Laboratory Biosafety

1. Laboratory Biosafety WSLH Teleconference June 27, 2007 Peter A. Shult, Ph.D. Director, Communicable Disease Division and Emergency Laboratory Response Wisconsin State Laboratory of Hygiene __________________________________________________________WSLH

2. Laboratory Biosafety • Historical perspective • Principles of biosafety • Elements of containment including the Biological Safety Cabinet (BSC) • Biosafety levels • Biosafety risk assessment • Biosafety beyond the laboratory walls • Biosecurity __________________________________________________________WSLH

3. Laboratory BiosafetyKey Resources (I) • Biosafety in Microbiological and Biomedical Laboratories (BMBL),5th Ed. U.S. Departmentof Health and Human Serviceshttp://www.cdc.gov/od/ohs/biosfty/bmbl5/bmbl5toc.htm http://www.slh.wisc.edu/wps/wcm/connect/extranet/comdis/ • Laboratory Biosafety Manual, 3rd Ed. World Health Organization, 2004 http://www.who.int.csr/resources/publications/biosafety/ WHO_CDS_CSR_LYO_2004_11/en/ __________________________________________________________WSLH

4. Laboratory BiosafetyKey Resources (II) • Primary Containment for Biohazards: Selection, Installation and Use of Biological Safety Cabinets, 2nd Edition U.S. Department of Health and Human Services Public Health Service Centers for Disease Control and Prevention and National Institutes of Health September 2000 http://www.cdc.gov/od/ohs/biosfty/bsc/bsc.htm • Control of Communicable Disease Manual, 18th Edition David L. Heyman, MD, Editor APHA __________________________________________________________WSLH

5. Laboratory BiosafetyKey Resources(III) • Public Health Guidance for Community-Level Preparedness and Response to Severe Acute Respiratory Syndrome (SARS),Version 2.3; July 20 2004 http://www.cdc.gov/ncidod sars/guidance • Biological Safety: Principles and Practices, 4th Ed ASM Press, 2006 • Laboratory Security and Emergency Response Guidance for Labs Working with Select Agents MMWR, December 6, 2002; Vol.51/ No. RR-19 http://www.cdc.gov/mmwr/PDF/RR/RR5119.pdf __________________________________________________________WSLH

6. Laboratory BiosafetyHistorical perspective (I) • Landmark studies by Pike and Sulkin • Questionnaire assessment • Between 1930 – 1978, 4,079 LAIs with 168 deaths • Most common causative agents of overt infection include: 1. Brucella spp. 6. M.tuberculosis 2. C. burnetti 7. B. dermatidis 3. HBV 8. VEE 4. S. typhi 9. C.psittaci 5. F. tularensis 10. C.immitis • No specific accident orexposure eventin > 80% __________________________________________________________WSLH

7. Laboratory BiosafetyHistorical perspective (II) • Followup worldwide literature search, 1979-2004 • 1, 141 overt infections, 24 deaths • Most common causative agents of overt infection include: 1. M. tuberculosis 6. HBV 2. Arboviruses 7. Shigella spp. 3. C. burnetti 8. Salmonella spp 4. Hantavirus 9. HCV 5. Brucella spp. 10. N. meningitidis • Many asymptomatic infections • Many newer agents, e.g. SARS-CoV, Cryptosporidium, etc. • No specific exposure event in most cases __________________________________________________________WSLH

8. Laboratory BiosafetyHistorical perspective (III) What types of laboratories involved? % of LAIs according to laboratory type 1930-19751979-2004 Clinical 17% 46% Research 59% 50% Production 3% 3% Teaching 3% 1% Unknown 18% < 1% • Reasons for increase in LAIs in clinical labs? • Better surveillance and reporting • Absence of biosafety containment equipment • Failure to use adequate containment procedures early in diagnostic process __________________________________________________________WSLH

9. Laboratory BiosafetyHistorical perspective (IV) What were the predominant means of exposure? • As mentioned before no specific exposure event identified in most cases • Those identified included: • Inhalation of aerosols generated by work practices or procedures or spills • Percutaneous inoculation • Contamination of mucous membranes • Ingestion __________________________________________________________WSLH

10. Laboratory BiosafetyPrinciples of Biosafety • The objective of biosafety is the containmentof potentially harmful biological agents • The purpose of containment is to reduce/eliminate exposure of lab workers, other persons and outside environment to biohazardous agents • Key elements of containment include: • Laboratory practice and technique • Safety equipment (primary barriers and PPE) • Facility design and construction (secondary barriers) • Risk Assessmentof the work to be done with a specific agent or under specific circumstances determines the appropriate combination of these elements to employ __________________________________________________________WSLH

