Cleanroom Management Guide
Uploaded by
MaxStudyCleanroom Management Guide
Uploaded by
MaxStudyYour Cleanroom -A Workshop
Mary Taylor
Micronova Manufacturing
Controlled Environments
Air Flow Control Gowning Control Regimented Cleaning Particle control and monitoring Bioburden control and monitoring
Room Classifications
Historic -- Mil Std 209 ISO FDA EU Harmonization
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)
The Cleanest Areas
Bio Tech: ISO 5, Grade A (was Class 100)
Aseptic/Sterile Core Filling Suites Cell Culture (Bio Hoods)
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
Full Gowning: shoe cover, gloves, hair cover, beard covers, coveralls, hood, aseptic: goggles, sterile mask, 2nd pair of sterile gloves.
Clean Areas ISO 7, 8 & Nonclassifed, 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, D
Gowning: frock/coverall, shoe cover, hair cover, beard cover, gloves, face mask
Former Class 10,000 = ISO 7: 0.5 micron 352,0000 Grade 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
Cleanroom Priorities
Air Exchanges Cleaning Gowning Material Transport Activity Flow
Air Flow
16
Cleaning & Sanitizing
Plan -- Cleanest to Dirtiest Validated & Standard Practices When in use Between uses Disinfectants vs. Detergents Documentation Training
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?
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
Cleaning Strategy When do we clean what?
Typically clean floors and work surfaces when in use, walls less frequently, ceilings less often
Aseptic 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?
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 after shutdowns Gown rooms ~~ Floors daily Non-classified, bioburden control ~~ Floors daily
Double Bucket System: The Bio Pharma Standard
Clean and dirty buckets Disinfectant in each bucket Increased area for cleaning 1000 square feet for ISO 7 and 8 areas
ISO Validated Methods: Floors
Pull and Lift overlapping strokes (string type or sponge type floor mops) Modified Figure 8 method (string mops)
ISO Validated Methods
Horizontal (walls) overlapping strokes Vertical (walls) ISO methods, the FDA standard.
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 with disinfectants Tools: Durable, non-reactive vs. non-reactive, autoclavable, compatible with disinfectants
Environmental Monitoring
Particles Bioburden Alert/Action Limits Challenges
References
FDA -- CDER, CBER ISO ISEP IEST USP Suppliers
Keeping it Clean
Adequate air flow Cleaning schedule Control materials and people entering clean area Appropriate gowning Product, activity flow
Next steps:
What are we doing now? What could we be doing
Techniques Frequency Tools, Materials