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VHP Bio-decontamination

Jon Nottingham, CAPE Europe Biovac December 2013

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Here is the your introduction to VHP:

� The VHP (Vaporised Hydrogen Peroxide)

process – history and process

description,

� Principal application techniques,

� Commercially available VHP equipment,

� Some applications,

� Qualification and validation

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Bio-decontamination in isolators – History of VHP

• Low concentration liquid hydrogen Peroxide was know to be

an effective disinfectant for many years. It was widely used

for example in the dairy industry.

• In the late 1980s the American Sterilizer Company (now

STERIS Corporation) demonstrated that hydrogen peroxide

was highly sporicidal as a vapour and much less damaging

to the environment than the sporicial agents being used at

the time.

• Vaporized Hydrogen peroxide was registered as a sterilant

by EPA in 1990.

• In 1992 the first VHP® vapour generators were introduced

into the pharmaceutical and research markets.

•

• Today there are more than 1500 VHP installations worldwide.

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VHP bio-decontamination – Definition and

application techniques:

• VHP bio-decontamination is best described as low temperature,

chemical surface bio-decontamination.

• There are 3 methods commercially available for applying VHP:

• As a vapour – VHP is kept in the vapour phase during the bio-

decontamination cycle.

• As a condened vapour – VHP concentration is taken over the

dew point so that the vapour condenses.

• As a spray – the VHP solution used is sprayed into the volume

to be bio-decontaminated

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Cleaning

VHP®

Bio-decontamination

The decontamination ladder

Manual cleaning: using

detergents and biocides

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Vaporized hydrogen peroxide vapour phase process

Hydrogen

Peroxide

35%

Vaporization

H2O2

Cold Sterilization

Process

0-80oC

H2O

O2

+

Sporicidal at Low Concentrations

(Typically 0.1-2 mg/L at 25oC)

Odorless, colorless

Non-Toxic

Residues

VaproxTM

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VHP Bio-decontamination – efficacy

Bacterial Spores

�Mycobacteria

�

Non-enveloped, non-lipid viruses(hydrophilic)

�Gram-negative

vegetative bacteria

�Fungi

�Large non-enveloped

viruses

�Gram-positivebacteria

�Enveloped, lipid

viruses(lipophilic)

Bacillus stearothermophilusBacillus pumilusBacillus subtilisBacillus anthracisBacillus cereusBacillus circulansClostridium sporogenesClostridium botulinumClostridium tetani

Mycobacterium smegmatisMycobacterium terraeMycobacterium bovisMycobacterium tuberculosisNocardia lactamdurans

Parvoviridae (mouse and canine parvovirus)

Picornaviridae (Polio Type 1, Swinevesicular virus, Rhionvirus 14)

Reoviridae (Blue-tongue, Avian reovirus)

Caliciviridae (Vesicular exanthema)Pseudomonas aeruginosaBurkholdia cepaciaSerratia marcesensEscherichia coliEscherichia coli O157Proteus vulgarisSalmonella choleraesuis

MoldsAspergillus nigerAspergillus terrusFusarium oxysporumPenicillium crysogenum

YeastsCandida parapsilosisSaccharomyces cerevisiaeRhodotorula glutinis

Adenovirus (Adenovirus 2)Poxviridae (Vaccinia)

Orthomyxoviridae (Influenza, Influenza A2)Paramyxoviridae (Newcastle)Herpesviridae (Pseudorabies, Herpes Simplex)Rhaboviridae (Vesicular stomatitis)Toga/Flaviviridae (Hog cholerae, BVD)

Enterococcus faeciumEnterococcus faecalisStaphylococcus aureusLactobacillus caseiListeria monocytogenesLegionella pneumophilia

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HOO .

.

HO 1O2

O*

H2O2

Breaks down Structure and

function of Internal +

External

Cell Components

Generates Hydroxyl Radicals and

Superoxide AnionsLipid • RNA • Carbohydrate DNA • Endotoxin •

Protein

H2O + O2

How it works - oxidation of cell

contents

“Hydrogen Peroxide antimicrobial activity is

dramatically increased when in a gaseous phase”

Journal of Microbiological Methods, 2007 Investigations of a prion infectivity

assay to evaluate methods of a decontamination. Fichet, et al..

