Document No.
HVAC System
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PERFORMANCE QUALIFICATION
PROTOCOL
FOR
HVAC SYSTEM
Signing of this Performance Qualification Protocol indicates agreement with the Validation Master Plan
approach of the equipment. Further if any changes in this protocol are required, protocol will be revised
and duly approved.
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HVAC System
Document No.
PREPARED BY:
Company
Written By:
ABB
Reviewed
By:
Jacobs Engineering
Name
Signature
Date
CHECKED BY:
Organization
Name
Designation
Signature
Date
Abc
Pharmaceuticals
(User Dept.)
Abc
Pharmaceuticals
(Engg. Dept.)
Abc
Pharmaceuticals
(QA Dept.)
APPROVED BY:
Organization
Abc
Pharmaceuticals
(HOD QA Dept.)
Abc
Pharmaceuticals
(Plant Head)
Name
Designation
Signature
Date
Document No.
HVAC System
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TABLE OF CONTENTS
1
OBJECTIVE................................................................................................................................................. 5
2
SCOPE .......................................................................................................................................................... 5
3
RESPONSIBILITIES .................................................................................................................................. 5
4
SYSTEM DESCRIPTION........................................................................................................................... 6
5
DOCUMENTATION REQUIREMENTS ................................................................................................. 9
6
DATA COLLECTION ................................................................................................................................ 9
7
CHANGE CONTROL ............................................................................................................................... 10
8
PRE-QUALIFICATION REQUIREMENTS .......................................................................................... 10
9
8.1
System Pre-requisites ............................................................................................................. 11
8.2
Test Equipment Calibration ................................................................................................... 12
TESTS AND CHECKS .............................................................................................................................. 13
9.1
Differential Pressure Monitoring ........................................................................................... 13
9.1.1
Objective ........................................................................................................................ 13
9.1.2
Test Method .................................................................................................................... 13
9.1.3
Acceptance Criteria ....................................................................................................... 13
9.1.4
Test Material/Equipment................................................................................................ 13
9.2
Temperature and Humidity monitoring ................................................................................. 13
9.2.1
Objective ........................................................................................................................ 13
9.2.2
Test Method .................................................................................................................... 13
9.2.3
Acceptance Criteria ....................................................................................................... 13
9.2.4
Test Material/Equipment................................................................................................ 14
9.3
Airborne Particulate Testing .................................................................................................. 14
9.3.1
Objective ........................................................................................................................ 14
9.3.2
Test Method .................................................................................................................... 14
9.3.3
Acceptance Criteria ....................................................................................................... 14
9.3.4
Test Material/Equipment................................................................................................ 14
9.4
Microbiological Environmental Monitoring .......................................................................... 15
9.4.1
Objective ........................................................................................................................ 15
9.4.2
Test Method .................................................................................................................... 15
9.4.3
Acceptance Criteria ....................................................................................................... 15
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9.4.4
9.5
HVAC System
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Test Material/Equipment................................................................................................ 15
Recovery Test ........................................................................................................................ 16
9.5.1
Objective ........................................................................................................................ 16
9.5.2
Method ........................................................................................................................... 16
9.5.3
Acceptance Criterion ..................................................................................................... 16
9.5.4
Test material/ Equipment ............................................................................................... 16
9.6
Test Program and Sampling Points ........................................................................................ 17
9.7
Test Results ............................................................................................................................ 17
10
CHECKLIST OF ALL TESTS AND CHECKS ..................................................................................... 18
11
VARIANCE SHEET .................................................................................................................................. 19
12
REFERENCES ........................................................................................................................................... 20
13
LIST OF APPENDICES............................................................................................................................ 21
14
SUMMARY (ABC ABC) ........................................................................................................................... 23
15
APPROVALS ............................................................................................................................................. 24
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HVAC System
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OBJECTIVE
The objectives of this Performance Qualification (PQ) are as follows:

To verify that the equipment performs in accordance with the design and user requirements as
defined by set acceptance criteria and complies with relevant cGMP requirements.

To demonstrate that the system will perform reproducibly and consistently within its operating
range
Following execution of the protocol a summary report will be written and approved. All results,
conclusions, exceptions and variances will be addressed and final disposition of the equipment will be
stated. Successful completion of this protocol and approval of the summary report will verify that the
HVAC System meets all the acceptance criteria and is ready for GMP use.
