Webinar Slides from October 11 2017 - Vaisala · , Pharmaceutical Engineering Guide, Volume 3, Sterile Product Manufacturing Facilities (2011). PDA: PDA Technical Report No. 34. Design

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Webinar Slidesfrom October 11th 2017

Vaporized H2O2Bio-Decontamination in Isolators &Transfer Hatches

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Meet the Presenters

Webinar Vaporized hydrogen peroxide bio-decontamination2

Piritta MaunuLife Science Regulatory and Industry Expert at Vaisala with over 15 years of experience in biotechnology and life science applications.

Sanna LehtinenProduct Manager at Vaisala with 20 years of experience in life science applications and wide product management experience from leading international high tech companies.

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Vaisala within Industrial & Life Science Industries


Our Goal is to Help Customers• Reduce their risk of lost or

adulterated product • Reduce their risk of failing to

meet GxP regulations and/or guidelines

Our OfferingMeasurement instrumentation, continuous monitoring systems and validation for regulated or highly controlled life science environments.

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Agenda

1. Why H2O2?

2. Terminology, Regulations and Definitions

3. Bio-Decontamination Measurements

4. Technology Comparison

5. Cycle Development

6. Typical Process Conditions

7. From Monitoring to Controlling (H2O2, ppm levels)

8. How to Select the Right Sensor?


1. Why H2O2?

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Benefits of H2O2 Bio-Decontamination

Easy to use

Destroys all biological contaminants

Works in low temperature processes

Processes can be validated

Compatible with a wide variety of materials

Environmentally friendly process

Leaves no real residues – only water vapor and oxygen

2017 Industrial Instruments seminar

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H2O2 Measurement Applications

Referense: Transparency Market Research: Hydrogen Peroxide (H2O2) Measurement Market


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H2O2 Vaporization Process


2 H2O22H2O + O2

6-59% liquid H2O2

Vaporization e.g. heat plate, typically around 100°C

Low temperature process, often in room temperature

Ventilators No residues

Typically 500-1200 ppm

Aeration

2. Terminology, Regulations and Definitions

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Isolators, cRABS and Transfer Hatches


Isolators and closed Restricted Access Barrier Systems for e.g.

• Aseptic filling• Sterility testing• Pharmacy compounding

Transfer Hatches (THs) or material pass through cabinets for

• Moving supplies and things from one purity area to another

• Transferring materials in cleanrooms

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Relevant Regulations


European Medicines Agency (EMA): Eudralex Volume 4, EU GMP, Annex 1, Manufacture of

Sterile medicinal products (2009)

Food and Drug Administration (U.S.): Guidance for Industry, Sterile Drug Products Produced by

Aseptic Processing — Current Good Manufacturing Practice 2004.

EN ISO: 14644 Part 1, Part 2 (2015) Cleanrooms and associated

controlled environments. 13408, Aseptic Processing of Health Care Products,

– Part 6 Isolator systems (2005 & Amendment 1: 2013)

https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2008_11_25_gmp-an1_en.pdf

https://www.fda.gov/downloads/Drugs/Guidances/ucm070342.pdf

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Relevant Regulations


PIC/S: PI012-3 , Recommendation of Sterility testing (2007).

PI-014-3, Recommendations, Isolators used for Aseptic Processing and Sterility Testing (2007).

PI 007-6, Validation of aseptic processes (2011).

PE009-13, Guide to Good Manufacturing Practices of Medicinal Products, Annexes (2017). Annex 1 Isolator technology (21-25).

PE010-4, Guide to Good Practices for the Preparation of Medicinal Products in Healthcare Establishments (2014).

https://www.picscheme.org/layout/document.php?id=157





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Relevant Regulations and Guides


European Pharmacopoeia (Ph. Eur.) 2.6.1 Sterility 5.1.1 Methods of preparation of sterile products 5.1.2 Biological indicators 5.1.9 Guidance for using the test for sterility

ISPE ISPE Baseline®, Pharmaceutical Engineering Guide,

Volume 3, Sterile Product Manufacturing Facilities (2011).

