Document No.HVAC System Page 1 of 24 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. Page 2 of 24 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 ................................ 9 7 CHANGE CONTROL ........... 15 9..............................................................................................................3 Acceptance Criteria ........ 11 8.................................................................................. 12 TESTS AND CHECKS ............3 Acceptance Criteria .......... 13 9.... 15 ........................................................................................................... 15 9.................................................3 Acceptance Criteria ...............................................................................................................................................................................................................................Document No............................ 13 9................................................................................................................................................... 5 4 SYSTEM DESCRIPTION.................................................................................2 Test Method .......................................................... 13 9.......................................................................................................................................... 10 9 8...............................1 Objective ......................3...................................2.......................................................................................................................................................................................................................................3 Airborne Particulate Testing ..........1.................2............................................................... 14 9......................................................1 Objective ...............2 Temperature and Humidity monitoring ................3 Acceptance Criteria ............................... 5 2 SCOPE ...1...................................................... 13 9..1 System Pre-requisites ........2............4 Test Material/Equipment. 5 3 RESPONSIBILITIES ............................3.....................................................4 Test Material/Equipment..2 Test Equipment Calibration .............................................................................................................................................................4............ 13 9............... 14 9....1 Objective ......................................... 13 9........................................................... 14 9..........4 Test Material/Equipment.........................................................................................................................................2 Test Method ........ 9 6 DATA COLLECTION ................................................................................................................. 13 9......................................................................................................................................................................... 14 9.......................... 14 9....4.............1 Differential Pressure Monitoring ...... 13 9.................................................................................................................. 15 9......................................................... 13 9...................3.................................1 Objective ..................1... 14 9.................1............................................ 13 9.......................................................... 10 8 PRE-QUALIFICATION REQUIREMENTS .....2............................................................................................4 Microbiological Environmental Monitoring ..............................................3.................................................................2 Test Method .......................................................................................2 Test Method ..................................... 6 5 DOCUMENTATION REQUIREMENTS ...........4...................... HVAC System Page 3 of 24 TABLE OF CONTENTS 1 OBJECTIVE................................................................ .................................................................................................................... 16 9...................................................................................................................................7 Test Results .......................................................................... 21 14 SUMMARY (ABC ABC) ............................................................................................................ 23 15 APPROVALS .......................................... 17 9. 24 ................ 16 9.................................................................................. 20 13 LIST OF APPENDICES...................................6 Test Program and Sampling Points ....................................................................................... 16 9.......................................... 15 Recovery Test .............. 17 10 CHECKLIST OF ALL TESTS AND CHECKS ........................................ 16 9.5............................................................................5.....................................................................5.............5......................................... 19 12 REFERENCES .........4 Test material/ Equipment .............................................................................................................................................................3 Acceptance Criterion .1 Objective .....................................................4...............................Document No......................................4 9... 