Design and operation of clean rooms

1. Title of the Course: Industrial Pharmacy and Pharmaceutical
Technology-III
Course No. PHAR 4105
Design and Operation of Clean Rooms
“A room in which the concentration of airborne particles is controlled, and which is
constructed and used in a manner to minimize the introduction, generation, and retention
of particles inside the room and in which other relevant particles inside the room and in
which other relevant parameters, e.g. temperature, humidity and pressure, are controlled
as necessary.”
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.
What Makes a Room Suitable for Aseptic Processes?
Biological contaminants are ubiquitous. Microorganisms such as bacteria or fungi roam
free in most environments and can cause disease. A major goal of aseptic applications,
including surgery, pharmaceutical compounding or medical implant packaging is
to prevent contaminants and the potential for disease,
How do we create the ideal setting?
Building a microorganism-free space is exactly what regulatory guidelines aim to achieve.
Asepsis is the objective, and certified facilities are bound by regulations that dictate
design and protocol for optimizing aseptic processing.
Building the ideal ISO-compliant room consists of a combination of design and materials,
which we’ll discuss here, but after the cleanroom is ready for operation, continued
success depends on other important issues:
1. Establish and execute a robust training program for workers (gowning, work processes,
and cleaning techniques, as examples)
2. Procured equipment should be properly specified and installed, warrantied and well-
maintained

2. 3. Cleanroom should consistently pass performance testing of such operational factors as
air change rate and particle count
When the cleanroom’s integrity is compromised due to issues like poor control over
contaminants or wall seam breaches, time-consuming (i.e., expensive) shutdown,
cleaning, re-certification and revalidation are necessary to become operational
again. Bottom line: start with a well-designed cleanroom and follow documented
procedures to maintain it.
DESIGN
Many regulations list specific requirements for medical, bio or pharmaceutical processes,
but also allow some flexibility so that labs can accommodate unique technologies or
workflows (reference the USP guidelines for pharmacy compounding, for instance). The
regulation will tell you what is necessary; how you choose to enhance the room’s
capabilities is between you and your certifier. This section discusses some of the options
regarding how the cleanroom will be built and accessorized.
The ability to clean easily, thoroughly and frequently are recurring themes from regulatory
agencies. Materials used for rooms and furnishings should resist damage from chemical
cleaners (as well as those used in the applications), and be free of obstructions like
support braces, seam gaps and protruding hardware. It’s much easier to sanitize a flat,
smooth surface than it is one with angles and corners. Particles are small; they’ll take any
opportunity to find a hiding place. One design strategy is coved corners along floors and
walls that dispense with hard-to-clean right angles. Another would be meticulous seam
sealing of wall and ceiling panels, using a cleanroom-compatible sealant.
Paneling materials such as fiberglass-reinforced plastic (FRP) and chlorinated polyvinyl
chloride (C-PVC) can be adhered to gypsum wallboard or concrete walls, giving you a
choice between creating a modular room or converting existing office space into a
cleanroom. Ceiling grids that house FFUs, lights and other modules can be suspended
or supported above these walls, completing the enclosed interior. Both design options are
less expensive than constructing a new cleanroom. Modular rooms give you the flexibility
to expand, scale-down or relocate, so may be preferred over existing construction.

3. Steel ceiling grids for Clean rooms are easy to wipe down for cleaning, and support all
necessary modules, including HEPA or ULPA fan/filter units, fluorescent lighting, ceiling
panels and options such as UV-C sterilizers and ionizing bars for neutralizing electro-
static discharges (ESD). These ceiling grids top off free-standing modular rooms, or can
be attached to existing facility walls when a room conversion is preferred.
Room-side replaceable fan/filter units are ideal for aseptic rooms. Filters can be replaced
from inside the cleanroom, without breaching the enclosure. Because they eliminates the
need for roof access, this reduces maintenance time and cost. Don’t forget to calculate
your FFU ceiling coverage based on room size and ISO level, then test your air change
rates to be in compliance.
MATERIALS
As with so many other projects, the devil’s in the details. For example, you might consider
installing an ultraviolet-C module in the ducting system: expose the airstream to radiation,
killing airborne bacteria and viruses before they reach the FFUs. Other considerations for
efficient cleanroom design? Try flush-mounted pass-throughs and windows that reduce
the surface area from ledges, making cleaning easy and fast.
Now that you have some ideas about the design of the ISO 5 – 8 aseptic cleanroom, you
should consider your building materials options. The first is steel. Terra’s steel BioSafe
rooms come in powder-coated steel, or 304 or 316 stainless steel. The highest grade is
316; its cost is greater, but so is its resistance to corrosion. Stainless steel is made even
cleaner by electro-polishing, a reverse plating process that removes metal impurities
using electricity and chemicals. An ultra-smooth surface is the result: fewer peaks and
valleys where particulates can hide.

