Webinar Slides from October 11 2017 - Vaisala · , Pharmaceutical Engineering Guide, Volume 3,...
Transcript of Webinar Slides from October 11 2017 - Vaisala · , Pharmaceutical Engineering Guide, Volume 3,...
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Webinar Slidesfrom October 11th 2017
Vaporized H2O2Bio-Decontamination in Isolators &Transfer Hatches
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Meet the Presenters
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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
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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?
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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
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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
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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
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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)
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Relevant Regulations
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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).
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Relevant Regulations and Guides
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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.
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Bio-Decontamination vs. Sterilization
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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
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100 = 0, sterile product
106
103
100
10-3
10-6
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Sterility Assurance Limit, SAL
Typical sterility assurance limit, SAL = 10-6
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100 = 0, sterile product
106
103
100
10-3
10-6
10-6
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Sterility Assurance Limit, SAL
Typical sterility assurance limit, SAL = 10-6 (even up to 10-12).
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100 = 0, sterile product
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
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Our topics today
4. Technology Comparison
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Different Measurement Technologies
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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
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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
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Only H2O vapor present H2O and H2O2 vapor present
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H2O2 ppm as a function of RS/RH sensor readings at 20.0˚C
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H2O2 ppm as a function of RS/RH sensor readings at 20.0˚C
25% RH
~ 85% RS
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H2O2 ppm as a function of RS/RH sensor readings at 20.0˚C
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
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6. Bio-Decontamination Process Conditions
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Typical Process Conditions
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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.
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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.
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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
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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?
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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
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-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.
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