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VHP vapour phase bio-decontamination – theoretical

cycle

Typical VHP® Cycle

Dehumidification

Condition

Sterilization

Aeration

100 %

VHP®

Concentration

More

Less0 %

Relative

Humidity

Cycle

Phase

Gas Concentration

Relative Humidity

Condensation Point

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VHP-Sporicidal Efficacy

0.1

1

10

0 0.5 1 1.5 2 2.5 3 3.5

Vapor Conc. (mg/L)

Avg. D-V

alue (min)

Bacillus stearothermophilus spores

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VHP bio-decontamination – the “Wet or condensing” process

0

100

200

300

400

500

600

0 20 40 60 80 100 120

Time Minutes

Gas Concentration ppm

Condensation Index x 10

Theory Gas Concentration ppm

Condensate grms x 10

GassingDwell

Dew pointplateau

Fractional -ve kill 106 10

mins in dwell

Aeration 1ppm (OEL)2 hours

Diagram with kind permission of Bioquell

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Closed Loop gas generators - Steris VHP®

1000, ARD or M100S, Bioquell Clarus L and

C, PEA VHP gas generator, Skan integrated

system, Bosch SafeVAP, Steris

M1000/M100,

Examples of Low temperature VHP

Closed loop Bio-decontamination equipment

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Examples of Low temperature “vapour” Open loop

Using modular generators

Steris T4 at Hikma , Portugal

Steris M100SSX at

Imperial college

London

Remote operator interface for T4

Steris M100 at

NVI Holland

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VHP closed loop generator

STERIS®

VHP® 1000 Flow Diagram

Sealed

Enclosure

H2O2Reservoir

Vaporizer

HEPA

Filter

Desiccant

Chamber

Pre-Heater

Catalytic

Converter

HEPA

Filter

H2O2Cartridge

STERIS®

VHP® 1000 Flow Diagram

Sealed

Enclosure

H2O2Reservoir

Vaporizer

HEPA

Filter

Desiccant

Chamber

Pre-Heater

Catalytic

Converter

HEPA

Filter

H2O2Cartridge

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The closed loop generator on the a sterility test isolator

Inlet manifoldReturn manifold

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Vapour Phase

• 600 – 1000 ppm ( 1 mg/l = 720 ppm) for typical isolator applications,

• 400 to 600 ppm for most common room decontamination

Condensed/Spray

Around 400 ppm for typical isolator applications (probes only measure vapour phase),

Around 200 ppm for most common room decontamination

H2O2 Concentration measuring devices – Target

concentrations

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Dräger POLYTRON/ATI electrochemical cells

0 - 50 ppm Low concentration – LC,

Minimum resolution 0.1 ppm, accuracy +/- 20% using SO2

calibration method,

High concentration – HC

Scale configurable to 1000ppm, 4000 ppm or 7000 ppmaccuracy +/- 20% full scale using SO2 calibration method, +/-10% using H2O2

Both can be integrated into the isolator, example chart recorder output

Dräger PAC III Personnel Monitor – Operator surveillance 0 – 10 ppm.

H2O2 Concentration measuring devices – Routine measurement

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Bio-decontamination system qualification – Actual

cycle from the sterility test isolator

Time at

or above

average

800 = 50 -

25 =25'

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Integrated VHP system for a CL3 lab

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Pharmaceutical production plant – Large capacity

integrated VHP distribution system

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Examples of VHP transfer hatches

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Bio-decontamination system cycle development

CYCLE DEVELOPMENT

(H2O2) Temperature

mapping

CI tests with

Gas concentration

measurement

If required optimise cycle -

Highest concentration

Shortest cycle

Check results

Against initial

Criteria for base

Cycle calculation

Programme

base cycle

and record initial

conditions

Adjust parameters

and repeat temperature

Mapping. Record final

configuration

Start here

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Bio-decontamination

system qualification

Bio-decontamination

system qualification

Tests must include

alarm testing with

BMS if applicable

IQ/OQ of gas

generator Rooms/HVACI

Q/OQ

BMS IQ/OQ

PQ testing of

system

Define rational

for choice of load

patterns and kill

level

Cycle

development

Choose

representative

configurations. May

not need to use BIs

Base cycle

calculation

Base cycle

should be

supplied by

generator

manufacturer

VHP Bio-decontamination qualification

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Contact info

Jon Nottingham MSc P. Eng, BSc Ind, Eng.

• 22 years Isolator and Bio-decontamination Specialist,

• Validation Specialist,

• Pharmaceutical Engineer,

• Member of PDA BI task force.

CAPE EUROPE Ltd.

• Company has been in existence for over 8 years,

• Team of specialists offering expertise in Applications Engineering,

• Design, Build and Validation of VHP Bio-decontamination Systems

• and Controlled Aseptic Process Environments.

• Manufacturers and suppliers of Rapid transfer ports

Tel 0044 (0)7909598533

Fax 0044(0)1264338859

E-mail: Cape-europe@ntlworld.com