Download - HVAC__.pdf
HVAC
• H-V-A-C• H-VAK• Pharmaceutical plant air quality
Management• Air Conditioning
www.pharmatechbd.blogspot.com
HVAC
• H = Heating• V = Ventilation• A = Air• C = Conditioning
www.pharmatechbd.blogspot.com
HVACWhat is HVAC?
Controlling components and parameters of air
Why?As it has great effects on product quality
How?
By using AHU
www.pharmatechbd.blogspot.com
HVAC
DefinitionThe simultaneous control of various components and parameters of air to the specific limit as required for the manufacturing of quality medicine is known as air conditioning.
www.pharmatechbd.blogspot.com
Component Quantity Harmful Effects Examples
Nitrogen 78.02%
Oxygen 20.71% Oxidation Fe++ Fe+++
Carbon dioxide 0.03% Carboxylation
Argon 0.001%
Component of Air
• Gases
www.pharmatechbd.blogspot.com
Component Quantity Harmful Effects Examples
Dust Particles 0.01% Contamination All products
Drug Particle Cross Contamination All products
Microorganism Microbial contamination, Endotoxin contamination
Antacid &Sterile
Preparation
Component of Air
• Solid
www.pharmatechbd.blogspot.com
Component Quantity Harmful Effects
Examples
Moisture 0-1.5% Hydrolysis, Dissolution, Microbial growth
Aspirin, Ranitidine
Component of Air
• Liquid
www.pharmatechbd.blogspot.com
Component Quantity Harmful Effects Examples
Temperature 30-400
CDrug
Degradation, Microbial growth.
Thermo labile Drugs. Vitamins, Antibiotics.
Light Photo degradation
Nimesulide
Pressure Contamination All productsFlow Contamination All productsMovement Contamination All products
Parameters of Air
www.pharmatechbd.blogspot.com
Zone Grade
Process Particles Limit
Air change/hr
Filter
A Aseptic filling in final container
Class 100 ≥40 HEPA
B Background of Zone A
Class 100 ≥ 20 HEPA
C Sterile solution preparation
Class 10,000 ≥ 20 HEPA
D Dispensing of starting materials for products terminally sterilized.
Class 100,000 ≥ 20 HEPA
E Production and packing of non sterile products.
Class 100,000 ≥ 6 ≥ EU 12
F Secondary packaging
Optically Clean
≥ 4 ≥ EU 9
G Warehousing, QC Labs, General Area.
General Area Depends on heat load
≥ EU 6
www.pharmatechbd.blogspot.com
Zone Grade
Process Particles Limit(> 0.5 micron /M3
Air change/hr
Filter
A Aseptic filling in final container
Class 100 ≥40 HEPA
B Background of Zone A
Class 100 ≥ 20 HEPA
C Sterile solution preparation
Class 10,000 ≥ 20 HEPA
D Dispensing of starting materials for products terminally sterilized.
Class 100,000 ≥ 20 HEPA
E Production and packing of non sterile products.
Class 100,000 ≥ 6
F Secondary packaging
Optically Clean
≥ 4
G Warehousing, QC Labs, General Area.
General Area Depends on heat load
www.pharmatechbd.blogspot.com
Area Temperature(0c)
Humidity( % RH)
Particles( per M3)
Air Change
Aseptic filling 15-25 30-45 100 >40
Weighing, Processing ( Aseptic)& Filtration of Sterile product
15-25 45-55 10,000 20-40
Weighing, Processing of Sterile product with terminally sterilization.
15-25 45-55 100,000 20-40
Ophthalmic ointment 20-28 30-40 10,000 5-20
Weighing, processing and packing of non-sterile product.
20-28 45-75 100,000 5-20
a. Capsule 20-25 40-50 100,000 5-20
b. Hygroscopic Tablet 20-25 40-50 100,000 5-20
c. Dry Syrup 20-25 40-50 100,000 5-20
d. Liquid 20-28 45-75 100,000 5-20
Secondary Packing 20-28 45-75 Clean 5-20
Warehouse
a. Cool store 0-8 45-75 Clean 5-20
b. Controlled store 20-25 45-75 Clean 5-20
c. Normal store 30-35 45-75 Clean 5-20www.pharmatechbd.blogspot.com
HVAC
• Product quality depends on air quality• Products can only be as pure as the
environments in which they are produced.
www.pharmatechbd.blogspot.com
Product Quality
• Efficacy• Product Stability• Patient’s safety• Product Purity• Patient’s Acceptability• Regulatory Compliance
www.pharmatechbd.blogspot.com
Harmful Effects of Air
• Purity : Product will not be pure due to contaminants
• Stability : Product will be physically and chemically unstable
• Efficacy : Less effective due to decomposition• Safety : May not be safe for patient • Shelf life: Less Shelf life due to decomposition• Acceptability : May be unacceptable to patients
www.pharmatechbd.blogspot.com
Factors that contribute to quality products:
i. Starting materials and packaging materialsii. Validated processesiii. Personneliv. Proceduresv. Equipmentvi. Design and quality of premises
vii. Manufacturing environment
www.pharmatechbd.blogspot.com
Factors contributing to quality products
Starting materials
Personnel
ProceduresValidated processes
Equipment
Premises
Environment
Packing materials
www.pharmatechbd.blogspot.com
Environmental factors have a direct influence on a product:
Some environmental factors have a direct influence on a product:
1. Light, for light sensitive products (photo-degradation)2. Temperature, for temperature sensitive products (many
injectables, vaccines)3. Humidity, often for capsules and always for effervescent
tablets4. Air movement, affecting contamination and cross-
contamination5. Microbial contamination can lead to the destruction of
the product and to grave accidents in the case of injectables or sterile products.
6. Particulate contamination is critical in injectable forms
www.pharmatechbd.blogspot.com
Environmental factors have a direct influence on a product:
• These factors, if not properly controlled, can lead to:
• - product degradation (Physical-Chemical change)
• - product contamination• - sensitization or allergic reactions.• - loss of product and profit• Cross contamination In the case of highly potent
drugs, can lead to grave accidents.www.pharmatechbd.blogspot.com
Harmful effects of temperature
• Thermal degradation of Drugs:
• Microbial Growth
www.pharmatechbd.blogspot.com
Harmful effects of temperature
Thermal degradation of Drugs: Chemical Change: Thermo labile drugs
are decomposed if they are stored in higher temperature.
