1. CBER Regulatory Laboratory Planning & Preparedness for SARS-related Biologics Products Kathryn M. Carbone MD Associate Director for Research, Acting, Center for Biologics Evaluation and Research, FDA

2. SARS: The CBER Focus Encourage & Facilitate Needed Biologics Product Development: –Development of Vaccines, Immunoglobulins –Protect the Safety of the Blood Supply Work to assure adequacy of U.S. medical supplies in the event of a SARS outbreak in the U.S.

3. CBER Research in Support of Biologics Product Development Cadre of experienced medical and basic scientists who perform biologics product review as part of a review team and also perform research in CBER’s intramural program Research focuses on science discovery that facilitates Biologics development: –Pathogenesis, animal disease models, assay & standards development, novel technology (proteomics, genomics, nanotechnology), immunology, molecular biology, biostatistics, epidemiology and clinical science. Extensive extramural collaborations

4. CBER SARS Research Working Group Organized among CBER Staff to prepare for the scientific challenges of anticipated Biologics product development in response to SARS Pro-actively develop broad scientific SARS expertise applicable to anticipated Biologics products Fostering research collaborations between Offices within CBER Rapid discussions of research plans and preliminary data Establishment of coordinated research facilitation processes (e.g., IRB application to RIHSC) Facilitate extramural research collaboration via coordinated contacts with NIH, CDC, Academia, etc. Establish clear communication pathways among researcher-reviewers within CBER Identify needs and coordinate development and use of CBER resources for SARS research (e.g., BSL3)

5. Supporting Vaccine Development CBER, CDC and NIH engaged in joint facilitation of availability of appropriate GLP laboratory isolates for seed stock CBER provided expertise and guidance on: –Manufacturing issues (e.g., up-front recommendations for cell banks, testing needed, etc.) –Use of animal models for vaccine evaluation (non-clinical safety and efficacy evaluations) –Clinical trial design

6. SARS Vaccine: Major Issues Live attenuated vs. killed/component/recombinant –Potential concerns virulence/reversion vs. immunopathogenesis/efficacy –Killed vaccine likely fastest development pathway

7. SARS Vaccine: Major Issues Defining protective antigen/variation & surrogates/durability of protection Determining safety & efficacy: –Animal models/immune surrogates as become known –Field trials likely needed to evaluate protection and for possible immunopathogenesis –LSTs should be feasible if epidemic continues Special populations –IRB challenges in rapidly mobilizing SARS and other EID studies

8. SARS Vaccines: Intramural Studies and Extramural Collaborations –Virus inactivation characteristics –Virus attenuation characteristics –Characteristics of protective immune responses Infection/Disease prevention –Characteristics of immunopathogenic immune responses Infection/Disease enhancement

9. SARS Vaccines: Intramural Studies and Extramural Collaborations –Determining which viral epitopes elicit antibody responses that are most effective for neutralization Surrogate immune markers of vaccine efficacy –Studies of immune globulins to define which populations of antibody provides the highest degree of immunoprotection and to define those which are prominent in enhancing viral infection.

10. At this time no evidence of need for donor screening –Most SARS infected donors will be deferred during screening procedures due to presence of symptoms/signs (e.g., fever) Continued evaluation of new clinical, virological and epidemiological data in preparation to modify approach if indicated SARS & Blood Safety

11. Guidance issued: Recommendations for the Assessment of Donor Suitability and Blood Product Safety in Cases of Suspected Severe Acute Respiratory Syndrome (SARS) or Exposure to SARS. Participation in joint WHO conferences to assess the SARS epidemic worldwide and to consider measures to safeguard the blood supply. –Provided input in the development of a WHO guidance on donor deferral SARS & Blood Safety:Recent Activities

12. Held public discussion at Blood Product Advisory Committee 6/03 about the epidemiology, pathogenesis of SARS agent and the Canadian experience Participated in the FDA sponsored public workshop on “SARS Diagnostics: Scientific and Regulatory Challenges” Collaborating with NIAID/NIH scientists to study the viremia of SARS-CoV agent in blood using animal models

13. Summary CBER scientists can play a significant role in facilitating the development of SARS-relevant biologics products Early identification of critical research questions in support of product development is key to provide a scientific basis for product review and licensing CBER SARS Research Working Group is actively pursuing key questions relevant to biologics product development through intramural research, extramural collaborations and other interactions with the medical research community