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 PREPARED BY: Written By: Reviewed By: ABB Company Name Signature Date Jacobs Engineering CHECKED BY: Organization Abc Pharmaceuticals (User Dept.) Abc Pharmaceuticals (Engg. Dept.) Abc Pharmaceuticals (QA Dept.) Name Designation Signature Date APPROVED BY: Organization Abc Pharmaceuticals (HOD QA Dept.) Abc Pharmaceuticals (Plant Head) Name Designation Signature Date
Page 3 of 24 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 8.1 System Pre-requisites... 11 8.2 Test Equipment Calibration... 12 9 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
Page 4 of 24 9.4.4 Test Material/Equipment... 15 9.5 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
Page 5 of 24 1 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 meets all the acceptance criteria and is ready for GMP use. 2 SCOPE This protocol covers all aspects of Performance Qualification for the 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 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
Page 6 of 24 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 is to provide environmental Conditions suitable for process ongoing in different area, Raw Material / Finished Goods storage conditions & Human comfort. Complete 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
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 99.5% 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
Page 8 of 24 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.
Page 9 of 24 Future Provisions for 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.
Page 10 of 24 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.
Page 11 of 24 8.1 System Pre-requisites No. 1 2 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. Completed Yes or No Verified By Date Yes/No* Yes/No* Note:- * -Circle one, which is appropriate.
Page 12 of 24 8.2 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 Equipment Owner Equipment Number Due Date Signature Date Reviewed by Date
Page 13 of 24 9 TESTS AND CHECKS 9.1 Differential Pressure Monitoring 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.
Page 14 of 24 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 m 3 and not more than 2.000 particles 5 microns per m 3. Class 1,00,000 Grade C Not more than 3.500.000 particles 0.5 microns per m 3 and not more than 20.000 particles 5 microns per m 3. 9.3.4 Test Material/Equipment Particle Counter
Page 15 of 24 9.4 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 Not more than 10 colony forming units per m 3 of air sampled. Grade 10,000 ISO Class 8 Not more than 100 colony forming units per m 3 of air sampled. Class 1,00,000 9.4.4 Test Material/Equipment Air sampler
Page 16 of 24 9.5 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 tr all is the recovery time of whole zone tr i is the recovery time of each location N is the number of tested locations tr all = N ( 1/ tr i ) 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.
Page 17 of 24 9.6 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.
Page 18 of 24 10 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. Tests or Checks Executed [Y/N] Comment 9.1 Differential Pressure Monitoring 9.2 Temperature and Humidity Monitoring 9.3 Air Borne Particulate Monitoring 9.4 Microbiological Monitoring 9.5 Recovery Test Environmental
Page 19 of 24 11 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: Date: Reviewed by Date
Page 20 of 24 12 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.
Page 21 of 24 13 LIST OF APPENDICES Appendix No. 1 Signature Sheet Document Title
Page 22 of 24 SIGNATURE SHEET Appendix 1 Name Company Signature Initials Function / Activity
Page 23 of 24 14 SUMMARY (ABC ABC) -------------- --------------------------------
Page 24 of 24 15 APPROVALS The following approvals signify that the PQ is complete and acceptable. EXECUTED BY: Organization 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.) Name Designation Signature Date Abc Pharmaceuticals (QA Dept.) APPROVED BY: Organization Abc Pharmaceuticals (HOD QA Dept.) Name Designation Signature Date Abc Pharmaceuticals (Plant Head)