11. Laboratory BiosafetyElements of Containment Laboratory Practice and Technique • Arguably the most important element of containment • Awareness of potential hazardsand training and experience are critical • Applies to pre-analytical, analytical and post-anaytical processes • What about non-traditional testing sites and personnel? • Behavioral factors • Need for clear focus on work – all ages • “Creative innovation” and risk taking • Suggested age relation • Lose the bad habits: sniffing, “hot looping”, etc. • Working in absence of other containment elements __________________________________________________________WSLH

12. Laboratory BiosafetyElements of Containment Safety Equipment (Primary barriers and PPE) • Available for each possible route of exposure • Aerosol: BSCs, covered centrifuge carriers, loop incinerators or disposable loops, PPE (respirators, PAPRs) • Percutaneous: sharps disposal; retractable needles • Mucous membrane contact: goggles or safety glasses, face shields, gloves • Ingestion: automatic pipetting devices __________________________________________________________WSLH

13. Laboratory BiosafetyElements of Containment The Biological Safety Cabinet (I) Arguably the single most important piece of safety equipment in the laboratory! • Information Resources • Importance of the Biological Safety Cabinet • The principal device used to provide containment of infectious splashes or aerosols generated by many microbiological procedures • Provides protection to the operator, the laboratory environment and work materials • Which type is for you? __________________________________________________________WSLH

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15. Laboratory BiosafetyElements of Containment The Biological Safety Cabinet (II) • Follow proper BSC work practices and procedures • BMBL5, Appendix A • They don’t work at all if you don’t use them! • Need for a lab-specific algorithm for BSC use • A POLICY ISSUE • Tie into risk assessment __________________________________________________________WSLH

16. Laboratory BiosafetyElement of Containment Facility Design and Construction (Secondary Barriers) • Contributes to laboratorian safety, however, primary role is to protect persons outside of the lab and persons in the community from agents that might be accidentally released. • Recommended secondary barriers depend on the risk of transmission of specific agents • BSL-1/BSL-2 vs. BSL-3 __________________________________________________________WSLH

17. Laboratory BiosafetyBiosafety Levels • 4 biosafety levels • Consist of combinations of lab practices and techniques, safety equipment and lab facilities • Purpose: To categorize risk associated with infectious agent and define the appropriate safety practices, equipment and facilities for handling the agent safely • Appropriate BSL determined by: • Microbiological agent Risk Group • Mode of transmission • Procedural protocols • Experience of staff • Likelihood of aerosol generation • Work involves use of amplified agent • Other? __________________________________________________________WSLH

18. W.H.O. Agent Risk Group Classification __________________________________________________________WSLH

19. Recommended Biosafety Levels for Infectious Agents “Biosafety in Microbiological and Biomedical Laboratories”,5th Ed __________________________________________________________WSLH

20. Laboratory Biosafety Risk Assessment __________________________________________________________WSLH

21. Handling Unusual Test Requests in the Clinical Lab What is meant by “unusual test request”? • “Novel” agents, high public health impact • SARS, Monkeypox, Avian influenza, smallpox • Agents of particular public health importance • Mumps, measles, rubella, hantavirus, etc. • “Novel” agents, impact uncertain • hMNV, Coronaviruses (non-SARS), Bocavirus, HPV • Rare or exotic agents • B virus, HFVs, chikungunya, dengue, etc. __________________________________________________________WSLH

22. Handling Unusual Test Requests Considering the request Assessments needed • Type of request • Diagnostic capability • Does it exist in lab? Should it be used? • Can it/should it be developed? • Biosafety considerations • Expertise and Experience • Regulatory restrictions on testing __________________________________________________________WSLH

23. Laboratory BiosafetyRisk Assessment(I) • Whose responsibility? • Technically, the lab director • Practically, the bench microbiologist • Primary factors to consider: • Agent hazards • Laboratory procedures planned • Potential for aerosol generation • Consider facility, equipment needed; appropriate PPE • Capability of the staff • Training, technical proficiency, good habits • Known vs. unknown agent risk • For known or suspected agent, consult BMBL agent summary statements, other references • For unknown agent… __________________________________________________________WSLH

24. Laboratory BiosafetyRisk Assessment(II) Risk Assessment for Unknown Agents • Reason for the need • The Age of Emerging Diseases • SARS, avian influenza, influenza A (H2N2) • Key element of the assessment • In addition to above, patient information is critical • Evaluate completeness of patient information to assess risk of specimen testing • When should it be undertaken? • During emergency response (BT or EID) vs. routinely? • Need new biosafety model in the laboratory! • Standard (“Universal”) precautions for blood and fluids • Enhanced precautions for respiratory (and other?) specimens needed??? __________________________________________________________WSLH

