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Recommended Practices for Cleanrooms
Laminar Airflow assures full product protection such as basic microbial culture and not recommended for operator / environment protection. Continuous flushing of working area by a unidirectional and ultra-filtered airflow allows operation in sterile and particle free conditions. The Airflow pattern will be 100% supply and 0% exhaust.
Procedures To Be Followed To Maintain Cleanliness Level
- Areas surrounding the Cleanroom should be less pressured than the Cleanroom
- Airlock rooms to be provided before Clean Room to reduce entry of contamination
- Separate change rooms to be provided for male and female workers. Change rooms are not only used to change the cloths but they also acts as a buffer zone between the Cleanroom and the contaminated areas.
- Whenever going inside the Cleanroom trough the air lock, ensure that the previous air lock door is closed back before entering the next air lock. Always “open & close” the doors slowly, as this action will pump a lot of air. At any cost the doors should not be left open
- Air Shower to be used to reduce particles entry during human movement
- Existing Windows to be closed permanently to avoid cross contamination
- Good smooth and scratch resisting flooring with skirting to be provided
- Corners to be provided with coving to avoid dust accumulation and for easy cleaning
- The room should be considered a restricted area. Only authorized personnel should be allowed to enter during operation
- No paper products / cotton buds should be allowed inside the Clean Room
- All personnel entering the room facility should remove their shoes and socks. They shall step on the wet/tacky mat in approved manner
- All personnel / visitors should wear Clean Room garments while entering Clean room
- Clean Room Garments are to be stored properly in a laminar air flow storage cabinet
- Personnel should not carry any personnel items such as pencils, pens, hand kerchiefs etc. into the Clean Room
- Persons with skin ailments or coughing etc should not be allowed
- Avoid talking inside the Cleanroom
- For cleaning the Cleanroom it is always better to use liquid detergents and the cleaning process should be slow and the cleaning personnel should also wear Cleanroom garments
- Do not use any blowing equipment inside or nearby a Cleanroom, instead, it is always recommended to use a vacuuming equipment for cleaning
- Movement of materials from and to the Cleanroom must be as minimum as possible
- Avoid touching by hand the material inside the Cleanroom, instead use forceps wherever possible
- A sitting person sheds over 100000 particles, a moving person emits over one million particles and walking person emits 5 million particles of 0.5 micron size
CGMP Requirement
Selection of airborne particulate cleanliness classes for cleanrooms and zones
| Air Classification | Maximum Concentration limits ( Particle/m3) for particles equal to and larger than the considered sizes | |||
|---|---|---|---|---|
| Static – (At rest) | Dynamic – (At Operation) | |||
| 0.5µm | 5 µm | 0.5 µm | 5 µm | |
| Class A | 3500 | 0 | 3500 | 0 |
| Class B | 3500 | 0 | 35000 | 2000 |
| Class C | 350000 | 2000 | 3500000 | 20000 |
| Class D | 350000 | 20000 | NOT DEFINED | NOT DEFINED |
The average of particles concentrations measured at each of the locations do not exceed the concentration limits mentioned in the above table (EU GMP Standards)
- Temperature should be maintained within 22±2 deg.C.