Physical Change: Temperature may change the color, odor and taste of drugs
www.pharmatechbd.blogspot.com
Harmful effects of temperature
Thermal degradation of Drugs:
Safety: The degradation may produce toxic product
Efficacy: Drug will be less effective due to thermal degradation
Stability: Both physical and chemical stability of some drugs are affected by temperature
Shelf life: Thermal Degradation will decrease the shelf life of drugs and dosage form
www.pharmatechbd.blogspot.com
Harmful effects of temperature
Microbial load: Microbial growth is accelerated by the optimum temperature. 370c temperature promotes the bacterial growth. Microbial load of some drugs, excipients or dosage form will increase if they are stored to 370c.
www.pharmatechbd.blogspot.com
Dust Particle Control• Harmful effects of dust particle:
– Cross contamination: – Microbial contamination: – Particulate contamination: – Sensitization or allergic reaction:– Product loss
1. Microbial contamination can lead to the destruction of the product and to grave accidents in the case of injectables or sterile products.
2. Particulate contamination is critical in injectable forms
www.pharmatechbd.blogspot.com
www.pharmatechbd.blogspot.com
www.pharmatechbd.blogspot.com
www.pharmatechbd.blogspot.com
Harmful Effects of Moisture
• Hydrolysis of drugs: Hydrolysis is considered as the major cause of drug decomposition. It may be defined as the reaction of drugs with water. A prime example of this phenomenon is the decomposition of aspirin into salicylic acid and acetic acid.Aspirin ------ Salicylic Acid + Acetic AcidMany drugs are susceptible to hydrolysis and degraded by moisture present in the air.
www.pharmatechbd.blogspot.com
Harmful Effects of Moisture
• Oxidation of drugs: Moisture can increase the rate of oxidation of some drugs. Ferrous Sulphate crystals are more rapidly oxidized in moist air.Fe++ ---- Fe+++
www.pharmatechbd.blogspot.com
Harmful Effects of Moisture
• Physical changes due to chemical decomposition:
• Color Change• Odor Change• Taste Change• Production of Toxic Chemicals
www.pharmatechbd.blogspot.com
Harmful Effects of Moisture
• Physical Stability• Drug dissolution: Moisture is rapidly
absorbed on the surface of hygroscopic drugs causing solution of the drug in that moisture. Ranitidine, Ascorbic Acid, Cloxacillin, Flucloxacillin are very hygroscopic drugs that absorb moisture from air and dissolved in it.
www.pharmatechbd.blogspot.com
Harmful Effects of Moisture
Physical Stability:• Agglomeration of powder: Fine powder may
form lump due to the absorption of moisture from air.
• Moisture regain: Materials may regain moisture from air after drying if it is exposed to humid air.
• Cake Formation: Fine powder may form cake due to the absorption of moisture from air.
www.pharmatechbd.blogspot.com
Harmful Effects of Moisture
• Microbial Growth: Microbial growth is accelerated by the presence of moisture. Above 60% RH promotes the bacterial growth. Microbial load of some drugs, excipients or dosage form will increase if they are exposed to humid air.
www.pharmatechbd.blogspot.com
What are contaminants ?Contaminants are1. Products or substances other
than product manufactured 2. Foreign products3. Particulate matter4. Micro-organisms5. Endotoxins (degraded micro-
organisms)
www.pharmatechbd.blogspot.com
Contaminants• Contaminants can be:
1. Products or substances other than the product manufactured (e.g. products resulting from air pollution).
2. Foreign products, such as metal parts from equipment, paint chips,etc.
3. Particulate matter, especially dangerous in injectables.4. Micro-organisms – a particular problem for sterile
products.5. Endotoxins: Even if killed by thermal treatment, micro-
organisms are degraded to endotoxins and can cause damage.
www.pharmatechbd.blogspot.com
Contaminants
• Contaminants are in fact the presence of anything in the manufactured product which should not be there.
Cross-contamination is a particular case of contamination
www.pharmatechbd.blogspot.com
Sources of contaminants
• Contaminants can originate from:
Environment • particles, • micro-organisms, • dust containing other products.
www.pharmatechbd.blogspot.com
Sources of contaminantsEquipment • residues of other products,• oil, • particles, • rust, • gaskets, • Metal• leaching of plastic components, metal parts (broken
sieves in granulators), brittle gaskets, oil, chips of paint, etc.
www.pharmatechbd.blogspot.com
Sources of contaminants
Contamination can be brought by operators
objects falling into the product, skin particles, dandruff, fibres from uniforms.
www.pharmatechbd.blogspot.com
Sources of contaminants
Contamination can be brought by premises
Particle shading Paint chipsConstruction material
www.pharmatechbd.blogspot.com
Cross-Contamination (1)
What is Cross-Contamination ?
Definition of Cross-Contamination:Contamination of a starting material, intermediate product, or finished product with another starting material or product during production. (WHO) Annex 1, Glossary
www.pharmatechbd.blogspot.com
Contamination
Contaminant from
EnvironmentOperators
Contaminant from
Equipment
CrossContamination
Productfrom
EnvironmentOperators
Productfrom
Equipment
Cross-Contamination ( 3 )
www.pharmatechbd.blogspot.com
Cross Contamination• Definition of Cross-Contamination:• According to WHO, cross-contamination is “Contamination of a
starting material, intermediate product, or finished product with another starting material or product during production”. WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-second Report. Geneva, World Health Organization, 1992 (WHO Technical Report Series, No. 823). Annex 1: Good manufacturing practices for pharmaceutical products.
• In other words, cross-contamination is the presence in a particular product of small, traceable quantities of other pharmaceutical products manufactured
• at the same time in the same premises• previously on the same equipment or in the same premises
www.pharmatechbd.blogspot.com
Cross Contamination• Cross-Contamination is thus only concerned with the
presence of traces of products manufactured in-house !
• Adequate analytical detection is important to detect traces of contamination.
• Validated analytical methods, especially developed for detection purposes, may be necessary to detect cross-contamination.
