General Session 4: Pharmacogenomics

FDA Pharmacogenomic Guidances April 2003, CDRH: Multiplex Tests for Heritable DNA Markers, Mutations and Expression Patterns: Draft Guidance for Industry and FDA Reviewers. March 2004, CDER: Pharmacogenomic Data Submissions. April 2005, CDER/CDRH/CBER/OCP: Drug-Diagnostic Co-development Concept Paper

Roche AmpliChip CYP450 Test (CDRH de novo 510(k) K042259) Genotypes two cytochrome P450 genes (29 polymorphisms in CYP2D6 gene, 2 in CYP2C19) to provide the predictive phenotype of the metabolic rate for a class of therapeutics metabolized primarily by CYP2D6 or CYP2C19 gene products. The phenotypes are (1) Poor metabolizers: (3) Extensive metabolizers: (2) Intermediate metabolizers: (4) Ultrarapid metabolizers: Cytochrome P450s are a large multi-gene family of enzymes found in the liver, and are linked to the metabolism of approximately % of all drugs. Among them, the polymorphic CYP2D6 and CYP2C19 genes are responsible for approximately 25% of all CYP450-mediated drug metabolism. A polymorphism in these enzymes can lead to an excessive or prolonged therapeutic effect or drug-related toxicity after a typical dose by failing to clear a drug from the blood or by changing the pattern of metabolism to produce toxic metabolites.