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Types of clean room, component of HVAC system, HVAC qualification and validation parameter


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Utility Validation (HVAC Validation System):

Utility Validation ( HVAC Validation System) Prepared By – Sojitra Rajanit Guided by – Hasumati Raj. Shree Dhanvantary Pharmacy College, Kim 1


Introduction Types of clean room Component of HVAC System HVAC Qualification Validation Parameter Contents 2


HVAC – H eating Ventilation and Air Conditioning The need and reason for pharmaceutical air handling system The technical requirements for air handling system Different types of air handling system Qualification and Validation requirements Introduction 3

What is clean room ?:

What is clean room ? A room in which the concentration airborne is controlled and which is constructed and use in a manner to minimize the introduction , generation and retention of particle inside the room and in which other relevant parameter. e.g., temperature, humidity and pressure are controlled as necessary 4

Why clean room necessary ?:

It controls 3 types of contamination transfer Air borne contamination Direct contamination by personnel, equipment etc. Contamination from fluids like cleaning fluids, solution etc. As air borne particulate are reduced , chances of particles entry in the process reduced. Protect product , personnel and environment Why clean room necessary ? 5

Types of clean room ?:

Horizontal clean room – Horizontal laminar flow (HEPA filter in wall force clean air from one side of room to other.) Vertical clean room – Vertical laminar flow (HEPA filter on the ceiling push clean air down to the floor.) Types of clean room ? 6

The manufacturing environment is critical for product quality:

Environment consist of, Light Temperature Humidity Air movement Microbial contamination Particulate contamination Uncontrolled environment can be leads to product degradation Product contamination Loss of product and profit The manufacturing environment is critical for product quality 7

HVAC consist of following parts:

Air conditioner AHU s Dehumidifier/Heater Filter Dust extractors Ducting Supply fans Smoke detector Dumpers humidity/ temperature/ pressure sensor Bag filters Heating/ cooling coil HVAC consist of following parts 8

HVAC Specification:

HVAC Specification 9 Temperature 18-23 c Relative Humidity 45% ± 5% Dry powder- 30% ± 5% Moisture sensitive drug- 5% ± 5% Air Velocity 80-120 ft/min Air flow Laminar Airflow Pressure Gradient 15 Pascal Particulate Count NMT 100 Particle of 0.5 mm/ Temperature 18-23 c Relative Humidity 45% ± 5% Dry powder- 30% ± 5% Moisture sensitive drug- 5% ± 5% Air Velocity 80-120 ft/min Air flow Laminar Airflow Pressure Gradient 15 Pascal Particulate Count


21 CFR part 211 (requirement for building and facilities) Under 211 .42 (C) Operation shall be perform within the specifically defined area and such other control necessary to prevent contamination. Temperature and humidity controlled. A system of monitoring environmental condition. Under 211.46 (C) Air filtration system including pre-filter and particulate matter air filtration shall be used when appropriate on air supply to production areas. USFDA 10

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Air flow pattern:

Air flow pattern 12

HVAC Qualification:

Validation master plan User requirement specification Design qualification Installation qualification Operation qualification Performance qualification Re-qualification HVAC Qualification 13

User requirement specification:

Room dimension Machine horse power and lighting load Temperature R.H Pressure gradient Class of air Air changes per hour User requirement specification 14

Design qualification:

Technical data: General Make and model no. Noise level Overall dimension in mm. Weight in kg. Design qualification 15

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C asing Outer skin Inner skin Material of frame structure Insulation material and thickness Fan Type and make Fan speed in RPM Fan BHP Recommended motor Operating voltage and frequency 16

Design qualification:

Chilled water and hot water coils Make Air quantity through coil Face area sq. feet Selected water velocity across coil Material of cooling coil Tube diameter Design qualification 17

Installation qualification:

System Description Equipment Delivery Utilities / Facility / Environment Assembly & Installation Installation qualification 18

Installation qualification:

IQ Should include, Instrumentation checked against current engineering drawings and specifications Verification of materials of construction Installation of equipment and with piping Calibration of measuring instruments requirements Collection and collation of supplier operating and working instructions and maintenance requirements Installation qualification 19

Installation qualification:

Practical aspect of IQ (Cont….) Calibration of measuring instruments. Calibration of additionally used instruments. Initial cleaning records. Basic commissioning checks. Maintenance requirements. IQ process checks that the correct components are installed in the correct location. Materials of construction Spare parts Change controls Installation qualification 20

Installation qualification:

IQ Document should contain, Instrument name, model, I.D. No., Personnel responsible for activities and Date. A fully verified installation that complies with the documented design. (all deviations will have been recorded and assessed.) All equipment documentation and maintenance requirements would be documented. Completed calibration of measuring instruments. Verification of Materials of construction. Installation qualification 21

Operation qualification:

Operation Qualification Checks , Ability to provide air of sufficient quality and quantity to ensure achievement of specified clean room conditions. Ability to maintain temperature, relative humidity and pressure set points. Ability to maintain any critical parameters stated in the DQ consistently. Operation qualification 22

Operation qualification:

Includes the tests that have been developed from knowledge of processes, systems and equipment. Tests to include a condition or a set of conditions encompassing upper and lower operating limits, sometimes referred to as ‘worst case’ conditions. Operation qualification 23

Operation qualification:

