Overview of Federal Regulations, Guidelines The comments and slides presented here solely represent my and Policies Governing Biosafety and views and do not represent the positions of Biocontainment in High Containment the U.S. Government or of AAAS…

Laboratories All content and discussion is solely and exclusively taken from publically available material.

Marci Wright, PhD Presentation to the Biocontainment Work Group Department of Health and Mental Hygiene State of Maryland 15 November 2012

Outline The history of the issue with the Federal government Government Accountability Office How many Trans-Federal Task Force on Optimizing Biosafety and BSL‐3 and BSL‐4 Biocontainment Oversight (2009)* labs are in the US?  What the Trans-Federal Task Force determined Framework for existing Federal oversight Do they have sufficient Role of state and local oversight Recommendation1.2: Develop a Federal Registry Federal biosafety oversight?  Existing Federal oversight Statutes, Regulations, Guidelines and Policies Sen. Joseph Lieberman (D‐CT) Are they secure?  Industry Best Practices and an International Model Sen. Barbara Collins (R‐ME) Senate Committee on Homeland Security & Governmental Affairs Government Accountability Office Trans-Federal Task Force on Optimizing Biosafety and Biocontainment Oversight 2007 GAO report: 2007: Chaired by HHS and USDA “no single Federal agency has the mission and, therefore, is accountable for Charge: evaluate existing Federal tracking the number of all BSL-3 and BSL-4 labs within the United States….” oversight of high (HCL) and “no Federal agency is responsible for determining the risk associated with maximum (MCL) containment expanding the number of high and maximum containment laboratories.” laboratories, and make recommendations for enhancing Federal oversight without hindering 2008 Commission on Weapons of Mass Destruction report: research.

“…consider centralizing the regulatory functions for biosafety and biosecurity by 2009: Identified16 recommendations developing a new oversight mechanism for high-containment laboratories….” to enhance Federal oversight, including a recommendation to establish a Federal registry of all U.S. HCLs (2.2) The Report of the Trans-Federal Task Force on Optimizing Biosafety and Biocontainment Oversight (July 2009) http://www.phe.gov/Preparedness/legal/boards/biosafetytaskforce/Pages/default.aspx.

Trans-Federal Task Force on Optimizing Biosafety Trans-Federal Task Force on Optimizing Biosafety and Biocontainment Oversight and Biocontainment Oversight

Existing HCL Oversight Recommendation 1.2: “Multiple, complementary, and sometimes overlapping biosafety and “Develop a registry of all Issue: no USG mechanism to identify biocontainment oversight and track all HCLs in the U.S. requirements exist at [these] levels”: high and maximum containment research  Identification/tracking/accounting  Capacity assessments  Federal facilities in the United  State  Oversight quality assurance  Municipal States”  Information sharing  Institutional Short and long term steps to explore Layered and deliberately redundant mechanisms to address this gap in approach to lower risk from working biosafety and biocontainment with hazardous biological agents oversight. The Report of the Trans-Federal Task Force on Optimizing Biosafety and Biocontainment Oversight (July 2009) The Report of the Trans-Federal Task Force on Optimizing Biosafety and Biocontainment Oversight (July 2009) http://www.phe.gov/Preparedness/legal/boards/biosafetytaskforce/Pages/default.aspx. http://www.phe.gov/Preparedness/legal/boards/biosafetytaskforce/Pages/default.aspx. HCL or High Containment Lab Definitions HCL or High Containment Lab Definitions Biosafety Level 3 Laboratory (Minimal) Biosafety Level 3 Laboratory (Minimal)

Engineering controls: Engineering controls:  Secure access via anteroom  Secure access via anteroom  Two interlocking doors  Two interlocking doors  Sealed penetrations  Sealed penetrations  Hands free sink at lab exit  Hands free sink at lab exit  Ducted, negative airflow into lab  Ducted, negative airflow into lab  Specialized exhaust (e.g. HEPA)  Specialized exhaust (e.g. HEPA)

Administrative controls: Administrative controls:  Occ Health program  Occ Health program  Initial and, thereafter, annual  Initial and, thereafter, annual certification/validation certification/validation  Personnel training/proficiency  Personnel training/proficiency

