(CNN) As Molly Howell, a state health official in North Dakota, watched a webinar on how to distribute what's expected to be the first Covid-19 vaccine, her head began to spin.
"How are we going to do this?" she texted a colleague who was also on the webinar.
Her colleague responded with an exploding head emoji.
Monday, Pfizer announced that initial Phase 3 clinical trial results show its vaccine is more than 90% effective. If approved, Pfizer's vaccine will also be the most fragile vaccine used in the United States, and the state health officials charged with its distribution worry the process will not go smoothly.
Pfizer's vaccine needs to be stored at about minus 75 degrees Celsius, which is about 50 degrees colder than any vaccine currently used in the United States. Doctors' offices, pharmacies and state labs don't have freezers that go nearly that low.
The solution is a set of handling and storage requirements that a doctor at the US Centers for Disease Control and Prevention described as "very complex."
The CDC has asked states to be ready to receive Pfizer's vaccine by November 15, but state officials say the first time they heard the specific requirements was on October 15, giving them just weeks to prepare.
State health officials were "shocked" when they heard the storage requirements for the new vaccine, according to Dr. Kelly Moore, associate director of the Immunization Action Coalition, which is supporting the frontline workers who will administer the coronavirus vaccine. Those requirements include procuring and handling large amounts of dry ice, which is in short supply in many parts of the country.
"We all are going into this expecting that there are going to be major glitches," she said.
Howell, North Dakota's immunization program manager, calls the prospect of administering Pfizer's vaccine "overwhelming" and "daunting."
Claire Hannan, executive director of the Association of Immunization Managers, which also helps states with their vaccine programs, sent Howell the exploding head emoji.
"These challenges are so unprecedented. I don't have anything to compare [them] to," Hannan told CNN.
Even those on the inside have doubts about how the process is going.
"All of the squares of the quilt have not been knit together very squarely at this point," said Dr. William Schaffner, a longtime adviser on vaccines to the CDC. "There are probably more questions than answers."
The federal government's vaccine effort is being led by the CDC, the Department of Defense, and Operation Warp Speed, a part of the Department of Health and Human Services.
In an email to CNN, an HHS spokesperson said the CDC, in coordination with the Department of Defense, is working closely with states and other jurisdictions "to advise and guide every logistical detail in regards to vaccine distribution. Operation Warp Speed is a whole-of-America effort and will be successful because of the partnership and teamwork between the federal and state governments, industry, the healthcare community and academia."
Gen. Gustave Perna, formerly the commanding general of the US Army Materiel Command, is chief operating officer of Operation Warp Speed.
On "60 Minutes" Sunday, Perna said he would hold himself personally accountable if the distribution of the vaccine doesn't go smoothly.
"Me. Conversation's over. It's pretty easy -- me," Perna said when asked where the buck stops if the distribution doesn't go according to plan. "I hold myself 100% personally accountable to that end."
"Perna is the best logistician in the US government," said Dr. Nelson Michael, director of the Center for Infectious Disease Research at the Walter Reed Army Institute of Research. "You have the entire weight of a four-star general who knows how to move bullets and beans from Point A to Point B and get them there at the right time."
CNN asked Pfizer to address the concerns from state officials about keeping the vaccine at the right temperature, also known as the "cold chain."
"Most vaccines need cold chain storage and we have already initiated development of innovative cold-chain solutions and distribution logistics to facilitate vaccine supply," according to Pfizer spokesperson Steven Danehy. "We have also developed packaging and storage innovations to be fit for purpose for the range of locations where we believe vaccinations will take place."
As states work to implement solutions, deadlines have already been missed.
Four Covid-19 vaccines are currently in large-scale Phase 3 clinical trials, but only Pfizer's has to be kept at around minus 75 degrees Celsius, or minus 103 degrees Fahrenheit.
The specific requirement is minus 75 degrees Celsius plus or minus 15 degrees. The lowest requirement for a current vaccine in the US is about minus 20 degrees.
"These [Pfizer Covid-19] vaccines will thaw if exposed to open air for five minutes," said Moore, the doctor helping states implement their coronavirus vaccine programs.
Moore serves on the external advisory board for Pfizer's coronavirus vaccine.