4. Plastic wall panels made of FRP or C-PVC is another choice. Seams in-between FRP
panels are closed off with sealants approved for use in cleanrooms, and have the added
benefit of expanding or contracting to accommodate temperature-induced changes
without cracking. FRP panels are available as Class A or Class C; the material is similar,
but the Class A is Factory Mutual (FM) approved for facilities that need materials with low
flame spread due to work with flammable chemicals or supplies. These FRP panels have
a patented surfacing technology that ensures a uniform seal to enhance durability,
prevent generation of particles and suppress microbial growth.
C-PVC panel seams are welded to create uniform surfaces where germs and
contaminants won’t gather, and their unique solvent-fee silicone adhesive allows
installation on most wall surfaces. C-PVC panels are also FM rated and certified to
achieve ISO 5 cleanliness. These compressed panels offer excellent chemical resistance
and prevent particle emission and microbial growth.
All of these all panel options share two important characteristics:
1. They do not contribute to the population of contaminants in the room. They are non-
shedding, non-out-gassing and scratch-resistant
2. Most common cleaners can be used to sterilize surfaces; they are resistant to damage
from chemicals such as isopropyl alcohol (IPA), and stand up to the rigors of hydrogen
peroxide vapor and UV sterilization
Cleanroom Air Flow Filter and Filtration Systems
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

5. environment. Laminar filters are often composed of stainless steel or other non-shed
materials to ensure the number 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-unidirectional 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.
What is laminar flow?
Laminar flow is defined as airflow in which the entire body of air within a designated space
is uniform in both velocity and direction.
What is a laminar flow hood?
Clean benches and biological safety cabinets are common examples of laminar flow
hoods. They are laboratory enclosures designed to carefully direct HEPA filtered air.
Some of these hoods protect items placed on the work surface from contamination.
Others prevent exposing the user to contaminants in the work area. Laminar flow hoods
are often used to work with biological samples, semiconductors or other sensitive
materials.
According to the CDC, the laminar air flow principle was first developed in the early 1960s.
It's still incredibly relevant for modern labs, having literally shaped the way air safely
moves in many generations of laboratory enclosures. Today, many categories of laminar
flow hoods exist. Although they differ depending on the science performed within, there
is one common denominator: all use this type of unidirectional airflow to aid in maintaining
sterility, preventing cross-contamination and reducing turbulence.
Just what exactly is laminar air flow, why is it effective and what does it look like in labs
today? Let's explore.

6. What is zoned airflow?
Zoned airflow is not truly laminar. Zoned airflow is used when equipment cannot achieve
all of the protection required of a Class II biosafety cabinet with standard laminar airflow.
Each zone, or column, of airflow is defined and has its own range in airspeed. This allows
for higher speed barrier air columns to be utilized as an engineering solution to equipment
that otherwise would have poor containment or product protection ratings.
How does laminar airflow differ from dilution flow?
Dilution flow is not the same as laminar air flow. The dilution flow principle is used in
equipment such as filtered glove boxes. In these instances, HEPA-filtered air mixes with
and dilutes interior airborne contaminants inside the glove box, and those contaminants
are removed via a filtered exhaust system. After the contamination source has been
sealed, the dilution rate—or air changes per minute—will determine how much time must
lapse before materials can be removed from the main chamber.
What is turbulent flow?
While laminar air flow helps to reduce turbulence, turbulent flow encourages it by creating
unintentional swirls of air that place particles randomly on surfaces within an enclosure.
Turbulent flow can be disruptive to work that requires a dust-free environment and can
lead to contamination. Obstructions, like items left inside enclosures, can create this
unwanted turbulence.
LAF Cabinet Configuration :
LAF cabinets are available in both horizontal and vertical configurations. In either case,
these devices provide a clean, sterile environment for the handling of materials. ISO 5
(Fed Std Class 100) HEPA filtered air continually flows over the operator’s work area to
protect product or materials from contamination. HEPA or High-Efficiency Particulate Air
is a type of air filter that must satisfy certain standards of efficiency. To qualify as HEPA
the filter must remove 99.97% of 0.3 µm particles. This size constitutes the Most
Penetrating Particle Size (MPPS), which is the most difficult size of particle to filter.

