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1. Organization Set-up
Design Criteria
The Facility should be designed to help to protect the
product.
One of the Process and Operational critical requirement is
the role in how a facility is organized to prevent
contamination and mix of products.
Considerations of potential product hazards and
containment requirements.
Fitting or integrating the process or operational
requirements into a project site is considered essential for a
successful project. The main goal is to protect the product.
The implementation of the facility design to achieve this is
facility modeling.
1. Organization Set-up
Design Criteria
Site and Building Considerations in the aspect of
Sanitization :
Environmental Protection is essential
Operator protection is essential
Product
1. Organization Set-up
Layout Consideration
The main goal is to protect the product from contamination.
Layout and facility design should achieve the ways for facility
modeling.
The process specialist, architect, layout engineer, HVAC engineer
and QA should collaborate for successful integration design.
Product and Process requirements and information.
Conceptual layout should be enhanced and refined to produce an
equipment and facility layout.
The layout should determine equipment relationship and
integrate equipment needs as well access and movement
requirements for people, components etc.. To permit
development of an efficient layout.
1. Organization Set-up
Room Function/Finishes
Room for aseptic processing for product or components.
Room/area immediately adjacent to the above,
Warehousing
Office
Plant utilities
Circulation area
1. Organization Set-up
minimal ledges
Joints
No corners (that are difficult to access)
Importantly near the product and process equipment.
1. Organization Set-up
necessary.
Door swings should be opposite direction of airflow to
1. Organization Set-up
1. Organization Set-up
1. Organization Set-up
Room Classification
Electrical System
Pharmaceutical
Power distribution
Lighting
Outlets and
miscellaneous
Equipment
Grade 8 Environment
2. Basic Training
2. Basic Training
Parasites or
decomposers. Fungi contain no chlorophyll and cannot synthesize food.
Instead they secrete enzymes that digest food material outside the
organisms.
Bacteria: Bacteria are tiny single-cell microorganisms, usually a few
micrometers in length that normally exist together in millions. A gram of
soil typically contains about 40 million bacterial cells. A milliliter of fresh
water usually holds about one million bacterial cells. Bacteria come in
three main shapes:
- Spherical (like a ball) : These are usually the simplest ones. Bacteria
shaped like this are called cocci (singular coccus).
- Rod shaped: These are known as bacilli (singular bacillus). Some of
the rod-shaped bacteria are curved; these are known as vibrio.
- Spiral: These known are as spirilla (singular spirillus). If their coil is
very tight they are known as spirochetes.
2. Basic Training
Virus
Viruses are too small to be seen directly with a light microscope.
Viruses infect all types of organisms, from animals and plants to
bacteria and archaea. although there are millions of different types.
Viruses are found in almost every ecosystem on Earth and these
minute structures are the most abundant type of biological entity.
The study of viruses is known as virology, a sub-specialty of
microbiology.
2. Basic Training
2. Basic Training
2. Basic Training
2. Basic Training
2. Basic Training
Gowning Training:
Good personnel hygiene including the following:
Bathing or showering routinely.
Washing the hair.
Trimming facial hair
Cleaning the fingernails.
Wearing clean clothing and shoes.
Clean room personnel must believe in and practice
2. Basic Training
Gowning Training:
Five criteria must be met for a fabric to be used as a clean
room garment:
Comfortable to wear.
Function
2. Basic Training
Gowning Training:
Pre-Gowning Procedure:
Remove all street garments that are not required for warmth
and or modesty.
Bouffant/Hair net (Make sure to contain all hair)
Shoe covers: Contain all laces and lassels.
Wash hand: Using bactericidal soap and dry thoroughly.
First sterile gloves: Follow aseptic technique by touching only
the inside of gloves. Sanitize.
Sanitize gloves after donning each articles, if required.
Mask: Adjust for a snug facial fit.
Hood: Ensure snug fit and proper neck seal.
ENTER THE CHANGE AREA WALKING ACROSS THE TACKY MAT.
2. Basic Training
Gowning Training:
Gowning Procedure: Maintain Proper Gown Control Prior to
..\sterile_gowning_procedure.pdf
Personnel Process:
Bathing will remove microorganisms, but will increase the
number of particles emitted from the body.
