Room Environment For Medical Devices - ISO 14644
Unikal Consultants, Ahmedabad
What is the purpose of a clean room?
The purpose of every clean room is
to control an environment by limiting the presence of
sub-micron particles and modifying inadequate
environmental conditions. The level to which
the environment is controlled is what separates
one clean room from another.
For instance, a Class 10 clean room
has 10 particles of size 0.5 microns per cubic foot of
air, where as a Class 100,000 clean room has 100,000
particles of size 0.5 micron per cubic foot of air.
The need for clean rooms :
The electronic, high-tech, semiconductor,
pharmaceutical, aerospace, medical and many other
industries depend on clean room technology. As products
such as cell phone circuit boards become smaller, the
chance of contamination in manufacturing becomes higher.
For pharmaceutical and medical device
manufacturing companies, clean, safe and contaminant-free
products are imperative to manufacturing and distributing
a viable product.
What are the attributes to create and
use a clean-room :
The largest threat to contaminate devices
is personnel working on processing them!
Why? The following statistics have been
taken from "The Austin Index" to illustrate personnel
Personnel sampled were fully clothed in
clean room garments and engaged in one of the following:
Standing or sitting with no movement
resulted in 100,000 particles/minute 0.3 microns or larger
Sitting or standing, light head, hand and
forearm movement resulted in 500,000 particles/minute, 0.3
microns and larger
Sitting or standing, average body and arm
movement, toe tapping, resulted in 1,000,000 particles /
minute, 0.3 microns and larger
Changing positions, sitting to standing,
resulted in 2,500,000 particles/minute, 0.3 microns or
5a. Slow walking (2 mph), 5,000,000
particles/minute, 0.3 microns and larger.
5b. Average walking (3.57 mph), 7,500,000
particles/minute, 0.3 micron and larger.
5c. Fast walking (5 mph) 10,000,000 particles/minute, 0.3
microns and larger
Climbing stairs, 10,000,000
particles/minute, 0.3 microns and larger
Let’s see how clean room works to maintain
Like anything technical, how a cleanroom
works is essentially basic, but wrapped up in a whole lot
of jargon, standards, rules and regulations. The basic
principles are actually perfectly understandable.
Cleanrooms do not eliminate contamination
altogether. They control it to an acceptable level. How do
they do this?
There are three things that keep a cleanroom “clean”:
1. The internal surfaces of the cleanroom and the
2. The control of air through the cleanroom;
3. The way the cleanroom is operated.
Each of the three things above is as important as the
other. Let’s look at them in more detail.
Everything in a cleanroom should be “smooth and
impervious”. The whole idea is to have surfaces that:
• Don’t generate their own contamination ie, don’t create
dust, or peel, flake, corrode or provide a nice place for
bugs to grow
• Are easy to clean i.e., all surfaces are easily
accessible and are easily decontaminated
• Are rigid and robust and won’t crease, crack, shatter or
This means that a painted wall is better than a bare brick
wall; a stainless steel bench is better than a wooden one.
Cleanrooms need a lot of air. As a general rule of thumb,
the cleaner the cleanroom needs to be, the more air it
will need to use.
Air handling systems are designed to circulate air through
the room, removing contamination as air is generated and
keeping the temperature and humidity stable.
Particles (contamination) in the air tend
to either float around or slowly settle to the ground,
depending on how big they are. The air handling system
delivers air into the room in such a way that it captures
any particles and sweeps them out of the room. The air
taken out of the room and is usually re-circulated through
the air handling system where filters remove the
contamination. Typically, the air is then recycled back
into the room.
The amount of air we put into the room is
important as well. As noted earlier, generally the cleaner
the cleanroom the more clean air you will need to put in.
