Clean Room

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What is a Cleanroom?
Typically used in manufacturing or scientific research, a cleanroom is a controlled environment that has a low level of pollutants such as dust,
airborne microbes, aerosol particles, and chemical vapors. To be exact, a cleanroom has a controlled level of contamination that is specified by
the number of particles per cubic meter at a specified particle size. The ambient air outside in a typical city environment contains 35,000,000
particles per cubic meter, 0.5 mm and larger in diameter, corresponding to an ISO 9 cleanroom which is at the lowest level of cleanroom
standards.
Cleanroom Overview
Cleanrooms are used in practically every industry where small particles can adversely affect the manufacturing process. They vary in size and
complexity, and are used extensively in industries such as semiconductor manufacturing, pharmaceuticals, biotech, medical device and life
sciences, as well as critical process manufacturing common in aerospace, optics, military and Department of Energy.
A cleanroom is any given contained space where provisions are made to reduce particulate contamination and control other environmental
parameters such as temperature, humidity and pressure. The key component is the High Efficiency Particulate Air (HEPA) filter that is used to
trap particles that are 0.3 micron and larger in size. All of the air delivered to a cleanroom passes through HEPA filters, and in some cases where
stringent cleanliness performance is necessary, Ultra Low Particulate Air (ULPA) filters are used.
Personnel selected to work in cleanrooms undergo extensive training in contamination control theory. They enter and exit the cleanroom through
airlocks, air showers and/or gowning rooms, and they must wear special clothing designed to trap contaminants that are naturally generated by
skin and the body.
Depending on the room classification or function, personnel gowning may be as limited as lab coats and hairnets, or as extensive as fully
enveloped in multiple layered bunny suits with self contained breathing apparatus.
Cleanroom clothing is used to prevent substances from being released off the wearer’s body and contaminating the environment. The cleanroom
clothing itself must not release particles or fibers to prevent contamination of the environment by personnel. This type of personnel contamination
can degrade product performance in the semiconductor and pharmaceutical industries and it can cause cross-infection between medical staff and
patients in the healthcare industry for example.
Cleanroom garments include boots, shoes, aprons, beard covers, bouffant caps, coveralls, face masks, frocks/lab coats, gowns, glove and finger
cots, hairnets, hoods, sleeves and shoe covers. The type of cleanroom garments used should reflect the cleanroom and product specifications.
Low-level cleanrooms may only require special shoes having completely smooth soles that do not track in dust or dirt. However, shoe bottoms
must not create slipping hazards since safety always takes precedence. A cleanroom suit is usually required for entering a cleanroom. Class
10,000 cleanrooms may use simple smocks, head covers, and booties. For Class 10 cleanrooms, careful gown wearing procedures with a zipped
cover all, boots, gloves and complete respirator enclosure are required.
Cleanroom Air Flow Principles
Cleanrooms maintain particulate-free air through the use of either HEPA or ULPA filters employing laminar or turbulent air flow principles.
Laminar, or unidirectional, air flow systems direct filtered air downward in a constant stream. Laminar air flow systems are typically employed
across 100% of the ceiling to maintain constant, unidirectional flow. Laminar flow criteria is generally stated in portable work stations (LF hoods),
and is mandated in ISO-1 through ISO-4 classified cleanrooms.
Proper cleanroom design encompasses the entire air distribution system, including provisions for adequate, downstream air returns. In vertical
flow rooms, this means the use of low wall air returns around the perimeter of the zone. In horizontal flow applications, it requires the use of air
returns at the downstream boundary of the process. The use of ceiling mounted air returns is contradictory to proper cleanroom system design.
Cleanroom Classifications
Cleanrooms are classified by how clean the air is. In Federal Standard 209 (A to D) of the USA, the number of particles equal to and greater than
0.5mm is measured in one cubic foot of air, and this count is used to classify the cleanroom. This metric nomenclature is also accepted in the
most recent 209E version of the Standard. Federal Standard 209E is used domestically. The newer standard is TC 209 from the International
Standards Organization. Both standards classify a cleanroom by the number of particles found in the laboratory's air. The cleanroom classification
standards FS 209E and ISO 14644-1 require specific particle count measurements and calculations to classify the cleanliness level of a
cleanroom or clean area. In the UK, British Standard 5295 is used to classify cleanrooms. This standard is about to be superseded by BS EN ISO
14644-1.
Cleanrooms are classified according to the number and size of particles permitted per volume of air. Large numbers like "class 100" or "class
1000" refer to FED_STD-209E, and denote the number of particles of size 0.5 mm or larger permitted per cubic foot of air. The standard also
allows interpolation, so it is possible to describe e.g. "class 2000."
Small numbers refer to ISO 14644-1 standards, which specify the decimal logarithm of the number of particles 0.1 µm or larger permitted per
cubic metre of air. So, for example, an ISO class 5 cleanroom has at most 105 = 100,000 particles per m³.
Both FS 209E and ISO 14644-1 assume log-log relationships between particle size and particle concentration. For that reason, there is no such
thing as zero particle concentration. Ordinary room air is approximately class 1,000,000 or ISO 9.

ISO 14644-1 Cleanroom Standards
Class
maximum particles/m
3

FED STD 209E
equivalent
>=0.1 µm >=0.2 µm >=0.3 µm >=0.5 µm >=1 µm >=5 µm
ISO 1 10 2
ISO 2 100 24 10 4
ISO 3 1,000 237 102 35 8 Class 1
ISO 4 10,000 2,370 1,020 352 83 Class 10
ISO 5 100,000 23,700 10,200 3,520 832 29 Class 100
ISO 6 1,000,000 237,000 102,000 35,200 8,320 293 Class 1,000
ISO 7 352,000 83,200 2,930 Class 10,000
ISO 8 3,520,000 832,000 29,300 Class 100,000
ISO 9 35,200,000 8,320,000 293,000 Room Air
BS 5295 Cleanroom Standards
maximum particles/m
3

Class >=0.5 µm >=1 µm >=5 µm >=10 µm >=25 µm
Class 1 3,000 0 0 0
Class 2 300,000 2,000 30
Class 3 1,000,000 20,000 4,000 300
Class 4 20,000 40,000 4,000

Cleanroom Air Flow Principles
Cleanrooms are facilities designed for conducting research or
manufacturing products that require extremely clean environments.
Typically, cleanrooms employ a broad range of techniques to prevent air
particles, bacteria, and other contaminants from entering the workspace,
often by means of employee dress code and washing, pass-thru lockers and
chambers, and intensive detail to cleaning. However, one of the major
forces keeping a cleanroom particle free is the air filter system. Cleanrooms
employ many different types of filters, including HEPA filters and ULPA
filters , but there are two standard air flow patterns that are consistently
used: laminar flow and turbulent flow.

