Vials vital for COVID-19 vaccine

Researchers around the world are edging closer to a safe and effective vaccine to halt the COVID-19 pandemic, with more than 300 candidates in development. Once one or more vaccines against SARS-CoV-2, the virus that causes the disease, gain regulatory approval, the next step is delivering the product to health-care providers. They, in turn, will inoculate people.

That distribution will require packaging. Specifically, this means strong vials that protect their contents and won’t chemically react with the vaccine solution. On a global scale, this adds up to a dizzying number of vials—hundreds of millions of small, cylindrical bottles that each will hold at least one dose of vaccine.

Earlier this year, worry spread that a shortage of these small bottles would hamper distribution of the vaccine. Since then, makers of pharmaceutical vials around the world have announced they are stepping up their production.

Contrary to some earlier reports, companies contacted by C&EN say they and their suppliers have enough raw materials, including sand, to meet the additional demand. The challenge instead is to turn those raw materials into enough vials to distribute a COVID-19 vaccine widely. Companies say they’re optimistic about meeting that goal.

Vaccines, like many liquid pharmaceutical products, are generally packaged in glass—but not the commonplace glass of beer bottles or pickle jars. For decades, drugmakers have depended on vials made of borosilicate glass, though containers crafted from newer materials are entering the market.

Borosilicate glass originated with the German chemist and glassmaker Friedrich Otto Schott, who invented it in 1897. The company he founded, Schott AG, continues to produce Fiolax borosilicate glass for pharmaceutical uses. Jörg Döscher, head of strategic marketing and innovation for the company’s tubing business, says Schott and other companies manufacture 50 billion borosilicate glass containers each year to bring vaccines and other medical products to patients.

Like the soda-lime glass found in windowpanes or food and beverage containers, borosilicate glass is made primarily from silicon dioxide, the main constituent of sand. But soda-lime glass contains proportionally more sodium oxide, which is derived from sodium carbonate—also called soda ash—and more calcium oxide, which originates from calcium carbonate—limestone. Borosilicate glass has added boron oxide and other compounds that help stabilize the glass, Döscher says.

Borosilicate glass “is a chemically inert material and remains unchanged under all normal environmental circumstances,” Döscher says. It is stable and retains its shape at temperatures as high as 500 °C and as low as 0 °C. These properties allow borosilicate vials to store drugs safely and prevent contamination, he says.

“Pharmaceutical products really need to interact as little as possible with the packaging,” says Robert Schaut, scientific director for Corning Pharmaceutical Technologies. Shifts in pH introduced by packaging can speed up degradation of delicate active ingredients, for example. Metals or other contaminants can leach out of vials or other packaging materials, such as elastomer seals on tiny bottles. For some products, the migration of boron from vials can speed up degradation, Schaut says, meaning that borosilicate glass isn’t the best packaging material for them.

Borosilicate glass can’t rest on its laurels. Corning, maker of the popular Pyrex borosilicate glassware, and other companies are crafting medical vials made from novel materials. They say these materials resist the process of delamination, in which thin bits of glass flake—or spall—off the interior. The tiny chips of glass can interact with the ingredients in a vial, leading to drug degradation, Schaut says.

In recent years, Corning researchers took a close look at what causes delamination in borosilicate containers.

They found that when borosilicate tubing is heated to form a vial, the material’s temperature gets high enough for boron and sodium to evaporate from the glass’s surface, says Schaut, a materials scientist. This evaporation in turn causes changes in the surface of the glass.

“It’s those changes in surface chemistry, on the order of a few hundred nanometers, that ultimately cause these flakes to form later when they’re exposed to the drug product,” Schaut says. “You can imagine how excited we were as chemists and scientists to put the pieces together of how that process occurs.”

Corning researchers tweaked the ingredients in soda-lime glass by adding aluminum and some potassium to develop a formula that prevents delamination and resists breakage, he says. From this work emerged Valor glass containers, which Schaut coinvented. The company debuted these containers in 2017, describing them as superior to their borosilicate rivals.

Corning’s novel product is attracting sales. Pfizer signed a multiyear deal with Corning in May to buy Valor glass vials for some of its drugs that are already on the market. A month later, Corning got $204 million from the US Biomedical Advanced Research and Development Authority (BARDA) to expand domestic manufacturing of Valor glass vials to hold COVID-19 vaccines.

Another company, SiO2 Materials Science, is turning to plastic medical vials that are lined with a glass-like coating.

Lawrence Ganti, president and chief business officer of SiO2 Materials Science, says the company’s vials start as shells of a medical-grade cyclic olefin polymer or copolymer. Using a process called plasma-enhanced chemical vapor deposition, the company applies a nanoscale layer of organosilica to the inside of the plastic shells, creating a chemically inert interior, the company says.

“This coating provides the protective properties of glass but does not have any of the typical problems of glass,” Ganti says. “We have fused the two materials into a better, safer, more durable hybrid.” The company’s website says the resulting vials are mechanically strong and shatterproof.

The hybrid products also have a much lower carbon footprint than glass vials, Ganti says, because the manufacturing process requires less heat and water than glass vial production.

In June, the firm landed a $143 million contract with BARDA to make vials for COVID-19 vaccines and therapeutics.

Regardless of the materials they use for medical vials, manufacturers across the globe are stepping up output to meet demand for packaging COVID-19 vaccines. For instance, DWK Life Sciences announced earlier this month that it was expanding and modernizing its facility in Tennessee to double production capacity for its borosilicate glass vials. The company makes products with brand names familiar to those working in laboratories—Duran, Wheaton, and Kimble—though borosilicate lab glassware has somewhat different qualities than the material used to shape drug vials.

Meanwhile, Italy’s Stevanato Group inked a deal in June with the Coalition for Epidemic Preparedness Innovations (CEPI) to supply 100 million borosilicate glass vials. Each will hold 20 doses of a COVID-19 vaccine, Stevanato says. CEPI, a partnership founded in 2017 to develop vaccines for future epidemics, has formed a coalition with the World Health Organization (WHO) and the global vaccine alliance Gavi. The coalition, called Covax, intends to distribute 2 billion doses of a COVID-19 vaccine by the end of 2021 and to “guarantee fair and equitable access,” according to the WHO.

Glassmakers suggest they’ll be able supply what the world needs once vaccines get regulatory approval. In June, the CEOs of Stevanato, Schott, and the German firm Gerresheimer issued a statement confirming their readiness to supply the needed borosilicate glass containers. Gerresheimer CEO Dietmar Siemssen says in the statement, “We are fully prepared to support the global market demand for potential Covid-19 vaccines with our vials.”