Installation and Functional Verification Protocol

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Title Page

For

Hot Detergent and Hot PUW

Generation and Distribution System

Author Authors Title / Position

Maria Kaluzna

Validation Engineer Pfizer

Document Number Revision Number Revision Date

1 24JUN24

Approvals PagePrepared By:__Maria Kaluzna________________Date:_21Jun 2024_____

Validation Engineer

Approved By:__Daniel Crandol_____________Date:_21Jun 2024__

Validation Manager

Your signature attests that you have reviewed this document and it complies with relevant validation policies & procedures.

Approved By:_Frank Roche_______________Date:_21Jun 2024___

Engineering

Your signature attests that that you have reviewed this document and confirm its accuracy against the associated specifications and design.

(align with Responsibilities Protocol Section-10)

Approved By:__Calvin Moore_____________Date:_22 Jun 2024_____

Your signature attests that you have reviewed this document and confirm it complies with cGMPs regulatory requirements, local and corporate policies.

(align with Responsibilities Protocol Section-10)

Approved By:__Nick Walsh__________Date:__21Jun 2024_______

Maintenance/ Calibrations Engineer

Your signature attests that you have reviewed this document and it complies with relevant calibrations policies & procedures.

(align with Responsibilities Protocol Section-10)

Approved By:__James Egan_____________Date:_21Jun 2024_____

Manufacturing

Your signature attests that you have reviewed this document and confirm it complies with relevant manufacturing policies & procedures

(align with Responsibilities Protocol Section-10)

Approved By:__Cian Brennan _____________Date:_22 Jun 2024_____

HR/Training

Your signature attests that you have reviewed this document and confirm it complies with relevant manufacturing policies & procedures

(align with Responsibilities Protocol Section-10)

Approved By:__ Kathy McDonald _____________Date:_21Jun 2024_____

EHS

Your signature attests that you have reviewed this document and confirm it complies with relevant manufacturing policies & procedures

(align with Responsibilities Protocol Section-10)

Approved By:__Matthew Doyle __________Date:__21Jun 2024____

Your signature attests that you have reviewed this document and it complies with relevant calibrations policies & procedures.

(align with Responsibilities Protocol Section-10)

Document Revision HistoryRevision Date of Issue Reason for revision update

A 12 Jan 2012 Issued for review

0 14 Mar 2012 Issued for approval and use

1 24 Jun 2024 Approved

Table of Contents TOC o "1-3" h z u 1Title Page PAGEREF _Toc45658109 h 12Approvals Page PAGEREF _Toc45658110 h 23Document Revision History PAGEREF _Toc45658111 h 34Table of Contents PAGEREF _Toc45658112 h 45Protocol Objective PAGEREF _Toc45658113 h 66System Description PAGEREF _Toc45658114 h 67Scope PAGEREF _Toc45658115 h 77.1System Impact Assessment PAGEREF _Toc45658116 h 77.2Component Impact Assessment PAGEREF _Toc45658117 h 77.3Summary Table - Operational Critical Components PAGEREF _Toc45658118 h 87.4P&ID Scope PAGEREF _Toc45658119 h 108Reference Documentation PAGEREF _Toc45658120 h 119Definitions/ Glossary PAGEREF _Toc45658121 h 1210Responsibilities / Subject Matter Experts PAGEREF _Toc45658122 h 1311Installation Verification Testing Procedures PAGEREF _Toc45658123 h 1411.1P&ID Walkdown Testing Procedure PAGEREF _Toc45658124 h 1411.2Equipment Installation Verification Procedure PAGEREF _Toc45658125 h 1611.3Instrument Installation Verification Procedure PAGEREF _Toc45658126 h 1811.4Piping Installation Verification Procedure PAGEREF _Toc45658127 h 2011.5Calibration Program Verification PAGEREF _Toc45658128 h 2111.6Preventative Maintenance Program Verification PAGEREF _Toc45658129 h 2111.7Draft SOP Verification PAGEREF _Toc45658130 h 2111.8Test-Instrument Calibration Verification PAGEREF _Toc45658131 h 2112Progression Approval to Proceed to Functional Verification PAGEREF _Toc45658132 h 2212.1Operational-Critical-Instrument Calibration Verification Form PAGEREF _Toc45658133 h 2313Functional Verification Testing Procedures PAGEREF _Toc45658134 h 2513.1Hot Detergent System Level Control PAGEREF _Toc45658135 h 2613.2Hot Detergent System Flow Control PAGEREF _Toc45658136 h 2813.3Hot Detergent System Temperature Control PAGEREF _Toc45658137 h 3013.4Hot Detergent System Detergent Dosing Control PAGEREF _Toc45658138 h 3213.5Hot PUW System Level Control PAGEREF _Toc45658139 h 3413.6Hot PUW System Flow Control PAGEREF _Toc45658140 h 3413.7Hot PUW System Temperature Control PAGEREF _Toc45658141 h 3413.8Approved SOP Verification PAGEREF _Toc45658142 h 3414Protocol Quality Procedures PAGEREF _Toc45658143 h 3514.1Signature Log PAGEREF _Toc45658144 h 3514.2Deviation Procedure PAGEREF _Toc45658145 h 3514.3Change Control Procedure PAGEREF _Toc45658146 h 3515IOQ Protocol Summary Report PAGEREF _Toc45658147 h 3616List of Appendices PAGEREF _Toc45658148 h 3716.1Appendix A - Protocol Signature Log PAGEREF _Toc45658149 h 3816.2Appendix B - Installation Verification GMP checksheets PAGEREF _Toc45658150 h 3916.2.1P&ID Walkdown Installation Verification PAGEREF _Toc45658151 h 3916.2.2Equipment Installation Verification PAGEREF _Toc45658152 h 4016.2.3Instrument Installation Verification PAGEREF _Toc45658153 h 5016.2.4Piping Installation Verification PAGEREF _Toc45658154 h 6516.2.5Calibration Program Verification PAGEREF _Toc45658155 h 7116.2.6Preventative Maintenance Program Verification PAGEREF _Toc45658156 h 7316.2.7Draft SOP Verification PAGEREF _Toc45658157 h 7516.2.8Test-Instrument Calibration Verification PAGEREF _Toc45658158 h 7716.3Appendix C: OQ GMP check-sheets PAGEREF _Toc45658159 h 7916.3.1Hot Detergent System Level Control PAGEREF _Toc45658160 h 7916.3.2Hot Detergent System Flow Control PAGEREF _Toc45658161 h 8216.3.3Hot Detergent System Temperature Control PAGEREF _Toc45658162 h 8516.3.4Hot Detergent System Detergent Dosing Control PAGEREF _Toc45658163 h 8816.3.5Hot PUW System Level Control PAGEREF _Toc45658164 h 9116.3.6Hot PUW System Flow Control PAGEREF _Toc45658165 h 9416.3.7Hot PUW System Temperature Control PAGEREF _Toc45658166 h 9716.3.8Approved SOP Verification PAGEREF _Toc45658167 h 10016.4Appendix D: Deviation log PAGEREF _Toc45658168 h 10116.5Appendix E: Deviation Form PAGEREF _Toc45658169 h 10216.6Appendix F: Change Control Log PAGEREF _Toc45658170 h 11016.7Appendix G: Change Control Form PAGEREF _Toc45658171 h 11116.8Appendix H: Component Impact Assessment PAGEREF _Toc45658172 h 116 16.9 Appendix I: Traceability Matrix PAGEREF _Toc45658173 h 121

Protocol ObjectiveThe objective of this protocol is to provide testing evidence that will prove that the Hot Detergent and Hot PUW Generation and Distribution system is fit for its intended use. Testing will incorporate both installation verification and functional verification test.

System DescriptionPrepare a summary System Description. Suggestions include drawing a process flow / block diagram; listing critical operational features; and, describing the major equipment components in the context of their installation and functional features.

The Hot Detergent and Hot PUW Generation and Distribution Skid will be used to generate and re-circulate two different cleaning fluids:

Hot Detergent Solution: A dilute detergent solution heated to 80C.

Hot PUW2 Process Water: Water heated to 80C.

The skid will consist of the equipment items outlined below together with all necessary instrumentation for control and monitoring of the process:

Hot PUW2 Process Water Tank 1

Hot Detergent Solution Tank 1

Centrifugal Recirculation Pumps 4

Detergent Dosing Pump 1

Heat Exchangers 2

1. The Detergent Tank is fed directly from the 25C PUW1 water loop.

2. The PUW1 process water is mixed with concentrated detergent and heated in a Plate and Frame heat exchanger to 80C.

3. A duty/standby pump arrangement is used to re-circulate the hot detergent solution.

4. The hot detergent solution supply temperature is maintained by a closed loop control system, which modulates steam flow to the heat exchanger HX-211.

5. The PUW2 hot process water tank is fed directly from the 25C PUW1 water loop.

6. The PUW1 Process water is heated to 80oC in a plate and frame heat exchanger.

7. A duty/standby pump arrangement is used to re-circulate the PUW2 fluid.

8. The PUW2 hot process water supply temperature is maintained by a closed loop control system, which modulates steam flow to the heat exchanger HX-411.

The system is comprised of a number of tanks and piping, in addition to heat exchangers, which are utilised for the purpose of generating and transporting hot water (steam) for the purpose of sterilising medical production systems. This is done to guarantee that the medicines that are created are free of impurities and are suitable for consumption without any contaminants. In order to bring water to a temperature that is safe for consumption, the system is comprised of a boiler that provides heat. Following this, the pure steam is channelled through a network of pipes and pipings, which are then utilised for the purpose of tank sterilisation. In addition, the pure hot steam is utilised in the process of sterilising piping systems, filters, and items that are contained within sterilisers. Sterilisers for pharmaceutical products are utilised in certain tanks that are included within the system. In clean room systems, the system also dehumidifies the air, and the detergents are employed for additional cleaning once the cleaning process has been completed. The 50-PUW1-S6-148-IH pipeline, which is responsible for transporting hot vapour, is considered to be one of the most important pipelines in the system. In the event that this pipeline is not properly managed, for instance if the valve opening breaks in this pipeline, it will ultimately result in a buildup of high pressure, with the potential for an explosive situation. The system supplies and distributes cleaning and rinsing solutions for permanent vessels, process lines, in-line equipment, and associated piping. The equipment of the Hot Detergent and Hot PUW Generation and Distribution system will undergo cleaning cycles with precisely regulated flowrates, durations, temperatures, and chemical concentrations. This process aims to sterilise the medical production systems and guarantee that the pharmaceuticals produced are devoid of impurities and contaminants. The device produces thermal energy to raise the temperature of water to a level that is considered safe.

ScopeSystem Impact AssessmentThe Hot Detergent and Hot PUW Generation and Distribution is considered a direct impact system because:

Its is involved in the cleaning of product contact equipment.

Its function may have an impact of product quality and patient safety.

This system operates by cleaning equipment that comes into touch with the product and simultaneously produces and circulates two cleaning fluids. This process directly affects the quality of the product. The manufacturing and distribution of hot detergent and hot PUW are explained using a "direct impact" approach.

The Hot Detergent and Hot PUW Generation and Distribution is considered a direct impact system because: This system has a direct impact on product quality as it cleans product contact equipment in a process and this system is used to generate and re-circulate two different cleaning fluids. This is why hot Detergent and Hot PUW Generation and Distribution' is considered a 'direct impact' system. Explanation: The system has a direct impact on the quality of the products because it has a cleaning system in which the product is equipped in the process. The direct impact system also facilitates to recirculate and manufacture the two separate cleaning fluids. It has a direct impact on the manufacturing of a medicinal product for the safety of a patient. The breakdown of this system would influence patient's security and product quality. Detergents are a class of molecules known as surfactants whose unique property is to break apart the forces formed by the interaction of hydrophobic-hydrophilic molecules among the sample. The molecular head is attracted to water known as hydrophilic while the tail is attracted to dirt and grease called hydrophobic.

"Commissioning and Qualification" is covered in ISPE Baseline Guide, Volume 5. The terminology "qualification" and "commissioning" are defined and made clearer in Baseline Guide 5, "Commissioning and Qualification," along with the degree of regulation pertaining to the former. After boundaries have been logically established, the following criteria can be used to evaluate systems: Direct Impact, where the system "is expected to have a direct impact on product quality"; No Impact, where the system "will not have any impact, either directly or indirectly, on product quality". Indirect Impact: In this scenario, the system will usually support a Direct Impact system even though it is not anticipated to have a direct influence on product quality.

System Direct Impact

Indirect Impact

No Impact

WFI System X

Chilled Water System X

Utilities Monitoring System X

Electronic Batch Record System X

Non-Process HVAC X

Laminar Flow Area X

Sprinkler System X

Typical System Impact Matrix

Verification / Qualification Protocol

The Impact Spectrum

Your factory is made up of numerous different systems such as:

Parking facilities

Elevators

Office air conditioner

Chilled water production

Air conditioner

Building management system

Autoclave

Purified water system

Clean-In-Place (CIP) system

GEP

Each of these systems is made up of many different items, components, subsystems and instruments.

There is a tendency among novice CQV, C&Q, validation technicians and engineers to qualify 100% of the components in every system. The safest approach is surely that.

Nevertheless, as the economist Thomas Sowell observed,

Trade-offs are the only solutions.

A 100%-of-items-in-every-system approach certainly has its drawbacks.

Qualify -the design and use of these systems can affect their impact Verification / Qualification Protocol.

The approach of qualifying 100% of items in every system is not the solution due to its trade-offs, such as being expensive and wasteful, making medicines less affordable, increasing regulatory burden, and not being a one-time cost. Additionally, every item must be documented and managed according to the change control procedure. The biggest trade-off is the risk of something being missed, as not every system or item has a critical impact on product quality and patient safety. To address these issues, impact assessments can be conducted at system-level and component-level levels. System-level impact assessment determines which systems within the plant are crucial, while component-level impact assessment identifies which components are crucial to product quality. Good Engineering Practices (GEPs) are used to manage the design, installation, and commissioning of systems and their components within a facility, and these systems must also be qualified by regulatory authorities like FDA and EMA when approving medicines being manufactured in that facility.

Use conventions:

Upstream/ Downstream side of valves;

Last valve on distribution system;

Instrumentation controlled by a skid part of skid system.

7.2. Component Impact AssessmentThe Component Impact Assessment will drive the scope of the installation and functional verifications. Product contact plus operational critical components must be included in the installation verifications. The operationally critical components will drive the functionality testing.

Evaluating the impact of the equipment will increase the ability to install and operate. Contact elements and critical work elements should be included in the installation analysis. The functionality of the product will lead to experimental studies.

The second step evaluates the importance of physical properties that affect product quality, evaluates the system's components' criticality in terms of product quality. This guide specifies the process of determining the relationship between the type of interference on the product or one of its components and criticality of the machine or equipment. The approach for determining the relationship between the criticality of a system or one of its components and the type of influence it has on the product is outlined in the Guide.

Direct effects may have non-essential properties as well as essential properties. However, indirect effects may not have significant characteristics.

If the latter is found to occur during the impact evaluation, System Impact Assessment process, the components must be assessed, and the system's impact or the component's criticality must be reconsidered again.

Please see section 16.8, Appendix H for details. 7.3. Summary Table - Operational Critical Components# *Operational Critical Component **Additional components in the loop (if applicable) Rationale

1 P-207 (Detergent Centrifugal Transfer Pump) Linked to FL-399, HX-211. It is on the hot detergent supply line and it must work to control flow. Detergent Centrifugal Transfer Pump. Essential for transfers of detergent, which affects the effectiveness of the systems cleaning.

2 P-209 (Detergent Centrifugal Transfer Pump) Linked to FL-399, HX-211. It is on the hot detergent supply line and it must work to control flow, Helps maintain proper flow of detergent solution, critical for effective cleaning and product safety.

3 P-415(PUW2 Centrifugal Transfer Pump) Linked to FL-401, HX-411. It is on the hot PUW2 supply line and it must work to control flow. Ensures proper flow of purified water, essential for rinsing after cleaning to remove residual detergent.

4 P-417(PUW2 Centrifugal Transfer Pump) Linked to FL-401, HX-411. It is on the hot PUW2 supply line and it must work to control flow. Same rationale as P-415, ensuring proper flow of purified water for rinsing.

5 P-223 (Detergent Metering Pump) Linked to V034 Sanitary Diaphragm Valve and V036 Sanitary Diaphragm Valve, FS 005L (Low Flow switch) and FA005L. It is on the process line and it must work to control the flow of concentrated detergent. Detergent Metering Pump. Controls precise concentration of detergent solution, operationally critical for effective cleaning.

6 LS-003 (Low Level Switch Tuning fork type) Linked to LAL003LL.

It is located on the hot PUW2 tank, T-411. It must work to alert low levels in the tank.

7 LS-004 (Low Level Switch Tuning fork type) Linked to LA004LL

Hot detergent Tank. It is located on the hot detergent tank, T-211. It must work to alert low levels in the tank. It is part of the hot detergent tank and used to track the level when it gets too low.

8 LS-005 (High Level Switch Tuning fork type) LA005H.

It is located on the hot PUW2 tank, T-411. It must work to alert high levels in the tank.

9 LS-006 (High Level Switch (Tuning fork type) LA006, SG002 Vessel sight glass (sanitary design). It is located on the hot detergent tank, T-211. It must work to alert high levels in the tank. It is part of the hot detergent tank and used to track the level when it gets too high.

10 LT-001 (Hydrostatic Pressure type level Transmitter) LIT001, Hot PUW Tank. It is located on the hot PUW2 tank, T-411. It must work to regulate the amount of PUW entering the tank. Part of the Hot PUW2 Tank. Used to measure the tank level.

11 LT-002 (Hydrostatic Pressure type level Transmitter) LIT002, Hot Detergent Tank T-211. It is located on the hot detergent tank, T-211. It must work to regulate the amount of PUW entering the tank. Part of the Hot Detergent Tank and is used to measure the tank level.

12 TI-007 (Bimetalic Temperature indicator) Hot PUW2 Tank T-411. It is located within the thermowell on hot detergent tank, T-411. It must work to provide a temperate reading of inside the vessel. Part of the Hot PUW2 tank and is used to record the tanks temperature. Bimetalic Temperature indicator provides temperature monitoring for detergent solution, operationally critical for effective cleaning.

13 TI-008 (Bimetalic Temperature indicator) Hot Detergent Tank T-211. It is located within the thermowell on hot detergent tank, T-211. It must work to provide a temperate reading of inside the vessel. Part of the Hot detergent tank and is used to record the tanks temperature.

14 TI-009 (Bimetalic Temperature indicator) 65-PUW2-S6-160-IH, close to HX-411 Hot PUW2 Heat Exchanger. It is located on the hot PUW2 supply line. It must work to provide a temperature reading of fluid in the line. Indicate the temperature on the supply line.

15 TI-010 (Bimetalic Temperature indicator) 65-DETERGENT-SS1-154-IH next to HX-211 Hot Detergent Exchanger. It is located on the hot detergent supply line. It must work to provide a temperature reading of fluid in the line, indicate the temperature on the supply line.

