Teleconference August 5, 2008

1. NIH Blue Ribbon Panel on Risk Assessment of the BUMC National Emerging Infectious Diseases Laboratories Teleconference August 5, 2008

2. Topics • Work Plan • Update re Risk Assessment studies • Community Engagement Plan • Boston municipal prohibition on use of rDNA in BSL-4 lab

4. Risk Assessments And Risk Communication (Analyses to include impact of risk mitigation and emergency response plans) rDNA BSL-4 (Understanding Scope and Implications) Community Engagement (Strategies for Earning and Sustaining Public Trust)

5. BRP Work Plan • Risk Assessment Studies • BRP will provide ongoing review and advice regarding reports • Risk Mitigation and Emergency Response Plans • To be analyzed as part of risk assessments • BRP will provide ongoing review and advice regarding reports • Risk Communication • BRP will provide input on reports • Community Engagement and Relations • Municipal Prohibition on rDNA BSL-4

6. Risk Assessment Studies • Scope • 12 infectious agents • 12 archetypal scenarios • Analyses to include impact of: • Risk mitigation measures • Municipal emergency response plans • Contract with Tetra Tech • Administered by Army • Statement of Work being finalized • Detailed work plan review by Blue Ribbon Panel and NIH • Ongoing oversight • Blue Ribbon Panel • NIH Coordinating Committee • Timeline: • Target RA completion date: February 2009 • Public Comment: March –April 2009 • Court Filings: May 2009

7. Boston Community Consultations √ May 16th Blue Ribbon Panel meeting in Boston √ July 16th BRP meeting on community engagement ? September BRP meeting to present draft community relations plan: • “High and Maximum Containment Laboratories: Fundamental Principles and Proposed Strategies For Earning and Sustaining Public Trust”

8. Draft Report onEarning and Sustaining Public Trust • Scope: • Specific to BU/BUMC NEIDL • Broad applicability to all BSL-3 and BSL-4 research • Approach: • Articulate fundamental principles • Recommend best practices and proposed strategies • Specific implementation mechanisms left up to local jurisdiction

9. Background Premises (Draft) • Infectious diseases continue to be a major cause of morbidity and mortality worldwide. • Furthermore, in our globalized society, infectious agents that once were endemic to only certain regions are now a potential threat to public health internationally. • High and maximum containment laboratories are essential elements in the national and international infrastructure of research resources to address these pressing public health concerns. • These laboratories not only perform basic research critical to understanding these infectious agents, but also serve as a critical component of the public health response to infectious diseases outbreaks by providing the means for the development of new diagnostic, therapeutic and preventive strategies.

10. Background Premises (Draft) • Of paramount importance is the safety of these facilities, which is undergirded by long-standing, widely accepted biosafety practices and containment standards. • Also key is public trust and understanding of these facilities, as is true of all publicly funded resources. • Toward that end, these facilities must be conceptualized, planned, constructed, and operated in a manner that promotes transparency of their research agendas and fosters community engagement, particularly with respect to the local impact of these facilities. • In the same vein, institutions must be publicly accountable for upholding the highest standards of safety and for being responsible stewards of publicly funded resources.

11. Background Premises (Draft) • Toward that end, the NIH Blue Ribbon Panel has identified a number of fundamental principles and proposed strategies to foster community engagement and to enhance community relations. • These were developed as part of its consideration of the risk assessments and community relations issues associated with the Boston University Medical Center (BUMC) National Emerging Infectious Diseases Laboratories (NEIDL) and are offered to aid the U.S. government and BUMC in fulfillment of their commitment to the Federal courts to develop “a community relations plan to improve community input and involvement.”[1] • In the context of the BUMC NEIDL, these recommendations are applicable only to the extent that the outcome of the ongoing risk assessment studies and court cases point to the acceptability of conducting research under high and maximum containment conditions. • That particular case notwithstanding, the Panel views these recommendations as broadly applicable to high and maximum containment laboratories in operation or under contemplation for construction in this country. • [1] In response to an October 20, 2006 order by the Federal District Court

12. Draft Principles • Rigorous independent local review of BSL3 and BSL-4 research • Maximal transparency regarding facility operation, nature of research, and oversight of research • Community representation • Appropriate technical expertise • Ongoing oversight

