1	FDA/IVD Industry Overview Association of Medical Diagnostics Manufacturers Thirty Third Annual Meeting Rockville, Maryland April 20, 2006 Jonathan S. Kahan Partner Hogan & Hartson L.L.P. 555 Thirteenth Street, NW Washington, DC 20004-1109 Phone: (202) 637-5794 Fax: (202) 637-5910 E-Mail: JSKAHAN@HHLAW.COM
2	IVD Initiatives and Directions Major Issues Status of Analyte Specific Reagents (ASRs) CLIA/“Homebrews” vs. FDA Regulated Tests Challenges of New Technology Current State of the Office of In Vitro Diagnostics (OIVD) History/Goal Compliance Post-Marketing Activities Market Access Success Moving Forward
3	ASRs Issues of Nonuniformity Between CLIA and FDA Processes Unresolved Letters to Manufacturers/Compliance Actions Tepnel Diagnostic Ltd. (August 26, 2005) – Warning Letter Marketing Gel-Based ELUCIGENE Genetic Assays CF-HT, CF-29, CF Poly-T, CF7, Ashplex 1, Ashplex 2, Gaucher and TRP without Approval/Clearance Intended For “In Vitro Diagnostic Use” to Detect Various Human Genetic Mutations Such As Those in Cystic Fibrosis and Cardiovascular Disease Nanogen Corporation (August 11, 2005) Marketing the NanoChip Molecular Biology Workstation, NanoChip Electronic Microarray and Several Devices Marketed as ASRs Described as “an Automated Multi-Purpose Instrumentation That Facilitates Detection of Known Sequences…”
4	CLIA/“Home Brews” vs. FDA Regulated Tests De facto Two Pathway Approach CLIA vs. FDA Regulated FDA Lacks Resources Enforcement Discretion Risk-Based Approach Medically Necessary and Groundbreaking Technologies Should Not be Hindered
5	CLIA/“Home Brews” vs. FDA Regulated Tests IVD Manufacturers Have Significant Competitive Disadvantages Lower Regulatory Hurdles for Home Brews Manufactured Tests With Analytical Utility Not Being Marketed - Need to Demonstrate Clinical Utility “Home Brews” Allow Flexibility and Cost Effective Development/Introduction of New Technologies
6	CLIA/“Home Brews” vs. FDA Regulated Tests IVD Industry Has Proposed IVAT Approach to: Simplify and Standardize the Regulation of IVD Products Address Discrepancy Between Clinical Utility (FDA) and Analytical Performance (CLIA) Assessments Agency Concerns About Clinical Utility Appear to be Founded on Risk-Based Concerns Open Discussion About Fresh Alternatives and Pathways/Risks Needed Now – Current Approach Has Not Been Effective
7	CLIA/“Home Brews” vs. FDA Regulated Tests Examples: OvaCheck™, Correlogic Systems, Inc. Oncotype DX™, Genomic Health, Inc. Many CLIA laboratories offer other multi-analyte tests for cancer, staging, drug/disease relationships Where will FDA Draw the Line?