In a letter on October 26, the CDC asked states to be ready to receive Pfizer's vaccine by November 15. State officials interviewed by CNN said it was unlikely they could be.
Already most states have missed November 2 planning deadlines, according to Hannan and to a CDC spokesperson.
"It would be hard to with a straight face say, 'Oh, we're all set,'" said Christine Finley, Vermont's immunization program manager. "[This] equals a challenge I don't think we've ever seen before."
A review by CNN of the 46 state vaccine plans that are online shows only a few states have detailed plans for maintaining the vaccine's cold chain. Most states have just some details in their plans, and a few states don't even mention their cold chain plans.
In the past, the CDC has managed relationships with state health agencies, but during the pandemic, the CDC has been sidelined, and is now doing the work along with Operation Warp Speed.
That has not always gone smoothly, with "an element of having too many bosses," said Laurel Wood, coordinator for public health for the Immunization Action Coalition. "There are many cooks involved."
While the CDC historically has enjoyed good relationships with state health departments, she said there's been some tension between Operation Warp Speed and the states.
One state program manager was "almost in tears" after receiving a "castigation" by an Operation Warp Speed official who was unhappy with a plan she filed, Wood said.
"You've got people coming at you from a thousand different directions."
CNN asked the HHS spokesperson for a response to the state officials' concerns.
"Only one vaccine candidate requires ultra-cold storage and transport, and they have demonstrated the capability to ship and store directly from manufacturing sites to administration sites to reduce the time in transit, while monitoring temperatures of packaging at all times," according to the statement. The spokesperson did not explain how Pfizer has demonstrated that capability.
"[Operation Warp Speed] has been diligently working with vaccine manufacturers to ensure administration sites have the capabilities to receive and maintain a vaccine with cold-storage requirements for up to 10 days. Administration sites can repack opened shipping containers with dry ice multiple times for an additional 15 days. If a shipment of vaccine doses is at risk of expiring, OWS will guide the movement of those doses to sites with larger demand," the statement continued.
There are ultra-low temperature freezers that can keep a vaccine at minus 75 degrees. Buying them for sites across the country might seem like the obvious solution to keeping a vaccine so cold.
But the CDC has told states not to purchase them.
"I just want to let all of the listeners know, to not start going online right now in purchasing freezers," CDC's Dr. Amanda Cohn said at a meeting of the agency's Advisory Committee on Immunization Practices. "We are working on solutions through our distribution and administration planning for these very complex storage and handling requirements at this time."
That advice was repeated in CDC's vaccine "playbook" sent out to states in September and October.
Instead, the CDC wants doctors and nurses to maintain the vaccine with dry ice -- something they've never had to do before.
The dry ice will go into a box developed by Pfizer, which the company calls a "thermal shipper."
Pfizer will use that box to ship the vaccine, opting out of the government's plan to use McKesson, a third-party distributor, which is expected to handle other coronavirus vaccines when they become available.
Clinics can then use the shipper to store the vaccine until it's ready to thaw, dilute and inject into arms. Health care workers, essential workers, and those at high risk for Covid-19 complications, such as the elderly, are expected to be among the first to get vaccinated.
States will administer the vaccination programs. Public health nurses, as well as private doctors, nurses, and pharmacists will give the shots.
At Pfizer's webinar with state health officials last month, the company laid out its specific requirements.
Once sites receive their thermal shippers filled with vaccine, they're supposed to replenish the dry ice within 24 hours. If they don't use the vaccine within five days, they're supposed to replenish the dry ice again, and then again five days later.
Clinic staff must act fast when removing vaccine from the shippers. According to Pfizer's instructions, the boxes can be opened only twice a day, and each time for no more than a minute.
At any point, the vaccine can be removed from the shipper and put in the refrigerator, where it is good for only five days -- any longer than that and the vaccines have to be thrown away. When ready to use, nurses dilute the vaccine, making five doses with one vial. Those five shots have to be given within six hours. If more than six hours pass, the vaccines have to be thrown out.
This whole process has to happen twice for each patient, since the vaccine is given in two doses spaced three weeks apart.
That's why heads began to explode on the Pfizer webinar, according to five people who attended it.
Health care workers have never had to procure dry ice before, much less when it's in short supply, as it is in some parts of the country. Handling dry ice can be hazardous -- it can burn the skin, and in spaces with poor ventilation, can produce potentially deadly fumes.