16 CT-001 (Conductivity transmitter) CIT001, PT002, FT002, 65-DETERGENT-SS1-154-IH. It is on the hot detergent supply line and must work to regulate the dosage of detergent supplied. Is on the hot detergent supply line and is used to record the conductivity on the supply line. Conductivity transmitter measures conductivity of purified water, critical for ensuring proper rinsing and removal of detergent residues. It is on the hot detergent supply line and must work to regulate the dosage of detergent supplied.

17 FS-005 (Low Flow switch) FA005L, 25-PROCESS-S6-162-NI, close to FL-401. It is located on the process line. It must work to alert low flow coming from the detergent metering pump, P-223. Low Flow switch. Detects low flow conditions, which could indicate issues with cleaning or rinsing processes.

18 FT-001 (Magnetic flow Transmitter) Monitors flow in piping systems, FIT001. V041, PT001, V007, 65-PUW2-SS1-160-IH. It is on the hot PUW2 supply line and must work to measure the flow of fluid in the supply line. Magnetic flow Transmitter. Handles detergent, which again critical for operational control and frequently relevant for product operation. Measures and provides feedback on detergent solution flow, operationally critical for ensuring proper cleaning.

19 FT-002 (Magnetic flow Transmitter) FIT002, 65-DETERGENT-SS1-154-IH, CT001, V014. It is on the hot detergent supply line and must work to measure the flow of fluid in the supply line. Measures and provides feedback on purified water flow for rinsing.

20 FT-003 (Magnetic flow Transmitter) FIT003, 65-PUW2-S6-164-IH, PI005, XV005. It is on the hot PUW2 return line and must work to measure the flow of fluid in the line.

21 FT-004 (Magnetic flow Transmitter) FIT004, TT004, PI006, 65-DETERGENT-S6-163-IH. It is on the hot detergent return line and must work to measure the flow of fluid in the line.

22 TT-001(3 wire RTD Temperature transmitters) TIT001, TI009, 65-PUW2-S6-160-IH, 25-VENT-S6-173-NI. It is on the hot PUW2 supply line and must work to record temperature of the supply. 3 wire RTD Temperature transmitters. Monitors and transmits temperature data, vital for operational control. Provides temperature measurement and feedback, essential for controlling detergent solution temperature.

23 TT-002 (3 wire RTD Temperature transmitters) TIT002, TI010, V042, PSV002, 25-VENT-S6-172-NI. It is on the hot detergent return line and must work to record temperature of the supply.

24 TT-003 (3 wire RTD Temperature transmitters) TIT003, PI005, 65-PUW2-S6-164-IH. It is on the hot PUW2 return line and must work to record temperature.

25 TT-004(3 wire RTD Temperature transmitters) Linked to TCV-006

TIT004,

65-DETERGENT-S6-163-IH, FT004. It is on the hot detergent return line and must work to record temperature (of the return detergent). 3 wire RTD Temperature transmitters. Monitors and transmits temperature data, vital for operational control.

26 TCV-005 (Steam Temperature control valve) V020, 65-PLANT STEAM-CS5-183-IH, 5-PLANT CONDENSATE-CS5-184-IH, V021, 100-PLANT STEAM-CS5-241-IH. It is on the plant steam line and must work to control steam temperature coming from the Heat exchanger, HX-411.

27 TCV-006(Steam Temperature control valve) V019, 65-PLANT STEAM-CS5-183-IH, close to HX-211, 100-PLANT STEAM-CS5-241-IH. It is on the plant steam line and must work to control steam temperature coming from the Heat exchanger, HX-211. Steam Temperature control valve. Monitors and transmits data about the temperature of steam, which also plays a role in operational control.

28 PT-001 (Sanitary Diaphragm type Pressure Indicating transmitters) PIT001, TI009, FT001, 65-PUW2-S6-160-IH, on the way to X-411. It is located on the hot PUW2 supply line. It must work to measure the pressure on the supply line.

29 PT-002 (Sanitary Diaphragm type Pressure Indicating transmitters) Linked to system pressure controls, PIT002, TI010, CT001, 65-DETERGENT-SS1-154-IH, close to HX-211. It is located on the hot detergent supply line. It must work to measure the pressure on the supply line. Sanitary Diaphragm type Pressure Indicating transmitters. Monitors pressure in the system, which is essential for safety. Measures and provides feedback on purified water flow for rinsing.

30 PI-003 (Diaphragm type pressure indicator) V003, P-209, SCS209, 65-PUW2-S6-159-IH. Located on the hot PUW2 supply line. It must work to give a pressure reading.

31 PI-004 (Diaphragm type pressure indicator) V010, V012, 65-DETERGENT -S6-153-IH, close to P-207. Located on the hot detergent supply line. It must work to give a pressure reading.

32 PI-005 (Diaphragm type pressure indicator) Ft003, TT003, 65-PUW2-S6-164-IH, HOT PUW2 RETURN. Located on the hot PUW2 return line. It must work to give a pressure reading. Diaphragm type pressure indicator, Provides pressure monitoring for detergent solution line, operationally critical for proper flow and preventing over-pressurization.

33 PI-006 (Diaphragm type pressure indicator) XV006, FT004, 65-DETERGENT-S6-163-IH, HOT DETERGENT RETURN. Located on the plant steam line. It must work to give a pressure reading. Diaphragm type pressure indicator. Provides pressure monitoring for purified water line.

34 PI-007 (Local pressure indicators c/w bourdon type gauges) V018, V019, 100-PLANT STEAM-CS5-241-IH. Located on the hot detergent return line. It must work to give a pressure reading

35 PI-008 (Diaphragm type pressure indicator) V035, 25-PROCESS-S6-162-NI, near FL401. P-223. Located on the process line. It must work to give a pressure reading. Monitors pressure of steam supply, operationally critical for proper heating of detergent solution.

36 HX-211 (Detergent Plate Heat Exchanger) 65-PLANT STEAM-CS5-183-IH, 65-DETERGENT-SS1-154-IH HOT DETERGENT SUPPLY, 65-DETERGENT -S6-153-IH, V013. PUW2 Plate Heat Exchanger. Maintains required temperature of detergent solution, operationally critical for effective cleaning.

37 HX-411 (PUW2 Plate Heat Exchanger) 65-PUW2-S6-160-IH, HOT PUW2 SUPPLY, 65-PUW2-S6-159-IH, V005, ST003, V025, 65-PLANT STEAM-CS5-183-IH. PUW2 Plate Heat Exchanger. Critical component product,

38 PSV-001 25-VENT-S6-173-NI, 65-PUW2-S6-160-IH, close to HX-411. PUW2 Sanitary Pressure Relief Valve. Helps maintain safe pressure levels in purified water lines, preventing over pressurization and potential equipment damage.

39 PSV-002 25-VENT-S6-172-NI, TT02, next to XH-211, next to 65-DETERGENT-SS1-154-IH HOT DETERGENT SUPPLY. Detergent Sanitary Pressure Relief Valve. Maintains safe pressure levels in detergent lines.

40 T-411 (Hot PUW2 Tank) Lines: 100-VENT-S6-168-NI, 0-PUW1-S6-148-IH, 65-PUW2-S6-164-IH, 80-PUW1-S6-486-IH, 80-PUW1-S6-486-IH, 80-PUW2-S6-155-IH & LIT001, LT001, LS003, LAL003, TI007, SG001, ZS030, LS005, LA005, XV008, PRV001. Hot PUW2 Tank. Handles PUW2 used in processes that directly affect product safety.

41 T-211 (Hot Detergent Tank) Surrounded by: 50-DRAIN-S6-170-NI, 80-DETERGENT-S6-149-IH, 100-VENT-S6-166-NI, 50-PUW1-S6-147-IH, 80-PUW1-S6-486-IH, XV009, LA006, LS006, SG002, ZS031, TI008, LS004, LA004, XV004, XV002, LT002, LIT002, SG006. Hot Detergent Tank Product contact critical component,

42 XV-008 (Actuated Sanitary Ball Valve) On 50-PUW1-S6-148-IH, next to Hot PUW2 Tank. Is on line 148 and controls the supply of 25C PUW1 entering the Hot PUW2 tank.

43 XV-009 (Actuated Sanitary Ball Valve) On 50-PUW1-S6-147-IH, next to Hot Detergent Tank. Is on line 147 and controls the supply of 25C PUW1 entering the Hot detergent tank.

7.4. P&ID ScopeIn Protocol Section-7.4 include a copy/scan of the P&ID and either draw a scope bubble or yellow-highlight the in-scope components.

A piping and instrumentation diagram, or P&ID, shows the piping and related components of a physical process flow. Its most commonly used in the engineering field.

P&IDS are foundational to the maintenance and modification of the process that it graphically represents. At the design stage, the diagram also provides the basis for the development of system control schemes. For processing facilities, its a graphic representation of:

Key piping and instrument details

Control and shutdown schemes

Safety and regulatory requirements

Basic start up and operational information

Piping and Instrumentation Diagrams (P&IDs) are visual representations that depict the functional connections between piping, instrumentation, and system equipment components in the field of instrumentation and control. They are commonly developed by engineers who are creating a manufacturing process for a physical plant. Typically, these facilities necessitate intricate chemical or mechanical procedures, which are carefully planned using P&IDs to build a plant and ensure plant safety. P&IDs also serve as a point of reference for Process Safety Information (PSI) in Process Safety Management (PSM). When encountering an issue, it is advisable to begin by examining the P&ID (Process and Instrumentation Diagram). Piping and Instrumentation Diagrams (P&IDs) are highly useful records that are essential to have readily available. They serve multiple purposes, such as optimising an existing process, replacing equipment, or providing guidance for the design and execution of a new facility.

The use of Management of Change (MOC) allows for safe and efficient planning of modifications based on the provided record.

Field techs, engineers, and operators use P&IDs to better understand P&IDs. P&IDs are used by field techs, engineers, and operators to better understand P&IDs.

Understand the process and how the instrumentation is used to understand the process.

The two are interconnected. They're also great for educating people.

Contractors are involved.

P&IDs, in the realm of instrumentation and control, are schematic diagrams that depict the functional connections between pipe, instrumentation, and system equipment components. Engineers involved in constructing a physical plant typically develop these.

Reference DocumentationDocument # Document Description Document Location

##.####.##.# P&ID Engineering Library

##.####.##.# Instrument List Engineering Library

##.####.##.# Equipment List Engineering Library

##.####.##.# E&I Drawings Engineering Library

##.####.##.# Line List Engineering Library

##.####.##.# Commissioning Protocol Engineering Library

##.####.##.# Site VMP

QA Library

##.####.##.# URS QA Library

##.####.##.# System Impact Assessment QA Library

##.####.##.# Validation Plan QA Library

##.####.##.# FRS Engineering Library

##.####.##.# Validation SOP QA Library

##.####.##.# Change Control SOP QA Library

##.####.##.# Deviation Procedure QA Library

##.####.##.# Training SOP QA Library

##.####.##.# Site documentation policy QA Library

##.####.##.# Site Glossary QA Library

Definitions/ GlossaryAcronym Definition

BDS Bulk Drug Substance

EHS Environment, Health & Safety

E&I Electrical & Instrumentation

FDA The United States Food and Drug Administration is a federal agency of the Department of Health and Human Services.

FRS Functional Requirement Specification

GMP Good Manufacturing Practices

IQ Installation Qualification

ISPE HYPERLINK "https://ispe.org/" International Society for Pharmaceutical Engineering

OQ Operational Qualification

P&ID Piping & Instrumentation Diagram

QA Quality Assurance

QC Quality Control

SME Subject Matter Expert.

SOP Standard Operating Procedure

URS User Requirement Specification

VMP Validation Master Plan

Responsibilities / Subject Matter ExpertsValidation

Prepare Protocol

Departmental Review & Approval of Protocol

Execute Protocol, including dotting is & crossing ts

Co-Ordinate input from other responsible departments

Document Deviations

Prepare Report

Quality Assurance

Headers are not typically displayed on Process Unit/Utility P&IDs. Lines to or from a header must end with a number enclosed in arrow boxes. If a header serves only two or three users within a unit and can be shown with the correct sequence of branches, it should be fully displayed on the Process Unit/Utility P&ID. The Verification Body's quality manual should include procedures for ensuring the required level of quality and reliability in verification activities. This includes quality assurance measures such as review and auditing. This includes the reviews and audits outlined in Table 2, 'Quality assurance steps for verification bodies'.

Location Target Task Verification Body Internal Auditor External Technical Expert

Verification body Specific verification protocol Review Review

Test body Test plan Review -

Test body Tests system performance and test body quality management system Test system audit -

Test body Test performance Test performance audit -

Test body Test report Review -

Verification body Verification report Review Review

Verification body Statement of verification Review Review

Table - Quality assurance steps for verification body.

Review and approval of the validation protocol and report.

Confirm CV adheres to regulatory requirements and validation SOPs.

Review and approve any deviations/investigations related to cleaning studies.

Quality control

The national accreditation bodies are responsible for ensuring that ETV Verification Bodies comply with the standards set by ISO/IEC 17020 for inspection bodies type A, as well as this General Verification Protocol. This includes the requirement for a quality management system that adheres to the principles of EN ISO 9001. Additionally, the analytical laboratories must adhere to the requirements of ISO/IEC 17025 for the specific methods of testing and calibration. The Verification Body holds the ultimate responsibility for ensuring that the verification process is carried out in accordance with this General Verification Protocol. It is the duty of the Verification Body to oversee and monitor the test body's adherence to the procedures outlined in this GVP and the relevant specific verification protocol.

Verification Body

Assessment, quality assurance and control

Test Body

Quality assurance and control

AssessmentsResults

Analytical Laboratory

Accreditation Body

Results

Assessment

Figure-Principles of quality assurance in ETV (indicative only).

Complete testing of samples taken under this protocol.

Adhere to all SOPs / WIs/ Protocols associated with testing of cleaning validation samples.

Review and approve samples.

Manufacturing

The primary goal of Environmental Technology Verification (ETV) is to facilitate the adoption of environmental technologies by offering technology innovators, manufacturers, and investors the opportunity to obtain third-party validation of the effectiveness of novel environmental solutions. This enables makers to substantiate the dependability of their assertions, while aiding technology buyers in identifying advancements that align with their requirements. The anticipated effect on technology markets is to expedite the adoption and dissemination of cutting-edge environmental technologies.

Protocol and report evaluation and authorization (review and approval).

Follow/adhere any, all Standard Operating Procedures (SOPs) related to the functioning of the system/equipment.

Implement suitable measures to regulate the utilisation of the equipment. Implement appropriate controls on the use of the equipment.

Follow the established steps for setting up. Set-up according to procedures.

Ensure that all duties/tasks linked to the procedure have been done with the required training.

Implementation/execution of cleaning protocols, procedures.

Engineering

ETV prioritises quantitative and measurable factors that can be assessed through testing and are directly linked to a technology's performance and its environmental benefits. The environmental value contributed is assessed from a life-cycle standpoint, taking into account the primary advantages and impacts during the technology's lifespan, utilising a simplified and restricted life-cycle methodology. ETV differs in its purpose and does not offer the same data as other specialised environmental tools that rely on life-cycle information, such as Life-Cycle Analysis (LCA), Environmental Product Declaration (EPD), or Product Environmental Footprint (PEF).

Engineering is accountable for ensuring the secure functioning and upkeep of equipment. Responsible for the safe operation and maintenance.

Ensure that the system is prepared and capable of being executed. Verify system readiness for execution.

Adhere to the procedures for managing changes. Follow Change Control Procedures.

Apply suitable measures to regulate the use of equipment. Implement appropriate controls on the use of equipment.

Maintenance/ Calibrations

The looking into handle might be archived to guarantee an satisfactory level of quality and

unwavering quality. Portrayal of the strategy for recording surveys might be included within the quality manual. Non-analytical estimation strategies need to be clearly depicted in

the test arrange, counting required calibration and quality control. The records of test information (crude information) should be put away, exchanged, maintained and controlled in arrange to guarantee information judgment for a period characterized within the test arrange, but not shorter than 5 a long time from completion of the test.

Responsible for maintaining equipment and system.

Ensuring equipment is within calibration date.

Calibrating new equipment.

HR / Training

A strategy on instruction, preparing and information of modern staff within the test body should be included in a quality manual and should portray how the test body guarantees that tests are done by staff with satisfactory competences and information of their obligations.

The faculty capable for carrying out the test exercises might have the taking after:

sound specialized and professional preparing covering all the test exercises done by the test body;

palatable information of the prerequisites of the test methods they carry out and satisfactory specialist to carry out those strategies;

the capacity to draw up reports and records illustrating that test strategies have been carried out and prerequisites of this GVP and the particular confirmation convention have been fulfilled.

EHS

Conduct verification activities with utmost professional integrity and technical competence in the relevant field. Ensure complete independence from any external pressures or inducements, such as financial incentives, that could potentially affect judgement or the outcome of verification activities. This is particularly important when dealing with individuals or groups with a vested interest in the results.

Review and approve risk assessments for new equipment. Installation Verification Testing Procedures.

Installation Verification Testing ProceduresP&ID Walkdown Testing Procedure1. Description of Test

The objective of the test is to verify all direct impact components are installed and orientated correctly as per the functional illustration on the P&ID.

Test bodies must meet the applicable requirements outlined in part C Quality management with regards to their involvement in the verification process (C.I), quality management (C.III), and quality assurance and control for tests and analyses (C.IV). Additionally, the verification protocol specific to the technology being tested, as outlined in Chapter B.IV, may impose additional requirements on test bodies, especially in terms of quality assurance and control, to ensure the accuracy and reliability of test results and data for the technology under consideration.

Linkage to Requirements Challenged

Confirm correct installation and orientation of direct impact components as per the P&ID schematic illustration.

In the event of a need, the proposer shall decide on test bodies. The Verification Body is usually involved in discussions with the proposer to ensure that designated test bodies meet its qualification standards. The proposers determine who become test bodies although Verification Body itself may have this capacity for testing. In such cases, it is necessary for the proponent to designate analytical laboratories where the samples are to be tested.

For each PFD, multiple P&IDs will be required to provide all the needed data.

Among other information, P&ID contains details about piping and therefore it is an integral part of this drawing. An alternative approach could involve numbering each pipe and providing separate details about every line in a table attached along with this drawing.

If possible, larger units should be shown as bigger symbols in this diagram so that they are identified by their physical sizes.

https://miro.medium.com/v2/resize:fit:640/format:webp/1*jk6TGE4QI8avf_n4m74ybQ.jpeg

P&ID for Benzene Distillation (adapted from Kauffman, D., Flow Sheets and Diagrams, AIChE Modular Instruction, Series G: Design of Equipment, series editor J. Beckman, AIChE, New York, 1986, vol. 1, Chapter G.1.5, AIChE copyright 1986 AIChE, all rights reserved)

Utility connections are identified by a numbered box in the P&ID. The number within the box identifies the specific utility. The key identifying the utility connections is shown in a table on the P&ID.

Acceptance Criteria

All direct impact components are functionally installed and orientated correctly as per the P&ID specification.

Perform HAZOP design/review. It is utilized as a reference archive for the management of handle security data (PSI) in Prepare Security Administration (PSM).It permits getting the fundamental data to be able to analyze the dangers of the prepare, the potential disappointments and the existing shields in arrange to minimize the most noteworthy number of blunders in operation, plan or humans. conditional acknowledgment of existing information, in which case the conditions for acknowledgment shall be point by point in the particular confirmation convention; these conditions may incorporate the re-testing of particular prerequisites or basic estimations.

