akashdeepsinghjandu1
TRANSCRIPT
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MCC PRESENTATION - GMP MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTSMANUFACTURING ENVIRONMENTS
Presented by :Presented by :
Akashdeep Singh JanduAkashdeep Singh Jandu
Module 1
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GMP GMP MANUFACTURING ENVIRONMENTSMANUFACTURING ENVIRONMENTS
Presentation OutlinePresentation OutlineModule 1: Module 1: Introduction to GMP EnvironmentsIntroduction to GMP EnvironmentsModule 2:Module 2: Air Conditioning System ComponentsAir Conditioning System ComponentsModule 3:Module 3: Types & Configurations of AC SystemsTypes & Configurations of AC SystemsModule 4: Module 4: Pressure Cascades & building LayoutsPressure Cascades & building LayoutsModule 5:Module 5: Validation, Qualification & Maintenance Validation, Qualification & Maintenance
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GMP GMP MANUFACTURING ENVIRONMENTSMANUFACTURING ENVIRONMENTS
Topics for this ModuleTopics for this Module• What makes up the manufacturing What makes up the manufacturing
environment (not just Environmental environment (not just Environmental Control System)Control System)
• Contamination & cross-contaminationContamination & cross-contamination• How cleanrooms are definedHow cleanrooms are defined• Levels of Protection Levels of Protection ∆∆
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Module 1: Introduction to GMP Module 1: Introduction to GMP Manufacturing EnvironmentsManufacturing Environments
• The primary objective of manufacturing in an The primary objective of manufacturing in an ideal GMP environment is that this should lead ideal GMP environment is that this should lead to a high quality product being produced.to a high quality product being produced.
• Manufacturing in an ideal environment not only Manufacturing in an ideal environment not only leads to better quality products but should also leads to better quality products but should also result in :result in :
* Improved production rates.* Improved production rates.* Operator comfort, satisfaction and safety. * Operator comfort, satisfaction and safety. ∆∆
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Factors Contributing to Quality Factors Contributing to Quality ProductsProducts
Raw Materials
Personnel
Procedures
Validated processes
Equipment
Premises
Environment
Packing Materials
Validated processes
Equipment
Premises
Environment
The most important!
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Design considerationsDesign considerations for a manufacturing facility for a manufacturing facility
Preventcontact
with dust
Preventcontact
with fumes
Acceptablecomfort
conditions
cross-contamination
Protect fromproduct
Protect fromambient
contamination
contaminationPrevent
of staff
Correcttemperatureand humidity
Avoiddust
discharge
Avoidfume
discharge
Avoideffluent
discharge
PERSONNELPROTECTION
PRODUCTPROTECTION
ENVIRONMENTPROTECTION
GMP MANUFACTURINGENVIRONMENT
Three primary considerations to be addressed to ensure a safe and productive manufacturing facility
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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 ∆
The manufacturing environment is critical for product quality
PIC/S PH 1/97 (Rev.3) #3.3 & 3.12
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Contaminants are :Contaminants are :1.1.Products or substances other than Products or substances other than
product manufactured product manufactured 2.2.Foreign productsForeign products3.3.Particulate matterParticulate matter4.4.Micro-organismsMicro-organisms5.5.Endotoxins (degraded micro-organisms)Endotoxins (degraded micro-organisms)
Cross-contamination is a particular case of Cross-contamination is a particular case of contaminationcontamination ∆∆
What are Contaminants ?
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What is Cross-What is Cross-Contamination ?Contamination ?Definit ion of Cross-Definit ion of Cross-ContaminationContamination
““Contamination of a starting material, Contamination of a starting material, or of a product with another starting or of a product with another starting material or product.”material or product.”
Cross – Contamination (1)
PIC/S PH 1/97 (Rev.3) Pg. 134
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From where does Cross-Contamination From where does Cross-Contamination originate?originate?
