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Amjad Ganma

M. Sc Pharmaceutical Validation (London)

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,

comprised of material/personnel airlocks.


Preparation room closely related to aseptic processing
room.
Room/area immediately adjacent to preparation room,
comprising material airlocks, personnel clean change,
secondary packaging and other associated areas.
Room for ancillary/support functions includes:

Warehousing
Office
Plant utilities
Circulation area

1. Organization Set-up

Surface Finishes and Materials of Construction


Finish materials should be non-shedding, non-porous and

resistant to sustaining microbial growth.


Surfaces should be smooth and easy to clean with

minimal ledges
Joints
No corners (that are difficult to access)
Importantly near the product and process equipment.

Finishes should be able to withstand repeated


Cleaning
Sanitization with various chemicals
Resist surface oxidation.

1. Organization Set-up

Surface Finishes and Materials of Construction


Doors hardware should be carefully considered
Easy Cleaning
Hands Off proximity sensors and openers wherever

necessary.
Door swings should be opposite direction of airflow to

assist in maintaining the differential pressure.


10. ISO_Controlled Environment Design.pdf

1. Organization Set-up

GMP Requirement for Electrical Systems


GMP considerations when designing, selecting and installing

electrical equipment within aseptic processing areas are limited


to ensuring that equipment is cleanable, ledge and crevice free,
non-shedding and sealed.
The criteria for equipment appear to be identical from Grade 5
to Grade 8 environments, the degree of these aspects may
differ (e.g. equipment in grade 5 environment will require a
high standard). Recessed electrical devices will help achieve the
standard required in each of these areas.
Sealed components are specified, no only to alleviate the risk of
contamination, but also to cope with the different pressure
regimes of adjacent rooms. In Grade 5 environment, the term
sealed refers to being hermetically sealed, whereas in Grade
8 environments, the term sealed to a high degree of
protection against the ingress of water and dust.

1. Organization Set-up

GMP Requirement for Electrical Systems


Sealing properties of the fixtures should withstand water jet

pressures in wash down areas.


Stainless steel or aluminum fixtures, because they are nonshedding and resistive to corrosive environments, may
considered appropriate. Materials should be compatible with
room cleaning agents, which may be corrosive.
Wiring and wiring accessories should be hidden within the:
Building fabric to improve cleanliness.
Particularly in higher classification areas.
The number of penetrating through walls, ceiling, or floors for
services to equipment should be minimized.

1. Organization Set-up
Room Classification
Electrical System
Pharmaceutical

Power distribution

Lighting

Outlets and
miscellaneous
Equipment

Grade 8 Environment

Grade 5 and Grade 7


Environment

Non, Outside Area

None, Outside Area

None, Outside Area

Cleanable, ideally nonshedding

Cleanable and sanitizable,


minimum ledges, nonshedding, sealed, crevice free.

Cleanable and sanitizable,


minimum ledges, nonshedding, sealed, crevice
free.

Cleanable, ideally nonshedding

Cleanable and sanitizable,


minimum ledges, nonshedding, sealed, crevice free.

Cleanable and sanitizable,


minimum ledges, nonshedding, sealed, crevice
free.

2. Basic Training

Microbiology for Non-Microbiologist:


The FDA Requirement

Control of microbiological contamination . 21 CFR


211.113.

2. Basic Training

Microbiology for Non-Microbiologist:


The Characteristics of Microorganisms
Fungi: molds, yeasts, mushrooms, rusts, and smuts.

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

Microbiology for Non-Microbiologist:


Mycoplasma species are often found in research laboratories as

contaminants in cell culture. Mycoplasma cell culture


contamination occurs due to contamination from individuals or
contaminated cell culture medium ingredients. The accepted
name was chosen because Mycoplasma were observed to have a
fungi-like structure - hence "Myco," and it also had a flowing
plasma-like structure without a cell wall - hence "plasma."
The Characteristics of Microorganisms
Mycoplasma: Mycoplasma is the smallest known cell and is about

0.1 micron (m) in diameter.

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

Microbiology for Non-Microbiologist:


What is Microbe?
Bacteria are named with two names.
The first name is the Genus and is always capitalized.
The second name is the species and is never capitalized.
The names of bacteria are always written in italics, or underlined.

(example: Escherichia coli or Escherichia coli).

Microbes are Bacteria, Fungi, Yeast, Algae and Virus.

