Transcript Clean rooms- t�r�s telpas.ppt

MCC PRESENTATION - GMP
MANUFACTURING ENVIRONMENTS
Module 1
Presented by :
Deryck Smith Consulting
Engineers
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GMP
MANUFACTURING ENVIRONMENTS
Presentation Outline
Module
Module
Module
Module
Module
1:
2:
3:
4:
5:
Introduction to GMP Environments
Air Conditioning System Components
Types & Configurations of AC Systems
Pressure Cascades & building Layouts
Validation, Qualification & Maintenance
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GMP
MANUFACTURING ENVIRONMENTS
•
•
•
•
Topics for this Module
What makes up the manufacturing
environment (not just Environmental
Control System)
Contamination & cross-contamination
How cleanrooms are defined
Levels of Protection 
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Module 1: Introduction to GMP
Manufacturing Environments
• The primary objective of manufacturing in an
ideal GMP environment is that this should lead
to a high quality product being produced.
• Manufacturing in an ideal environment not only
leads to better quality products but should also
result in :
* Improved production rates.
* Operator comfort, satisfaction and safety. 
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Factors Contributing to Quality
Products
Personnel
Validated processes
processes
Validated
Procedures
Raw Materials
The most important!
Equipment
Equipment
Packing Materials
Premises
Environment
Environment
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Design considerations
for a manufacturing facility
Three primary considerations to be addressed to ensure a safe and
productive manufacturing facility
GMP MANUFACTURING
ENVIRONMENT
PERSONNEL
PROTECTION
Prevent
contact
with dust
PRODUCT
PROTECTION
Protect from
product
cross-contamination
ENVIRONMENT
PROTECTION
Avoid
dust
discharge
Prevent
contact
with fumes
Protect from
ambient
contamination
Avoid
fume
discharge
Acceptable
comfort
conditions
Prevent
contamination
of staff
Avoid
effluent
discharge
Correct
temperature
and humidity
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The manufacturing environment is
critical for product quality
The environment comprises aspects such as:
1.
Light
2.
Temperature
3.
Humidity
4.
Air movement
5.
Microbial contamination
6.
Particulate contamination
Uncontrolled environments can lead to:

Product degradation & contamination

Loss of Product & Profit 
PIC/S PH 1/97 (Rev.3) #3.3 & 3.12
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What are Contaminants ?
Contaminants are :
1. Products or substances other than
product
manufactured
2. Foreign products
3. Particulate matter
4. Micro-organisms
5. Endotoxins (degraded micro-organisms)
Cross-contamination is a particular case of
contamination 
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Cross – Contamination (1)
What is Cross-Contamination ?
Definition of CrossContamination
“Contamination of a starting material,
or of a product with another starting
material or product.”
PIC/S PH 1/97 (Rev.3) Pg. 134
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Cross – Contamination (2)
From where does Cross-Contamination
originate?
1. Poorly designed air handling systems and
dust extraction systems
2. Poorly operated and maintained air
handling systems and dust extraction
systems
3. Inadequate procedures for personnel and
equipment
4. Insufficiently cleaned equipment 
PIC/S PH 1/97 (Rev.3) # 3.14
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Cross-contamination (3)
Contaminants
from
Environment
& Operators
Contamination
Contaminants
from
Equipment
Product
from
Environment
& Operators
Cross
Contamination
Product
from
Equipment
PIC/S PH 1/97 # 5.10
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Cross-Contamination (4)
Cross-contamination can be minimized by
1. Personnel procedures
2. Adequate premises
3. Use of closed production systems
4. Adequate, validated cleaning procedures
5. Appropriate Levels of Protection of
product
6. Correct air pressure cascade 
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How are Contaminants Removed?
• By efficient filtration of supply air.
• By dilution of contaminants or flushing
contaminants by supplying adequate air
quantities to the room. 
More about this later!
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Where Do Contaminants Come From?
• Outside air carries dust which is a contaminant
• People generate contaminants:
 We completely shed our outer skin every 24 hrs.
 Particles of 0,3 micron & greater are liberated at a
rate varying between of 100 000 to 10 million per
minute
 A person walking will liberate 5000 bacteria/minute
and a single sneeze can produce up to 1 million
bacteria.
• The manufacturing process itself can generate
contaminants eg paint off equipment, dust
from belt drives, etc 
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Why All the Concern About Dust?
Dust Is a Bacteria Carrier
Virus
(0,006µm to 0,03µm)
Dust Particle
Bacteria
(0,5µm to 500µm)
(0,2µm to 2µm)
Typical size relationship between
dust, bacteria and viruses
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Airborne Contaminants
Particle sizes
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Removal of Bacteria
• As dust is a carrier, dust must be
controlled.
• Ambient bacteria is removed by
filtration.
• Internal bacterial distribution can be
controlled by directional air flow and
air flushing or dilution.
• Surface bacteria is controlled by
adherence to strict cleaning sop’s. 
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Defining the Environment
• What is the manufacturing environment ?
• How does the manufacturing environment
effect contamination and crosscontamination ?
• Cleanroom concept