The more air that goes in, the faster the room cleans
itself. This can be important for rooms that occasionally
experience high amounts of contamination, or something
like a sampling room or dispensary where the room needs to
be cleaned quickly between operations. So, as the amount
of air introduced into a cleanroom is tightly controlled,
so is the amount of air that is taken out. Generally
cleanrooms are pressurized, which is achieved by taking
out slightly less air than is put in. The extra air then
leaks out under the door or through the tiny cracks or
gaps that are inevitably in any cleanroom. As a rule,
within a facility the area you need to be the cleanest
operates at the highest pressure. The flow of air out of
the cleanroom helps to stop any external contamination
from getting in.
A good air handling system makes sure that
air is kept moving throughout the cleanroom. The properly
locating where the air is brought in and taken out is the
key to good cleanroom design. The location of the supply
and return air should take the highest priority when
laying out the room.
The most effective way of maintaining the
air quality in a cleanroom is to operate it properly. This
• minimizing the amount of contamination
that escapes from your manufacturing operations
• strictly controlling access to the cleanroom to trained
personnel – people are the largest source of cleanroom
• regularly cleaning your cleanroom to strictly controlled
• regular maintenance of equipment
• regular monitoring of the filters and air flows and
frequent recertification of the cleanroom.
This requires defining the number of times
the air is changed within a cleanroom. It is simply
calculated by taking the total volume of air introduced
into the cleanroom over an hour and dividing it by the
volume of the room.
HEPA is one of the most important elements
of a cleanroom. They are large, box shaped filters that
remove contamination very efficiently, but they take quite
a bit of energy to push the air through them. They must
also be monitored and tested regularly to make sure they
are still integral.
DOP testing or integrity testing is a testing procedure to
ensure that a HEPA filter has no holes and is properly
sealed in its frame.
A micron is a millionth of a metre. A human hair is around
100 microns thick. Bacteria are 1 or 2 microns wide.
Particles less than 50 microns cannot be seen by a naked
An airlock is a room where personnel, materials or
equipment are transferred to a cleaner environment. It can
be the size of a small box, through to a large room where
personnel change into and out of cleanroom garments.
Grades A through to D refer to cleanroom cleanliness for
the Pharmaceutical Industry for European, Australian and
some Asian countries. Grade A is the cleanest, for sterile
operations, through to Grade D for packing or support
operations. These Grades can be related to the ISO
Thus there is a need to use clean room technology to
reduce the contamination which will ultimately affect
cleanliness of the product and in our case medical device
being manufactured in the environment.
Cleanliness level is classified under
The cleanliness of a clean room is measured by the size
and number of dust particles in a given volume of air. The
rating or classification by the number of particles in a
given volume of air and under specific conditions is
called cleanliness level class.
CLEANROOM AND CLEAN ZONE CERTIFICATION
Regulations vary from country to country, but in most
places, the national rule is established by referring to
US Federal standard 209E and now ISO 14644.
New series of standards ISO 14644-1 have derived its
structure from Federal Standard 209 E, at the same time
there are some significant differences that affects
medical device and pharmaceutical manufacturers.
ISO 14644-1 primarily addresses the cleanroom
classification system and the ISO 14644-2 contains
specifics on "how" to test and monitor clean-rooms or
clean zones for compliance.
ISO 14644 International clean-room standard:- Part 1 was
first published in 1999. It is a 12 part standard. It is
applicable to Electronics, healthcare, biotechnology,
pharmaceuticals. It replaced FS 209E in 2001 and this was
Accepted by EU GMP in 2003 for classification but not
monitoring of cleanroom and FDA aseptic filling guide in
What is the content of these standards series?
ISO 14644-1 - Classification of air cleanliness
ISO 14644-2 - Specifications for testing and monitoring to
prove continued compliance by ACP. Both parts deal with
particles only Details are given below with reference to
each of these parts. They are divided in two # 1 & 2
ISO 14644-1:2015 - Part 1: Classification of air
cleanliness Explanation: Classification is the process of
qualifying cleanroom environment by number of particles
using a standard method. This was we can determine
classification of clean-room according to standards e.g.
Room x is ISO class y. This is distinct from routine
environmental monitoring and also distinct from process
monitoring e.g. ongoing assessment of aseptic filling.