Work Practices controls: Work Practices controls:  Enhanced PPE  Enhanced PPE  Open manipulations in BSC or  Open manipulations in BSC or other 1° containment other 1° containment  Decon on site  Decon on site Image taken from the WHO Biosafety Manual, 3rd Ed. 2004 Image taken from the WHO Biosafety Manual, 3rd Ed. 2004 CDC/NIH. Biosafety in Microbiological and Biomedical Laboratories, 5th Edition. 2007 CDC/NIH. Biosafety in Microbiological and Biomedical Laboratories, 5th Edition. 2007

Definitions Federal Regulations Some Infectious Microorganisms That May Be Manipulated Using BSL3 principles, practices and facilities*

Recombinant or Select Non-recombinant synthetic Agents non-synthetic microorganisms microorganisms OSHA General Duty OSHA Standards Select Agent Regulations Import / Transportation Select Agents: Regulations Risk Group 2: Clostridium botulinum, Bacillus anthracis Risk Group 3: Burkholderia mallei, pseudo, Monkeypox Virus, SARS-CoV, HPAI aH5N1

Non Select Agents: Risk Group 2: Chlamydophila psittaci, C. trachomatis Risk Group 3: Mycobacterium tuberculosis; 1957 non/com hH2N2, JEV, HIV, WNV Risk Group 4: Herpes B virus (simian)

* Determination of biosafety levels are based on biological risk assessments. Refer to Biosafety in Microbiological and Biomedical Laboratories, 5th Edition (CDC/NIH, 2007) for a discussion of the biological risk assessment process. The Report of the Trans-Federal Task Force on Optimizing Biosafety and Biocontainment Oversight (July 2009) Risk Groups: NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules. March 2013 http://www.phe.gov/Preparedness/legal/boards/biosafetytaskforce/Pages/default.aspx. STATUTE STATUTE OSH Act, 1970 OSH Act, 1970 Occupational Safety and Health Administration Occupational Safety and Health Administration Laboratory Safety Standards General Duty Clause

“furnish to each of [its] employees employment and a place of employment which are Exposure Control Personnel Training: Record Keeping: free from recognized hazards that are causing or likely to cause death or serious Plan: physical harm to [its] employees.” Purpose: Scope: Responsibilities:  Exposure  All occupational  Hazard determination settings that are Communications  This provision allows  All occupational  Identify and mitigate covered by OSH Act. OSHA to enforce settings that are serious hazards  Procedures for  Training records workplace safety covered by OSH Act. based on national evaluating incidents  All employees for even when specific consensus standards whom the standard is  Incident records hazards are not  Includes all U.S. and industry best  Implementation of relevant covered in an HCLs. practices (CDC, NIH standard and risk  OSHA 300 Log existing standard. NIOSH, ANSI). mitigation SOPs  Includes all U.S. HCLs  For HCLs: administrative, work

29CFR1910 29 U.S.C. 654(a)(1), Section 5(a)(1) practice, and engineering controls.

STATUTE STATUTE OSH Act, 1970 OSH Act, 1970 NSP Act, 2001 Occupational Safety and Health Administration Occupational Safety and Health Administration Personal Protective Equipment Standards Bloodborne Pathogens Standard “protective equipment, including personal protective equipment for eyes, face, head, eliminate or minimize employee exposure to human blood or other potentially and extremities, protective clothing, respiratory devices,andprotective shields infectious materials. and barriers, shall be provided, used, … wherever it is necessary by reason of hazards … capable of causing injury or impairment...” Eye and Face Respiratory Protection: Hand Protection: Purpose: Scope: Responsibilities: Protection:  Full or partial face  Measures to prevent  Protects workers  All employees with  Identify and mitigate  Eye or face shields respiratory protection to absorption of harmful from pathogenic “reasonably hazards, including to prevent injury from prevent transmission of substances; … microorganisms that anticipated” needlestick hazards hazards: liquid aerosols through filter punctures; chemical are present in human exposure to human chemicals, acids or media. burns; thermal burns blood and can cause blood and body fluids  Write/implement ECP caustic liquids, gases  Medical evaluation disease in humans,  Train employees or vapors  Annual fit test  Handwashing facilities including HBV and  Includes all U.S.  Offer HBV vaccine  Mucous membranes HIV. HCLs in which  Keep records  Soap / paper towels  N-95 respirators, PAPRs  Gloves applicable work is  Safety glasses, performed 29CFR1910.1030 29CFR1910.132-134/138 goggles, face shields STATUTE STATUTE OSH Act, 1970 OSH Act, 1970 Occupational Safety and Health Administration Occupational Safety and Health Administration Additional Relevant Standards Proposed Standard: Provisions in the following standards also help eliminate or minimize exposure to Reducing Occupational Exposure to LAIs biological agents and toxins: Rule Making Process  OSHA must demonstrate that the standard: Occupational Exposure to Hazardous Chemicals in Laboratories (Laboratory Standard) 29 CFR 1910.1450 1. substantially reduces a significant risk of material impairment or harm 2. employs the most cost-effective means of achieving its protective goal Hazardous Waste Operations and Emergency Response (HAZWOPER) 29 CFR 1910.120 Purpose: Scope: Responsibilities:

