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Corning accelerates COVID-19 vaccine delivery with an innovation in pharmaceutical packaging
A radical new glass formulation is poised to cut vaccine manufacturing timelines in half. Design of experiments in JMP® paved the way for its discovery.
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Challenge: Even with COVID-19 vaccine distribution underway, it could take months or even years for pharmaceutical companies to manufacture adequate quantities to satisfy worldwide need. The speed at which manufacturing production lines can operate has long been limited by one critical factor: Even the best medical-grade glass vials are prone to cracking and chemical degradation if plant machinery runs too fast.
Solution: Scientists and engineers at Corning used design of experiments to develop a revolutionary new glass formulation – Valor® Glass – that is purpose-built to accelerate pharmaceutical manufacturing. JMP and JMP Pro put best-in-class DOE tools into the hands of every scientist involved in this effort.
Results: Corning’s innovation is set to increase manufacturing throughput by as much as 50%, setting what Vice President Brendan Mosher has called “a new standard for quality and performance in pharmaceutical packaging.” By increasing the capacity of the standard pharmaceutical production line from 300 vials per minute to 750, Valor Glass is set to accelerate delivery of COVID-19 vaccine as soon as they secure regulatory approval.
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As nations around the world face the deadliest pandemic in a century, scientists have raced to develop a safe and effective vaccine for COVID-19. As of September 2020, 40 vaccine candidates had entered clinical trials, and more than 90 were under active preclinical investigation in animals. But vaccine discovery is only the first hurdle to attaining worldwide herd immunity through vaccination; manufacturing at scale will almost certainly cause a major bottleneck in distribution.
With many vaccine candidates requiring multiple doses per person, experts estimate that between 7 billion and 15 billion doses
of vaccine will be required worldwide in 2021 alone. Pharmaceutical companies now face unprecedented pressure to accelerate production much in excess of previous standard timelines. “The challenge is not making the vaccine itself, it’s filling vials,” Pascal Soriot, Executive Director and CEO of AstraZeneca, told reporters in mid-2020.
As is the case for many of the novel COVID-19 vaccine candidates to emerge in 2020, vaccine is made in large batches but packaged in small glass vials, each containing between one and ten doses for distribution. The process by which vials are filled, however, has historically been a source of delays and in-process stoppages that slow the speed at which a drug or vaccine can reach patients.
Modern pharmaceutical production lines are highly automated, and while state-of-the-art machinery can in theory operate at top speeds, doing so causes even borosilicate vials – the industry’s gold standard – to break or delaminate particles into the vials’ contents. Borosilicate’s chemical durability at extreme temperatures is also a concerning limitation for manufacturers of vaccines that require ultra-cold chain storage, much like the COVID-19 vaccine developed by Pfizer and BioNTech in 2020.
To resolve these and other glass-related production limitations, Corning Incorporated established a development partnership with several pharmaceutical industry leaders. As early as 2012, scientists began exploring the glass formulation space to develop a new premium product for use in life sciences applications. Corning and its partners tested over 200 different glass compositions before creating a novel aluminosilicate glass that is more than 10 times stronger and more chemically durable than the previous gold standard.
Valor® Glass was born, and a vital new innovation came to market just months before COVID-19 was discovered in Wuhan, China.
“Valor Glass sets a new standard for quality and performance in pharmaceutical packaging,” said Brendan Mosher, Vice President and General Manager of Corning Pharmaceutical Technologies. “It is purpose-built for pharmaceuticals and is uniquely positioned to enable faster, more reliable drug manufacture and delivery – attributes that are critical to the SARS-CoV-2 pandemic response.”
This is the story of how Corning built a deeply knowledgeable R&D organization and created a new category of glass that doubled pharmaceutical production capacity overnight.
A quest to deliver on three fronts: chemical durability, strength and machinability
What began in 2011 as a very small project evolved over time to an entire division within Corning’s Life Sciences organization. At first, explains Michael Anderson, now Senior Statistical and Measurement Development Engineer, the team was aiming primarily to improve the strength and chemical durability of pharmaceutical packaging in collaboration with its original development partner, Merck. Anderson joined the team around 2013, first as a statistician supporting the project’s engineering group and then as metrology expert in R&D.
Corning was aware that one of the pharmaceutical industry’s most concerning manufacturing problems was boron contamination; especially caustic drugs were causing the lining of traditional borosilicate glass vials to delaminate over time, ultimately spoiling whole batches of drugs and vaccines. “But the pain points that pharmaceutical makers face change over time,” Anderson says; once Corning had a solution for chemical durability, they were then asked by their development partners to resolve the problem of breakage. Eventually, Pfizer also came on board, and factory optimization took center stage as scientists sought to reduce the friction caused by traditional vial coatings.
“If you want to fill 500 million vials on existing equipment in the next six months, suddenly how fast those parts move is your No. 1 concern,” Anderson explains. “That’s the feature we call machinability,” that is, how fast a manufacturing line can run.
To tackle all three challenges in a single glass formulation required years of experimentation, building product knowledge, going back to the drawing board on occasion and optimizing incrementally. It has been a long process, Anderson says, but one that owes its success to Corning’s deep roots in glass science and dedication to statistical process knowledge.
At Corning, everyone is a process engineer
Corning is an organization in which the scientific spirit runs deep, and its directors – many former R&D scientists and statisticians themselves – have championed the widespread adoption of statistical approaches. Statistics, Anderson explains, is part of every job description within Corning, from materials to manufacturing to supply chain logistics. Their mantra? Everyone is a process engineer, and every process engineer has to have data analysis skills.
