maintaing a gmp cleanroom - · pdf fileclean areas – iso 7, 8 & non-classifed, ......

Your Cleanroom --A Workshop

Mary TaylorMicronova 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)

Full Gowning: shoe cover, gloves, hair cover, beard covers, coveralls, hood, aseptic:goggles, sterile mask, 2nd pair of sterile gloves.

SpecificationsISO 5: >0.5 micron 3,520

Grade A: 0.5 micron 3,500 in operation & at rest

FDA 100: ISO 5, 1 cfu

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, 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 operationGrade C: 350,000 at rest; 3,500,000 in operationFDA: ISO 7, 352,000; 10 cfu

Presenter

Presentation Notes

Although the focus for cleanroom mops is the aseptic fill area. There are special needs throughout the plant in the Biotech industry. There are a number of areas that require disinfectants and some areas that require detergents for grease removal. There are hoods that may require special cleaning as well as the outside of process tanks and the cat walks that surround them.

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 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)

Presenter

Presentation Notes

Where do I start? Cleaning should be unidirectional from the most critical to the least critical area of the cleanroom (cleanest to dirtiest). Consider the airflow. Consider the airflow in certain areas – you may have a vertical airflow in the room and horizontal airflow at your workstations or cabinets. The more critical the surface the more critical the cleaning method. For the past several years the experts have advocated the straight line wiping/mopping method. Again, moving from cleanest to dirtiest with a slight overlap. The Modified figure 8 Motion has been more readily accepted for mopping floors since it is ergonomically better for employees. This follows the same stringent wiping pattern but covers more surface area. Remember, no more than shoulder distance for the total curve of the motion. More recently some experts have acknowledged the efficacy of a side to side cleaning for say a wall – as long as the general direction of the cleaning pattern is cleanest to dirtiest. When looking at the vertical air flow model the floor is the surface that is cleaned most regularly. Walls next. Maybe ceilings on a weekly or monthly basis. Again, look at the classification of the room and the traffic. Just as it is important not to contaminate from room to room, also from surface to surface. Look to regulatory bodies – IES, ISO , FDA for specific recommendations and guidance.

ISO Validated Methods• Horizontal (walls) overlapping strokes• Vertical (walls)• ISO methods, the FDA standard.

Presenter

Presentation Notes

Where do I start? Cleaning should be unidirectional from the most critical to the least critical area of the cleanroom (cleanest to dirtiest). Consider the airflow. Consider the airflow in certain areas – you may have a vertical airflow in the room and horizontal airflow at your workstations or cabinets. The more critical the surface the more critical the cleaning method. For the past several years the experts have advocated the straight line wiping/mopping method. Again, moving from cleanest to dirtiest with a slight overlap. The Modified figure 8 Motion has been more readily accepted for mopping floors since it is ergonomically better for employees. This follows the same stringent wiping pattern but covers more surface area. Remember, no more than shoulder distance for the total curve of the motion. More recently some experts have acknowledged the efficacy of a side to side cleaning for say a wall – as long as the general direction of the cleaning pattern is cleanest to dirtiest. When looking at the vertical air flow model the floor is the surface that is cleaned most regularly. Walls next. Maybe ceilings on a weekly or monthly basis. Again, look at the classification of the room and the traffic. Just as it is important not to contaminate from room to room, also from surface to surface. Look to regulatory bodies – IES, ISO , FDA for specific recommendations and guidance.

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

Presenter

Presentation Notes

In conclusion – cleaning the cleanroom involves a great deal of planning. Make sure you get everybody concerned involved at the drafting/planning stage. Choose tools and methods that work. Be aware of what’s available. If you are concerned about improving yield or being closed down by the Medicines Control Board then don’t cut corners. Get the system that works for you. Just because it’s involved doesn’t mean it should be complicated. Keep it simple and precise.

Next steps:

•What are we doing now?•What could we be doing –

–Techniques– Frequency– Tools, Materials

•What will we implement?

maintaing a gmp cleanroom - · pdf fileclean areas – iso 7, 8 & non-classifed, ......

Documents