Sanitation 29 CFR 1910.141  If enacted, would  Patient support  Worker infection cover contact  Infectious agent control plan Medical Services and First Aid 29 CFR 1910.151 transmissions not transport  Occ Health Program  Work in laboratories  Hazard Access to Employee Exposure and Medical Records 29 CFR 1910.1020 covered by the BBP Standard (e.g. Communications Hazard Communication 29 CFR 1910.1200 MRSA)  May include HCLs  Record Keeping

Retention of DOT Markings, Placards and Labels 29 CFR 1910.1201 http://www.regulations.gov/#!documentDetail;D=OSHA-2010-0003-0236

STATUTE OSH Act, 1970 Occupational Safety and Health Administration HCL Performance Record Occupational Safety and Health Administration General Duty Clause and Lab Safety Standards Standard Industrial Inspections: Academic/Private Private Record Keeping Infectious Clinical / Federal Classification: Research/R&D R&D Regulations: Agent Diagnostic Intramural NIH Funded no NIH $  HCLs and MCLs are  OSHA conducts  HCLs are partially Mycobacterium either classified facility inspections, exempt from OSHA Tuberculosis under the broad SIC either as an record keeping w/GFP Reporter 8731 category for unplanned activity or regulations. Outside “commercial physical in the context of the of a fatality or Bacillus and biological National Emphasis catastrophe, HCLs Anthracis research” or SIC Program (NEP). are not required to w/GFP reporter 8733 for non- HCLS are not report injuries and commercial specifically targeted illnesses unless Synthetically organizations (e.g. in the NEP. specifically derived hH2N2 academic requested by OSHA n/contemporary institutions). or BLS. wildtype

29 U.S.C. 654(a)(1), Section 5(a)(1) and 29 CFR 1910 Sample Survey Results A Review of Biocontainment Lapses and Laboratory-acquired Scientific Research and Development Injury and Illness Data Infections: Intramural NIAID Incidents from 1982-2003 US Department of Labor, Bureau of Labor Statistics (2006)

 Overall injury and illness rates for NAICS Code 5417 is well below the national  one clinical infection without secondary consequences average  four silent infections in more than 3 million hours  DART rate: 2.3 is the national average and 0.6 is the NAICS Code 5417 average  Includes continuous exposure of personnel to HIV+ HBB fluids. One case required prophylaxis; no infection occurred.

The Report of the Trans-Federal Task Force on Optimizing Biosafety and Biocontainment Oversight (July 2009) DHS Environmental Impact Statement Process for the National Bio and Agro-Defense Facility, Appendix B. 2009. http://www.phe.gov/Preparedness/legal/boards/biosafetytaskforce/Pages/default.aspx. http://www.dhs.gov/xlibrary/assets/nbaf_feis_appendix_b.pdf

STATUTE STATUTE Bioterrorism Bioterrorism HHS and USDA/APHIS Act, 2002 HHS and USDA/APHIS Act, 2002 Select Agent Regulations Select Agent Regulations

Outline the requirements for possession, use, and transfer of select agents and Outline the “requirements for possession, use, and transfer of select agents and toxins. The biological agents and toxins listed … have the potential to pose a severe toxins. The biological agents and toxins (BSAT) listed … have the potential to pose a threat to public health and safety, to animal health, or to animal products. severe threat to public health and safety, to animal health, or to animal products”.