- RH to be maintained within 50±5%
- Air flow pattern shall be mixed flow in Class D and Uni-directional Flow in Class A, B & C
- Should meet the required air changes as detailed in Annexure
Federal standard 209 E Class Limits
| Class Limits | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Class Name | ≥0.1µm | ≥0.2µm | ≥0.3µm | ≥0.5µm | ≥5µm | ||||||
| Volume Units | Volume Units | Volume Units | Volume Units | Volume Units | |||||||
| SI | English | (m3) | (ft3) | (m^3) | (ft^3) | (m^3) | (ft^3) | (m^3) | (ft^3) | (m^3) | (ft^3) |
| M1 | 350 | 9.91 | 75.7 | 2.14 | 30.9 | 0.875 | 10.0 | 0.283 | – | – | |
| M1.5 | 1 | 1240 | 35.0 | 265 | 7.50 | 106 | 3.00 | 35.3 | 1.00 | – | – |
| M2 | 3500 | 99.1 | 757 | 21.4 | 309 | 8.75 | 100 | 2.83 | – | – | |
| M2.5 | 10 | 12400 | 350 | 2650 | 75.0 | 1060 | 30.0 | 353 | 10.0 | – | – |
| M3 | 35000 | 991 | 7570 | 214 | 3090 | 87.5 | 1000 | 28.3 | – | – | |
| M3.5 | 100 | – | – | 26500 | 750 | 10600 | 300 | 3530 | 100 | – | – |
| M4 | – | – | 75700 | 2140 | 30900 | 875 | 10000 | 283 | – | – | |
| M4.5 | 1000 | – | – | – | – | – | – | 35300 | 1000 | 247 | 7.00 |
| M5 | – | – | – | – | – | – | 100000 | 2830 | 618 | 17.5 | |
| M5.5 | 10000 | – | – | – | – | – | – | 353000 | 10000 | 2470 | 70.0 |
| M6 | – | – | – | – | – | – | 1000000 | 28300 | 6180 | 175 | |
| M6.5 | 100000 | – | – | – | – | – | – | 3350000 | 100000 | 24700 | 700 |
| M7 | – | – | – | – | – | – | 10000000 | 283000 | 61800 | 1750 | |
Selection ISO 14644-1 airborne particulate cleanliness classes for cleanrooms and clean zones
| ISO Classification number | Maximum concentration limits (particles/m^3 of air ) for particles equal to and larger than the considered sizes shown below: | ||||||
|---|---|---|---|---|---|---|---|
| ≥0.1µm | ≥0.2µm | ≥0.3µm | ≥0.5µm | ≥1µm | ≥5.0µm | ||
| ISO Class 1 | 10 | 2 | |||||
| ISO Class 2 | 100 | 24 | 10 | 4 | |||
| ISO Class 3 | 1000 | 237 | 102 | 35 | 8 | ||
| ISO Class 4 | 10000 | 2370 | 1020 | 352 | 83 | ||
| ISO Class 5 | 100000 | 23700 | 10200 | 3520 | 832 | 29 | |
| ISO Class 6 | 1000000 | 237000 | 102000 | 35200 | 8320 | 293 | |
| ISO Class 7 | 352000 | 83200 | 2930 | ||||
| ISO Class 8 | 3520000 | 832000 | 29300 | ||||
| ISO Class 9 | 35200000 | 8320000 | 293000 | ||||
The Meanings of the Cleanrooms Classification
| Class 1 : | This Cleanrooms class is mainly used within the microelectronic industry when manufacturing integrated circuits which requires submicron resolution. |
| Class 10: | This Cleanroom class is mainly used within the semiconductor industry using band widths below 2micrometer. |
| Class 100: | This cleanroom class is, according to many, the most useful critical cleanliness class. Cleanrooms class 100 are often, incorrectly, known as sterile rooms and are used when >bacterial free < and /or >particle free< environments are required. Cleanroom class 100 is used in aseptic manufacturing within the pharmaceutical industry, for example .This cleanroom class is frequently used during the manufacture of integrated circuits; and also during isolation and treatment of patients who are especially sensitive to bacterial infections, e.g. after bone marrow transplantation. |
| Class 1000: | This cleanroom class is mainly used when producing high quality optics; When carrying out mounting work and testing of gyroscopes for aircrafts; and also when mounting high quality miniature bearings. |
| Class 10000: | Cleanrooms of class 10000 are used for mounting procedures in hydraulic or pneumatic equipment and on some occasions are also used within the food and beverage industry. Class 10000 cleanrooms are also commonly used within the pharmaceutical industry. |
| Class 100000: | This classroom class is used by many industries, for example when working with optical products, when building large electronic systems based on smaller components, when building hydraulic and pneumatic systems and also within the food and beverage industry. The pharmaceutical industry also makes frequent use of this class of cleanrooms. |
The Scope of the various currently available standards is presented below:
ISO 14644-1 Classification of air cleanliness
This standard covers the classification of air cleanliness in cleanrooms and associated controlled environments. This classification is in accordance with the standard as specified and is only concerned with the concentration of airborne particles. It must be stressed that this standard cannot be used to characterize the physical, chemical, radiological, or viable nature of airborne particle.
