Workgroup Report: Review of Genomics Data Based on Experience with Mock Submissions--View of the CDER Pharmacology Toxicology Nonclinical Pharmacogenomics Subcommittee John K. Leighton,1 Paul Brown,1 Amy Ellis,1 Patricia Harlow,1 Wafa Harrouk,1 P. Scott Pine,2 Timothy Robison,1 Lilliam Rosario,1 and Karol Thompson2 1Office of New Drugs, and 2Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA Abstract Over the past few years, both the U.S. Food and Drug Administration (FDA) and the pharmaceutical industry have recognized the potential importance of pharmacogenomics and toxicogenomics to drug development. To resolve the uncertainties surrounding the use of microarray technology and the presentation of genomics data for regulatory purposes, several pharmaceutical companies and genomics technology providers have provided the FDA with reports of genomics studies that included supporting toxicology data (e.g., serum chemistry, histopathology) . These studies were not associated with any active drug application and were exploratory or hypothesis generating in nature. For training purposes, these reports were reviewed by the Nonclinical Pharmacogenomics Subcommittee consisting of the Center for Drug Evaluation and Research pharmacology and toxicology researchers and reviewers. In this article, we describe some of these submissions and report on our assessment of data content, format, and quality control metrics that were useful for evaluating these nonclinical genomics submissions, specifically in relation to the proposed MIAME/MINTox (minimum information about a microarray experiment/minimum information needed for a toxicology experiment) recommendations. These genomics submissions allowed both researchers and regulators to gain experience in the process of reviewing and analyzing toxicogenomics data. The experience will allow development of recommendations for the submission and review of these data as the state of the science evolves. Key words: data visualization, electronic data files, MIAME/MINTox, mock submission content, quality control metrics, toxicogenomics. Environ Health Perspect 114:573-578 (2006) . doi:10.1289/ehp.8318 available via http://dx.doi.org/ [Online 3 November 2005] Address correspondence to J.K. Leighton, Office of Oncology Drug Products, U.S. FDA, Building 22, Room 2118, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002 USA. Telephone (301) 796-2330. Fax: (301) 796-9867. E-mail: leightonj@fda.hhs.gov The views expressed in this article are those of the authors and do not necessarily reflect the views of the U.S. Food and Drug Administration. We thank Expression Analysis, GlaxoSmithKline, Iconix, and Schering-Plough for providing the mock submissions for review. We also thank past and present members of the Nonclinical Pharmacogenomics Subcommittee for their contribution. The authors declare they have no competing financial interests. Received 13 May 2005 ; accepted 3 November 2005. The full version of this article is available for free in HTML or PDF formats. |