Cleanroom Basics

Cleanrooms are necessary for various kinds of scientific research that
require particle- and bacteria-free environments. For example, when
scientists grow cultures, it is important to reduce the introduction of other
bacteria so that results will not be compromised. Manufacturing various
kinds of products like microprocessors also requires particle-free
environment, because even a human hair contacting the small chips of a
microprocessor can inhibit or destroy functionality.

Cleanrooms are either hard- or soft-walled. A hard wall cleanroom is a
permanent structure or part of a larger permanent structure, while a soft
wall cleanroom can be transported or augmented depending on
requirements, and primarily exists within a larger, permanent structure.
Modular, soft wall cleanrooms are needed for medical emergencies or when
smaller runs of environment-sensitive materials are produced within a
larger facility.

Cleanrooms are graded depending on how clean the air in the facility is.
There are two standards used for this determination: the ISO and United
States federal standards. ISO grades are numbered sequentially, advancing
from 1. A cleanroom graded ISO 1 contains ten or fewer particles per 0.1
micrometer cubed area. A cleanroom graded ISO 2 contains 100 or fewer
particles per 0.1 micrometer cubed area. The rest of the series feature the
amount of particles rising by a factor of 10 per level. US federal standards
are numbered 10, 100, 1000, etc., with the lower class number representing
a cleaner facility. Class 1 cleanrooms have one or fewer particles per 0.5
micrometer cubed area. Class 10 cleanrooms have 10 or fewer particles per
0.5 micrometer cubed area. Ascending class grades rise by a factor of 10.

Because people often work in cleanrooms, they are required to follow dress
and behavior guidelines to limit the amount of particles they will bring into
a cleanroom or particles they will shed while working in the environment.
Workers must change from street clothes into specially designed outfits,
often with full hood coverings, gloves, and breathing masks. Workers must
also enter through an air shower to eliminate remaining particles on the
cleanroom suit, and then pass items into the cleanroom through a small
chamber that prevents outside air from entering the clean environment.

Cleanroom Air Filtration

Cleanrooms employ air filtration to limit the particles in the environment
air. Typically, this is through the use of either a highly efficient particulate
air (HEPA) or ultra low particulate air (ULPA) filter. These filters can
remove roughly 99.9 percent of all microparticles in room air by applying
either laminar air flow or turbulent air flow techniques to the environment
air.

Laminar air flow refers to air that flows in a straight, unimpeded path.
Unidirectional flow is maintained in cleanrooms through the use of laminar
air flow hoods that direct air jets downward in a straight path, as well as
cleanroom architecture that ensures turbulence is lessened. Laminar air
flow utilizes HEPA filters to filter and clean all air entering the
environment. Laminar filters are often composed of stainless steel or other
non-shed materials to ensure the amount of particles that enter the facility
remains low. These filters usually compose roughly 80 percent of the
ceiling space. Cleanrooms employing laminar air flow are typically referred
to as Unidirectional Airflow Cleanrooms.

Non-unindirectional airflow cleanrooms utilize turbulent airflow systems to
clean particulate air and maintain a clean environment. While laminar air
flow filters are often a component of turbulent airflow systems, they are not
the only systems employed. The entire enclosure is designed to use laminar
flow and random, non-specific velocity filters to keep the air particle-free.
Turbulent airflow can cause particle movement that can be difficult to
separate from the rest of the air, but non-unidirectional airflow systems
count on this random movement to move particles from the air through the
filter.
Air Velocity Measurement

We conduct Air Velocity Measurement / tests to determine the average filter face velocity and uniformity, and the average room
airflow velocity and uniformity within a clean room. The average airflow velocity is calculated by dividing the total of the airflow
grid velocities by the number of readings taken.

DOP/PAO HEPA Filter Integrity Test

We conduct complete HEPA/ULPA filter integrity testing services. These are offered for both the Pharmaceutical and
Microelectronics industries. All filter integrity tests performed by us are executed in accordance with IES-RP-CC-001-86 & ISO
14644. We are equipped to perform HEPA Filter Integrity Test with both Di–Octal Phthalate (DOP) and Poly Alpha Olefin (PAO)
depending on client-facility's specific requirements. The tests assure that client's filters are in conformance with various
standards and/or governing agency requirements. Testing and evaluating filters minimum once annually and potentiality twice
annually is required for optimum performance. Proper documentation and certification is provided by us and this also helps
predict potential performance issues and increases filter life.

Particle Count Test

We are QAtech a reputed name in offering clean room validation services. Our Particle Count Test provides complete airborne
particle count cleanliness classification. The test is performed to determine the actual particle count level within the facility at
the time of the test. The test identifies particle count on basis of As-Built, At-Rest, or Operational as per ISO 14644 , EU GMP .
The particle size(s) of interest, the room occupancy state and the room classification shall be known prior to the beginning of
the tests and shall be as specified in the URS documents.

Room Pressurization Test

We conduct Room Pressurization Test for industrial clean rooms. As a part of the validation process, this test verifies that a
pressure differential meet the specified requirements.

Airflow Visualization Test

We offer Airflow Visualization Test as a part of the validation process. Visualization is carried out by using water fogger and
taking Video Graph. The purpose of the airflow visualization test is to show the actual airflow pattern throughout the
unidirectional clean room. The test can also be used to demonstrate the effects on airflow caused by equipment. It is best to
perform this test after all airflow velocity and uniformity tests and room pressurization tests have been performed. The test
determining the airflow patterns within a room using ISO 14644 guides. This visual monitoring service is important in:
Clean Room laminar flow tests
• Airflow balancing
• Fuming Hoods
• Point Exhaust tests
• Personnel safety exhausts verification
• Pressure balancing between rooms and spaces
• Leak detection in ducts

Light Intensity Test

The purpose of the lighting level tests is to verify that the installed light levels and uniformity meet the specified requirements.
We make use of modern testing instruments for assessment of lighting lux levels and intensity.