• An absence of cross-contamination being detected may just mean the absence of adequate analytical procedures.
www.pharmatechbd.blogspot.com
Cross-Contamination (2)From where does Cross-Contamination
originate?1. Poorly designed air handling systems
and dust extraction systems2. Poorly operated and maintained air
handling systems and dust extraction systems
3. Inadequate procedures for personnel and equipment
4. Insufficiently cleaned equipmentwww.pharmatechbd.blogspot.com
insufficient control over
1.Design of premises and systems quality 2.Air handling and dust extraction systems3.Operation and maintenance of air handling
and dust extraction systems4.Procedures for cleaning of equipment and
for restriction of movement of personnel5.Procedures for cleaning of premises
www.pharmatechbd.blogspot.com
Sources of cross-contamination
• cross-contamination can be either airborne or physically transferred:
• by bringing traces of a product through ventilation systems
• by transfer of contaminants• from one room to another due to poor pressure
cascade• through clothing into another product• through badly cleaned equipment retaining traces of a
product and contaminating another product.
www.pharmatechbd.blogspot.com
Cross-Contamination (4)Cross-contamination can be minimized
by:1. Personnel procedures2. Adequate premises3. Use of closed production systems4. Adequate, validated cleaning
procedures5. Appropriate levels of protection of
product6. Correct air pressure cascade
www.pharmatechbd.blogspot.com
• There are different ways to prevent or reduce the effect of cross-contamination.
• Personnel procedures: Clean clothing, and for clean rooms (C, B, A) to be washed in special laundries; Personal hygiene on entering a pharmaceutical area.
• Adequate premises: Minimisation of possibility of accumulation of dust; Premises with good ventilation and dedusting system.
•
www.pharmatechbd.blogspot.com
• Closed production systems: Closed systems, in which product is transferred from one piece of equipment to another one, without being exposed to the atmosphere.
• Validated cleaning procedures: Manual cleaning procedures may not be
reproducible.
•www.pharmatechbd.blogspot.com
• Level of Protection concept 2: A good hygiene, or Level of Protection concept, specifying requirements for environmental conditions; entry procedures for
personnel and material is fundamental for keeping cross-contamination under control.
• Maintaining the correct air pressure differential between rooms helps prevent cross-contamination.
• The module on HVAC deals precisely with the last of these ways, namely a good air handling system.
www.pharmatechbd.blogspot.com
Level of Protection Concept
1. Defines environmental requirements
2. Helps prevent contamination and cross-contamination
3. Allows production under optimal hygiene conditions
4. Takes into account• product sensitivity to contamination• therapeutic risk
www.pharmatechbd.blogspot.com
Therapeutic risks
Manufacturing Environm
ent requirem
ents
Cleanroom
Class A / B
Cleanroom
Class C
Cleanrm
. Class D
Others
www.pharmatechbd.blogspot.com
Levels of ProtectionParameters to be defined:1.Air cleanliness requirements (filters
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 operations4.Building design and finishes
Annex 1, 17.3, 17.4
www.pharmatechbd.blogspot.com
Levels of ProtectionTypes of Cleanroom Classes• International WHO A, B, C, D
• National EC, PIC/S, TGA, etc. : A, B, C, D US FDA : critical and controlled ISPE: level 1, 2 or 3 or
cleanroom class Companies : various others
Annex 1, 17.3, 17.4www.pharmatechbd.blogspot.com
• Therapeutic Goods Administration (TGA). TGA is Australia's regulatory agency for medical drugs and devices.
• Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (jointly referred to as PIC/S)
www.pharmatechbd.blogspot.com
etc.
XFilling for aseptic process
XFilling for terminal sterilisation
XDepyrogenisation of containers
XXXPreparation of solutions for aseptic filling
XPreparation of solution for terminal sterilisation
XWashing of containers
DCBA
Annex 1, 17.3, 17.4, 17.5
Cleanroom Class
www.pharmatechbd.blogspot.com
Levels of ProtectionBased on the cleanroom class requirements, various Levels of Protection have to be created, including:• Correlation between process operations and cleanroom classes • Type of operation permitted in each Level of Protection
www.pharmatechbd.blogspot.com
• Definition of cleanroom class (parameters, building materials, room requirements, HVAC 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 procedures )www.pharmatechbd.blogspot.com
Annex 1, 17.4
Air Handling System
Production RoomWith
DefinedRequirements
SupplyAir
OutletAir
www.pharmatechbd.blogspot.com
Parameters influencing Levels of Protection (2)
1 Number of particles in the air2 Number of micro-organisms in the
air or on surfaces3 Number of air changes for each
room4 Air velocity5 Air flow pattern6 Filters ( type, position )7 Air pressure differentials between
rooms8 Temperature, humidity
www.pharmatechbd.blogspot.com
Cleanroom Classdefined by
Critical Parameters
Air HandlingSystem
Additional Measures
Parameters influencing Levels of Protection (3)
www.pharmatechbd.blogspot.com
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
Annex 1, 17.10 to 17.16www.pharmatechbd.blogspot.com
Zone Grade
Process Particles Limit(> 0.5 micron /M3
Air change/hr
Filter
A Aseptic filling in final container
Class 100 ≥40 HEPA
B Background of Zone A
Class 100 ≥ 20 HEPA
C Sterile solution preparation
Class 10,000 ≥ 20 HEPA
D Dispensing of starting materials for products terminally sterilized.
Class 100,000 ≥ 20 HEPA
E Production and packing of non sterile products.
Class 100,000 ≥ 6
F Secondary packaging
Optically Clean
≥ 4
G Warehousing, QC Labs, General Area.
General Area Depends on heat load
www.pharmatechbd.blogspot.com
•“AHU must be located outside the space they are controlling!”
Air Handling System
Production RoomWith
DefinedRequirements
SupplyAir
OutletAir
www.pharmatechbd.blogspot.com
+
Production Room
Exhaust air treatment
Central air handling unit
Terminal air treatmentat production room level
Fresh air treatment(make-up air)
Main subsystems
www.pharmatechbd.blogspot.com
4 sub-systems
• A conventional Air Handling System has 4 sub-systems:
1. Air handling of the incoming (fresh) air: elimination of coarse contaminants and protection from frost if necessary. In the case of air re-circulation, the fresh air is also called make-up air.
2. Central air handling unit (AHU), where the air will be conditioned (heated, cooled, humidified or de-humidified and filtered), and where fresh air and re-circulated air, if any, (indicated here by the dotted line) will be mixed.
3. Air handling in the rooms under consideration (pressure differential system, additional filtration, air distribution).
