This document outlines the validation process for an HVAC system used in a pharmaceutical plant. It discusses the need for HVAC systems to control contamination and provide comfortable working conditions. The validation process includes creating a validation master plan, writing user requirement specifications, designing and qualifying the system, installing and qualifying it, operating and performance qualifications, and requalification. Key validation parameters that are measured include air flow, room air changes, filter integrity, pressure differentials, particulate counts, temperature and humidity controls, and air flow patterns.

1. VALIDATION OF HVAC SYSTEM
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PRESENTED BY :
Mr. Nagare Digambar
F.Y.M Pharm
Quality Assurance
GUIDED BY :
Dr. Patel V. P.
HOD of Quality
Assurance Dept.

2. CONTENT
 Introduction
 What is clean room?
 Why clean room necessary?
 AHU
 HVAC Qualification
 Validation parameter
 References
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3. INTRODUCTION
 Heating, ventilation and air-conditioning (HVAC) system are
used in the pharmaceutical plant to prevent contamination and
to provide comfortable working conditions.
 HVAC are called Air Handling Units (AHU)
 AHU comprises of air supply, coarse filtration, heating or
cooling and HEPA filtration.
 Flow of air into the room may be horizontal or vertical.
 AHU producing class A (class 100 L) Class B (class 100 T)
Class C (class 10,000) HEPA filters may be located in AHU.3/20/2017 3

4. AHUs in several categories of premises:
 Dust can be roughly classified by particle size:
1) Coarse dust: (50 to 500 µ )
2) Fine dust: (1.0 to 50 µ )
3) Ultrafine dust: (0.5 to 1.0 µ )
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5. WHAT IS CLEAN ROOM?
 A room in which the concentration of airborne particle
is controlled and which is constructed and used in a manner
to minimize the introduction, generation and retention of
particles inside the room and in which other relevant
parameters.
 e.g.. Temperature, humidity and pressure, are controlled
as necessary.
(ISO 14644-1)
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6. 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, solutions etc.
 As airborne particulate are reduced, chances of particles entry
in the process reduced.
 Protection product, personnel & environment.
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7.  Protection product are three level
Level 1: General
an area routine house keeping and maintenance
Level 2: Protected
an area to protect the exposed drug sub from
contamination and degradation
Level 3: Controlled
an area controlled and monitored to prevent
contamination or degradation of drug.3/20/2017 7

8. CLASSIFICATION OF CLEAN ROOM
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9. FOUR BASIC PRINCIPLES OF CLEAN ROOM
Not To Bring Any Dust
Not To Accumulate Any Dust
Not To Generate Any Dust
To Remove Any Dust Quickly
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10. TYPES OF CLEAN ROOMS
 Horizontal Clean Room – Horizontal
Laminar flow
(HEPA filters in a wall force clean air from one
side of the room to other.)
 Vertical Clean Room – Vertical Laminar flow
(HEPA filters on the ceiling push clean air down
to the floor.)
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11. AIR FLOW PATTERN TURBULENT AIR FLOW
AND LAMINAR AIR FLOW
some of the Important criteria are:
 Building structure & finishers
 Air-filtration
 Air change rate
 Room pressure
 Location and air terminals
 Temperature
 Humidity
 Flow of personnel
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12. Air flow pattern
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Prefilter
AHU
Main filter
Uni-directional TurbulentTurbulent
1 2 3

13. AIR HANDLING UNITS (AHU)
 May need to supply heating, cooling, or both
 A furnace generates heat
◦ Fuel oil or natural gas
◦ Electric heating elements
 A refrigeration system absorbs heat
◦ Air conditioner
◦ Heat pump
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14.  Smaller air handlers may contain a fuel-burning heater or a
refrigeration evaporator placed directly in the air stream
 Large commercial air handling units contain coils that
circulate water
◦ Boiler provides hot water or steam
◦ Chiller provides chilled water
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15. Typical AHU components:
1. Supply duct
2. Fan compartment
3. Flexible connection
4. Heating and/or cooling coil
5. Filter compartment
6. Return and fresh air duct
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16. AIR HANDLING UNITS (AHU) Consist of
1) Circulating system : circulated air used in the AHU, HEPA
filters.
2) Full fresh air system : AHU can be designed with 100%
supply of fresh air.
Low Humidity air and rotating desiccant wheel can be used.
 Positioning of chemical drier as follows:
-full flow of fresh / return air
-bypass air flow
-return air only
-fresh air only 3/20/2017 16

17.  Full fresh air system:
a) Displacement concept (low pressure differential ,high air flow)
-low turbulent displacement air flow greater than 0.2 m/s
-pressure differential 5 to 20 Pascal.
-cubicle temp 25o C.
-room cooling 40 C.
b) Pressure differential concept (high pressure differential ,low air
flow)
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18. AHU system
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19. HVAC QUALIFICATION
Validation Master Plan
User Requirement
Specification
Design Qualification
Installation
Qualification
Operation Qualification
Performance
Qualification
Re- Qualification.
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20. THE VALIDATION MASTER PLAN
 This document should contain
 Validation policy
 Organizational structure of validation activities
 Facilities, equipment and processes to be validated
 Documentation format to be used for protocols and
reports
 Planning and scheduling
 Change control
 References to documents
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21. USER REQUIREMENT SPECIFICATION
It mainly requires:
Room temperatures and relative humidity's
Clean room classifications for the areas
Single pass or re-circulated HVAC systems
Room pressures / Air flow directions
GMP requirements.
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22. DESIGN QUALIFICATION
Based on the URS supplier designs the equipment-First
step in the qualification of new HVAC systems.
 It documents the design of the system and will include :
1. Functional Specification.
2. Technical / Performance specification for equipment.
3. Detailed Air Flow Schematics.
4. Detailed layout drawing of the system.
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23. INSTALLATION QUALIFICATION
 System Description
 Equipment Delivery
 Utilities / Facility / Environment
 Assembly & Installation
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24. Practical aspect of IQ
 Calibration of measuring instruments.
 Calibration of additionally used instruments.
 Initial cleaning records.
 Maintenance requirements.
 IQ process checks that the correct components are installed in
the correct location.
 Materials of construction
 Spare parts
 Change controls
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25. 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.
Eg: * 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
* Sign off. (Compliance Certificate by Engineering Dept & QA)3/20/2017 25

26. 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.
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27. VALIDATION PARAMETERS
1. Air flow measurement
2. Room air changes per hour.
3. Filter Integrity Testing (HEPA Leak test)
4. Pressure Differentials
5. Particulate count measurement
6. Recovery test
7. Temperature and Relative Humidity
8. Air Flow Pattern
9. Microbial Count 3/20/2017 27

28. REFERENCES
1. “Validation in pharmaceutical industry” ; edited by
P.P. Sharma ; first edition 2007 ; 169-192.
2. “Pharmaceutical Process Validation” ;An
international 3rd edition; edited by R. A. Nash and
A. H. Wachter ; 413-432.
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