8	New Technology Challenges Variety of Technologies and Applications Impact FDA’s Regulatory Review Process Requires Diversity in Staff Training and Experience Uncertainty Regarding Regulatory Route - Agency Guidance Needed for Platform Technologies and Approaches Multiplex Testing Genomics (DNA, mRNA, other, novel genetic analytes) Proteomics
9	New Technology Challenges Pharmacogenomics Clinical Measurements Based on More Subtle Changes in Global RNA Expression Microarrays Defining Clinical Utility and Correlation to Disease Avian Flu and Emerging Diseases Developing Biodefense is Still a Priority
10	New Technologies - Clearances OIVD Can Be Flexible Tag-It Cystic Fibrosis Kit (K043011) Invader UGT1A1 Molecular Assay (K051824) Influenza A/H5 (Asian Lineage) Virus Real-Time PCR Primer and Probe Set (K060159)
11	Guidances/Concept Papers Automated Fluorescence in situ Hybridization (FISH) Enumeration Systems Guidance (March 23, 2005) Drug-Diagnostic Co-Development Concept Paper (April 2005) Herpes Simplex Virus Types 1 and 2 Serological Assays Guidance (January 9, 2006) Hepatitis A Virus Serological Assays Guidance (February 9, 2006) Pharmacogenetic Tests and Genetic Tests for Heritable Markers Guidance (February 9, 2006)
12	What More Can be Done? OIVD/Industry Cooperation Is the Pre-IDE Process Working? Has MDUFMA Impacted Work Flow? Broadening Technological Expertise within OIVD Industry Proposals
13	OIVD History and Goal Established November 2002 Goal - Focus on “Total Product Life Cycle” to: Improve Regulation Speed Important Products to Market OIVD Has Encouraged Interaction Pre-IDE Meetings De novo Downclassification “Invitations” to Meet/Discuss Pathways
14	OIVD Impact “Total Product Life Cycle” Impact on: Regulation Compliance Product Approval Timelines Postmarketing Oversight – New Opportunities
15	Regulation Regulation by Guidance and Special Controls (de novo) Public Presentations ASRs Critical Path Initiatives Limited Formal Rulemaking and Revision to Current Regulations
16	Compliance Letters to Manufacturers Biolmagene, Inc. (May 25, 2005) Marketing PATHIAM without Approval/Clearance PATHIAM is “a hardware dependent, Web-enabled software allowing pathologists to view and analyze immunohistochemically-stained (IHC-stained) slides from any computer via the Internet.” Access Genetics (August 1, 2005) – Warning Letter Marketing of Genetic Assays without Approval/Clearance (Thrombophilia Tests (Factor 5 Leiden, Factor 2 Prothrombin, MTHFR), Human Papillomavirus, Chlamydia & Gonorrhea PAP and Cystic Fibrosis)
17	Compliance Letters to Manufacturers (continued) EXACT Sciences Corporation (Lab Corp) (January 19, 2006) Letter Regarding Regulatory Strategy and PreGen-Plus Compliance Genomic Health, Inc. (January 23, 2006) Letter of Invitation to Discuss Regulatory Status of Oncotype DX
18	OIVD Performance Shortening the Time to Market PMAs and 510(k) Notices - Original CDRH/Original OIVD Submission: PMA 510(k) Notices De novo 2006: 1 / 1 2005: 38 / 5 2,617 / 415 2 / 3 2004: 39 / 12 3,917 / 486 3 / 7 2003: 31 / 3 4,132 / >500 1 / 4 Review times relatively unchanged
19	OIVD Premarket Customer Perception Survey* FY 2004 vs. FY 2003
20	Postmarketing Developing a “Culture of Collaboration” on Postmarket Safety Developing World-Class Data Sources and Systems Enhancing Risk/Benefit Communication Efforts Focusing Improved Enforcement Strategies on Postmarket Issues
21	Postmarketing Challenges Difficult to Separate Performance Error by User From Clinically Significant Differences Between Study and Market Populations Link Between Safety and Effectiveness Clinical Laboratories Need to be Partners With Manufacturers in Postmarketing
22	Moving Forward Regulatory Directions May Change – CDRH Recognizes Need to Find New Ways of Conducting Reviews ASRs and Home Brew Tests Continue To Be an Issue Balance Increased Home Brew Regulation With Risk Review of Increasingly Complex IVDs and Device Technologies Requires Diversity in Staff Training and Experience Risk-Based Approach Unchanged, But New Technologies May Raise New Risks Clearer, More Predictable, More Transparent, and Potentially Less Burdensome Regulatory Pathways to Market Need to be Available
23	FDA and Industry FDA Regulatory Initiatives Relating to IVDs Have Been Frequent and Increasing in Number Manufacturers, Laboratories, and Physicians Should Try to Keep Abreast of New Developments Where Possible, Trade Associations, Professional Associations, and Interested Parties Should Make Their Views Known About the Need to Continue Streamlining the IVD Clearance/ Approval Process Agency Feedback and Open Communication a Must