4. Air exhaust system (filtration).
www.pharmatechbd.blogspot.com
FilterSilencer
Terminal filter
Weather louvre Control damper
FanFlow rate controller
Humidifier
Heating coil
Cooling coilwith
droplet separator
Production Room
Overview components
+
Prefilter
Exhaust Air Grille
Heater
Secondary Filter
Re-circulated air
www.pharmatechbd.blogspot.com
• Weather louvre
• Silencer
• Flow rate controller
• Control damper
• To prevent insects, leaves, dirt and rain from entering
• To reduce noise caused by air circulation
• Automated adjustment of volume of air (night and day, pressure control)
• Fixed adjustment of volume of air
Components
www.pharmatechbd.blogspot.com
• Heating unit
• Cooling unit /dehumidifier
• Humidifier
• Filters
• Ducts
• To heat the air to the proper temperature
• To cool the air to the required temperature or to remove moisture from the air
• To bring the air to the proper humidity, if too low
• To eliminate particles of pre-determined dimensions and/or micro-organisms
• To transport the air
www.pharmatechbd.blogspot.com
• Flow rate controller
• Control damper
• Humidifier
• Cooling battery
• Filters
• Ducts
• Blocked
• Poorly adjusted, bad pressure differential system
• Bad water/steam quality/poor drainage
• No elimination of condensed water/poor drainage
• Incorrect retention rate/damaged/badly installed
• Inappropriate material/internal insulator• leaking
Problems with components
www.pharmatechbd.blogspot.com
+
Production Room
Exhaust air
Return air(re-circulated)
Fresh air(make-up air)
Supply air
Air types
www.pharmatechbd.blogspot.com
Function of AHU
• Heating• Cooling• Humidification• Dehumidification• Filtration
www.pharmatechbd.blogspot.com
Measurement of Humidity
Air
Dry Air Moist Air
Saturated Air Unsaturated Air
www.pharmatechbd.blogspot.com
Dry air Air which is free from water Moist air The mixture of dry air and waterSaturated air When air contains maximum amount of moistureUnsaturated air Air which is not saturatedAbsolute
humidityWeight of water per pound of dry air.Unit: grains/ lb. dry air
Relative humidity
Ratio of actual amount of water & maximum amount of water
Dew point Temperature at which condensation will just begin with the existing moisture.
Humidity Control
• Various Terms
www.pharmatechbd.blogspot.com
Determination of Volume of Air
1. Length, height and width of tablet process room are 12 ft, 8 ft and 10 ft respectively. Determine the Volume of air of that room.
Ans.: Volume of air = Volume of Room= Length, x height x width= 12 x 8 x 10= 840 ft3.
www.pharmatechbd.blogspot.com
Determination of weight of Air
2. Length, height and width of tablet process room are 12 ft, 8 ft and 10 ft respectively. Determine the weight of dry air of that room.
Ans.: Volume of air = Volume of Room= Length, x height x width= 12 x 8 x 10= 840 ft3.Weight of air = Volume x Density
= 840 ft3 x 0.0807 lb/ ft3.= 67.788 lb.
www.pharmatechbd.blogspot.com
Air temperature ( 0F) Maximum amount of moisture(Grains/ lb. dry air.)
54 6260 7867 9981 16185 185
Determination of Maximum amount of moisture in Air
• Moisture content capacity of air depends on temperature. • Higher temperature air can contain more moisture.
www.pharmatechbd.blogspot.com
Maximum amount of moisture in Air
3. Length, height and width of tablet process room are 12 ft, 8 ft and 10 ft respectively. Calculate the maximum amount of moisture at 600F. air of that room.
Ans.: Volume of air = Volume of Room= Length, x height x width= 12 x 8 x 10= 840 ft3. Weight of air = Volume x Density
= 840 ft3 x 0.0807 lb/ ft3.= 67.788 lb.
Maximum Amount of moisture= 67.788 lb x 78 Grains/ lb. dry air= 5287.464 grains= 0.755 lb
www.pharmatechbd.blogspot.com
Determination of AH , % RH4. Capsule process room contains 67.788 lb. dry
air and 4000 grains moisture. Calculate the AH.Answer:AH (Absolute Humidity)= Wt. of moisture per lb. of dry air.= Wt of moisture / Wt of dry air= 4000/67.788= 59 grains/ lb. dry air
www.pharmatechbd.blogspot.com
Determination of AH , % RH5. Liquid process room contains 100.5 lb. moist air
and 0.5 lb. moisture. Calculate the AH.Answer:AH (Absolute Humidity)= Wt. of moisture per lb. of dry air.= Wt of moisture / Wt of dry air= (0.5 x 7000 grains) / (100.5-0.5)= 3500 / 100= 35 grains/ lb. dry air
www.pharmatechbd.blogspot.com
Determination of AH , % RH6. Capsule process room contains 100.5 lb. moist
air and 0.5 lb. moisture at 600F. Calculate the AH & %RH.
Answer:AH (Absolute Humidity)= Wt. of moisture per lb. of dry air.= Wt of moisture / Wt of dry air= (0.5 x 7000 grains) / (100.5-0.5)= 3500 / 100= 35 grains/ lb. dry air
www.pharmatechbd.blogspot.com
%RH = (Actual amount of moisture / amount of moisture in saturation) x 100
• = 35/78*100• =44.87 %
www.pharmatechbd.blogspot.com
Determination of AH , % RH3. % RH of a room is 80%. The air of the room
contains 0.25 lb. moisture. Calculate the amount of moisture at saturated condition.
Answer:%RH = (Actual amount of moisture / amount of
moisture in saturation) x 100Amount of moisture in saturation = (Actual amount
of moisture / RH) x 100= (0.25 / 80) x100= 0.3125 lb.
www.pharmatechbd.blogspot.com
Instruments
• Hygrometer: It is an instrument containing dry bulb temperature and wet bulb thermometer.
• Dry bulb thermometer: Temperature recorded by a dry bulb thermometer
• Wet bulb thermometer: Temperature recorded by a wet bulb thermometer
• Observe the dry bulb temperature & wet bulb temperature. Determine the difference. Now various parameters can be determined by using either psychometric table or psychometric chart
www.pharmatechbd.blogspot.com
Psychometric Table
DefinitionA Psychometric table is a representation of various thermodynamic parameters of moist air.
www.pharmatechbd.blogspot.com
Psychometric Table
Determination of Relative humidity:1. Observe the dry bulb temperature & wet
bulb temperature.2. Determine the difference. 3. Now cross point of dry bulb temperature
and depression of temperature in the Psychometric Table indicates the Relative Humidity
www.pharmatechbd.blogspot.com
Dry Bulb Tem.