25. Laboratory BiosafetyRisk Assessment(III) Other Considerations in the Clinical Laboratory • Strict BSL-2 practices and procedures should be the minimum standard • Biosafety cabinets (BSCs) are a must! • But the reality is… • Needs to be an organizational priority • At minimum, develop algorithm for their use based on risk • What about a possible BSL3 agent but no BSL3 lab? “Mix &match” PPE and good practice with equipment and facility based on risk assessment → BSL 2+ • Be aware of the potential for exposure to a BSL4 agent • Look for “just in time” guidance, e.g. SARS __________________________________________________________WSLH

26. Laboratory BiosafetyBiosafety Beyond the Laboratory Walls • Specimen collection sites • Specimen transport: route and packaging • Specimen labeling and requisition – “A heads up” • Close communication with ICP and clinicians • Don’t forget your rapid test sites! __________________________________________________________WSLH

27. Locations of Sentinel Laboratories and Rapid Test Sites in Wisconsin-2005 Bayfield Douglas Ashland Iron Vilas Washburn Sawyer Burnett Price Florence Oneida Forest Barron Rusk Marinette Polk Lincoln Taylor Langlade Oconto Chippewa Dunn St. Croix Menominee Marathon Clark Pierce Shawano Eau Claire Door Pepin Waupaca Wood Portage Kewaunee Buffalo Outagamie Trempealeau Jackson Brown Manitowoc Waushara Winnebago Juneau Adams Monroe Calumet LaCrosse Marquette Fond du Lac Sheboygan Vernon GreenLake Sauk Columbia Dodge Richland Washington Ozaukee Crawford Sentinel Laboratories Dane Milwaukee Jefferson Waukesha Iowa Grant Rapid Test Sites Green Walworth Racine LaFayette Rock __________________________________________________________WSLH Kenosha

28. Laboratory BiosafetyAddressing Rapid Test Site Biosafety Needs • Obvious need for basic biosafety training • Role for WSLH and clinical labs to participate in training • Strategies to enhance biosafety & reduce potential exposure • Collect & communicate patient travel history and risk factors to testing staff • In most cases, no BSC. Therefore: • Techniques to minimize aerosol production • Consider use of personal protective equipment (PPE) during test performance • Consider use of physical barriers for test performance (e.g., bench shields) • Sequester/isolate testing area __________________________________________________________WSLH

29. Biosecurity • What is biosecurity? • Select Agent Regulations • Elements of a facility security plan __________________________________________________________WSLH

30. Biosecurity What is biosecurity? • Protection of high-consequence microbial agents and toxins, or critical relevant information, against theft or diversion by those who intend to pursue intentional misuse • A concern in light of recent terrorism events • Relationship to biosafety • Its all about risk assessment and containment! • Need for general biosecurity planning??? • No current federal requirement for such a plan • Excellent review in Section VI of BMBL 5th Ed. • Enhanced emphasis under Select Agent regulations • Specific requirement for a facility security plan __________________________________________________________WSLH

31. BiosecuritySelect Agent Regulations What is the Select Agent Regulation and who is affected? Establishes a listing of agents thought to pose a threat to public safety Requires entities that possess any of these agents to follow the guidelines within this regulation Requires a Facility Security Plan http://www.cdc.gov/od/sap __________________________________________________________WSLH

32. Biosecurity Select Agent Regulation • Clinical labs likely to be exempt unless they possess S.A.’s • What are diagnostic/clinical labs required to do if they encounter* a select agent? • Notification • Contact WSLH • Contact CDC by phone • Select agent handling protocol • Within 7 days of identification: • Transfer to registered entity • Destroy---autoclave, incinerate • Documentation • APHIS/CDC form 4; maintain copy for 3 years • APHIS/CDC form 2 if transferred* __________________________________________________________WSLH

33. Biosecurity Elements of a Facility Security Plan • Required under Select Agent Regulations • Pragmatic applications apart from select agents • Conduct risk assessment as precursor to security plan • Element of plan include: • Physical security • Data and IT security • Personnel security assessment policy • Controlled access to areas containing select agents • Select Agent accountability including receipt and transfer • Emergency response plan • Incident reporting system __________________________________________________________WSLH

34. Laboratory Biosafety Any Questions? __________________________________________________________WSLH