As the Covid-19 crisis stretches into its seventh month, researchers around the world are continuing to work frantic hours to develop a vaccine against the coronavirus, which has so far infected 9.5 million people and killed nearly 500,000. More than 140 vaccine candidates are currently in testing, mostly in preliminary stages. A handful have reached early human studies, with three progressing to Phase III clinical trials designed to measure whether or not they confer immunity to the virus.
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But the science of producing a safe, broadly effective vaccine is just the first step. Actually exiting the pandemic will require the subsequent manufacturing of the best-performing ones, bottling them up, shipping them around the world, and doling them out to vulnerable populations. In the case of Covid-19, that’s pretty much everybody on the planet, which means making somewhere between 7 and 15 billion doses. (Many vaccines have to be given in two doses—a primer and a boost.) No one has ever tried to do that before. And as these historic efforts to produce an unprecedented number of shots in so short a time are ramping up, vaccine makers say the biggest bottleneck they’re encountering is a cruelly literal one.
“The challenge is not making the vaccine itself, it’s filling vials. There just aren’t enough vials in the world,” Pascal Soriot, the executive director and CEO of AstraZeneca, told reporters in a press briefing last month. AstraZeneca is working with the University of Oxford on one of the front-runners in the Covid-19 vaccine race. But it’s just one of many pharmaceutical firms scrambling to source containers for that critical bottling step. Executives from AG Schott, one of the world’s major medical glass producers, recently told The Wall Street Journal that the company has received requests from vaccine makers for a billion vials—double what it can produce this year.
Medical glass is strong, but it’s still breakable. So manufacturers typically don’t make lots of excess inventory. They make what pharmaceutical companies order. And pharmaceutical companies typically don’t put in those orders until they know they’ve got a vaccine that works, plus distribution contracts in place to provide bulk doses to customers. But nothing about these times is typical. Governments and nonprofits are pumping money into ramping up vaccine manufacturing capacity in parallel with clinical testing so that individual companies don’t have to assume so much risk for paying for trials and production themselves. They’re also experimenting with nanotechnology borrowed from the semiconductor industry to make an end run around traditional forms of glass.
In the US, this concerted effort has been dubbed Operation Warp Speed. The US government’s Biomedical Advanced Research and Development Authority, or Barda, has so far invested approximately $2.2 billion in Covid-19 vaccine makers, including AstraZeneca, Johnson & Johnson, and Moderna Therapeutics, according to the agency’s portfolio. In partnership with the National Institutes of Health, these companies are planning to start Phase III trials this summer. Their goal is to not have a long gap between the time they prove that a vaccine works and when they can start making it available to lots of people.
Avoiding a scenario in which an effective vaccine gets rationed to a chosen few also means overcoming the glass bottle shortage. The issue was on the US government’s radar early on in the pandemic, according to a 60-page whistleblower complaint filed by Rick Bright, the former director of Barda who was abruptly ousted from his post in April. In it, Bright claimed that between January and March he repeatedly and unsuccessfully urged administration officials to secure supplies needed for a mass immunization campaign, including needles, syringes, and glass vials.
In June, Barda finally signed contracts worth $347 million with two American vial makers. The first, New York-based Corning, has a long history of working with vaccine makers. Its Pyrex glass was used to bottle the first polio vaccines in the 1950s. Today, it manufactures “millions of vials per month,” a company spokesperson told Business Insider earlier this week. With the infusion of Barda cash, the company expects to increase that figure tenfold over the next three years, according to the spokesperson.
But closing the glass gap will take time. Supply chain experts say that booting up a new manufacturing site capable of making an additional 100 to 500 million vials per year will take at least six to eight months. That’s if glass vial makers can get their hands on the raw materials to feed those production lines. Medical glass has to be able to withstand huge temperature swings and keep chemically finicky vaccine components stable. Making it requires melting down an especially angular species of sand found in beaches and riverbeds, with grains jagged enough that they lock together to form a sturdy glass solid. This type of sand is in such high demand—for use in everything from solar panels to concrete—that it’s sparked a violent boom in illegal sand mining in recent years. A major United Nations report published last year called sand extraction “one of the major sustainability challenges of the 21st century.”
Whether or not vaccine makers will face a glass crunch will depend on how swiftly they actually come up with a vaccine. “If we are talking about having the first working vaccine candidates early next year, then I don’t think we need to worry about glass so much,” says Prashant Yadav, a health care supply-chain researcher at the Center for Global Development. If, on the other hand, any of the leading vaccine candidates currently or about to go into Phase III testing turn out to be blockbusters—data which is expected to arrive before the end of the year—then there could be a problem. “We’ll have no means of delivering it widely, because we won’t have the vials yet,” says Yadav.
