ME4102

Professional Development I -
Standards in Mechanical Engineering
Dr SNG Wei Meng, Daniel
daniel.sng@nus.edu.sg, E2-02-32

Department of Mechanical Engineering

College of Design and Engineering

1
Healthcare Service Infrastructure

2
Information
• Medical technology, or medtech, encompasses a wide range of
healthcare products or services.
• Areas covered:
Information technology

Biotech

Medical devices
Mechanical Engineering Related
Healthcare service infrastructure

3
A typical clean room

4
What’s a Clean Room
• An area/room which is designed, constructed, used and maintained in
such a manner, so as to preclude or reduce the introduction,
generation or retention of viable and non-viable particulates.
• Clean room is also regulated and monitored for RH, Temp. and ∆P.
• So, in a clean room, conditioned air is supplied

5
Quality, GMP and Cleanroom are related
What’s Quality?
• Meeting the predetermined requirements of the user for a particular
product or service.
• Totality of characteristics of an entity that bear on its ability to fulfill
implied or stated needs.

6
Quality, GMP and Cleanroom are related
What’s GMP (Good Manufacturing Practice)?
• GMP is that part of QA, which ensures that the products are
consistently produced and controlled to the quality standards
appropriate to their intended use and as required by the marketing
authorization.

7
Quality, GMP and Cleanroom are related
• A clean room is a rigorously controlled environment that has a low
level of environmental pollutants such as dust, airborne microbes,
aerosol particles and chemical vapors.
• The air entering a clean room is filtered and then continuously
circulated through high efficiency particulate air (HEPA) and/or ultra-
low particulate air (ULPA) filters to remove internally generated
contaminants.
• Staff wearing protective clothing must enter and exit through
airlocks, while equipment and furniture inside the clean room is
specially designed to produce minimal particles.

8
Mechanism of Filtration through HEPA

• HEPA filters are composed of a mat of randomly arranged fibres. The fibres are typically composed of
fiberglass and possess diameters between 0.5 and 2.0 micron. Key factors affecting function are fibre
diameter, filter thickness, and face velocity. The air space between HEPA filter fibres is much greater than 0.3
µm. The common assumption that a HEPA filter acts like a sieve where particles smaller than the largest
opening can pass through is incorrect. Unlike membrane filters, where particles as wide as the largest
opening or distance between fibres cannot pass in between them at all, HEPA filters are designed to target
much smaller pollutants and particles. These particles are trapped (they stick to a fibre) through a
combination of the three mechanisms -- Interception, Impaction and Diffusion.
9
10
Why Clean Rooms?
• Clean, safe and contaminant-free environment is imperative for
manufacturing efficacious, safe and good quality drug products.
• Also critical to protect employees from contact with hazardous
materials or pathogens and prevent health problems from prolonged
exposure to chemicals or allergens.
• Clean rooms are part of GMP requirement and GMP is statutory in
nature.

11
Why Clean Rooms?
Clean areas:

• Play a major role in the quality of pharmaceuticals.

• Design requires careful consideration of its intended use.
• Must be designed meticulously, by professionals.
• Must be treated as a critical system.

12
Definition of Clean Area
As per ISO 14644:
• Room in which the concentration of airborne particle is controlled, and which is
constructed & used in a manner to minimize the introduction, generation, and
retention of particles inside the room and in which other relevant parameters
(e.g., temperature, humidity, and Pressure) are controlled as necessary.
As per WHO-GMP:
• An area with defined environmental control of particulate and microbial
contamination, constructed and used in such a way as to reduce the
introduction, generation, and retention of contaminants within the area.
As per USP Chapter 1116:
• A room in which the concentration of airborne particles is controlled to meet a
specified airborne particulate Cleanliness Class. In addition, the concentration of
microorganisms in the environment is monitored; each Cleanliness Class defined
is also assigned a microbial level for air, surface, and personnel gear.
13
What is Contamination?
• Addition of foreign substance and altering of product quality.
• Contaminants are particulate, liquid, gaseous, film or biological in nature. Some
authorities also include radiation and electromagnetic interference (EMI) as
contaminants.

What is difference b/w contamination & Cross-contamination?

