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The Biden administration’s plan to stretch supplies of monkeypox vaccine by giving people fractional doses of the product is running into problems, with some local health officials saying they are unable to extract the targeted number of doses from vials.

The administration announced on Aug. 9 that it would authorize use of one-fifth doses of Bavarian Nordic’s monkeypox vaccine, Jynneos, meaning each vial of vaccine should generate five vaccinations. In practice, however, drawing that many doses is proving to be impossible in a number of hands.

“Our team is getting three to four [doses] currently,” said Jeffrey Duchin, health officer for Seattle and King County Health Department, who added that that rate is “problematic because the actual number of doses we are getting is lower than the official allocation which assumes five doses per vial.”

Claire Hannan, executive director of the Association of Immunization Managers, said her group is hearing similar dose withdrawal rates from other jurisdictions that have started to use the fractional dosing approach.

Demetre Daskalakis, deputy coordinator for the monkeypox response for the White House, acknowledged that the administration is hearing that vaccination clinics are not uniformly getting five doses out of every vial.


“Definitely we’ve heard that from jurisdictions,” Daskalakis, who was seconded to the White House job from the Centers for Disease Control and Prevention, told STAT. There’s a range, he said, with most reporting they are getting between three and five doses. 

The administration is offering advice on how to maximize the number of doses that can be drawn, Daskalakis said, noting the use of so-called low dead space syringes — which locations may not currently have in stock — will help to increase the number of doses people can extract from a vial.

“It is a learning curve,” Daskalakis said. “We’re learning together.”

Duchin said the Seattle and King County Health Department is trying to purchase supplies of low dead space syringes.

Another problem some clinics are reporting is that the caps on vials sometimes break before all available doses have been withdrawn. 

“You lose the rest of the doses,” said Caitlin Rivers, an infectious diseases epidemiologist at Johns Hopkins Bloomberg School of Public Health.

A senior administration official, who asked not to be identified, said the foil that holds the caps in place on the Jynneos vials is very fragile. If the vials aren’t handled gently, the caps can become loose and vaccine doses can be lost.


Hannan also reported that her organization has heard some health workers are having difficulty learning how to administer vaccine intradermally, which is not a technique many would use on a regular basis.

Practice, work-arounds and other solutions will likely resolve many of these issues over time. But the fractional dose approach has gotten off to a rocky start and precious doses of vaccine are being lost in the process.

“I think the challenge is that the public heard this announcement as if it were ready to go,” said Rivers, who wrote about the issues on Substack. “And I think state and local [health departments] weren’t ready to implement it quite yet, but they’re the ones that receive the pressure to respond to questions or concerns from the community. So I know it puts a big crunch on them to have to be put in that position.”

Fractional doses have been used in other health emergencies to stretch scant supplies of vaccine. When a large outbreak of yellow fever in Angola and the Democratic Republic of the Congo threatened to exhaust global vaccine supplies in 2016, the World Health Organization instructed the countries to use one-fifth of a dose per person. 

A clinical trial conducted about a decade ago on the Bavarian Nordic vaccine showed that two fractional doses, if administered intradermally (into the skin), generated a similar immune response to that seen in people who received two standard doses administered subcutaneously (under the skin). That is the evidence on which the current approach was authorized.

When the administration announced it was going to greenlight use of a fractional dose approach<, the move was not presented as something that was going to be phased in, though there was acknowledgement that health workers might need to be trained on how to administer a one-fifth dose of vaccine using the intradermal approach. Rather the message was: This is what we’re going to do going forward.

And dose allocations were quickly modified. After the announcement, locations that were eligible to receive 10,000 doses, for example, got 2,000 vials instead. In theory, it is the same amount of vaccine. In practice, at present, it is not.

Rivers suggested that vaccine allocations shouldn’t be lowered until it is clear health departments can operationalize the fractional dosing plan effectively. “Because then … when we’re figuring out how to get 5 doses out, there’s some wiggle room,” she said. “Those lost doses really matter.” 

People at the delivery end of the vaccination campaign have expressed fears that they will lose doses, if they cannot get five doses per vial. But Daskalakis said that is not the intent here. 

The administration knows that regardless of what studies show about how many fractional doses can be pulled from a vial, “real world is real world.” He said if jurisdictions don’t manage to vaccinate five times as many people with their allocations, they can ask for more vaccine.

“If they burn through their vaccine, there’s more allocation coming right behind,” he said. “We’re learning how many doses can get pulled and we’ll know that from the administration data that we get back from the jurisdictions compared to what their allocation is.”

“We’re going to really rely on them to provide us with administration data so that we can get a real-world estimate of how many doses are actually associated with X number of vials in the allocation,” Daskalakis said.

The United Kingdom’s Health Security Agency, which last week announced it too would use fractional doses of monkeypox vaccine, said Monday that it will first test whether the vaccine can be effectively administered this way before rolling out the approach more broadly across the country.

Two London area health units and a third in Manchester will begin “small scale piloting” of the dose-sparing approach, Dame Jenny Harries, the HSA’s chief executive, said in a statement.

“We are working with these three clinics to assess the operational feasibility of using intradermal injections, including staffing models, vaccination throughput, volume, and patient experience,” Harries said. “We will continue to update you on progress, learning and evaluation.”

Asked if a more gradual introduction of the program might have made sense in this country, Daskalakis said the nature of the event required action.

“I think hard things are hard and this is a skill that has to be relearned. So I think that in reality, the emergency scenario in this really means we need to learn and go at the same time,” he said.

Correction: An earlier version of this story listed the wrong title for Jeffrey Duchin, who is the health officer for Seattle and King County.

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