16 9...........................................................................................................................................................................................5 HVAC System Page 4 of 24 Test Material/Equipment............................ 9.................................................. 18 11 VARIANCE SHEET .....................................2 Method .......................................... 2 SCOPE This protocol covers all aspects of Performance Qualification for the HVAC System serving the Abc Pharmaceuticals Limited. Submits the draft protocol for review. Makes any necessary corrections to the protocol and answers queries from the reviewers. All results. Scope incorporates qualification of all HVAC system components. Abc. Abc. Himachal Pradesh (India).Document No. Ensures that the protocol is in compliance with current ABC policies and procedures. Ensures compliance with design specifications. 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. 3 RESPONSIBILITIES All work is to be performed under Abc Pharmaceuticals Limited. ABB Personnel The following are the responsibilities of Jacobs Engineering Validation Personnel: Writes the protocol using the approved template. Ensures that the content is sufficient. Himachal Pradesh (India) oversight and according to ABC approved procedures. 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. Tablets. This protocol will define the methods and documentation used to qualify the HVAC System for PQ. 1 HVAC System Page 5 of 24 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. clearly defined technically sound and accurate. conclusions. Submits the corrected protocol for approval . Capsules and Liquid Orals Manufacturing Facility. exceptions and variances will be addressed and final disposition of the equipment will be stated. “E” and “F”. Raw Material / Finished Goods storage conditions & Human comfort. Dry Bulb Temperature (Room Temperature) Relative Humidity Pressure differentials Class of Cleanliness. 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. Complete HVAC System is controlled and monitored with BMS. “O” area is the process area where product is exposed to the environment. based on the cleanliness maintained. HVAC System Page 6 of 24 Jacobs Engineering Review the protocol as submitted by ABB and ensure compliance with design specifications. The system designed and installed shall meet the requirement of various processing zones with regard to following parameters. Function of HVAC System is to provide environmental Conditions suitable for process ongoing in different area.Document No. which has been specified in the URS.: UR/UG/17. URS No. 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. “E” area is the area where product is enclosed and not exposed to the environment . approved and after. 4 SYSTEM DESCRIPTION This plant is designed as per cGMP of national and international regulatory guidelines. System Overview The system has been categorized in three area classifications namely “O”. Complete Production area is divided in different Zones as per inside design conditions. HVAC System Page 7 of 24 “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. Door interlocks for Air Lock rooms have been provided. the impact of Air removal through dust extraction system has been considered while designing the HVAC system. Once through AHU are provided with Heat Recovery Wheel to recover the waste Tonnage of Refrigeration. Recovery time shall be established. Room relative pressures have been maintained to avoid cross contamination. minimum air changes as applicable and air infiltration/ exfiltration from openings.Document No. Details of various zones are given in the enclosed drawings. These measuring devices are installed locally in the room where environmental conditions are to be monitored. Accordingly. Dry Bulb and Wet Bulb indicating thermometers for Room Temperatures and RH. 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. areas where solvents are present and high dust generation areas. Environmental Monitoring . Gowning shall be required for O and E areas. The HVAC system shall operate with dust extraction system simultaneously to control dust levels in various areas. 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.Room Pressures. Pressure readings are taken from Magnehelic Gauges. class of cleanness as per the requirement of process. Dedicated AHUs are provided for various zones to considering containment aspects as cGMP. Data Logging by BMS . Once through system has considered for AHU’s serving multi-product areas. temperatures and RH. System has been designed considering Heat Loads. 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 .5% efficiency down to 3μ . Temperature and RH Room conditions shall be monitored by manual recording of the pressures. RH. and Differential Pressure etc. These shall be in addition to local environmental monitoring. Control of Room Temp. Pressures By manually adjusting air flow quantities with the help of dampers. HVAC System Page 8 of 24 Sensors for Temperature. hot water control valve will modulate the hot water flow as per the requirement. as required shall be installed to log the values in BMS works station for trend analysis. 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. (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. chilled water control valve will modulate the chilled water flow as per the requirement. By sensing the room temp/return air temp. 