WALTHAM, Mass.—Thermo Electron Corp. in late January unveiled LeadStream an integrated ADMETox offering that provides an integrated system for sample distribution, assays and high-througput LCMS all managed by Trillium software specifically tuned to ADMETox processes. Aimed at the research arms of big pharma, Thermo officials say LeadStream will help coordinate what are often disparate processes in preclinical profiling and provide faster results and compound candidates with a higher chance of success.
"ADME is a bottleneck in drug discovery," says Hansjörg Haas, director of ADMETox for Thermo Electron. "Today it is done in de-centralized, uncoordinated laboratories, which have a very low capacity and that is inefficient. There is also inefficient and costly data creation and fragmented data management. Pharma has focused on target discovery and HTS and these processes are well-oiled and well established. Then it hits preclinical profiling and that is just not aligned yet."
The solution, Thermo officials believe, lies in an integrated offering which both centralizes the ADMETox processes and provides a high level of data management and automation. This is in contrast with the more common situation in ADMETox today where the lab may have a mass spectrometer from one company, LIMS from a second and other equipment from still other suppliers.
"As far as we know, LeadStream is the only ADMETox offering that is a complete turnkey solution that looks at the entire process from beginning to end," says Haas. The idea is to eliminate "islands of automation" found within current ADMETox labs.
"There are lots of solutions that exist for ADMETox, but they tend to be a single technique," says Marc Casper, president of the life and laboratory sciences segment of Thermo Electron. "So what the pharmaceutical company is relying on is effectively integrating four or five or six of these islands and using a manager process hoping that everything can be run in a way to come up with a coherent answer. We are saying that if this is going to be a profound change, there has to be one complete solution and that is what Thermo is bringing to the market."
LeadStream promises to provide sample and data management for every sample introduced in the lab from the beginning of the process to the very end. That means each time a sample is passed from one instrument to the next there is a data trail that shows exactly where the sample has been and what the results were.
It also provides for the creation of decision criteria allowing scientists and lab managers to set data parameters. Samples that fall outside the acceptable range do not progress in the process. "So it is not just the instruments themselves, it is decision making – something we call 'facilitated decision making'," says Haas.
That, in a nutshell is the challenge of ADMETox work as it is currently conducted, says, Russell Robins, director of pharmacokinetics with Pfizer. "To me there are three major process streams: one is material, bringing together the compounds of interest and materials management; another is the analytical platforms themselves, the screens and the technology to support them; and then the informatics outflow from that," Robins says. "The input and the output are coupled and the challenge is to bring all three of those work streams together to render a decision on the discovery timescale and that remains the biggest challenge in the industry. We have gotten very efficient at collecting data, but turning that data into a decision still remains challenging."
With LeadStream, Thermo mangement hopes it has found the tool that can help scientists automate the data collection process, develop faster decision making based on the data values from disparate tests and provide a more robust screening tool.
"We feel that there can be significant time savings in the ADMETox process working like this," says Haas. "A typical validation may take three to four months and using our tools we can take that down to two to three weeks."