Prerequisites and/or Assumptions

All commissioning activities are complete and commissioning punch-list items are closed out.

All testers shall be trained and educated in the test method listed in section-5 below: it is crucial to the success of the testing effort that the testing process be well understood by all participants.

Test Method

On a blank copy of the P&ID draw in the direct-impact system boundary in black-ink.

Walk down the P&ID and using a yellow-highlighter confirm each component is correctly installed and orientated as represented on the P&ID.

Confirm all component tag numbers are correct.

Confirm all lines are correctly labelled.

Confirm all lines where applicable are correctly insulated.

Ensure all flow direction components are orientated correctly.

Ensure all instruments indicators are orientated correctly so as operators can readily view them in the field.

Ensure all commissioning filters are installed in filter-housings.

On the P&ID any additions shall be drawn in using blue-ink, any deletions shall be crossed-out using red ink, comments shall be inserted using green-ink, and sign and date any entries on the P&ID using black-ink.

Expected Results and Actual results

In the IQ GMP test-sheet(s) overleaf, reach a conclusion as to whether each test step has been successfully completed by transcribing bold text from the Expected Results column into the corresponding Actual Results field.

Assess each step listed and determine whether the step has passed or failed.

The person performing the test should be identified and the date the testing was performed should be recorded.

At the bottom of the test script a validation peer (other than the person performing the test) shall review the script post execution.

Quality Assurance (QA) shall approve the completed test.

Validation Peer Review

HYPERLINK "https://ie.linkedin.com/in/aisling-field-b779b9171"

AISLING FIELD Aisling Filed 18 MAR 24 Print Name Signature Date Equipment Installation Verification Procedure1. Description of Test

The objective of the test is twofold:

To verify that all direct impact equipment components are of the correct specification as per the detailed mechanical data sheets

To verify that all direct impact equipment components are installed and configured correctly as per the functional illustration on the P&ID.

2. Linkage to Requirements Challenged

Confirm correct installation and primary specifications of direct impact equipment components as detailed in the P&ID and URS.

3. Acceptance Criteria

All direct impact components are of the correct specification, are functionally installed and configured as per the P&ID, the vendor handover documentation is complete, and appropriate material certification is available.

4. Prerequisites and/or Assumptions

All commissioning activities are complete and commissioning punch-list items are closed out.

5. Test Method

On the equipment IQ GMP test sheets confirm the equipment description and critical design features. Inspect the installed equipment item in the field and while referencing the vendors documentation package verify specification conformance.

Confirm that the vendor handover package is in place and contains correct material certificates.

In the field visually confirm the following:

Equipment/instrument item is installed as per P&ID, is securely fitted and is free from damage.

Nameplate is securely fitted, clearly legible and its details conform to the design specification. Instrument and cabling are correctly tagged and details conform to the design specification.

All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID.

6. Expected Results and Actual results

In the equipment IQ verification forms, reach a conclusion as to whether each test step has been successfully completed by transcribing bold text from the Expected Results column into the corresponding Actual Results field where appropriate.

Assess each step listed and determine whether the step has passed or failed.

The person performing the test should be identified and the date the testing was performed should be recorded.

At the bottom of the test script a validation peer (other than the person performing the test) shall review the script post execution.

Quality Assurance (QA) shall approve the completed test.

Validation Peer Review

BRIAN ROCHE Brian Roche 18 MAR 24

Print Name Signature Date

Instrument Installation Verification Procedure1. Description of Test

The objective of the test is twofold:

To verify that all direct impact instruments are of the correct specification as per the detailed instrument data sheets

To verify that all direct impact instruments components are installed and configured correctly as per the functional illustration on the P&ID.

2. Linkage to Requirements Challenged

URS refers to major P&ID components. The system P&ID details all necessary process instrumentation: confirm correct installation and specification of direct impact instrument components.

3. Acceptance Criteria

All direct impact instruments are of the correct specification, are functionally installed and configured as per the P&ID, the vendor handover documentation is complete, and appropriate material, calibration and loop-check certification is available.

4. Prerequisites and/or Assumptions

All commissioning activities are complete and commissioning punch-list items are closed out.

5. Test Method

On Part-1 of the instrument GMP test sheets confirm the instrument description and critical design features. Inspect the installed instrument item in the field and while referencing the vendors documentation package verify conformance:

Manufacturer,

Calibrated Range,

MOC,

Loop Checked,

On Part-2 of the instrument GMP test sheets confirm that the appropriate vendor documentation is available in accordance with the following:

Vendor handover package is in place.

Material Certification is available for wetted parts,

Calibration Certification is available.

Loop Checks heet is available (Yes/No).

In the field visually confirm, on Part-3 of the instrument GMP test sheets confirm, the following:

Instrument item is installed as per P&ID, is securely fitted and is free from damage.

Instrument and cabling is correctly tagged and details conform to the design specification.

Instrument orientated correctly and is accessible for calibration and maintenance.

Expected Results and Actual results

In the instrument verification forms, reach a conclusion as to whether each test step has been successfully completed by transcribing bold text from the Expected Results column into the corresponding Actual Results field where appropriate.

Assess each step listed and determine whether the step has passed or failed.

The person performing the test should be identified and the date the testing was performed should be recorded.

At the bottom of the test script a validation peer (other than the person performing the test) shall review the script post execution.

Quality Assurance (QA) shall approve the completed test.

Validation Peer Review

JONATHAN WALSH Jonathan Walsh 16MARCH24

Print Name Signature Date

Piping Installation Verification Procedure1. Description of Test

The objective of the test is to verify all direct impact pipes are installed and orientated correctly as per the functional illustration on the P&ID and piping Isometrics.

2. Linkage to Requirements Challenged

Confirm correct installation and orientation of direct impact piping as per the P&ID schematic illustration and piping isometrics.

3. Acceptance Criteria

All direct impact components are functionally installed and orientated correctly as per the P&IDs and isometrics specifications.

4. Prerequisites and/or Assumptions

All commissioning activities are complete and commissioning punch-list items are closed out.

5. Test Method

Pre-populate the piping verification with the Tag # and material-of-construction (MOC) details.

In the field enter the details of the weld log for every each pipe Tag #.

Confirm the Weld Log is complete, as the Weld Log collates material-of-construction certificates and weld inspection certificates.

In the field record the details of the Pressure Test Pack for every each pipe Tag #.

Confirm the Pressure Test is complete verifying the absence of leaks

In the field enter the details of the Construction Dossier for every each pipe Tag #.

Confirm all slopes have been checked and verified as correct from the Construction Dossier.

6. Expected Results and Actual results

Assess each step listed and determine whether the step has passed or failed.

The person performing the test should be identified and the date the testing was performed should be recorded.

At the bottom of the test script a validation peer (other than the person performing the test) shall review the script post execution.

Quality Assurance (QA) shall approve the completed test.

Validation Peer Review

ADAM CHANEY Adam Chaney 19MARCH24

Print Name Signature Date

Calibration Program VerificationDuring installation verification we need to verify that instruments are in the calibration system. Here summarize a Calibration Program Verification procedure that complements the form in Protocol Section-16.2.5.

To verify that we are validating in-house installation during installation verification, we shall have the instruments in the calibration system. Calibration is a test procedure (only one) for verification testing and takes measurements as if you were calibrating, and then with the same results but obtain numerical values that does not depend on the concentration (mg/mL) or the quantity (%) by the test obtained by the test procedure. Calibration verification refers to testing materials of known concentration in the same manner as patient samples in order to ensure that the calibration of the instrument or test system for patient test results is in alignment with the requirements for calibration across the reportable range. The manufacturer of the test system should provide instruction on how to perform calibration and the frequency with which it should be done. Calibration must conform to or exceed the performance of the manufacturers instructions and the laboratories.

This protocol ensures that the Hot Detergent and Hot PUW Generation and Distribution system's critical instruments are within calibration at the time of execution, as listed and verified in Testing Sections, 16.2.5, of this protocol.

Preventative Maintenance Program VerificationDuring IQ, we need to verify that instruments are in the Preventative Maintenance system. Here summarize a Preventative Maintenance Program Verification procedure that complements the form in Protocol Section-16.2.6.

All of the reagents utilized for a test strategy are changed to modern part numbers, unless the research facility can illustrate that changing reagent parcel numbers does not influence the range utilized to report understanding test comes about, and control values are too not unfavourably affected by reagent part number changes.

There is major preventive upkeep or replacement of basic parts that may impact the tests execution. This incorporates when the research facility sends a test framework to the producer for repairs. The laboratory must check the calibration of a repaired test framework some time recently continuing patient testing and announcing comes about.

Control materials reflect an abnormal drift or move, or are exterior of the laboratorys satisfactory limits and other implies of surveying and correcting unsatisfactory control values come up short to recognize and redress the issue.

The laboratory has decided that the test systems reportable extend for quiet test results ought to be checked more regularly.

Pumps: Each pump in the system underwent preventative maintenance to guarantee their mechanical integrity and proper functioning.

Heat exchangers: Preventative maintenance was conducted on both heat exchangers in the system, and the heating elements were examined to verify their proper functioning.

Filters: Preventative maintenance was performed on each of the filters in the system to ensure their suitability for the intended function.

Pressure Safety Valves: Each of the PSV's in the system underwent preventative maintenance to ensure their proper functioning at the designated pressure.

Temperature Indicator: Preventative maintenance was performed on both temperature indicators of the tanks to maintain accurate temperature readings.

Level transmitter: Preventative maintenance was performed on both level indicators of the tanks to ensure accurate level readings.

Draft SOP VerificationPrior to proceeding to functional verification, we need to ensure the required SOPs are in-draft. Propose a list of necessary standard operating procedures for the Hot Detergent and Hot PUW Generation and Distribution system and enter the equivalent details into the form in Protocol Section-16.2.7. Ensure the details in the list of draft SOPs aligns with Protocol Section-13.8 Approved SOP Verification and its associated form in Protocol Section-16.3.8.

Standard operating procedures (SOPs) are a great way to ensure that a process or procedure is consistently followed throughout an organisation, regardless of whether there are temporary or permanent staff changes. This helps to minimise inconsistency and enhance quality. Standard operating procedures (SOPs) should include precise work instructions and can be utilised as part of a people training programme. They can also indicate conformity with organisational and regulatory regulations. It helps alleviate worries about safety and reduces the likelihood of misunderstandings. Standard Operating Procedures (SOPs) are useful for re-creating project operations when no other references are accessible, which is especially useful for evaluating historical data for present application. Furthermore, when auditing procedures, inspectors often employ SOPs as checklists. In the end, having a proper SOP will help you save time and effort while also making your work more credible, easier to compare, and more legally defendable. Using published methods does not eliminate the requirement for standard operating procedures. A standard operating procedure (SOP) for a standard analytical technique, for instance, should go into more depth than what's actually in the published method itself when outlining the steps to follow.

Standard Operating Procedures can be employed in a staff training programme as they offer exact job instructions and showcase adherence to organisational and regulatory requirements. It eradicates the potential for misinterpretation while simultaneously resolving safety apprehensions.

SOP-235 Operational and maintenance of CIP wash tanks 12

SOP-157 CIP procedures for bioreactors 4.3

SOP-1002 Operational and maintenance of steam supply line 6.7

SOP-645 Operational and maintenance of hot detergent line 15.6

SOP-880 Operational and maintenance of PUW1 supply line 3.9

SOP-184 Operational and maintenance of pumps in generation and distribution system 1.7

SOP #: 11302 Operation of the Hot detergent system

Revision 1

SOP #: 11303 Operation of the Hot PUW2 system Rev/0

SOP #: 11304 Cleaning the Hot PUW2 and Hot Detergent system Rev.0

SOP #: 11325 Examine the attachments and connections on the Hot detergent and hot PUW generation and distribution skid. Rev.2

SOP #: 11330 Assembling and disassembling the Hot detergent and hot PUW generation and distribution skid Rev.3

Test-Instrument Calibration VerificationSuggest a list of test instruments that may be required for the testing phase. Enter the equivalent details into the form in Protocol Section-16.2.8

Twice a day, at least four hours apart, check and record the incubator's temperature. A NIST certified thermometer must be used to verify thermometers at least once a year, following the guidelines outlined in SOP JSELEB-111. The JSEL Quality Manual's appendix G contains a list of equipment and their SOP numbers for calibration of laboratory equipment.

List of test instruments that may be required for the testing phase.

Steam Temperature control valve,

3 wire RTD Temperature transmitters,

Sanitary Diaphragm type Pressure Indicating transmitters,

Magnetic flow Transmitter,

Conductivity transmitter,

Bimetalic Temperature indicator,

Hydrostatic Pressure type level Transmitter,

Actuated Sanitary Ball Valve,

High Level Switch (Tuning fork type),

High Level Switch (Tuning fork type). 12. Progression Approval to Proceed to Functional VerificationThe signatories below verify the following:

That the installation verification testing phase is sufficiently complete and permission is given to progress to the functional verification testing phase.

All critical deviations from the installation verification testing phase have been closed out, or a change control initiated in its place.

All critical items are installed.

All operational critical instruments will remain in a calibrated state during the functional verification testing phase.

Prepared By:____Maria Kaluzna_______________Date:15MAR24___

Validation Engineer

Approved By:__Daniel Crandol_____________Date:_18MAR24__

Validation Manager

Your signature attests that you have reviewed this document and it complies with relevant validation policies & procedures.

Approved By:_Frank Roche_______________Date:_19MAR24___

Engineering

Your signature attests that that you have reviewed this document and confirm its accuracy against the associated specifications and design.

(align with Responsibilities Protocol Section-2)

Approved By:__Calvin Moore_____________Date:_22MAR24_____

Your signature attests that you have reviewed this document and confirm it complies with cGMPs regulatory requirements, local and corporate policies, that it complies with relevant Quality Assurance policies & procedures(align with Responsibilities Protocol Section-2)

Approved By:__Nick Walsh__________Date:__25MAR24_______

Maintenance/ Calibrations Engineer

Your signature attests that you have reviewed this document and it complies with relevant calibrations policies & procedures.

(align with Responsibilities Protocol Section-2)

Approved By:__James Egan_____________Date:_25MAR24_____

Manufacturing

Your signature attests that you have reviewed this document and confirm it complies with relevant manufacturing policies & procedures

(align with Responsibilities Protocol Section-2)

Approved By:__Cian Brennan _____________Date:_26MAR24_____

HR/Training

Your signature attests that you have reviewed this document and confirm it complies with relevant manufacturing policies & procedures

(align with Responsibilities Protocol Section-2)

Approved By:__ Kathy McDonald _____________Date:_26MAR24_____

EHS

Your signature attests that you have reviewed this document and confirm it complies with relevant manufacturing policies & procedure

(align with Responsibilities Protocol Section-2)

Approved By:__Matthew Doyle __________Date:__25MAR24____

Your signature attests that you have reviewed this document and it complies with relevant calibrations policies & procedures.

(align with Responsibilities Protocol Section-2)

12.1.Operational-Critical-Instrument Calibration Verification FormPage _ 1__ of _ _3_

Operational-Critical-Instrument Calibration Verification Form

Critical instruments associated with the system will remain in a calibrated state during the anticipated OQ execution timeframe? (Yes/No) Verified By / Date

Tests that are considered non-quantitative (e.g., Prothrombin Time (PT) and Activated Clotting Time (ACT), which are measured in units of time) do not require calibration verification.

In order to meet the calibration verification requirements for automated cell counters, the laboratory must adhere to the manufacturer's instructions for operating the instrument. Additionally, the laboratory must test two levels of control materials each day of testing. The control results must meet the laboratory's criteria for acceptability.

The laboratory must follow the manufacturer's instructions for operating the instrument and test three levels of control materials (the lowest, mid-level, and highest level available) more than once per testing day. The results of the tests must meet the laboratory's acceptability criteria, and the control materials must be traceable to National Institute of Standards and Technology (NIST) reference materials in order for the calibration verification requirements for automated chemistry analyzers to be considered met.

Providing that the calibration procedure for the test system incorporates three or more levels of calibration material, as well as a low, a medium, and a high value, and that it is carried out at least once every six months, then the requirement for calibration verification is also satisfied.

New lot numbers are assigned to all reagents used in a test procedure, unless the laboratory can prove that changing lot numbers does not impact the reporting range of patient test results or affect control values.

There is major preventive maintenance or replacement of critical parts that may influence the tests performance.This includes when the laboratory sends a test system to the manufacturer for repairs. The laboratory must check the calibration of a repaired test system before resuming patient testing and reporting results

Page _ 2__ of _ 3__

LS-003 MK 15MAR24

LS-004 MK 15MAR24

LS-005 MK 15MAR24

LS-006 MK 15MAR24

LT-001 MK 15MAR24

LT-002 MK 15MAR24

TI-007 MK 15MAR24

TI-008 MK 15MAR24

TI-009 MK 15MAR24

TI-010 MK 15MAR24

CT-001 MK 15MAR24

FS-005 MK 15MAR24

FT-001 MK 15MAR24

FT-002 MK 15MAR24

FT-003 MK 15MAR24

FT-004 MK 15MAR24

TT-001 MK 15MAR24

TT-002 MK 15MAR24

TT-003 MK 15MAR24

TT-004 MK 15MAR24

XV-008 MK 15MAR24

XV-009 MK 15MAR24

Comments:

MK 15MAR24

Reviewed By:

Validation Daniel Crandol Date: 18MAR24

Approved By:

(QA) Calvin Moore Date: 22MAR24

Page _3 __ of _ 3__

Operational-Critical-Instrument Calibration Verification Form

Critical instruments associated with the system will remain in a calibrated state during the anticipated OQ execution timeframe? (Yes/No) Verified By / Date

Auxiliary P&ID's refer to the P&ID's that depict the equipment pipes and instrumentation associated with a certain item of equipment. An illustrative instance would be the supplementary apparatus, piping, and instrumentation required for a substantial compressor. The objective is to maintain the Process Unit P&ID's with minimal visual distractions.

The size, service, line number, Piping Material Specification, type of tracing and whether insulated shall be indicated for each line on the P&ID's. Where lines leave/enter a P&ID the destination/origin equipment tag shall be indicated.

When it comes to piping layout and design, any specific requirements should be clearly documented on the P&ID's. These drawings must include the relevant keywords and symbols referenced in each illustration.

Additional remarks/notes to elucidate the P&IDs will be included as necessary. For instance, the P&ID must specify that a valve must be situated adjacent to a vessel orifice.

Headers aren't typically proven at the Process Unit/ Utility P&ID`s. A line to or from a header will be terminated with a wide variety enclosed in an arrow boxes. When a header serves simplest or 3 customers inside a unit and may be proven with the best collection of branches, it will be completely proven at the Process Unit/Utility P&ID.

Distribution P&ID's should accurately depict the sequence of take-offs from the headers based on the physical layout of the equipment. This is essential for assisting in piping layout and line sizing, ultimately enabling the achievement of an efficient piping layout.