2. Basic Training

Microbiology for Non-Microbiologist:


Microbes in Facility
Bacteria can double themselves by splitting in half. This doubling time

varies with the type of bacteria.


E. coli has a doubling or generation time for 20 minutes.
With this generation speed, a single E. coli bacterial cell can grow as
indicated in this table.

Endotoxins- gram negatives we are always


looking to prevent in products. Cause
serious adverse events in patients, such as,
fevers, shock and even death.
Endospores- Spore forming bacteria, they
can survive heat, UV. If spores survive the
Aseptic Process they can germinate and
grow in favorable conditions

2. Basic Training

Microbiology for Non-Microbiologist:


Pyrogens:
When bacteria are killed using an autoclave, their

skeletal remains are still present on the item that


was sterilized.
These are known as pyrogens.
When injected into the body, pyrogens will cause
the patient to have a fever.
A dry heat oven /Tunnel is used to eliminate
pyrogens.

2. Basic Training

Microbiology for Non-Microbiologist


Sources of Bacteria
Humans
1 gram of fecal matter container 109 bacteria.
40% of fecal matter is microbial matter.
Our body has 1kg of bacteria at any one time.
These are reasons we humans are the greatest contributor to

contamination in the clean room. We can slough off bacteria from


our skin, and we can carry soil in with us.

Other sources of Bacteria:


Bio-burden is the bacteria in the environment.
- These comes from water, air, personnel, raw material, working
surfaces and the manufacturing area.

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

these basic steps in good hygiene practices.

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

design to contain contaminating


particles and bacteria shed from the skin and
clothing of personnel.
Posses antistatic characteristics.
Ability to withstand sterilization.
Durability.

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

and throughout aseptic operations, an operator should not


engage in any activity that poses an unreasonable
contamination risk to the gown.
See the Sterile Gowning Procedure in the picture.

..\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

Cleanroom Behavior: Emission of Particles

1x

5 x*

50 x*

* 100.000 Particles (Contaminant emission =


dust skin particles, hair, germs, viruses,
smoke etc)

10 x*

100 x*

25 x*

150x/300x*

Size: 0.001 micron to 10 micron 1 micron =


1/1.000mm

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

Cleanroom Behavior: Inappropriate behavior

Fast walking causes


turbulences due to low
pressure points

Seizing something quickly from


above creates turbulences and
contamination outbursts.

If installations and appliances are


set horizontally to the air current,
turbulence is created on the
underside.

2. Basic Training

Cleanroom Behavior: Dos Behavior in the Cleanroom


Training: All staff working at a Clean Workplace must be trained

repeatedly in all aspects which are relevant to the work in question.


Staff: At the clean workplace only the required amount of staff should
be present.
Checks: As far as possible, all monitoring and inspections should be
carried out from outside.
Visitors: If inspections, service staff or visitors enter the Clean Workplace, the same rules of behavior apply as for permanent workers in the
area.
Moving about: The movement of people between the clean workplace
and the surrounding areas should be kept to a minimum.
Private items: It is not permitted to take food, cigarettes, jewelry and
other personal items to the clean workplace.
Materials: Apart from the materials directly needed or the production
goods to be processed immediately, no objects or materials may be
stored in the vicinity of the Clean Workplace.

2. Basic Training

Cleanroom Behavior: Dos Behavior in the Cleanroom


Movements: At the clean workplace, the staff must move in a controlled

and considered manner. Since the emission of particles and germs is


related to the workers activity and the type of movement, quick and abrupt
movements might cause a strong current and thus are to be avoided at all
times.
Working Clothes: Care must be taken that the prescribed working clothes
are worn in the cleanroom in the correct way at all times.
Contacts: In order to avoid contaminating the gloves unnecessarily (dust,
fats, salts, gems), nothing may be touched at the workplace apart from the
appropriate equipment and tools. (Do not fold arms, do not scratch, do not
touch door handles or telephone receivers).
Communication: Speaking, coughing and sneezing may never take place in
the direction of the critical working area.
Jobs: When temporarily not working or merely observing at the clean
workplace, the staff must move as far away as possible from the critical
area.
Handling: Interventions in the critical work area must take place in such a
way that neither the hand nor the arm of the staff comes between the
HEPA filter and the object.

2. Basic Training

Understanding Disinfection:

Sterilization and Disinfection is a


fundamental tool of infection control. A large number of equipments and
instruments are designed for reuse, they also can transmit pathogens if any
of the steps involved in reprocessing, cleaning, disinfection, or sterilization
are inadequate.