2
SCOPE
This protocol covers all aspects of Performance Qualification for the HVAC System serving the Abc
Pharmaceuticals Limited, Abc, Himachal Pradesh (India); Tablets, Capsules and Liquid Orals
Manufacturing Facility. Scope incorporates qualification of all HVAC system components.
This protocol will define the methods and documentation used to qualify the HVAC System for PQ.
3
RESPONSIBILITIES
All work is to be performed under Abc Pharmaceuticals Limited, Abc, Himachal Pradesh (India) oversight
and according to ABC approved procedures.
ABB Personnel
The following are the responsibilities of Jacobs Engineering Validation Personnel:
 Writes the protocol using the approved template.
 Ensures that the protocol is in compliance with current ABC policies and procedures.
 Ensures that the content is sufficient, clearly defined technically sound and accurate.
 Ensures compliance with design specifications.
 Submits the draft protocol for review.
 Makes any necessary corrections to the protocol and answers queries from the reviewers.
 Submits the corrected protocol for approval
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Jacobs Engineering

Review the protocol as submitted by ABB and ensure compliance with design specifications.
Abc Pharmaceuticals Limited (ABC) Validation Personnel
The following are the primary responsibilities of the ABC Validation Personnel:
 Overall CGMP compliance for IQ
 Review and Pre-Approval of this IQ Protocol
 Issue of controlled copies of the protocol for execution
 Execution of this IQ protocol
 Document Control of this IQ Protocol until such document is completed, approved and after.
 Regulatory Compliance Review of the completed IQ Protocol
 Review and Approval of the executed IQ Protocol
 Training (of ABC and contract staff) and documentation of training for any ABC procedures required
for execution of the IQ.
4
SYSTEM DESCRIPTION
This plant is designed as per cGMP of national and international regulatory guidelines. The system designed
and installed shall meet the requirement of various processing zones with regard to following parameters,
which has been specified in the URS. URS No.: UR/UG/17.
Dry Bulb Temperature (Room Temperature)
Relative Humidity
Pressure differentials
Class of Cleanliness,
Function of HVAC System is to provide environmental Conditions suitable for process ongoing in different
area, Raw Material / Finished Goods storage conditions & Human comfort. Complete HVAC System is
controlled and monitored with BMS.
System Overview
The system has been categorized in three area classifications namely “O”, “E” and “F”, based on the
cleanliness maintained.

“O” area is the process area where product is exposed to the environment.

“E” area is the area where product is enclosed and not exposed to the environment
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
HVAC System
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“F” area is the Non-critical areas not directly related to production
Both “O” and “E” area are supplied with Terminal EU 9 filters with 99.5% efficiency down to 3μ ; the
difference being that in “O” area the number of air changes maintained at a minimum 20 per hour and in
“E’ area the number of air changes maintained as per heat load requirement . Gowning shall be required
for O and E areas.
Complete Production area is divided in different Zones as per inside design conditions, class of cleanness
as per the requirement of process. Dedicated AHUs are provided for various zones to considering
containment aspects as cGMP. Details of various zones are given in the enclosed drawings.
Once through system has considered for AHU’s serving multi-product areas, areas where solvents are
present and high dust generation areas. Once through AHU are provided with Heat Recovery Wheel to
recover the waste Tonnage of Refrigeration.
System has been designed considering Heat Loads, minimum air changes as applicable and air infiltration/
exfiltration from openings.
Room relative pressures have been maintained to avoid cross contamination. Air locks have been provided as
additional protection for cross contamination with Air Lock acting source of air between two adjacent areas
where protection is desirable. For pressure balancing of entire system, the impact of door gaps & other
openings on infiltration and ex-filtration has been considered for all areas while designing the HVAC system
to maintain pressure differentials. Door interlocks for Air Lock rooms have been provided. Recovery time
shall be established.
The HVAC system shall operate with dust extraction system simultaneously to control dust levels in various
areas. Accordingly, the impact of Air removal through dust extraction system has been considered while
designing the HVAC system.
Environmental Monitoring - Room Pressures, Temperature and RH
Room conditions shall be monitored by manual recording of the pressures, temperatures and RH. Pressure
readings are taken from Magnehelic Gauges, Dry Bulb and Wet Bulb indicating thermometers for Room
Temperatures and RH. These measuring devices are installed locally in the room where environmental
conditions are to be monitored.
Data Logging by BMS
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Sensors for Temperature, RH, and Differential Pressure etc. as required shall be installed to log the values in
BMS works station for trend analysis. These shall be in addition to local environmental monitoring.
