Biocontainment laboratories Current issues and challenges

Transcription

1 The 2009 Belgian Biosafety Symposium Design and Construction of Biocontainment Laboratories 3 rd Dec 2009 Biocontainment laboratories Current issues and challenges Uwe Müller-Doblies Institute for Animal Health Pirbright Laboratory

2 Biocontainment laboratories Current issues and challenges 1 1. Introduction 2. Implementation of CEN CWA Biorisk Management Standard 3. Safety Case Approach to high consequence activities 4. One Biosafety 2

3 Institute for Animal Health Centre of excellence for research on infectious diseases of farm animals ~380 staff + research students + visiting workers Compton Pirbright 3

4 IAH: Pirbright Laboratory 1. African Horse Sickness Virus 2. African Swine Fever Virus 3. Bluetongue Virus 4. Classical Swine Fever Virus 5. Foot and Mouth Disease Virus 6. Rinderpest 7. Peste de Petits Ruminants 8. Lumpy Skin Disease Virus 9. Sheep & Goat Pox Virus 10. Swine Vesicular Disease 11. Epizootic Hemorrhagic Disease of Deer 4

5 Vacuum Drains

6 CL4 Isolation Units

7 Necropsy facility Air supply via socks creating vertical laminar flow Exhaust at low level Prefilters changeable from below

8 Current Issues Quantifying controls air filters, directional air flow, pipe work, concrete, seals Safety Performance Indicators Green Containment Sustainability: flexible space usage standardisation Systems for biorisk management Forms of Contract for construction of high containment facilities condition based maintenance One Biosafety 8

9 International Veterinary Biosafety Workgroup 9

10 International Veterinary Biosafety Workgroup Need to exchange information and share problems/issues relating to large animal (CL3+) biocontainment facilities network of biosafety officers and directors of national high containment animal facilities First Meeting USA, 1991 Subsequent meetings in Europe, North America, Australia, New Zealand, Singapore, Argentina. 10

11 International Veterinary Biosafety Workgroup IVBW: Sharing Best Practice best practice containment solutions best practice pathogen handling protocols validation of procedures facility design risk assessment and management Risk Groups and Biosafety Levels Facility Maintenance Decontamination Solutions in Developing Countries 11

12 IVBW: Outputs Desirable features of biocontainment facilities for agricultural and research animals Rev sci Tech Off Int Epiz (OIE Technical Bulletin) Handbook for Veterinary Containment Facilities 2006 workshops every 18 months on different topics in changing locations 12

13 Biocontainment laboratories Current issues and challenges 2 1. Introduction 2. Implementation of CEN CWA Biorisk Management Standard 3. Safety Case Approach to high consequence activities 4. One Biosafety 13

14 CWA as seen by some quality managers another hat

15 CWA as seen by some facility directors looks good. We are seen to be doing the right thing.

16 CWA as seen by some biosafety officers QuickTime and a decompressor are needed to see this picture. an elephant inside a boa?

17 QuickTime and a decom pr essor are needed t o see t his pict ure. CWA as seen by a converted biorisk officer a logic extension to ISO AND OHSAS 18001

18 Standards for Veterinary Biosafety? OIE guidelines national regulations for veterinary biosafety national human biosafety guidelines CEN Biorisk Management Standard IVBW Handbook for Veterinary Containment Facilities EU Minimum Containment Standards for FMDV Laboratories 18

19 Minimum Containment Standards for Laboratories handling FMDV 1985, 1993, (2009) EU FMD Directive 2003/85/EC 1. Minimum Containment Standards for FMD Laboratories for countries free of FMDV 2. Minimum Standards of Biorisk Management for Laboratories Undertaking Diagnostic Investigations of Low-risk Samples During an Outbreak of FMD 19

20 CWA15793 Risk Assessments Which risk assessment methodology for which application? sensitivity specificity time & cost reproducibility HAZOP CHAZOP FMEA SWIFT Bow Tie LOPA Human Factor Analysis 20

21 Factors determining the fumigation strategy Fumigation Requirements Fumigant Specific Issues Sealability Environmental Conditioning Operational Requirements Toxicity Pressure differentials no hot and cold spots Frequency Penetration into porous materials (e.g. paper/cloth) Work Place Exposure Limits validation requirements fumigant concentrations ventilation in adjacent spaces means of testing sealability before fumigation stable relative humidity Temperature >20 degree C air mixing in the space emergency or planned 4log or 6 log Overpressure protection with or without soiling BIs or target organisms fumigant dispersion properties Material Compatibility 21

22 Biocontainment laboratories Current issues and challenges 3 1. Introduction 2. Implementation of CEN CWA Biorisk Management Standard 3. Safety Case Approach to high consequence activities 4. One Biosafety 22

23 Piper Alpha An explosion and resulting fire destroyed it on July 6, 1988, killing 167 men. Piper Alpha must never happen again... Safety Case Approach 23

24 The Cullen Report Offshore Safety Case New improved Safety Regime Safety Case Process 1993 Goal Setting Approach 75% reduction in incidents offshore 24

25 Piper Alpha and FMDV 167 deaths in 22 minutes >3.4 billion GBP Safety Case regime in outbreak 200 m GBP 2001 outbreak 8 billion GBP No proven transmission chain HSE: FMDV facilities high hazard industries Single Regulatory Framework IEC61508 philosophy 25