Adherence to Scope: Registered entity: Consideration of Scope: Registered entity: technical guidance is technical guidance is mandated for  All occupational  Can be institution mandated for  All occupational  Training informing the settings of entities (assigns an RO) or informing the settings of entities  Transfers Biosafety Plan: that are registered person (is the RO) Biosafety Plan: that are registered  Theft, Loss, and Release with the National with the National  BMBL Select Agent  Security Risk  BMBL Select Agent  Restricted Experiments  OSHA Standards Program. Assessment / Personnel  OSHA Standards Program.  AM resistance  NIH Guidelines Reliability  NIH Guidelines  Toxins

 Includes all HCLs  Includes all HCLs (LD50 <100ng/kg) located in SAP  Biosafety, Security, and located in SAP registered entities. Incident Response Plans registered entities. 42 CFR 73, 7 CFR 331, 9 CFR 121 42 CFR 73, 7 CFR 331, 9 CFR 121 Public Health Security and Bioterrorism Preparedness and Response Act, 2002 Public Health Security and Bioterrorism Preparedness and Response Act, 2002 STATUTE STATUTE Bioterrorism Bioterrorism HHS and USDA/APHIS Act, 2002 HHS and USDA/APHIS Act, 2002 Select Agent Regulations Select Agent Regulations What’s New Infectious Clinical / Federal Academic/Private Private Tier 1 Agents: Registered entity: Research/R&D R&D Agent Diagnostic Intramural NIH Funded no NIH $  BSAT that present the greatest  Ongoing personnel risk of deliberate misuse with reliability program for Mycobacterium the most significant potential for those with access to Tier Tuberculosis mass casualties or devastating 1 Agents w/GFP Reporter effects to the economy, critical Bacillus infrastructure; or public  New physical security Anthracis confidence requirements (Tier 1) w/GFP reporter Ebola virus, Marburg virus, Variola major virus, Variola minor virus, Francisella New Additions to BSAT List: Synthetically tularensis, Yersinia pestis, Botulinum  SARS-associated CoV (BSL3) derived hH2N2 neurotoxin and botox producing Clostridia,  Chapare Virus n/contemporary Bacillus anthracis, Burkholderia mallei,  Lujo Virus Burkholderia pseudomallei wildtype

42 CFR 73, 7 CFR 331, 9 CFR 121 Public Health Security and Bioterrorism Preparedness and Response Act, 2002 42 CFR 73, 7 CFR 331, 9 CFR 121

STATUTE STATUTE US Government Import, Transfer, and Export Regulations HHS and USDA/APHIS CDC Foreign Quarantine Regulations These regulations cover transportation of infectious microorganisms within and to the United States (Department of Transportation and USDA/APHIS), and importation Infectious Clinical / Federal Academic/Private Private from other countries (HHS/CDC and USDA/APHIS). Research/R&D R&D Agent Diagnostic Intramural NIH Funded no NIH $ CDC Foreign Quarantine Regulations Mycobacterium Tuberculosis Import Regulations for Infectious Biological Agents, Infectious Material, and Vectors w/GFP Reporter

 Prevent introduction of exotic communicable diseases into the US Bacillus Anthracis  Through the Etiologic Agent Import Permit Program, any importation of w/GFP reporter etiological agents of human disease must be accompanied by a permit from CDC. Synthetically derived hH2N2 n/contemporary wildtype

42 CFR 71.51 42 CFR 73, 7 CFR 331, 9 CFR 121 STATUTE STATUTE US Government Import, Transfer, and Export Regulations USDA/APHIS

These regulations cover transportation of infectious microorganisms within and to the Plant and Health Protection Acts United States (Department of Transportation and USDA/APHIS), and importation Academic/Private Private from other countries (HHS/CDC and USDA/APHIS). Infectious Clinical / Federal Research/R&D R&D Agent Diagnostic Intramural NIH Funded no NIH $ USDA/APHIS Plant and Animal Health Protection Acts: Mycobacterium Tuberculosis Plant Protection Act w/GFP Reporter  control importation, entry, exportation, or movement in interstate commerce of any plant, plant product, biological control organism, noxious weed Bacillus*  “Organism and Soil” / “Plants and Plant Products” permits granted through Anthracis the Plant Protection and Quarantine (PPQ) Service w/GFP reporter Animal Health Protection Act Synthetically  control importation or movement in interstate commerce of any animal … to derived hH2N2 prevent the introduction or dissemination of any pest or disease in the US n/contemporary  Permits are granted through Veterinary Services (VS) Centers wildtype