Control Philosophy
Temperature
Control of Room Temp. (Summer)
To control the temperature of room there will be one two way control valve in chilled water line of AHU and
temp sensor will be installed in the room / Return Air duct. By sensing the room temp/return air temp.
chilled water control valve will modulate the chilled water flow as per the requirement.
Control of Room Temp. (Winter)
To control the temp of room there will be one two way control valve in hot water line of AHU and temp
sensor will be installed in the room / Return Air duct. By sensing the room temp/return air temp. hot water
control valve will modulate the hot water flow as per the requirement.
Relative Humidity
Control of Room RH (< 55% RH)
AHU is equipped with hot water coil and hot water coil is with two way control valve and RH sensor is
installed in the room/return air path. By sensing the room RH two way control valve will modulate the hot
water as required to control the RH.
Control of Room RH (< 40%)
Area where RH below 40% is required dedicated dehumidifier are provided there. Desicant in the
dehumidifier absorb the humidity and maintain the RH as per the requirement.
Pressures
By manually adjusting air flow quantities with the help of dampers.
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Future Provisions for HVAC System
It is envisaged to install terminal HEPA filters in place of EU-9 terminal super fine filters for O and E
areas. Hence, all parts & equipment installed shall be compatible for higher-pressure drops due to change
in filters.
Chilled Water System for HVAC and Process
5 Nos. (4 working + 1 standby), each of 375 TR capacity water cooled screw chillers are being installed with
primary & Secondary Pumping system to provide chilled water to AHUs & process equipments at various
locations. Secondary Chilled Water Pumping System has been provided with VFD and pump logic controller
for flow control of secondary chilled water as per actual HVAC and Process Load requirement.
2 Nos. (1working + 1 standby), each of 440 Kilo Watt plate type hot water calorifier (Hot Water Generator)
are being installed for pumping hot water to all AHU. Hot water System is equipped with Hot Water Pumps
with Variable Frequency Drive (VFD).
1 No. cooling tower with 5 cells (4 working + 1standby), each of capacity 1650 Gallons Per minute each cell
to reject heat dissipated by chillers and air compressors are being installed.
Both the CHW and HW piping on the service floor shall be designed to follow the reverse return method.
This is to ensure that pressure drop between the off take from supply header, upto return header, is same
for all for AHU’ s. This will help in correct quantity of water going in all AHU’ s at equal pressure
differential.
5
DOCUMENTATION REQUIREMENTS
The PQ File should include:
 This PQ Protocol.
 All printouts and handouts generated during the qualification procedure.
 All laboratory test results or their referenced location.
 All executed routine check sheets.
 A Signature Sheet [Appendix 1], where all people, performing the qualification tests, are listed.
 Any change control actions that may have occurred during the qualification activities.
 Any variances, exceptions or investigation reports generated during the qualification activities.
6
DATA COLLECTION
All individuals executing this Protocol shall complete the Signature Sheet [Appendix I]. All personnel
shall have suitable documented training or experience.
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All approvals shall be made in BLUE ink.
All data entry shall be made in BLUE ink.
All corrections to this Protocol, which are not retyped, are to be made in BLUE ink. All written
corrections to this Protocol or to data entered in this Protocol should be made by using a single line to
delete the error. The person who makes the correction shall initial and date it and add comment to explain
reason for correction.
After performing the qualification tests, collect all relevant printouts, check sheets, Laboratory test results
and certificates and retain for inclusion in the PQ File. If more Data Sheets or Variance Sheets are
required, they are to be attached to this Protocol as Appendices and to be listed in Section 13. List of
Appendices.
7
CHANGE CONTROL
Any changes or modifications to the system shall be performed in accordance with the ABC Project
Change Control Procedure (SOP No: BQA-011)
Change Control Forms raised during the execution of this PQ will be filed along with the protocol. An
assessment will be made for each change to determine whether or not any re-validation is required.
8
PRE-QUALIFICATION REQUIREMENTS
The results of any tests should meet the limits and acceptance criteria specified in the test documents. Any
deviations (as per BQA-017) or issues should be rectified and documented prior to PQ commencing. Open
action items resulting from these tests shall be listed in the Comments section.
Document No.
8.1
No.
1
2
HVAC System
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System Pre-requisites
Description of Pre-requisite
Verify that the OQ of the Dispensing Booth has
been executed and approved.
OQ Protocol Document No: OQ/F/HVC-01/00
Verify that the IQ/OQ summary report for the
Dispensing Booth has been approved.
IQ/OQ summary report document No.
