The rapid development of COVID-19 vaccines is one of medicine’s greatest achievements, but distribution hasn’t been easy. Vials full of doses often must be kept in extreme cold, and once opened have to be used quickly, sometimes prompting health workers to run out into the street looking for someone to take the leftovers.

Now vaccination campaigns in the U.S. and some other countries are moving from mass demand to more targeted efforts to reach the hesitant — and doctors want easier ways to deliver shots.

The ideal in many instances would be a pre-filled syringe, simple to store with no excess to worry about. But drugmakers haven’t made that a priority yet, and other measures to deliver vaccines to smaller, farther-flung populations are coming along slowly, presenting a challenge in the next phase of the immunization effort.

Doctors’ offices and clinics “need to reach people in their persuadable moment,” Kentucky Public Health Commissioner Steven Stack said April 21 at a briefing hosted by the Association of State and Territorial Health Officials. “And it’s difficult to do that when these products are shipped in 10-dose vials, or even sometimes five-dose vials.”

Campaign Needs

Large shipments of vials filled to the brim suit the needs of a campaign aimed at eventually vaccinating most of the world’s population. More than 1 billion shots have been administered globally, according to Bloomberg’s vaccination tracker, and more than a fifth of them in the U.S. alone. Large lots remain a priority globally, even as the U.S. campaign enters a new, more targeted stage.

Long the container of choice for immunizations, multi-dose vials consist of just a glass vessel and rubber stopper. While they require less testing and are cheaper to use than pre-filled syringes, the vaccine within them expires six to 12 hours after the first use.

Almost a third of Americans are fully immunized, but getting to a level at which vaccines will keep the virus largely at bay will increasingly require reaching residents who have misgivings about the shots. Those are most likely to be given at locations like primary-care doctor’s offices and clinics, where fewer doses might be needed each day, experts said.

“In the accelerated effort to make vaccines available to the world as quickly as possible, the easiest and fastest option was to go to multi-dose vials,” said Bernie Clark, vice president of biologics marketing and strategy for Catalent Pharma Solutions. “There will be different needs in the future, versus when we were in the middle of the pandemic last year.”

Pre-filled syringes could become more common in the next year or two, said Christopher Cassidy, vice president of pharmaceutical systems at Schott North America, a maker of both vials and syringes. The need will become especially great if booster shots are required to battle new variants of the coronavirus, he said.

Yet the devices aren’t a major focus for vaccine manufacturers that have been racing to get shots developed, cleared and distributed. Pfizer Inc., whose Covid vaccine developed with partner BioNTech SE was the first authorized in the U.S., isn’t currently developing a pre-filled version, a spokesman said. Coming up with slightly more convenient packaging hasn’t been the first priority for Moderna Inc. either, according to a spokesperson.

Schott and Catalent, which also makes pre-filled syringes, say they’re in discussions with companies now around Covid vaccines, but that the shift will take time. Becton Dickinson and Co., one of the top makers of syringes, has said it’s investing about $1.2 billion over four years on manufacturing capabilities and technology for pre-fillable syringes and other drug delivery systems that could also be of use for pandemic response.

Government Contract

Last year, the U.S. government granted privately held ApiJect Systems Corp. a $138 million contract to produce pre-filled syringes for COVID-19 shots. At the time, ApiJect, which doesn’t have a history of making the devices, said it would make 100 million by the end of last year and half a billion by the close of 2021. A $590 million government loan to support the work was approved, which the Stamford, Connecticut-based company says hasn’t been finalized or funded.

ApiJect hasn’t produced any pre-filled syringes for commercial use, NBC reported last week. The company has manufactured some devices, now being tested by drugmakers, that will require regulatory review before they’re sold, according to Steven Hofman, a spokesman.

ApiJect can produce 45 million doses a month through a partnership with a contract development manufacturer in South Carolina, he said. Making 100 million syringes in 2020 was dependent on vaccine availability and regulatory clearance, he said.

“When we got the contracts there was some degree of uncertainty as to whether there would be enough glass vials and syringes” for the vaccine rollout, concerns that have since eased, Hofman said.

Vaccine Priorities

Other modifications — making shots that can be more easily stored at warmer temperatures and developing booster shots — should be higher priorities than pre-filled syringes, said Nicole Lurie, a strategic adviser to the Coalition for Epidemic Preparedness Innovations, which funds Covid vaccine development. When she served as a Health and Human Services official during the pandemic of H1N1 swine flu, Lurie said, pre-filled syringe production came at the expense of time and volume.

“Nobody’s ever going to be completely happy with everything,” she said Thursday. “So prioritizing is really, really important.”

Other steps are being taken to make dosing more convenient. Pfizer, which ships its vaccines in packages of 1,170 doses, will also begin offering smaller 25-vial pack sizes that contain 450 doses at the end of May. The move will give U.S. vaccine sites flexibility, said Tanya Alcorn, vice president, biopharma global supply chain.

Pfizer, whose vaccine must be kept in an ultra-cold freezer, is also developing new formulations, including a ready-to-use, six-dose vial that could be available by the end of the year and would be stored in a standard freezer. A freeze-dried powder version, which is stored as a single dose in a vial and could be refrigerated, is aimed at early 2022.

The company is also looking at whether its currently-available vaccine, which today can be kept for only five days in a refrigerator, can be stored there for longer periods. It’s one of the most common questions Pfizer gets from health-care providers, Alcorn said.

“We are always thinking of different infrastructures. Different countries have different needs. Even within a country you have cities, you have rural areas,” she said. “It’s important for us to have different programs and different offerings.”

Moderna also said earlier Thursday that it’s developing a version of its vaccine that could be stored for three months at refrigerator temperatures, which could facilitate distribution to doctors’ offices and other smaller settings. Currently, the vaccine can be stored one month in a refrigerator and up to seven months in a standard freezer.

Such changes will make it easier for rural clinics and urgent-care centers, which typically have refrigerators but may not have deep freezers, to store shots, said Cody Powers, a principal at consulting firm ZS who advises manufacturers of Covid vaccines.

Requests for pre-filled syringes are “probably good news. It means we’re far enough in the vaccine process where the modality starts to matter,” he said. “In much of the world, that’s a luxury.”