TCV-005 MK 15MAR24

TCV-006 MK 15MAR24

PT-001 MK 15MAR24

PT-002 MK 15MAR24

PI-003 MK 15MAR24

PI-004 MK 15MAR24

PI-005 MK 15MAR24

PI-006 MK 15MAR24

PI-007 MK 15MAR24

PI-008 MK 15MAR24

Comments: MK 15MAR24

Reviewed By:

Validation Daniel Crandol Date: 18MAR24

Approved By:

(QA) Calvin Moore Date: 22MAR24

13. Functional Verification Testing Procedures13.3.1Hot Detergent System Level Control

13.3.2Hot Detergent System Flow Control

13.3.3Hot Detergent System Temperature Control

13.3.4Hot Detergent System Detergent Dosing Control

13.3.5Hot PUW System Level Control

13.3.6Hot PUW System Flow Control

13.3.7Hot PUW System Temperature Control

13.3.8Approved SOP Verification

13.1. Hot Detergent System Level Control1. Short description of the test

The objective of this test is to confirm that the Hot Detergent Tank is filled and maintained to a level of 5775 litres +/-5% from the 25C PUW1 water loop.

2. Linkage to the requirements challenged

URS Section 3.3:

The system shall have the facility to maintain the level in the Hot Detergent Tank at 5775 litres +/-5%.

Operationally Critical Component(s):

Hydrostatic Pressure Type level transmitter LT-002

Low level Switch (tuning fork type) LS-004

High Level Switch (tuning fork type) LS-006

Acceptance criteria for the test

The level measurement LT-002 shall read 5775 litres +/-5% before, during and after the maximum instantaneous detergent drawdown.

Prerequisites and or assumptions

All commissioning activities are complete and commissioning punch-list items are closed out.

Level transmitter LT-002 is currently within calibration

5. Specific Test Steps

The Hot Detergent Tank is fed directly from the 25C PUW1 water loop.

At time = 0 (t0-min) confirm the level in the Detergent Tank.

Note the level in the tank every 5-minutes until it reaches 5775 litres +/-5%. The filling of the tank should stop automatically at this level.

Open the drain valve at the bottom of the tank and flow the water to drain. The tank should automatically start filling again from the 25C PUW1 water loop and maintain a level of 5775 litres +/-5%.

Note the level in the tank every 5-minutes for 30-minutes.

Close the drain valve and the level in the tank should maintain 5775 litres +/-5% for further 30-minutes with no further drawdown.

In the table provided confirm the level in the Hot Detergent Tank by recording the value at successive 5-minute intervals, noting the time for each measurement

Print out the readings of level in the tank (LT-002) from the computer control system during the test period and append to this test section.

6. Expected results and Actual results

In the check-sheets in Appendix-C1, reach a conclusion as to whether each test step has been successfully completed by transcribing bold text from the Expected Results column into the corresponding Actual Results field.

Assess each step listed and determine whether the step has passed or failed.

The person performing the test should be identified and the date the testing was performed should be recorded.

At the bottom of the test script a validation peer (other than the person performing the test) shall review the script post execution.

Quality Assurance (QA) shall approve the completed test.

Validation Peer Review

AISLING FIELD Aisling Field 18MAY24

Print Name Signature Date

13.2. Hot Detergent System Flow Control1. Short description of the test

The objective of this test is to confirm that the flow rate of the Hot Detergent transfer loop is maintained between 3,000 litres/hr +/-5% and 25,000 litres/hr +/-5%, before, during and after the transfer of water from the Hot Detergent Tank into reactors RE-119 and RE-140 (which are both to be filled at the same time at a rate of 11,000 litres/hr each).

2. Linkage to the requirements challenged

The system shall be capable of achieving and maintaining a maximum outward flowrate of the loop to reactors RE-119 and RE-140 of 25,000 litres/hr +/-5%

The system shall be capable of achieving and maintaining a minimum return flowrate of the loop to the Hot Detergent tank of 3,000 litres/hr +/-5% when filling the two reactors RE-119 and RE-140 at a rate of 11,000 litres/hr.

The maximum number of simultaneous users being washed by the CIP system shall be two.

Operationally Critical Component(s):

Magnetic Flow Transmitter FT-002,

Magnetic Flow Transmitter FT-004,

Hydrostatic Pressure Type level transmitter LT-002,

Hydrostatic Pressure Type level transmitter LT-119,

Hydrostatic Pressure Type level transmitter LT-140.

3. Acceptance criteria for the test

The online flow measurement FT-002 (on the outward flow loop) shall read 25,000 litres/hr +/-5% before, during and after the maximum transfer flowrate into RE-119 and RE-140.

The online flow measurement FT-004 (on the return loop) shall read 3,000 litres/hr +/-5% to before, during and after the maximum transfer flowrate into RE-119 and RE-140.

4. Prerequites and or assumptions

All commissioning activities are complete and commissioning punch-list items are closed out.

Flow transmitters FT-002 and FT-004 and level transmitters LT-002, LT-119 and LT-140 are currently within calibration.

5. Specific Test Steps

Check the Hot Detergent Tank is filled to a level of 5775 litres +/-5% from the 25C PUW1 water loop, noting the level reading on LT-002

Start the Hot Detergent Pump circulating.

Confirm the initial flow reading of FT-002 and FT-004 at time = 0 (t0-min) and note the flow every 5-minutes for 30-minutes.

Open the transfer valves to RE-119 and RE-140 and transfer 5,500 litres into each vessel (this will take approximately 30-minutes), noting the level on LT-119 and LT-140

Note the flow reading on FT-002 and FT-004 every 5-minutes during the transfer.

Note the level in the Hot Detergent Tank maintains 5775 litres +/-5% (LT-002) during the transfer

After transferring 5,500 litres into both RE-119 and Re-140 stop the transfer and maintain the CIP skid in normal recirculation operation mode for a further 30-minutes with no further drawdown.

In the table provided confirm the level in the Hot Detergent Tank (LT-002) and the flowrate readings of FT-002 and FT-004 by recording the value at successive 5-minute intervals, noting the time for each measurement.

In the same table also record the values for level in reactor RE-119 and reactor RE-140 from level-transmitters LT-119 and LT-140.

Print out the readings of FT-002, FT-004, LT-119 and LT-140 from the computer control system during the test period and append to this test section.

6. Expected results and Actual results

Assess each step listed and determine whether the step has passed or failed.

The person performing the test should be identified and the date the testing was performed should be recorded.

At the bottom of the test script a validation peer (other than the person performing the test) shall review the script post execution.

Quality Assurance (QA) shall approve the completed test.

Validation Peer Review

AISLING FIELD Aisling Field 18 MAY 24

Print Name Signature Date

Quality Control Review

MATTHEW DOYLE Matthew Doyle 18 MAY 24

Print Name Signature Date

13.3. Hot Detergent System Temperature Control1. Short description of the test

The objective of this test is to confirm that the supply temperature of Hot Detergent is maintained at 80C5C, before, during and after maximum instantaneous detergent drawdown when the two biggest users (reactors RE-119 and RE-140) are being be charged simultaneously.

2. Linkage to the requirements challenged

The Hot Detergent supply temperature shall be maintained by a closed loop control system, which modulates steam flow to the heat exchanger.

The control system shall be capable of controlling the supply temperature to within +/-5C of the setpoint (80C5C).

Operationally Critical Component(s):

Bimetalic Temperature Indicator TI-008,

3 wire RTD Temperature transmitter TT-002,

3 wire RTD Temperature transmitter TT-004,

Magnetic Flow Transmitter FT-002,

Magnetic Flow Transmitter FT-004,

Hydrostatic Pressure Type level transmitter LT-002,

Hydrostatic Pressure Type level transmitter LT-119,

Hydrostatic Pressure Type level transmitter LT-140.

3. Acceptance criteria for the test

The online temperature measurements TT-002 (on the outward loop) & TT004 (on the return loop) reads 80C5C before, during and after the maximum instantaneous detergent drawdown to fill RE-119 and RE-140.

4. Prerequites and or assumptions

All commissioning activities are complete and commissioning punch-list items are closed out.

Temperature transmitters TT-002 & TT-004, flow transmitters FT-002 and FT-004, level transmitters LT-002, LT-119 and LT-140 are currently within calibration.

5. Specific Test Steps

Check the Hot Detergent Tank is filled to a level of 5775 litres +/-5% from the 25C PUW1 water loop, noting the level reading on LT-002

Start the Hot Detergent Pump circulating and confirm the initial flow reading of FT-002 and FT-004 are 25,000 litres/hr

Note the initial temperature of TT-002 and TT-004 at time = 0 (t0-min) and commence heating the recirculating water to up 80C5C noting the temperature readings every 5-minutes.

Maintain the temperature at 80C5C for 30-minutes on the recirculation loop.

Open the transfer valves to RE-119 and RE-140 and transfer 5,500 litres into each vessel (this will take approximately 30-minutes), noting the level on LT-119 and LT-140

Note the flow reading on FT-002 and FT-004 and the level reading in the Hot Detergent Tank (LT-002) every 5-minutes during the transfer.

Note the temperature of TT-002 and TT-004 during the transfer. It should maintain 80C5C

After transferring 5,500 litres into both RE-119 and RE-140 stop the transfer and maintain the CIP skid in normal recirculation operation mode for a further 30-minutes with no further drawdown.

In the table provided confirm the temperature of TT-002 and TT-004, and in the reactors (LT-119 and LT-140) and the flowrate readings of FT-002 and FT-004 by recording the value at successive 5-minute intervals, noting the time for each measurement.

Print out the readings of TT-002, TT-004, FT-002, FT-004, LT-119 and LT-140 from the computer control system during the test period and append to this test section.

6. Expected results and Actual results

Assess each step listed and determine whether the step has passed or failed.

The person performing the test should be identified and the date the testing was performed should be recorded.

At the bottom of the test script a validation peer (other than the person performing the test) shall review the script post execution.

Quality Assurance (QA) shall approve the completed test.

Validation Peer Review

JONATHAN WALSH

Jonathan Walsh 25 MAY 24

Print Name Signature Date

13.4. Hot Detergent System Detergent Dosing Control1. Short description of the test

At 80C5C, 2% 0.05% detergent concentration is equivalent to 500 Scm-1 0.25 Scm-1. The objective of this test is to confirm that the supply detergent concentration, at a temperature of 80C5C, is maintained at 500 Scm-1 0.25 Scm-1, before, during and after maximum instantaneous detergent drawdown when the two biggest users (reactors RE-119 and RE-140) are being be charged simultaneously.

2. Linkage to the requirements challenged

URS Section 3.5:

The system shall have the facility to automatically dose STERIS 100 detergent to the required concentration (2% 0.05%)

Online conductivity measurement shall be provided to verify the detergent concentration

Operationally Critical Component(s):

Conductivity transmitter CT-001,

3 wire RTD Temperature transmitter TT-002,

3 wire RTD Temperature transmitter TT-004,

Magnetic Flow Transmitter FT-002,

Magnetic Flow Transmitter FT-004,

Hydrostatic Pressure Type level transmitter LT-002,

Hydrostatic Pressure Type level transmitter LT-119,

Hydrostatic Pressure Type level transmitter LT-140.

3. Acceptance criteria for the test

At 80C5C, the online conductivity measurement CT-001 read 500 Scm-1 0.25 Scm-1 before, during and after the maximum instantaneous detergent drawdown.

4. Prerequisites and or assumptions

All commissioning activities are complete and commissioning punch-list items are closed out.

Conductivity transmitter CT-001, temperature transmitters TT-002 & TT-004, flow transmitters FT-002 and FT-004, level transmitters LT-002, LT-119 and LT-140 are currently within calibration.

5. Specific Test Steps

Check the Hot Detergent Tank is filled to a level of 5775 litres +/-5% with PUW water loop (noting the level reading on LT-002).

Start up the hot detergent recirculation system. Give the system time to warm up until it is recirculating this water at 80C5C (noting the temperature readings on TT-002 and TT-004) at a flow of 25,000 litres/hr (noting the flow readings on FT-002 and FT-004).

Start introducing detergent into the recirculation system at time = 0 (t0-min) and note the conductivity measurement of the recirculating water every 5-minutes for the next 30 minutes. The concentration of detergent in the water is measured by its conductivity using CT-001 until it reaches a level of 500 Scm-1 0.25 Scm-1 (equivalent to a detergent concentration of 2% 0.05%).

Maintain the conductivity of the recirculation loop at 500 Scm-1 0.25 Scm-1 at a temperature of 80C5C and a flow of 25,000 litres/hr. Open the transfer valves to RE-119 and RE-140 and transfer 5,500 litres into each vessel (this will take approximately 30-minutes), noting the level on LT-119 and LT-140.

Note the conductivity readings (CT-001) for the recirculation loop every 5-minutes during the transfer, in addition to the temperature (80C5C) and the flow (25,000 litres/hr) and the level of Hot Detergent Tank.

After transferring 5,500 litres into both RE-119 and RE-140 stop the transfer and maintain the CIP skid in normal recirculation operation mode for a further 30-minutes with no further drawdown.

In the table provided confirm the conductivity of CT-001, the temperature of TT-002 and TT-004, and in the reactors (LT-119 and LT-140) and the flowrate readings of FT-002 and FT-004 by recording the value at successive 5-minute intervals, noting the time for each measurement.

Print out the readings of CT-001, TT-002, TT-004, FT-002, FT-004, LT-119 and LT-140 from the computer control system during the test period and append to this test section.

6. Expected results and Actual results

Assess each step listed and determine whether the step has passed or failed.

The person performing the test should be identified and the date the testing was performed should be recorded.

At the bottom of the test script a validation peer (other than the person performing the test) shall review the script post execution.

Quality Assurance (QA) shall approve the completed test.

Validation Peer Review

JONATHAN WALSH Jonathan Walsh 25 MAY 24

Print Name Signature Date

13.5. Hot PUW System Level Control1. Short Description of the Test

The objective of this test is to confirm that the Hot PUW2 Tank is filled and maintained to a level of 5775 litres +/-5% from the 25C PUW1 water loop.

2. Linkage to the requirements challenged

URS Section 4.4:

The system shall have the facility to maintain the level in the Hot PUW2 Tank at 5775 litres +/-5%.

Operationally Critical Component(s):

Hydrostatic Pressure Type level transmitter LT-001,

Low level Switch (tuning fork type) LS-003,

High Level Switch (tuning fork type) LS-005.

3. Acceptance criteria for the test

The level measurement LT-001 shall read 5775 litres +/-5% before, during and after the maximum instantaneous detergent drawdown.

4. Prerequisites and or assumptions

All of the commissioning operations have been finished, and all of the items on the commissioning punch list have been closed out.

Each and every tester is required to receive training and education in the testing process/method that is outlined in section 5 below: To ensure that the successful completion of the testing endeavour, it is essential that all participants have a solid understanding of the testing procedure.

At this moment, the level transmitter LT-001 is inside the calibration period- is currently within calibration.

5. Specific Test Steps

The Hot PUW2 Tank is fed/ supplied directly from the 25C PUW1 water loop.

At time = 0 (t0-min), verify the level in the heated PUW2 Tank.

Monitor the tank's level at 5-minute intervals until it reaches 5775 litres with a tolerance of +/- 5%. The tank should automatically cease filling at this particular level.

Activate the drain valve located at the base of the tank to release and remove the water. The tank should initiate automatic refilling from the 25C PUW1 water loop and sustain a volume of 5775 litres with a tolerance of +/-5%.

Monitor the tank level at 5-minute intervals for a duration of 30 minutes.

After closing the drain valve, the level in the tank should remain at 5775 litres +/- 5% for an additional 30 minutes without any further decrease.

Record the level in the Hot PUW2 Tank at repeated 5-minute intervals in the given table, noting the time for each measurement.

Retrieve and record the level readings of tank LT-001 from the computer control system throughout the testing period/ time, and add them to this specific test section.

6. Expected results and Actual results

Assess each step listed and determine whether the step has passed or failed.

The person performing the test should be identified and the date the testing was performed should be recorded.

At the bottom of the test script a validation peer (other than the person performing the test) shall review the script post execution.

Quality Assurance (QA) shall approve the completed test.

Validation Peer Review

BRIAN ROCHE Brian Roche 18 JUN 24

Print Name Signature Date

13.6. Hot PUW System Flow Control1. Short Description of the Test

The purpose of this test is to verify that the flow rate of the Hot PUW2 transfer loop remains within the range of 3,000 liters/hr +/-5% and 25,000 liters/hr +/- 5%. This verification is done before, during, and after the transfer of water from the Hot PUW2 Tank to reactors RE-119 and RE-140. Both reactors are to be filled simultaneously at a rate of 11,000 liters/hr each.

2. Linkage to Requirements Challenged

The system shall be capable of achieving and maintaining a maximum outward flowrate of the loop to reactors RE-119 and RE-140 of 25,000 litres/hr +/-5%..

The system shall be capable of achieving and maintaining a minimum return flowrate of the loop to the Hot PUW2 tank of 3,000 litres/hr +/-5% when filling the two reactors RE-119 and RE-140 at a rate of 11,000 litres/hr.

The maximum number of simultaneous users being washed by the CIP system shall be two.

Operationally Critical Component(s):

Magnetic Flow Transmitter FT-001,

Magnetic Flow Transmitter FT-003,

Hydrostatic Pressure Type level transmitter LT-001,

Hydrostatic Pressure Type level transmitter LT-119,

Hydrostatic Pressure Type level transmitter LT-140.

3. Acceptance Criteria for the Test

The online flow measurement FT-001 (on the outward flow loop) shall read 25,000 litres/hr +/-5% before, during and after the maximum transfer flowrate into RE-119 and RE-140.

The online flow measurement FT-003, located on the return loop, should display a reading of 3,000 litres/hr with an acceptable deviation of +/-5% both before, during, and after the maximum transfer flowrate into RE-119 and RE-140.

4. Prerequisites and/or assumptions

All operations related to commissioning have been finished and any remaining items on the commissioning punch-list have been resolved.

All testers must undergo training and education in the test method specified in section-5 below. It is essential for the testing endeavor's success that all participants have a thorough understanding of the testing process.

The flow transmitters FT-001 and FT-003, as well as the level transmitters LT-001, LT-119, and LT-140, are presently calibrated.

5. Specific Test Steps

1. Verify that the Hot PUW2 Tank is filled to a volume of 5775 litres with a tolerance of +/-5% using water from the 25C PUW1 water loop. Record the level reading on LT-001. 2. Initiate the circulation of the Hot PUW2 Pump. 3. Verify the first flow measurement of FT-001 and FT-003 at time = 0 (t0-min) and record the flow rate every 5 minutes for a duration of 30 minutes. 4. Activate/ open the transfer valves for RE-119 and RE-140 and proceed to transfer 5,500 litres into each vessel. This process will take approximately 30 minutes. Make sure to monitor the level on LT-119 and LT-140. 5. Record the flow measurement on FT-001 and FT-003 every 5 minutes during the transfer. 6. The level in the Hot PUW2 Tank remains at 5775 litres +/-5% (LT001) during the transfer. 7. Cease the transfer after moving 5,500 litres into both RE-119 and RE-140. Keep the CIP skid in regular recirculation operation mode for an additional 30 minutes without any further reduction in volume. 8. Please verify the level in the Hot PUW2 Tank (LT-001) and the flowrate readings of FT-001 and FT-003 in the accompanying table. Record the values at 5-minute intervals, noting the time for each measurement. 9. Additionally, document the values for the level in reactor RE-119 and reactor RE-140 obtained from the level-transmitters LT-119 and LT-140 in the same table. 10. Retrieve and record the data readings of FT-001, FT-003, LT-119, and LT-140 from the computer control system throughout the duration of the test, and add them to this specific test section.

