VALIDATION OF HVAC

SYSTEM
Prepared By:

Bilal Tahir
Ph.D Pharmaceutics
Roll no: 7

Submitted to:

Dr. Nasir Abbas

University of the Punjab.

Introduction
Is the science and practice of controlling indoor
climate to provide healthy and comfortable
interior conditions in a well designed environment
HVAC role in pharmaceutical industry
Heating, ventilation and air conditioning play an
important role in ensuring the manufacture of
quality pharmaceutical products.
A well designed HVAC system will also provide
comfortable conditions for operators.
HVAC system plays a role in product protection,
personnel protection, and environmental
protection.

INTRODUCTION
HVAC consists of,
1. Air conditioner
2. AHUs
3. Dehumidifier / Heater
4. Filters (Pre & HEPA)
5. Dust Extractors
6. Ducting (For delivery of controlled air)
7. Supply Fans
8. Smoke Detector
9. Dampers
10.Humidity / Temperature / Pressure sensors
11.Bag Filters
12.Heating / Cooling Coils

INTRODUCTION
HVAC (AHU) is
HEART
of Pharmaceutical Industries

INTRODUCTION
Area - 1

Area - 3

I
M
P
U
R
E

Area - 4

A
I
R

Area - 2

Impure Air

HVAC

Pure Air

Return Air

Impure Air
Exhaust

HVAC QUALIFICATION
To ensure that equipment is designed as
per requirement, installed properly.
Action of proving that any equipment
works correctly and leads to the
expected results.

QU
LIF
I

CA
TIO
N

HVAC QUALIFICATION
Validation Master
Plan
User Requirement
Specification
Design Qualification
Installation
Qualification
Operation
Qualification
Performance
Qualification
Re- Qualification.

VALIDATION

THE VALIDATION MASTER PLAN

This document should contain

Validation policy
Organizational structure of validation
activities
Summary of facilities, systems,
equipment and processes to be
validated
Documentation format to be used for
protocols and reports
Planning and scheduling
Change control

USER REQUIREMENT SPECIFICATION

It mainly requires:
Room temperatures and relative
humidities
Clean room classifications for the areas
i.e. B. C. or D.
Single pass or re-circulated HVAC
systems ?
Room pressures / Air flow directions
GMP requirements.

USER REQUIREMENT SPECIFICATION

Capacity of HVAC depends on,

1.
2.
3.
4.
5.
6.

Room Volume.
No. of Air Changes Required.
Production / Consumption Data
Seasonal fluctuation.
Air Classification of Rooms.
Future Development.
10

USER REQUIREMENT SPECIFICATION

Parameters to be defined in Levels of
Protection :

Air
1.
2.
3.
4.
5.

cleanliness requirements
filters type and position,
air changes,
air flow patterns,
pressure differentials,
contamination levels by particulate
matter & micro-organisms.
11

User Requirement Specification

should be approved by Production,

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.
12
3. Detailed Air Flow Schematics.
4. Detailed layout drawing of the

DESIGN QUALIFICATION
Compliance with GMPs and other
regulatory requirements.
Ensures that design,
1. meets the user requirements.
2. details facility airflow and pressure
cascade philosophy.
3. takes into account process and
personnel flow (cross-contamination
issues)
4. Details materials of construction.
5. Details safety requirements.
6. Full details of the intended

13

INSTALLATION QUALIFICATION

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

14

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

15

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

16

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.

17

OPERATION QUALIFICATION
ISPE definition : The purpose of OQ is to
establish, through documented testing,
that all critical components are capable
of operating within established limits and
tolerances.
The purpose of OQ is to verify and
document that an HVAC system provides
acceptable operational control under atrest conditions.

18

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.

19

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.
20

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
All drawings etc. done in as-built status
All maintenance/ cleaning instructions available

21

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.
22

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

23

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

24

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.

25

VALIDATION PARAMETERS

1.
2.
3.
4.
5.
6.
7.
8.
9.

Air flow measurement

Room air changes per hour.
Filter Integrity Testing (HEPA Leak test)
Pressure Differentials
Particulate count measurement
Recovery test
Temperature and Relative Humidity
Air Flow Pattern
Microbial Count
26

VALIDATION PARAMETERS
A.

PHYSICAL TESTS
A1.
NON-VIABLE PARTICLE COUNTS
Equipment
Optical Particle Counter (Discrete Particle
Counter)
Air sample is drawn into the instrument &
passed through light scattering device. The
signal that this generates is electronically
processed to display particle counts at
different size ranges.
Sample Volume
1 cubic ft
Sample Time
1 Min

27

VALIDATION PARAMETERS
Sample Location (ISO Standards)
No. of sampling location = NLT Sq. Rt.A
Where
A = Area of entrance plan
in Sq.Meter
No. of location rounded to nearest
higher integer
Minimum location 3
Evenly distributed within the area
under test and at a position related to
the working activity (typically at bench
height 1m from the floor and NMT 1 Ft
from work station.).

