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Rapid Decontamination
Systems
Brett Cole. Biosafety Pty Ltd
Monday 11th July 2016
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Rapid Decontamination Systems:
1. Introduction
2. Why decontaminate?
3. The general rules for a successful decontamination (penetration,
distribution, efficacy, adaptability)
4. Regulations and obligations – Australian Standards, ISO, Dept of
Health Services
5. Planning, Execution and Validation
6. The various common and emerging technologies used for rapid
decontamination and sterilization
7. Case Studies
8. Conclusion
9. Questions
Rapid Decontamination Systems:
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• Bachelor of Science with Honours Degree – Microbiology (Monash University)
• Masters Degree in Occupation Hygiene and Toxicology (Edith Cowan University)
• Over 15 Years experience in Infection, Waste and Contamination Control (Healthcare, Pharmaceutical and Laboratory)
• Committee Member of ABSANZ Regulatory Committee (OGTR, DAFF and AS/NZS)
• Member of Australia Institute of Occupational Hygiene (MAIOH)• Member of Australian Standards Committees (CH-029) Safety in
Laboratories Standards• Licensed Fumigation Company (Dept of Health and Human Services)• Member of ANZLAA, ABSANZ, SCRIA, ISPE and ACPIC
Professional Experience-
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Why Decontaminate?
▪ To create a Sterile baseline
▪ Renovation (Before or after)
▪ Between Population / Production Batches
▪ Commissioning
▪ De-Commissioning
▪ Contamination/Infection
▪ Preventative Maintenance
▪ Regulatory compliance
▪ GMP/Best Practice
▪ Other…
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What makes for a good decontamination?
All Decontamination methods can work based on the
following:
➢ Must reach ALL surfaces for a prescribed
amount of time, which means you must have:
1. Good and Complete Distribution
2. Thorough and Total Penetration
3. Sufficient Contact Time
4. At specified concentration
5. At required Environmental conditions
(temp/RH)
Any decontamination method requires a complete
and thorough distribution of the sterilant or high level
liquid disinfectant to get an effective decontamination
or kill
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What makes for a good decontamination?
Other considerations:
• Containment of fumigant
• Disposal of fumigant via ventilation, neutralization,
Filtration/Scrubbing
• Material compatibility
• Safety – all fatally toxic at use concentrations
• Regulatory compliance
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Microbial Resistance
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Sterilizers (Sporicides): Used to destroy or eliminate all forms of microbial life including fungi, viruses, and all forms of bacteria and their spores. Spores are considered to be the most difficult form of microorganism to destroy. Therefore, EPA considers the term Sporicide to be synonymous with "Sterilizer.“ (Log 6 Reduction)
Disinfectants: Used on hard inanimate surfaces and objects to destroy or irreversibly inactivate infectious fungi and bacteria but NOT necessarily their spores. Disinfectant products are divided into two major types: hospital and general use. (Log 4 Reduction)
Sanitizers: Used to reduce, but not necessarily eliminate, microorganisms from the inanimate environment to levels considered safe as determined by public health codes or regulations. (Log 2 Reduction)
Antiseptics and Germicides: Used to prevent infection and decay by inhibiting the growth of microorganisms. Because these products are used in or on living humans or animals, they are considered drugs and are thus approved and regulated by the Food and Drug Administration (FDA).
http://www.epa.gov/oppad001/ad_info.htm
Types of Antimicrobial applications:
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Size comparisons
Organism sizes vs. droplet/molecule
Showing the tight areas where organisms
can hide, this is a scratch in stainless steel
which is harboring bacteria
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ComplianceCompliance with:
• Australian Standards AS/NZS 2243.3-2010 Safety in Laboratories –
Microbiological Containment (Update out for public comment)
• AS/NZS 2252 Controlled Environments
• AS 2467 General Requirements for Fumigation
• OGTR PC3 and 4 Regulations
• DAWR (AQIS) QC 2 and 3 Requirements
• ISPE/ISO Regulations (Pharmaceutical)
• Good Manufacturing Practice (GMP)
• Licensed Fumigation Company (Dept of Health and Human Services
etc)
• Required Validation Methods for successful decontamination
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Planning for decontamination
• Define purpose and scope: rooms, equipment, HVAC
• Identify the players, area production managers,
• OH&S, facilities engineering, QC validation, security, emergency
services, other facility users
• Establish responsibilities (SWMS, SOP, Who’s who)
• Select decontaminating agent (Best fit-for-purpose)
• Establish the schedule and ordering
• Write SOPs, fumigation management plan (AS 2467 24 hour
notification)
• Define validation: BIs, full PQ, target dosage
• Hand back procedure
References: Harris (2010)B & V Testing, INC.