There's another potential problem. Doctors and nurses overtaxed with Covid-19 patients and other responsibilities will be challenged to follow directions perfectly -- directions where mere minutes matter.
"They're all so insanely busy," said Moore, the doctor who's helping doctors and nurses get ready.
"I know they were astonished when they got their first glimpse from Pfizer on all of the steps in this process, on the thermal shipper and how it worked," she said. "You could see all of the brains spinning."
"I could start to smell fumes from the gears turning in their minds about -- 'oh my -- how are we going to keep up with all of this? This is not what we expected.'"
The thermal shippers are essential to the success of the vaccine, but it's not clear that they work.
CNN asked Pfizer what tests they've done to show the thermal shippers are capable of keeping the vaccine at minus 75 degrees. The company didn't respond.
A spokesperson for the US Food and Drug Administration said before authorizing any vaccine, "the FDA will review vaccine stability information for each particular vaccine candidate. This information reflects anticipated distribution and storage conditions for a specific vaccine candidate, and our review is provided to ensure that the vaccine's quality, safety and efficacy is not compromised prior to its administration."
CNN asked the CDC, HHS and Pfizer how they know the thermal shippers work. They did not answer.
"When they don't answer questions, that's when I begin to get nervous," said Schaffner, a member of the CDC's Advisory Committee on Immunization Practices.
There are other questions, too.
At the August CDC meeting, Pfizer said the shipper could be used for 10 days, and it could be replenished with dry ice for an extended period, but it did not say how long that period was. In September, the group president of Pfizer's Biopharmaceuticals Group, Angela Hwang, said the vaccine can be stored in the shipper for 15 days. In November, a Pfizer spokesperson told CNN that unopened, the shipper can maintain its temperature for 10 days, which allows for extended shipping times, and once opened upon arrival, can be used as temporary storage for up to 15 days with dry ice being replenished every five days.
Such comments have caused confusion among state health officers. In addition, it's unclear where they will get dry ice. HHS has told state governors they will need to obtain the dry ice from local suppliers but has also acknowledged there could be difficulty obtaining dry ice in some parts of the country. The agency says it's exploring options to resolve this, including solutions to provide increased access to dry ice, but it has not yet said what those solutions will ultimately be.
Pfizer has told states that if they can't source dry ice locally, they can use the company's dry ice suppliers. But it has given few details on what that process will look like.
That's prompted at least one state, North Dakota, to buy its own dry ice machine -- an expensive proposition at $48,000, plus another $40,000 for three months' worth of liquid carbon dioxide, a necessary ingredient to make the ice, according to according to George Gerhardt at the North Dakota Department of Health.
Some states are disregarding the CDC's directive not to purchase ultra-low temperature freezers. North Dakota, for example, has spent $100,000 to purchase 13 ultra-low temperature freezers, according to Nicole Peske, a spokeswoman for the state health department.
As state health workers hurry to put their plans in place to distribute the Pfizer vaccine, they know three things are true.
One, if there are glitches in getting the vaccine out to the public, the blame will likely fall on them.
"I think that there's going to be a level of finger pointing," said Wood, the public health consultant who's helping states with their immunization plans. "People are going to turn around and say, 'well, public health just wasn't ready. This didn't happen the way that it should have, and these are unprofessional bureaucrats.'"
Second, if the distribution of Pfizer's vaccine doesn't go well, an already skeptical public could mistrust distribution of other coronavirus vaccines down the road.
"If we lose confidence in the very early, in the first stages, then the downstream ramifications I think are pretty profound," Wood said.
The third is that no matter how hard state officials work to plan out the details, no matter how many webinars they attend or CDC playbooks they read, everything right now is theoretical.
"There are definitely a lot of opportunities for errors to occur," Moore said. "You don't figure out where the bugs are until you turn the system on -- so far this entire system has just been on paper."
State public health officials are resourceful and innovative, Moore said, and right now they're forging ahead.
"It's going to be hard. Mistakes will be made, but we will learn from them, and we will get better and better," she said.
They try to be optimistic about the prospect of rolling out such an unprecedented immunization plan.
"It's a very big deal," said Howell, the North Dakota program manager. "I think we can do it."