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. (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. Control Philosophy Temperature Control of Room Temp. Desicant in the dehumidifier absorb the humidity and maintain the RH as per the requirement. .Document No. all parts & equipment installed shall be compatible for higher-pressure drops due to change in filters. Any change control actions that may have occurred during the qualification activities. All executed routine check sheets. All personnel shall have suitable documented training or experience. Chilled Water System for HVAC and Process 5 Nos. (4 working + 1 standby).Document No. cooling tower with 5 cells (4 working + 1standby). 5 DOCUMENTATION REQUIREMENTS The PQ File should include: This PQ Protocol. Hence. each of capacity 1650 Gallons Per minute each cell to reject heat dissipated by chillers and air compressors are being installed. are listed. HVAC System Page 9 of 24 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. . 1 No. 6 DATA COLLECTION All individuals executing this Protocol shall complete the Signature Sheet [Appendix I]. Any variances. 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. Hot water System is equipped with Hot Water Pumps with Variable Frequency Drive (VFD). where all people. All printouts and handouts generated during the qualification procedure. This will help in correct quantity of water going in all AHU’ s at equal pressure differential. each of 440 Kilo Watt plate type hot water calorifier (Hot Water Generator) are being installed for pumping hot water to all AHU. 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. Both the CHW and HW piping on the service floor shall be designed to follow the reverse return method. exceptions or investigation reports generated during the qualification activities. 2 Nos. (1working + 1 standby). upto return header. This is to ensure that pressure drop between the off take from supply header. performing the qualification tests. All laboratory test results or their referenced location. A Signature Sheet [Appendix 1]. is same for all for AHU’ s. which are not retyped. After performing the qualification tests. If more Data Sheets or Variance Sheets are required. check sheets.Document No. An assessment will be made for each change to determine whether or not any re-validation is required. they are to be attached to this Protocol as Appendices and to be listed in Section 13. All data entry shall be made in BLUE ink. Any deviations (as per BQA-017) or issues should be rectified and documented prior to PQ commencing. The person who makes the correction shall initial and date it and add comment to explain reason for correction. collect all relevant printouts. HVAC System Page 10 of 24 All approvals shall be made in BLUE ink. All corrections to this Protocol. Open action items resulting from these tests shall be listed in the Comments section. are to be made in BLUE ink. 8 PRE-QUALIFICATION REQUIREMENTS The results of any tests should meet the limits and acceptance criteria specified in the test documents. Laboratory test results and certificates and retain for inclusion in the PQ File. List of Appendices. 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. . 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. IQ/OQ summary report document No. OQ Protocol Document No: OQ/F/HVC-01/00 Verify that the IQ/OQ summary report for the Dispensing Booth has been approved. 1 2 HVAC System Page 11 of 24 System Pre-requisites Description of Pre-requisite Verify that the OQ of the Dispensing Booth has been executed and approved.* -Circle one. which is appropriate. Completed Yes or No Yes/No* Yes/No* Verified By Date .1 No. 8.Document No. Note:. All equipment / instrumentation must remain within the calibration due date for the duration of PQ test for which the item is used. 8.2 Page 12 of 24 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. 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. 3 Acceptance Criteria The relative differential pressures between rooms must be within the design values.2.1.2. 9.1 Objective The objective of this test is to show that the differential pressures between rooms are within designed values.1.4 Test Material/Equipment Installed pressure gauges External pressure measuring device 9. Monitor the pressure between rooms for a minimum of 5 days. The differential pressures between rooms to meet criteria as defined in the Room Book.Document No.2. 9. 9. Perform this monitoring under operational conditions.1 Objective The objective of this test is to prove that the temperature and humidity in the production areas are within acceptable limits. 9. . 9 TESTS AND CHECKS 9.1 Differential Pressure Monitoring HVAC System Page 13 of 24 9.2 Temperature and Humidity monitoring 9.3 Acceptance Criteria Temperatures should be within temperature range as defined in Room Book.1. Perform this monitoring under operational conditions.2 Test Method Use installed pressure gauges or either external pressure-measuring device for recording pressures. 9. Monitor the temperature and the humidity for a minimum of 5 days.2 Test Method Record the temperature and the humidity by using a dry bulb and wet bulb thermometer.1. 4 Test Material/Equipment Particle Counter .5 microns per m3 and not more than 2.3.3 Acceptance Criteria Class 10.00.HVAC System Document No.3.500. 9.6 “Test Program and Sampling Points”.4 Test Material/Equipment Dry Bulb and Wet Bulb Thermometer 9.00.2 Test Method Set up the particle counter according to appropriate test equipment operating procedures at the first sample point.000 particles 5 microns per m3.3.000 particles 0. Page 14 of 24 9.1 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 10.2. Sample points and frequency of testing see in chapter 9.000 particles 5 microns per m3. Monitor the particles daily for a minimum of 5 days.000(ISO Class 7 & ISO Class 8 ) 9.3.5 microns per m3 and not more than 20.000 particles 0. Perform this monitoring under rest conditions.000 Grade B Not more than 350. Repeat the measurement for every sample point.000 & Class 1. 