26 Safety and Risk Data 26

27 Setting a safety target for a facility handling high consequence animal pathogens Balance between cost of the facility and cost of a consequential release Cost benefit of the facility: FMD outbreaks through accidental introduction occur at a rate of years without an FMD facility, Benefit from operating FMD facilities: reduce the impact through rapid diagnostics, disease intelligence and preimport testing. target of 1 consequential release in 500 years puts the laboratory release into the noise of the natural signal 27

28 Integrated Protection Layers 28

29 Layer of Protection Analysis 29

30 Target Risk Concept people SOP PPE Barrier Shower off-site quarantine fomites lab SOP Barrier Process off-site Process effluent disinfection heat inactivation aerosol Lab SOPsMBSC 1 HEPA 2 HEPA Inward airflow 10-Dec IAH Target Risk Level for a consequential release years -1

31 IEC Functional safety of electrical/electronic/programmable electronic safetyrelated systems performance target setting layer of protection analysis assessment of safety instrumentation systems safety case approach safety life cycle management Safety Integrity Levels 31

32 Bowtie Risk Management Diagram Thesis Enterprise Risk Management Tool courtesy ABS Consulting

33 Environmental Protection 33

34 Operator Protection 34

35 Formalised Bowtie file Use of Thesis Software Courtesy of ABS Consulting 35

36 Setting a safety target for a facility handling high risk animal pathogens Balance between cost of the facility and cost of a consequential release Cost benefit of the facility: FMD outbreaks through accidental introduction occur at a rate of years, operating facilities limit the damage through early response and preimport testing target of 1 in 500 years puts the laboratory release into the noise of the natural signal 36

37 Controls Passive Controls Active Controls Management Controls air tight barrier construction Double Exhaust HEPA filtration, supply HEPA protection Supply Multiple compartment access lobbies Box in a box principle directional inward air flow Air changes Open door velocity air flow Barrier shower & change protocols Fully encapsulated suits latched alarms on loss of pressure differential HEPA filter validation Control system separate from alarm system Process validation 37

38 BIOCONTAINMENT AT AAHL Level 5 Plant room (clean) Level Pa HEPA FILTER AIR SUPPLY HEPA FILTER AIR EXHAUST Air distribution and treatment Level Pa SHWR -250 Pa -300 Pa -300 Pa -250 Pa Work floor Level 2 SEWAGE COLLECTION SEWAGE TREATMENT Level 1

39 What is achievable and what is sustainable? Are our engineering controls sustainable in a marginally funded lab with poor access to electricity, fresh water, service engineers? What biosafety measures are sustainable and acceptable under local conditions? How can we move biological agents both ways without common principles of containment barriers? Can we deny access to reference agents on the basis of insufficient evidence of suitable biocontainment at the receiving laboratory? 39

40 Safety Integrity Levels PFD (Probability of Failure on Demand) and RRF (Risk Reduction Factor) probability of dangerous failures per hour (PFHd) SIL PFD RRF PFHd to < to < , to < , ,000 40

41 Animal versus human biosafety in CL3/4 human biosafety operator is at risk most in vivo work is done in animal models that fit into isolators with exceptions animal biosafety operator is not at risk cattle and other livestock species do not fit into isolators -isolation rooms most in vivo work is done in the target species quarantine is used as a tertiary control 41

42 Cost Benefit Consider a chemical plant with a process that if it were to explode could lead to: * 20 fatalities * 40 permanently injured * 100 seriously injured * 200 slightly injured The rate of this explosion happening has been analysed to be about 1 x 10-5 per year, which is 1 in 100,000 per year. The plant has an estimated lifetime of 25 years. How much could the company reasonably spend to eliminate (reduce to zero) the risk from the explosion? If the risk of explosion were to be eliminated the benefits can be assessed to be: Fatalities: 20 x 1,336,800 x 1 x 10-5 x 25 yrs =6684 Permanent injuries: 40 x 207,200 x 1 x 10-5 x 25 yrs = 2072 Serious injuries: 100 x 20,500 x 1 x 10-5 x 25 yrs = 512 Slight Injuries: 200 x 300 x 1 x 10-5 x 25 yrs = 15 Total benefits = 9,283 42

43 Layers of Protection Vacuum vs Gravity 43

44 Showers in a risk model 44

45 Biocontainment laboratories Current issues and challenges 4 1. Introduction 2. Implementation of CEN CWA Biorisk Management Standard 3. Safety Case Approach to high consequence activities 4. One Biosafety 45

46 One Biosafety More emphasis on zoonotic diseases sustainable biocontainment solutions for countries and facilities without infrastructure to sustain hi-tech/himaintenance facilities and equipment. 46

47 Top Events Operator exposure tight primary containment Environmental Release primary containment secondary containment isolator overpressure suit isolation room within secondary containment 47

48 One Biosafety activity based containment solutions reduce the risk at source - diagnostics on inactivated samples an un-maintainable or unmaintained engineering control can be worse than a well managed procedure Which standards should developing countries follow? 48

49 Environmental/veterinary hazard group (Environmental Protection) Hazard Groups for Viruses Environmental and Human Health Hazard Groups vhg 4 FMDV Rinderpest ASFV ENDV, SVDV HPAI, Rabies Nipah, Ebola, Marburg vhg 3 BTV, (BVDV) VSV, NSDV RVFV, Akabane, EEE, WEE, VEE, JE, WNV Hendra vhg 2 vhg 1 RHDV, BVDV AI, NDV BSE, Q Fever OHFV, (TBE), HIV, HepEV CCHFV, Lassa, Junin, Machupo,KFDV hhg 1 hhg 2 hhg 3 hhg 4 Human hazard group (operator protection) 49

50 Thank you! Questions? 50