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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Your 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
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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 HEPA’s? 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 HEPA’s? – 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
•What will we implement?