Sterilization: The complete removal or destruction of all

forms of microbial life (Bacteria, Viruses, Fungi, Spores)


Probabilistic Notion:
No absolute assurance that there is 0 microorganisms.
Sterility Assurance Level (SAL) used as measure of sterility.
SAL: Probability of survival of microorganisms after sterilization

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

substance and debris), dust or other foreign material by manual


or chemical process.
Sanitizing: Process that reduces microbial population on object
to a safe level e.g 70% IPA
Decontamination: Process that removes pathogenic
microorganisms from an object to make it safe to handle.
Antiseptics: Chemicals to prevent growth or destroy.
Used on living tissues.
Disinfectants: Chemicals used for disinfection.
Used for objects& Destroys Pathogens

Sterilizing: Absence of Microorganisms

2. Basic Training

Understanding Disinfection
Cleaning agents and Disinfectants:
should be handled with care ,as they are potent and often hazardous.

should not be mixed which can result in drastic reduction in anti

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

A properly designed and maintained disinfection program that provides the


pharmaceutical manufacturing areas with an environment relatively free
from microorganisms on a consistent basis is an expectation of most
regulatory agencies worldwide.

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

product in next slide is illustrated to simplify the


Cause & Effect Diagram for Potential Causes of

Contaminated Product

2. Basic Training

Sources of Contamination:
External Impurities

Internal Impurities

Introduction of contaminated outside


air or circulating air *

Staff

Staff

Process

Impure process media or raw material

Production equipment, machines, tools


etc.

Inadequately cleaned materials, tools


etc.

Unsuitable building materials, work


materials
Mechanical abrasion in the cleanroom

* 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:

Microbiological Controlled Environment


Recommended limits for Microbiological monitoring of clean areas

during operation:

2. Basic Training

Microbiological Controlled Environment


Parameters that need to be controlled are: air flow

filtration, room pressurizations,


temperature, relative humidity

air

velocities,

Clean room location must designed that in and out air

locks, gowning and de-gowning, door interlocks,


visibility, personnel flow, material flow, the
introduction of components, location of utilities,
location of the equipment inside the clean room.

2. Basic Training

Microbiological Controlled Environment


Particles in Outdoor Air: Number of Particles / m on

Outdoor Air

2. Basic Training

Microbiological Controlled Environment


Elements of Microbial Monitoring
Sampling Methods
Media & Incubation Conditions
Sampling Locations
Frequency of Sampling
Alert & Action Limits
Trend Analysis
Out of Limits Investigations
Corrective Action

2. Basic Training

Microbiological Controlled Environments


Microbial Monitoring Frequency
Air, Surfaces and Personnel Monitoring Should be done
Frequently During Aseptic Operation.
Product Contact Surfaces Should be Monitored at the End
of the Aseptic Operation.
Monitoring Sites
Air monitoring should be done adjacent to the filling
location.
Product contact surfaces areas, non contact areas, open
vials, stopper track, etc.
Personnel monitoring should be done at the sleeves and
gloves.

3. Process Flow
Classification of Clearnroom

Classification for airborne environmental cleanliness


requirement 0.5
5

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

product, the design of personnel and material flows should


minimize or prevent the introduction of contamination to the
clean area. 04. Aseptic Processing Area.pdf
One-way personnel flow is preferred, providing physically separate entry

and exit routes or the separation can be achieved by ? ISO 14644-4


Process or operation waste should be removed from the aseptic area

without contaminating the product either by direct contact or passing


through areas.
Due to the problems in maintaining the Differential pressure , the airlock to

be used between rooms or areas of different air quality classification

3. Process Flow

Contact sterile materials only with sterile instruments:


Sterile instruments should always be used in handling of sterilized materials.

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.

Move slowly and deliberately:


Rapid movements can create unacceptable turbulence in a critical area. Such

movements disrupt the unidirectional airflow, presenting a challenge beyond


intended cleanroom design and control parameters. The principle of slow, careful
movement should be followed throughout the cleanroom.

Keep the entire body out of the path of unidirectional airflow:


Unidirectional airflow design is used to protect sterile equipment surfaces, container-

closures, and product.

