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March 3, 2003 — For all the science and technology necessary in the search for new drugs, ultimately there comes a time to make the drugs themselves — usually in large quantities. Andrey Zarur knows firsthand that the task is not easy.
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Zarur, a chemical engineer by trade, has spent more than a few nights checking fermentators and bioreactors at odd hours, tweaking the machines’ settings to ensure that drug samples cooking inside do so under the best conditions possible.
That experience led Zarur to launch BioProcessors Corp., a 2-year-old startup in Woburn, Mass., that takes a MEMS approach to cultivating biological products: Scale down the process to a few microliters and run samples through thousands of microdevices. The result is a high-speed, automated method of finding the best conditions to grow organic compounds.
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“Cells are very hard to work with,” Zarur said. “We saw a very large market for this, and then built the technology for it.”
Drug companies must find the best conditions possible to make cells do what they want them to do — secrete a protein, replicate an antibody or take some other action. By calibrating the growth environment to ideal conditions — that is, optimizing the manufacturing process — the cell will behave in the best way possible.
Current technology for this “process optimization” process, as the industry calls it, is a considerable pain for drug companies. It requires large flasks and spinners to test growth conditions for biological samples — a plodding approach that can take years to complete and cost millions of dollars.
BioProcessors uses MEMS technology on a massively parallel scale to conduct thousands of simple, cheap tests at once. Zarur gave the example of a pharmaceutical firm (he won’t say which) that recently hired BioProcessors to optimize its processes of growing an antibody. Zarur’s team ran 2,000 tests in four weeks at a cost of $1 million. With older technology, Zarur said, the same tests would have taken a year and cost $25 million.
With 20 employees, BioProcessors already earns several million dollars in annual revenues from top-tier pharmaceutical companies such as Amgen Inc. and Novartis AG.
Zarur said these companies are eager to farm out their process optimization, and improving it is a top priority.
“It’s probably the most critical bottleneck at this time,” said Govind Rao, a chemical engineering professor at the University of Maryland who has developed a similar milliliter-scale technology licensed to Fluorometrix Corp., also based in Massachusetts.
Drug companies are finding more and more drug molecules they’d like to explore, Rao said, thanks to high-throughput screening. Without a similar high-throughput system for process optimization, researchers must use liter-sized flasks “and that gets pretty limiting very quickly” because they can only test one or two conditions at a time.
Eric Henderson, chief scientist at Ames, Iowa-based BioForce Nanosciences Inc., said a MEMS-based approach like BioProcessors’ would be ideal for protein crystals, since they can easily be produced in large quantities once ideal conditions are determined. “For that type of application, it’s perfect,” Henderson said. BioProcessors “is trying to find the practical sweet spot for miniaturization.”
The bioreactors themselves are carved from clear plastic the size of a typical 96-well plate used for high-throughput screening. Several plates are sandwiched on top of each other, each with eight “units” performing a specific function and separated by membranes from the plates above and below. For example, the bottom plate might have eight microfluidic pumps sending a specific pH solution through the processor. That solution then seeps through the membrane to eight microfermentators in the plate above it holding the cellular samples to be tested.
Steve Squinto, executive vice president and head of research at Alexion Pharmaceuticals Inc., said his company has collaborated with BioProcessors for nearly a year to find optimal growth conditions for a protein Alexion is studying. Squinto said the protein “has been rather difficult to make.” If Alexion could improve the manufacturing process three or fourfold, he said, “it will become much more attractive to us.”
So far, BioProcessors has worked at the microlevel and doubled output of the protein, Squinto said. The company will soon scale up manufacturing to confirm that the same efficiency exists at one- or 10-liter volumes.
“It does go against convention,” Squinto said. “Most would have a hard time believing it’s true. That was our first reaction.” But now, he added, “we’re pretty satisfied.”
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Company file: BioProcessors Corp.
(last updated March 3, 2003)
Company
Bioprocessors Corp.
Headquarters
35-C Cabot Road
Woburn, Mass., 01801
History
Founded in October 2000 and originally headquartered in California, Bioprocessors uses technology familiar to founder Andrey Zarur in his previous work with bioreactors as a chemical engineer. The company also maintains an office in Palo Alto, Calif., but moved its headquarters to Massachusetts in October 2001 to be closer to potential investors and customers.
Industry
Drug discovery
Employees
20
Small tech-related products and services
Bioprocessors Corp. is developing a series of microfabricated devices called SimCells, part of a microfluidics platform designed to aid in miniaturization and automation of live cell growth, culture, harvest and testing. In the future, high-throughput bioprocessing will improve the yield, reproducibility, speed and information value of cell testing. The company is using this platform for creation of three key products: a microfermentor, microscreen and microassay. Anticipated applications include: drug discovery and screening; clone synthesis and selection; bioprocess development; biopharmaceutical molecule development; and toxicology analysis.
Selected strategic partners and customers
Investment history
In February 2000, Bioprocessors received $630,000 in seed financing from Rowland Capital, Sequoia International Investments and individual investors. In October 2001 the company completed a first round with participation from Rowland, Sequoia and Oxford Bioscience Partners, which led the round. The company is currently raising a $15 million to $20 million financing round, slated to close by the end of Q1 2003.
Barriers to market
The niche is crowded, and Bioprocessors will need to convince potential customers of the advantage their miniaturized methodology holds over current systems.
Competitors
Why they’re in small tech
“MEMS allows the three key features that make our platform unique: automation, parallelization and low cost,” said CEO Andrey Zarur. “Miniaturization is the only avenue that would let us to carry out cell culture research with the precision and control of large-scale systems, while allowing us to carry out tens of thousands of experiments simultaneously at an acceptable price.”
What keeps them up at night
“Actually, we work so hard during the day, that we seldom have the time or energy to lie awake at night — mostly we sleep very well,” Zarur said. “If we had time to lie awake worrying, then we would probably use it to work instead.”
Recent news and publications
Bioprocessors, Alexion collaborate
Bioprocessors Corp. closes first round for $6 million
Contact
— Research by Gretchen McNeely