Cleanroom

Recommended Practices for Clean Rooms

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 clean rooms 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 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:	Clean rooms 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.

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
To Demonstrate compliance by Particle Counting	>ISO 5	12 months
Schedule of additional	All Classes	12 months
Air flow Velocity or Volume	All Classes	12 months
Air Pressure difference	All Classes	12 months
Schedule of Optional tests	All Classes	24* months
Installed filter leakage	All Classes	24* months
Airflow Visualisation	All Classes	24* months
Recovery	All Classes	24* months
Containment Leakage	All Classes	24* months

* = Suggested time interval

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

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