1.1. Poorly designed air handling systems Poorly designed air handling systems and dust extraction systemsand dust extraction systems
2.2. Poorly operated and maintained air Poorly operated and maintained air handling systems and dust extraction handling systems and dust extraction systemssystems
3.3. Inadequate procedures for personnel and Inadequate procedures for personnel and equipmentequipment
4.4. Insufficiently cleaned equipmentInsufficiently cleaned equipment ∆∆
Cross – Contamination (2)
PIC/S PH 1/97 (Rev.3) # 3.14
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Cross-contamination (3)Cross-contamination (3)
Contamination
Contaminants from
Environment& Operators
Contaminants from
Equipment
CrossContamination
Productfrom
Environment& Operators
Productfrom
Equipment
PIC/S PH 1/97 # 5.10
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Cross-Contamination (4)Cross-Contamination (4)
Cross-contamination can be minimized byCross-contamination can be minimized by1.1. Personnel proceduresPersonnel procedures2.2. Adequate premisesAdequate premises3.3. Use of closed production systemsUse of closed production systems4.4. Adequate, validated cleaning Adequate, validated cleaning
proceduresprocedures5.5. Appropriate Levels of Protection of Appropriate Levels of Protection of
productproduct6.6. Correct air pressure cascade Correct air pressure cascade ∆∆
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How are Contaminants Removed?How are Contaminants Removed?
• By efficient filtration of supply air.By efficient filtration of supply air.• By dilution of contaminants or flushing By dilution of contaminants or flushing
contaminants by supplying adequate air contaminants by supplying adequate air quantities to the room. quantities to the room. ∆∆
More about this later!
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Where Do Contaminants Come From?Where Do Contaminants Come From?
• Outside air carries dust which is a contaminantOutside air carries dust which is a contaminant• People generate contaminants:People generate contaminants:
We completely shed our outer skin every 24 hrs.We completely shed our outer skin every 24 hrs. Particles of 0,3 micron & greater are liberated at a Particles of 0,3 micron & greater are liberated at a
rate varying between of 100 000 to 10 million per rate varying between of 100 000 to 10 million per minuteminute
A person walking will liberate 5000 bacteria/minute A person walking will liberate 5000 bacteria/minute and a single sneeze can produce up to 1 million and a single sneeze can produce up to 1 million bacteria.bacteria.
• The manufacturing process itself can generate The manufacturing process itself can generate contaminants eg paint off equipment, dust contaminants eg paint off equipment, dust from belt drives, etc from belt drives, etc ∆∆
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Why All the Concern About Dust?Why All the Concern About Dust?
Typical size relationship between
dust, bacteria and viruses
Virus
(0,006µm to 0,03µm)
Dust Particle
(0,5µm to 500µm)
Bacteria
(0,2µm to 2µm)
Dust Is a Bacteria Carrier
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Particle sizesParticle sizes
Airborne ContaminantsAirborne Contaminants
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Removal of BacteriaRemoval of Bacteria
• As dust is a carrier, dust must be As dust is a carrier, dust must be controlled.controlled.
• Ambient bacteria is removed by Ambient bacteria is removed by filtration.filtration.
• Internal bacterial distribution can be Internal bacterial distribution can be controlled by directional air flow and controlled by directional air flow and air flushing or dilution.air flushing or dilution.
• Surface bacteria is controlled by Surface bacteria is controlled by adherence to strict cleaning sop’s. adherence to strict cleaning sop’s. ∆∆
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Defining the EnvironmentDefining the Environment
• What is the manufacturing environment ?What is the manufacturing environment ?
• How does the manufacturing environment How does the manufacturing environment effect contamination and cross-effect contamination and cross-contamination ?contamination ?
• Cleanroom concept Cleanroom concept ∆∆
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What Is a Cleanroom ?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 How Are Cleanrooms Classified ?Classified ?
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Controlled Environment StandardsControlled Environment Standards
CONTROLLED ENVIRONMENT STANDARDSBS EN ISO 1 4644-1: 1999, Federal Standard and Approximate Equivalents.
-
-
-
•= Uni-directional (Laminar Flow) ** = Maximum number of viable microorganisms permitted per m³. Annex 1 # 3
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Facility Parameters That Facility Parameters That Need To Be ControlledNeed To Be Controlled
TemperatureTemperature
Humidity
Air Cleanliness
Room Pressure
Air movement
Lighting
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How Clean Should It Be?How Clean Should It Be?
Level of Protection ConceptLevel of Protection Concept
1.1. Defines environmental requirements Defines environmental requirements
2.2. Working to defined environments helps prevent Working to defined environments helps prevent contamination and cross-contaminationcontamination and cross-contamination
3.3. Allows production under optimal hygiene conditionsAllows production under optimal hygiene conditions
4.4. Takes into accountTakes into account• product sensitivity to contaminationproduct sensitivity to contamination • therapeutic risktherapeutic risk ∆∆
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Many Different Standards In UseMany Different Standards In Use
Levels of Protection & Cleanroom Class Levels of Protection & Cleanroom Class definitions currently in use.definitions currently in use.
