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Your Cleanroom --
A Workshop
Mary Taylor
Micronova Manufacturing
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Controlled Environments
Air Flow Control
Gowning Control Regimented Cleaning
Particle control and monitoring
Bioburden control and monitoring
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Room Classifications Historic -- Mil Std 209
ISO
FDA
EU
Harmonization
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Cleanroom Classifications
Class 10 ~ ISO 4
Class 100 ~ ISO 5, may be Aseptic, EU: A
Class 1000 ~ ISO 6, may be Aseptic, EU:A or B
Class 10000 ~ ISO 7, EU: B or C
Class 100,000 ~ ISO 8, D
ISO 9 Non-classified (may be a clean as ISO 7)
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The Cleanest Areas
Bio Tech: ISO 5, GradeA (was Class 100)
Aseptic/Sterile Core
Filling Suites
Cell Culture (BioHoods)
Full Gowning:shoe cover, gloves,
hair cover, beardcovers, coveralls,hood, aseptic:goggles, sterilemask, 2nd pair ofsterile gloves.
Specifications
ISO 5: >0.5 micron 3,520
Grade A: 0.5 micron 3,500
in operation & at rest
FDA 100: ISO 5, 1 cfu
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Clean Areas ISO 7, 8 & Non-classifed, Bioburden control
Formerly Class 10,000 and 100,000
Area adjacent to sterile fill -- Grade B
Cell Culture, Buffer and Media Preparation,Compounding, Fermentation, Formulation can be
ISO 7, 8 or unclassified. Grade C, DGowning: frock/coverall, shoe cover, hair cover,
beard cover, gloves, face mask
Former Class 10,000 =
ISO 7: 0.5 micron 352,0000Grade B: 3,500 at rest; 350,000 in operation
Grade C: 350,000 at rest; 3,500,000 in operation
FDA: ISO 7, 352,000; 10 cfu
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Cleanroom Priorities
Air Exchanges
Cleaning
Gowning Material Transport
Activity Flow
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Air Flow
16
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Cleaning & Sanitizing
Plan -- Cleanest to Dirtiest
Validated & Standard Practices
When in use Between uses
Disinfectants vs. Detergents
Documentation Training
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Cleaning Strategy What do we clean in what order?
Clean from cleanest to dirtiest Where are the HEPAs?
What is traffic flow? the exit door?
Where are air return vents?
Product contact surfaces? What stays in cleanroom?
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Cleaning Strategy
How do we clean what?
Use the validated methods and standard
practices.
Double bucket
Overlapping strokes
Floors Lift and pull, Modified Figure 8
Walls Horizontal, Vertical Strokes Surfaces
Ceilings
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Cleaning Strategy
When do we clean what?
Typically clean floors and work surfaceswhen in use, walls less frequently, ceilings
less oftenAseptic walls and floors daily, ceilings maybe
less
What are the room classifications?
How busy is the area, people, equipment? What is air flow, number of HEPAs?
Does the area get dirty, dusty, contaminated?
How do the surfaces appear?
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Common Frequencies
by classification when in use ISO 4/5 ~~ Floors, walls, ceilings daily
ISO 7 ~~ Floors daily, walls weekly,
ceilings monthly ISO 8/9 ~~ Floors daily (+), walls
monthly, ceilings quarterly, or aftershutdowns
Gown rooms ~~ Floors daily
Non-classified, bioburden control ~~Floors daily
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Double Bucket System:
The Bio Pharma Standard Clean and dirtybuckets
Disinfectant in each
bucket
Increased area forcleaning 1000square feet for ISO 7
and 8 areas
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ISO Validated Methods:
Floors Pull and Lift overlapping strokes
(string type or sponge type floor mops)
Modified Figure 8 method (string mops)
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ISO Validated Methods Horizontal (walls) overlapping strokes
Vertical (walls)
ISO methods, the FDA standard.
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Cleaning Strategy
Other considerations
Clean and/or Disinfect Detergents vs. Disinfectants
Quick drying vs. Wet for 10 to 15 minutes
Materials: Low Linting, Low particles,autoclavable or sterile, compatible withdisinfectants
Tools: Durable, non-reactive vs. non-reactive,autoclavable, compatible with disinfectants
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Environmental Monitoring
Particles
Bioburden
Alert/Action Limits Challenges
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References
FDA -- CDER, CBER
ISO
ISEP IEST
USP
Suppliers
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Keeping it Clean
Adequateair flow
Cleaning
schedule Controlmaterialsand peopleenteringclean area
Appropriategowning
Product,activity flow
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Next steps:
What are we doing now?
What could we be doing Techniques
Frequency
Tools, Materials
What will we implement?