Noise Level Test

We perform noise level test that measure the sound pressure. The measurements will vary based on the occupancy state-of-
the-art clean room. The purpose may vary but the procedures of testing are identical.

Air Exchange Rate

Air Exchange Rate tests determine the total air volume get in to the room within a clean room. The use of TSI Accubalance Air
Capture Hoods of Model No.8375, assures accurate test results. The hood measures air volume flowing through registers,
diffusers and grills. Weighing just 3.5 kgs, these air capture hoods are easy to use and carry. These hoods simply hold the
accubalance up to a diffuser or grill and read direct supply or exhaust airflow on the large digital display.

Containment Test

We conduct Containment Tests for client's clean room facility. The test is carried to demonstrate that airborne contamination
does not enter from a higher pressure area adjacent to the clean room by means of leaks in the construction materials. The test
is conducted by trained and experienced technicians using modern instruments that assure accurate results.

Recovery Test

We execute recovery tests for clients across Industries. These tests demonstrate the ability of the clean room to remove
particulate by purging the area with filtered air. It also testifies if the room can change from a "dirty" to "clean" state within the
specified time. The test is conducted by experienced technicians from team. Our technicians have enriching experience and
provide clients with high quality service. The ultimate goal of our company is to assure complete satisfaction of clients through
effective execution of services and by providing best array of clean room equipment. We ensure that client's clean room facility
is performing properly and accurately.

Temperature and Humidity Test

We conduct validation tests that include Temperature and Humidity Measurements / Tests. Two levels of temperature and
humidity tests are used by us depending on the requirement. In the first level, general temperature and humidity uniformity are
tested. The general level test is used to ensure that the clean room's HVAC system maintains the specified levels of
temperature and humidity required for occupant comfort. The second level or the comprehensive level test identified that the
clean room HVAC systems needs to maintain the specified levels of temperature and humidity required for both occupant
comfort and process temperature control.
Master Instruments List for HVAC

Sr. No. Instrument Name Make / Model Range Accuracy Qty
1
High Pressure
Diffuser
PMS / HPD III-50LPM 25 - 100 PSI ----- 1
2 FOG Generator MAX / FOG-1500WL 15000 CFM ----- 1
3 Handy Camera
Sony / DCR-DVD610 ----- ----- 2
Sony / DCR-SR68/SC ----- ----- 1
4 Particle Counter
Met-One / 3413 0 to 99,99,999 Counts ----- 1
Met-One / 3423 0 to 99,99,999 Counts ----- 1
PMS / Lasair II-350L
0 to 9,99,99,999
Counts
----- 6
5 Aerosol Photometer
ATI / TDA-2H 0.00005 to 120 µg/Liter 1% of Full Scale 2
TEC SERVICES / PH-4 0.0001 to 999 µg/Liter ----- 2
6 Aerosol Generator ATI / TDA-4B 8100 CFM ----- 4
7 Air Capture Hood
TSI AccuBalance /
8375
25 To 8,000 Ft/min
±3% of reading
±7ft/min
3
8
Vane Type
Anemometer
LUTRON / AM-4201
0.4 To 30.0 m/s, 80-
5910 Ft/min
±(2%
+0.2m/s),±(2%+40
Ft/min)
2
TSI / 5725
0.25 To 30.0 m/s, 50-
6000 Ft/min
±1.0% Of Reading
±4ft/min(±0.2m/s)
1

Modern Approaches to Pharma
Cleanroom Design
Presented here are some of the best and current practices required for the design and construction of
cleanrooms. The focus is upon pharmaceutical grade cleanrooms, although many of the good design concepts
can be applied to cleanrooms across different sectors.

Cleanroom design concepts

Contamination control is the primary consideration in cleanroom design; however, the relationships between
contamination control and airflow are not always well understood.
1


As a first step towards design and construction of the cleanroom and air handling systems, a basic specification
must be developed. For this the following factors must be accounted for:
2


• Defining the area of the clean space
• Establishing the correct cleanliness level (in relation to the international cleanroom standards)
• Establishing the optimal air change rate and determination of the supply airflow rate. (There should be not
less than 20 hourly air changes in the controlled area.)
• Establishing requirements for positive pressure differentials (normally 10-15 Pascals between adjacent
cleanrooms). This range allows doors to be opened and overcomes problems for cleanroom operators in
relation to the high pressure difference, which arises due to air leakage.
• Considering use of mini-environments for additional air cleanliness (such as localized unidirectional airflow or
isolators)
• Optimizing ceiling coverage in relation to air filters. With HEPA filters, the design should seek to include:
HEPA filters with differential pressures (P); adequate space for low pressure drop air flow; low face velocity;
fan design; motor efficiency; variable speed fans.
• Minimizing the pressure drop (air flow resistance)
• Adequate sizing and minimizing the length of ductwork
• Optimizing pressurization
• Reducing air flow when the cleanroom is unoccupied (to save energy consumption)
• Efficient use of components
• Defining the electrical systems that power air systems

The performance of a cleanroom is defined by a set of
complex interactions between the airflow, sources of contamination and heat, position of vents, exhausts, and
any objects occupying the space. Consequently, changes to any of these elements will potentially affect the
operation of the cleanroom and could invalidate aspects of the room design.

With cleanrooms used in the pharmaceutical industry, there are additional considerations aimed at minimizing
contamination. These are centered on the idea that cleanrooms should be constructed in a way which makes
them easy to clean and disinfect. It’s important that such cleanrooms have:

• A smooth and cleanable finish
• A final coating which is impervious to detergents and disinfectants
• No uncleanable recesses
• Very few projecting ledges
• Very few electrical sockets
• Pipes and conduits are appropriately boxed in

Qualification and validation
The design, building, and certification of a new cleanroom is covered by a formal and documented qualification
and validation process. Qualification and validation is undertaken in order to prove that equipment and
processes consistently do what they are supposed to do.

It is a Good Manufacturing Practice (GMP) requirement to prove control of the critical aspects of certain
operations. For this, testing and documentation is required (GMP refers to a set of regulations specific to the
production of medicinal products). The aim is to ensure that the device meets its specification or process
parameters and that it is capable of a consistent performance.