AS 2467 (2008) General Requirements for Fumigation
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Planning for decontamination:Execution of the process
• Prepare area; pre-clean, BI placement, fan, distribution, monitor
readiness, seal area, safety perimeter, signage
• Reach target temp/humidity; monitor
• Create safety perimeter/signage
• Introduce chemical and bring to target concentration for target
exposure time; monitor
• Monitor surrounding areas for leakage
• Ventilate and/or neutralize to below OEL
• Incubate/analyze BIs as specified
• Provide reporting as required
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Rapid Decontamination Systems:
• Formaldehyde
• Ozone (Cold Plasma/UV Generated)
• Vapourised Hydrogen Peroxide
• Ionised Hydrogen Peroxide
• Chlorine dioxide
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Formaldehyde :Decontamination Parameter Description
Technology NA –Frypans???
Manufacturer NA
Delivery Method In room – hot plate method
Target concentration required for 6-log reduction
0.3g of paraformaldehyde per cubic foot
of volume (NSF 49 Annex G)
8000-10000 ppm
Typical Cycle Condition – Charge – Dwell –Neutralisation - Aeration
Typical Cycle Length (BSC/Isolator) Overnight
Typical Cycle Length (Room – 250m3) 12-24 hours
Biological Indicators Used Typically
Other validation methods NA
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Formaldehyde:
Benefits:
• Scalable (just add more hot plates
1000cu ft / hot plate)
• Inexpensive
• True Gas (boiling point -19oC)
• Requires RH 65+%
• At the end of exposure neutralization is
done using ammonia bicarbonate
Challenges:
• Long Contact times (6-12 hours)
• Requires high concentrations to achieve
sporicidal effects (8000-10,000 ppm)
• Leaves Residue and Carcinogenic
• Carcinogen (USDHHS & IARC*)
• Creates residues (post exposure cleanup
required)
• Formaldehyde “falls out” upon contact with
cold surfaces
• Large space decontamination is troublesome
due to cleanup required, can all surfaces be
realistically wiped to remove all residues
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OzoneDecontamination Parameter Description
Technology Cold Plasma/UV Generated (185nm)
Manufacturer NA
Delivery Method In room
Target concentration required for 6-log reduction
up to 70 ug/ml
Typical Cycle Condition – Charge – Dwell - Aeration
Typical Cycle Length (BSC/Isolator) NA
Typical Cycle Length (Room – 250m3) 24-36 hours
Biological Indicators Used Geobacillus stearothermophilus
Other validation methods Chemical O3 Monitoring
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Ozone
Benefits• Person removed from the process (Safety)
• True Gas at room temp (boiling point -112oC)
• Low cost equipment • No post exposure cleanup required
Challenges• Generators do not generate enough for room decontamination (used mainly for odor
control)• Ozone is extremely volatile with short life span (20-30 min)• Limited efficacy1
• Long cycle time (up to 36 hours)• Requires high RH 80%-95%• Issues with large volume (getting concentration to all areas due to short life span. • Corrosive ( high oxidation potential 2.07) • Not US-EPA registered process• Not NSF approved for BSC cabinets
1 Foarde, Karin and Eaton, Cary, Ph.D. “Ozone Antimicrobial Efficacy” EPA/600/R-08-137, Dec 2007 http://www.epa.gov/nrmrl/pubs/600r08137/600r08137.pdf6 hours exposure 1000ppm 4.3log reduction of spores with high RH >80%
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Vapourised Hydrogen Peroxide:Decontamination Parameter Description
Technology VHP
Manufacturer Steris Corporation - USA
Delivery Method Vapourisation (via heat plate) or microdroplet through high airflow
Target concentration required for 6-log reduction
35 or 59% Hydrogen peroxide (Reagent)200-400ppm Target Concentration
Typical Cycle Condition – Charge – Dwell - Aeration
Typical Cycle Length (BSC/Isolator) 45 minutes
Typical Cycle Length (Room – 250m3) 4-6 hours depending on conditions (temp/RH)
Biological Indicators Used Steris NA333 biological indicators. 24- 72 hours incubation time, stainless steel coupon Geobacillus stearothermophilus
Other validation methods Real time H202 room concentration
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Vapourised Hydrogen Peroxide :
Benefits:
• Clean and simple to use.
