1 ENVIRONMENTAL CONTROL Air Handling, Air Conditioning and Refrigeration Compiled & delivered by, Mr. N. G. Shinde Assistant Professor, Department of Pharmaceutics, Satara College of Pharmacy, Satara ENVIRONMENTAL CONTROL Air Handling, Air Conditioning and Refrigeration Compiled & delivered by, Mr. N. G. Shinde Assistant Professor, Department of Pharmaceutics, Satara College of Pharmacy, Satara

Factors contributing to quality products Starting materials Personnel Procedures Validated processes Equipment Premises Environment Packing materials

The manufacturing environment is critical for product quality 1. Light 2. Temperature 3. Humidity 4. Air movement 5. Microbial contamination 6. Particulate contamination 7. Uncontrolled environment can lead to p roduct degradation ä product contamination  loss of product and profit The manufacturing environment is critical for product quality 1. Light 2. Temperature 3. Humidity 4. Air movement 5. Microbial contamination 6. Particulate contamination 7. Uncontrolled environment can lead to p roduct degradation ä product contamination  loss of product and profit

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

Cross-Contamination What is Cross-Contamination ? Contamination of a starting material, intermediate product, or finished product with another starting material or product during production.

Cross-Contamination 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

Contamination Contaminant from Environment Operators Contaminant from Equipment Cross Contamination Product from Environment Operators Product from Equipment Cross-Contamination

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

9 “ CLEANLINESS, CLEANLINESS and CLEANLINESS ”

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13 A Heating system (“H” in HVAC) A Ventilating system (“V” in HVAC) A Cooling system (“AC" in HVAC)

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HVAC 16 HVAC – Heating, Ventilation, Air-conditioning Temperature Humidity Pressure Ventilation 68°F (20°C) and 75°F (25°C) 30% relative humidity (RH) and 60% RH A slightly positive pressure to reduce outside air infiltration. Rooms typically have several complete air changes per hour

What can HVAC do? 17  Control airborne particles, dust and micro- organisms  Maintain room pressure (delta P)  Maintain space moisture (Relative Humidity)  Maintain space temperature  Control airborne particles, dust and micro- organisms  Maintain room pressure (delta P)  Maintain space moisture (Relative Humidity)  Maintain space temperature

What HVAC can’t do? 1. HVAC can not clean up the surfaces of a contaminated places, room or equipment 2. HVAC can not compensate for workers who do not follow procedures 18

Block Diagram 19

Local heating systems heat source, distributors, and Portable electric heaters, built-in electric resistance heaters, infrared heaters and wood stoves Local cooling systems Air circulation devices, such as paddle or desk fans Local ventilating systems Local air-conditioning systems 20 Components Of HVAC System

21 Clean Room Class Class Limits "not to exceed" particles per cu ft for particle sizes shown 0.1  m0.2  m0.3  m0.5  m5m5m Classification Of Clean Room : REGULATORY POINT OF VIEW US Federal Standard 209E

HEPA FILTER : At Glance 22 High Efficiency Particulate Air capture a minimum of 99.97% of contaminants at 0.3 microns in size.

: Monitoring and Testing of HVAC Clean Room Physical Air borne particulate matter HEPA integrity Air Changes per hour Flow pattern in room Pressure Diff across filter Temperature and Humidity Microbiological Settling Plate Slit Plate Surface Sampling

ParameterTest Frequency Particulate monitoring in air HEPA filter integrity testing (DOP testing Air change rates Air pressure differentials Microbiological monitoring by settle plates Temperature and humidity 6 Monthly Yearly 6 Monthly Daily 24

Air flow patterns Filtered air entering a production room or covering a process can be l turbulent l uni-directional (laminar) ä GMP aspect ä economical aspect New technologies: barrier technology/isolator technology. Filtered air entering a production room or covering a process can be l turbulent l uni-directional (laminar) ä GMP aspect ä economical aspect New technologies: barrier technology/isolator technology.

Uni-directional / laminar displacement of dirty air Turbulent dilution of dirty air 0,30 m/s Air flow patterns

Prefilter Air flow patterns AHU Main filter Uni-directional Turbulent 1 23 Annex 1, 17.3

Workbench (vertical ) Cabin/ boothCeiling Air flow patterns

Positioning of filters Filter in terminal position AHU mounted final filter Production Room + HEPA Filter

AHU Prefilter Final filter 21 Positioning of filters

Air re-circulation The filtered air entering a production room can be l 100% exhausted or l a proportion re-circulated ä GMP aspect ä economical reasons

Ventilation with 100% fresh air (no air re-circulation) W Washer (optional) Central Air Handling Unit Production Rooms Exhaust Unit

Ventilation with re-circulated air + make-up air Central Air Handling Unit Return air Exhaust Unit