6. Expected results and Actual results

In the check-sheets provided in Appendix-C1, determine if each test step has been properly executed by copying the bold text from the 'Expected Results' column into the relevant 'Actual Results' field.

Evaluate each individual stage and ascertain whether it has been successful or not.

It is important to identify the individual conducting the exam and record the date on which the testing took place.

After the test script is executed, a validation peer, who is not the person conducting the test, shall evaluate the script.

The completed test must be approved by Quality Assurance (QA).

Validation Peer Review

BRIAN ROCHE Brian Roche 18 MAY 24

Print Name Signature Date

13.7. Hot PUW System Temperature Control1. Short Description of the Test

The objective of this test is to confirm that the supply temperature of Hot PUW is maintained at 80C5C, before, during and after maximum instantaneous detergent drawdown when the two biggest users (reactors RE-119 and RE-140) are being be charged simultaneously.

2. Linkage to Requirements Challenged

The Hot PUW supply temperature might be kept up by a closed circle control framework, which balances steam stream to the warm exchanger.

The control system shall be capable of controlling the supply temperature to within +/-5C of the setpoint (80C5C).

Operationally Critical Component(s):

Bimetalic Temperature Indicator TI-007,

3 wire RTD Temperature transmitter TT-001,

3 wire RTD Temperature transmitter TT-003,

Magnetic Flow Transmitter FT-001,

Magnetic Flow Transmitter FT-003,

Hydrostatic Pressure Type level transmitter LT-001,

Hydrostatic Pressure Type level transmitter LT-119 ,

Hydrostatic Pressure Type level transmitter LT-140.

3. Acceptance Criteria for the Test

The online temperature measurements TT-001 (on the outward loop) and TT-003 (on the return loop) indicate a temperature of 80C5C before, during, and after the maximum instantaneous detergent drawdown to fill RE-119 and RE-140.

4. Prerequisites and/or assumptions

All the activities related to commissioning have been finished and all the remaining tasks on the commissioning punch-list have been resolved.

All testers must undergo training and education in the test method specified in section-5 below. It is essential for the success of the testing endeavour that all participants have a thorough understanding of the testing process.

The temperature transmitters TT-001 and TT-003, flow transmitters FT-001 and FT-003, and level transmitters LT-001, LT-119, and LT-140 are currently calibrated.

5. Specific Test Steps

1. Verify that the Hot PUW2 Tank is filled with a volume of 5775 litres, with a tolerance of +/-5%, from the 25C PUW1 water loop. Record the level reading on LT-001. 2. Commence the circulation of the Hot PUW2 Pump and verify that the initial flow readings of FT-001 and FT-003 are 25,000 litres per hour. 3. Record the initial temperature of TT-001 and TT-003 at time = 0 (t0-min) and begin heating the recirculating water until it reaches a temperature of 80C5C. Take note of the temperature measurements every 5 minutes. 4. Ensure that the temperature remains at 80C5C for a duration of 30 minutes on the recirculation loop. 5. Begin the transfer process by opening the transfer valves to RE-119 and RE-140. Transfer a total of 5,500 litres into each vessel. This process will take approximately 30 minutes. Make sure to observe and record the level on LT-119 and LT-140. 6. Monitor the flow readings on FT-001 and FT-003, as well as the level reading in the Hot PUW2Tank (LT-001), every 5 minutes during the transfer. 7. Take note of the temperature of TT-001 and TT-003 during transferring. The temperature should be maintained at 80C5C. 8. Cease the transfer after moving 5,500 litres into both RE-119 and RE-140. Keep the CIP skid in regular recirculation operation mode for an additional 30 minutes without any further reduction in volume. 9. Please verify the temperature of TT-001 and TT-003, as well as the temperature in the reactors (LT-119 and LT-140), and the flowrate readings of FT-001 and FT-003. Record these values at 5-minute intervals, noting the time of each measurement. 10. During the test time, get and add the readings of TT-001, TT-003, FT-001, FT-003, LT-119, and LT-140 from the computer control system to this test section.

6. Expected Results and Actual Results

Evaluate each individual stage and assess whether it has been successful or not.

The individual conducting the test should be recognised, and the date of testing should be documented.

After the test script is completed, a validation peer, who is not the person conducting the test, shall examine the script.

The completed test must be approved by Quality Assurance (QA).

Validation Peer Review

HYPERLINK "https://ie.linkedin.com/in/aisling-field-b779b9171"

AISLING FIELD Aisling Filed 18 MAY 24

Print Name Signature Date

13.8. Approved SOP VerificationIn Protocol Section-13.8 Approved SOP Verification ensure this list of approved SOPs aligns with Protocol Section-11.7 and its associated form in Protocol Section-16.2.7. Enter the equivalent details in the form collated in Protocol Section-16.3.8.

The affirmed SOP confirmation frame in segment 16.3.8 contains a list of endorsed SOPs for the utilize of the Hot cleanser and Hot PUW2 generation and Distribution/dissemination framework. These SOPs adjust with the draft SOPs laid out in segment 16.2.7. Their most later modification and successful date are included in case pertinent.

See Protocol Section-16.3.8.

SOP# Title Revision #

SOP-235 Operational and maintenance of CIP wash tanks 12

SOP-157 CIP procedures for bioreactors 4.3

SOP-1002 Operational and maintenance of steam supply line 6.7

SOP-645 Operational and maintenance of hot detergent line 15.6

SOP-880 Operational and maintenance of PUW1 supply line 3.9

SOP-184 Operational and maintenance of pumps in generation and distribution system 1.7

14. Protocol Quality Procedures14.1. Signature LogSummarize Signature-Log procedure that complements the log in Protocol Section-16.1.

The protocol signature log in section 16.1 contains a list of signatures of personnel who will approve (see section 2, Approvals page) and SMEs that will contribute to this protocol (see section 10, Responsibilities/Subject Matter Experts). Their printed names, initials and signatures are located in section 16.1, as well as confirmation of their GMP training.

Every individual who has made an entry into the procedure is required to complete the Signature Log Check form. This Signature Log Check sheet provides a concise summary of the individuals who participated in the verification of this equipment for an auditor.

14.2. Deviation ProcedureSummarize a protocol deviation procedure that complements the Deviation log in Protocol Section-16.4 and the Deviation Form in Protocol Section-16.5.

The deviation log in section 16.4 comprises a comprehensive record of the deviations that took place during the validation process of the Hot Detergent & Hot PUW2 system. This log includes the deviation number, a concise narrative of the deviation, the date when the deviation occurred, information on whether the deviation has been resolved, and whether there is an accompanying change number. The deviation forms for each logged deviation are stored in section 16.5. The deviation form provides confirmation of the system type (direct, indirect, or no impact), component type (critical or non-critical), and the specific items that are affected.

The protocol/procedure for deviation check sheets entails promptly addressing any identified issues by according to the prescribed procedure, promptly notifying the appropriate individuals, and expeditiously resolving the problem. The approach should provide a comprehensive explanation of the steps involved in identifying, recording, examining, and resolving any deviations. Distinct deviations can be categorised into many groups: Rectification/ correction of protocol generation mistakes.

Rectification of data entry errors during execution.

Repeating a test due to a clearly recognised technical problem, an identifiable technical error during execution. Simplifying the criteria of a test. Reducing the complexity of a test's criteria. An exam has been eliminated. A test has been removed.

14.3. Change Control ProcedureSummarize a Change Control deviation procedure that complements the Change Control log in Protocol Section-16.6 and the Change Control Form in Protocol Section-16.7.

The change control log in section 16.6 contains a list of changesettingsappliedduringsystemvalidation ofhotdetergent andhotPUW2.The log contains the change control #, P&ID,changesummary,changedate, pre-commitdate andpost-commitdate.Section 16.7storesthe changemanagementforms for each changemanagement saved.The change control form confirms the change #,impacton already committeditems, proposed change,systemimpact and component impact.Due to the proposedchange, various testsand documentation updates are required.The project engineer calculates thecost ofthechange anditsimpact on the projectschedule.Multiple signatures mustbeverifiedby therelevant staff.If the change check is accepted, the listofdocuments to update is checked.Once the post-change testing is completed and completed, multiplesignatures will be requiredfrom therelevant personnel.

Change management is a strategic process that ensures the smooth and systematic implementation of modifications to a product or system. It reduces the likelihood of introducing unwanted alterations to a system, which can lead to system defects or reversing modifications made by other programme users. The change control process is comprised of seven distinct steps:

Explain the proposed modification. Describe the suggested change.

Change must be documented/ recorded and supported with valid reasons, justified.

Evaluate the potential hazards and repercussions of the modification. Assess the change's risks and consequences.

The change control committee will either accept or reject the request for change.

Generate and evaluate the modification. Create and test the change.

Authorise/approve the upgrade and implement it. Conclude the modification and thoroughly verify that all paperwork is in proper condition. Close the change and double-check that all documentation is in order.

15. IOQ Protocol Summary ReportFollowing field execution of this validation protocol a validation report that cross-references the validation protocol will be prepared, summarising the results obtained, commenting on any deviations observed, and drawing the appropriate conclusions, including recommending changes to correct deficiencies.

Regulations mandate that equipment, systems, and utilities utilised for GMP manufacturing or services must exhibit suitability for their intended use and perform in accordance with their design and functional requirements. To fulfil these requirements, it is necessary to create certification protocols for the verification of installation, operation, and performance. These protocols must ensure that the installation is done correctly, that there are sufficient support utilities, that the operation is functioning properly across its whole range, and that the performance meets the stated standard operating procedures (SOPs) and operational set points. Protocols must be established, adhering to user and functional specifications, and receiving approval before implementation. Oftentimes, firms fail to implement proper protocols, or the protocols are discovered to be lacking essential information and frequently fail to provide the required testing for appropriateness and functional design criteria. IQs provide evidence that the process or equipment complies with all specifications, has been installed accurately, and has all necessary components and paperwork for ongoing operation. The installation qualification verifies that the equipment/system and its components are correctly installed in accordance with the original manufacturer's standards, as stated on page 43. During the IQ, it is necessary to do calibrations for both major and ancillary equipment. Additional factors to take into account include the design characteristics of the equipment, safety measures, environmental circumstances, and the supplier's paperwork pertaining to preventive maintenance. The design of an IQ incorporates several aspects such as equipment, process pipework, environment control systems, valves, lubricants, safety devices, alarms, instrumentation, and utilities.

16. List of AppendicesAppendix A:Signature Log

Appendix B:Installation Verification GMP checksheets

P&ID Walkdown Installation Verification

Equipment Installation Verification

Instrument Installation Verification

Piping Installation Verification

Calibration Program Verification

Preventative Maintenance Program Verification

Draft SOP Verification

Test-Instrument Calibration Verification

Appendix C:Functional Verification check-sheets

Hot Detergent System Level Control

Hot Detergent System Flow Control

Hot Detergent System Temperature Control

Hot Detergent System Detergent Dosing Control

Hot PUW System Level Control

Hot PUW System Flow Control

Hot PUW System Temperature Control

Appendix D:Deviation log

Appendix E:Deviation form

Appendix F:Change control log

Appendix G:Change control form

Appendix H:Component Impact Assessment

Appendix I:Traceability Matrix

15.1. Appendix A - Protocol Signature LogPage _1_ of _1_

Signature Log

Printed Name Signature Initials Date Company/Title/Department GMP Trained

(Yes / No)

MARIA KALUZNA Maria Kaluzna MK 25MAY24 Validation Yes

AISLING FIELD Aisling Field AF

26MAY24 Validation

Yes

BRIAN ROCHE Brian Roche BR 25MAY24 Validation Yes

JONATHAN WALSH Jonathan Walsh JW 24MAY24 Validation Yes

FRANK ROCHE Frank Roche FR 25MAY24 Engineering Yes

JAMES EGAN James Egan JE 26MAY24 Manufacturing Yes

CALVIN MOORE Calvin Moore CM 27MAY24 QA Yes

NICK WALSH Nick Walsh NW 25MAY24 Calibrations Yes

MATTHEW DOYLE Matthew Doyle MD 25MAY24 QC Yes

CIAN BRENNAN Cian Brennan CB 26MAY24 HR Yes

KATHY MC DONALD Kathy McDonald KMD 26MAY24 EHS Yes

Comments: MK 25 MAY 24

Reviewed By:

Validation Maria Kaluzna Date: 27 MAY 24

Approved By:

(QA) Calvin Moore Date: 27 MAY 24

16.2. Appendix B - Installation Verification GMP checksheetsP&ID Walkdown Installation VerificationP&ID # P&ID 227

P&ID Description Hot detergent and hot PUW generation and distribution

Test Step Expected Results Actual Results Pass / Fail Initials and Date

(dd/mmm/yyyy)

1 Walk down the P&ID and using a yellow-highlighter confirm each component is correctly installed and orientated as represented on the P&ID Components correctly installed Components correctly installed Pass MK 27/MAY/2024

2 Confirm all component tag numbers are correct Tag numbers correct Tag numbers correct Pass MK 27/MAY/2024

3 Confirm all lines are correctly labelled Lines correctly labelled Lines correctly labelled Pass MK 27/MAY/2024

4 Confirm all lines where applicable are correctly insulated Lines correctly insulated Lines correctly insulated Pass MK 27/MAY/2024

5 Ensure all flow direction components are orientated correctly Flow directions correct Flow directions correct Pass MK 27/MAY/2024

6 Ensure all instruments indicators are orientated correctly so as operators can readily view them Indicators orientated correctly Indicators orientated correctly Pass MK 27/MAY/2024

7 Ensure all commissioning filters are installed in filter-housings Filters installed Filters installed Pass MK 27/MAY/2024

Comments: N/A MK 27/MAY/2024 Validation Peer Review

JONATHAN WALSH Jonathan Walsh 27 MAY 24 Print Name Signature Date QA Approval

CALVIN MOORE Calvin Moore 27 MAY 24 Print Name Signature Date Equipment Installation VerificationSheet _1_ of 11 ____ Installation Verification

Tank Installation Verification Tag #: __ T-411 ___

Equipment Description and Critical Design Features

Inspect the installed equipment item and the vendors documentation and verify correct specification conformance Specified Actual Verification

(Pass/Fail) Initials / Date

1 Manufacturer RAD ENG RAD ENG PASS MK 27.MAY 24

2 Capacity 6000L 6000L PASS MK 27.MAY 24

3 M.O.C. 316L SS 316L SS PASS MK 27.MAY 24

4 Design Pressure Range FV to 1 Barg FV to 1 Barg PASS MK 27.MAY 24

5 Design Temp Range 0 to 177C 0 to 177C PASS MK 27.MAY 24

Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates Verification

(Pass/Fail) Initials Date

1 Vendor handover package is in place PASS MK 27.MAY 24

2 Material Certification is available for wetted parts PASS MK 27.MAY 24

Installation Verification

Visually inspect, and subsequently verify, the correct installation of the equipment item in the field Verification

(Pass/Fail) Initials Date

1 Equipment item is installed as per P&ID, is securely fitted and is free from damage PASS MK 27.MAY 24

2 Nameplate is securely fitted, clearly legible and its details conform to the design specification PASS MK 27.MAY 24

3 All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID PASS MK 27.MAY 24

Comments: N/A MK 27.MAY 24 Validation Peer Review

AISLING FIELD Aisling Field 27.MAY 24 Print Name Signature Date QA Approval

CALVIN MOORE Calvin Moore 27.MAY 24 Print Name Signature Date Sheet 2__ of 11 ____ Installation Verification

Tank Installation Verification Tag #: _ T-211 _____

Equipment Description and Critical Design Features

Inspect the installed equipment item and the vendors documentation and verify correct specification conformance Specified Actual Verification

(Pass/Fail) Initials / Date

1 Manufacturer RAD ENG RAD ENG PASS MK 27 MAY 24

2 Capacity 6000L 6000L PASS MK 27 MAY 24

3 M.O.C. 316LSS 316LSS PASS MK 27 MAY 24

4 Design Pressure Range FV to 1 Bar(g) FV to 1 Bar(g) PASS MK 27 MAY 24

5 Design Temp Range 0 to 177oC 0 to 177oC PASS MK 27 MAY 24

Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates Verification

(Pass/Fail) Initials Date

1 Vendor handover package is in place PASS MK 27.MAY 24

2 Material Certification is available for wetted parts PASS MK 27.MAY 24

Installation Verification

Visually inspect, and subsequently verify, the correct installation of the equipment item in the field Verification

(Pass/Fail) Initials Date

1 Equipment item is installed as per P&ID, is securely fitted and is free from damage PASS MK 27.MAY 24

2 Nameplate is securely fitted, clearly legible and its details conform to the design specification PASS MK 27.MAY 24

3 All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID PASS MK 27.MAY 24

Comments: N/A MK 27.MAY 24 Validation Peer Review

AISLING FIELD Aisling Field 27.MAY 24 Print Name Signature Date QA Approval

CALVIN MOORE Calvin Moore 27.MAY 24 Print Name Signature Date Sheet _3_ of _11_ ____ Installation Verification

Heat Exchanger Installation Verification Tag #: HX-211_____

Equipment Description and Critical Design Features

Inspect the installed equipment item and the vendors documentation and verify correct specification conformance Specified Actual Verification

(Pass/Fail) Initials / Date

1 Manufacturer Exchanger Plus Exchanger Plus Pass JW 19 APR 24

2 Capacity 569.4 kW 569.4 kW Pass JW 19 APR 24

3 M.O.C. 316L SS 316L SS Pass JW 19 APR 24

4 Design Pressure Range FV to 10 Barg FV to 10 Barg Pass JW 19 APR 24

5 Design Temp Range 0 to 150C 0 to 150C Pass JW 19 APR 24

Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates Verification

(Pass/Fail) Initials Date

1 Vendor handover package is in place Pass JW 19 APR 24

2 Material Certification is available for wetted parts Pass JW 19 APR 24

Installation Verification

Visually inspect, and subsequently verify, the correct installation of the equipment item in the field Verification

(Pass/Fail) Initials Date

1 Equipment item is installed as per P&ID, is securely fitted and is free from damage Pass JW 19 APR 24

2 Nameplate is securely fitted, clearly legible and its details conform to the design specification Pass JW 19 APR 24

3 All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID Pass JW 19 APR 24

Comments: N/A JW 19 APR 24 Validation Peer Review

MARIA KALUZNA Maria Kaluzna 19 APR 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 19 APR 24 Print Name Signature Date Sheet _4_ of _11_ ____ Installation Verification

Heat Exchanger Installation Verification Tag #: _ HX-411_____

Equipment Description and Critical Design Features

Inspect the installed equipment item and the vendors documentation and verify correct specification conformance Specified Actual Verification

