FDA: Sponsors Should Ensure Quality in Pharmacogenomic Data

Sponsors of clinical trials using pharmacogenomic data should use proper methodology to ensure high quality when they submit gene expression data from microarrays, according to a draft guidance from the FDA.

The draft document is intended as a companion to the agency’s March 2005 guidance, “Pharmacogenomic Data Submissions.” The new recommendations apply to the development of microarray data that might be submitted in support of investigational new drug submissions, new drug applications or biologic license applications.

The agency may request additional information beyond what is listed in the new draft guidance for microarray data supporting the clearance or approval of a diagnostic device.

“One of the most critical steps in performing RNA-based experiments, such as microarray gene expression experiments, is the isolation of high-quality, intact RNA,” the draft guidance states, offering a number of technical recommendations on this subject.

Sponsors are advised to use a labeling system “that has been documented to perform well on a given manufacturer’s array,” the draft guidance states. “It is critical that the sponsor begin the labeling process with high-quality RNA, free of contaminants that might affect the labeling efficiency or introduce labeling bias, as compromised RNA quality will affect subsequent steps of sample processing and ultimately lead to poorer quality microarray data.”

Sponsors should include pertinent information on reproducibility and accuracy of array hybridization in their submission packages, the draft guidance says. In order to provide this, it is recommended that sponsors establish and assess internal control metrics for quality and reliability.

Public comments on the draft guidance can be accessed at www.fda.gov/ohrms/dockets/98fr/07d-0310-gdl0001.pdf. Comments are due Nov. 27.