validation of hvac system

1. Validation of HVAC system
College: G. Pulla reddy college of Pharmacy
Subject: Pharmaceutical validation
Roll no: 170118885002
Name: K.Vaishali
Class : M. pharmacy, 1st
year
Department: Ph.Analysis

2. Contents
Introduction
Importance of HVAC
Clean rooms
Contamination
Parts of HVAC
Air flow pattern
Qualification of HVAC
Validation parameters
References

3. Air handling units by robatherm are especially designed to minimize the introduction, generation and
retention of particulate and microbial contaminations in pharmaceutical cleanrooms.

4. What is validation?
 Validation is establishing documented evidence which provides a
high degree of assurance that a specific process,equipment,
material, activity or system consistently produces a product
meeting its predetermined specifications and quality attributes.
 It's done on
• Analytical test
• Equipment
• Support process
• Facility system
Types of validation

5. Pharmaceutical utility systems
 Each pharmaceutical (but also cosmetics, food,chemical…) industry’s manufacturing
process use several support system with different functions and distributed with
centralized installations.
 These systems are not necessarily designed and customized for users of a single
production facility, but often serve an entire factory or part of it.
Pharmaceutical
utility systems
Process
waters
Drinking
and
sanitary
water
Electric
power
Air
conditioning
(HVAC
systems)

6. What is HVAC?
Heating, ventilation and air conditioning (HVAC) system
 It is integral component of pharmaceutical facility functionality.
The system is needed for maintenance of a suitable temperature,
for continuous flow of air, which ultimately prevents cross-
contamination and accumulation of air and to ensure the cooling of
air in the premises.

8. Control airborne
particles, dust and
micro-organisms –
Thru air filtration
using high efficiency
particulate air
(HEPA) filters.
Maintain space
temperature -
Temperature can
affect production
directly or indirectly
by fostering the
growth of microbial
contaminants on
workers.
What can HVAC do?

9. Maintain space moisture
(Relative Humidity) –
Humidity is controlled by
cooling air to dew point
temperatures or by using
desiccant dehumidifiers.
Humidity can affect the
efficacy and stability of
drugs and is sometimes
important to effectively
mould the tablets.
Maintain room pressure (delta P) –
Areas that must remain “cleaner”
than surrounding areas must be kept
under a “positive” pressurization,
meaning that air flow must be from
the “cleaner” area towards the
adjoining space (through doors or
other openings) to reduce the chance
of airborne contamination. This is
achieved by the HVAC system
providing more air into the “cleaner”
space than is mechanically removed
from that same space.

10. What HVAC can’t do?
HVAC can not clean up the surfaces of a contaminated surfaces, room or
equipment.
HVAC can not compensate for workers who do not follow procedure.
Impure
air
I
m
p
u
r
e
a
i
r
Impure air

11. WHAT IS CLEAN ROOM?
• A room in which the concentration of air borne 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.
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.
• Protects product, personnel & environment.

12. HOW IT IS ACCOMPLISHED?
• A clean room is continuously flushed with highly filtered air that is forced in
through HEPA filters.
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.)
FOUR BASIC PRINCIPLES OF CLEANROOM
• Not To Bring Any Dust
• Not To Accumulate Any Dust
• Not To Generate Any Dust
• To Remove Any Dust Quickly

13. A
B
F
E D
CG
A. Fluorescent light
standard, UV
sterilization bulbs
available
B. HEPA fan/filter units
provide laminar flow
of micro-filtered air
C. Minihelic gauge
measures filter
backpressure
D. Stainless steel work
surface (available
with electropolishing)
E. Variable-speed
blower adjusts air
speed to meet
containment
requirements
F. Options include
vacuum, DI water
and gas utilities
G. Status Indicator

15. CONTAMINATION
What are contaminants ?
1. Products or substances other than the product being manufactured.
2. Foreign products.
3. Particulate matter.
4. Micro-organisms.
5. Endotoxins (degraded micro-organisms).
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.

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

17. AHUs (air handling unit)

18. Basic HVAC system

19. Airflow Pattern
There are three different types of airflow patterns available for cleanrooms
designs:
Unidirectional (laminar):
The airflow is essentially where the air flows downwards or sideways in an
unimpeded path.

20. Non-unidirectional flow (turbulent flow):
where air streams are other than parallel to one another.
Mixed flow:
where airstreams may be parallel in one part of the cleanroom and not in other
parts.

21. 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.

