CBER Regulatory Laboratory Planning & Preparedness for SARS-related Biologics Products

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. SARS & Blood Safety • 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

11. SARS & Blood Safety:Recent Activities • 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

12. SARS & Blood Safety:Recent Activities • 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