Note:- * -Circle one, which is appropriate.
Completed
Yes or No
Yes/No*
Yes/No*
Verified By
Date
Document No.
8.2
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HVAC System
Test Equipment Calibration
Review the calibration status for the test equipment to be utilised and record the calibration due dates in
the table below. All equipment / instrumentation must remain within the calibration due date for the
duration of PQ test for which the item is used. If a due date potentially occurs during the testing period
then the instrument must be recalibrated before it can be utilised.
Equipment Name
Reviewed by
Equipment Owner Equipment
Number
Due Date
Date
Signature
Date
Document No.
9
TESTS AND CHECKS
9.1
Differential Pressure Monitoring
HVAC System
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9.1.1 Objective
The objective of this test is to show that the differential pressures between rooms are within designed
values.
9.1.2 Test Method
Use installed pressure gauges or either external pressure-measuring device for recording pressures.
Monitor the pressure between rooms for a minimum of 5 days. Perform this monitoring under operational
conditions.
9.1.3 Acceptance Criteria
The relative differential pressures between rooms must be within the design values. The differential
pressures between rooms to meet criteria as defined in the Room Book.
9.1.4 Test Material/Equipment
Installed pressure gauges
External pressure measuring device
9.2
Temperature and Humidity monitoring
9.2.1 Objective
The objective of this test is to prove that the temperature and humidity in the production areas are within
acceptable limits.
9.2.2 Test Method
Record the temperature and the humidity by using a dry bulb and wet bulb thermometer. Monitor the
temperature and the humidity for a minimum of 5 days. Perform this monitoring under operational
conditions.
9.2.3 Acceptance Criteria
Temperatures should be within temperature range as defined in Room Book.
HVAC System
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9.2.4 Test Material/Equipment
Dry Bulb and Wet Bulb Thermometer
9.3
Airborne Particulate Testing
9.3.1 Objective
The objective of this test is to verify that the HVAC facilities can provide the required clean room
classifications as defined in IS 14644 standards for Class 10,000 & Class 1,00,000(ISO Class 7 & ISO
Class 8 )
9.3.2 Test Method
Set up the particle counter according to appropriate test equipment operating procedures at the first sample
point. Monitor the particles daily for a minimum of 5 days. Perform this monitoring under rest conditions.
Repeat the measurement for every sample point.
Sample points and frequency of testing see in chapter 9.6 “Test Program and Sampling Points”.
9.3.3 Acceptance Criteria
Class 10,000
Grade B
Not more than 350.000 particles  0.5 microns per m3 and not more than
2.000 particles  5 microns per m3.
Class 1,00,000
Grade C
Not more than 3.500.000 particles  0.5 microns per m3 and not more than
20.000 particles  5 microns per m3.
9.3.4 Test Material/Equipment
Particle Counter
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9.4
HVAC System
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Microbiological Environmental Monitoring
9.4.1 Objective
The objective of this test is to verify that the HVAC facilities can provide the required cleanliness with
regard to microbiological contamination as defined in ISO 14644 Standards & EU Standards for Class
1,00,000 ( ISO 8) & Class 10,000 ( ISO 7 ) area.
9.4.2 Test Method
Set up the air sampler according to appropriate test equipment operating procedures at the first sample
point. Monitor the particles daily for a minimum of 5 days. Perform this monitoring under operational
conditions. Repeat the measurement for every sample point.
Sample points and frequency of testing see in chapter 9.6 “Test Program and Sampling Points”.
9.4.3 Acceptance Criteria
ISO Class 7
Grade 10,000
ISO Class 8
Class 1,00,000
Not more than 10 colony forming units per m3 of air sampled.
Not more than 100 colony forming units per m3 of air sampled.
9.4.4 Test Material/Equipment
Air sampler
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9.5
HVAC System
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Recovery Test
9.5.1 Objective
This test is performed to determine the ability of the installation to eliminate air borne particles so that
subsequent sampling/ dispensing operation can be performed without contaminating the lot.
9.5.2 Method
This test shall be performed at as built condition. Setup the particle counter in accordance with the
manufacturer’s instructions and the apparatus calibration certificate.
Place the Discrete Particle Counter Probe at the testing point. Adjust the single sample volume to the same
value used for determining the class of cleanliness. The delay time of the counter from starting each count
to the output recording should be adjusted to no more than 10 seconds. As far as possible, the particle size
used shall be same as that used for the determination of cleanliness class.
Generate particles to 100 times the target level.