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What Is a Cleanroom ?
A cleanroom is an
environment where
the particulate
contamination &
bacterial
contamination are
limited to
prescribed levels.
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How Are Cleanrooms Classified ?
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Controlled Environment Standards
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-
200
-
•= Uni-directional (Laminar Flow)
** = Maximum number of viable microorganisms permitted per m³.
Annex 1 # 3
CONTROLLED ENVIRONMENT STANDARDS
BS EN ISO 1 4644-1: 1999, Federal Standard and Approximate Equivalents.
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Facility Parameters That Need
To Be Controlled

Temperature
Humidity
Air
Cleanliness
Room
Air
Pressure
movement
Lighting
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How Clean Should It Be?
Level of Protection Concept
1.
Defines environmental requirements
2.
Working to defined environments helps prevent
contamination and cross-contamination
3.
Allows production under optimal hygiene conditions
4.
Takes into account
•
•
product sensitivity to contamination
therapeutic risk 
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Many Different Standards In Use
Levels of Protection & Cleanroom Class
definitions currently in use.
EC, PIC/S, TGA, WHO, etc. : A, B, C, D.
US FDA :
Critical and Controlled or
Class 100, 1000, etc.
ISPE :
Level 1, 2 or 3 or
Cleanroom class (ISO 5, 6, etc.).
Companies :
Various others such as White, Grey,
Black, Green, etc.
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Cleanroom Class Required Is Dependant on
Manufacturing Process Being Carried Out !
Cleanroom Class A / B
Cleanroom Class C
Cleanrm. Class D
Others
Manufacturing Environment
requirements
Therapeutic risks
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Levels of Protection
Parameters to be defined:
1. Air cleanliness requirements (filter type
and position, air changes, air flow
patterns, pressure differentials,
contamination levels by particulate matter
and micro-organisms)
2. Personnel and material transfer methods
3. Permitted operations
4. Building design & finishes 
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Levels of Protection
All operations within a pharmaceutical facilility must be
correlated to well-defined Cleanroom classes.
Example:
ISO 14644-1
ISO 5U
ISO 5T
ISO 7
X
Washing of Containers
X
Preparation of solution for terminal sterilization
Preparation of solutions for aseptic filling
X
Depyrogenisation of containers
X
X
X
X
Filling for terminal sterilization
Filling for aseptic process
ISO 8
X
Etc.
U = Uni-directional
T = Turbulent
Annex 1, # 3, Pg 41
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Levels of Protection
Based on the Cleanroom Class Requirements,
various Levels of Protection have to be created,
including:
1. Correlation between process operations and Cleanroom classes
2. Type of operation permitted in each Level of Protection zone
3. Definition of Cleanroom class (Contaminant parameters, building
4.
5.
materials, room requirements, air handling systems )
Requirements for personnel and material in the different classes
(clothing, training, type of materials, etc. )
Requirements on entry conditions for personnel and material
(change & clean-down procedures ) 
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Parameters Influencing the
Level of Protection (1)
How does an Air Handling System influence
the Cleanroom Class or Level of Protection ?
Air Handling
System
Supply
Air
Production Room
With
Defined
Requirements
Outlet
Air
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Parameters Influencing the
Level of Protection (2)
1
2
3
4
5
6
7
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Number of particles in the air
Number of micro-organisms in the air or on
surfaces
Number of air changes for each room
Air velocity
Air flow pattern
Filters ( type, position )
Air Pressure differentials between rooms
Temperature, humidity 
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Parameters Influencing the
Level of Protection (3)
Cleanroom Class
defined by
Critical Parameters
Air Handling
System
Additional Measures
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Parameters Influencing the
Level of Protection (4)
Air handling systems:
• are the main tool for reaching required
parameters
• but are not sufficient as such
Need for additional measures such as
 Appropriate gowning (type of clothing, proper
changing rooms)
 Validated sanitation
 Adequate transfer procedures for materials and
personnel 
Questions & Answers
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