Pharmacogenomic Electronic Submissions Eased for Wyeth

Wyeth can more smoothly prepare esubmissions of pharmacogenomic clinical data to the FDA under its recently expanded agreement with Expression Analysis.

Under the agreement, which was first developed in 2003 and formally implemented in July 2004, Expression Analysis provides Wyeth with contract pharmacogenomic testing services using the Affymetrix GeneChip platform, said Andrew Dorner, senior director for biological technologies at Wyeth. This helps Wyeth prepare the data for submission to the FDA.

Pharmacogenomics “examines the inherited variations in genes that dictate drug response and explores the ways these variations can be used to predict whether a patient will have a good response to a drug, a bad response to a drug, or no response at all,” according to the National Institutes of Health.

“All microarray services provided under the agreement are to be compliant with 21 CFR Part 58 (Good Laboratory Practices [GLP]) in support of clinical studies,” according to Expression Analysis. Expression Analysis, the Center for Drug Evaluation and Research and Schering-Plough collaborated in 2003 on the first-ever submission of electronic microarray data to the FDA. The goal was to help the agency understand how such data could be used in future regulatory submissions.

This does not necessarily mean, though, that Wyeth’s pharmacogenomic submissions to the FDA will end up completely in electronic format. “We submit all data to [Wyeth] electronically, but it’s their business what they do with it after that,” Steve McPhail, president and CEO of Expression Analysis, told PIR.

Dorner explained the process to PIR as follows: “Our relationship with Expression Analysis is an agreement by which our clinical pharmacogenomics samples are run on Affymetrix GeneChips. The data are transferred to Wyeth, where we do statistical analyses and data analyses of these baseline profiles, correlating them with patient symptoms.”

“We certainly can submit data to the FDA in electronic format — we were the first company to follow the voluntary genomic data submission guidelines (VGDs),” Dorner continued. But in practice, “it’s not all electronic — we tend to supply them with PDF files of reports, but when they want to see the data we submit it to them electronically,” he said. Expression Analysis has also made data esubmissions to the FDA in the past, said McPhail.

The VGD guidelines are part of an FDA initiative to obtain as much clinical pharmacogenomic data as possible “to see what is going on with this new technology,” Dorner said. Wyeth is cooperating closely with both the agency and Expression Analysis on pharmacogenomics, the subject of three recent FDA workshops. “They are working with industry. Draft comments were floated. It’s a continuing interactive process. The FDA has shown a lot of initiative in this area,” Dorner said.

“The main thing is the potential for pharmacogenomics using transcriptional profiling,” a genetic technique used to identify patients for clinical trials and predict the onset of disease and customize treatment regimens for individual patients. “The clinical outcomes are being explored heavily by industry and the FDA,” Dorner said. For now, Dorner added, “there is a lot of laboratory-to-laboratory variation” in transcriptional profiling. Expression Analysis is helping to standardize this area, he said.

All data produced under the agreement between Expression Analysis and Wyeth “has been generated in a regulatory-compliant fashion,” although the FDA guidance on pharmacogenomic data submission “is a bit vague on whether GLP is a requirement or not,” McPhail said. “Recently, they’ve been more clear that a GLP-like format is required,” he added, noting that confusion exists because GLP applies to preclinical testing, while the Clinical Laboratory Improvement Amendments (CLIA) of 1988 apply to human testing.

“Our compliance with those regulations allows any pharmaceutical partner we might have to submit data to the agency with confidence that a robust quality system is in place,” McPhail said. — Martin Gidron