• By products water and oxygen.
• Real time room conditions are
measured for fully validated cycles
with print outs.
• Integration with facility HVAC is
possible.
• High efficacy at low concentrations.
Full SAT validation for
pharmaceutical or GMP
applications.
Challenges:
• Expensive equipment compared
with other methods.
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Vapourised Hydrogen Peroxide:Case Study:
High Containment Laboratory:
• Krishnan et al (2006)
• 85m3 (3000 cubic feet)
• Open room with two BSC/Isolators
• Dry Cycle (Humidity brought down
to 40%)
• Cycle time = 200 minutes (3.3
hours) not including aeration
• Aeration took 24 hours
• Complete Kill was achieved (6-log
reduction)
• Suitable alternative to
formaldehyde
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Vapourised Hydrogen PeroxideDecontamination Parameter Description
Technology HPV
Manufacturer Bioquell - UK
Delivery MethodFlash Evaporation of Peroxide and high velocity distribution (Mobile “In Room” generators as well as Semi-fixed and Fixed decontamination solutions via hoses/pipework)
Target concentration required for 6-log reduction
30 to 35% Hydrogen peroxide (Reagent)The amount of HPV required to achieve >6log reduction is dependent on a number of factors such as enclosure size and starting conditions, hence PPM concentration is not used as a target to determine cycle efficacy. Bioquell offers both Parametric gassing cycles and Timed gassing cycles for GMP, validated through the use of biological and chemical indicators.
Typical Cycle Condition – Charge – Dwell - Aeration
Typical Cycle Length (BSC/Isolator) Under 60 minutes. Cycle time can be decreased with additional generators.
Typical Cycle Length (Room – 250m3) 24 hours including set up and pack up (2200m3 room)
Biological Indicators Used Bioquell HPV-BI Biological Indicator Type: 6-log Geobacillusstearothermophilus ATCC 12980
Other validation methods Bioquell Chemical Indicators
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Vapourised Hydrogen Peroxide
Benefits:
• Residue Free
• Excellent Material Compatibility,
• Fast, Safe (only by-products are
water vapour and oxygen)
• Proven research based efficacy
against a broad spectrum of
biological contaminants (see
published Bioquell’s efficacy
document)
• GMP Compliant
Challenges:
• Often confused with low
concentration aerosolised hydrogen
peroxide systems
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Vapourised Hydrogen PeroxideCase Study:
Laboratory:
• Bioquell Published Project
• 2200m3
• Multiple Machines used
• Complete Process in less
than 24 hours
• Complete Kill was achieved
(6-log reduction)
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Ionised Hydrogen Peroxide:Decontamination Parameter Description
Technology Ionised Hydrogen Peroxide (IHP)
Manufacturer TOMI Inc - USA
Delivery Method In room
Target concentration required for 6-log reduction
7% Hydrogen peroxide ionised at 17K Volts (Reagent)ppm Target Concentration
Typical Cycle Condition – Charge – Dwell - Aeration
Typical Cycle Length (BSC/Isolator) 60 minutes
Typical Cycle Length (Room – 250m3) 4-6 hours depending on conditions (temp/RH)
Biological Indicators Used Steris NA333 biological indicators. 24- 72 hours incubation time, stainless steel coupon Geobacillus stearothermophilus
Other validation methods Real time H202 room concentration using Draeger H2O2 Meter
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Ionised Hydrogen Peroxide
Benefits:
• Clean and simple to use.
• By products water and oxygen.