ISO 14644-2 Specification for testing and monitoring to prove continued compliance
This part of the overall standard specifies requirements for periodic testing of cleanrooms and associated controlled environments to prove their continued compliance with ISO14644-1, and for the designated class of environmental cleanliness.
ISO 14644-3 Metrology and test methods
This standard specifies the various methods and techniques which can be used to characterize and monitor various parameters in cleanrooms and other controlled environments.
ISO 14644-4 Design, Construction, and start-up:
ISO 14644-5 Cleanroom operations
This international standard specifies the basic requirements for operating cleanrooms and other controlled environments. It is primarily intended for those who are planning to carry out work in a cleanroom or any other controlled environment.
ISO 14698-1 General principles
This standard describes the principles and basic methodology for a formal system to assess and control bio-contamination where cleanroom technology is applied. The standard is used in order to allow reproducible monitoring of bio-contamination and also to allow selection of appropriate protective measures.
ISO 14698-2 Evaluation and interpretation of bio-contamination data
This part of the standard concerning cleanroom technology and bio-contamination control describes basic principles and methodological requirements for all microbiological data evaluation. The standard also covers the estimation of bio-contamination data obtained from sampling for viable particles in zone at risks, as specification by the selected system.
ISO 14698-3 Methodology for measuring the efficiency
This standard concerns the efficiency of various processes that incorporated one or more of the following actions: rinsing, cleaning, disinfection, combined cleaning and disinfection by either biochemical or mechanical means. Methods of measuring the efficiency of the processes of rinsing and/ or cleaning and /or disinfection and/or combined cleaning and disinfection of wet soiled surfaces on which microorganisms may be present either with or without the formation of a bio-film, is explained in relation to the application of cleanroom technology.
Air Velocities & Air Changes in Cleanrooms
| Class of Cleanroom | Airflow type | Average velocity(ft/min) | Air Changes /hr |
|---|---|---|---|
| ISO 8 (100,000) | N/M | 1-8 | 5-48 |
| ISO 7 (10,000) | N/M | 10-15 | 60-90 |
| ISO 6 (1,000) | N/M | 25-40 | 150-240 |
| ISO 5 (100) | U/N/M | 40-80 | 240-480 |
| ISO 4 (10) | U | 50-90 | 300-540 |
| ISO 3 (1) | U | 60-90 | 360-540 |
| Better Than ISO 3 | U | 60-100 | 360-600 |
Air Changes per hour= Average airflow velocity* x room area x 60 min/hr
Room Volume
N=non unidirectional; M= mixed flow room; U= Unidirectional flow.
Room Volume
N=non unidirectional; M= mixed flow room; U= Unidirectional flow.