Determine the recovery time with recovery rate test to target level.
9.5.3 Acceptance Criterion
Recovery time is given as
trall is the recovery time of whole zone
tri is the recovery time of each location
N is the number of tested locations
trall = N
∑ ( 1/ tri )
Recovery time shall be less than 10 minutes .
9.5.4 Test material/ Equipment
Aerosol Generator
Discrete Particle Counter
The apparatus should have valid calibration certificate.
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9.6
HVAC System
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Test Program and Sampling Points
Calculate the number of sample points for particulate testing according to ISO 14644 standards. Use less
sample points for temperature, humidity and microbiological monitoring. Mark the location of every
sample point in actual site drawings.
9.7
Test Results
Summarize the test results obtained in Appendix, “Test Results Summary”.
Report any deviations / non conformances in Appendix, “Deviation / Non-Conformance Report”.
Any out-of specification results shall be investigated.
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CHECKLIST OF ALL TESTS AND CHECKS
This checklist is provided to ensure that all tests or checks required for this protocol have been executed.
Reference
No.
9.1
9.2
9.3
9.4
9.5
Tests or Checks
Differential Pressure Monitoring
Temperature
and
Humidity
Monitoring
Air Borne Particulate Monitoring
Microbiological
Environmental
Monitoring
Recovery Test
Executed [Y/N]
Comment
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VARIANCE SHEET
Report any deviations from the acceptance criteria or exceptions from protocol instructions in the Record
Sheet as described in SOP No: BQA-017 –“Handling of Deviations”. Record the total number of
exceptions / deviations reported during the qualification activities of this Protocol. Record the Deviation
Number and Title in the Table below. Include all Deviation Record Sheets in the IQ File.
TOTAL NO. OF VARIANCES = __________
Variance No.
Variance Title
Status
Comments:
Signed:
Reviewed by
Date:
Date
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HVAC System
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REFERENCES
The Principle Reference is the following

Master Validation Plan for Abc Pharmaceuticals Limited Tablets, Capsules and Liquid Orals
Manufacturing Facility, VMP/00, Revision 00.
 Schedule – M – “Good Manufacturing Practices and Requirements of Premises, Plant and Equipment
for Pharmaceutical Products.”
 WHO Essential Drugs and Medicines Policy, QA of Pharmaceuticals, Vol 2 – Good Manufacturing
Practices and Inspection.
The following references are used to give addition guidance








FDA/ISPE Baseline Pharmaceutical Engineering Guide-Volume 5:- Commissioning and Qualification
Guide, First Edition / March 2001.
Code of Federal Regulations (CFR), Title 21, Part 210, Current Good Manufacturing Practice
(cGMP) in Manufacturing, Processing, Packing, or Holding of Drugs, General. April 1, 1998.
Code of Federal Regulations (CFR), Title 21, Part 211, Current Good Manufacturing Practice
(cGMP) for Finished Pharmaceuticals, April 1, 1998.
EU Guide to Good Manufacturing Practice, Part 4, 1997.
European Commission’s working party on control of medicines and inspections document, Validation
Master Plan, Design Qualification, Installation & Operational Qualification, Non Sterile Process
Validation, Cleaning Validation, October 1999.
GAMP Guide, Validation of Automated Systems in Pharmaceutical Manufacture, Version 4.0,
December 2001.
SOP No BQA)-017-“Handling of Deviations”.
SOP No BQA)-011-“Change Control Procedure”.
HVAC System
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LIST OF APPENDICES
Appendix No.
1
Document Title
Signature Sheet
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Document No.
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HVAC System
SIGNATURE SHEET
Name
Appendix 1
Company
Signature
Initials
Function / Activity
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HVAC System
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SUMMARY (ABC ABC)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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APPROVALS
The following approvals signify that the PQ is complete and acceptable.
EXECUTED BY:
Organization
Name
Designation
Signature
Date
Name
Designation
Signature
Date
Name
Designation
Signature
Date
Vendor
Abc Pharmaceuticals
(User Dept.)
Abc Pharmaceuticals
(Engg Dept.)
Abc Pharmaceuticals
(QA Dept.)
REVIEWED BY:
Organization
Abc Pharmaceuticals
(HOD User Dept.)
Abc Pharmaceuticals
(Engg Dept.)
Abc Pharmaceuticals
(QA Dept.)
APPROVED BY:
Organization
Abc Pharmaceuticals
(HOD QA Dept.)
Abc Pharmaceuticals
(Plant Head)