PDA: PDA Technical Report No. 34. Design and Validation of

Isolator Systems for the Manufacturing and Testing of Health Care Products. September/October 2001.

http://www.ispe.org/publications-guidance-documents/sterile-manufacturing

https://www.researchgate.net/publication/293417694_Highlights_from_the_new_PDA_technical_report_no34_Design_and_validation_of_isolator_systems_for_the_manufacturing_and_testing_of_health_care_products

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Bio-Decontamination vs. Sterilization


Method Bio-decontamination SterilizationApplications Isolators, cRABS, Transfer hatches,

room biodecontaminationSterilizers (e.g. for medical devices’ sterilization)

Target log reduction, SAL*

≥ 10-3 or 10-4 up to 10-12

* SAL = Sterility Assurance Level≥ 10-6 up to 10-12

Loads Variable loads / validated loads Only validated loadsVacuum No(Yes) Usually positive pressure in

the process ~ +10-15 Pa, max. +100 Pa; (with hazardous materials negative pressure can be used)

Yes

Target Bio-decontaminating surfaces Sterilizing surfaces or surfaces below Tyvek® membrane

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Sterility Assurance Limit, SAL

Typical sterility assurance limit, SAL = 10-6


100 = 0, sterile product

106

103

100

10-3

10-6

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Typical sterility assurance limit, SAL = 10-6



106

103

100

10-3

10-6

10-6

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Typical sterility assurance limit, SAL = 10-6 (even up to 10-12).



106

103

100

10-3

10-6

10-6

10-12

3. Bio-Decontamination Measurements

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Bio-Decontamination Measurements

H2O2, ppmHumidityTemperature

Potential other parameters:TimePressure (P) and differential pressure (dP)Airflow and velocityAirborne particles


Our topics today

4. Technology Comparison

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Different Measurement Technologies


Technology Benefits Challenges Measurementparameters

Electrochemical cells Sensor cell easy to change

Short lifespan, repeatability

ppm (H2O2)

NIR (near infrared technologies)

Stable, for R&D Expensive, big size, not for low measurements

ppm (H2O2/H2O), a (H2O2, µg/), a (H2O, g/m3)

Gas analyzers (lasertechnology)

High selectivity, detection limit, low measurements

Expensive, big size, heavy, noncontinuousmeasurement

ppb, only low level measurements

Vaisala capacitive thin-film polymer sensors

Several measurement parameters, stable, repeatability, small size

Vaisala HPP272 not for safety applications (≤1 ppm)

RH%, RS%, °C, ppm (H2O2), absolute H2O2, absolute H2O, H2O ppm by volume, saturation vapor pressure

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Capasitive Thin-Film Polymer Sensor


A = Sensor with catalytic layerB = Sensor without catalytic layer

1 = Catalytic layer2 = Thin film polymer between two electrodes3 = Alumina substrate

Vaisala PEROXCAP® HPP272 probe

Sensor measures: ppm, RS, RH, ˚C + many other calculated parameters

Difference between sensors B and A gives ppm result

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Relative Saturation vs. Relative Humidity


Only H2O vapor present H2O and H2O2 vapor present


H2O2 ppm as a function of RS/RH sensor readings at 20.0˚C



25% RH

~ 85% RS



25% RH

~ 100% RS

5. Cycle Development

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Typical Cycle Development PhasesIsolator cycle development steps are dependent on reliable measurements.