7 CFR 330, 340 9 CFR 122 7 CFR 330, 340 9 CFR 122

STATUTE STATUTE US Government Import, Transfer, and Export Regulations US Government Department of Transportation Regulations These regulations cover transportation of infectious microorganisms within and to the United States (Department of Transportation and USDA/APHIS), and importation from other countries (HHS/CDC and USDA/APHIS). Infectious Clinical / Federal Academic/Private Private Research/R&D R&D Agent Diagnostic Intramural DOT Transportation of Etiologic Agents: NIH Funded no NIH $

Infectious substances and materials known or suspected to contain them are Mycobacterium regulated as Division 6.2 (infectious) hazardous materials under the Pipeline and Tuberculosis Hazardous Materials Administration (PHMSA) Hazardous Materials Regulations w/GFP Reporter (HMR; 49 CFR 171-180) Bacillus* Anthracis  Each institution must package and ship infectious agents using approved shipping packaging and labeling w/GFP reporter  Each shipper mush be trained in the Safe Transport of Division 6.2 Infectious Synthetically Substances, Biological Specimens, Dry Ice and Related Materials derived hH2N2  the shipping courier must have a security plan to prevent unauthorized access n/contemporary  Civil or criminal penalties wildtype

49 CFR 171-180 and 49 CFR 802 STATUTE STATUTE FIFRA 1947 FIFRA 1947 Environmental Protection Agency Environmental Protection Agency Federal Insecticide, Fungicide, and Rodenticide Act Federal Insecticide, Fungicide, and Rodenticide Act

“provide federal control of pesticide distribution, sale, and use. All pesticides used Infectious Clinical / Federal Academic/Private Private in the United States must be registered (licensed) by EPA, properly labeled, will Research/R&D R&D Agent Diagnostic Intramural not cause unreasonable harm to the environment. Use of each registered pesticide NIH Funded no NIH $ must be consistent with use directions contained on the label or labeling.” Mycobacterium Purpose: Scope: Responsibilities: Tuberculosis w/GFP Reporter  This provision allows  All antimicrobial  Product cannot Bacillus EPA to enforce pesticides cause adverse health Anthracis standards regarding (sanitizers, effects the use of disinfectants,  Demonstrate efficacy w/GFP reporter when properly use, in disinfectants, sterilants) Synthetically sterilants and agreement with antimicrobial  Applicable to all U.S. efficacy data and derived hH2N2 pesticides. HCLs. labeling n/contemporary  User must use as wildtype indicated 7 U.S.C. 136-136y and 40 CFR 150-189 7 U.S.C. 136-136y and 40 CFR 150-189

Federal Guidelines GUIDELINE Voluntary* CDC/NIH Best Practice Biosafety in Biosafety in Microbiological and Biomedical Laboratories Microbiological and Biomedical Laboratories “the code of practice for biosafety – the discipline of addressing the safe handling and containment of infectious microorganisms and hazardous biological materials”

NIH Guidelines for Purpose: Scope:  Sets forth biocontainment Research Involving principles based on: Recombinant or  Introduced in 1984  Diagnostic, research, 1. work practices Synthetic Nucleic Acid  5th Edition (2007) and large scale 2. safety equipment Molecules  Uses containment production activities 3. facility safeguards and risk assessment principles to prevent  Human and Biological risk assessment: NIH Design laboratory associated agricultural Process to determine the Requirements infections (LAIs) etiological agents biocontainment required to Manual prevent LAIs