DEPRESSION OF WET BULB 0C
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0
21 95 91 86 82 78 73 69 65 61 57 53 49 45 42
22 95 91 87 82 78 74 70 66 62 58 54 50 47 43
23 96 91 87 83 79 75 71 67 63 59 55 52 48 45
24 96 91 87 83 79 75 71 68 64 60 57 53 49 46
25 96 92 88 84 80 76 72 68 65 61 58 54 51 47
26 96 92 88 84 80 76 73 69 66 62 59 55 52 49
27 96 92 88 84 81 77 73 70 66 63 59 56 53 50
28 96 92 88 85 81 77 74 70 67 64 60 57 54 51
29 96 92 89 85 81 78 74 71 68 64 61 58 55 52
30 96 93 89 85 82 78 75 72 68 65 62 59 56 53
32 96 93 89 86 82 79 76 73 70 67 64 61 58 55
34 96 93 89 86 83 80 77 74 71 68 65 62 59 56
36 96 93 90 87 84 81 78 75 72 69 66 63 61 58
www.pharmatechbd.blogspot.com
Psychometric chart
• Definition• A Psychometric chart is a graphical
representation of various thermodynamic parameters of moist air.
www.pharmatechbd.blogspot.com
Dry bulb temperature lines
These are the straight and vertical lines drawn parallel to the ordinate.
Wet bulb temperature lines
These are the straight but inclined lines which extend diagonally as shown on the chart
Absolute humidity lines
These are the straight and Horizontal lines drawn parallel to the abscissa.
Relative humidity lines These are the curved lines. The saturation lines show 100% Relative humidity
Psychometric chart
• Various Lines
www.pharmatechbd.blogspot.com
www.pharmatechbd.blogspot.com
AH & RH from psychometric chart
• Determine the dry bulb temperature and wet bulb temperature from the hygrometer. Then determine the cross point in the Psychometric chart.
• Now absolute humidity line passing though the cross point indicates the Absolute Humidity.
• Relative humidity line passing though the cross point indicates the Relative Humidity.
• Dew point can be find out from the cross point of Absolute Humidity line and saturation humidity line.
www.pharmatechbd.blogspot.com
Area Humidity(% RH)
Aseptic filling 30-45Weighing, Processing (Aseptic)& Filtration of Sterile product 45-55Weighing, Processing of Sterile product with terminally sterilization. 45-55Ophthalmic ointment 30-40Weighing, processing and packing of non-sterile product. 45-75a. Capsule 40-50b. Hygroscopic Tablet 40-50c. Dry Syrup 40-50d. Liquid 45-75Secondary Packing 45-75a. Cool store 45-75b. Controlled store 45-75c. Normal store 45-75
REQUIREMENT
www.pharmatechbd.blogspot.com
Dehumidifier
Dehumidifier
Desiccant Refrigeration
www.pharmatechbd.blogspot.com
Desiccant type Dehumidifier:
• Desiccant type Dehumidifier:• Desiccants are used in a desiccant type dehumidifier.
Desiccant can adsorb moisture from air. As a result the quantity of moisture in air will decrease. By passing the air through the desiccant again and again, we will get moisture free air. Desiccant type dehumidifier acts on this principle.
• When the unit is started, the fan begins to pass moisture-laden air through the desiccant, which adsorbs moisture from the air making the air moisture free. Desiccant becomes inactive due to adsorption of moisture. Desiccant can be again reactivated by passing hot air through it.
www.pharmatechbd.blogspot.com
De-humidification
Filter Pressure Gauges
AHU with fan Variable Speed
Controller
air
Air heater
Regeneration
Humid room air
Adsorber wheelDry air
www.pharmatechbd.blogspot.com
Refrigeration type Dehumidifier
• Components: • Refrigerants: Substances that are circulated in a closed
refrigeration system to transfer heat. • Examples:
Trichloro Monofluro Methane Dichloro Difluro Methane Monochloro Trifluro Methane
• Compressor: Circulates refrigerants through a closed system.
• Condenser: It receives hot, high-pressure refrigerants from the compressor and converts it into liquid refrigerants.
• Evaporator: liquid refrigerant is vaporized at lower pressure in evaporator.
www.pharmatechbd.blogspot.com
Refrigeration type Dehumidifier
• Principle:• The content ability of air is temperature
dependent. Hot air can contain more moisture than cool air. Refrigeration type dehumidifier can decrease the temperature of air. As a result air will be first saturated and then excess water will be separated from air. Refrigeration type dehumidifier acts on this principle.
www.pharmatechbd.blogspot.com
Refrigeration type Dehumidifier
• Principle:• Refrigerants are used in refrigerants type
dehumidifier. These refrigerants are evaporated in the evaporator. Heat is taken by the refrigerants as a latent heat for this conversion. As a result the evaporation coils become very cool. In contact with the evaporating coil, air also becomes very cool. As cool air can contain less moisture, the excess water will be separated from the air.
www.pharmatechbd.blogspot.com
Refrigeration type Dehumidifier
• When the unit is started, the fan begins to pull moisture-laden air across the evaporating coils making the cool and moisture free. Then the moisture free air is passed through the condenser where the air becomes hot due to the latent heat of condensation of refrigerants in the condenser.
www.pharmatechbd.blogspot.com
Temperature Control
• Air Cooler• Air Heater
www.pharmatechbd.blogspot.com
Air Cooler
• Components: • Refrigerants: Substances that are circulated in a closed
refrigeration system to transfer heat. • Examples:
Trichloro Monofluro Methane Dichloro Difluro Methane Monochloro Trifluro Methane
• Compressor: Circulates refrigerants through a closed system.
• Condenser: It receives hot, high-pressure refrigerants from the compressor and converts it into liquid refrigerants.