7. Smaller and larger particles are filtered at even greater efficiency. Particle capture
efficiency at 0.5µm with HEPA filtration will be significantly greater than at 0.3µm. It is at
0.5µm that periodic testing to ISO 14644-1 is typically performed.
Testing LAF Cabinet particle performance
It is good practice to periodically check that an LAF Cabinet is performing to specification.
Test frequency and number of sample points to test are considerations influenced by a
number of factors, such as application, risk assessment, workflow and workload. In this
example, an LAF used by a medical device manufacturer is checked every six months to
ensure compliance to ISO 14644-1 Class 5. Four sampling points are selected based
upon a risk assessment of the material and workflow. Two locations were selected based
upon their downstream positioning relative to equipment in the HEPA filtered air flow. As
a student-t test is required to be performed where areas are to be classified to ISO 14644-
1 with fewer than 9 sampling locations, a further two locations were selected to reduce
statistical variance.
Air Filter Mechanisms
Filters have different mechanisms to capture particles, these mechanisms are;
 Straining
 Impingement (Impaction);
 Interception
 Diffusional
Straining occurs when the smallest dimension of a dust particle is greater than the
distance between adjoining filter media fibers. Straining is not an important influence in
filtration except in the removal of long-fibered materials such as lint.

8. Interception occurs when a dust particle follows the air streamlines, but still comes in
contact with the fiber as it passes around it. If the forces of attraction between the fiber
and the dust particle are stronger than the tendency of the airflow to dislodge it, the
particle will be removed from the air stream.
Impingement is the mechanism by which large, high-density particles are captured. As
the dust-laden air passes through the filter media, the air tends to pass around the filter
fibers. However, due to inertia, the dust particles do not follow the air streamlines around
a fiber. Instead, they move straight ahead to collide with the filter fibers to which they
become attached.

9. Diffusional effect explains the capture of very small particles. As the dust-laden air
passes through the filter media, minute particles do not precisely follow the streamlines.
Instead, they are bombared by air (gas) molecules which cause them to take an erratic
path described as Brownian movement. This erratic path increases the probability that
particles will come in contact with fibers and will stay attached to them

10. As the total collecting efficiency of the filter is the sum of different filtration effects, it is
natural to assume that the collecting efficiency has a definite minimum value under certain
condition. Both the interception effect and the inertial effect increase with increasing
particle size, whereas the diffusion effect decreases. This should therefore imply that
there is a definite particle size, which is the hardest to collect in an filter (MPPS).
Sources of Contamination
The airborne contamination level of a cleanroom is largely dependent on the particle
generating activities in the room, besides the personnel who also contribute to the
contamination levels. It has been found that many of these contaminants are generated
from five basic sources
(1) the facilities,
(2) people,
(3) tools,
(4) fluids and
(5) the product being manufactured.
Review the list below to gain a better understanding of where the contamination
originates.
1) Facilities
• Walls, floors and ceilings
• Paint and coatings
• Construction material (sheet rock, saw dust etc.)
• Air conditioning debris
• Room air and vapors
• Spills and leaks
2) People
• Skin flakes and oil
• Cosmetics and perfume
• Spittle • Clothing debris (lint, fibers etc.)

