Rapid Decontamination Systems - PharmOut€¦ · Rapid Decontamination Systems: 1. Introduction 2. ... Manufacturer ClorDiSys Solutions - USA Delivery Method Dry Gas introduced from

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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


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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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• 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


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


35 or 59% Hydrogen peroxide (Reagent)200-400ppm Target Concentration


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)


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 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


7% Hydrogen peroxide ionised at 17K Volts (Reagent)ppm Target Concentration




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


1 mg/L (Reagent) or 360 ppm720 ppm.hours Standard Cycle




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 – 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]

mailto:[email protected]

Documents

Rapid Decontamination Systems - PharmOut€¦ · Rapid Decontamination Systems: 1. Introduction 2. ... Manufacturer ClorDiSys Solutions - USA Delivery Method Dry Gas introduced from