• Evaporator: liquid refrigerant is vaporized at lower pressure in evaporator.
www.pharmatechbd.blogspot.com
RefrigerantsNumerical designation Chemical name Chemical
Formula
111213
Trichloro Monofluro MethaneDichloro Difluro MethaneMonochloro Trifluro Methane
CCl3FCCl2F2CClF3
www.pharmatechbd.blogspot.com
Principle of Air Cooler• Refrigerants are used in air cooler. These
refrigerants are evaporated in the evaporator. Heat is taken by the refrigerants as a latent heat for this conversion. As a result the evaporation coils become very cool. In contact with the evaporating coil, air also becomes very cool. This cool air is distributed in the room.
www.pharmatechbd.blogspot.com
Principle of Air Cooler• Condenser receives hot, high-
pressure refrigerants from the compressor and converts it into liquid refrigerants. Heat is released from the refrigerant at this conversion. Air from out site the room is passed across the condenser to transfer heat.
www.pharmatechbd.blogspot.com
Principle of Air Cooler• When the unit is started, the fan begins to
pull hot air of the room across the evaporating coils making the cool and this cool air is distributed in the room. At the same time fan passes the out site air across the condenser and keep it cool by removing heat from the condenser.
www.pharmatechbd.blogspot.com
Hot Water Coil• Ideal for a wide variety of
basic, custom, and heavy-duty industrial applications, hot water coils are designed to meet a variety of heating applications. Applications include booster heat, reheat, waste heat reclamation, pre-heat, fluid process heat & more.
www.pharmatechbd.blogspot.com
Chilled water coil
• For applications including comfort cooling, dehumidification, process cooling, and more.
www.pharmatechbd.blogspot.com
Filter classesDust filters
Standard Aerosol
FineCoarse ULPAHEPA
10 µ m > Dp > 1 µ mDp > 10 µ m Dp < 1 µ m
F5 - F9G1 - G4 U 14- 17H 11 - 13
EN 1822 StandardEN 779 Standard
www.pharmatechbd.blogspot.com
ULPA (Ultra Low Penetration Air) filter.
• a filter with a higher efficiency than a HEPA filter was offered. It had a DOP efficiency of 99.999% and the 12 in. (304.8 mm.) deep version had a clean pressure drop of 273.6 Pa when operating at a face velocity of 250 fpm (1.27 m/s). This filter has helped meet the requirement for cleaner air in facilities needed for the manufacture of microelectronics. It is identified by the generic name ULPA (Ultra Low Penetration Air) filter.
www.pharmatechbd.blogspot.com
www.pharmatechbd.blogspot.com
www.pharmatechbd.blogspot.com
www.pharmatechbd.blogspot.com
HEPA filters
• The first HEPA filters were developed in the 1940's by the USA Atomic Energy Commission to fulfill a top-secret need for an efficient, effective way to filter radioactive particulate contaminants. They were needed as part of the Manhattan Project, which was the development of the atomic bomb. The first HEPA air filters were very bulky compared to the HEPA air filters that are produced today.
www.pharmatechbd.blogspot.com
Filter• The filtration efficacy depends on several mechanisms,
and results in a rough filter classification.
• The diagram shows the commonly used classification, with current abbreviations G = Gross, F= Fine, H= High, U= Ultra.
• Filters are certified by the suppliers (challenge/efficiency test), but are often not properly installed or can be damaged. Leak tests (integrity tests), showing leakage of air through the filter itself or through its frame, therefore, have to be performed. Integrity tests are usually only carried out on the Aerosol filters (HEPA & ULPA).
www.pharmatechbd.blogspot.com
Filter• Integrity or penetration testing is performed to
detect leaks from the filter media, filter frame and seal. The challenge is a poly-dispersed aerosol usually composed of particles ranging in size from one to three microns. The test is done in place and the filter face is scanned with a photometer probe; the measured downstream leakage is taken as a percentage of the upstream challenge. Integrity tests should be carried out with filters installed in the system and should be carried out by an independent body (not the filter supplier).
www.pharmatechbd.blogspot.com
Filter
• The efficiency test, on the other hand, is used to determine the filter's rating. This test uses a mono-dispersed aerosol of 0.3 micron size particles, relates to filter media, and usually requires specialized equipment. Downstream readings represent an average over the entire filter surface. Therefore, leaks in a filter may not be detected by an efficiency test.
www.pharmatechbd.blogspot.com
Average EfficiencyIntegral Value
Peak ArrestanceLocal Value
Retention in%
Penetration Efficiency Penetration
F9 85 0.15
H11 95 0.05
H12 99.5 5x10-3 97.5 25x10-3
H13 99.95 5x10-4 99.75 25x10-4
U14 99.995 5x10-5 99.975 25x10-5
Classification of filters according to their efficiency
www.pharmatechbd.blogspot.com
Primary panel filter
Secondary filter
HEPA or tertiaary filter
www.pharmatechbd.blogspot.com
Humidifier SilencerHeating and
cooling units
www.pharmatechbd.blogspot.com
Control damper for air flow
De-humidification
Filter Pressure Gauges
AHU with fan Variable Speed
Controller
Humid room air
Air heater
Regeneration air
Humid room airAdsorber wheel Dry
air
Air handling unitwww.pharmatechbd.blogspot.com
Swirl Type air diffusors with
terminal filters1 Filter2 Tightening frame3 Register outlet4 Screw fixation for register
1
2
34
www.pharmatechbd.blogspot.com
Low induction swirl diffusor
(preferred)
High induction office type diffusor
(avoid)www.pharmatechbd.blogspot.com
Annex 1, 17.26
Regulation of room pressure – pressure differentials concept
Room pressure gauges
Room pressure indication panel
www.pharmatechbd.blogspot.com
Pressure cascade injectablesProtection from micro-organisms and
particles
Annex 1, 17.24, 17.25
www.pharmatechbd.blogspot.com
Pressure cascade solidsProtection from cross-contamination
www.pharmatechbd.blogspot.com
HeatingVentilation andAir Conditioning (HVAC)
Part 3: Design, qualification and maintenance
Air Handling Systems
Supplementary Training Modules on GMP
Module 3, Part 3: Qualification and maintenance Slide 130 of 27WHO -EDM
www.pharmatechbd.blogspot.com
Characteristics of air handling systems
In the following slides, we will study alternatives in air handling systems
Turbulent or uni-directional airflows Filter position Air re-circulation vs fresh air Return air systems (positions) Overpressure requirements
www.pharmatechbd.blogspot.com
Uni-directional / laminardisplacement of dirty air
Turbulent dilution of dirty air
0,30 m/s
Annex 1, 17.3
Air flow patterns (1)
www.pharmatechbd.blogspot.com
Air flow patterns (1)• There are 2 ways to supply air to a room or a
piece of equipment:• • Turbulent air flow• Uni-directional flow, often called laminar flow
• The air speed in the uni-directional flow is defined by the WHO at:
• 0,45 m/s for horizontal units• 0,30 m/s for vertical units (most commonly
used)www.pharmatechbd.blogspot.com
Air flow patterns (1)
• It is important to know that the WHO definition(*) for the air speed differs from those of other guidelines.
• For the air exhaust, in case of a vertical unit, a low return is more favourable, as the air is better distributed in the room.
• Objects in the room can significantly disturb the flow of air, and even block it, so that there might be pockets without air circulation.