All validation activities should be well planned and clearly defined. This is usually through a validation master
plan. In establishing a validation plan, all critical parameters that may be affected and impact product quality
must be identified. Validation typically consists of the following steps:

• User requirement specification, where the user outlines the objective for the project
• Design qualification (DQ), where the finalized design is compared with applicable national and international
standards
• Factory acceptance testing (FAT). The FAT is undertaken by executing a suite of documented tests on a
completed system or item of equipment—for example, cleanroom control systems.
• Installation qualification (IQ), which is testing to verify that the equipment is installed correctly
• Operational qualification (OQ), which is testing to verify that the equipment operates correctly
• Performance qualification (PQ), which is testing to verify that product can be consistently be produced to
specification

A protocol describing each test and the acceptance criteria must be prepared, and once the testing is complete,
a validation report should be written.

Design process

Prior to the construction of a cleanroom or the modification of an existing cleanroom, a design must be
produced together within working drawings. The design is a set of documents containing explanatory notes
(texts) and drawings. This will take the form of a design specification, and the produced document should be
checked against industry standards.

The design process has been enhanced in recent years
by the use of computer models, in particular computational fluid dynamics (CFD).
3
CFD is a branch of fluid
mechanics that uses numerical methods and algorithms to solve and analyze problems that involve fluid flows.
Computers are used to perform the calculations required to simulate the interaction of liquids or gases within
defined boundary conditions. With cleanrooms, this involves studying the way that air behaves within the clean
zone. Here, numerical simulation results in velocity, pressure, and temperature values to be calculated for each
of the individual cleanroom air volumes. The combination of these factors provides for a detailed airflow
distribution.

CFD, therefore, enables cleanrooms and the equipment within the cleanroom to be accurately designed at the
early stage of the design process. CFD models are not only used to visualize airflow patterns in cleanrooms but
are also working to analyze particle migration paths.

With or without the aid of computer design, the design process should contain the following steps:

• Design: basic design; working drawings
• Design specification
• Construction: installation drawings; executing of construction/installation; field supervision; executive
drawings
• Start-up
• Testing
• Commissioning
• Operation

In relation to the construction process detailed plans are required. The issues that require addressing, through
documentation, include:

• Process flow charts
• Cleanroom or separation concept
• Layouts of premises with room specifications
• Specifications for control equipment
• Personnel (number and qualification) for each room
• Utilities (electricity)
• Waste disposal
• Safety requirements

These various factors must relate to the main elements of the installation such as air handling units, air ducts,
cleanroom construction, connections to dynamic pass-through hatches, dampers and control valves,
measurement sensors, and so on.

Risk assessment

A relatively new dimension to modern cleanroom design is the formal adoption of quality risk management.
This is now a regulatory expectation. In applying risk assessment to the design process, the most important
guidance document is ICH Q9.4 ICH Q9 was adopted as part of EU GMP in 2008 and by the FDA in 2010.

Qualification steps

Once construction is complete and initial qualifications completed, the performance qualification is performed.
With the PQ phase the cleanroom is tested to ensure that it meets accepted standards in the “in operation”
state, as defined by ISO 14644 which is where personnel are present. The tests required include:

• Airborne particle count for classification and test measurement of cleanrooms and clean air devices
• Air pressure difference test
• Installed filter system leakage test
• Airflow direction test and visualization
• Temperature test
• Humidity test
• Recovery test (to show that the cleanroom can recovery to its expected level of airborne particulates after an
elevated rise in airborne particulates)

Of the above tests, the most important of all tests is the particle counting test given that this is a direct
measure of contamination. The particle count test is used for proving that the cleanroom functions in
conformity with the requirements and that it fulfils the set standards in terms of meeting its required
classification. For this test, ISO 14644-1 provides a formula for calculating the minimum number of sample
locations based on the room size. ISO 14644-1 also requires the volume of the air sample to be sufficient to
count 20 particles from the biggest particle defined for a given class.

Ongoing compliance

For a new facility, each phase is tested. For an established cleanroom, the operational state is verified on a six-
month or annual basis, as per ISO 14644-2: Specifications for testing and monitoring to prove continued
compliance.
5
Cleanroom verification is performed in either the “at rest” or “in operation” occupancy state and
should address the following parameters:

• Air cleanliness class
• Pressure differences between rooms
• Air velocity (for unidirectional airflow) or the air flow rate (for turbulent airflow)
• Installed filter leak test of HEPA filters

Conclusion

Cleanroom design, construction, and certification can represent a challenging area. For the pharmaceutical
sector, these challenges center on the avoidance of high levels contamination that might present a risk to the
medicinal product processed within the cleanroom. Modern approaches to cleanroom design can help to
minimize the contamination risks.
6


These approaches include the adherence to quality risk management to identify sources of contamination; the
utilization of validation phases, which ensures rigorous testing; and the application of computer aided design,
such as computational fluid dynamics, which allow for predictive models to be used to help identify
contamination sources relating to unwanted air movement.
Principles of Cleanroom Validation
A cleanroom is a modular environment in which the following environmental factors are kept under control;
temperature, airborne particulates, microbes, relative humidity, differential pressure, and air flow.
Cleanroom Validation is performed for a variety of reasons. To ensure that the design of the facility is fit for its
intended purpose; to ensure that the facility, equipment, and environment meets User Requirement
Specifications (URS); to ensure that the facility, equipment, and environment meet defined regulatory
requirements; to ensure that the facility, equipment, and its environment function together as a system to
meet defined standards.
Cleanrooms are validated and then certified to a chosen class of ISO 14644-1. Each class of ISO14544-1 has
its unique requirements that must be made for a facility to be classified in the specified classification.
CLEANROOM VALIDATION LIFE CYCLE
Validation of a new cleanroom follows a specified lifecycle. The life cycle comprises five phases each of which
accomplishes particular tasks to control variation in the modular environment.
Cleanroom validation work is accomplished through five phases. It starts off with the design control phase and
ends with monitor and control. Changes to equipment and control factors after the cleanroom has been
validated are grounds for cleanroom re-validation.