CDC/NIH. Biosafety in Microbiological and Biomedical Laboratories, 5th Edition. 2007 * Select Agent Regulations mandate that all registered entities should consider BMBL as part of compliance with the Select Agent Program. The Report of the Trans-Federal Task Force on Optimizing Biosafety and Biocontainment Oversight (July 2009) * NIH Grants Policy Statement recommends BMBL for use in developing and implementing health and safety operating http://www.phe.gov/Preparedness/legal/boards/biosafetytaskforce/Pages/default.aspx. procedures and practices for both personnel and facilities GUIDELINE GUIDELINE Voluntary* Voluntary CDC/NIH Best Practice CDC/NIH Best Practice Biosafety in Microbiological and Biomedical Laboratories Biosafety in Microbiological and Biomedical Laboratories Private Infectious Clinical / Federal Academic/Private “the code of practice for biosafety – the discipline of addressing the safe handling and Research/R&D R&D Agent Diagnostic Intramural containment of infectious microorganisms and hazardous biological materials” NIH Funded no NIH $

Organization: Biological Risk Resources: Mycobacterium Assessment: Tuberculosis  Biorisk Assessment Evidence based literature w/GFP Reporter  Biosafety Principles  Agent and procedure Bacillus*  BSL, ABSL 1-4, and hazards Appendices: Anthracis equivalent agricultural  Facility safeguards Applicable Federal regulations laboratory criteria  Personnel Decontamination w/GFP reporter  Lab Biosecurity proficiency 1° Containment Synthetically  Occ Heath Agricultural Biosafety  Special populations derived hH2N2  Agent Summary Arthropod and Primate n/contemporary Statements wildtype CDC/NIH. Biosafety in Microbiological and Biomedical Laboratories, 5th Edition. 2007 * Select Agent Regulations mandate that all registered entities should consider BMBL as part of compliance with the Select Agent CDC/NIH. Biosafety in Microbiological and Biomedical Laboratories, 5th Edition. 2007 Program. * Select Agent Regulations mandate that all registered entities should consider BMBL as part of compliance with the Select Agent * NIH Grants Policy Statement recommends BMBL for use in developing and implementing health and safety operating Program. * NIH Grants Policy Statement recommends BMBL for use in developing and implementing health and safety operating procedures and practices for both personnel and facilities procedures and practices for both personnel and facilities

GUIDELINE GUIDELINE T&C of NIH T&C of NIH NIH funding NIH funding Guidelines for Research Involving Recombinant or Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules Synthetic Nucleic Acid Molecules “specify practices for constructing and handling recombinant nucleic acid “specify practices for constructing and handling recombinant nucleic acid molecules, synthetic nucleic acid molecules ... and cells, organisms and viruses molecules, synthetic nucleic acid molecules ... and cells, organisms and viruses containing such molecules” containing such molecules” Purpose: Scope: Responsibilities: Covered activities: Layered Oversight: Enforcement:

 Provides oversight of  All research  Establish Institutional  Risk Group 1 – Risk  Exempt (BSO  NIH can suspend, limit or rDNA and synthetic conducted at Biosafety Committee and Group 4 human determination?) terminate $ for non- research activities at institutions receiving Biosafety Officer (for BSL-3 etiologic agents  IBC approval compliance with the NIH the local (IBC) and any NIH funding for or large scale activities) to  IBC/IRB approval Guidelines funding agency (NIH research, including review covered research and  Animal and plant  IBC, NIH OBA OD and RAC) levels. research testing in specify required biosafety biocontainment approval  Compliance is mandated humans levels and additional safety  IBC, RAC and NIH in NIH Grants Policy requirements to conduct the Director approval Statement research. NIH Grants Policy Statement NIH Grants Policy Statement NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules. March 2013 NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules. March 2013 * Select Agent Regulations mandate that all registered entities should consider NIH Guidelines as part of * Select Agent Regulations mandate that all registered entities should consider NIH Guidelines as part of compliance with the Select Agent Program compliance with the Select Agent Program GUIDELINE GUIDELINE T&C of NIH T&C of NIH NIH funding* NIH funding* Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules Federal Federal Infectious Clinical / Academic/Private Private Infectious Clinical / Academic/Private Private Intramural Research/R&D R&D Intramural Research/R&D R&D Agent Diagnostic Agent Diagnostic Research NIH Funded no NIH $ Research NIH Funded no NIH $ Mycobacterium Mycobacterium Tuberculosis N/A Tuberculosis N/A w/GFP Reporter w/GFP Reporter ? ? Bacillus* Bacillus* Anthracis N/A Anthracis N/A w/GFP reporter w/GFP reporter Synthetically Synthetically derived hH2N2 derived hH2N2 n/contemporary N/A n/contemporary N/A wildtype wildtype ? ?

