1	CBER IVD UPDATE Jay S. Epstein, M.D. Director, Office of Blood Research and Review, CBER FDA/INDUSTRY IVD ROUNDTABLE May 11, 2005
2	Vision for CBER INNOVATIVE TECHNOLOGY ADVANCING PUBLIC HEALTH Protect and improve public and individual health in the US and, where feasible, globally Facilitate the development, approval and access to safe and effective products and promising new technologies Strengthen CBER as a preeminent regulatory organization for biologics
3	Outline Our People MDUFMA Performance Selected Accomplishments Progress on Center and Agency initiatives Current Challenges
4	Current CBER Management Jesse L. Goodman, M.D., M.P.H., Director Karen Midthun, M.D. Medical Deputy Director Mark Elengold, Deputy Director for Operations Robert Yetter, Ph.D., Associate Director for Review Management Diane Maloney, J.D., Associate Director for Policy Sheryl Lard-Whiteford, Ph.D. CBER Ombudsman Kathryn Carbone, M.D., Associate Director for Research
5	New CBER Managers Director of the Office of Compliance and Biologics Quality: Mary Malarkey Director of the Office of Cellular, Tissue, and Gene Therapies: Celia Witten, Ph.D., M.D. Deputy Director, Office of Blood Research and Review: Jonathan Goldsmith, M.D.
6	OBRR Division Leadership: IVD’s Division of Emerging and Transfusion Transmitted Diseases- Hira Nakhasi, Ph.D. Donor screening and supplemental tests (HIV, HCV, HBV, HTLV, CMV, HAV, WNV, TSE, Chagas disease, malaria, leishmania, BT agents) Retroviral diagnostic tests Division of Blood Applications- Alan Williams, Ph.D. Regulatory Project Management Branch– Sayah Nedjar, Ph.D. Devices Review Branch Blood grouping reagents HLA tests Division of Hematology- Basil Golding, M.D. Bacterial detection in blood products
7	Recent DETTD Reorganization
8	IVD Review Performance Application Receipts MDUFMA Performance Selected Accomplishments
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11	MDUFMA IVD Performance 510(k)s FY 2003 FDA Time Total Time Type n (Days, Avg) (Days, Avg) Cycles Traditional 18* 69.0 94.2 1.39 Abbreviated 1 54.0 54.0 1.00 Special 7 18.4 18.4 1.00 2 Withdrawn; 6 Additional Traditional 510(k)s are pending. *Times may increase with completion of pendings. Data as of March 31, 2005. SEs/NSEs Only.
12	MDUFMA IVD Performance 510(k)s FY 2004 FDA Time Total Time Type n (Days, Avg) (Days, Avg) Cycles Traditional 30* 71.7 99.0 1.43 Abbreviated 1 87.0 87.0 1.00 Special 3 27.3 27.3 1.00 1 Exempt; 2 Additional Traditional 510(k)s are pending. *Times may increase with completion of pendings. Data as of March 31, 2005. SEs/NSEs Only.
13	MDUFMA IVD Performance 510(k)s FY 2005 FDA Time Total Time Type n (Days, Avg) (Days, Avg) Cycles Traditional 1* 80.0 80.0 1.00 Abbreviated 0 -- -- -- Special 0 -- -- -- 6 Additional Traditional 510(k)s are pending. *Times may increase with completion of pendings. Data as of March 31, 2005. SEs/NSEs Only.
14	MDUFMA Performance All 510(k)s FY 2005 FDA Time Total Time Type n (Days, Avg) (Days, Avg) Cycles Traditional 12* 66.4 76.2 1.25 Abbreviated 2 74.5 85.0 1.50 Special 1 28.0 28.0 1.00 6 Additional Traditional 510(k)s are pending. *Times may increase with completion of pendings. Data as of April 30, 2005. SEs/NSEs Only.