PHASE ONE: DESIGN QUALIFICATION
Cleanroom validation starts with Design Qualification (DQ). The purpose of this phase is to prove through
objective evidence that the design is fit for its intended purpose. Design Qualification is a verification exercise
against requirements defined in the acceptance criteria of your DQ protocol.
The protocol should address the following:
 User Requirement Specifications(URS)
 Vendor documents and specifications
 Facility layout
 Purchase orders
 Design documentation
 Factory Acceptance Tests(FATs)
 As build drawings
 Data sheets
The output of the Design Qualification phase is a phase report and an Standard Documentation List (SDL) file
that documents the following:
1. Design requirements
2. Bidding requirements
3. Purchasing and order documentation
4. Vendor supplied documents list
5. As build drawings
6. Component lists
7. Inspection lists
8. Factory Acceptance Tests
The approval of the Design Qualification, DQ phase is a pre-requisite for the initiation of the Installation
Qualification, IQ phase.
PHASE TWO: INSTALLATION QUALIFICATION
The purpose of this Installation Qualification (IQ) phase is to confirm through verification that equipment— as
installed—confirms to user requirements and design requirements. Verification is focused on the following
items that should be called for in your IQ protocol:
 HVAC calibration
 P&ID loop verification
 HEPA filter integrity test data review
 Critical equipment calibration status
 Site Acceptance Tests(SATs)
 Installation Qualification tests
 Piping and welding documentation
 Utility verification
 System standard operating procedures and work instructions
The output of this phase should be an IQ report addressing all the above elements, and an SDL file that
documents the following elements:
1. Project changes
2. IQ tests performed
3. Calibration
4. Supplier supplied documents
5. Equipment certificate
6. Installation deviations
7. Site Acceptance Tests (SAT)
8. Consumable list
9. Spare part list
10. Environmental review report
11. List of Operational and Instructional documents
IQ approval is a pre-requisite for the start of the Operational Qualification (OQ) phase.
PHASE THREE: OPERATION QUALIFICATION
The objective for this Operational Qualification (OQ) phase is to show through objective evidence that the
cleanroom operates in conformance with design requirements and user defined requirements, and that it
consistently operates within a defined range of conditions.
The OQ protocol should address the following:
 Testing HVAC (Heating-Ventilation-Air Conditioner) system operation against specified functional
requirements
 Critical Alarms
 Interlock Alarms
 Critical operating parameters defined on the room data sheet
 Filter integrity tests
 Standard operation for the cleanroom
 Air speed and air flow
 Air flow patterns
 Pressure differential
The OQ phase should also address worst case scenarios. To design the worst case scenario for the operation of
the cleanroom, critical operating parameters are identified from the cleanroom data sheet. Operation ranges,
and extreme ranges, are set for each critical parameter and a worst case designed and documented. It should
include the following:
1. Maximum and minimum temperatures
2. Maximum and minimum humidity
3. Maintenance schedules
4. Personnel contamination
The worst case scenario is usually carried out at the specified High and specified Low parameters.
The output of this phase is an OQ report addressing alarms and functional requirements of the cleanroom
specified in the user requirement specifications.
PHASE FOUR: PERFORMANCE QUALIFICATION
The purpose of Performance Qualification (PQ) of the cleanroom is to demonstrate with objective evidence that
the cleanroom consistently operates within defined parameters to produce the defined, desired environmental
outcome. Cleanroom performance qualification involves testing and monitoring of the following:
1. Airborne particulate levels
2. Surface particulate levels
3. Viable microbial particulates
4. Relative humidity
5. Differential pressure
6. Temperature
The output of the PQ phase is a PQ report that analyzes the performance of the cleanroom using specified
equipment parameters. PQ is a pre-requisite for certification.


CLEANROOM CERTIFICATION
Validated cleanrooms are validated to a required class of cleanliness. The level of cleanliness chosen is driven
by user requirements. Cleanroom classes are defined in ISO1464-1:
Methods for evaluation and measurements for Certification are specified in ISO14644-3. It calls out for the
following ten tests.
1. Airborne particle count test
2. Airflow test
3. Air pressure differencial test
4. Filter leakage test
5. Flow vizualization test
6. Airflow direction test
7. Temperature test
8. Humidity test
9. Recovery test
10. Containment leak test
Once certified to a particular class the cleanroom factors are monitored to ensure that parameters have not
drifted, or changed, and that the environment is under control.
MONITOR AND CONTROL
A constant monitoring program is required after certification. Requirements for compliance are found in ISO
14644-2.
Statistical analysis for cleanroom parameters is encouraged as a tool for monitoring the cleanroom after
certification to ensure compliance. The tool of choice is statistical process control, SPC.
Cleanroom Insulation
The problems with cumbersome insulation designs become very pronounced in the manufacturing cleanroom
environment, where thousands of feet of fairly narrow reactor piping form a congested maze of plumbing once
the insulation has been installed.
One of the newer materials that provides a new option in cleanroom insulation is a PVDF-based, high-purity
foam. This specialty plastic material is a closed-cell foam that in a thickness of only one-quarter inch offers
chemical and heat resistance as well as other properties that are equivalent to eight times of what conventional
foam provides for cleanroom applications. In other words, one-quarter inch of PVDF-based insulation is
equivalent to two inches of open-celled insulation.
What to Know When Considering a
Cleanroom
1. What’s the application?
Better quality or better yield is the primary reason for investing in a cleanroom space. It goes straight to your
bottom line.
You need to know the requirement for your specific product or process. If the product you are manufacturing is
regulated by a government agency, or you are contracting with a private firm that requires a certain level of
clean manufacturing, they should have the cleanroom standards already documented. Check with them first.
There are different levels of cleanrooms. ISO, the International Standards Organization, ranks cleanrooms ISO
Class 1 (the cleanest) through ISO Class 9. The lower the ISO rating the cleaner the environment.
Measurement of contamination is done in “parts-percubic- meter.” An ISO Class 6 cleanroom, for example, is
rated at 35,200 parts per cubic meter. That means the room can have no more than 35,200 particles greater
than .5 micron in size per cubic meter. These are particles that are not visible to the human eye. (As a
comparison, a particle of cigarette smoke is between .5 and 2 micron in size. The end of a piece of human hair
is about 60 to 100 microns in size).
Particle counts are performed at the work surface height. The pre-filters remove the dirt and dust you can see
(call them baseballs and boulders). HEPA filters capture the particles you can’t see with a human eye. A light
manufacturing area (defined as an environment that is not generating smoke or oil mist, such as storm window
assembly and packaging) with pre filtration on an HVAC system might be equivalent to an ISO Class 8 room,
with 3,520,000 parts per cubic meter that measure greater than .5 micron. This is comparable to room air.


