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Your window into Astellas’ world of patient-centered and science-driven healthcare, as told by the experts who bring it to life.
Spring 2022.
Researchers working in manufacturing process development shared a common challenge.
"If only we could test more reaction conditions, we could find a better manufacturing process."
Delivering new medicine to patients requires more than identifying a promising drug candidate. Researchers must also establish a reliable way to manufacture it. In recent years, medicines produced through chemical synthesis have become increasingly complex, and the number of reaction conditions that must be assessed during manufacturing process development has continued to grow. Some manufacturing processes involve around 20 steps before reaching the active pharmaceutical ingredient, each requiring multiple variables to be evaluated.
The more conditions researchers can compare, the greater the chance of identifying a better process. In practice, however, time and materials are limited to pursue all the experiments they wanted to try.
Astellas researchers were determined to change that. A shared ambition led to the development of a robotic high-throughput experimentation (HTE) platform that could efficiently compare and evaluate a large number of conditions.
Yuta Sumii
Senior Researcher
Process Technology Exploration
Technology Scouting & Integration Labs
"We wanted to explore more possibilities and create an environment where researchers could make better decisions. At that time, we felt frustrated because we had limitations in how much we could explore. Testing and comparing more conditions would help us identify better manufacturing processes," says Yuta Sumii, who was leading manufacturing process development for several projects.
Researchers began meeting whenever they could, discussing ideas and developing prototypes in between their day-to-day work. By combining commercially available equipment with their own ideas, they first developed a semi-automated experimental platform.
Yuta recalls, "It started as a grassroots effort. Everyone genuinely believed there was a better way and wanted to find it. We met every week to discuss performance and challenges, continually refining the system we truly needed."
Mikio Ishihara
Technology Scouting Lead
Technology Scouting & Integration Labs
The semi-automated experimental platform significantly expanded the range of reaction conditions researchers could explore. As the team began using it, however, they also started to see what would be needed to make it truly practical.
"Todays candidate compounds are increas'ingly complex to manufacture, yet we can't spend more time developing the processes. Imagine assembling a complicated piece of furniture with a 20-page instruction manual within the same time for one with only five pages. You quickly realize the old way of working just doesn't get you there," says Mikio Ishihara, who has led this initiative.
"If we wanted to run more experiments while assuring consistency and reliability, we needed a higher level of automation."
Researchers were looking for more than automation. The system had to work even in the early stages of development, when only small amounts of material were available.
It also had to deliver consistent results, every time. As the team shared the lessons learned and the challenges they were facing, they reached out to Shimadzu Corporation (Shimadzu) and brought them in as a key partner in the effort.
Because the researchers had built and operated the HTE platform themselves, they could clearly explain what they needed and hoped to achieve. Astellas researchers spoke candidly about the challenges in creating and delivering greater VALUE faster for patients, and Shimadzu worked alongside them to find solutions. As those conversations continued, trust between the two companies grew, leading to full-scale joint development.
Creating a robotic HTE platform involved overcoming many technical hurdles. One of the biggest was automating the sealing of reaction vessels. It may sound simple, but it turned out to be one of the most significant technical challenges faced by the team.
The approach uses approximately 100 small glass vessels to evaluate many reaction conditions simultaneously. Every vessel must be securely sealed, even though the caps are exposed to harsh conditions and can degrade over time.
Mikio explains, "Existing automation systems could not deliver the performance we needed. We had to seal many vessels automatically while maintaining consistent quality and reliable experimental results."
Through repeated experiments and data-driven decisions, Astellas and Shimadzu identified the best approach. Those efforts became the foundation for the robotic HTE platform.
Yuta recalls, "When we first saw the completed machine spring to life, members of both companies broke into applause. All the excitement and energy we had poured into the work was beginning to connect to VALUE for patients. It was a moment that reminded me how rewarding this work is."
The robotic HTE platform has fundamentally changed the way researchers conduct experiments to manufacture new medicines.
Reaction conditions that once had to be evaluated one at a time can now be tested in parallel. The system can also conduct experiments with as little as approximately 5 mg of material. This enables researchers to explore a wide range of conditions from the early stages of development, even when only small amounts of a candidate compound are available. This helps accelerate development.
Mikio explains, "What once took researchers a week to evaluate across 10 conditions can now be expanded to as many as 2,000."
Researchers can now evaluate conditions that previously would have been left unexplored because of time or material constraints. As a result, they can make better decisions based on stronger evidence.
The robotic HTE platform is now being used in multiple projects, including oncology programs. Yet the team is already looking ahead to what comes next.
Mikio says, "Automation is only a milestone. Our next step is to make better use of the large volumes of data generated through experiments. We envision AI supporting researchers' decision-making, while researchers continue to make the final call. Our goal is to create an experimental environment that enables both greater speed and higher quality."
Driven by a passion to create and deliver greater VALUE faster for patients, the team continues to open up new possibilities.
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