EC, PIC/S, TGA, WHO, etc. : EC, PIC/S, TGA, WHO, etc. : A, B, C, D.A, B, C, D.US FDA : US FDA : Critical and Controlled or Critical and Controlled or
Class 100, 1000, etc.Class 100, 1000, etc.ISPE :ISPE : Level 1, 2 or 3 or Level 1, 2 or 3 or
Cleanroom class (ISO 5, 6, etc.).Cleanroom class (ISO 5, 6, etc.).Companies : Companies : Various others such as White, Grey, Various others such as White, Grey,
Black, Green, etc.Black, Green, etc.
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Therapeutic risks
Man
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Cle
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Cleanroom Class Required Is Dependant on Manufacturing Process Being Carried Out !
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Levels of ProtectionLevels of ProtectionParameters to be defined:Parameters to be defined:
1.1. Air cleanliness requirements (filter type Air cleanliness requirements (filter type and position, air changes, air flow and position, air changes, air flow patterns, pressure differentials, patterns, pressure differentials, contamination levels by particulate matter contamination levels by particulate matter and micro-organisms) and micro-organisms)
2.2. Personnel and material transfer methodsPersonnel and material transfer methods3.3. Permitted operationsPermitted operations4.4. Building design & finishes Building design & finishes ∆∆
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Levels of ProtectionLevels of Protection
All operations within a pharmaceutical facilility must be All operations within a pharmaceutical facilility must be correlated to well-defined Cleanroom classes. correlated to well-defined Cleanroom classes.
Example:Example:
ISO 14644-1 ISO 5U ISO 5T ISO 7 ISO 8
Washing of Containers X
Preparation of solution for terminal sterilization X
Preparation of solutions for aseptic filling X X X
Depyrogenisation of containers X
Filling for terminal sterilization X
Filling for aseptic process X
Etc.
U = Uni-directional
T = TurbulentAnnex 1, # 3, Pg 41
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Based on the Cleanroom Class Requirements, Based on the Cleanroom Class Requirements, various Levels of Protection have to be various Levels of Protection have to be created, including:created, including:
1.1. Correlation between process operations and Cleanroom classes Correlation between process operations and Cleanroom classes 2.2. Type of operation permitted in each Level of Protection zoneType of operation permitted in each Level of Protection zone3.3. Definition of Cleanroom class (Contaminant parameters, building Definition of Cleanroom class (Contaminant parameters, building
materials, room requirements, air handling systems )materials, room requirements, air handling systems )4.4. Requirements for personnel and material in the different classes Requirements for personnel and material in the different classes
(clothing, training, type of materials, etc. )(clothing, training, type of materials, etc. )5.5. Requirements on entry conditions for personnel and material Requirements on entry conditions for personnel and material
(change & clean-down procedures )(change & clean-down procedures ) ∆∆
Levels of Protection
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Parameters Influencing the Parameters Influencing the Level of Protection (1)Level of Protection (1)
Air Handling System
Production RoomWith
DefinedRequirements
SupplyAir
OutletAir
How does an Air Handling System influence the Cleanroom Class or Level of Protection ?
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Parameters Influencing the Parameters Influencing the Level of Protection (2)Level of Protection (2)
11 Number of particles in the airNumber of particles in the air22 Number of micro-organisms in the air or on Number of micro-organisms in the air or on
surfacessurfaces33 Number of air changes for each roomNumber of air changes for each room44 Air velocityAir velocity55 Air flow patternAir flow pattern66 Filters ( type, position )Filters ( type, position )77 Air Pressure differentials between roomsAir Pressure differentials between rooms88 Temperature, humidityTemperature, humidity ∆∆
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Parameters Influencing the Parameters Influencing the Level of Protection (3)Level of Protection (3)
Cleanroom Classdefined by
Critical Parameters
Air HandlingSystem
Additional Measures
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Parameters Influencing the Parameters Influencing the Level of Protection (4)Level of Protection (4)
Air handling systemsAir handling systems::• are the main tool for reaching required are the main tool for reaching required
parametersparameters
• but are not suff icient as suchbut are not suff icient as such
Need for additional measures such asNeed for additional measures such as� Appropriate gowning (type of clothing, proper Appropriate gowning (type of clothing, proper
changingchanging rooms)rooms) � Validated sanitationValidated sanitation� Adequate transfer procedures for materials and Adequate transfer procedures for materials and
personnelpersonnel ∆∆∆∆
Questions & AnswersQuestions & Answers