When Bruce Y. Lee was helping the U.S. government model delivery plans for H1N1 influenza vaccines, he came to expect one constant: The schedule would always change.
“We’d constantly have to update the models as new production numbers came out,” said Lee, a professor at CUNY Graduate School of Public Health & Health Policy, who developed computational models to guide the national response to the H1N1 flu pandemic in 2009. “That just became accepted.”
The shifting timelines are already apparent with Covid-19 vaccine distribution in the U.S. — even before the rollout starts in the coming days. The Trump administration declared in May that 300 million vaccine doses would be available by January 2021, with the first distributed in October of this year. By October, that had shifted to 100 million doses by the end of the year, according to Health and Human Services Secretary Alex Azar. Currently, the plan is for 40 million doses to be distributed in December, though some in health care are skeptical of even that prediction.
Pharmaceutical and vaccine production involves complex coordination, involving product development, manufacturing, packaging, storage, distribution, and regulatory review, and each stage can cause unexpected delays.
The manufacturing process can — and usually does — go awry at some point. “Manufacturing never goes 100%, there’s always issues and stock you have to throw out,” said Lee. “You bake a thousand cakes, you’re not going to get a thousand successful cakes.”
At every stage of production, manufacturers must test the product to show that each batch, from each different facility, is equivalent to the original. This will inevitably reveal issues that need addressing as Covid-19 vaccines are produced at unprecedented scale and speed. “Not only do we want it yesterday, but we need a lot of it yesterday,” said Thomas Denny, chief operating officer of the Duke Human Vaccine Institute. “If you try and do something quickly in your kitchen, even if you have a recipe, sometimes things go wrong.”
Every feature of the final vaccine, including buffers, glass, pipette tips, dry ice, and packaging, then comes with its own potential production issues. Pfizer recently had to cut its end-of-year supply projections for Covid-19 vaccines in half, because of delays in scaling up the raw material supply chain.
As more vaccines are rolled out, this will increase the pressure on available supplies. “You’re dealing with a limited supply chain,” said Denny. “I would not be surprised, as we get two or three vaccines being manufactured, if we see some challenges.”
Another challenge for those making predictions about vaccine availability is that manufacturing capacity is a closely guarded secret, and companies are unlikely to reveal precise details even to major buyers such as the U.S. government, said Lee.
“Vaccine manufacturers hold their production capacity pretty close to their vest because it’s a point of a negotiation.” he said. Companies want to have flexibility in their contracts so they can balance production of various drugs and vaccines. “These companies are businesses and want to maximize their revenue. They’ll continue to make other products they can sell while manufacturing their vaccine.”
Even during a medical emergency, companies won’t reveal this information, said Mark Capofari, who was director of global logistics at Merck from 1995 to 2007 and currently lectures on supply chain management at Penn State University. During the AIDS crisis, when Merck made a key treatment drug, Crixivan, production capacity wasn’t shared outside the company, he said.
Once vaccines have been fully prepared, some degree of waste is inevitable, said Lee, meaning it will take more than 80,000 vaccines to inoculate 40,000 people (each person gets two doses). Vaccine is wasted if vials are broken, stored at the wrong temperature, or opened and only a portion of the doses inside are used. Wastage of between 1% and 10% is fairly common, said Lee, and this adds unpredictability to the system.
Distributing vaccines to the right people, and at the required storage temperatures, is its own complex logistical feat. Any problems with distribution can affect manufacturing, and vice versa. “You have to match supply and demand. If you don’t, you can end up with vaccines not being used, and people not being vaccinated,” said Lee.
There’s a limited amount of storage where vaccines can be kept to one side before being sent out, meaning the entire system has to work smoothly to quickly send vaccines to locations where they can be used as soon as they’re produced. “Once you make it and pack it, you just have to move it,” said Capofari. “You only have so much time from a cold-chain perspective to get it to the clinic.”
The package delivery companies FedEx and UPS are involved in distributing Pfizer’s vaccine, and both face their own limitations, especially during the holiday season. These companies seem to be at capacity, said Capofari. “I don’t know how much you can put lift into the system now.”
Despite the many variabilities, the U.S. government is still making optimistic predictions. Earlier this week, Azar said the government is “very confident” there will be enough doses for everyone in the U.S. who wants to be vaccinated by the second quarter of 2021.
Others are less sure. “This is all the world of guesstimates. I would think you’ll see these estimates reissued and refined every couple of weeks as we go through this process,” said Denny.
Given the current information, it’s reasonable to expect that vaccine rollout in the U.S. will continue well into the third quarter of 2021, agreed Denny, Lee, and Capofari. But even this prediction is dependent on everything going to plan.
“This is a best guess with everything aligning with everything you hope it will align,” said Denny. “Rarely do we get everything to work out with that type of alignment.”