Integrating process safety values into organic chemical manufacturing guides Alessandro Agosti’s work each day. He is the head of process safety and reaction scale-up at Olon, an Italy-based manufacturer of pharmaceutical chemicals.
Olon’s chemists, engineers, and process safety experts help pharmaceutical companies bridge the gap from research and development to manufacturing. Agosti is an organic chemist by training and his role is to determine how pharmaceutical companies can smoothly and safely transition to plant-scale production of new chemicals.
Efficiency, high-quality products, and safe manufacturing methods go together, he says. An unsafe process is wasteful and expensive, a maxim he stresses as he scales up production for client companies.
▸ Hometown: Bergamo, Italy
▸ Current position: Head of process safety and reaction scale-up, Olon
▸ Education: BA, industrial organic chemistry, University of Milan, 2004; PhD, organic chemistry, University of Bern, 2008
▸ Motivation: “I am curious in life and always seek new stimuli, which I think is important in work as well. Avoid limits and try to always challenge oneself.”
▸ Book recommendation:Chernobyl: History of a Tragedy by Serhii Plokhy
▸ Favorite multimedia: Economist Radio, the Guardian’s Audio Long Reads, and TED talks
▸ Special interest: Archery, particularly working with people with disabilities
“If you love organic chemistry, this is a dream job,” he says. “Studying reactions is never boring. They are always changing and there are always surprises, and some can become quite weird when you examine the details,” he says. In one recent case, for example, simply modifying the order in which chemicals were added to a reactor minimized impurities and drastically increased stability.
Agosti grew up near Milan, in an area with a history of chemical and pharmaceutical manufacturing. Economically, the region has benefited greatly from manufacturing. The industry’s influence is visible in regional schools and a culture that emphasize the importance of technology and the sciences, he says. That environment helped lead him to a science education.
His home was Bergamo, a medieval city and tourist destination with Roman roots. The old town is known for its red tile roofs and cobblestone streets, and it is encircled by Venetian defensive walls. He now lives a few kilometers away.
Bergamo is also near the town of Seveso. In 1976, before Agosti was born, an accident at a chemical plant owned by Roche subsidiary Icmesa resulted in a release of a chemical cloud including sodium hydroxide, 2,4,5-trichlorophenol, and highly toxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). No people died directly from exposure, but thousands of animals died or were slaughtered out of fear of contamination.
The community was shocked and angry. The accident led to a host of scientific studies and new standardized safety regulations, known collectively as the Seveso Directive. First established by the European Economic Community in 1982, the directive was most recently updated by the European Commission in 2012.
Seveso, Agosti says, was one of the drivers of his interest in chemistry and underscored the importance of process safety.
He began his chemical studies as a child and carried them on to university and postdoctoral studies in Italy, Switzerland, and the US. Then he embraced the chemical industry full-time. He worked at the Laboratory for Process Research at the University of Zurich before moving back to Italy and on to Olon.
Olon provides pharmaceutical products as well as process development and manufacturing support for pharmaceutical companies worldwide. The company manufactures active pharmaceutical ingredients either for the generic market or for custom development and manufacturing. It has 11 facilities: 8 in Italy, 1 in Spain, 1 in the US, and 1 in India.
Most of Olon’s production sites host a dedicated research and development team to develop chemical syntheses, Agosti explains. This fosters close contact between Olon’s process development experts and the production staff.
As a research scientist in process development, Agosti leads the process safety and reaction scale-up group, which travels globally to work with site R&D teams to help transition from making a few grams of a substance to large-scale production.
“We support scale-up activities such as crystallization and reaction understanding, and we use simulation software to understand the expected behavior of the system once it is in a large reactor,” Agosti says. “We try to embed process safety straight from the beginning of the development of the scale-up design.”
The importance of process safety is not always recognized in the production design process, he notes.
“Most of the time process safety is the last step of the engineering development. But then there is no time to make the changes. We are trying to train the R&D team to find and correct potential process safety problems at the beginning—change the sequence of reactions or the chemical conditions, for instance—not as the last step in the development process, when you have, for instance, only 10 days left before start-up.”
In addition to his work at Olon, Agosti is an associate editor of the journal ACS Chemical Health & Safety (ACS also publishes C&EN). Agosti stresses that safety, control, and product quality are intertwined.
“A safe process is also for me a high-quality process. A safe process means you have full control of your transformation and you understand the thermal behavior and other attributes of your reaction,” he explains.
“An unsafe process, like a potential runaway, may not lead to an explosion, but lack of control also will lead to quality issues, and the result may not be a high-quality product.”
Also, good process design includes evaluating the environmental footprint and developing efficient catalytic systems to minimize the use of raw materials and generation of waste, Agosti says.
“I think everyone involved in the manufacturing process should make these considerations,” Agosti says. Developing good chemistry to preserve the earth should be a fundamental goal, he believes.
Agosti has taken this message to local schools he attended years ago, meeting with students and faculty and teaching seminars on the roles of chemistry and other sciences in drug development and production.
“I am glad to be back where I grew up and to return what I obtained from a public education,” he says. He believes that chemistry professionals have a responsibility to get more involved in education at secondary schools and universities, particularly when it comes to safety and lab practices.
Noting a spate of lab accidents around the world, Agosti says, “What is called for is more than series of rules; there is a need to create a mindset for safety.”
Jeff Johnson is a freelance writer based in Washington, DC. A version of this story first appeared in ACS Chemical Health & Safety: cenm.ag/alessandroagosti.