28

VALIDATION PARAMETERS
Frequency
GMP compliance Quarterly

Acceptance Criteria

29

VALIDATION PARAMETERS
A2. PRESSURE DIFFERENTIALS
Introduction
Correct degree of overpressure can be maintained
relative to the adjacent areas of lower classification to
ensure that air moves from clean areas to less clean
areas.
Equipment
Electronic manometer (portable and easy to use),
Incline manometer
Sample Location
Between adjacent areas connected either by a door or
grille.
Frequency of sampling
Continuously by gauges / manometer & recorded daily.

30

VALIDATION PARAMETERS
Acceptance Criteria
> 10 Pa
between classified area &
adjacent area of lower classification
> 15 Pa
between classified area &
unclassified area

Action
HEPA filter blockage
Increase fan speed
Increase air flow to specific area by
altering dampers
31

VALIDATION PARAMETERS
A3.

AIRFLOW VELOCITY

Equipment :- Anemometer.

Reading should be taken 10cm from the

surface of filter.
Record velocity reading from all the four
corners and the Centre of the filter
surface.
Repeat twice at each location
For Grade A laminar flow workstations,
the air flow rates shall be 0.3 meter per
second + 20% (for vertical flows) and
0.45 + 20% (for Horizontal flows)

32

VALIDATION PARAMETERS
Air velocity exceeding the stated value
may cause excessive air movement &
affect work zone protection.
Air velocity below the limit may be
insufficient to maintain critical work
zone protection.
Action: Deviation indicates blockage of
filter
Solution : Alteration of fan speed
HEPA filter
replacement

33

VALIDATION PARAMETERS
A4. HEPA FILTER INTEGRITY TEST
(DOP Test)
Purpose : To confirm that there is no
damage to filter, seals and there is no
leakage of particles.
Equipment : 1. Aerosol generator (Using
Dioctylphthalate)
2. Photometer
Scan at 1 inch from filter surface. Traverse
at NMT 10Ft. Min. Cover entire range.
Make separate passes at peripheries.
34

VALIDATION PARAMETERS
A5. TEMPERATURE & RELATIVE HUMIDITY

Use a sling psycrometer to measure

the dry bulb and wet bulb temperature of
the air.
Check the wick of the sling psycrometer,
it should be always in wet conditions in
order to record correct wet bulb
temperature.
Sling the psycrometer in air for about a
minutes time and record the dry bulb
and wet bulb temperature.
Check the wet bulb depression i.e.
difference between dry bulb and wet

35

VALIDATION PARAMETERS
ACCEPTANCE CRITERIA
Temperature : NMT 27
degree centigrade
Humidity : NMT 55 %
FREQUENCY :Daily

36

VALIDATION PARAMETERS
A6.
AIR CHANGE RATE (ACR)
Introduction
Conventional clean rooms operate on the
principle that the air supplied to the room is
of sufficient quantity to dilute or remove the
contamination generated within the room.
Measurement of the air supply volume and
determination of the air change rate (ACR) is
a measure of the frequency of air turnover in
the clean room.
This gives some idea as to how quickly
contamination may be removed from the
clean room provided there is acceptable
mixing of air in the room.
The ACR can be determined by measuring
the mean air velocity at the supply HEPAs or

37

VALIDATION PARAMETERS
Equipment
Anemometer
Sample locations
At least four positions are tested
across the filter or grille face to
obtain the mean supply air velocity.
Frequency of sampling
GMP compliance Quarterly
38

VALIDATION PARAMETERS
Results and interpretation of results
The ACR (per hour) can be calculated using the
following formula: ACR = Air supply volume (m/s) x
3600/ Room volume (m)
Air Volume = Sum ( Avg. Velocity x Filter area)
Where there is more than one supply HEPA in a room
the air supply volume for each filter should be
determined and the volumes summed (to give a total
air supply volume) before multiplying by 3600 and
dividing by the room volume.
To achieve the level of cleanliness in an aseptic room
and a clean support room the ACR should be greater
than 20 air changes per hour.

39

VALIDATION PARAMETERS
Requirement : Class B = 60, C & D = 20 ACPH
Action
Change the filter

ACR to be rebalanced

B.

MICROBIOLOGICAL TESTS

Solid growth media (e.g. settle and contact

plates) Soybean Casein Digest Agar medium
can be used for both Bacteria & Fungi tested.
The recommended size of solid media is 90 mm
in diameter (for settle plates)
55 mm (surface area 25 cm) for contact plates.

40

VALIDATION PARAMETERS
Sampling conditions
Sampling in the at rest condition may be
continued at an agreed frequency to
monitor baseline contamination levels.
The operational conditions and the
activities being performed at the time of
testing should be recorded.
Incubation conditions
Incubation of samples, inverted, at 20 25C for at least 5 days is suitable for the
growth of mould and fungi.
Incubation of samples, inverted, at 30 -

41

VALIDATION PARAMETERS
Recommended Limits for
microbiological monitoring of clean
areas

Total Viable Count

(Guidelines)
Conditions : In operation
Grade
EU
Schedule M
Sampling
(90mm / 4 Hrs)
(1000cc)

A
B
<7
C
<10

(90mm / 2 Hrs)

<1
<10

<1

<100

<50

US

(90mm / 4 Hrs)

<1
<5

Air

<1
<3
<5

42

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

43

s
k
n
a
Th

44