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Efficient Lab Equipment at the Heart of Drug Development

17 December 2015

Mr. Shigeru Yonekubo at Kissei Pharmaceutical Co., Ltd. is right at the center of advanced drug development. In this interview, he explains how his company benefits from flash purification systems and organic microwave synthesizers from Biotage.

 

"Our vision is to be a research and development oriented company which develops innovative pharmaceuticals for the people of the world. We develop new prescription drugs and provide them at the forefront of medical care, in particular for our primary areas of research: the urinary system, kidneys and dialysis, metabolism and endocrine system, gynecology, ophthalmology, and our recent entry into the central nervous system."

– Why has Isolera become your first choice?

“The quality is good. It has good gradient accuracy, the flow rate for the pump itself is stable, and there are few pulsations in the flow. In addition, Isolera allows for real-time monitoring, so we can see the chromatogram on our computers over the intranet. It’s really convenient to monitor the progress while doing other work, and then get the compound when it elutes. Our researchers want a system that operates and performs well under pressure. We don’t just repeat the same reactions. We can’t get a patent for the same compound twice – that would make our work pointless. Instead, we need to keep creating things that no one else in the world has done before. So we are always trying something new, that is how we spend every day. We need a system that does what we expect. If I change A, then I want B to happen. In this sense, Isolera is extremely good, it is easy for us to run purifications under our specific conditions.”

– Purification is a post-processing step. It seems reasonable to not spend too much time and money on it.

Isolera flash purification system.

“That’s correct. When I entered the company and we did about 20 purifications a day with the open column method, it took over half a day to complete. Now with the automated purification systems it can all be completed in two to three hours. It only takes about five minutes per purification, and saving time is very important for researchers. Each purification takes time to set up, time to run, and time to check. With these instruments, it is ready almost immediately. It also reduces the amount of solvent used significantly, which is becoming increasingly important for companies recently. It doesn’t matter how low the initial costs are if the running costs are high. Reducing our impact on the environment is also an important responsibility. The key reasons we transitioned to automation are that each purification is completed in a short time, and we can reduce the amount of solvent used.”

– How do you use the Spektra software features?

“After using it I think it’s great. We didn’t understand how good it was until we tried it. Pharmaceuticals are becoming more complex with three-dimensional structures, and many of them have very weak UV absorption. Even with substances that have a broad peak with normal UV, Spektra’s all-wavelength monitoring lets us detect sharp peaks and collect fractions.”

– You have a service contract on the Isolera.

“When we looked into it, we found out that the cost was about the same as having someone come in for repairs, so we decided to enroll. Our instruments are used all the time, so having one of them down for a few days would have a major impact on our business. We need to run at full performance, so having someone come immediately if we run into some trouble is critical. In the end, the service contract saves us money."

– What are the advantages of microwave synthesis?

Initiator organic microwave synthesizer system.“The shorter reaction times obviously. We can do in about an hour what used to take all night. If a synthesis took 10 hours, we’d start the process in the afternoon, and it would be ready the next day. Now it’s all done in the same day. For high-temperature reactions we previously needed to use solvents with high boiling points such as DMSO. These solvents are hard to evaporate after the reaction. With microwaves we can do high-temperature reactions at 150 or 180°C with common solvents that are easily evaporated afterwards. The Initiator is also very easy to operate. Usually we would need to include a recirculation device, which takes up space and needs time to warm up. Microwaves are more convenient, you just set it up and it automatically heats the reaction to the right temperature, keeps track of the time, and finishes. Nobody at our lab hesitates to use microwaves for organic reactions, it allows you to finish the same reaction quicker. On busy days, the next reaction is always lined up and ready to go as soon as one reaction finishes.”

– Your Initiators are all equipped with robots for automation.

“Yes, they are useful when synthesizing several compounds in sequence. For example, we often synthesize ten compounds with the same substrate and different substituents. In those cases, the robots are convenient because we can prepare ten vials and process them under the same conditions. You just set it up and everything is synthesized automatically. I also like that we can do multiple reactions over night. Or if we have a meeting, we can set up the process and leave, and it is done when we come back. Since we introduced the Initiators, the reactions we run and the number of new compounds we synthesize throughout the year has increased by 50%. We can use our time much more effectively.”

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