Multiple filling rooms:


Aseptic filling validation should be performed on all filling lines within a facility on a

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)

Selection of disinfectant: The selection of suitable disinfectants and the

verification of their effectiveness in surface challenge testing is critical in the


development of a cleaning and sanitization program :
The number and types of microorganisms to be controlled
the nature of the surface material being disinfected and its compatibility with
the disinfectant /corrosiveness of the disinfectant to equipment with repeated
application
the concentration, application method, and contact time of the disinfectant
the amount of organic compounds on the surface that may inactivate a
disinfectant
the safety considerations for operators applying the disinfectant
the compatibility of the disinfectant with cleaning agents and other disinfectants
the planned disinfectant rotation
the spectrum of activity of commercially available disinfectants
Thee steps that need to be taken to avoid the contamination of pharmaceutical
products by a disinfectant.

4. Sanitization:

The cGMP 21 CFR 211.67, Equipment Cleaning and Maintenance


requirements for written procedures for cleaning, maintenance, and
sanitization of pharmaceutical manufacturing equipment
a) the assignment of responsibility,
b) establishment of schedules,
c) details of cleaning operations,
d) protection of clean equipment prior to use,
e) inspection for cleanliness immediately prior to use,
f) maintenance of cleaning and sanitization records
g) Staff involved in disinfection require training in microbiology, industry
practices for cleaning and sanitization, safe handling of concentrated
disinfectants, the preparation and disposal of disinfectants, and
appropriate application methods
Dilutions:
It should be emphasized that the preparation of the correct dilutions is
critical because many disinfectant failures can be attributed to use of
disinfectant solutions that are too dilute

4. Sanitization : Concentration Exponents of


Common Antiseptics, Disinfectants, and Sterilants
Red. in disinf.
activity for 3 fold
dilution

Disinfectant

Concentration
Exponents

Hydrogen peroxide

0.5

1.7

Sodium hypochlorite

0.5

1.7

Mercuric chloride

Chlorhexidine

Formaldehyde

Alcohol

19683

Phenol

729

Quaternary ammonium compounds

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: Important issue


need to be taken in consideration

MICROBIAL RESISTANCE TO DISINFECTANTS: periodically subjected to


use-dilution testing with the agents used in the disinfection program
The rotation of an effective disinfectant with a sporicide is encouraged
The daily application of sporicidal agents is not generally favored
because of their tendency to corrode equipment and because of the
potential safety issues with chronic operator exposure
Disinfectants applied on potential product contact surfaces are
typically removed with 70% alcohol wipes
handling of concentrated disinfectants and the mixing of incompatible
disinfectants. For example, concentrated sodium hypochlorite
solutions (at a concentration of more than 5%) are strong oxidants
and will decompose on heating, on contact with acids, and under the
influence of light, producing toxic and corrosive gases including
chlorine.

4. Sanitization: Important issue


need to be taken in consideration

Material Safety Data Sheets for all the disinfectants used in a


manufacturing area should be available to personnel handling
these agents
Endotoxins are not appreciably retention by 0.2m sterilizing
filter, so any potential endotoxins contamination to the product
from compounding and sterile filtrate receiving tank should be
preclude by developing reliable reproducible cleaning
procedures for these vessels
Its good practice to place the equipment in a service area and
not in aseptic area, and to place the outlet of any drain in a
service area due to high moisture level of potential airborne
contamination
Steam traps and other component should be located ourtside
the clean room to preclude any stagnant condensate/water in
the clean room

4. Sanitization: CLASSIFICATION OF
DISINFECTANTS
Chemical Entity

Classification

Example

Aldehydes

Sporicidal agent

2% Glutaraldehyde

Alcohols

General purpose disinfectant,


antiseptic, antiviral agent

70% Isopropyl alcohol, 70% alcohol

Chlorine and sodium hypochlorite

Sporicidal agent

0.5% Sodium hypochlorite

Phenolics

General purpose disinfectant

500 g per g Chlorocresol, 500 g per


g chloroxylenol

Ozone

Sporicidal agent

8% Gas by weight

Hydrogen peroxide

Vapor phase sterilant, liquid


sporicidal agent, antiseptic

4 g per g H2O2 vapor, 10%25%


solution, 3% solution

Substituted diguanides

Antiseptic agent

0.5% Chlorhexidine gluconate

Peracetic acid

Liquid sterilant, vapor phase sterilant

0.2% Peracetic acid, 1 g per g


peracetic acid

Ethylene oxide

Vapor-phase sterilant

600 g per g Ethylene oxide

Quaternary ammonium compounds

General purpose disinfectant,


antiseptic

-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

For product contact part .disinfection of critical surface with 70%


IPA,even its not sporicidal procedure, since there is no concern for
spore based on the environmental monitoring data.
In clean room, cleaning fluid are the only source of water available to
support microbial growth, so the water sources from controlled loop
have less than 10cfu\100ml, this mean 10 liters of buckets have 1000
cfu without consideration the organism that were introduced with
the detergent. These organism that would be introduced on the floor
which is not a problem if the disinfection program is effective.
Alcohol are not sporicidal, but spores cant germinate and proliferate
in alcohol , so this spres can be removed by !!
Its impossible to allow sufficient time for disinfectant to be fully
active as specified by disinfectant supplier, since its understood that a
disinfectant agent after entering the microbial cell during the wet
period,may continue to act intracellularely even after drying of the
surface