9.3 Airborne Particulate Testing 9.000 Grade C Not more than 3. Class 1. Not more than 100 colony forming units per m3 of air sampled.000 ( ISO 8) & Class 10.4. 9. Monitor the particles daily for a minimum of 5 days.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. Perform this monitoring under operational conditions.000 Not more than 10 colony forming units per m3 of air sampled.4. Repeat the measurement for every sample point.000 ISO Class 8 Class 1.2 Test Method Set up the air sampler according to appropriate test equipment operating procedures at the first sample point.00.00. 9.4.4.3 Acceptance Criteria ISO Class 7 Grade 10.4 HVAC System Page 15 of 24 Microbiological Environmental Monitoring 9. Sample points and frequency of testing see in chapter 9.6 “Test Program and Sampling Points”. 9. 9.4 Test Material/Equipment Air sampler .000 ( ISO 7 ) area.Document No. Generate particles to 100 times the target level. Place the Discrete Particle Counter Probe at the testing point. 9.5.5.5. 9. As far as possible.5.Document No. .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. Adjust the single sample volume to the same value used for determining the class of cleanliness.2 Method This test shall be performed at as built condition.5 HVAC System Page 16 of 24 Recovery Test 9. The delay time of the counter from starting each count to the output recording should be adjusted to no more than 10 seconds. 9.3 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 . 9.4 Test material/ Equipment Aerosol Generator Discrete Particle Counter The apparatus should have valid calibration certificate. Setup the particle counter in accordance with the manufacturer’s instructions and the apparatus calibration certificate. the particle size used shall be same as that used for the determination of cleanliness class. Determine the recovery time with recovery rate test to target level. 9. 9. Use less sample points for temperature. “Test Results Summary”. humidity and microbiological monitoring.Document No. . Any out-of specification results shall be investigated. “Deviation / Non-Conformance Report”.6 HVAC System Page 17 of 24 Test Program and Sampling Points Calculate the number of sample points for particulate testing according to ISO 14644 standards. Mark the location of every sample point in actual site drawings. Report any deviations / non conformances in Appendix.7 Test Results Summarize the test results obtained in Appendix. 5 Tests or Checks Differential Pressure Monitoring Temperature and Humidity Monitoring Air Borne Particulate Monitoring Microbiological Environmental Monitoring Recovery Test Executed [Y/N] Comment . 10 Page 18 of 24 CHECKLIST OF ALL TESTS AND CHECKS This checklist is provided to ensure that all tests or checks required for this protocol have been executed.1 9.HVAC System Document No.2 9.4 9.3 9. 9. Reference No. OF VARIANCES = __________ Variance No.HVAC System Document No. Variance Title Status Comments: Signed: Reviewed by Date: Date . Record the Deviation Number and Title in the Table below. TOTAL NO. Record the total number of exceptions / deviations reported during the qualification activities of this Protocol. Include all Deviation Record Sheets in the IQ File. 11 Page 19 of 24 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”. Document No. 1997. December 2001. QA of Pharmaceuticals.Commissioning and Qualification Guide. Code of Federal Regulations (CFR). Non Sterile Process Validation. or Holding of Drugs. Packing. 1998. Revision 00. Capsules and Liquid Orals Manufacturing Facility. Validation Master Plan. 1998. GAMP Guide. April 1. Installation & Operational Qualification. . Vol 2 – Good Manufacturing Practices and Inspection. VMP/00. General. October 1999. Version 4. Validation of Automated Systems in Pharmaceutical Manufacture.” WHO Essential Drugs and Medicines Policy. 12 HVAC System Page 20 of 24 REFERENCES The Principle Reference is the following Master Validation Plan for Abc Pharmaceuticals Limited Tablets. Title 21. Current Good Manufacturing Practice (cGMP) in Manufacturing. First Edition / March 2001. Plant and Equipment for Pharmaceutical Products. Schedule – M – “Good Manufacturing Practices and Requirements of Premises. EU Guide to Good Manufacturing Practice. Current Good Manufacturing Practice (cGMP) for Finished Pharmaceuticals. Part 210. Part 211. Processing. Cleaning Validation. Title 21.0. Code of Federal Regulations (CFR). The following references are used to give addition guidance FDA/ISPE Baseline Pharmaceutical Engineering Guide-Volume 5:. April 1. SOP No BQA)-017-“Handling of Deviations”. Part 4. SOP No BQA)-011-“Change Control Procedure”. Design Qualification. European Commission’s working party on control of medicines and inspections document. HVAC System Document No. 1 Document Title Signature Sheet Page 21 of 24 . 13 LIST OF APPENDICES Appendix No. Document No. Page 22 of 24 HVAC System SIGNATURE SHEET Name Appendix 1 Company Signature Initials Function / Activity . 14 HVAC System Page 23 of 24 SUMMARY (ABC ABC) ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- .Document No. ) Abc Pharmaceuticals (Plant Head) .) APPROVED BY: Organization Abc Pharmaceuticals (HOD QA Dept.) Abc Pharmaceuticals (Engg Dept. EXECUTED BY: Organization Name Designation Signature Date Name Designation Signature Date Name Designation Signature Date Vendor Abc Pharmaceuticals (User Dept.) Abc Pharmaceuticals (QA Dept.) REVIEWED BY: Organization Abc Pharmaceuticals (HOD User Dept.) Abc Pharmaceuticals (Engg Dept.) Abc Pharmaceuticals (QA Dept. 15 Page 24 of 24 APPROVALS The following approvals signify that the PQ is complete and acceptable.HVAC System Document No.