1. Dehumidification studies2. Temperature and vapor distribution study/smoke studies3. Preliminary lethality study with indicators (BIs or EIs)4. Worst case lethality study with indicators (BIs / EIs + CIs)5. Aeration study6. Process validation7. Regular requalification

BI = Biological indicator, CI = Chemical indicator, EI = Enzymatic indicator


6. Bio-Decontamination Process Conditions

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Typical Process Conditions


Parameter Phase ValuesH2O2 Decontamination 700 – 1200 ppm

Humidity After dehumidification phase 5 – 35 %

Humidity At the end of bio-decontamination 60 – 100 %

Temperature Throughout the process 18 – 40°C

Time Total bio-decontamination cycle time

2 – 4 hours

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Control of Condensation is Needed

Relative saturation (RS) value is needed to be able to control a condensation phenomenon.


Process type Humidityvalues

Condensing environment

Dry < 100 % Avoided

Micro-condensing

~ 100 % Being at a sub-micron level is invisible to the naked eye

Wet ≥ 100 % Visible condensation to naked eye

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Example of Bio-Decontamination Cycle

Typical non-condensing bio-decontamination process in isolators.


7. From Monitoring to Controlling (H2O2, ppm levels)

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Target: Online Monitoring & Controlling

Provides continuous measurement dataGuarantees that a process works as plannedProcess can be directed based on real values Can decrease a number of biological, chemical or

enzymatic indicators.Makes process to process comparison fasterSaves time Saves money Guarantees the safety of the products produced Convinces the GMP Inspectors


8. How to Select the Right Sensor?

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Nine Things to Consider When Selecting a Sensor

1. How many parameters a sensor can measure?

2. Sensor’s re-calibration interval?

3. Is a sensor reading repeatable?

4. Are sensor materials suitable for your application?

5. Does a sensor tolerate condensation?

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Nine Things to Consider When Selecting a Sensor

6. Expected lifetime of a sensor?

7. Can a sensor be located to the exact measuring point?

8. Is it easy to attach a sensor to your measuring locations?

9. Is it easy to connect a sensor to other devices like PLC or display?


MaterialDesorption

maximum [ppm]PTFE 1.3PFA 1.3LCP 3.0PPS 28.5PC 57.2

PBT 67.2ABS 74.2IXEF 82.3

Material Selection Matters

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Material Selection Matters


-40

-35

-30

-25

-20

-15

-10

-5

0

PTFE

+ m

embr

ane

outs

ide

Al a

nodi

zed

PEEK AB

S

PTFE

+ 3

16L

stee

l net

PTFE

+ L

CP

+ m

embr

ane

PTFE

por

ous

316L

316L

+ m

embr

ane

outs

ide

H2O

2 er

ror [

ppm

]

Filter material

Material effect to PPM @200ppm (Ref=PTFE)membrane = PTFE

-114,40

Membrane creates microclimate inside sensor filter

Membrane doesn’t have an effect on results

Good results with: PTFE LCP 316L

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Vaisala HPP272 PEROXCAP® PROBE

Capacitive thin-film polymer sensorBased on the world leading

humidity measurement technology (HUMICAP®)3 in one (˚C, RH/RS, H2O2 ppm)Stable and repeatableWithstands highly condensing H2O2

environmentsTraceable H2O2 factory calibrationMakes validation process easier


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Things to Remember

1. H2O2 is effective and safe to use

2. Terminology: Sterilization, bio-decontamination and SAL

3. Measurements: ppm (H2O2), humidity, temperature

4. Available measurement technologies

5. Reliable measurements are crucial in cycle development

6. Typical bio-decontamination process conditions

7. Monitoring, controlling or both?

8. Nine things to consider when selecting a sensor


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Validating H2O2 Bio-Decontamination –the Easy Way

Visit the product page at www.vaisala.com/HPP272 for datasheet, technology description, video, user guide, etc.


http://www.vaisala.com/en/products/instruments-sensors-and-other-measurement-devices/instruments-industrial-measurements/hpp272

Documents

Webinar Slides from October 11 2017 - Vaisala · , Pharmaceutical Engineering Guide, Volume 3, Sterile Product Manufacturing Facilities (2011). PDA: PDA Technical Report No. 34. Design