The mechanical process of washing will remove bacteria from
microcolonies accumulated on the skin, bacterial cells will be
spread over the entire surface of the body, particularly near
the perineum and on the face
2. Basic Training
Gowning Procedure:
The washing process will remove the outer oily sebum layer
of the skin, causing skin scales to dry, curl up, and peel off
the body.
This causes an increase in particulate dispersion rates
immediately after showering.
Within two hours after bathing the surface of the skin will
resume its original pattern of microcolonies.
Therefore, employees working in clean rooms should bathe
at least two hours before they enter the clean room
environment to minimize the extent of the skin particulate
shedding due to the bathing process
2. Basic Training
1x
5 x*
50 x*
10 x*
100 x*
25 x*
150x/300x*
2. Basic Training
Cleanroom Behavior:
Movements no faster than air
flow.
Controlled, not abrupt,
movements.
Never taking objects against
the air flow.
Protective clothing always
sealed.
2. Basic Training
2. Basic Training
2. Basic Training
2. Basic Training
Understanding Disinfection:
process.
Expressed as log 10 (Probability of survival)
SAL of 6: <1 chance in a million (10-6) that a particular item is
contaminated.
2. Basic Training
Understanding Disinfection:
Cleaning: The removal of adherent visible soil (blood, protein
2. Basic Training
Understanding Disinfection
Cleaning agents and Disinfectants:
should be handled with care ,as they are potent and often hazardous.
microbial activity.
Care should be taken to ensure that the disinfectant does not cause
corrosion or discoloration of paint work or flooring.
Two or more disinfectants are used at regular intervals to obviate the
proliferation of resistant strains of micro organisms and for that
disinfectants used should be of different chemical type and with
different spectrum of anti microbial activity.
Disinfectants and cleaning agents should not be stored more than 24 hrs
as organisms can grow on storage.
Disinfectants are available as concentrated solutions and hence they
should be diluted. Dilutions should be made with freshly collected
distilled water. Used solutions of cleaning agents and disinfectants must
be discarded and the empty containers must be washed at the end of
the day.
2. Basic Training
Understanding Disinfection
Reasons For Using A Disinfectant
Destroy or remove microorganisms that are present
Prevent entry of microorganisms into a manufacturing
facility
Prevent dissemination of microorganisms throughout a
manufacturing facility
Eliminate and prevent buildup of pyrogens
2. Basic Training
Sources of Contamination
Percentage distribution of the sources of
contamination.
Process
: 30 40 %
People
: 30 40 %
Equipment
: 20 30 %
Process Media
: 5 10 %
Air
: 5 10 %
It is important to take the contamination from people into
account , which contributes considerable 30% of the total
contamination in the cleanroom.
2. Basic Training
Source of Contamination.
Example "Fishbone" diagram for contaminated
Contaminated Product
2. Basic Training
Sources of Contamination:
External Impurities
Internal Impurities
Staff
Staff
Process
* poor filter quality, not airtight filter seal surfaces, leakage in the ducting
system, abrasion in air recirculation equipment and in the ducting system
2. Basic Training:
during operation:
2. Basic Training
air
velocities,
2. Basic Training
Outdoor Air
2. Basic Training
2. Basic Training
3. Process Flow
Classification of Clearnroom
Class 100,000
ISO 8
3,520,000
29300
Class 10,000
ISO 7
352,000
2930
Class 1,000
ISO 6
35,200
293
Class 100
ISO 5
3520
29
Micro Settling Plates Action Levels (diam. 90mm; cfu/4hours)
Class 100- 1 CFU however samples from class 100 (ISO 5)
environments should normally yield no microbial
contaminants.
Class 1,000- 3 CFU / 4 hours
Class 10,000- 5 CFU/ 4 hours
Class 100,000- 50 CFU/ 4 hours
3. Process Flow
Material Movement
Material/Personnel Flow, in order to produce an acceptable sterile
3. Process Flow
Between uses, sterile instruments should be held under class 100 (ISO 5) conditions
and maintained in a manner that prevents contamination. Instruments should be
replaced as necessary throughout an operation.
