The average non-scientist probably doesn’t give chromatography much thought — or even have a solid idea of what it is. But patients who take certain drugs for cancer or autoimmune disease depend on it. Most of us benefit from chromatography, in products such as the foods we eat and the computer monitors that sit on our desks.
In the journey from lab bench to store shelves, the development of those products involved chemical engineers such as Giorgio Carta, the University of Virginia School of Engineering’s Lawrence R. Quarles Professor of Chemical Engineering. Carta is well-known in the area of preparative and process chromatography, terms that encompass several techniques for separating mixtures of chemical or biological substances into individual components. Widely published and cited as an author or editor of papers, journals and books, Carta has mentored dozens of graduate students and many more undergraduates at UVA for 35 years. His lab specializes in processes for isolating biological molecules for technology applications, often referred to as bioseparations.
Since 2009, Carta also has chaired or co-chaired the PREP International Symposium, Exhibition and Workshops on Preparative and Process Chromatography, Ion Exchange, Adsorption Processes and Related Separation Techniques. The 2019 symposium took place in July in Baltimore with Carta once again at its helm. He has served on its organizing committee since 1997.
Preparative chromatography is a purification process — isolating a substance for a specific use such as manufacturing a therapeutic drug, food product or electronics, or for scientific analysis. “Process” in this context refers to preparative chromatography that takes place at the manufacturing scale. The symposium, now in its 32nd year, is the longest-running, most recognized international scientific conference and exposition in the field.
Leading academics and representatives of manufacturers from numerous industries, including several companies that underwrite the symposium, traveled from across the United States — and from 24 other countries — to attend the symposium. There were more than 350 participants, including graduate and undergraduate students, whose attendance, in many cases, was funded by the corporate sponsors. Most of the students in Carta’s lab were there to learn but also to help run the four-day conference.
With three organizing objectives — continuing education and workforce training, exhibiting the latest technology in the field and, most importantly, scientific exchange through research presentations — the symposium is critical to industry and academia alike. It is also a conduit through which companies discover rising talent in the field — students who conversely build the networks they need to find excellent jobs when they graduate.
Antonio Ubiera, a senior director in downstream process development, biopharmaceutical product development and supply at GlaxoSmithKline, has been to the symposium numerous times, including when he was a student, and several members of his team were there in 2019. Attendance offers myriad advantages, he said.
“It’s an annual meeting of the best minds in process chromatography,” said Ubiera, who earned his Ph.D. in 2004 from UVA, where he worked in Carta’s bioseparations lab. “It provides an excellent opportunity for GlaxoSmithKline scientists to present ongoing bioprocess research, receive peer review, and stay up to date on the state of the art of chromatography. The opportunity to have an ongoing dialogue year after year is fantastic, as industry and academics come together to discuss latest trends, new advances, and work to expand the field. In this way, we get better at what we do as bioprocess scientists and engineers.”
“Getting better” is a salient point for the manufacture of products with the potential to do so much good, but in which precision and efficiency are so critical to the people who depend on them.
Carta’s lab focuses on advancing the underlying science — and developing or improving methods and materials — used in chromatography for bioseparation applications to make them more effective and efficient. The basic science applies across all chromatography applications and scales, from the lab to commercial production. But, Carta said, it’s important to understand why bioseparations and the subset of protein separations are distinct areas of study within chromatography.
Biological molecules have three characteristics that make them trickier to deal with than ordinary organic molecules: They are large, highly complex and inherently unstable.
“Unlike, say molecules derived from petroleum, they have to be treated gently because they could be altered in ways that can impair their biological functions,” Carta said.
In the case of biopharmaceutical drugs, for example, molecules that work in the lab to block the immune system or attack cancer cells, could be rendered unsafe or ineffective by impurities or improper treatment. Process chromatography is one of the principal means of achieving the necessary purity on a manufacturing scale.