11. • Hair
3) Tool Generated
• Friction and wear particles
• Lubricants and emissions
• Vibrations • Brooms, mops and dusters
4) Fluids
• Particulates floating in air
• Bacteria, organics and moisture
• Floor finishes or coatings
• Cleaning chemicals
• Plasticizers (out-gasses)
• Deionized water
5) Product generated
• Silicon chips
• Quartz flakes
• Cleanroom debris
• Aluminum particles
This is a partial list of some of the commonly known contaminants. Preventing these
contaminants from entering the cleanroom environment is the key objective of cleanroom
design and use.
Key Elements of Contamination Control
We will look at several areas of concern to get a better idea of the overall picture of
contamination control. These are the things that need to be considered when providing
an effective contamination control program.

12. HEPA (High Efficiency Particulate Air Filter) - These filters are extremely important for
maintaining contamination control. They filter particles as small as 0.3 microns with a
99.97% minimum particlecollective efficiency.
CLEANROOM ARCHITECTURE - Cleanrooms are designed to achieve and maintain an
airflow in which essentially the entire body of air within a confined area moves with uniform
velocity along parellel flow lines. This air flow is called laminar flow. The more restriction
of air flow the more turbulence. Turbulence can cause particle movement.
FILTRATION - In addition to the HEPA filters commonly used in cleanrooms, there are a
number of other filtration mechanisms used to remove particles from gases and liquids.
These filters are essential for providing effective contamination control.
CLEANING - Cleaning is an essential element of contamination control. Decisions need
to made about the details of cleanroom maintenance and cleaning. Applications and
procedures need to be written and agreed upon by cleanroom management and
contractors (if used). There are many problems associated with cleaning. Managers need
to answer the following questions before proceeding with any cleanroom cleaning
program:
CLEANROOM GARMENTS - The requirements for cleanroom garments will vary from
location to location. It is important to know the local garment requirements of the
cleanroom management. Gloves, face masks and head covers are standard in nearly
every cleanroom environment. Smocks are being used more and more. Jump suits are
required in very clean environments.
HUMANS IN CLEANROOMS - There are both physical and psychological concerns when
humans are present in cleanrooms. Physical behavior like fast motion and horseplay can
increase contamination. Psychological concerns like room temperature, humidity,
claustrophobia, odors and workplace attitude are important. Below are several ways
people produce contamination: 1. Body Regenerative Processes-- Skin flakes, oils,

13. perspiration and hair. 2. Behavior-- Rate of movement, sneezing and coughing. 3.
Attitude-- Work habits and communciation between workers.
COMMODITIES - Care is taken when selecting and using commodity items in
cleanrooms. Wipers, cleanroom paper and pens and other supplies that service the
cleanroom should be carefully screened and selected. Review of the local cleanroom
requirements for approving and taking these items into the cleanroom are essential. In
fact, many cleanroom managers will have approval lists of these types of items.
COSMETICS - Many cosmetics contain sodium, magnesium, silicon, calcium, potassium
or iron. These chemicals can create damaging particles. Cleanroom managers may ban
or restrict cosmetics in the cleanroom. This is usually dependent upon the threat to the
product being made in the cleanroom. A recent mirror on a space telescope was fogged
up from the cologne that was present in the cleanroom.
MEASUREMENT AND INSTRUMENTATION - Some important measurements related to
contamination control are particle count, air flow & velocity, humidity, temperature and
surface cleanliness. Cleanroom managers usually have specific standards and/or
instruments to measure these factors.
ELECTROSTATIC DISCHARGE (ESD) - When two surfaces rub together an electrical
charge can be created. Moving air creates a charge. People touching surfaces or walking
across the floor can create a triboelectric charge. Special care is taken to use ESD
protective materials to prevent damage from ESD. Cleaning managers should work with
their personnel to understand where these conditions may be present and how to prevent
them.
General Cleanroom Regulations
Below is a list of general regulations recommended as a minimum for the successful
operation of a cleanroom. All professional cleaning personnel should be aware and follow
these regulations at all times.

