1. OBRR Response to BPAC Recommendations on the Office Research Program Office Site Visit: July 22, 2005 BPAC Recommendations: February 10, 2006 C.D. Atreya, Ph.D. Associate Director for Research Office of Blood Research and Review, CBER, FDA BPAC Meeting, August 16, 2007

2. OBRR Response Overall CBER and OBRR management thank the Blood Products Advisory Committee for its in- depth review and general support of OBRR’s research program Recommendations of the Committee have received close attention at FDA resulting in program changes to: –Establish a structured and transparent management system for OBRR research –Improve research focus and prioritization

3. Issues Raised by the Committee Sufficient time and qualified personnel available to perform mission related research Environment Retention Support for mission critical research Alternate funding paths; outside leveraging Adequate laboratory space Research Prioritization Process Need for a transparent process Need for broad expertise vs. tightly focused research Visibility of OBRR research

4. Sufficient Time and Qualified Personnel to Perform Mission Related Research OBRR is committed to Resolving regulatory scientific challenges by providing adequate time for its research/review staff to engage in relevant laboratory work Ensuring that research/review staff are up to date with current scientific and technological advances by encouraging attendance at scientific meetings and supporting other training opportunities Conducting periodic workload assessments to address any imbalances in a timely fashion

5. Support for Mission Critical Research Within CBER, OBRR Provides seed monies and non-FTE postdoctoral positions for research to investigators embarking on new priority research projects Participates in cross-office partnerships for core research support facilities, major equipment purchases and service contracts (e.g. flow cytometry, TaqMan, sequencing facilities etc.) Evaluates laboratory space needs as part of an inter-office team effort CBER relocation to the White Oak facility, targeted for 2012, is expected to provide additional laboratory space for OBRR research staff

6. Support for Mission Critical Research OBRR actively seeks external support: When appropriate, OBRR leverages outside collaborations and partnerships –OBRR participates in developing CBER SOPPs and MOU templates to facilitate management of the application process for external grants –OBRR took a leadership role in bringing GWU under CSTP to allow student participation in CBER labs –Successful OBRR collaborations have been established with other government components including NIAID, NHLBI, NCI, DoD, USAMRIID

7. Research Prioritization A ‘Senior Leadership Team’ (SLT) has been established in OBRR to –Identify and monitor progress in critical areas of regulation and Critical Path research within the Office –Collect input from both research-reviewers and full- time regulatory scientists on regulatory science needs –Develop a comprehensive, prioritized Office research portfolio consistent with CBER’s overall plan Applications for external grants are reviewed both at the Division and Office levels to ensure mission relevance

8. Visibility of OBRR Research OBRR uses research to address scientific issues that are critical to regulation. Visibility of OBRR research is important to ensure: a) public availability of scientific information b) external measures of quality and significance To promote these objectives we: –Publish scientific work in peer reviewed journals –Present at local, national and international meetings –Organize scientific workshops of regulatory interest –Present scientific information to Advisory Committees –Provide ‘information booths’ at major scientific conferences and regulatory meetings –Provide opportunities for our scientific staff to interact with external scientists through invited seminars

9. OBRR Managed Research Plan: Identifying Key Scientific Needs Anticipated regulatory science needs are identified by analyzing the recent (1–2 year) product application submissions, public health needs and policy portfolio: –Regulatory review workload by product class –Guidance documents –Analysis of product failures and safety reports –Observations at inspections –Input from scientific workshops –Interactions with regulated industry, other HHS agencies and international partners (e.g. WHO) Research is targeted to identified scientific needs where the output could lower regulatory barriers to product development, or improve product safety, efficacy, consistency and availability

10. Key Scientific Needs Identified - I Practical and effective control of an expanding number of known and emerging transfusion transmitted infectious diseases requires new technology for donor testing and product processing: –Adaptable platforms for rapid response to EID and BT agents –Novel methods to detect malaria, other parasites, and TSEs –Nanotechnology-based donor screens –New pathogen reduction methods for blood components and derivatives Efficacy and safety of Immune Globulin products enhanced by improved characterization of effectiveness –For treatment of primary immune deficiency disorders –For passive immunization against pandemic Influenza, anthrax, botulism, smallpox, and other EIDs

11. Key Scientific Needs Identified - II Improvements in storage enhancing blood component safety, quality and availability –Tests for sterility to improve safety and permit extended shelf-life –Biomarkers of quality/efficacy to reduce needs for clinical trials Advancements in development of better predictive pre clinical tests of safety and efficacy for blood substitutes (e.g. HBOCs) –Biochemical characterization of HBOCs linking structure to clinical risk outcome –Better preclinical models to predict HBOC safety and efficacy

12. Key Scientific Needs Identified - III Pharmacogenomic and proteomic studies to improve safe use of blood products –Genetic determinants to predict risk for development of clotting factor inhibitors –Genomic based blood grouping and typing to improve blood compatibility determinations RFID technology for blood product labeling and tracking is a promising approach to reduce errors in blood transfusion management

13. OBRR Managed Research Plan: Developing the Research Portfolio Based on Identified scientific needs Available resources and expertise Feasibility of success and public health significance of the expected outcomes OBRR has identified six high priority areas for the current research program

14. Priority Research Areas - I Novel methods of pathogen reduction and inactivation in blood and blood products Expected Regulatory Impact: –More rapid assessment of candidate commercial methods Open new avenues to achieve safe and effective pathogen reduction for cellular blood products Provide insight into the mechanisms of cellular damage by pathogen reduction methods

15. Multiplex platforms and high-sensitivity methods for pathogen detection including genetic variant EIDs and BT agents Expected Regulatory Impact: –More rapid assessment of candidate commercial methods Provide insight into the practical limitations associated with the new technologies Priority Research Areas - II

16. Development of infectious agent panels for assay standardization, and standards and reagents for product lot release testing Expected Regulatory Impact: -Strategic preparations through development of lot release panels for new infectious agents -Replenishment or replacement of existing control panels –International standards for hematological products to ensure product potency Priority Research Areas - III

17. Development and evaluation of proteomics and genomics based biomarkers for efficacy, quality, toxicity and consistency of blood components, blood derived products, and their analogues, including “blood substitutes” Expected Regulatory Impact: –Provide surrogate biomarkers of product efficacy and safety for more efficient clinical trials Priority Research Areas - IV

18. Development of predictive models for preclinical evaluation of blood components, blood derivatives and their analogues including blood substitutes, and to study pathogenesis of blood borne EID agents Expected Regulatory Impact: –An appropriate animal model to improve HBOC safety –In vivo infectivity studies of blood components could support changes to current policies on donor deferral and reentry Priority Research Areas - V

19. Development of methods to evaluate efficacy of immune globulins of pandemic and BT importance Expected Regulatory Impact: –Provide scientific basis for dose labeling of immune globulin products to prevent known and emerging infectious diseases –Establish protective levels of specific antibodies in immune globulins to treat immune deficient patients Priority Research Areas - VI

20. Concluding Remarks OBRR and CBER have carefully considered all of the recommendations of the BPAC review of OBRR research. In particular, program changes have been made in response to the major recommendation of BPAC for more structured and transparent management of research. OBRR and CBER have developed and are implementing a managed research program based on prospective evaluation of regulatory science needs, our available resources, and the expected impact of the research. We look forward to ongoing and frequent discussions of the managed research program to assist OBRR to prioritize, focus and streamline our research to best address the scientific needs of regulation. Thank you!!