(Pass/Fail) Initials / Date

1 Manufacturer Exchanger Plus Exchanger Plus Pass JW 20 APR 24

2 Capacity 569.4 kW 569.4 kW Pass JW 20 APR 24

3 M.O.C. 316L SS 316L SS Pass JW 20 APR 24

4 Design Pressure Range FV to 10 Barg FV to 10 Barg Pass JW 20 APR 24

5 Design Temp Range 0 to 150C 0 to 150C Pass JW 20 APR 24

Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates Verification

(Pass/Fail) Initials Date

1 Vendor handover package is in place Pass JW 20 APR 24

2 Material Certification is available for wetted parts Pass JW 20 APR 24

Installation Verification

Visually inspect, and subsequently verify, the correct installation of the equipment item in the field Verification

(Pass/Fail) Initials Date

1 Equipment item is installed as per P&ID, is securely fitted and is free from damage Pass JW 20 APR 24

2 Nameplate is securely fitted, clearly legible and its details conform to the design specification Pass JW 20 APR 24

3 All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID Pass JW 20 APR 24

Comments: N/A JW 20 APR 24 Validation Peer Review

MARIA KALUZNA Maria Kaluzna 20 APR 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 23 APR 24 Print Name Signature Date Sheet _5 of 11_ _ Installation Verification

Pump Installation Verification Tag #: _ P-207_____

Equipment Description and Critical Design Features

Inspect the installed equipment item and the vendors documentation and verify correct specification conformance Specified Actual Verification

(Pass/Fail) Initials / Date

1 Manufacturer PUMP MAN PUMP MAN PASS MK 28 MAY 24

2 Capacity 25M3/hr & 7 Bar(g) 25M3/hr & 7 Bar(g) PASS MK 28 MAY 24

3 M.O.C. 316L SS 316L SS PASS MK 28 MAY 24

4 Design Pressure Range FV to 10 Bar(g) FV to 10 Bar(g) PASS MK 28 MAY 24

5 Design Temp Range 0 to 115oC 0 to 115oC PASS MK 28 MAY 24

Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates Verification

(Pass/Fail) Initials Date

1 Vendor handover package is in place PASS MK 28 MAY 24

2 Material Certification is available for wetted parts PASS MK 28 MAY 24

Installation Verification

Visually inspect, and subsequently verify, the correct installation of the equipment item in the field Verification

(Pass/Fail) Initials Date

1 Equipment item is installed as per P&ID, is securely fitted and is free from damage PASS MK 28 MAY 24

2 Nameplate is securely fitted, clearly legible and its details conform to the design specification PASS MK 28 MAY 24

3 All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID PASS MK 28 MAY 24

Comments: N/A MK 28 MAY 24 Validation Peer Review

BRIAN ROCHE Brian Roche 29 MAY 24 Print Name Signature Date QA Approval

CALVIN MOORE

Calvin Moore 29 MAY 24 Print Name Signature Date Sheet _6 of 11_ ____ Installation Verification

Pump Installation Verification Tag #: __ P-209 ____

Equipment Description and Critical Design Features

Inspect the installed equipment item and the vendors documentation and verify correct specification conformance Specified Actual Verification

(Pass/Fail) Initials / Date

1 Manufacturer Pump Man Pump Man PASS MK 29 MAY 24

2 Capacity 25 m3/h & 7 barg 25 m3/h & 7 barg PASS MK 29 MAY 24

3 M.O.C. 316L SS 316L SS PASS MK 29 MAY 24

4 Design Pressure Range FV to 10 barg FV to 10 barg PASS MK 29 MAY 24

5 Design Temp Range 0 to 115C 0 to 115C PASS MK 29 MAY 24

Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates Verification

(Pass/Fail) Initials Date

1 Vendor handover package is in place Pass MK MK 29 MAY 24

2 Material Certification is available for wetted parts Pass MK MK 29 MAY 24

Installation Verification

Visually inspect, and subsequently verify, the correct installation of the equipment item in the field Verification

(Pass/Fail) Initials Date

1 Equipment item is installed as per P&ID, is securely fitted and is free from damage Pass MK MK 29 MAY 24

2 Nameplate is securely fitted, clearly legible and its details conform to the design specification Pass MK MK 29 MAY 24

3 All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID Pass MK MK 29 MAY 24

Comments: N/A MK 29 MAY 24 Validation Peer Review

AISLING FIELD Aisling Field 18 MAR 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 19 MAR 24 Print Name Signature Date Sheet _7 of 11_ ___ Installation Verification

Pump Installation Verification Tag #: P-415______

Equipment Description and Critical Design Features

Inspect the installed equipment item and the vendors documentation and verify correct specification conformance Specified Actual Verification

(Pass/Fail) Initials / Date

1 Manufacturer Pump Man Pump Man Pass MK 26 MAY 24

2 Capacity 25 m3/h & 7 barg 25 m3/h & 7 barg Pass MK 26 MAY 24

3 M.O.C. 316L SS 316L SS Pass MK 26 MAY 24

4 Design Pressure Range FV to 10 barg FV to 10 barg Pass MK 26 MAY 24

5 Design Temp Range 0 to 115C 0 to 115C Pass MK 26 MAY 24

Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates Verification

(Pass/Fail) Initials Date

1 Vendor handover package is in place Pass MK 26 MAY 24

2 Material Certification is available for wetted parts Pass MK 26 MAY 24

Installation Verification

Visually inspect, and subsequently verify, the correct installation of the equipment item in the field Verification

(Pass/Fail) Initials Date

1 Equipment item is installed as per P&ID, is securely fitted and is free from damage Pass MK 26 MAY 24

2 Nameplate is securely fitted, clearly legible and its details conform to the design specification Pass MK 26 MAY 24

3 All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID Pass MK 26 MAY 24

Comments: N/A MK 26 MAY 24 Validation Peer Review

AISLING FIELD Aisling Field 27 MAY 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 27 MAY 24 Print Name Signature Date

Sheet _8_ of 11 ____ Installation Verification

Pump Installation Verification Tag #: _P-417_____

Equipment Description and Critical Design Features

Inspect the installed equipment item and the vendors documentation and verify correct specification conformance Specified Actual Verification

(Pass/Fail) Initials / Date

1 Manufacturer Pump Man Pump Man Pass MK 25 MAY 24

2 Capacity 25 m3/h & 7 barg 25 m3/h & 7 barg Pass MK 25 MAY 24

3 M.O.C. 316L SS 316L SS Pass MK 25 MAY 24

4 Design Pressure Range FV to 10 barg FV to 10 barg Pass MK 25 MAY 24

5 Design Temp Range 0 to 115C 0 to 115C Pass MK 25 MAY 24

Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates Verification

(Pass/Fail) Initials Date

1 Vendor handover package is in place Pass MK 25 MAY 24

2 Material Certification is available for wetted parts Pass MK 25 MAY 24

Installation Verification

Visually inspect, and subsequently verify, the correct installation of the equipment item in the field Verification

(Pass/Fail) Initials Date

1 Equipment item is installed as per P&ID, is securely fitted and is free from damage Pass MK 25 MAY 24

2 Nameplate is securely fitted, clearly legible and its details conform to the design specification Pass MK 25 MAY 24

3 All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID Pass MK 25 MAY 24

Comments: N/A MK 25 MAY 24 Validation Peer Review

DANIEL CRANDOL Daniel Crandol 25 MAY 24 Print Name Signature Date QA Approval

CALVIN MOORE Calvin Moore 25 MAY 24 Print Name Signature Date Sheet _9_ of _11_ ____ Installation Verification

Pump Installation Verification Tag #: P-223______

Equipment Description and Critical Design Features

Inspect the installed equipment item and the vendors documentation and verify correct specification conformance Specified Actual Verification

(Pass/Fail) Initials / Date

1 Manufacturer Pump Safe Pump Safe Pass MK 27 MAY 24

2 Capacity 0.55kW 0.55kW Pass MK 27 MAY 24

3 M.O.C. 316L SS 316L SS Pass MK 27 MAY 24

4 Design Pressure Range 5 barg Max 5 barg Max Pass MK 27 MAY 24

5 Design Temp Range 10C min - 40C Max 10C min - 40C Max Pass MK 27 MAY 24

Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates Verification

(Pass/Fail) Initials Date

1 Vendor handover package is in place Pass MK 27 MAY 24

2 Material Certification is available for wetted parts Pass MK 27 MAY 24

Installation Verification

Visually inspect, and subsequently verify, the correct installation of the equipment item in the field Verification

(Pass/Fail) Initials Date

1 Equipment item is installed as per P&ID, is securely fitted and is free from damage Pass MK 27 MAY 24

2 Nameplate is securely fitted, clearly legible and its details conform to the design specification Pass MK 27 MAY 24

3 All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID Pass MK 27 MAY 24

Comments: N/A MK 27 MAY 24 Validation Peer Review

AISLING FIELD Aisling Filed 28 MAY 24 Print Name Signature Date QA Approval

CALVIN MOORE Calvin Moore 28 MAY 24 Print Name Signature Date Sheet _10_ of 11__ ____ Installation Verification

Filter Installation Verification Tag #: FL-399______

Equipment Description and Critical Design Features

Inspect the installed equipment item and the vendors documentation and verify correct specification conformance Specified Actual Verification

(Pass/Fail) Initials / Date

1 Manufacturer Thro Flow Thro Flow Pass MK 29 MAR 24

2 Capacity 1.5 ml Mesh 1.5 ml Mesh Pass MK 29 MAR 24

3 M.O.C. 316L SS/PTFE 316L SS/PTFE Pass MK 29 MAR 24

4 Design Pressure Range FV to 10 Barg FV to 10 Barg Pass MK 29 MAR 24

5 Design Temp Range 0 to 150C 0 to 150C Pass MK 29 MAR 24

Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates Verification

(Pass/Fail) Initials Date

1 Vendor handover package is in place Pass MK MK 29 MAR 24

2 Material Certification is available for wetted parts Pass MK MK 29 MAR 24

Installation Verification

Visually inspect, and subsequently verify, the correct installation of the equipment item in the field Verification

(Pass/Fail) Initials Date

1 Equipment item is installed as per P&ID, is securely fitted and is free from damage Pass MK MK 29 MAR 24

2 Nameplate is securely fitted, clearly legible and its details conform to the design specification Pass MK MK 29 MAR 24

3 All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID Pass MK MK 29 MAR 24

Comments: N/A MK 29 MAR 24 Validation Peer Review

BRIAN ROCHE Brian Roche 29 MAR 24 Print Name Signature Date QA Approval

CALVIN MOORE Calvin Moore 29 MAR 24 Print Name Signature Date Sheet _11_ of 11__ ____ Installation Verification

Filter Installation Verification Tag #: _FL-401_____

Equipment Description and Critical Design Features

Inspect the installed equipment item and the vendors documentation and verify correct specification conformance Specified Actual Verification

(Pass/Fail) Initials / Date

1 Manufacturer Thro Flow Thro Flow Pass MK 30 MAY 24

2 Capacity 1.5 ml Mesh 1.5 ml Mesh Pass MK 30 MAY 24

3 M.O.C. 316L SS/PTFE 316L SS/PTFE Pass MK 30 MAY 24

4 Design Pressure Range FV to 10 Barg FV to 10 Barg Pass MK 30 MAY 24

5 Design Temp Range 0 to 150C 0 to 150C Pass MK 30 MAY 24

Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates Verification

(Pass/Fail) Initials Date

1 Vendor handover package is in place Pass MK 30 MAY 24

2 Material Certification is available for wetted parts Pass MK 30 MAY 24

Installation Verification

Visually inspect, and subsequently verify, the correct installation of the equipment item in the field Verification

(Pass/Fail) Initials Date

1 Equipment item is installed as per P&ID, is securely fitted and is free from damage Pass MK 30 MAY 24

2 Nameplate is securely fitted, clearly legible and its details conform to the design specification Pass MK 30 MAY 24

3 All process and utility connections, and instrumentation are connected up to the correct nozzles/flanges, as per P&ID Pass MK 30 MAY 24

Comments: N/A MK 30 MAY 24 Validation Peer Review

BRIAN ROCHE Brian Roche 30 MAY 24 Print Name Signature Date QA Approval

CALVIN MOORE Calvin Moore 30 MAY 24 Print Name Signature Date Instrument Installation VerificationSheet _1_ of _18_ ___ Installation Verification Part-1: _Temperature __ Transmitter Description and Critical Design Features

Inspect the installed instrument item and the vendors documentation and verify correct specification conformance

Tag # Specified Manufacturer Actual Specified Range Actual Specified MOC Actual Loop Checked

(Yes/No) Verification

(Pass/Fail) Initials / Date

_TCV-005__ SPIRAX SPIRAX 0 TO 177C 0 TO 177C CS CS Yes Pass AF 18 APR 24

__TCV-006_ SPIRAX SPIRAX 0 TO 177C 0 TO 177C CS CS Yes Pass AF 18 APR 24

__TT-001__ E&H E&H 0 TO 177C 0 TO 177C 316L SS 316L SS Yes Pass AF 18 APR 24

__TT-002__ E&H E&H 0 TO 177C 0 TO 177C 316L SS 316L SS Yes Pass AF 18 APR 24

__TT-003__ E&H E&H 0 TO 177C 0 TO 177C 316L SS 316L SS Yes Pass AF 18 APR 24

TT-004 E&H E&H 0 TO 177C 0 TO 177C 316L SS 316L SS Yes Pass AF 18 APR 24

Comments: The stated range for the above was not provided in either the P&ID or URS. Therefore, the specified range above was derived from P&ID 227 for tanks, as the temperature should not exceed these specifications.

Validation Peer Review

AISLING FIELD Aisling Field 18 APR 24 Print Name Signature Date QA Approval

CALVIN MOORE Calvin Moore 18 APR 24 Print Name Signature Date Sheet _2_ of _18_ ____ Installation Verification Part-2: _Temperature__ Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates

Tag # *Vendor handover package is in place

(Yes/No) Material Certification is available for wetted parts (Yes/No) Cert # Calibration Certification is available (Yes/No) Cert # Loop Checksheet is available (Yes/No) Checksheet # Verification

(Pass/Fail) Initials / Date

__TCV-005__ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 18 APR 24

__TCV-006__ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 18 APR 24

__TT-001__ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 18 APR 24

__TT-002__ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 18 APR 24

__TT-003__ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 18 APR 24

TT-004 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 18 APR 24

Comments: Certs and check sheets can be found in the engineering library. Validation Peer Review

DANIEL CRANDOL Daniel Crandol 19 APR 24 Print Name Signature Date QA Approval

CALVIN MOORE Calvin Moore 19 APR 24 Print Name Signature Date Sheet _3_ of __18 ___ Installation Verification Part-3: _Temperature__ Installation Verification

Visually inspect, and subsequently verify, the correct installation of the instrument item in the field

Tag # Instrument item is installed as per P&ID, is securely fitted and is free from damage (Yes/No) Instrument and cabling is correctly tagged and details conform to the design specification (Yes/No) Instrument orientated correctly and is accessible for calibration and maintenance (Yes/No) Verification

(Pass/Fail) Initials Date

_ TCV-005 ___ Yes Yes Yes Pass MK 22 MAY 24

__ TCV-006 __ Yes Yes Yes Pass MK 22 MAY 24

__ TT-001 __ Yes Yes Yes Pass MK 22 MAY 24

__ TT-002__ Yes Yes Yes Pass MK 22 MAY 24

__ TT-003__ Yes Yes Yes Pass MK 22 MAY 24

TT-004 Yes Yes Yes Pass MK 22 MAY 24

Comments: N/A MK 22 MAY 24 Validation Peer Review

AISLING FIELD Aisling Field 23 MAY 24 Print Name Signature Date QA Approval

CALVIN MOORE CALVIN MOORE 24 MAY 24 Print Name Signature Date Sheet _4_ of _18_ ___ Installation Verification Part-1: _ Pressure __ Transmitter Description and Critical Design Features

Inspect the installed instrument item and the vendors documentation and verify correct specification conformance

Tag # Specified Manufacturer Actual Specified Range Actual Specified MOC Actual Loop Checked

(Yes/No) Verification

(Pass/Fail) Initials / Date

_ PT-001 ___ DWN DWN FV to 1Barg FV to 1Barg 316L SS 316L SS Yes Pass JW 04 JUN 24

__ PT-002__ DWN DWN FV to 1Barg FV to 1Barg 316L SS 316L SS Yes Pass JW 04 JUN 24

__ PI-004 __ DWN DWN FV to 1Barg FV to 1Barg 316L SS 316L SS Yes Pass JW 04 JUN 24

__ PI-005__ DWN DWN FV to 1Barg FV to 1Barg 316L SS 316L SS Yes Pass JW 04 JUN 24

__ PI-006__ DWN DWN FV to 1Barg FV to 1Barg 316L SS 316L SS Yes Pass JW 04 JUN 24

PI-007 DWN DWN FV to 1Barg FV to 1Barg 316L SS 316L SS Yes Pass JW 04 JUN 24

PI-008 DWN DWN FV to 1Barg FV to 1Barg 316L SS 316L SS Yes Pass JW 04 JUN 24

PRV-001 MANKENBERG MANKENBERG FV to 1Barg FV to 1Barg 316L SS 316L SS Yes Pass JW 04 JUN 24

PRV-002 MANKENBERG MANKENBERG FV to 1Barg FV to 1Barg 316L SS 316L SS Yes Pass JW 04 JUN 24

Comments: The stated range for the aforementioned parameters was not provided in either the P&ID or URS. Therefore, the specified range mentioned above was derived from P&ID 227 for tanks, as the pressure range should not exceed these parameters.