2. Know the basic principles behind how a cleanroom works.
The majority of cleanrooms are positive-pressure rooms—designed to keep contaminants from entering the
room. Air is introduced into the cleanroom, typically at the ceiling level, after passing through a fan-powered
HEPA filter that removes particles as small as .5 microns. This creates a pressurized room in which the air
pressure in the room is greater than outside the room—hence, positive pressure. The air, and the
contaminants in the air, are then pushed down toward the floors, and ultimately pushed out vents in the lower
portions of the walls of the room.
This means that air and contaminants from the processes in the room are constantly flowing out of the room.
In addition, the air exiting the room, either through vents or when doors are opened, is at a pressure sufficient
enough to prevent contaminants from entering via those openings.
Negative-pressure rooms are designed to keep contaminants from leaving the room. A negative pressure room
is used in instances of infectious diseases and pathogens, bio contaminants, and some hazardous processes
using chemicals, flammables, and potentially explosive liquids and powders. Your concern is not what gets into
the room, but what gets out.
In a negative pressure room, air is pulled out of the enclosure through reversed HEPA filters, creating a
negative pressure inside the room (which prevents contaminants from leaving the room), while air is
constantly being drawn in through venting and other openings. The force of the air entering the room prevents
contaminants from escaping.
Because they are so prevalent, for purposes of this article we will be discussing positive-pressure rooms.
3. ISO standards are the industry norm for rating cleanrooms.
ISO standards were adopted by the industry in 2001. If you do any serious research into ISO standards, you
are likely to come across the Federal Standard 209E for cleanrooms, which was the industry norm until ISO
standards were developed. The federal standards were officially cancelled by the U.S. Department of
Commerce in November 2001, but they are still widely referenced.
“ISO classifications expanded the horizon for classifying clean space,” according to Richard Matthews of
Filtration Technology, Inc., in Greensboro, NC, who chaired the ISO board that developed these standards.
Here are the Federal standards and their ISO equivalents. Note that ISO created three new levels that the
Federal standard did not address.

Whenever possible, refer to the ISO standards because they are internationally accepted. If you are dealing
with partners in other countries, this will make issues much simpler.
4. It’s all about air changes per hour, sometimes.
With some exceptions, a cleanroom is a cleanroom is a cleanroom. Achieving a cleaner class of cleanroom is all
about airflow. It’s a matter of bringing clean air in through HEPA filters in the ceiling and moving contaminated
air out through vents in the walls or floors. The greater the number of HEPA filters and vents, the greater the
rate of air change. You can see from this chart what the requirements are:

It’s easy to clean the air. The more difficult question is: Are you moving the air out of the area properly?
Where does air enter the clean space and how conveniently is it moved out, carrying with it the contaminants
from the manufacturing process? Placement of work tables, chairs, and equipment becomes more crucial. An
item incorrectly placed creates “dead space” where particles are trapped.
These cleaner environments are prevalent in micro-electronics and will play a big part in nanotechnology as we
get more involved in that industry. At these levels it is very important that you consult with a knowledgeable
expert.