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37 Air conditioning It is the process of treating the air so as to control its temp., humidity, cleanliness and distribution simultaneously to meet the requirements of the conditioned space. Applications: Promoting the human comfort Maintenance of proper conditions for manufacture, processing and preserving of material and equipment. Environmental test chamber Maintenance of animal and equipment Air conditioning It is the process of treating the air so as to control its temp., humidity, cleanliness and distribution simultaneously to meet the requirements of the conditioned space. Applications: Promoting the human comfort Maintenance of proper conditions for manufacture, processing and preserving of material and equipment. Environmental test chamber Maintenance of animal and equipment

38 Types of equipment 1.Self contained air conditioner/ Unitary/ Packaged 2.Central air conditioner/ Field erected 1.Self contained air conditioner/ Unitary/ Packaged These system include window mounted or wall bracket conditioners. Most of this units are air cooled through water cooled type. Room air enters the casing at the front panel. It is mixed with part of the outdoor air and this mixture is forced over a cooling coils by a centrifugal fans.

39 Central air conditioning system In this system one or several areas are air conditioned by duct network. Air cleaning is done by filters. Cooling is achieved by using water or by direct expansion in refrigerated coils or air washers. Heating is achieved by using steam or hot water coils. Central air conditioning system In this system one or several areas are air conditioned by duct network. Air cleaning is done by filters. Cooling is achieved by using water or by direct expansion in refrigerated coils or air washers. Heating is achieved by using steam or hot water coils.

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43 Definitions Humidity: The amount of water vapour present in moist air per unit mass of the dry air in given volume. Dew point: The temperature at which the liquid droplets just appear when the moist air is cooled continuously. Dry bulb temperature: The actual temperature of gas or mixture of gases indicated by an error free temperature measuring device. Wet bulb temperature: Dynamic equilibrium temperature attained by a water surface when exposed to air under adiabatic conditions.

44 Measurement of humidity Direct method A known volume of air is drawn through phosphorus pentoxide. The moisture present in the air get absorbed and determined by chemical or gravimetric method. From the difference of initial and final masses humidity is estimated. Measurement of humidity Direct method A known volume of air is drawn through phosphorus pentoxide. The moisture present in the air get absorbed and determined by chemical or gravimetric method. From the difference of initial and final masses humidity is estimated.

45 Psychrometric methods Determination of wet bulb and dry bulb temperatures. Psychrometric methods Determination of wet bulb and dry bulb temperatures.

46 Dew point method In this method formation of mist and disappearance of mist is considered and dew point is calculated. A cooled and polished disk is placed in vessel containing the gas whose humidity is to be determined. The temp. of the disk is gradually lowered using liquid air or liquid carbon dioxide or ether. Soon mist condenses on polished surface. The temperature at which mist just appeared is noted. The temp. of disk is slowly increased and disappearance of mist is observed and temp. is noted. The average of these two temperatures represent accurate dew point. Dew point method In this method formation of mist and disappearance of mist is considered and dew point is calculated. A cooled and polished disk is placed in vessel containing the gas whose humidity is to be determined. The temp. of the disk is gradually lowered using liquid air or liquid carbon dioxide or ether. Soon mist condenses on polished surface. The temperature at which mist just appeared is noted. The temp. of disk is slowly increased and disappearance of mist is observed and temp. is noted. The average of these two temperatures represent accurate dew point.

47 Humidification The process of increasing the moisture in the air. Approaches: The air may be brought in contact with water in such a way that only a part of the water is evaporated. Cooling towers are utilized. The incoming air is heated to higher temp. then cooled adiabatically with water to achieve desired humidity. The air may be mixed with stream of air of higher humidity. Humidification The process of increasing the moisture in the air. Approaches: The air may be brought in contact with water in such a way that only a part of the water is evaporated. Cooling towers are utilized. The incoming air is heated to higher temp. then cooled adiabatically with water to achieve desired humidity. The air may be mixed with stream of air of higher humidity.

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49 Dehumidification Removal of moisture from the air. Dehumidification is achieved by bringing the moist air in contact with cold surface (solid/liquid). In pharmaceutical industry many operations are carried out at stated temperature and humidity to get optimum results. In many parts of India (Bengal, Kerala) air is very humid so it becomes very difficult to carryon operations with hygroscopic substances even in AC room. Hence, dehumidifiers are installed for such operations. Dehumidification Removal of moisture from the air. Dehumidification is achieved by bringing the moist air in contact with cold surface (solid/liquid). In pharmaceutical industry many operations are carried out at stated temperature and humidity to get optimum results. In many parts of India (Bengal, Kerala) air is very humid so it becomes very difficult to carryon operations with hygroscopic substances even in AC room. Hence, dehumidifiers are installed for such operations.

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Air handling systems: l Play a major role in the quality of pharmaceuticals l Must be designed properly, by professionals l Must be treated as a critical system Conclusion

52 Thank you