Classification of filters according to the EN 1822
| Filter Class | Overall Value Efficiency (%) | Overall Value Penetration (%) | Leak test Efficiency (%) | Leak test Penetration (%) |
|---|---|---|---|---|
| H 10 | 85 | 15 | ||
| H 11 | 95 | 5 | ||
| H 12 | 99.5 | 0.5 | ||
| H 13 | 99.95 | 0.05 | 99.75 | 0.25 |
| H 14 | 99.995 | 0.005 | 99.975 | 0.025 |
| U 15 | 99.999 5 | 0.000 5 | 99.997 5 | 0.002 5 |
| U 16 | 99.999 95 | 0.000 05 | 99.999 75 | 0.000 25 |
| U 17 | 99.999 995 | 0.000 005 | 99.999 9 | 0.000 1 |
Schedule of tests to demonstrate continuing compliance
| Test Parameter | Class | Maximum Time Interval |
|---|---|---|
| To Demonstrate compliance by Particle Counting | ≤ISO 5 | 6 months |
| >ISO 5 | 12 months | |
| Schedule of additional | All Classes | 12 months |
| Air flow Velocity or Volume | ||
| Air Pressure difference | All Classes | 12 months |
| Schedule of Optional tests | All Classes | 24* months |
| Installed filter leakage | ||
| Airflow Visualisation | All Classes | 24* months |
| Recovery | All Classes | 24* months |
| Containment Leakage | All Classes | 24* months |
Sources, route of transfer and control and monitoring methods used in classrooms
| Hazard | Route | Control methods | Monitoring Methods |
|---|---|---|---|
| Supply air | Airborne | Air filters | Filter integrity test |
| Areas adjacent to the cleanroom | Airborne Contact | Overpressure; air movement control Cleanroom mats | Room pressure differential Mat inspection |
| Various airborne dispersions | Airborne | Ventilation | Air supply rate or velocity Counts of airborne particles Counts of airborne micro-organisms Control of airflow |
| Floors, Walls and other Surfaces | Contact | Cleaning (and ,where required, disinfection) | Surface Counting of Particles, and micro-organisms |
| People | Airborne Contact | Cleanroom garments Gloves | Surface counts; inspection for tears; particle penetration testing Inspection for punctures Surface contamination counts |
| Machines | Airborne Contact | Ventilation Design of machine cleaning or disinfection | Air extract rates and airflow patterns Surface contamination |
| Raw materials | Mainly contact | Control of manufacturing of raw materials Cleaning if solids, or filtration if fluids sterilization | Particle and bacterial counts within, or on, the materials Filtration systems Sterilisation system |
| Containers and packaging | Mainly Contact | Control of their composition and manufacturing environment sterilization | Particles and microbial Counts on surface Sterilisation Systems |
R=recommended
NR=not recommended
AS=application specific
NR*=not recommended in non directional flow
NR=not recommended
AS=application specific
NR*=not recommended in non directional flow
Garments Systems for different classes of cleanrooms according to IEST-RP-CC-003.2
| Apparel Type | ISO 7&8(100K &10k) | ISO 6(1000) | ISO 5(100) | ISO 4&3 (10 & 1) |
|---|---|---|---|---|
| Frock | R | AS | AS(NR*) | NR |
| 2 piece suit | AS | AS | AS | AS |
| Coverall | AS | R | R | R |
| Shoe Cover | R | AS | AS(NR*) | NR |
| Boot | AS | R | R | R |
| Special Footwear | AS | AS | AS | AS |
| Hair Cover | R | R | R | R |
| Hood | AS | AS | R | R |
| Facial Cover | AS | AS | R | R |
| Powered headgear | AS | AS | AS | AS |
| Woven gloves | AS | AS | AS | NR |
| Barrier gloves | AS | AS | AS | R |
| Inner suit | AS | AS | AS | R |
Garments Systems for Aseptic Cleanrooms (IEST RP CC-003.2
| Apparel Type | ISO Class 7 Class(10 000) | ISO Class 6& 5 Class(1000&100) | ISO Class 4&3 (10 & 1) |
|---|---|---|---|
| Frock | NR | NR | NR |
| 2 piece suit | NR | NR | NR |
| Coverall | R | R | R |
| Shoe Cover | NR | NR | NR |
| Boot | R | R | R |
| Special Footwear | AS | AS | AS |
| Hair Cover(bouffant) | R | R | R |
| Hood | AS | R | R |
| Facial Cover | R** | R** | R** |
| Powered headgear | AS | AS | AS |
| Woven gloves | NR | NR | NR |
| Barrier gloves | R | R | R |
| Inner suit | AS | AS | R |
R=recommended
NR=not recommended
AS=application specific
R**=Surgical mask recommended
NR=not recommended
AS=application specific
R**=Surgical mask recommended
Recommended frequency of change of garment according to the IEST RP-CC-003
| Class Of Room | ISO 7 & 8 Class 1000 &100000 | ISO 6 (Class 1000) | ISO 5 (Class 100) | ISO 4 (Class 10) | ISO 3 ( Class1) |
|---|---|---|---|---|---|
| Frequency | 2 per week | 2 to 3 per week | daily | Per entry to 2 per day | On each entry |