“The potential dangers of contaminants in these drugs could be large, so the process has to work and it has to work well at reasonable costs,” Carta said. “It’s extremely important to society that we promote the education of people in this field — that we promote scientific progress, but in close connection with the industrial technology that has been developed.”
Biopharmaceuticals — therapies derived from biological sources, such as proteins — form a relatively new class of drugs that have emerged over the past 30 or 40 years, but large-scale production has ramped up even more recently. While life-changing or life-saving, these medications can be prohibitively expensive. Carta pointed to two examples: Herceptin, one of the earlier biological drugs, which treats a particular type of breast cancer, and Humira, which is prescribed for an array of autoimmune conditions, from psoriasis to Crohn’s disease.
“Herceptin really, really saves lives,” Carta said. “There is no question that a lot of women are alive today, hundreds of thousands, maybe in the millions, because of it, but it’s extremely expensive. The same with Humira — people with advanced rheumatoid arthritis are reborn when they take this drug, but at a huge cost.”
One problem is that pharmaceutical companies must fund all the therapies they develop that don’t pan out with the profits of those that do. Many will fail unavoidably, Carta said.
“Say the protein works but is overly unstable. If you can’t make it reliably and safely, it’s of no use. This is where chromatography research can help,” he said. “We can potentially shorten the time from discovery to clinical applications. Obviously, it’s not sustainable that we have treatments that cost tens or hundreds of thousands of dollars per person per year. Improving the process and reducing the cost will come eventually.”
Preparative chromatography relies on contact with a matrix packed into a column — essentially a tube of varying sizes depending on the scale of production — through which the molecules to be purified must pass, Carta explained. Engineering the matrix to interact in certain ways with the molecules is an example of the work he and his students do in the laboratory.
"Chromatography research can potentially shorten the time from drug discovery to clinical applications. Improving the process and reducing the cost will come eventually."
Lawrence R. Quarles Professor of Chemical Engineering Giorgio Carta
His students regularly publish in journals and present their work at professional conferences, often winning awards for their research (read more here). Industry funds nearly all of their work; current and recent sponsors include Ajinomoto Co. Inc., Bio-Rad Laboratories, MedImmune, Merck & Co. Inc., Pfizer, and Bristol-Myers Squibb.
Because of these relationships — and possibly because a relatively small number of U.S. university labs focus on preparative and process chromatography in contrast to the international research community — Carta’s graduates are always in demand by employers for the research skills they develop in his lab.
“I also think there’s huge opportunity for new faculty to become involved in this area of research, because industry is very interested in funding this work,” Carta said. “One, they want to make progress in the field, and two, they recognize that their funding will help create Ph.D. students who are trained and educated in this area.”
Industry representatives accounted for more than 80 percent of the symposium’s 2019 attendees, up several points from a decade ago when Carta became its chair, but on par with the past five years. Part of what makes the symposium such a draw for industry and academia is a schedule packed with exhibits, tutorials and training workshops in addition to the presentation of new research. Education is a key objective of the conference, Carta said.
For similar reasons, a two-week short course on protein chromatography that Carta led twice a year on Grounds always filled to capacity. The course, which he developed with University of Natural Resources and Life Sciences Vienna Professor Alois Jungbauer, helps fill a need for engineers, scientists and technical managers, as well as students, who want a deeper understanding of chromatographic processes and their scale-up.
Ubiera noted that GlaxoSmithKline has regularly sent at least two scientists to participate in the short course at UVA in years past, for much the same reasons it is a corporate sponsor of the PREP symposium.
”It helps to develop our people and advance our ability to design efficient and well-understood manufacturing processes that ensure the quality, safety and reliable supply our products,” Ubiera said.
“Giorgio’s leadership means that UVA chemical engineering is known worldwide for producing and promoting important science and education at all levels in bioseparations and process chromatography,” said William Epling, chair of the Department of Chemical Engineering. “He is also a dedicated teacher who has mentored multiple generations of engineering leaders, who are working every day to change people’s lives for the better.”