5. Modularity
Things change. You can count on that. A cleanroom with a modular design allows the original layout to be
expanded without having to rebuild from scratch. Your need for clean manufacturing space will increase or
expansion will dictate that you move to larger facilities. Modularity in a cleanroom is important. With a modular
design you can, with ease, expand the size of your cleanroom as your needs increase, without having to toss
out part or all of your original cleanroom investment. And in the event you move to a new facility, you can
disassemble your modular cleanroom and take it with you.
There are also cleanroom designs that incorporate casters so that the enclosure can be easily moved around
your factory floor. An example where this might be applicable is an injection mold facility where the
manufacturing area is ISO Class 9, but production has an order for an I.V. component that requires an ISO
Class 7 environment (an I.V. system has to be manufactured in at least an ISO Class 7 cleanroom). You can
create this environment on the factory floor by enclosing the injection-mold machine in a portable cleanroom
outfitted with casters and a HEPA unit installed in the ceiling grid. Simply roll the enclosure to the appropriate
machine and attach softwall curtains to contain it.
Another advantage to a modular cleanroom is in its tax benefits. A modular cleanroom can be written off in
seven years. An existing room within your facility that is transformed into a cleanroom—referred to as “stick-
built”—has to be written off over a much longer period of time.
6. Envision future plans.
Don’t make the mistake of trying to get along with a minimum of cleanroom space. You will be surprised at the
speed your cleanroom needs increase. Better to plan for too much space than not enough.
7. Don’t underestimate air conditioning needs.
You might start with three workers in your cleanroom, and then find you need to increase to five or six. All that
extra body heat, as well as any heat-producing machinery in your clean area, and that cleanroom quickly starts
getting hot and uncomfortable. Also take into consideration that basic cleanroom clothing includes a hair
covering, booties, and a smock. Anything cleaner than Class 7 requires additional safeguards: masks, beard
covers, goggles, etc. It is better to err on the side of too much when planning for air conditioning.
This is where you get into the difference between single-pass and recirculating rooms. A single-pass room is a
simple design in which air is pumped into the room from the top and blown out vents at the bottom. If you
have to air condition your cleanroom, then you don’t want to just blow that expensive air-conditioned air
through the cleanroom and out into a warehouse or other environment where it does little good. A recirculating
design uses a double-ceiling system (the space between the ceilings is called a plenum) or a double wall (the
space in the walls is called an air chase), or a combination of these two. Cooled, clean air is introduced through
the HEPA filters and then flows out of the room, carrying with it any contaminants, into either the air chase or
the ceiling plenum, where it is reintroduced into the room after once again passing through the HEPA filters.
When you plan and budget for your cleanroom, consider that installation of a recirculating system for that
enclosure is going to be at least 50% of the installation costs. If it is possible to place the cleanroom in an area
where air conditioning is already in place that will be a huge money-saver.
8. Not considering all that is needed.
It pays to bring in an expert early in the planning process. They can help you troubleshoot airflow problems,
the types of testing procedures you must employ, and how to develop cleanroom protocols. A knowledgeable
professional will point out things you will not even consider.
9. Think about process flow.
Give some thought to the workflow in your cleanroom. You want materials to come in one end and exit the
other, and in the meantime, completing all the necessary assembly and packaging that is needed. The goal is
not only to improve productivity and yield but to maintain or improve the speed of the manufacturing process.
Again, this is an area where you should employ a consultant.
10. The need for interior isolation.
Every cleanroom ISO Class 7 or cleaner should have an anteroom for gowning, set off from the larger
cleanroom with softwall curtains at least. This keeps street dirt from getting into the clean area. Interior
isolation is also important in food processing and pharmaceuticals to prevent cross-contamination. A recent
Simplex project called for dividers for a vitamin processing operation. If vitamin B12 meanders into the Vitamin
C work area, that’s cross-contamination—a huge problem. Cross contamination can mean manufacturing
shutdowns and product recalls and lost profits.
11. Clearance issues.
People are often eager to use as much of their space as possible. It is a good idea to give yourself some extra
room overhead between the outside ceiling of your cleanroom and the ceiling of your building— Simplex
recommends three feet—to allow you to change out the pre-filters, HEPAs and ULPAs without a big hassle. The
other issue to consider is that without enough clearance, a minimum of six inches, you run the risk of starving
your filters for air.
12. More need for clearance.
Regarding installation of the room itself, three feet is important all the way around the side walls. It will make
the installation easier, as you will have more room to work with. The common space solution is to place the
cleanroom against the walls and this is often done. This is great for maximizing the footprint but will make the
install more difficult.
13. Look for a cleanroom with extensive plans and instructions.
The performance of your cleanroom hinges a great deal on the quality of the assembly. Look for a company
that supplies the approval drawings with layout and elevations, and also shows the HEPA and lighting layout.
Look for a manufacturer that supplies installation drawings with every panel marked with a letter or number
that corresponds to the panel or part on the drawing. For large cleanrooms and critical applications you might
need to consider a specialty contractor knowledgeable in cleanroom construction.
14. Establish cleanroom operating procedures and have them documented.
Make sure your employees read them, are familiar with them, and follow them—always. The single biggest
source of contamination in a clean area is— you guessed it—the worker in that area. If your cleanroom
requirements call for gowning and booties, then no employee should ever enter that space without them. To do
otherwise contaminates your workplace and sacrifices the integrity of your manufacturing process.
NOTE: Maintaining clean environments can be a complicated and critical task. The information provided here is
meant to give the reader a basic understanding of the issues involving the selection of a cleanroom. We
recommend that you always consult and work with a cleanroom professional when implementing any sort of
isolation procedures in your workplace, laboratory, or hospital, thus ensuring that you maintain the highest
standards.
Modular Cleanrooms for Business
Startups and New Product
Development
Regulations, cost, location, size, performance—how do you choose the right cleanroom?
Selecting a cleanroom for a new business or product is not a difficult process. There are many considerations
and options, but focusing first on requirements will help make the decision-making easier.
CLEANROOM SELECTION CRITERIA
Rules mandated by government regulations, ISO guidelines, or customer requirements are the first
consideration in selecting the right cleanroom. For example, government regulation USP 797 outlines specific
requirements for the manufacture of pharmaceutical products, and ISO 14644-5:2004 guidelines specify basic
requirements for cleanroom operations. Most often regulations or customer specifications will dictate the
cleanliness level or required rating, which provides a good starting point for choosing the right cleanroom.
Cost is an important consideration, especially if starting a new business or new product line. Prices can vary
greatly from custom, fixed wall construction to modular, free-standing, soft wall or hard wall prefabricated
cleanroom systems. Fixed wall rooms are typically most expensive, with soft wall rooms the least expensive.
Additionally, size, shape, configuration, and accessories will affect the overall cost.
The location of the cleanroom site within the existing building structure, and the number of processes and
workers in the cleanroom will determine the size and shape of the room.
In addition to meeting performance needs, many companies consider the visual aesthetics of a cleanroom very
important, wanting to project a high-tech image with visual appeal to attract new customers.
ADVANTAGES OF MODULAR CLEANROOMS
Modular, free-standing cleanrooms have many distinct advantages over their fixed wall counterparts. Using
modular rooms greatly reduces design, engineering, and construction time, thereby reducing costs. Since they
are not an integral part of a larger structure, modular rooms can be taken down and moved to other facilities,
or even sold as an asset. Fixed wall cleanrooms do not have this flexibility.
Expanding a modular cleanroom can be easily accomplished by taking off a wall and adding another module.
The prefabricated design allows the room to be expanded, relocated, or reconfigured into a different shape or
made into multiple smaller rooms.
All air handling and filtration equipment modules are built into the modular room ceiling. Hook-ups for
electrical and plumbing are engineered in as part of the design.
The amount of time it takes to construct a modular room is much less than constructing a permanent walled
structure. It can take several months to construct a fixed wall cleanroom because of the amount of design,
engineering, and the various trades involved. However, a fairly sophisticated modular room can be constructed
in a week or two. Onsite assembly of a modular cleanroom is also less disruptive to surrounding operations in
comparison to their fixed wall counterparts.
Modular cleanroom systems offer potential tax advantages for businesses. They are not typically considered
part of the building and can often be depreciated faster than built-in, fixed wall cleanrooms. Tax consultants
can provide specific tax advantage information.
MODULAR, SOLID WALL CLEANROOM CONSTRUCTION CONSIDERATIONS
There are two basic types of modular, solid wall cleanrooms: recirculating and non-recirculating. Product and
process requirements will determine which type of room is best suited for a company’s needs.
Recirculating cleanrooms recirculate the air within the cleanroom and prevent it from mixing with outside air,
allowing for better control of the temperature and humidity. Air is recirculated back to the high efficiency
particulate absorbing (HEPA) filters located in the cleanroom’s ceiling. This is accomplished by using air return
chambers in the room’s walls or through existing walls of the building. The recirculating cleanrooms will have
less contamination loading on the HEPA filters because the system is recycling previously cleaned air. With less
contamination loading, the filters will last longer and perform better.
Non-recirculating, sometimes called single pass rooms, draw in air from above the room into the ceiling HEPA
filters. The filtered air is then blown into the cleanroom and exits through an approximate two-inch space
located below the walls or through adjustable wall grills. Nonrecirculating cleanrooms are less costly to
construct than recirculating rooms due to the lack of return air ductwork.
CLEANROOM PERFORMANCE CONSIDERATIONS
Most businesses are aware of their cleanroom performance requirements because of customer, industry, or
government specifications. These performance requirements identify the cleanroom class level required at a
given state or condition. There are three levels of condition (states) for testing and characterizing the
performance of cleanrooms: as-built, at-rest, and operational. Specific test methods for these three
classifications are outlined in ISO 14644-3:2005.
Most cleanrooms are rated and sold in the as-built category—an empty room with the filter system running,
but without workers and production equipment. However, adding workers and equipment will introduce
contamination and affect the room rating. A cleanroom may be rated ISO 6 at rest, but at ISO 7 during
operation (Table 1). To comply with performance requirements, the as-built empty room should be tested and
benchmarked, followed by testing and documentation of the at-rest and operational states. If contamination in
the at-rest or operational states is not in compliance, corrective steps need to be taken. These steps can range
from examining the production process and number of workers in the cleanroom, to testing the room’s air flow
performance.