4. Sanitization

Automatic cleaning system

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

MECHANISM OF DISINFECTANT ACTIVITY


Target

Disinfectant

Cell wall

Formaldehyde, hypochlorite, and glutaraldehyde

Cytoplasmic membrane, action on membrane


potential

Anilides and hexachlorophene

Membrane enzymes, action on electrontransport chain

Hexachlorophene

Action on ATP

Chlorhexidine and ethylene oxide

Action on enzymes with

Ethylene oxide, glutaraldehyde, hydrogen peroxide, hypochlorite, and


iodine

Action on general membrane permeability

Alcohols, chlorhexidine, and quaternary ammonium compounds

Cell contents, general coagulation

Chlorhexidine, aldehydes, and quaternary ammonium compounds

Ribosomes

Hydrogen peroxide

Nucleic acids

Hypochlorites

Thiol groups

Ethylene oxide, glutaraldehyde, hydrogen peroxide, and hypochlorite

Amino groups

Ethylene oxide, glutaraldehyde, and hypochlorite

General oxidation

Hypochlorite

4. Sanitization: Facility Sanitization


Two Bucket
Fill water in the two suitable different color
bucket (Example: Yellow and Blue)
Soak the MOP in the Yellow color bucket
and wring the same in yellow bucket .
Soak the MOP in the blue color bucket and
let the water drip but wring into Yellow
bucket .

4. Sanitization

AFTER FILLING
PHENOLICS ARE USED IMMEDIATELY AFTER BATCH
OPERATIONS

70% IPA IS USED IMMEDIATELY BEFORE BATCH

OPERATIONS

AFTER MAJOR CONTAMINATION EVENTS:


FACILITY: 1 X with 0.5% HYPOCHLORITE
EQUIPMENT: 1 X with 0.5% HYPOCHLORITE AND 2 X

PHENOLICS
FACILITY: TWO PASSES WITH PHENOLICS

4. Sanitization

DAILY: If NO batch operations were conducted in the


room:
FLOOR ONLY with PHENOLIC

MAJOR CONTAMINATION OR HEPA SHUTDOWN: FULL FACILITY

WITH
0.5% SODIUM HYPOCHLORITE FOLLOWED BY TWO FULL
FACILITY DISINFECTIONS WITH PHENOLICS

WEEKLY: (or after each batch operation):


WALLS, FLOOR AND FIXTURES with PHENOLIC
MONTHLY: FULL FACILITY (CEILING, WALLS, FLOOR)
DISINFECTION with 0.5% SODIUM HYPOCHLORITE

4. Sanitization:

Material Handing
Step One: Wash the parts by filtered water (WFI)

Step Two: Disinfect on Entry Side of Cleanroom


Step Three: Disinfect on Clean side of the cleanroom

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:

DISINFECTING THE FLOORS


REPLENISH THE MOP
START FROM THE BACK OF THE ROOM AND

MOP TOWARDS THE BACK WALL


REVERSE MOP
Repeat
DOUBLE BUCKET

4. Sanitization:

DISINFECTION OF WALLS
START AT THE WALL FURTHEST FROM THE DOOR
USE THE DOUBLE BUCKET METHOD

MOVE THE MOP IN ONE DIRECTION ONLY


RINSE AND REPLENISH USING THE DOUBLE
BUCKET METHOD AFTER EVERY ROW

Example for the type of Organism

Types of Microorganisms Found in


Cleanrooms: Cleaning and Disinfection in
Cleanrooms.pdf

The End

Amjad Ganma, M.Sc (London)


Quality Unit Manager
Tabuk Pharmaceutical Manufacturing Co.,
Tabuk, Saudi Arabia
Per. Email: amjad_ganma@yahoo.com
Off. Email : amjad@tpmc.com.sa
Mobile num: 00966509522269

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