• During the qualification phase, the air flow is visualized if possible, and air samples are taken in different points, to make sure that there are no such pockets, in which case adjustments to the layout or to the air handling systems must be made.
• (*) WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-second Report. Geneva, World Health Organization, 1992: 59-60 (Technical Report Series, No. 823). Annex 1, 17.3.
www.pharmatechbd.blogspot.com
Air flow patterns (2)
Filtered air entering a production room or covering a process can be turbulent uni-directional (laminar)
GMP aspect economical aspect
New technologies: barrier technology/isolator technology.
Annex 1, 17.3, 17.4www.pharmatechbd.blogspot.com
Air flow patterns (2)• As seen in the previous slide, filtered air entering a
production room or covering a process can be
• Turbulent
• Uni-directional (laminar)
ï Two aspects have to be considered:
• GMP aspect: uni-directional air (laminar) installations give a better protection, because of the displacement effect rather than the dilution effect.
• Economical aspect: turbulent air installations are cheaper, as less air has to be treated.
www.pharmatechbd.blogspot.com
Air flow patterns (2)• For certain operations, namely in class A, a “laminar
flow” must be used.• It should be said here that such installations can give a
false impression of security, and that the purpose of such installations is that there should be, whenever possible, no human interventions under them during the process.If interventions have to occur, they should be performed in a well-documented way, and recorded and evaluated for possible damage to the products.
• The use of barrier technology systems (isolator technology) is highly recommended in cases of operations in class A, or for sterility testing operations.
www.pharmatechbd.blogspot.com
PrefilterAir flow patterns (3)
AHU
Main filter
Uni-directional TurbulentTurbulent
1 2 3
Annex 1, 17.3
www.pharmatechbd.blogspot.com
Air flow patterns (3)• This slide shows an HVAC installation feeding 3 rooms, each one
with terminal filters, all terminal filters protected by a remote pre-filter.
• Room 1 has a turbulent air flow, with low level exhaust.
• Room 2 has a uni-directional air flow, over the largest part of the surface, hence the large number of filters, with low level air returns.
• Due to the high cost of the ventilation in class A areas, the tendency is to keep these areas as small as possible.
• Room 3 has a turbulent air flow, with ceiling exhaust.
• Good design practices recommend that cleanrooms A, B and C (ISO Class 5, 6 & 7) should have low level air returns.
www.pharmatechbd.blogspot.com
Workbench (vertical) Cabin/ booth Ceiling
Air flow patterns (4)
www.pharmatechbd.blogspot.com
Air flow patterns (4)• Uni-directional (laminar) flow units exist mostly as vertical, but also as
horizontal, units.
• Often, we are just dealing with LF workbenches (mainly used in sterility testing) or LF cabins/booths, routinely used in production, for instance on top of a filling machine.
• In some cases, the units can be integrated into the ceiling of a room and also connected to the central air conditioning system.
• Due to the high air velocity, it is important to have objects with good aerodynamical properties under the laminar flow. If not, turbulences and, therefore, particles are unavoidable.
• Laminar flow units are comparatively expensive. Surfaces covered by them should be reduced to a minimum.
• Only the product in a critical production phase, and not the personnel, should be under laminar flow (aseptic filling, sterile blending, etc.). Manual interventions should be restricted to a minimum, and should be recorded and evaluated for possible consequences.
www.pharmatechbd.blogspot.com
Positioning of filters (1)
Filter in terminal position AHU mounted final filter
Production Room
+
Production Room
HEPA Filter
HEPA Filter
www.pharmatechbd.blogspot.com
Positioning of filters• In some of the previous slides, we have seen filters both
in the central air handling units ( AHU ) and terminally mounted at the production rooms.
• The filtered air entering a production room can be coming from:
• an air-handling unit, equipped with pre-filtration and the main (HEPA) filter, but at some distance from that room (left drawing);
• an air-handling unit, equipped with pre-filtration in the AHU, and an additional filter (HEPA) situated immediately on the air outlet (right drawing).
www.pharmatechbd.blogspot.com
Positioning of filters• In many cases, there are only filters in the AHU. However, for injectables
and sterile forms, it is recommended that they be placed in terminal position, though there is a growing tendency to have terminal filters in all rooms where open products are handled. It is recommended that classes A & B (ISO 4, 5 & 6) have terminal HEPA filters. (Refer to: WHO Export Committee on Specifications for Pharmaceutical Preparations. Thirty-second Report. Geneva, World Health Organization, 1992:59-60 (Technical Report Series, No. 823). Annex 1, 17.3.)
• If we look at the advantages and disadvantages of terminal or non-terminal filters, we can say that generally speaking, the terminal positioning
• is more expensive;• provides a better protection (any problem arising from the ducts is
eliminated);• is the preferred method in cleanroom classes with high requirements.
www.pharmatechbd.blogspot.com
Prefilter
AHU
Main filter
1 2 3
Low level exhausts
Ceilingexhausts
Positioning of filters (2)
www.pharmatechbd.blogspot.com
Positioning of filters• Filters can be in different positions, when one considers
the central AHU and the rooms.
• This slide shows an HVAC installation feeding 3 rooms, each one with terminal filters, all filters protected by a remote pre-filter.
• Room 1 has a turbulent air flow, with low level exhaust.
• Room 2 has a uni-directional (laminar) air flow over the largest part of the surface, hence the large number of filters.
• Room 3 has a turbulent air flow, with ceiling exhaust.
www.pharmatechbd.blogspot.com
AHUPrefilter
Final filter
21
Positioning of filters (3)
www.pharmatechbd.blogspot.com
Positioning of filters• This slide shows an HVAC installation feeding two
rooms, each one without terminal filters, but with remote final filters protected by a pre-filter.
• Room 1 has a turbulentair flow, with low level exhaust.
• Room 2 has a turbulent air flow, with ceiling exhaust.
• If there is no filter in terminal position, it should be ascertained that there are no elements between the main filter and the air outlets which could add contamination. No elements such as fans, heating/cooling batteries, should be situated downstream of the final filter.
www.pharmatechbd.blogspot.com
Air re-circulation
The filtered air entering a production room can be
100% exhausted or a proportion re-circulated
GMP aspect economical reasons
Annex 1, 15.10, 17.24
www.pharmatechbd.blogspot.com
Air re-circulation• The filtered air entering a production room can be
• eliminated at 100% (exhaust air)• a proportion re-circulated
• Re-circulated air must be filtered, at an efficiency rate which is such that cross-contamination can be excluded.