14. 1. All personal items such as keys, watches, rings, matches, lighters and cigarettes
should be stored in the personal locker outside the gowning room.
2. Valuable personal Items such as wallets may be permitted in the cleanroom provided
they are NEVER removed from beneath the cleanroom garments.
3. NO eating, smoking or gum chewing allowed inside the cleanroom.
4. Only garments approved for the cleanroom should be worn when entering.
5. NO cosmetics shall be worn in the cleanrooms. This includes: rouge, lipstick, eye
shadow, eyebrow pencil, mascara, eye liner, false eye lashes, fingernail polish, hair
spray, mousse, or the heavy use of aerosols, after shaves and perfumes.
6. Only approved cleanroom paper shall be allowed in the cleanroom.
7. Approved ball point pens shall be the only writing tool used.
8. Use of paper or fabric towels is prohibited. Use of hand dryers equipped with HEPA
filters is suggested.
9. Gloves or finger cots should not be allowed to touch any item or surface that has not
been thoroughly cleaned.
10. Only approved gloves, finger cots (powder-free), pliers, tweezers should be used to
handle product. Finger prints can be a major source of contamination on some products.
11. Solvent contact with the bare skin should be avoided. They can remove skin oils and
increase skin flaking.
12. Approved skin lotions or lanolin based soaps are sometimes allowed. These can
reduce skin flaking.
13. All tools, containers and fixtures used in the cleaning process should be cleaned to
the same degree as the cleanroom surfaces. All of these items are a source of
contamination.
14. NO tool should be allowed to rest on the surface of a bench or table. It should be
place on a cleanroom wiper.
15. Only cleanroom approved wipers are allowed to be used. The wipers must be
approved for the Class of cleanroom being cleaned.
16. ALL equipment, materials and containers introduced into a sterile facility must be
subjected to stringent sterilization prior to entrance.

15. 17. NO ONE who is physically ill, especially with respiratory or stomach disorders, may
enter a sterile room. This is a good practice in any cleanroom environment.
Personal Actions Prohibited in Cleanrooms
1. Fast motions such as running, walking fast or horseplay.
2. Sitting or leaning on equipment or work surfaces.
3. Writing on equipment or garments.
4. Removal of items from beneath the cleanroom garments.
5. Wearing the cleanroom garment outside the cleanroom.
6. Wearing torn or soiled garments.
Minimal List of Items to be Covered during an initial Cleanroom Walkthrough
1. Cleanroom entry and exit protocols
2. ISO5 and ISO6 areas
3. service bays, process bays
4. differential pressures between areas
5. particle counters 6. fire extinguishers
7. eyewashes and safety showers
8. ringdown/emergency phones
9. emergency gas off buttons
10. hazardous gas alarm lights, detectors, and status panel
11. wet process benches – location, purpose
12. doors – entry, emergency exit, service bay, sliding

16. 12 points to consider when setting up a cleanroom
There are many elements to take into consideration when you set up a cleanroom. Along
with the practicalities of how much space you have and how much space you need for
your equipment, you also need to consider:
1. HEPA (High Efficiency Particulate Air) filters: These filters support contamination control
by filtering particles as small as 0.3 microns. Air should be continually circulated through
HEPA filters to remove contaminants in the air and to supply fresh air for people working
in the cleanroom.
2. Ventilation: Ventilation is required to maintain air quality and replace process exhaust.
This is very energy-intensive, so you need extra space for cooling unit components as
well as larger air passageways, noise suppressors, a backup generator and large intake
and exhaust stacks.
3. Air pressure: Cleanrooms should have a static pressure which is higher than atmospheric
pressure in order to prevent infiltration by wind. Airlocks also help minimize or prevent
changes in pressure that could compromise the process.
4. Temperature and humidity: Temperature control means stable and consistent conditions
for materials and equipment. Humidity control prevents corrosion and condensation of
internal surfaces and eliminates static electricity. These two factors are integral to the
function of a clean room as well as to the comfort of the people working within it.
5. Architecture: In order to maintain a consistent air flow throughout the cleanroom, the air
needs as unrestricted path as possible. If air flow is restricted, the resulting turbulence
can then cause movement of particles which in turn raises the risk of airborne
contaminants.
6. Measuring equipment: A cleanroom needs to be constantly measured to ensure that
factors such as particle count, air flow, humidity, temperature, and cleanliness are at the
appropriate levels.
7. Electrostatic discharge: Moving air and moving people both create an electrical charge.
Electrostatic discharge protective materials should be used to prevent potential damage.
8. Lighting: A dimly lit cleanroom won’t do you any favors. You won’t be able to clean
properly so particles will build up, and you may misread instrument displays. Lighting in
a cleanroom should be consistent and uniform with few dark spots.