To ensure optimal cleanroom performance, air flow design and frequency of air changes should be evaluated.
Cleanrooms are classified according to the number and size of particles permitted per volume of air in a
specific amount of time. There is a relationship between cleanroom class ratings and the room’s air changes
per hour. For a cleaner room rating, more air exchanges become necessary. For example, a typical ISO 7 Class
room will have 60-150 changes of air per hour, while an ISO 6 Class room will have 150-240 changes (Table
2).

All areas within a cleanroom should have similar air changes during each hour to ensure required performance.
For example, a cleanroom with only one air return or exit, located at the opposite end of the room from the fan
and filter, will produce stagnant air spots. This type of design causes air to flow almost horizontally across the
room to the venting location, in a line-of-sight fashion. Areas of inadequate air movement retain higher levels
of contamination. Adding or moving air returns will enable a more vertical and even air flow, improving overall
air quality. The right balance of filter systems and air returns must be maintained to create positive air
pressure inside the cleanroom. Positive air pressure produces an outward air movement, preventing the inflow
of contaminants and assisting in expelling particles generated by workers and equipment.
Cleanroom air flow performance can be cost-effectively upgraded by adding fan-filter modules (FFM). For
example, FFMs cover approximately 5-15% of an ISO 8 class cleanroom ceiling. Upgrading to an ISO 7
cleanroom requires 15-25% ceiling coverage, and covering 25-40% of the ceiling changes the room to an ISO
6 class (Table 2).
OPTIONS
To make a cleanroom fully functional, a variety of additional accessories, from lighting and doors to furniture
and changing rooms, need to be considered. Accessories can be selected while working with the modular
cleanroom company during the room design and specification phase.
Most cleanrooms have adjacent gowning areas where workers change into special garments, minimizing
particulate contamination before entering the production area of the cleanroom. Some gowning rooms are
equipped with air showers as a way to further reduce particulate contamination that might settle on the surface
of a cleanroom garment. Some gowning rooms may have special benches for people to use while changing into
boots, gloves, gowns, and masks.
Many companies may use the gowning room for transferring production material and equipment in and out of
the clean environment. However, pass-through or double-door airlocks are more efficient and keep the
introduction of particulate contamination to a minimum.
Specially produced cleanroom furniture and tools should be used because they are designed for low particulate
generation. For example, tables are smooth and sealed so they don’t shed particulates and can be easily wiped
down.
SITE CONSIDERATIONS
The modular cleanroom location within a building is very important. Physical space, temperature/humidity, and
cleanliness will affect selection decisions and overall project cost.
Most modular cleanrooms can be installed with as little as 25 inches of clearance over the inside clear height of
the room on non-recirculating rooms, and about 30 inches with recirculating rooms.
A typical cleanroom should operate at about 66-70 degrees Fahrenheit to ensure a comfortable environment
for workers wearing cleanroom garb such as lab coats, head coverings, gloves, and masks.
Non-recirculating cleanrooms work best when the space surrounding the cleanroom is air-conditioned. If
supplemental air conditioning is necessary, it can be brought into the space above the cleanroom or directly
into the HEPA filters, ensuring the room’s temperature is cooler than the surrounding space.
Recirculating cleanrooms provide better temperature control between the interior cleanroom and the
surrounding building space. The room air does not mix with the external air and only requires cooling to
compensate for the internal heat load. Processes requiring humidity control will require special environmental
control systems and are usually only available with recirculating cleanrooms. Typically, systems are made to
just add or just remove humidity depending on the surrounding environment.
ON-SITE INSTALLATION
Installation of a modular, hard wall cleanroom is quick and easy. With modular systems everything is
prefabricated at the factory, so specialists are not needed to assemble the room, just local trades or internal
people. It’s not uncommon to start a project on a Monday and finish on Friday.
MAINTENANCE CONSIDERATIONS
Regular cleanroom maintenance is very straightforward and is needed to ensure cleanroom performance and
certification.
Interior surfaces are wiped down daily on a regular basis or before each shift using a solution of deionized
water and 10% alcohol. The cleanroom floors are routinely mopped as well. Vertical surfaces, such as walls can
be cleaned less frequently depending on product requirements. All contact points such as door handles and
user-operated equipment should also be wiped down on a daily or shift basis, again, depending on process
requirements.
HEPA filters have a pre-filter that needs to be changed regularly—depending on loading. The HEPA filter
modules are fairly maintenance free, but are required to be certified every year. Additionally, proper air flow
and leak checks are usually part of the regular certification for a cleanroom.
Certification of a room can be performed by either internal personnel or external companies. Most companies
prefer an external, third-party firm to perform the certification, providing them with an independent analysis.
Customer or product requirements may require independent certification.
SUMMARY
Determining the right cleanroom for a new product or business requires balancing many selection aspects—
from process requirements and cost, to performance and construction. The decision process is not complex,
but a clear understanding of cleanroom requirements, regulations, operation, and available options will make
cleanroom specification and design easier.

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