15	CBER PMA Performance FY 03 – 05 Receipt Cohorts as of 4/30/2005 7 Original PMAs received (aggregate) First Action Goals: 5 met, 2 pending Final Action Goals: 3 FDA decision: 3 < 320 days 2 < 180 days 4 pending
16	CBER BLA Performance FY 03 – 05 Receipt Cohorts as of 4/30/05 FY 06 goal 75% review/act on in 10 mos FY 03 Receipt = 0 FY 04 Receipt = 9 1 pending, 8 met 89% within goal FY 05 Receipt = 1 pending
17	CBER BLA PAS FY 06 Goal: 75%Review/Act on 4 months Manufacturing Supplements FY 03 n = 75, 99% within goal (closed) FY 04 n = 96, 100% within goal (closed) FY 05 n = 17, 8 w/in goal, 9 pending
18	Selected 2004-5 Device Approvals Trinity Uni-Gold Recombigen HIV (fingerstick and venipuncture WB, serum, plasma) for antibodies to HIV-1; CLIA waived for WB OraSure OraQuick ADVANCE Rapid HIV-1/2 Antibody Test (fingerstick and venipuncture WB, plasma, oral fluid) for antibodies to HIV-1 and HIV-2; CLIA waiver for WB and oral fluid Bio-Rad Multispot HIV-1/HIV-2 Rapid Test (serum and plasma), first test to distinguish between antibodies to HIV-1 and HIV-2 First HIV- and HCV NAT approval for donors of cells, organs, and tissues (Gen Probe)
19	Selected Accomplishments: Guidance on NAT Final Guidance on implementation of NAT for HIV-1/HCV for donors of Whole Blood and Source Plasma was published on October 21, 2004 Testing by licensed NAT to be implemented by April 2005 Final guidance on unit and donor management is under development
20	Selected Accomplishments: IVD Reference Panels New reference panels RNA panels for HIV subtypes RNA panel for West Nile virus Upgraded HBsAg panel A more stringent sensitivity requirement will be established through guidance
21	Center and FDA Initiatives: Critical Path Public Workshop: October 7, 2004 “From Concept to Consumer: CBER Working with Stakeholders on Scientific Opportunities for Facilitating the Development of Vaccines, Blood and Blood Products, and Cellular, Tissue, and Gene Therapies”
22	Critical Path Initiative Blood and Blood Products Panel Session: Opportunities for FDA and Industry COMMUNICATION Increase communication with Industry; issue Guidance Documents faster; Establish a mandate; Develop consistency with other agencies in regulatory guidelines.
23	Critical Path Initiative, cont. RESEARCH & DEVELOPMENT Set standards in advance of product development; Help with R&D in specific areas; Help to reduce product development time.
24	Critical Path Initiative, cont. CLINICAL DEVELOPMENT Set objective, firm approval requirements; Provide more guidance on structure of clinical trials; Make better use of alternatives to clinical trials.
25	Critical Path Initiative, cont. FDA APPLICATION REVIEW Accelerate product reviews; Facilitate introduction of new donor screening tests; Use alternative measures to validate product or process changes.
26	Critical Path: Examples of Opportunities Development of assays for antibodies against anthrax Evaluation of candidate diagnostic and donor screening tests for TSE’s Development and validation of multiplex NAT to detect bacteria and parasites in blood Development of nanotechnology for blood screening and diagnostic use Development of assays to measure microbial contaminants of plasma-derived products Development of animal models to test efficacy of vaccinia immune globulins
27	Microarray for Detection of Blood-borne and BT Pathogens
28	Center and FDA Initiatives: Migration Studies Migration studies allow sponsor to validate transfer of: Manual assay to instrument platform Semi-automated assay to fully automated assay Assay from one instrument platform to another (new, improved, or different automation In addition to reproducibility study and analytical sensitivity studies
29	Center and FDA Initiatives: West Nile Virus Nationwide testing since July 2003 using WNV NAT under INDs resulted in donations interdicted from asymptomatic donors with confirmed or suspected WNV infections In 2003, 818 WNV presumptive viremic blood donors officially reported to CDC’s ArboNet 6 confirmed T-T cases (4/6 had low viremia ~0.11 pfu/ml) In 2004, 199 presumptive viremic donors officially reported to CDC’s ArboNet from 28 states using MP-NAT as well as ID-NAT in select areas starting May ’04 1 reported case of T-T (detectable only by ID-NAT) FDA is working to enhance the accuracy of the assays Panel development Isolation and characterization of WNV strains Developing animal model of infection
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31	Ongoing Challenges: IVD’s MDUFMA implementation Continue to meet performance goals Least burdensome approach West Nile virus Approval of tests HIV, HCV and HBV NAT New multiplex assays and high through-put platforms Malaria, Leishmania and Chagas Disease Test development and guidance on donor selection Counterterrorism Development of detection technologies for BT agents Guidance on unit and donor management in event
32	Ongoing Challenges: External Laboratory Accreditation OBRR is working actively toward ISO accreditation for the IVD lot release laboratory Rate of progress is resource limited Use of user fees would require an Act of Congress Other CBER lot release components also are working on external laboratory accreditation FDA’s first priorities are for public health in the US, and lot release for other markets would be seen in that light
33	Thanks! We are proud of CBER and its mission Both traditional & cutting edge products and technologies offer tremendous promise to protect and enhance health Innovation is critical We see a bright and promising future & seek and need your continued input and engagement jgoodman@cber.fda.gov epsteinj@cber.fda.gov