MODULE 3 -VALIDATION OF HVAC SYSTEM

A. INTRODUCTION

Importance of HVAC Clean rooms Contamination Parts of HVAC Air flow pattern
Qualification of HVAC Validation parameters.

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

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

 Prospective

 Concurrent

 Retrospective

 Revalidation
 B. 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 have following areas

 Process water

 Drinking and sanitary water

 Electric power

 Air conditioning (HVAC systems)

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.

What can HVAC do?

 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.

 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.

What HVAC can’t do?

 HVAC cannot clean up the surfaces of a contaminated surfaces, room or

equipment.

 HVAC cannot compensate for workers who do not follow procedure.

 C. 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.

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

1. Not to Bring Any Dust

2. Not to Accumulate Any Dust

3. Not to Generate Any Dust

4. To Remove Any Dust Quickly

 D. CONTAMINATION
What are contaminants?

 Products or substances other than the product being manufactured.

 Foreign products.

 Particulate matter.

 Micro-organisms.

 Endotoxins (degraded micro-organisms).

Cross-Contamination from where does Cross-Contamination originate?

 Poorly designed air handling systems and dust extraction systems.

 Poorly operated and maintained air handling systems and dust extraction
systems.

 Inadequate procedures for personnel and equipment.

 E. HVAC SYSTEM
It consists of

i. Air conditioner

ii. AHUs (air handling unit)

iii. Dehumidifier / Heater

iv. Filters (Pre & HEPA)

v. Dust Extractors

vi. Ducting (For delivery of controlled air)

vii. Supply Fans

viii. Dampers

ix. Humidity / Temperature / Pressure sensors

x. Mixer

xi. Heating / Cooling Coils

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.

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.
 F. 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.

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. Auto control system

10. Easy change over

11. Overall good construction and workmanship, etc.

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.

Installation Qualification

It must include:-

1. Instrumentation checked against current engineering drawings and

specifications.

2. Properly served by the required utilities.

3. Verification of materials of construction.

4. Installation of equipment and with piping.

5. Calibration of measuring instruments.

6. Operation manuals and spare parts lists to assure the proper and
continuous operation of the system.

7. Components are installed at specified location.

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.
OPERATION QUALIFICATION

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.

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

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 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.
 G. 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

STEPS TO FOLLOW

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.

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

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=AxV

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

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.

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.

Acceptance Criteria:

Clean room or clean zone shall meet the acceptance criteria for an air borne
particulate as referred in standard ISO 14644-1.

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.

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.

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 Per standard.

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
requirements.