22. USER REQUIREMENT SPECIFICATION
Customer of the equipment has certain expectations about the equipment which he
wants to use. Some of the general requirements may be stated in the form of certain
parameters
like:
1. Size of the equipment
2. Speed of the equipment
3. Effectiveness of the equipment
4. Availability of spares, change parts, and prompt services at reasonable cost
5. Ease of operation, cleaning, and maintenance
6. Low dust and sound generation
7. Lesser breakdowns
8. Materials of construction
9. Autocontrol system
10. Easy change over
11. Overall good construction and workmanship, etc.

23. DESIGN QUALIFICATION
• Based on the URS supplier designs the equipment-First step in the
qualification of new HVAC systems.
It must include
1. Functional Specification.
2. Technical / Performance specification for equipment.
3. Detailed Air Flow Schematics.
4. Detailed layout drawing of the system.

24. IQ Should include:-
 Instrumentation checked against current engineering drawings and specifications.
 Properly served by the required utilities.
 Verification of materials of construction.
 Installation of equipment and with piping.
 Calibration of measuring instruments.
 Operation manuals and spare parts lists to assure the proper and continuous operation of
the system.
 Components are installed at specified location.

25. IQ should provide documented evidence that the installation
was complete and satisfactory. The purchase specifications,
drawings, manuals, spare parts lists, and vendor details should
be verified during IQ.

26. The purpose of OQ is to establish, through documented testing, that all critical components
are capable of operating within established limits and tolerances.
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.
Includes the tests that have been developed from knowledge of processes, systems and
equipment.

27. OQ protocols to be written and approved prior to completion. It
includes following:
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 maintenance/ cleaning instructions available

28. • 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 the critical parameters, as defined in the DQ are being achieved.
PQ Should include
• Test to include a condition or set of conditions encompassing upper and lower operating
limits.
• Tests should be conducted under “in use”, condition either or simulated as close as possible
to the actual process
• PQ is used to demonstrate consistent achievement of critical parameters over time. ( under
manufacturing conditions)
• Any changes to the HVAC system should be revalidated before proceeding to the PQ phase.

29. VALIDATION
• Document act of proving that any procedure, process, system / equipment
actual leads to expected results.
• To ensure that system provides continuously required environmental conditions
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

30. Air Flow Pattern
1. Take the titanium tetra chloride stick.
2. Burn the stick.
3. Place the burning stick in front of running Air Handling Unit (AHU).
4. Observed the flow of air with the help of smock distribution in the room.
5. Make chart diagram of the flow of air in the room for each room.
The distribution of smoke is observed. It should be uniform.

31. Air flow velocity &Changes per hour
For this test, the area of HVAC is divided into four hypothetical grids and the air velocity is measured at
each grid and then the average air velocity (V) is calculated.
Record the velocity readings taken at the center of the grids, and at the junction of dividing lines (center of
HEPA Filter) .Calculate the Average Velocity as
V = (V1+V2+V3+V4)
4
V = Velocity observed at each point
Now calculate the area of the filter by multiplying the length and
width of the filter in feet.
l = length of HEPA filter
w = width of HEPA filter
A = l x w
CLASS
Number of
Air Changes
/ Hour
CLASS 100 NLT 250
CLASS 10
000
60 + 10 %
CLASS 1 00
000
40 + 10 %

32.  Calculate the total air volume per minute supplied in the clean room by the
following formula:
A = Area of HEPA filter in square feet
V = Average air velocity in feet per minute
T = A x V
 Calculate the total air in the room multiplying the length, width and height of
the room in feet. Volume = L x W x H
 Now we can calculate the Air
Changes per hour using the
following formula: Air Changes
per Hour =
T X 60
Volume

33. Filter Leak Test
1. Place the velometer at the front of AHU unit.
2. Check the velocity of air to the all corner of the AHU.
3. The air velocity should be within the higher limit of HEPA filter.
4. In case it is found to exceed the upper limit, a gas cut (silicon) is used to
decrease the leakage.
Thermal Anemometers Velometer Rotating Vanes

34. Particles Count
• Useful in detecting significant deviations in air cleanliness from qualified
processing classifications
• Immediate understanding of air quality can be realized
• Useful as a tool for qualification and monitoring before /during and after
operations
On the air system before one hour of test operation.
1. Take the suitable particle counter and operate it to check the particles in
the room at non working operation.
2. Collect the information from particle counter and fill them in the format.
3. Operate the particle counter when work is on progress in the area.The
particles should be count when more than one hour work has been
progressed in the area. Record the data in the format.
4. Operate the particle counter for all the room maintaining grade A, grade B,
grade C & grade D.