To hedge against a more immediate shortfall, Barda is betting on a company that has developed vial-making technology that doesn’t rely on the traditional sand-to-glass supply chain. Instead, it uses manufacturing processes honed in Silicon Valley to coat an almost imperceptibly thin layer of silicate inside plastic containers. “We’re basically taking the best of glass and plastic and combining the benefits of both into a hybrid material,” says Christopher Weikart, chief scientist at SiO2 Materials Science, which signed a $143 million partnership with Barda to make vials to support Covid-19 vaccine efforts.
Based in Auburn, Alabama, the company has developed many recognizable plastic containers over the years. It made the first milk jug with handles in the 1960s, and, later, the pocket-size pop-top tubes for mini-M&Ms. It’s only since Weikart arrived in 2011 that the company has turned to producing containers specifically for the pharmaceutical industry.
Plastic alone doesn’t make for great drug packaging, especially for so-called “biologics”—the bits of protein, nucleotides, antibodies, and other things that cells typically make that comprise an increasing proportion of modern medicines. The properties that make plastic polymers light and durable also makes them too breathable. Air, water, and other gases and liquids can easily permeate them. Plastic polymers themselves can also leach into the drugs, causing contamination. Both issues can alter how safe and effective a drug is by the time it reaches a patient.
Weikart’s team was tasked with figuring out how to make a plastic container that didn’t have these problems. He found the answer in plasma. You know, that fourth state of matter, the one that comes after solid, liquid, and gas. Plasma is basically a partially ionized gas, meaning its molecules have been excited to such a degree that electrons escape their orbits. Glowing ensues. But more importantly, the process of turning a gas into a plasma can be harnessed to lay down or strip layers off of materials one atom at a time. This is how the electronics industry makes nearly all integrated circuits, and it’s the technology that drove their miniaturization. Those microprocessor chips inside your phone and your computer? Their many layers of materials were deposited or etched away by plasma-based processes.
Using similar techniques, Weikart’s team engineered a way to suck all the air out of plastic containers—like a vial, syringe, or another shape—and replace it with silicon dioxide gas. Then, at a very low pressure, they apply an electromagnetic field across the container, which converts the gas into a plasma. As their electrons kick off, the silica and oxygen molecules become very reactive and attach to the polymer surface. There they stick. The result is a layer of pure silica, otherwise known as glass. “An oxygen molecule is a tiny substance, so in order to keep it out you need a really, really dense barrier,” says Weikart. “That’s why we put down this very dense form of silica.”
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The silica layer stretches 20 to 50 nanometers across. It’s sandwiched between an adhesion layer, which helps it stick to the plastic, and a sheet of silica mixed with carbon to protect the glass layer from dissolving into the contents of the container. All together, the plasma-deposited coating measures less than half a micron thick—about 1/10th the diameter of a red blood cell, and 1/150th the width of a human hair.
Prior to the pandemic, SiO2 was making about 14 million of these 10-millimeter glass-coated plastic vials per year for pharmaceutical clients. But it had yet to break into the vaccine market. Since the Barda contract was signed, the company has hired 123 additional employees and is now on track to produce 40 million vials annually, according to SiO2’s chief business officer, Lawrence Ganti. He expects they will hire at least 100 more people as they ramp up to meet the contract’s additional demands, which include scaling to 120 million vials by November.
Ganti says SiO2 is currently shipping the vials to five vaccine producers, including Moderna, as well as a few companies making treatments for Covid-19, which he declined to name. Not all of them have been selected for Operation Warp Speed. Though the contract is intended to support companies Barda has invested in, Ganti says it also permits SiO2 to sell to non-Barda-funded pharma clients.
Yaday says he is conflicted about the research agency’s decision to back a relative newcomer in the midst of a global pandemic. “Is this a good move for innovation? Absolutely,” he says. In the long run, Yaday expects companies like SiO2 to be essential in creating new, more nimble ways to package drugs and vaccines that don’t rely on sand and glass. But should the US wager its ability to deliver large volumes of a Covid-19 vaccine on a new technology—especially when there are several large glass bottle manufacturers in Europe with long track records and deep ties to the vaccine industry? “That’s the part I just don’t know,” he says.
Updated 6/26/2020 4:25 pm ET: This story was updated to correct the amount of a contract between Barda and SiO2. It is for $143 million, not $143.
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