NIH Grants Policy Statement NIH Grants Policy Manual NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules. March 2013 NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules. March 2013 * Select Agent Regulations mandate that all registered entities should consider NIH Guidelines as part of * Select Agent Regulations mandate that all registered entities should consider NIH Guidelines as part of compliance with the Select Agent Program compliance with the Select Agent Program

REQUIREMENT REQUIREMENT NIH Owned NIH Owned NIH NIH Design Requirements Manual (DRM) Design Requirements Manual (DRM) “promulgates minimum performance design standards for NIH owned and leased “NIH grant-supported construction or modernization” new buildings and renovated facilities, ensures that those facilities will be of the highest quality to support Biomedical research” The minimum design Grantees are not subject to the Covered activities: requirements for NIH grant- NIH site specific requirements Purpose: supported construction or contained in the NIH Design  Provides minimum  Lays out specific BSL3 and modernization are set forth in 42 Requirements Manual but performance design ABSL3 facility design CFR 52b.12. The NIH Design should meet the intended standards. requirements, including Requirements Manual design objectives in such HVAC incorporates the regulatory cases. Scope: standards for construction or  Outlines a set of criteria for the NIH BSL-3 certification modernization grants and those  NIH owned and and validation process. for major A&R projects. leased new buildings and renovated facilities NIH Grants Policy Statement (http://grants.nih.gov/grants/policy/nihgps_2012/nihgps_ch10.htm) NIH Grants Policy Statement (http://grants.nih.gov/grants/policy/nihgps_2012/nihgps_ch10.htm) NIH Design Requirements Manual for Biomedical Laboratories and Animal Research Facilities (DRM).2008. NIH Design Requirements Manual for Biomedical Laboratories and Animal Research Facilities (DRM).2008. Industry Best Practices GUIDELINE Industry Best Practices STANDARD Clinical Labs Clinical Laboratory Standards Institute International Organization for Standardization (ISO) Protection of Laboratory Workers from Laboratory Quality Assurance and Medical Laboratory Safety Standards Occupationally Acquired Infections

“detailed recommendations for the protection of workers from disease agents ISO15189 transmitted from aerosols, droplets, blood and body substances.” Focus on HIV, HBV, “Medical laboratories — Particular requirements for quality and competence” HCV. - quality management system

Outlines: ISO15190 “Medical laboratories -- Requirements for safety” Protection Techniques -risk group classification Med Waste Management -designing for safety Diagnostic Instrumentation and Equipment -hazard identification -incident reporting - aerosols Enforcement: - BSCs College of American Pathologists (CAP) Laboratory Accreditation Program - PPE - Personnel training

Clinical and Laboratory Standards Institute M29-A3, 3rd Ed. http://www.iso.org

Industry Best Practices WORKSHOP Canadian Human Pathogens AGREEMENT and Toxins Act (2009) When enacted, will function as a National Registry:

European Committee for Standardisation  Requires that all institutions involved in CWA 15793:2011 a controlled activity with all Risk Group Biorisk Management “Standard” 2 – Risk Group 4 agents be licensed.  Possession “The organization shall establish, document, implement and maintain a biorisk  Producing / Storing management system in accordance with the requirements of this laboratory biorisk  Transfer / Import management standard.”  Abandoning  Disposing Outlines management practices for: Biological Hazard Identification Risk Assessment and Management  Requires that a licensee:* Work Practices Occupational Health  Identify licensee location and Training Emergency Response “to establish a safety and security name, and license period Laboratory Biosecurity regime to protect the health and safety  Facility description of the public against the risks posed by  Inventory of all agents used Enforcement: human pathogens and toxins” tied to international laboratory accreditation programs Criminal penalty for noncompliance CEN CWA 151793:2011 Biorisk Management Standard Guidance document at: http://www.absa.org/pdf/CENprCWA_55_2011_Guidanceon_CWA15793.pdf Canadian Human Pathogens and Toxins Act. 2009 Thank You