” Erbelding said. “I think we have to include children if we’re going to get to herd immunity.”
It will also be important to immunize children in racial and ethnic populations hit hardest by the pandemic, she added.
Pfizer and Moderna’s clinical trials in adults each enrolled about 50,000 participants. They had to be that
large to show significant differences between the volunteers who received a vaccine and those who got a placebo. But because it is rarer for children to become seriously ill with COVID-19, that kind of trial design in children would not be feasible, because it would require many more participants to show an effect.
Instead, the companies will look at vaccinated children for signs of a strong immune response that would protect them from the coronavirus.
The Pfizer-BioNTech vaccine was authorized in December for anyone 16 and older. The company has continued its trial with younger volunteers, recruiting 2,259 adolescents from 12 to 15 years of age. Teenagers are roughly twice as likely to be infected with the coronavirus as younger children, according to the Centers for Disease Control and Prevention.
Results from that trial should be available by summer, said Keanna Ghazvini, a spokeswoman for Pfizer.
“Moving below 12 years of age will require a new study and potentially a modified formulation or dosing schedule,” Ghazvini said. Those trials will most likely start later in the year, but the plans will be made final after the company has data from older children, she added.
Moderna’s vaccine, which was also authorized in December, is on a similar track for pediatric testing. In December, the company began testing adolescents ages 12 through 17, and plans to enroll 3,000 volunteers in this age group. The company expects results “around midyear 2021,” said Colleen Hussey, a spokeswoman for Moderna.
Based on the results, Moderna plans to assess the vaccine later this year in children between the ages of 6 months and 11 years.
Infants may have some antibodies at birth from vaccinated or infected mothers, but that maternal protection is unlikely to last through the first year of age. And with their relatively weak immune systems, babies might be particularly susceptible to infection if community transmission is high.
The trials will also assess the vaccine’s safety in children — and hopefully ease any fears that parents have.
Given the low risk of COVID-19 in children, some parents might be skeptical of the urgency to inoculate their children, Offit said.
“For that reason, the vaccine would have to be held to a very high standard of safety,” he said.
More than 42 million people in the United States have been immunized, with few lasting side effects. And the FDA has set up multiple systems to monitor any serious reactions to the vaccine.
“They’re really looking at the data very, very closely,” said Dr. Kristin Oliver, a pediatrician and vaccine expert at Mount Sinai Hospital in New York.
Once a vaccine for children is available, schools can reintroduce extracurricular activities that involve close contact, like band practice, team sports and choir. But in the meantime, there is ample evidence that schools can reopen with other precautions in place, Oliver said.
“I don’t think we need to anticipate having a vaccine in order to open schools in the fall,” she said. Oliver also urged parents to make sure children are immunized for other diseases. According to the CDC, orders for nonflu childhood vaccines through the Vaccines for Children Program are down 10.3 million doses overall.
“Now’s the time to really catch up on missed doses of those vaccines,” she said. “Measles, HPV, tetanus boosters, pertussis boosters — all of that is really important.”
Just down the road from the U.S. Centers for Disease Control and Prevention, in a community flush with resident health professionals, the Decatur, Georgia, school system had no shortage of expert input on whether to resume in-person classes amid the coronavirus pandemic.
Scores of public health and medical professionals from the affluent, politically liberal Atlanta suburb have weighed in about what’s best for their own kids’ schools.
One emergency medicine doctor said initial reopening plans for the district’s
5,000-plus students weren’t safe enough. A pediatrician doing epidemiology work for the CDC advocated delaying. Others, including a leader of the CDC’s COVID19 vaccine efforts, argued the district could get students back in classrooms safely — and that not doing so jeopardized their development and mental health.
“The challenge for me has been trying to weigh all of these things that I’m being told by experts and nonexperts alike to try to make the best decision that we can,” Superintendent David Dude said. “And that’s what I, and I’m sure other superintendents, have been struggling with.”
Each side argued data and science supported their view in a debate over reopening schools that sometimes veered into vitriol. The division in Decatur illustrates the challenges U.S. schools — many in communities without so much expertise — have faced in evaluating what’s safe.
Health officials say there’s growing evidence that children aren’t the main drivers of community spread and
that transmission is relatively low in schools if mask-wearing, social distancing and contact tracing is in effect. The CDC says that for schools to open safely, they and their surrounding communities must adopt prevention measures.
Without specific reopening instructions from federal and state leaders, school administrators have had to become amateur epidemiologists, Dude said.
When he first consulted privately with CDC and other professionals — who he said wouldn’t speak out publicly at that point in the process because the pandemic response had been politicized — people accused him of not being transparent. When he rolled out fall reopening plans, some parents and teachers questioned whether it was safe and which virus metrics were used. When he hit the brakes on reopening,
other parents got riled up, complaining about the abrupt change or how virtual schooling wasn’t tenable.
Tiffany Tesfamichael, a single parent who moved to Decatur because of the well-regarded schools, was upset that her freshman daughter had to struggle through remote learning while neighbors citing concerns about virus spread protested against opening schools, but not against opening businesses.
Dude ended up asking a giant committee of volunteers — many with relevant expertise — to make recommendations, including parameters for reopening and protocols to limit virus spread in classes.
Then he decided a new plan for January: Students at the seven elementary schools could return, staying in cohorts of 15 or fewer and attending only in the mornings, to avert the logistical
nightmare of an unmasked lunch crowd. Older students would stay remote because it was too difficult to arrange them in small cohorts.
Some CDC employees and other health professionals objected to that part, arguing in a letter to a community news website that safe, in-person learning was doable for older students using precautions other than cohorting, and that decision-makers were misreading evidence about virus transmission in schools. A hospital doctor treating COVID-19 patients countered with her own letter, warning that reopening as cases surged would be irresponsible.
The expert insights made parent Kerry Ludlam reconsider her own stance.
“I think letters like that are so powerful because you think you feel one way and then you read a letter with all of these experts . ...
And you’re like, ‘Well, their opinion is different from mine. Have I been wrong all the time?’ ” Ludlam said.
She remained inclined to keep her middle schoolers in distance learning, partly because an autoimmune disorder increases her vulnerability. But she said learning more about other families’ circumstances and academic challenges convinced her that parents should at least be offered the choice of face-to-face learning.
Without it, some families moved to private schools or other suburbs offering in-person classes. Republican Gov. Brian Kemp had pushed a largely voluntary approach to precautions, even after a summer surge in cases, and urged schools to reopen.
Around Decatur, neighbors dodged the issue in polite conversation as tensions rose during school board meetings and on social media.
Some commenters suggested that advocates of resuming in-person classes were OK with gambling teachers’ lives in a desperate grasp for normalcy, or that perhaps people urging continued remote learning couldn’t see past their privilege to understand how much other families were struggling.
Ludlam worries about the conversations yet to come.
From behind their keyboards and screens, “people just kind of let it fly — forgetting that at some point, the world is going to get back to normal, and we’re going to see each other at school or the pool or, you know, the grocery store and have time to stand and talk,” Ludlam said. “And we’re going to have to face the things we said to each other and the things we accused each other of.”