35. Acceptance Criteria:
Clean room or clean zone shall meet the acceptance criteria for an air borne
particulate as referred in standard ISO 14644-1.
ISO 14644-
1
> 0.1 m
(Particles /
Mt3)
> 0.2 m
(Particles /
Mt3)
> 0.3 m
(Particles
/ Mt3)
> 0.5 m
(Particles /
Mt3)
> 1.0 m
(Particles /
Mt3)
> 5.0 m
(Particles /
Mt3)
ISO 1 1 2 0 0 0 0
ISO 2 100 24 10 4 0 0
ISO 3 1 000 237 102 35 8 0
ISO 4 10 000 2 370 1 020 352 83 0
ISO 5 1 00 000 23 700 10 200 3 520 832 29
ISO 6 10 00 000 2 37 000 1 02 000 35 200 8 320 293
ISO 7 NA NA NA 3 52 000 83 200 2 930
ISO 8 NA NA NA 35 20 000 8 32 000 29 300
ISO 9 NA NA NA 3 52 00 000 83 20 000 2 93 000

36. EU GGMP
Static (at rest) Dynamic (in operation)
> 0.5 m
(Particles / Mt3)
> 5.0 m
(Particles / Mt3)
> 0.5 m
(Particles / Mt3)
> 5.0 m
(Particles / Mt3)
GRADE A 3 500 1 3 500 1
GRADE B 3 500 1 3 50 000 2 000
GRADE C 3 50 000 2 000 35 00 000 20 000
GRADE D 35 00 000 20 000 Not defined Not defined
GRADE E Not defined Not defined Not defined Not defined
Cleanliness Class Verification (Non viable Particle Count) EU GMP

37. Particle counter machine

38. Pressure Drop across the HEPA and Fine filters of Air Handling Unit
Objective:
 The purpose of this test is to check the Clogged or clean
condition of the across HEPA filters, Fine Filter and Pre -
filter, of the Air Handling Unit.
Test Equipment:
 Differential pressure Transmitter or Manometer
Procedure for HEPA, Fine and Pre Filters:
1. Ensure that the differential pressure transmitter is
connected to before the filter and after the filter.
2. Check the status of the filter whether the filter is in clean
condition or Clogged condition.
Acceptance Criteria:
• HEPA, Pre and Fine filters should be in clean condition.
Manometer
Clogged filter

39. Temperature and Relative Humidity Test
Objective:
 To demonstrate the ability of the HVAC system to provide temperature and Relative
Humidity within the specified range.
Test Equipment:
 Temperature and Relative Humidity Sensor
Display Unit for Temperature and Relative Humidity
Procedure:
 Observe the temperature and relative humidity through respective display unit
wherever installed. Use Hygrometer to check the reading of Temperature and RH in
other rooms.
 Temperature and RH in the area to be checked and recorded in Static as well as
Dynamic Condition.
Static Condition:
 In static condition all the machines shall be kept switched ‘OFF’. Only restricted man
movement shall take place.
Dynamic Condition:
 In dynamic condition machines having maximum loads shall run and restricted man
movement shall take place.
Acceptance Criteria
 Temperature and relative humidity should meet the requirement as specified in system
specification. Hygro meter
Hygro meter
Sensor

40. Sound level Test
Objective:
To verify that the sound level is in limit in the clean room
area.
Test Equipment:
Sound Level Meter, duly calibrated with traceability to
national / international standard.
Procedure:
Take the reading at 5 locations in the room and take the
average of the sound in the unit of decibels.
Acceptance Criteria:
The clean room or clean zone shall meet the acceptance
criteria for sound level as mentioned below.
Sound Level
Meter
S.
N
Cleanliness
Class
Sound Level
Limit
( db )
1
Class 100 / ISO
5
NMT 60
2
Class 10, 000 /
ISO 7
NMT 80
3
Class 1,00, 000 /
ISO 8
NMT 80

41. Air Borne Viable Particle Monitoring
Objective:
 To determine the air borne microbial contamination level in critical area.
Air borne microbial count by settling plate exposure
method:
 Pre incubated SCDA Media plates shall be exposed in Locations mentioned for 4
hours and incubated for 48 hours at 30°C to 35°C followed by next 72 hours at
20°C to 25°C.Record the results in respective format. PDA plates shall be
exposed weekly to monitor the fungal counts. SCDA plates shall be incubated once
in fifteen days to monitor the anaerobic Microorganisms
Acceptance Criteria:
 All the Parameters performed in the area should meet the following requirements.
Petri Dish

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References
• Validation in pharmaceutical industry concepts, approaches &
guidelines by P.P.Sharma , 1st edition published by vandana
publications PVT.LTD dehli (page no. 165- 191)