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Clean Room Environment For Medical Devices - ISO 14644

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 contamination.

Personnel sampled were fully clothed in clean room garments and engaged in one of the following:

1. Standing or sitting with no movement resulted in 100,000 particles/minute 0.3 microns or larger

2. Sitting or standing, light head, hand and forearm movement resulted in 500,000 particles/minute, 0.3 microns and larger

3. Sitting or standing, average body and arm movement, toe tapping, resulted in 1,000,000 particles / minute, 0.3 microns and larger

4. Changing positions, sitting to standing, resulted in 2,500,000 particles/minute, 0.3 microns or larger.

5. 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

6. Climbing stairs, 10,000,000 particles/minute, 0.3 microns and larger

Let’s see how clean room works to maintain defined standards:

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 equipment within;
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 dent easily.

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 involves :

• 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 contamination
• regularly cleaning your cleanroom to strictly controlled procedures
• 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 eye.

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 Classes.

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 specific conditions.

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 2004.

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.