Celsis In Vitro Technologies this week announced that it is entering into a co-marketing agreement with Promega, under which it will pre-qualify its cryopreserved hepatocytes for use with Promega's bioluminescent ADME/Tox assays, including the P450-Glo CYP450 assay and the GSH-Glo glutathione assay.
Terms of the deal call for Celsis IVT to prevalidate its cells on Promega's kits and make that data available to Promega and Promega customers on the Celsis website. The deal, which will run for two years and is renewable, is the first formal agreement between the two companies.
The deal is noteworthy for Celsis IVT because it "is one of the first in terms of our hepatocytes being used to add value to another company's kit," according to Philip Vorwald, vice president and general manager of Celsis IVT.
According to Vorwald, the agreement does not involve revenue sharing, but instead includes product validations; marketing activities, including joint activities at trade shows, joint posters and papers; conference co-sponsorships; and Web site links in which Celsis IVT and Promega share data for this particular assay.
"In the future, we want to do more of these types of agreements, where you are eliminating sources of error by working with another company," Vorwald said.
Promega's ability to make hepatocytes is limited, so it made sense to partner with a company such as Celsis IVT that specializes in providing cells and other in vitro testing products, said James Cali, lead scientist for ADME/Tox at Promega.
"We can give investigators profound guarantees that our assay chemistries are quality controlled," said Cali.
He also said, however, that although Promega tests as many cell samples as possible with its assay chemistries, "we can never guarantee that the content, in this case hepatocytes, from any given source are always going to perform the way they should."
"Our thinking about the design of our assays has always had the hepatocytes in mind," Cali added.
Conventional methods for ADME/Tox include mass spectrometry and liquid chromatography. Although effective, these techniques are also labor intensive and low throughput.
"An optical assay in an add-and-read format allows researchers to increase the throughput and decrease the amount of effort that goes into getting these [ADME/Tox] data points," Cali said.
"We have noticed that other companies … continue to come out with cell-based assay kits, in Promega's case GSH-Glo and P450-Glo, which are used in ADME/Tox testing with hepatocytes," said Vorwald.
As a supplier of hepatocytes, Celsis IVT has "always been curious that we provide one of the primary components of their kits that they do not have," he said.
Celsis IVT suggested to Promega that it would make sense for it to prevalidate some of its hepatocytes, and for both companies to participate in co-marketing activities for the cells.
Previously, Promega's Glo kits came with a reaction buffer and the luciferase substrate. "After people ordered the kits, they had to do their own hepatocyte testing, essentially involving trial and error, to see which cells worked or were the best ones for the kit, and were therefore validated with the kit," said Vorwald.
"We are now doing all of this for them at Celsis IVT, and linking up with both Web sites so when you purchase a Promega kit, you can immediately go to a table that has prevalidated hepatocytes for the kit," he added.
Celsis has discovered over the last decade that many user-dependent factors such as media, the concentration of various components, and pH can affect chemical reactions, Vorwald said.
The risk of variability "is even magnified more because you are dealing with live cells, and many things can influence them," he added.
As far as Promega is concerned, "We are about two weeks away from the commercial launch of a new product for measuring CYP 3A4 induction in human hepatocytes and other cell sources that express human CYP 3A4,." Cali said.
Promega's P450-Glo CYP 3A4 assay uses a substrate celled luciferin IPA, a derivative of the luciferase's light-generating substrate. Luciferin IPA is also a substrate of CYP3A4.
CYP3A4 oxidizes luciferin IPA and converts it from a non-light-generating substrate to a light-generating substrate. This assay can be done very rapidly in a miniaturized format using primary human hepatocytes.
"We are pretty excited about this CYP 3A4 assay, because whereas the researchers have typically had to use 6-, 12-, and 24-well cell culture formats, we can miniaturize it into a 96-well format," said Cali. This miniaturized format provides scientists with a lot more data out of a vial of cells or a plate of fresh cells.