17. 9. Future-proofing: Make sure your cleanroom is as flexible in design as possible to
accommodate future expansion, new equipment or changes to processes.
10.Materials used for internal surfaces: In a cleanroom, you cannot use any surface material
that may shed particles and contaminate the air. They also need to be resistant to
breakdown when cleaned, so they need to be compatible with your cleaning products.
11.Showers and laundry facilities: This will depend on your requirements and materials, but
you may need to provide showers and laundry facilities for decontamination purposes.
This means you will need to consider plumbing and hazardous waste treatment.
12.Hazardous materials: If your cleanroom handles hazardous materials, extra
considerations include using a negative air pressure system and the special treatment of
waste air, as well as personal protection, and separate entrances and exits.
Cleanroom Class Limits
Class limits (maximum allowable particles)
ISO FED STD 209E 0.1 µm 0.3 µm 0.5 µm 5.0 µm
CLASS 3 1 1,000 / 35 102 / 3 35 / 1
CLASS 4 10 10,000 / 350 1,020 / 30 352 / 10 0
CLASS 5 100 100,000 / 3,500 10,200 / 300 3,520 / 100 0
CLASS 6 1,000 1,000,000 / 35,000 102,000 / N/A 35,200 / 1,000 7
CLASS 7 10,000 350,000 N/A 352,000 / 10,000 70
CLASS 8 100,000 3,500,000 N/A 3,520,000 / 100,000 700
ISO 14644-1 (per cubic meter)
Fed Std. 209 E USA (per cubic foot)
ISO standard requires results to be shown in cubic meters (1 cubic meter = 35.314 cubic feet)

18. Cleanroom Class 1
 540 to 600+ air changes per hour (98%+ ceiling coverage)
 ULPA filters (99.9995% on .12 microns)
 Gel/Flush grid ceiling systems with raised floors are required
 Outside/makeup air to be prefiltered with a HEPA filter
Cleanroom Class 10
 540 to 600 air changes per hour (85-90% ceiling coverage)
 99.999% on 0.3 microns, with a raised floors
 90%+ coverage with low wall returns
 Gasketed grids with negative plenums acceptable
 HEPA filters on makeup air
Cleanroom Class 100
 400 to 480 air changes per hour (60-80% ceiling coverage)
 99.99% HEPA filters
 Raised floor assures optimal performance. Low wall returns work when they are no further
than 12' from the center of the room¹
 Gasketed ceiling grid
Cleanroom Class 1,000
 120 to 150 air changes per hour (40-50% ceiling coverage)
 99.99% HEPA filter
 Gasketed ceiling grid
 Raised floor delivers best performance, but low wall returns are very common¹
Cleanroom Class 10,000
 45 to 60 air changes per hour (10-20% ceiling coverage)
 99.97% or 99.99% HEPAs
 Low wall or ceiling returns acceptable in most applications¹