While the company may set high expectations for statistical literacy, however, Corning also provides employees with best-in-class equipment and tools to implement efficient and effective statistical methods and experimental design. Unlike other companies, Anderson says, “Corning has prioritized making sure that people have the tools they need.”
For Corning, that involved licensing JMP and JMP Pro software, an industry favorite that pairs robust statistics with user-friendly visualization. “JMP will deal with an unbalanced data set. It will tell you what the risks are, deal with it, and let you make an intelligent choice rather than just saying no,” Anderson says. What JMP has to offer is “a competitively priced product that is a mix of both common use for any engineer and advanced-use statistical tools that allow you to look at any problem that someone in the engineering and research fields would have to deal with on a daily basis.”
In the development of what became Valor Glass, Anderson laughs, “it's almost hard to think of when JMP wasn't used.” One of the key areas that was proof of concept for the software was in design of experiments (DOE).
Design of experiments, a more strategic approach to experimentation where even failures provide valuable insight
DOE is a branch of applied statistics that uses controlled tests to identify and analyze the factors that affect a parameter or group of parameters. In DOE, scientists have a robust data collection and analysis approach that provides a better picture of interactions between factors and allows for the manipulation of multiple input factors at one time.
Anderson explains that DOE in JMP was the key to optimizing component ratios and variations in process setups for Valor formulations, among other things. “There’s the chemical strengthening that is used to make the glass so strong and also the external coating that is used to make the vials fly twice as fast through fill lines in factories,” he explains, adding that within each characteristic, there are other sub-characteristics that also require optimization.
“Truism in materials: there's no one-size-fits-all. If you increase one [factor], typically you compromise something else. We wanted our coating to be as transparent as possible but also to be able to survive whatever processes it goes through [when it is filled], for example,” he says. “The amount of formulation and response surface and mixture DOEs that we have done in order to optimize component ratios to figure out sub-components within those components is tremendous.”
Fortunately, Corning has prioritized R&D at the enterprise level in a way that many of its competitors have not; by allocating enough funding for experimentation to allow development teams to fail. “Being able to fail is expensive, but it’s a critical part of experimentation,” Anderson says. “And at Corning, I have never encountered any significant resistance around conducting experiments. We want to learn as much as possible for the money that we’re spending. When I say, ‘I want to do this as a fully designed experiment,’ I never hit resistance. [DOE] is bred into Corning at this point.”
In JMP, a one-stop-shop for DOE and statistical learning of all kinds
Design is only half of DOE, however. Analysis is equally important, regardless of which type of design a team implements. In the development of Valor Glass, it was crucial for the team to not only identify the key factors, their strengths and interactions, but also to understand how these effects looked when plotted, Anderson explains. In some cases, it was as simple as visualizing uniformity down the side of a vial; “by visualizing it, you'll immediately know whether or not something's wrong.”
Data visualization speeds the analytical process by allowing for quality checks at a glance and is an area in which JMP excels, Anderson says. An array of Profilers in the software are an easy way for users to interactively explore design spaces, visually spotting viable operating regimes and factor set points. “That immediate ability to interactively graph your data is what sold me on JMP 29 years ago – and really, it continues to. I think everyone loves Graph Builder as a center of their JMP world,” Anderson says.
The Graph Builder platform in JMP is often seen as a point of entry for those new to applied industrial statistics, and Corning’s extensive catalogue of internal training and continuing education resources helps users build skills from these foundations. The company’s internal statistics classes have evolved to keep pace with the tools, including Corning’s entry-level Interpretation of Data course, Anderson says. More advanced courses include DOE, quality systems and measurement system analysis.
Among these development opportunities, Corning provides specialized JMP training through a collaboration with SAS Education and annual JMP Days offered at beginning, intermediate and advanced levels. An internal forum also hosts user groups focused on a wide range of applications.
From 30 minutes to mere seconds, custom scripts streamline repeat analyses
As the sheer volume of data intake grows with Corning’s Digital Transformation initiative and factory technologies, not just at Corning but across the industry, become more integrated, R&D teams are looking for custom tools to query and analyze data – and avoid the potential pitfalls of data siloing. Scripting, Anderson explains, is helping engineers to customize add-ins that can pull data from multiple databases at once, optimizing the benefits the organization gets not only on a production level but also in development.
Custom scripts written in JMP Scripting Language also help to bypass time-consuming data cleaning tasks and repetitive analyses. And it’s as straightforward as setting the conditions for data capture and organization. “At the end of the day when [the engineers] are done measuring some parts, I'll go in and run a script that will take me 15 seconds,” Anderson says. “Doing this by hand [as we did in the past] takes me at least 30 minutes.”
From 300 to 750 vials per minute, Valor Glass doubles production line speeds – for COVID-19 vaccines and beyond
A formulation meticulously optimized on all the parameters, Valor Glass set a new gold standard for pharmaceutical packaging upon its release and approval by the FDA in late 2019. Its benefits were clear: while traditional production lines could only run at speeds of between 300 and 400 vials per minute, Valor Glass vials enable manufacturers to run plants at speeds of up to 750 vials per minute – more than doubling a facility’s overall capacity virtually overnight.
By the first few months of 2020, as the novel coronavirus SARS-CoV-2 was spreading rapidly around the world, it became apparent just how timely Corning’s innovation was. That innovation was recognized by the United States Department of Defense in June 2020 when the Biomedical Advanced Research and Development Authority awarded Corning a $204 million grant to rapidly expand the production of Valor Glass.
With Valor Glass now set to accelerate delivery timelines for COVID-19 vaccines around the world, Corning’s 10-year investment in meticulous, data-driven R&D has paid off not only in design firsts, but in a real impact on society. Hastening vaccine distribution may quite literally save lives.
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