Validation Peer Review

DANIEL CRANDOL Daniel Crandol 05 JUN 24 Print Name Signature Date QA Approval

CALVIN MOORE Calvin Moore 05 JUN 24 Print Name Signature Date Sheet _5_ of _18_ ____ Installation Verification Part-2: _ Pressure __ Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates

Tag # *Vendor handover package is in place

(Yes/No) Material Certification is available for wetted parts (Yes/No) Cert # Calibration Certification is available (Yes/No) Cert # Loop Checksheet is available (Yes/No) Checksheet # Verification

(Pass/Fail) Initials / Date

_ PT-001__ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 10 JUN 24

__ PT-002 __ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 10 JUN 24

__ PI-004 __ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 10 JUN 24

__ PI-005__ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 10 JUN 24

__ PI-006__ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 10 JUN 24

PI-007 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 10 JUN 24

PI-008 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 10 JUN 24

PRV-001 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 10 JUN 24

PRV-002 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 10 JUN 24

Comments: Certs and check sheets can be found in the engineering library. Validation Peer Review

BRIAN ROCHE Brian Roche 10 JUN 24 Print Name Signature Date QA Approval

CALVIN MOORE Calvin Moore 11 JUN 24 Print Name Signature Date Sheet 6__ of _18_ ___ Installation Verification Part-3: _ Pressure __ Installation Verification

Visually inspect, and subsequently verify, the correct installation of the instrument item in the field

(Pass/Fail) Initials Date

_PT-001__ Yes Yes Yes Pass MK 25 MAY 24

_PT-002__ Yes Yes Yes Pass MK 25 MAY 24

__PI-004__ Yes Yes Yes Pass MK 25 MAY 24

__PI-005__ Yes Yes Yes Pass MK 25 MAY 24

__PI-006__ Yes Yes Yes Pass MK 25 MAY 24

PI-007 Yes Yes Yes Pass MK 25 MAY 24

PI-008 Yes Yes Yes Pass MK 25 MAY 24

PRV-001 Yes Yes Yes Pass MK 25 MAY 24

PRV-002 Yes Yes Yes Pass MK 25 MAY 24

Comments: N/A MK 25 MAY 24 Validation Peer Review

BRIAN ROCHE Brian Roche 25 MAY 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 25 MAY 24 Print Name Signature Date Sheet _7_ of _18_ ___ Installation Verification Part-1: _Flow __ Transmitter Description and Critical Design Features

Inspect the installed instrument item and the vendors documentation and verify correct specification conformance

Tag # Specified Manufacturer Actual Specified Range Actual Specified MOC Actual Loop Checked

(Yes/No) Verification

(Pass/Fail) Initials / Date

__FT-001__ KRONE KRONE 2,500 TO 30,000 L/HR 2,500 TO 30,000 L/HR 316L SS 316L SS Yes Pass AF 13 JUN 24

__FT-002__ KRONE KRONE 2,500 TO 30,000 L/HR 2,500 TO 30,000 L/HR 316L SS 316L SS Yes Pass AF 13 JUN 24

_FT-003__ KRONE KRONE 2,500 TO 30,000 L/HR 2,500 TO 30,000 L/HR 316L SS 316L SS Yes Pass AF 13 JUN 24

__FT-004__ KRONE KRONE 2,500 TO 30,000 L/HR 2,500 TO 30,000 L/HR 316L SS 316L SS Yes Pass AF 13 JUN 24

_FS-005__ E&H E&H 2,500 TO 30,000 L/HR 2,500 TO 30,000 L/HR 316L SS 316L SS Yes Pass AF 13 JUN 24

Comments: N/A AF 13 JUN 24 Validation Peer Review

MARIA KALUZNA Maria Kaluzna 14 JUN 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 14 JUN 24 Print Name Signature Date Sheet __8 of __18 ____ Installation Verification Part-2: __Flow_ Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates

Tag # *Vendor handover package is in place

(Yes/No) Material Certification is available for wetted parts (Yes/No) Cert # Calibration Certification is available (Yes/No) Cert # Loop Checksheet is available (Yes/No) Checksheet # Verification

(Pass/Fail) Initials / Date

_ FT-001__ Yes Yes See Comment Yes See Comment Yes See Comment Pass 14 JUN 24

__FT-002__ Yes Yes See Comment Yes See Comment Yes See Comment Pass 14 JUN 24

__ FT-003__ Yes Yes See Comment Yes See Comment Yes See Comment Pass 14 JUN 24

__ FT-004__ Yes Yes See Comment Yes See Comment Yes See Comment Pass 14 JUN 24

__ FS-005__ Yes Yes See Comment Yes See Comment Yes See Comment Pass 14 JUN 24

Comments: Certs and check sheets can be found in the engineering library. Validation Peer Review

MARIA KALUZNA Maria Kaluzna 17 JUN 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 18 JUN 24 Print Name Signature Date Sheet _9_ of _18_ ___ Installation Verification Part-3: _ Flow__ Installation Verification

Visually inspect, and subsequently verify, the correct installation of the instrument item in the field

(Pass/Fail) Initials Date

__ FT-001__ Yes Yes Yes Pass MK 18 JUN 24

__ FT-002__ Yes Yes Yes Pass MK 18 JUN 24

__ FT-003__ Yes Yes Yes Pass MK 18 JUN 24

_ FT-004__ Yes Yes Yes Pass MK 18 JUN 24

__ FS-005__ Yes Yes Yes Pass MK 18 JUN 24

Comments: N/A MK 18 JUN 24 Validation Peer Review

AISLING FIELD Aisling Field 18 JUN 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 18 JUN 24 Print Name Signature Date Sheet __10 of _18_ ___ Installation Verification Part-1: _ Conductivity __ Transmitter Description and Critical Design Features

Inspect the installed instrument item and the vendors documentation and verify correct specification conformance

Tag # Specified Manufacturer Actual Specified Range Actual Specified MOC Actual Loop Checked

(Yes/No) Verification

(Pass/Fail) Initials / Date

__ CT-001 _ HENKEL HENKEL *0 100 mS/cm *0 100 mS/cm 316L SS 316L SS Yes Pass JW 15 JUN 24

__-__

Comments: Values not found Calibration Range: Factory Calibrated0 to 99.99 S/cm for cell constant 0.010 to 999.99 S/cm for cell constant 0.10 to 9999.99 S/cm for cell constant 1 Validation Peer Review

AISLING FIELD Aisling Field 20 JUN 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 20 JUN 24 Print Name Signature Date Sheet 11__ of _18_ ____ Installation Verification Part-2: _Conductivity__ Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates

Tag # *Vendor handover package is in place

(Yes/No) Material Certification is available for wetted parts (Yes/No) Cert # Calibration Certification is available (Yes/No) Cert # Loop Checksheet is available (Yes/No) Checksheet # Verification

(Pass/Fail) Initials / Date

__CT-001__ Yes Yes See Comment Yes See Comment Yes See Comment Pass JW 15 JUN 24

__-__ Comments: Certs and check sheets can be found in the engineering library. Validation Peer Review

AISLING FIELD Aisling Field 20 JUN 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 20 JUN 24 Print Name Signature Date Sheet _12_ of _18_ ___ Installation Verification Part-3: __Conductivity_ Installation Verification

Visually inspect, and subsequently verify, the correct installation of the instrument item in the field

(Pass/Fail) Initials Date

_ CT-001 __ Yes Yes Yes Pass JW 15 JUN 24

__-__ Comments: N/A JW 15 JUN 24 Validation Peer Review

AISLING FIELD Aisling Field 20 JUN 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 20 JUN 24 Print Name Signature Date Sheet _13_ of _18_ ___ Installation Verification Part-1: _Level__ Transmitter Description and Critical Design Features

Inspect the installed instrument item and the vendors documentation and verify correct specification conformance

Tag # Specified Manufacturer Actual Specified Range Actual Specified MOC Actual Loop Checked

(Yes/No) Verification

(Pass/Fail) Initials / Date

_ LS-003 __ E&H E&H 0 TO 6000 L 0 TO 6000 L 316L SS 316L SS Yes Pass JW 15 JUN 24

__ LS-004__ E&H E&H 0 TO 6000 L 0 TO 6000 L 316L SS 316L SS Yes Pass JW 15 JUN 24

__ LS-005_ E&H E&H 0 TO 6000 L 0 TO 6000 L 316L SS 316L SS Yes Pass JW 15 JUN 24

__ LT-001__ E&H E&H 0 TO 6000 L 0 TO 6000 L 316L SS 316L SS Yes Pass JW 15 JUN 24

__ LT-002__ E&H E&H 0 TO 6000 L 0 TO 6000 L 316L SS 316L SS Yes Pass JW 15 JUN 24

Comments: N/A JW 15 JUN 24 Validation Peer Review

MARIA KALUZNA Maria Kaluzna 21 JUN 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 21 JUN 24 Print Name Signature Date Sheet _14_ of __18 ____ Installation Verification Part-2: _ Level__ Documentation Verification

Confirm that the vendor handover package is in place and contains correct material certificates

Tag # *Vendor handover package is in place

(Yes/No) Material Certification is available for wetted parts (Yes/No) Cert # Calibration Certification is available (Yes/No) Cert # Loop Checksheet is available (Yes/No) Checksheet # Verification

(Pass/Fail) Initials / Date

__ LS-003__ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 19 JUN 24

__ LS-004_ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 19 JUN 24

__ LS-005_ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 19 JUN 24

__ LT-001_ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 19 JUN 24

_ LT-002__ Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 19 JUN 24

Comments: Certs and check sheets can be found in the engineering library. Validation Peer Review

AISLING FIELD Aisling Field 21 JUN 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 21 JUN 24 Print Name Signature Date Sheet _15_ of __18 ___ Installation Verification Part-3: Level ___ Installation Verification

Visually inspect, and subsequently verify, the correct installation of the instrument item in the field

(Pass/Fail) Initials Date

__ LS-003__ Yes Yes Yes Pass MK 19 JUN 24

__LS-004__ Yes Yes Yes Pass MK 19 JUN 24

__ LS-005__ Yes Yes Yes Pass MK 19 JUN 24

__ LT-001__ Yes Yes Yes Pass MK 19 JUN 24

__ LT-002__ Yes Yes Yes Pass MK 19 JUN 24

Comments: N/A MK 19 JUN 24 Validation Peer Review

AISLING FIELD Aisling Field 21 JUN 24 Print Name Signature Date QA Approval

LAURA KEATING Laura Keating 21 JUN 24 Print Name Signature Date Sheet 16 of 18 Instrument Installation Verification Part-1: Valves Transmitter Description and Critical Design Features

Inspect the installed instrument item and the vendors documentation and verify correct specification conformance

Tag # Specified Manufacturer Actual Specified Range Actual Specified MOC Actual Loop Checked (Yes/No) Verification (Pass/Fail) Initials / Date

XV-003 MS ARMATUREN MS ARMATUREN N/A N/A 316L SS 316L SS Yes Pass MK 27 May 24

XV-004 MS ARMATUREN MS ARMATUREN N/A N/A 316L SS 316L SS Yes Pass MK 27 May 24

XV-008 HABONIM HABONIM N/A N/A 316L SS 316L SS Yes Pass MK 27 May 24

XV-009 HABONIM HABONIM N/A N/A 316L SS 316L SS Yes Pass MK 27 May 24

XV-001 GEA TUCHENHAGEN GEA TUCHENHAGEN N/A N/A 316L SS 316L SS Yes Pass MK 27 May 24

XV-002 GEA TUCHENHAGEN GEA TUCHENHAGEN N/A N/A 316L SS 316L SS Yes Pass MK 27 May 24

XV-005 GEA TUCHENHAGEN GEA TUCHENHAGEN N/A N/A 316L SS 316L SS Yes Pass MK 27 May 24

XV-006 GEA TUCHENHAGEN GEA TUCHENHAGEN N/A N/A 316L SS 316L SS Yes Pass MK 27 May 24

XV-007 GEA TUCHENHAGEN GEA TUCHENHAGEN N/A N/A 316L SS 316L SS Yes Pass MK 27 May 24

Comments:

N/A MK 27 May 24

Validation Peer Review

AISLING FIELDAisling Field 21 JUN 24

Print NameSignatureDate

QA Approval

LAURA KEATING Laura Keating 21 JUN 24

Print Name Signature Date

Sheet 17 of 18 Instrument Installation Verification Part-2: Valves Documentation Verification Confirm that the vendor handover package is in place and contains correct material certificates

Tag # *Vendor handover package is in place

(Yes/No) Material Certification is available for wetted parts (Yes/No) Cert # Calibration Certification is available (Yes/No) Cert # Loop Check sheet is available (Yes/No) Check sheet # Verif icati on

(Pas s/Fai l) Initials / Date

XV-003 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 27 May 24

XV-004 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 27 May 24

XV-008 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 27 May 24

XV-009 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 27 May 24

XV-001 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 27 May 24

XV-002 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 27 May 24

XV-005 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 27 May 24

XV-006 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 27 May 24

XV-007 Yes Yes See Comment Yes See Comment Yes See Comment Pass MK 27 May 24

Comments: Certs and check sheets can be found in the engineering library.

Validation Peer Review

AISLING FIELDAisling Field 21 JUN 24

Print NameSignatureDate

QA Approval

LAURA KEATINGLaura Keating 21 JUN 24

Print NameSignatureDate

Sheet 18 of 18 Instrument Installation Verification Part-3: Valve Installation Verification

Visually inspect, and subsequently verify, the correct installation of the instrument item in the field

XV-003 Yes Yes Yes Pass MK 17 JUN 24

XV-004 Yes Yes Yes Pass MK 17 JUN 24

XV-008 Yes Yes Yes Pass MK 17 JUN 24

XV-009 Yes Yes Yes Pass MK 17 JUN 24

XV-001 Yes Yes Yes Pass MK 17 JUN 24

XV-002 Yes Yes Yes Pass MK 17 JUN 24

XV-005 Yes Yes Yes Pass MK 17 JUN 24

XV-006 Yes Yes Yes Pass MK 17 JUN 24

XV-007 Yes Yes Yes Pass MK 17 JUN 24

Comments:N/A MK 17 JUN 24

Validation Peer Review

AISLING FIELDAisling Field 21 JUN 24

Print NameSignatureDate

QA Approval

LAURA KEATINGLaura Keating 21 JUN 24

Print NameSignatureDate

16.2.4. Piping Installation VerificationSheet 1 of 6 Piping Installation Verification Tag # MOC *Weld Log # *Weld Log Complete

(Yes/No) Pressure Test Pack-# Pressure Test Complete (Yes/No) Construction Dossier # **Slopes Checked

(Yes/No) Verification (Pass/Fail) Initials / Date

50-PUW1-S6-147-IH *a S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

50-PUW1-S6-148-IH *b S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

80-DETERGENT-S6-149-IH

*c S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

80-DETERGENT-S6-150-IH

*d S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

80-DETERGENT-S6-151-IH

*e S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

65-DETERGENT-S6-152-IH

*f S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

65-DETERGENT-S6-153-IH

*g S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

*Weld Log collates material-of-construction certificates and weld inspection certificates **Construction Dossier collates slope-check documentation

Comments: Weld log, Pressure test pack and Construction Dossier documents can be found in the engineering library.

Inline component *: a. XV-009, b. XV-008, c.XV-002, XV-004, XV-007, d.V-008, e.V-009, f.V-011, g.V-010, PI-004, V-012

Validation Peer Review

JONATHAN WALSHJonathan Walsh 21 JUN 24

Print NameSignatureDate

QA Approval

LAURA KEATINGLaura Keating 21 JUN 24

Print NameSignatureDate

Sheet 2 of 6 Piping Installation Verification Tag # MOC *Weld Log # *Weld Log Complete

(Yes/No) Pressure Test Pack-# Pressure Test Complete (Yes/No) Construction Dossier # **Slopes Checked

(Yes/No) Verification (Pass/Fail) Initials / Date

65-DETERGENT-SS1-154- IH *a SS1 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

80-PUW2-S6-155-IH *b S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

80-PUW2-S6-156-IH *c S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

80-PUW2-S6-157-IH *d S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

65-PUW2-S6-158-IH *e S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

65-PUW2-S6-159-IH *f S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

65-PUW2-S6-160-IH *g S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

25-PROCESS-S6-161-NI

*h S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 19 JUN 24

*Weld Log collates material-of-construction certificates and weld inspection certificates **Construction Dossier collates slope-check documentation

Comments: Weld log, Pressure test pack and Construction Dossier documents can be found in the engineering library.

Inline component *: a.V-042,V-014 b.XV-001,XV-003 c.XV-001 d.V-002, e.V-004, f.V-003,PI-003, V-005 g.V-007, V-041 h.V-036

Validation Peer Review

JONATHAN WALSHJonathan Walsh 21 JUN 24

Print NameSignatureDate

QA Approval

LAURA KEATINGLaura Keating 21 JUN 24

Print NameSignatureDate

Sheet 3 of 6 Piping Installation Verification Tag # MOC *Weld Log # *Weld Log Complete

(Yes/No) Pressure Test Pack-# Pressure Test Complete (Yes/No) Construction Dossier # **Slopes Checked

(Yes/No) Verification (Pass/Fail) Initials / Date

25-PROCESS-S6-162- NI *a S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

65-DETERGENT-S6-

163-IH *b S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

65-PUW2-S6-164-IH

*c S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

100-VENTS6-166-NI S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

25-DRAIN-S6-167-NI

*d S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

100-VENTS6-168-NI S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

25-DRAIN-S6-169-NI

*e S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

50-DRAIN-S6-170-NI S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

*Weld Log collates material-of-construction certificates and weld inspection certificates **Construction Dossier collates slope-check documentation

Comments: Weld log, Pressure test pack and Construction Dossier documents can be found in the engineering library. Inline component *: a.V-034,V-040 b.V-044,XV-006,PRV-002 c.V-043,XV-005,PRV-001, d.V-032,SG-006 e.V-033,SG-007 Validation Peer Review

JONATHAN WALSHJonathan Walsh 21 JUN 24

Print NameSignatureDate

QA Approval

LAURA KEATINGLaura Keating 21 JUN 24

Print NameSignatureDate

Sheet 4 of 6 Piping Installation Verification Tag # MOC *Weld Log # *Weld Log Complete

(Yes/No) Pressure Test Pack-# Pressure Test Complete (Yes/No) Construction Dossier # **Slopes Checked

(Yes/No) Verification (Pass/Fail) Initials / Date

50-DRAIN-S6-171-NI S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

25-VENT-S6-172-NI

*a S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

25-VENT-S6-173-NI

*b S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

50-DRAIN-S6-174-NI S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

50-DRAIN-S6-175-NI S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

80-DRAIN-S6-176-NI S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

15-DRAIN-S6-177-NI

*c S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

15-DRAIN-S6-178-NI

*d S6 See Comment Yes See Comment Yes See Comment Yes Pass MK 21 JUN 24

*Weld Log collates material-of-construction certificates and weld inspection certificates **Construction Dossier collates slope-check documentation

Comments: Weld log, Pressure test pack and Construction Dossier documents can be found in the engineering library.

Inline component *: a.PSV-002 b.PSV-001 c.V-030 d.V-031.

Validation Peer Review

JONATHAN WALSHJonathan Walsh 21 JUN 24

Print NameSignatureDate

QA Approval

LAURA KEATINGLaura Keating 21 JUN 24

Print NameSignatureDate

Sheet 5 of 6 Piping Installation Verification Tag # MOC *Weld Log *Weld Log Pressure Test Pressure Test Construction **Slopes Checked Verification Initials / Date

# Complete (Yes/No) Pack-# Complete (Yes/No) Dossier # (Yes/No) (Pass/Fail) 15-DRAIN-179-S6-NI *a S6 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

15-DRAIN-180-S6-NI *b S6 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

50-DRAIN-181-S6-NI *c SS1 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

50-DRAIN-182-S6-NI *d SS1 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

65-PLANT STEAM-CS5-

183-IH *e CS5 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

15-PLANT STEAM-CS5-

184-IH *f CS5 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

20-CONDENSTATE-CS5-

185-IH CS5 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

40-CONDENSTATE-CS5-

186-IH *7 CS5 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

*Weld Log collates material-of-construction certificates and weld inspection certificates **Construction Dossier collates slope-check documentation

Comments: Weld log, Pressure test pack and Construction Dossier documents can be found in the engineering library.