IQ reports must be completed and signed off. OQ protocols to be written and approved prior to completion. Measurement reports are required to demonstrate achievement of critical parameters as detailed in DQ. E.G : * All relevant SOPs should be in place * Temperature measurement report * Humidity measurement report * Differential pressure measurement report * Air flow direction measurement report * Room particle count measurement report * All drawings etc. – done in ‘as-built’ status * All maintenance/ cleaning instructions available * All O & M staff to be trained to use and maintain the system. * Sign off. (Compliance Certificate by Engineering Dept. & QA) Operation qualification 24

Performance qualification:

The purpose of PQ is to verify and document that an HVAC system provides acceptable control under ‘ Full Operational ‘ conditions. PQ should follow successful completion of IQ and OQ. PQ verifies that over time, the critical parameters, as defined in the DQ are being achieved. Performance qualification 25

Performance qualification:

PQ Should include, Tests, using production materials, qualified substitutes or simulated product, that have been developed from knowledge of the process and facilities, systems or equipment. Test to include a condition or set of conditions encompassing upper and lower operating limits. PQ is used to demonstrate consistent achievement of critical parameters over time .( under manufacturing conditions) PQ is ongoing. Performance qualification 26

Qualification Complete \Documentation:

Verification of design documentation, including Description of installation and functions Specification of the requirements Instructions for performance control Operating procedures Maintenance instructions Maintenance records Training of personnel (program and records) Environmental records Discussion on actions if OOS values Walking around the plant Finally certification (Sign Off) by Engineering, User (Production) and QA Heads . Qualification Complete \Documentation 27

Validation :

Document act of proving that any procedure, process, system / equipment ACTUALLY leads to expected results . To ensure that system provides continuously required environmental conditions. Validation 28

Validation Parameter:

HEPA filter leak test. Temperature control test. Humidity control test. Test for air flow pattern. Pressure control test. Particle count test. Airborne microbial sampling. Air flow velocity test. Validation Parameter 29

HEPA filter leak test:

Purpose : To ensure against filter damage. Method : Installation of DOP aerosol (0.3mm) upstream of the filter through a test port and search for leak downstream with an aerosol photometer. Acceptance criteria : An unacceptable leak is defined as 0.01% of the reference calibration curve. HEPA filter leak test 30

Temperature control test:

Purpose : To demonstrate the ability to control temp. at 72F ± 10% all year round. Equipment : Calibrated dry-bulb thermometer, thermocouple and recorder. Method : Air conditioning system and all light to be in continuous operation at least 24hr prior to test. Measure and record temp at 15 min internal for 2hr . Repeat the test for at rest and dynamic condition. Acceptance criteria : It should be capable of maintaining a dry-bulb temp. of 72F ± 10% . Temperature control test 31

Humidity control test:

Purpose : To demonstrate the capability to control humidity at specified level for each room. Equipment : Calibrated dry-bulb and wet bulb thermometer and recorder . Method : Measure and record humidities at rest and dynamic condition. Operate the system at least 6hr prior to test. Record the wet/dry temp. at the beginning and at end. Acceptance criteria : RH should be within tolerance limit. Humidity control test 32

Air flow pattern test:

Purpose : To demonstrate minimum turbulence and determine air flow pattern. Equipment : white visible or yellow smoke generator, anemometer, 35mm camera. Method : Generate white smoke. Film the smoke as it travel. Measure and maintain temp. at 15min interval for 2hr. Repeat the test for as rest and dynamic condition. Acceptance criteria : It should be capable of maintaining a dry bulb temp. of 72F ± 10 %. Air flow pattern test 33

Pressure control test:

Purpose : To demonstrate the capability of system to control pressure level within the specified levels. Equipment : Pressure gauge. Method : All HVAC and laminar units to be used in continuous operation during the test. All doors and sterile facility must be closed. Pressure reading are taken with high and low pressure tubings at selected location. Acceptance criteria : Pressure differentials should be above 0.02 at the primary environments. Pressure control test 34

Particle count test:

Purpose : To establish that within clean room, a count of less than 100 particle per cubic foot, 0.5mm is maintained. Equipment : Light scattering particle counter. Method : Using particle analyzer, count particle grater than or equal to 0.5 microns at height of 40 inches in the center of each grid. Acceptance criteria : The particulate count shall not be exceed 100 particle of 0.5 microns per cubic foot of air. Particle count test 35

Air borne microbial sampling:

Purpose : To determine air borne microbial contamination level. Equipment : Andersons air sampler (1 cubic foot/min). Method : Sampling time 20mins at every location. Plates are placed in an incubator, maintained inverted to prevent condensation drop for a periods of 18-24 hrs. at 35 c. After incubation the number of colonies on each plates is counted using a standard bacterial colony counter. Acceptance criteria : No of colonies per cubic meter of air, limit established is 3.5 colonies in class 100. Air borne microbial sampling 36

Air flow velocity test:

Purpose : To demonstrate that air system is balanced and capable of delivering sufficient air volume. Equipment : Hot wire anemometer. Method : Measurement take at 15min intervals. Record the pressure readings (in inches) Acceptance criteria : Average measure clean air velocity shall be higher than 90 foot/min and not exceeding 150 foot/min at 6 inches downstream from the filter face. Air flow velocity test 37


“Validation in pharmaceutical industry” ; edited by P.P. sharma ;first edition 2007 ; 169-192 “Pharmaceutical Process Validation” ; An international 3 rd edition; edited by R. A. Nash and A. H. Wachter; 413-432 References 38

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