19. Cleanroom Class 100,000
 20 to 30 air changes per hour (5% ceiling coverage)
 HEPA filters or 95% HEPAs (95%+ ASHRAE box filters²) located downstream of the
HVAC unit
 Heat load may require more air changes
1. Room layout with equipment must be evaluated to look for return air paths and possible
cross contamination.
2. 95% ASHRAE filters when new may only be 70% and could affect the particle level.
Important point to consider concerning filter coverage
A 300 sq. ft. cleanroom may need 90% coverage (38 HEPAs) for Class 100 at the
"operational" mode, 60% coverage (23) in the "at rest" mode, and only 40% (15) to meet
Class 100 at "as built". The same rules can and do apply to Class 1,000 and Class 10,000
levels.
Types of Cleanrooms
Cleanrooms have evolved into two major types and they are differentiated by their method
of ventilation. These are non-unidirectional and unidirectional airflow cleanrooms.
Unidirectional airflow cleanrooms were originally known as ‘laminar flow’ cleanrooms and
non-unidirectional flow cleanrooms as ‘turbulently ventilated’. The use of the term ‘laminar
flow’ was a mistake, as laminar flow has a meaning in physics and engineering that does
not apply to the airflow in a cleanroom. Unidirectional airflow is the correct way of
describing the airflow and is the term used in the ISO standards. Unidirectional airflow
cleanrooms use very much more air than non-unidirectional airflow cleanrooms, and give
superior cleanliness. air extract high efficiency air filter production equipment.
The two major types of cleanroom are cleanroom receiving clean filtered air through a
high efficiency air filter and air diffuser in the ceiling. This air mixes with the room air and
removes airborne contamination through air extracts at the bottom of the walls. The air
change rates are normally equal to, or more than, 20 per hour, this being much greater
than in ordinary rooms, such as in offices. In this non-unidirectional style of cleanroom,

20. the contamination generated by people and machinery is mixed with and diluted by the
supply air, and then removed. High efficiency filters are installed across the whole ceiling
and the air to the room is supplied through these. This air sweeps down through the room
in a unidirectional way at a velocity generally between 0.3 m/s (60 ft/min) and 0.5 m/s
(100 ft/min) and exits through the floor, thus removing the airborne contamination from
the room. This system uses much more air than the non- unidirectional airflow cleanroom
but, because of the directed air movement, it minimises the spread of contamination about
the room and sweeps it out through grilles in the floor. An alternative configuration has
the high efficiency filters installed across the whole of one wall with the air being removed
at the opposite wall. Separative devices, such as unidirectional airflow benches or
isolators, are used in both non-unidirectional and unidirectional airflow cleanrooms. These
give a localised supply of filtered air and enhanced air conditions where required, e.g. at
the area where the product is open to contamination.
ISO 14644-3: Methods of evaluation and measurements of clean room
Metrology and test methods
1. Airborne particle count for classification of the installation and test measurement
2. Airflow test
3. Air pressure difference test
4. Installed filter system leakage test
5. Flow visualization 6. Airflow direction test
7. Temperature test
8. Humidity test
9. Recovery test
10.Containment leak test
Cleanroom Commissioning Procedures
Cleanroom (HVAC System) Commissioning
1. Hydronic Balance Testing
2. Sound Measurement Testing

21. 3. Vibration Testing
4. Alarms and Interlocks Testing
5. Air Flow rate testing in ductwork
6. Air Volume Stpply and Return, Testing and Balancing
7. Fan RPM and Amperage Confirmation
8. Temperature, Humidity (Coil Duties) and Static Pressure Testing (Duct Leak)
9. Differential Pressure Testing and Balancing
10. Loop Checks
11. HEPA Filter Integrity Testing
12. Component (Air coil, AHU, FCU, Filters) Operation Testing (Test sequences,
Shutdown, and Start-up Procedures)
13. Process and Instrumentation Diagram (P&ID) confirmation = As-Built P&ID
14. Utilities Check „ Instrumentation Calibration
15. Electrical Power Tests
16. Motor Run Tests
17. Lubrication Checks
18. Isometric Drawing Checks
19. Safety Checks
Cleanroom (Finishing) Commissioning
1. Floor, Wall, Ceiling
2. Doors and Airlocks and Interlocks
3. Lighting and other Fixtures
Cleanroom Certification Measurements
Standard Measurements
1. Air velocity / Air velocity distribution
2. Filter Airflow rate
3. AHU Airflow rate
4. Filter leakage test
5. Room pressurisation

22. 6. Cleanliness classification
7. Temperature and Humidity
Optional Measurements
1. Containment leak test / Enclosure integrity test
2. Parallelism - Airflow direction test Airflow visualisation
3. Recovery time
4. Microbiological count (Air, surfaces)
5. 3rd Party Certification