Cell biology firm Stem Cell Innovations this week took steps to register its cell-based assay platform with the European agency responsible for authorizing methods that comply with an EU directive to phase out animal-based toxicity testing.
Certification by the agency, ECVAM (European Center for the Validation of Alternative Methods), could give the company a leg up in the European market, according to CEO Jim Kelly.
The Houston, Texas-based company opened a facility in Leiden, the Netherlands, last year, “partly because of ECVAM,” Kelly told CBA News. While ECVAM doesn’t have the authority to enforce the use of alternative methods, Kelly said that the agency’s determination that the platform is as effective as rats or mice would be “a stamp of approval” for the company’s approach.
ECVAM was created in 1991 to support an EU directive to protect animals used for experimental and other scientific purposes. It requires that member states “actively support the development, validation and acceptance of methods which could reduce, refine or replace the use of laboratory animals.”
The directive specifically states that animal-based studies should not be performed “if another scientifically satisfactory method of obtaining the result sought, not entailing the use of an animal, is reasonably and practicably available.” ECVAM is charged with assessing these alternative methods to determine whether they generate equivalent results.
Recognizing that this regulatory environment could be favorable for its business model, SCI set up its Leiden shop last year, and this week submitted its ACTIVTox suite to the agency for validation.
Kelly said that the validation process could take up to a year or longer.
So far, he said, there have been “very few cell-based assays that are rigorous enough to have been submitted” to ECVAM, “so we’re pretty confident that we can meet the criteria to get validated, and that’s really why we submitted it.”
SCI’s ACTIVTox platform is based on the company’s C3A human liver cell line, and includes a series of cell-based fluorescence and absorbance assays. The C3A line was originally developed at Amphioxus Cell Technologies, a company that Kelly founded in 1995.
Last February, Amphioxus acquired the assets of pluripotent stem cell developer Plurion and then merged with Interferon Sciences to form Stem Cell Innovations. Kelly said that the goal of the expanded company is to extend the cell-based in vitro capability developed at Amphioxus to different cell types using Plurion’s stem cell technology, called PluriCells.
“Now we’re using human stem cells to develop cells for heart, lung, intestines, and so on, to plug into the same sort of infrastructure” as ACTIVTox, he said.
While the liver cell line is the company’s most advanced, Kelly said that the firm has signed several “small agreements” to supply motor neurons for drug-screening programs.
“We’re pretty confident that we can meet the criteria to get validated, and that’s really why we submitted it.”
“Over the next 18 months or so, we hope to really have a panel of cells — liver, heart, kidney, et cetera — where you could really do extensive in vitro tox testing before you go into humans,” Kelly said. “Even in Phase 1, failing is very expensive. It’s much easier to fail in the test tube.”
However, Kelly acknowledged that despite the apparent promise of cell-based alternatives to animal testing, adoption among pharmaceutical customers has been less than robust.
“The pharmaceutical industry is in some ways pioneers, and in other ways they’re fairly conservative,” he said. “There’s a fair amount of enzyme assay-based toxicity [testing], where you look at isolated p450s and that kind of thing, but there are still relatively few cell-based toxicology assays” in use.
Kelly added that in the US, because FDA regulations specify that pharmaceutical firms must use rats and mice in particular tests, toxicologists at pharma companies have been reluctant to adopt alternative methods, even if it could save time or money.
These factors have kept cell-based screening relegated to lead discovery rather than further downstream in lead optimization, Kelly said.
“The companies that have used it seem to like it, but at the same time, we haven’t really gotten a Pfizer or someone to really make it part of their standard drug-discovery program,” he said.