BOSTON — As the US Food and Drug Administration prepares to release its pharmacogenomic data-submissions guidelines on Friday, the agency has launched an initiative to gain microarray expertise by working closely with prominent players in the space.
Generally, the FDA has taken these steps to learn how pharmas may incorporate microarray data into drug discovery, to understand those data, and to become comfortable with them, according to several sources interviewed for this article.
The agency also hopes to learn as much as it can about the ways in which drug makers using disparate microarray technologies will likely submit data from array experiments.
As part of the initiative, the FDA hopes to enlist a handful of microarray manufacturers — among them Applied Biosystems, Illumina, Affymetrix, Agilent, GE Healthcare — to find a way to compare the data produced by these different platforms, according to Yvonne Dragan, director of the division of systems toxicology at the FDA's National Center for Toxicological Research.
Tentatively named Quality Control and Threshold Evaluation, this project fits with the FDA's Critical Path initiative, which is intended to aid pharmaceutical development, said Dragan.
"FDA and NCTR are interested in different [means] of utilizing [microarray] tools — both developing in-house expertise and assessing what's available" from outside firms, Dragan said.
Researchers involved in the initiative would provide the FDA with information or training about how to interpret microarray data for others within the FDA, Dragan said. "The pharmacogenomics guidelines would be the right place to go to understand what the FDA is going to do" with microarray data, she added.
"Obviously, what people would like to do is look at data across different platforms, and pull out biology," said Tracy Ferea, ABI's manager of microarray products. The company is involved in other cross-platform projects as well, said Ferea, but she was not willing to disclose those collaborators.
This self-education project also includes a preliminary effort led by Leming Shi, a senior scientist at NCTR's division of systems toxicology, who is engaging "all the array manufacturers" in the project to develop "cross-platform comparison," said Dragan.
The project includes ABI, Illumina, Affy, Agilent, and GE Healthcare, as well as Ambion, Clontech, and Stratagene, she said. The last three may provide control RNA samples with which to test and compare the microarrays of the other companies, Dragan added.
The cross-platform comparison project began earlier this year, Dragan said. "We've had one face-to-face meeting" with tool companies and RNA suppliers, she said. Jerry Zemaitis, vice president of sales and marketing at Genomics Collaborative, who has been following the project, said the groups have met within the last month-and-a-half. Zemaitis spoke with Pharmacogenomics Reporter at the IBC Biomarker Pipeline meeting, held here this week.
The shape of the project is still under discussion, but "it's certainly going to occur," Dragan said.
All sources interviewed for this article declined to disclose the financial details of any collaboration.
ABI's Rat Race
One recent FDA microarray collaboration may shed light on the kind of information the agency hopes to gain.
Earlier this week, ABI announced a joint research program with the NCTR. For this partnership, the FDA will rely on ABI's new whole-rat expression array to study the toxicogenomics of a class of diabetes drugs in which one member is linked to hepatotoxicuty.
The collaboration is the first of its kind for ABI, according to Ferea. Another similar but undisclosed partnership with the FDA is "in the works" and in the "early stages" of development, she added.
"We're going to be doing a validation — an extension of these studies — using TaqMan as well," added Ferea, the microarray products manager.
The ABI-NCTR study of glitazone-based diabetes drugs — preliminary results of which were presented as a poster at the Society of Toxicology conference in New Orleans last week — will be published in a peer-reviewed journal in several months, said Dragan.
Lu Zhang, an ABI senior scientist involved in the project, presented the poster in New Orleans. According to her team's findings, the expression profile for Rezulin, a glitazone-based drug that Warner-Lambert voluntarily removed from the market in 2000 due to liver toxicity, differs significantly from those of the two drugs in that class that continue to be sold.
Asked why the NCTR and ABI focused on this class of diabetes drugs, Zhang said the market for these types of drugs is huge. However, she said that this information would not immediately be used to help the FDA identify compounds associated with potentially toxic expression patterns.
Also, since the NCTR's interest in the project is scientific — the research group was interested in finding out how expression profiles could distinguish pharmacologic effects within a particular class of compounds — results from this research will not be transferred to other parts of the agency for decision-making, said Dragan.
"NCTR is not in the regulatory part of FDA," she said. "The utility here is that we get a better understanding" of the microarray platforms, which pharma will likely use to produce data for submission to the FDA, she said. "And the preclinical models use rat and dog, so the utility of the whole-rat genome array is quite useful for that purpose," she added.
ABI worked closely with NCTR researchers, said Ferea, who oversees all of ABI's microarray collaborations. "We worked on the study design with them, we generated the samples and prepared them, we did the labeling, and some of the preliminary data analysis," said Ferea.