OBRR Response to BPAC Recommendations on the Office Research Program Office Site Visit: July 22, 200

1
OBRR Response to BPAC Recommendations on the
Office Research ProgramOffice Site Visit July
22, 2005BPAC 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 OBRRs 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 CBERs 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 PlanIdentifying Key
Scientific Needs

• Anticipated regulatory science needs are
  identified by analyzing the recent (12 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 PlanDeveloping 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
Priority Research Areas - II

• 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

16
Priority Research Areas - III

• 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

17
Priority Research Areas - IV

• 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

18
Priority Research Areas - V

• 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

19
Priority Research Areas - VI

• 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

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!!