• Contamination: Mixing of foreign substance which may alter the product quality.
• Cross-contamination: Mixing of a raw material (RM), intermediate or finished into
another RM, Intermediate or finished product which may alter the product quality.
Sources of particulate matter (contaminant):
• The supply air, i.e., externally sourced
• The Internal particle generation
• The infiltration from adjacent spaces

14
Why All the Concern About Dust?
• Dust is a Bacteria Carrier

15
Eliminating sub-micron airborne
contaminants are challenging
• Minuscule particles cannot be handled by regular cleaning tools
(Mops, Vacuum cleaners etc.)
• ASHRAE 6 defines particles smaller than 2.5 μm in diameter as fine
mode and those larger than 2.5 μm as coarse mode. Fine mode
particles generally are less likely to settle in ambient conditions and
are just as likely to deposit on vertical surfaces as on horizontal
surfaces. Coarse mode particles will generally settle, and thus have a
shorter lifetime in the airborne state.
• For example, in an eight-foot high (≈2.5 m) room, a particle in the 50
micron range might take 60 seconds to settle, while a 1 micron
particle might take 15 hours to settle.

16
A clean room animation

17
Clean Room Basic Terms

18
19
Clean Room Basic Terms
Air Lock:
• An enclosed space with two or more
interlocking doors. Its function is to act as
a buffer zone between the clean room
and the outside atmosphere. It helps keep
the clean room pressurized and free from
infiltrating dirt. Two types of Air locks are
Personnel Air Lock (PAL) and Material Air
Lock (MAL)
Air Shower:
• An enclosed chamber designed to clean
personnel and their garments of
contamination, prior to entering the clean
room, by means of high velocity of air
jets.

20
Clean Room Basic Terms
Garments:
• These are lint-free garments made of Pass box
synthetic fabrics such as Nylon, Dacron
etc.
Pass Box:
• A small enclosure that mounted through
the clean room wall and allows product
to be passed through efficiently. Pass box
cut down on personnel traffic, hence
reducing contamination.
Sticky Mat:
• Located at the clean room or air shower
entrance, sticky mats are multiple layers
of treated film with adhesive to clean
shoe bottoms and sides before entering
the room.

21
Clean Room Basic Terms
HEPA filter:
• High Efficiency Particulate Air filter, capable of filtering out 0.3 micron particles or larger with
99.97% efficiency.
ULPA filter:
• Ultra Low Particulate Air filter, capable of filtering out 0.12 micron particles or larger. ULPA's
operate with 99.9999% efficiency.
HVAC:
• The system consisted of AHU(s), ducts and Terminal HEPA filters to supply conditioned air. HVAC
helps to provide desired RH, Temp., Diff. Pressure in the controlled area.
AHU:
• Device used to condition and circulate air as part of a heating, ventilating, and air-conditioning
(HVAC) system. Usually, an air handler is a large metal box containing a blower, heating and/or
cooling elements, filter racks or chambers, sound attenuators, and dampers. AHUs usually
connect to duct work that distributes the conditioned air through the building, and returns it to
the AHU.

22
Removal of Microbes
• As dust is a carrier, dust must be controlled.
• Ambient microbe is removed by filtration.
• Internal microbe distribution can be controlled by directional air flow
and air flushing or dilution.
• Surface microbe is controlled by adhering strictly to cleaning SOPs.

23
 ?

Air side of a HVAC

system

24
 Basic air-conditioning system

To heat sink Cooling tower

Water
Chiller
Compressor
power input Chilled water
Air handling unit
Fresh air (AHU)
Cold air
Exhaust air
Room

Heat load into

room 25
How Air Conditioning Works?

26
An AC Unit

Condenser

Evaporator

27
A HVAC System for a Big Building

Cooling coil

AHU Refrigerant Loop Water Loop 2

Water Loop 1

Air Loop

28
A HVAC System for a Big Building

29
Marina Bay Sands Integrated Resort: Ned Kahn Tipper Water
Wall

The façade of a cooling tower was covered with 10,000 hinged

metal channels that fill with water and tip either left or right.
The result is a complex and unpredictable dance of water and
metal where each element alters the behavior of the elements
surrounding it.

30
Location of AHUs

31
Thank you!
Q&A

32