• Scalable (each unit can do 35m3
and three systems can do up to
105m3)
• Easily Transportable
Challenges:
• None noted
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Chlorine dioxide gas:Decontamination Parameter Description
Technology Chlorine dioxide gas (ClO2 or CD)
Manufacturer ClorDiSys Solutions - USA
Delivery Method Dry Gas introduced from outside target area
Target concentration required for 6-log reduction
1 mg/L (Reagent) or 360 ppm720 ppm.hours Standard Cycle
Typical Cycle Condition – Charge – Dwell - Aeration
Typical Cycle Length (BSC/Isolator) 85 minutes
Typical Cycle Length (Room – 250m3) 2-4 hours depending on conditions (temp/RH)
Biological Indicators Used NAMSA Tyvek Strip in Tyvek Envelope Geobacillusstearothermophilus – 36 hours incubation
Other validation methods Real time Cl02 room concentration
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Chlorine dioxide gas:
Benefits:
• Dry gas process - No residue
• Scalable (one machine does up to
1983m3)
• Real time room conditions are
measured for fully validated cycles
with print outs (GMP compliant)
• Able to penetrate HEPA filters
• Rooms, BSC, Isolators, HVAC are
able to done at same time
• Fastest Process
Challenges:
• Expensive equipment compared
with other methods
• Oxidiser
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Chlorine dioxide gasCase Study:
PC3 Laboratory:
• Griffith University Glycomics Facility
• 276m3
• Multiple rooms with BSC’s
• Cycle (Humidity raised to 65%)
• Cycle time = 180 minutes (3 hours)
including aeration
• Aeration took less than 1 hour
• Complete Kill was achieved (6-log
reduction)
• Complete project completed in 7
hours (set up to pack up)
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Comparisons between technologies
Key
H2O2-1 = Wet VHP Process
H2O2-2 = Fogging Process
H2O2-3 = Dry VHP Process
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Comparisons between technologies
Key
H2O2-1 = Wet VHP Process
H2O2-2 = Fogging Process
H2O2-3 = Dry VHP Process
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Biosafety Case Studies
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Case Study: BioSperix Cell Isolator:
PC2 Suite 1 x Biosperix Isolator
Equipment: 1 x Generator, 1 x Carbon Scrubber
Total Cycle Time = 4 hours
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Case Study: BioSperix Cell Isolator
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Case Study: Facility Handover - Cyclotron Facility
Three Areas with GMP Critical Areas with 3 stage physical clean, ISO 14644-1
Validation and Sterilization
Total Project Duration = 6 days (1 day for decontamination)
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Case Study: Facility Decontamination – Redundant Penicillin Facility
Facility with 2 stage physical clean and Inactivation using Chlorine dioxide gas
Total Project Duration = 8 days (6 days prep, 1 day gas, 1 day aeration)
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Case Study: Facility Decontamination – Redundant Penicillin Facility
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Case Study: Facility Decontamination – Redundant Penicillin Facility
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Case Study: Facility Decontamination – Animal Facility – Pinworm Outbreak
Facility with single stage physical clean and pinworm egg Inactivation using
Chlorine dioxide gas
Total Project Duration = 7 days (6 day clean, 1 day gas)
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Case Study: Facility Decontamination – Animal Facility – Pinworm Outbreak
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Case Study: Facility Decontamination – New PC3 Facility – Griffith University
Glycomics (~800m3 over two levels)
Facility Decontamination using Chlorine dioxide gas
Total Project Duration = 2 days (Day 1 – General PC3, Day 2 – Animal)
including BSC, Ante Room and HEPA Housings
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Case Study:
Facility Decontamination – New PC3 Facility – Griffith University Glycomics
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Summary:
• Decide Why you are decontaminating and what level of decontamination you require (6-log, 4-log etc)
• Viable alternatives to formaldehyde gas exist for efficacious and safe decontamination of pharmaceutical production areas and isolators/BSC
• Understand the physical properties and behaviour of your decontaminant of choice to ensure efficacy and safety
• Different decontaminants may be appropriate for different applications
• All decontaminants have benefits and challenges• All decontaminants are dangerous to humans. They are all
designed to kill• Planning and safety are the two most important aspects of
successful decontamination
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Acknowledgements:
I would like to acknowledge of the following people for assisting in
compiling the information on the various technologies:
• Mr Brendan Edwards (Allied Scientific) – VHP Steris Corporation
• Mr Bernie Crampsie (Biodecon Solutions) – VHP Bioquell
• Mr Darren Spittal (LAF Technologies) – IHP Sterimist
• Mr Mark Czarneski (ClorDiSys Solutions) – Chlorine dioxide gas
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ANY QUESTIONS?
Thank you for your time!
Please feel free to email me at [email protected]