13. Proposed Strategies • Independent and transparent local review and oversight of research • Phase-in of research operations • Community liaison activities

14. Current Scope of Local Independent Review • Currently IBC review mandated only for rDNA and Select Agent research • Review includes: • Community representatives • Biosafety and scientific expertise • Authority to approve/disapprove rDNA protocols • Ongoing oversight throughout life of research project • Meetings and minutes open to public (Note: details pertaining to security or commercial confidential may be redacted) • No such review and oversight mandated for work with non-recombinant infectious agents and non-Slect Agents

15. BRP Recommendation: Expanded Scope of Independent Review • BRP recommends independent review body to review and provide ongoing oversight all BSL-3 and BSL-4 research • Institutional implementation: all infectious disease research in high or maximum containment ought have review and oversight by a local review body • For the BUMC NEIDL this body would optimally include: • Independent Chair, 2 community reps, 2 BU reps, 2 public health commission representative experts, 2 independent scientists • BPHC act as secretariat for the body

16. Independent Review: Expertise • Scientific and Safety Review • National peer review of scientific merit (for funding decisions) • Local review • Encompasses scientific merit, biosafety, and community perspectives • Expertise needed: • Infectious diseases, microbiology, molecular biology • Biosafety • Community perspectives

17. Phase-in of Research Operations • Standard practice for launching high and maximum containment labs entails phasing in operations • Training • Systems assessment • Local independent review of research protocols proposing to initiate BSL-3 or BSL-4 research includes an assessment of the institutional and investigator safety record for prior research with infectious agents

18. Community Liaison Activities • Institutions with maximum containment laboratories should develop community liaison activities to foster: • Input from community about impact of lab on community • Can help further inform community representatives on local independent review body • Communication to the community about operation of the lab • Education about research and health targeted at adults and children

19. Potential BRP Meeting In Boston • Location: Community venue • Date: Mid-September • Time: 7:00 – 10:00 PM • Purposes: • Present draft report: “High and Maximum Containment Laboratories: Fundamental Principles and Proposed Strategies For Earning and Sustaining Public Trust” • Hear from community • Presentation from Boston Public Health Commission on plans for review and oversight of research at the NEIDL

20. Update re rDNA BSL-4 Research • Since 1994 the City of Boston has an ordinance that prohibits use of rDNA under BL-4 conditions. • SECTION 3.00 RESTRICTIONS • 3.01. RDNA use requiring containment defined by the [NIH Guidelines for Research Involving Recombinant DNA Molecules] as "BL4" shall not be permitted in the City of Boston. • The Boston Public Health Commissioner has confirmed [1] that the restriction applies not only construction of agents that must be done under BL-4 conditions, but to their subsequent use in research, as well. • Note: In the event of a public health emergency, the BPH Commissioner has the authority to override this prohibition and allow such work at the BSL-4 level (e.g., diagnostic analyses of patient samples) [1] In a June 11, 2008 telephone conversation with NIH OBA staff.

21. Boston rDNA BSL-4 Prohibition: Clarifying Scope and Implications • Developing a set of Q/As, to be reviewed by Boston Public Health Commission, NIH and BUMC, regarding scope and implications of Boston prohibition on rDNA BSL-4 research • What is the prohibition? • What was the impetus for its enactment? • What rDNA can be done? What rDNA cannot be done? • What are the implications of this restriction on the NEIDL fulfilling its mission as a National Biocontainment Lab? • Q/A’s will provide factual basis for incorporation into court filings

22. Discussion

23. Backpocket Slides

24. NIH Guidelines: RG-4 Agents and BSL-4 Containment • Under the NIH Guidelines, organisms are classified according to Risk Groups (1-4) that provide a starting point in the risk assessment process. • Risk Group 4 agents (e.g., Ebola virus, Herpes B virus) are typically worked with under BL-4 conditions, unless there are mitigating circumstances. • Section III-D-2-a states experiments utilizing DNA from Risk Group 4 agents may be performed under BL-2 conditions only after “demonstration that only a totally and irreversibly defective fraction of the agent’s genome is present in a given recombinant.”