rotating basis. Also, the differences in air flow and turbulence can have a direct
impact on the performance of the room
4. Sanitization
a)
b)
c)
d)
e)
f)
g)
h)
i)
4. Sanitization:
Disinfectant
Concentration
Exponents
Hydrogen peroxide
0.5
1.7
Sodium hypochlorite
0.5
1.7
Mercuric chloride
Chlorhexidine
Formaldehyde
Alcohol
19683
Phenol
729
0.8 to 2.5
2.4-15.6
Aliphatic alcohols
6.0 to 12.7
729-1146673
Phenolic compounds
4 to 9.9
81-52905
4. Sanitization: CLASSIFICATION OF
DISINFECTANTS
Chemical Entity
Classification
Example
Aldehydes
Sporicidal agent
2% Glutaraldehyde
Alcohols
Sporicidal agent
Phenolics
Ozone
Sporicidal agent
8% Gas by weight
Hydrogen peroxide
Substituted diguanides
Antiseptic agent
Peracetic acid
Ethylene oxide
Vapor-phase sterilant
-Propiolactone
Sporicidal agent
Concentration dependent on
application, Benzalkonium
chloride
100 g per g
-Propiolactone
4. Sanitization
It must be assured that no humidity remain after cleaning ( e.g film or liquid
under equipment)
Cleaning solution must be freshly prepared from contaminant free detergent
with sterile WFI f its not sterilized by filtration. There must be strict limitation
for the time of use for these solution as number of microorganism may
rapidly increased given sufficient time for exponential groth
Its not acceptable to leave wipes or cleaning tools exposed to the
environment for drying after cleaning process
Wipes for cleaning and disinfectant should be sterile and disposable or
sterilized between each use
Its not acceptable to have cleaning solution ready to use during the day
unless it kept well protected in closed container
The area that can be cleaned with a single wipe or portion of cleaning
solution dispensed in a bucket should be limited in order to prevent
uncontrolled spreading of an eventual contamination over a large area
For cleaning of the rooms, formal validation studies are not required why !!!
4. Sanitization
4. Sanitization
Advantage
a)
No critical intervention in the filling system is needed during setup of
the equipment
b)
Higher security of cleaning and sterilization of pipes and tubes that may
be difficult to sterilize in an autoclave
c)
Configure both CIP system and the component for cleaning, execute
the cycle and return the component to service or subsequent
sterilization
d)
Highly reliable and achieve a reproducible process
e)
Repeatable temperature, time and reagent concentration control
f)
Reduce the number of aseptic connection points to a minimum,
therefore, reduce the brisk of microbial contamination at such point
g)
Higher capacity and control of process parameters
4. Sanitization
Antiseptic An agent that inhibits or destroys microorganisms on living
tissue including skin, oral cavities, and open wounds
Disinfectant A chemical or physical agent that destroys or removes
vegetative forms of harmful microorganisms when applied to a surface
pH of the disinfectant.
Many disinfectants are more active in the ionized form, while others
are more active in the nonionized form. The degree of ionization
will depend on the pK a of the agent and the pH of the
disinfection environment. For example, phenol, with a pK a of 10,
will be more effective at a pH below 7 where it is nonionized
4. Sanitization
Disinfectant
Cell wall
Hexachlorophene
Action on ATP
Ribosomes
Hydrogen peroxide
Nucleic acids
Hypochlorites
Thiol groups
Amino groups
General oxidation
Hypochlorite
4. Sanitization
AFTER FILLING
PHENOLICS ARE USED IMMEDIATELY AFTER BATCH
OPERATIONS
OPERATIONS
PHENOLICS
FACILITY: TWO PASSES WITH PHENOLICS
4. Sanitization
WITH
0.5% SODIUM HYPOCHLORITE FOLLOWED BY TWO FULL
FACILITY DISINFECTIONS WITH PHENOLICS
4. Sanitization:
Material Handing
Step One: Wash the parts by filtered water (WFI)
4. Sanitization:
PROCESS FLOW
USE STERILE POLYPROPYLENE WASTE BAGS
DISCARD AND REPLENISH DISINFECTOR AFTER EVERY
ROOM.
DISINFECT THE CLASS 100 ROOMS FIRSTWORK
FROM
CLEANER TO DIRTIER ROOMS
WASH THE MOP AND BUCKET HARDWARE BEFORE
AUTOCLAVING FOR THE NEXT USE
4. Sanitization:
4. Sanitization:
DISINFECTION OF WALLS
START AT THE WALL FURTHEST FROM THE DOOR
USE THE DOUBLE BUCKET METHOD
The End