• In case of re-circulation, every possible measure of protection must be taken to ensure that the air coming from a production unit and loaded with product particles does not flow to other production units, thereby contaminating them.
• It makes sense to re-circulate the air for reasons of energy conservation, but there can be a contradiction between pharmaceutical requirements and energy conservation.
• There are also cases, in which air re-circulation is prohibited, for example if solvents are used or cytotoxic products are manufactured.
www.pharmatechbd.blogspot.com
Ventilation with 100% fresh air (no air re-circulation)
Annex 1, 17.24
W
Washer (optional)
Central Air Handling Unit
Production Rooms
Exhaust Unit
www.pharmatechbd.blogspot.com
Ventilation with 100% fresh air (no air re-circulation
• This slide illustrates a typical 100% fresh air setup, where a central unit distributes the fresh, treated air to different production rooms.
• The exhaust air is collected in a central duct, treated (filtered or washed) and eliminated. The degree of exhaust air filtration will depend on contaminants in the exhaust air and also on environmental regulations.
www.pharmatechbd.blogspot.com
Ventilation with re-circulated air + make-up air
Central Air Handling Unit
Return air
Exhaust Unit
www.pharmatechbd.blogspot.com
Ventilation with re-circulated air + make-up air
• This slide illustrates a typical re-circulated air setup, where a central unit distributes a mixture of fresh and re-circulated air to different production rooms.
• A part of the exhaust air is collected in a central duct, treated (filtered) and exhausted. The rest is re-circulated (dotted line).
• With control dampers, the proportions of fresh and re-circulated air can be adjusted.
www.pharmatechbd.blogspot.com
Definition of Conditions
air
as builtair air
at rest in operation
www.pharmatechbd.blogspot.com
Qualification / Validation issues
A good design is essential, but it has to be complemented by: Qualification of air handling systems Process validation Maintenance and periodic re-qualification Adequate documentation
www.pharmatechbd.blogspot.com
• We have now seen why air handling plants are necessary, what their components are and what the alternatives are in their design.
• However, we also have to remember that, once a ventilation system is installed, it is necessary to see how well it performs in comparison to its planned purpose, which is to provide a quality environment of specified parameters for the product.
• .
www.pharmatechbd.blogspot.com
• We are now going to see how it is possible to • achieve • demonstrate • document the required purity in practice by: • systems qualification and• process validation (media fill, for instance)
• Additionally, good maintenance is essential.
• The whole process is of course supported by adequate documentation
www.pharmatechbd.blogspot.com
Qualification (OQ, PQ) (1)
Test
Differential pressure on filters
Turbulent / mixed airflow Description Uni-directional
airflow / LAF
Room differential pressure
Airflow velocity / uniformity
Airflow volume / rate
Parallelism
Air flow pattern
2 2
N/A 2, 3
2, 3 Optional
2 2
2 N/A
2 3
1 := As built (ideally used to perform IQ)
2 = At rest (ideally used to perform OQ)
3 = Operational (ideally used to perform PQ)
IQ tests are not mentioned on this slide
Annex 1, 17. 4
www.pharmatechbd.blogspot.com
Ask the question: “What are the alert and action Limits and what procedures are followed if these points are exceeded?”
www.pharmatechbd.blogspot.com
Qualification (OQ, PQ) (2)
Test Turbulent / mixed airflow DescriptionUni-directional
airflow / LAF
Recovery timeRoom classification (airborne particle)Temperature, humidity
N/A 2
2 2,3
N/A 2,3
1 := As built (ideally used to perform IQ)
2 = At rest (ideally used to perform OQ)
3 = Operational (ideally used to perform PQ)
Annex 1, 17. 4
IQ tests are not mentioned on this slide
www.pharmatechbd.blogspot.com
Microbiological validation1. Definition of alert / action limits as a
function of cleanliness zone
1. Identification and marking of sampling points
2. Definition of transport, storage, and incubation conditions
www.pharmatechbd.blogspot.com
air
Sampling point
Cleanroom monitoring program (1)
Cleanrooms should be monitored for micro-organisms and particles
www.pharmatechbd.blogspot.com
Cleanroom monitoring program (2)
Routine monitoring program as part of quality assurance
Additional monitoring and triggers
1. Shutdown 2. Replacement of filter elements3. Maintenance of air handling
systems4. Exceeding of established limits
Annex 1, 17.37
www.pharmatechbd.blogspot.com
Cleanroom maintenance program (1)
Schedule of Tests to Demonstrate Continuing Compliance
Test Parameter Class Maximum TimeInterval
Test Procedure
A, B<= ISO 5
6 Months ISO 14644 -1 Annex AParticle Count Test
C, D> ISO 5
12 Months ISO 14644 -1 Annex A
Air Pressure Difference All Classes 12 Months ISO 14644 -1 Annex B5
Air Flow All Classes 12 Months ISO 14644 -1 Annex B4
www.pharmatechbd.blogspot.com
Cleanroom maintenance program (2)
Schedule of Additional Optional Tests
Test Parameter Class Maximum TimeInterval
Test Procedure
Installed Filter Leakage All Classes 24 Months ISO 14644-1 Annex B6
Containment Leakage All Classes 24 Months ISO 14644-1 Annex B4
Recovery All Classes 24 Months ISO 14644-1 Annex B13
Air Flow Visualisation All Classes 24 Months ISO 14644-1 Annex B7
www.pharmatechbd.blogspot.com
1. Description of installation and functions2. Specification of the requirements3. Operating procedures4. Instructions for performance control5. Maintenance instructions and records6. Maintenance records7. Training of personnel (program and records)
Documentation requirements
www.pharmatechbd.blogspot.com
1. Verification of design documentation, including description of installation and functions specification of the requirements
2. Operating procedures3. Maintenance instructions4. Maintenance records5. Training logs6. Environmental records 7. Discussion on actions if OOS values8. Walking around the plant
Inspecting the air handling plant
www.pharmatechbd.blogspot.com
Air handling systems:
Play a major role in the quality of pharmaceuticals Must be designed properly, by professionals Must be treated as a critical system
Conclusion
www.pharmatechbd.blogspot.com
This series of explanations will now be followed by:
Group discussion, with a simple exercise Short test
Further proceedings
www.pharmatechbd.blogspot.com
Group Session
www.pharmatechbd.blogspot.com
Group Session – modified layout
MAL = Material Air Lock
PAL = Personnel Air Lockwww.pharmatechbd.blogspot.com