1	Two Documents to Perpend Pharmacogenomic Data Submissions – Guidance Drug-Diagnostic Co-Development Concept Paper – Preliminary Concept Paper
2	Two Documents CDER documents CDRH and CBER partnership Broad application to diagnostics
3	PDS When to submit pharmacogenomic data What format and content How and when data used in decision making
4	Pharmacogenomics Use of pharmacogenomic or pharmacogenetic tests in conjunction with drug therapy PGS guidance relates to test evaluation during drug development In contrast to co-development Same message – don't forget the diagnostic; think early
5	Valid Biomarkers Analytical test system well developed Scientific framework for use well developed
6	Probable Valid Biomarker Predictive value apparent Not widely or independently accepted
7	Value of Process Inform FDA of issues Inform sponsors of questions Facilitate development of knowledge, policies, guidances
8	Formats -- flexible Articles Using public standards for data display (Minimum Information about a Microarray Experiment or MIAME) Full report on experiment
9	Distinction Mandatory Voluntary Independent Pharmacogenomic Review Group (IPRG) Firewall from review staff CDRH involvement
10	IPRG Rules of engagement Growing experience Heterogeneity to interests and needs Outcomes on target
11	Co-Development Tri-center effort Eye on the ball – clinical use not development Selection not dosing Drug-diagnostics in general not genomic
12	Review History Estrogen receptor Her 2 test EGFR
13	Learn From Past Analytical performance Clinical performance – validity and utility
14	Analytical Performance Device description Analytical studies Software and instrumentation Bottom line – lock in performance Use analytical information and feasibility studies to plan experiments to establish clinical performance
15	Clinical Validity Not different than existing guidance CLSI STARD initiative OSB statistical guidance
16	Clinical Validity Clinical sensitivity Clinical specificity Predictive values Likelihood and odds ratios
17	Clinical Validity Diagnostic performance Drug performance Two are independent but linked Addendum to demonstrate that drug efficacy affects predictive value of diagnostic results
18	Clinical Utility Quite new and unique Cross-walk between CDER and CDRH Highlights need for concurrent studies
19	Clinical Utility Allows for different approaches Blind to diagnostic Use diagnostic to select (beguiling allows for enrichment)
20	Phase 3 Studies Ideal time to study drug and diagnostic Ideal time to collect invaluable samples Ideal time to learn if diagnostic makes a difference Not the only time
21	Concept Paper Work in progress Sections unvetted Administrative sections on dual processes Extensive insight into labeling options
22	Work Plan Obtain comments Publish draft guidance Obtain comments
23	Work Plan Publish final guidance Workshops along the way??? Improve connectivity to IVD industry
24	Good News Timing is right for input from industry CDER. CBER and CDRH can work together; co-review; pull off administrative coordination Agency has developed worked groups to share knowledge and explore review policy and practices
25	Bad News Tought stuff No material or method standards Complex and nuanced biology Complex business (financial) issues Daunting educational challenges for use of new technology
26	Good Science Driving forces in private sector Driving forces in government (FDA critical path) CDRH user fee hires have provided new review strength – AmpliChip; CF multiplex system Broad regulatory tool box to draw from