Inline component *: a.V-028 b.V-029 c.V-006 d.V-013 e.TCV-006,V-019,TCV-005,V-020 f.V-021,ST-001,SG-003,V-022,V-023 7.ST-002,SG-005,V-024,V- 025

Validation Peer Review

Maria Kaluzna28 MAY 24

MARIA KALUZNA Print Name

Signature

Date

QA Approval

CALVIN MOORE Calvin Moore 28 MAY 24

Print Name

Signature

Date

Sheet 6 of 6 Piping Installation Verification Tag # MOC *Weld Log *Weld Log Pressure Test Pressure Test Construction **Slopes Verification Initials / Date

# Complete (Yes/No) Pack-# Complete (Yes/No) Dossier # Checked (Yes/No) (Pass/Fail) 40-CONDENSTATE-CS5-

187-IH *a CS5 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

100-PLANT STEAM-CS5-

241-IH *b CS5 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

80-CONDENSTATE-CS5-

242-IH CS5 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

40-COMPRESSED AIR- SS1-502-NI *c SS1 See Comment Yes See Comment Yes See Comment Yes Pass AF 27 MAY 24

*Weld Log collates material-of-construction certificates and weld inspection certificates **Construction Dossier collates slope-check documentation

Comments: Weld log, Pressure test pack and Construction Dossier documents can be found in the engineering library.

Inline component *: a.ST-003,SG-004,V-026,V-027 b.V-016,XV-022 c.V-039

Validation Peer Review

Maria Kaluzna28 MAY 24

MARIA KALUZNA Print Name

Signature

Date

QA Approval

CALVIN MOORE Calvin Moore 28 MAY 24

Print Name Signature

Date

HYPERLINK "https://www.google.com/url?sa=i&url=https%3A%2F%2Fm.made-in-china.com%2Fproduct%2FPharmaceutical-Equipment-Stainless-Steel-Sanitary-Grade-Welded-Pipe-Tube-2057398275.html&psig=AOvVaw1rpoJ42ePTuYvSut1B9nMw&ust=1719250837392000&source=images&cd=vfe&opi=89978449&ved=0CBMQjhxqFwoTCMCK3NGi8oYDFQAAAAAdAAAAABAJ" t "_blank"

Pharmaceutical Equipment Stainless Steel Sanitary Grade Welded Pipe/Tube - China Stainless Steel Sanitary Tube, Stainless Steel Tube | Made-in-China.com

https://tedisteel.en.made-in-china.com/product/YJSROBPClWVN/China-Pharmaceutical-Equipment-Stainless-Steel-Sanitary-Grade-Welded-Pipe-Tube.html

16.2.5. Calibration Program Verification

https://www.getreskilled.com/validation/validation-protocol/

Page _1__ of __1_

CALIBRATION PROGRAM VERIFICATION FORM

No. Steps Yes/No Verified By Date

1 Critical component list attached and cross referenced from commissioning documents Yes MK 01 JUN 24

2 Calibration list attached and cross referenced from site calibration program Yes MK 01 JUN 24

3 All critical components confirmed to be entered into the site calibration program Yes MK 01 JUN 24

Deviation Report Required (Yes/No) : No

Acceptance Criteria Met: (Yes/No): Yes

Comments: N/A MK 01 JUN 24

Reviewed By:

Validation Daniel Crandol Date: 02 JUN 24

Approved By:

(QA) Calvin Moore Date: JUN 24

16.2.6. Preventative Maintenance Program VerificationPage _1__ of __2_

Preventative Maintenance Program Verification Form

No. Description Verified By / Date

1 Component: Pumps (P-207,P-209,P-415,P-417,P-223) MK 03 JUN 24

Centrifugal pumps: P-207,P-209,P-415,P-417 Metering pump: P-223 PM#:1 001-1004, 1007 Location: Hot Detergent / PUW Skid, Reactor cleaning. Effective Date:

03 JUN 24 2 Component: Heat Exchangers (HX-211,HX-411) MK 04 JUN 24

Detergent Plate Heat Exchanger: HX-211, PUW2 Plate Heat Exchanger: HX-411 PM#: 994 Location: Cleaning Skid System, Hot Detergent / PUW Skid.

Isolate one process circulation loop from another. The hot detergent solution supply temperature is maintained by a closed loop control system, which modulates steam flow to the heat exchanger HX-211. The PUW2 hot process water supply temperature is maintained by a closed loop control system, which modulates steam flow to the heat exchanger HX-411. Effective Date:

04 JUN 24

3 Component: Filters (FL-399,FL-401) MK 05 JUN 24

Inline filters: Detergent Cartridge Filter FL-399, PUW2 Cartridge Filter FL-401 PM#: 876 Location: Hot Detergent / PUW Skid, Reactor cleaning. Effective Date:

05 JUN 24 4 Component: Pressure Safety Valves (PSV-002,PSV-001) MK 03 JUN 24

PUW2 Sanitary Pressure Relief Valve PSV-001, Detergent Sanitary Pressure Relief Valve PSV-002 PM#: 1024 Location: PSV-001 in HX-411 Outlet, PSV-002 in HX-211 Outlet;

Cleaning Skid System. Page _2_ of __2_

Effective Date:

03 JUN 24 5 Component: Temperature Indicator (TI-007,TI-008) MK 03 JUN 24

Bimetalic Temperature indicators PM#: 007 Location: TI-007-T-411 thermowell, TI-008-T-211 thermowell. Hot Detergent and Hot PUW Skid.

Effective Date:

03 JUN 24 6 Component: Level Transmitter (LT-001,LT-002) MK 03 JUN 24

Hydrostatic Pressure type level Transmitters PM#: 409 Location: Hot Detergent and Hot PUW Skid.

LT-001-T-411, LT-002-T-211. Effective Date:

04 JUN 24 Comments: N/A MK 05 JUN 24

Reviewed By:

Validation Daniel Crandol Date: 03 JUN 24

Approved By:

(QA) Calvin Moore Date: JUN 24

16.2.7. Draft SOP VerificationPage _1 __ of _ 2_

Standard Operating Procedure Verification Form

No. Description Verified By / Date

1 Title: Operation of the Hot detergent system AF 15 MAR 24

SOP #: 11302 Revision #: 1 Date: 15 MAR 24 2 Title: Operation of the Hot PUW2 system MK 03 FEB 24

SOP #: 11303 Revision #: 0 Date: 03 FEB 24 3 Title Cleaning the Hot PUW2 and Hot Detergent system MK 16 FEB 24

SOP #: 11304 Revision #: 0 Date: 16 FEB 24 4 Title: Examine the attachments and connections on the Hot detergent and hot PUW generation and distribution skid.

AF 08 APR 24

SOP #: 11325 Revision #: 2 Date: 08 APR 24 5 Title: Assembling and disassembling the Hot detergent and hot PUW generation and distribution skid

AF 20 APR 24

SOP #: 11330 Revision #: 3 Date: 20 APR 24 6 Title: Operation and maintenance of CIP wash tanks MK 12 JAN 24

SOP #: SOP-235 Revision #: 12 Page _2_ of __2_

Date: 12 JAN 24 7 Title: CIP procedures for bioreactors MK 08 JAN 24

SOP #: SOP-157 Revision #: 4.3 Date: 08 JAN 24 8 Title: Operation and maintenance of steam supply line MK 30 APR 24

SOP #: SOP-1002 Revision #: 6.7 Date: 30 APR 24 9 Title: Operational maintenance of hot detergent line FR 22 JAN 24

SOP #: SOP-645 Revision #: 15.6 Date: 22 JAN 24 10 Title: Operational maintenance of PUW1 supply line FR 17 APR 24

SOP #: SOP-880 Revision #: 3.9 Date: 17 APR 24 11 Title: Operation and maintenance of pumps in generation and distribution system MK 30 APR 24

SOP #: SOP-184 Revision #: 1.7 Date: 30 APR 24 Comments:

Reviewed By:

Validation Daniel Crandol Date: 30 APR 24

Approved By:

(QA) Calvin Moore_ Date: APR 24

16.2.8. Test-Instrument Calibration VerificationPage _1 _ of _2 __

Test Instrument Calibration Verification Form

Objective: To document all test instruments used in the execution of this protocol.

Test Instrument Description Identification Number Calibration Date Calibration Due Date Verified By / Date

Steam Temperature control valve TCV-005 21 JUN 24 20 DEC 24 MK 21 JUN 24

Steam Temperature control valve TCV-006 21 JUN 24 20 DEC 24 MK 21 JUN 24

3 wire RTD Temperature transmitters TT-001 21 JUN 24 20 DEC 24 MK 21 JUN 24

3 wire RTD Temperature transmitters TT-002 21 JUN 24 20 DEC 24 MK 21 JUN 24

3 wire RTD Temperature transmitters TT-003 21 JUN 24 20 DEC 24 MK 21 JUN 24

3 wire RTD Temperature transmitters TT-004 21 JUN 24 20 DEC 24 MK 21 JUN 24

Sanitary Diaphragm type Pressure Indicating transmitters PT-001 21 JUN 24 20 DEC 24 MK 21 JUN 24

Sanitary Diaphragm type Pressure Indicating transmitters PT-002 21 JUN 24 20 DEC 24 MK 21 JUN 24

Magnetic flow Transmitter FT-001 21 JUN 24 20 DEC 24 MK 21 JUN 24

Magnetic flow Transmitter FT-002 21 JUN 24 20 DEC 24 MK 21 JUN 24

Magnetic flow Transmitter FT-003 21 JUN 24 20 DEC 24 MK 21 JUN 24

Magnetic flow Transmitter FT-004 21 JUN 24 20 DEC 24 MK 21 JUN 24

Conductivity transmitter CT-001 21 JUN 24 20 DEC 24 MK 21 JUN 24

Bimetalic Temperature indicator TI-007 21 JUN 24 20 DEC 24 MK 21 JUN 24

Bimetalic Temperature indicator TI-008 21 JUN 24 20 DEC 24 MK 21 JUN 24

Bimetalic Temperature indicator TI-009 21 JUN 24 20 DEC 24 MK 21 JUN 24

Bimetalic Temperature indicator

Hydrostatic Pressure type level Transmitter TI-010 21 JUN 24 20 DEC 24 MK 21 JUN 24

LT-001 21 JUN 24 20 DEC 24 MK 21 JUN 24

Hydrostatic Pressure type level Transmitter LT-002 21 JUN 24 20 DEC 24 MK 21 JUN 24

Actuated Sanitary Ball Valve XV-008 21 JUN 24 20 DEC 24 MK 21 JUN 24

Actuated Sanitary Ball Valve XV-009 21 JUN 24 20 DEC 24 MK 21 JUN 24

High Level Switch (Tuning fork type) LS-004 21 JUN 24 20 DEC 24 MK 21 JUN 24

High Level Switch (Tuning fork type) LS-006 21 JUN 24 20 DEC 24 MK 21 JUN 24

Comment:

N/A MK 21 JUN 24

Reviewed By: Validation Maria Kaluzna Date: 21 JUN 24

Approved By: (QA) Calvin Moore Date: 21 JUN 24

HYPERLINK "https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.youtube.com%2Fwatch%3Fv%3DqzwYmeWcty4&psig=AOvVaw3aaMABw2LZhcZh_mvZaVjn&ust=1719266050738000&source=images&cd=vfe&opi=89978449&ved=0CBMQjhxqFwoTCJCIyqvb8oYDFQAAAAAdAAAAABAE" t "_blank"

Calibration of instruments in pharmaceutical industry - How to perform calibration

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Master Pressure Calibrators: Precision Tools for Accurate Pressure Instrument Calibration

16.3. Appendix C:OQ GMP check-sheetsHot Detergent System Level ControlTest Step # Operational Test Step Description Expected Result Actual Result Pass / Fail Initials Date

(dd/mmm/yyyy)

1 Confirm the initial level in the hot detergent tank

LT-002 = 0 0 PASS GPC 11/Feb/2020

2 Fill the hot detergent tank from the PUW1 water loop until it stops filling automatically. LT-002 = 5775 litres 5% 5775 PASS GPC 11/Feb/2020

3 Open the drain valve and the tank should automatically start filling again from the PUW1 water loop to remain full. LT-002 = 5775 litres 5% 5775 PASS GPC 11/Feb/2020

4 Close the drain valve and check that the level in the tank remains full in normal operation mode for a further 30-minutes LT-002 = 5775 litres 5% 5775 PASS GPC 11/Feb/2020

5 Print out the associated trends for level LT-002 the test period and append to this test section. Trends attached Trends attached PASS GPC 11/Feb/2020

Aisling Field 13/Feb/2024

Reviewed By (Validation Peer Review) Date

Calvin Moore 13/Feb/2024

Approved By (Quality Assurance) Date

In the following table, at successive 5-minute intervals record the level in the hot detergent tank of the level transmitter LT-002. Ensure that during the time period the values are recorded correspond to the following:

The 30-minutes for filling the hot detergent tank (starting at t0-min)

Automatic filling during the draining of the hot detergent tank

The 30-minutes following the closing of the drain valve

Time

minutes Time

HH/MM Expected

LT-002 (Litres) Actual

LT-002 (Litres) Pass / Fail Initials Date

(dd/mmm/yyyy)

t0-min 13:00 0 0 PASS GPC 11/Feb/2020

t5-min 13:05 <5,775 916 PASS GPC 11/Feb/2020

t10-min 13:10 <5,775 1832 PASS GPC 11/Feb/2020

t15-min 13:15 <5,775 2750 PASS GPC 11/Feb/2020

t20-min 13:20 <5,775 3664 PASS GPC 11/Feb/2020

t25-min 13:25 <5,775 4580 PASS GPC 11/Feb/2020

t30-min 13:30 5,775 5% 5775 PASS GPC 11/Feb/2020

t35-min 13:35 5,775 5% 5775 PASS GPC 11/Feb/2020

t40-min 13:40 5,775 5% 5775 PASS GPC 11/Feb/2020

Maria Kaluzna 14 FEB 2024

Reviewed By (Validation Peer Review) Date

Calvin Moore 14 FEB 2024

Approved By (Quality Assurance) Date

Time

minutes Time

HH/MM Expected

LT-002 (Litres) Actual

LT-002 (Litres) Pass / Fail Initials Date

(dd/mmm/yyyy)

t45-min 13:45 5,775 5% 5775 PASS GPC 11/Feb/2020

t50-min 13:50 5,775 5% 5775 PASS GPC 11/Feb/2020

t55-min 13:55 5,775 5% 5775 PASS GPC 11/Feb/2020

t60-min 14:00 5,775 5% 5775 PASS GPC 11/Feb/2020

t65-min 14:05 5,775 5% 5775 PASS GPC 11/Feb/2020

t70-min 14:10 5,775 5% 5775 PASS GPC 11/Feb/2020

t75-min 14:15 5,775 5% 5775 PASS GPC 11/Feb/2020

t80-min 14:20 5,775 5% 5775 PASS GPC 11/Feb/2020

t85-min 14:25 5,775 5% 5775 PASS GPC 11/Feb/2020

Comments: N/A MK 14 FEB 24

Aisling Field 14 FEB 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 14 FEB 24

Approved By (Quality Assurance) Date

Hot Detergent System Flow ControlTest Step # Operational Test Step Description Expected Result Actual Result Pass / Fail Initials Date

1 Start the hot detergent pump circulating FT-002 = 25,000 litres/hr 5%

FT-004 = 25,000 litres/hr 5C FT-002 = 25,000 litres/hr

FT-004 = 25,000 litres/hr PASS GPC 11/Feb/2020

2 Confirm the initial flow reading of FT-002 and FT-004 FT-002 = 25,000 litres/hr 5%

FT-004 = 25,000 litres/hr 5% FT-002 = 25,000 litres/hr

FT-004 = 25,000 litres/hr PASS GPC 11/Feb/2020

3 Open the transfer valves to RE-119 and RE-140 and transfer 5,500 litres into each vessel, confirming the level reading on LT-119 and LT-140 (this will take approximately 30-minutes).

Confirm the flow readings FT-002 and FT-004 LT-119 = 5,500 Litres

LT-140 = 5,500 Litres

FT-002 = 25,000 litres/hr 5%

FT-004 = 3,000 litres/hr 5% LT-119 = 5,500 litres

LT-140 = 5,500 litres

FT-002 = 25,000 litres/hr

FT-004 = 3,000 litres/hr PASS GPC 11/Feb/2020

4 After the transfer stops, maintain the hot detergent system in normal recirculation mode for a further 30-minutes with no further drawdown. FT-002 = 25,000 litres/hr 5%

FT-004 = 25,000 litres/hr 5% FT-002 = 25,000 litres/hr 5%

FT-004 = 25,000 litres/hr 5% PASS GPC 11/Feb/2020

5 Print out the associated trends for level LT-119 and LT-140, flow FT-002 and FT-004 during the test period and append to this test section. Trends attached Trends attached PASS GPC 11/Feb/2020

Maria Kaluzna

14 FEB 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 14 FEB 24

Approved By (Quality Assurance) Date

In the following table, at successive 5-minute intervals record the online indicator values of flow transmitters FT-002 and FT-004 and level-transmitters LT-119 and LT-140. Ensure that during the time period the values are recorded correspond to the following:

The 30-minutes before the transfer from the hot detergent tank to the reactors RE-119 and RE-140 (starting at t0-min)

During the transfer to RE-119 and RE-140 to the full 5,500L charge to each reactor

The 30-minutes following the stopping of the transfer to RE-119 and RE-140

Time

Mins Time

HH/MM Expected

Flow FT-002 / FT-004

Litres/hr Actual

FT-002

Litres/hr Actual

FT-004

Litres/hr Expected

LT-119

Litres Expected

LT-140

Litres Actual

LT-119

(Litres) Actual

LT-140

(Litres) Pass / Fail Initials Date

(dd/mmm/yyyy)

t0-min 13:00 FT-002 25,000 5%

FT-004 25,000 5% 25,490 25,490 0 0 0 0 PASS GPC 11/Feb/2020

t5-min 13:05 FT-002 25,000 5%

FT-004 25,000 5% 24,966 24,966 0 0 0 0 PASS GPC 11/Feb/2020

t10-min 13:10 FT-002 25,000 5%

FT-004 25,000 5% 25,019 25,019 0 0 0 0 PASS GPC 11/Feb/2020

t15-min 13:15 FT-002 25,000 5%

FT-004 25,000 5% 24,699 24,699 0 0 0 0 PASS GPC 11/Feb/2020

t20-min 13:20 FT-002 25,000 5%

FT-004 25,000 5% 25,243 25,243 0 0 0 0 PASS GPC 11/Feb/2020

t25-min 13:25 FT-002 25,000 5%

FT-004 25,000 5% 24,699 24,699 0 0 0 0 PASS GPC 11/Feb/2020

t30-min 13:30 FT-002 25,000 5%

FT-004 25,000 5% 25,243 25,243 0 0 0 0 PASS GPC 11/Feb/2020

t35-min 13:35 FT-002 25,000 5%

FT-004 3,000 5% 24,446 2,917 <5,500 <5,500 1,000 1,000 PASS GPC 11/Feb/2020

t40-min 13:40 FT-002 25,000 5%

FT-004 3,000 5% 25,009 3,109 <5,500 <5,500 2,000 2,000 PASS GPC 11/Feb/2020

Maria Kaluzna15 FEB 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 16 FEB 24

Approved By (Quality Assurance) Date

Time

mins Time

HH/MM Expected Flow

FT-002/ FT-004

Litres/hr Actual

FT-002

Litres/hr Actual

FT-004

Litres/hr Expected

LT-119

Litres Expected

LT-140

Litres Actual

LT-119

(Litres) Actual

LT-140

(Litres) Pass / Fail Initials Date

(dd/mmm/yyyy)

t45-min 13:45 FT-002 25,000 5%

FT-004 3,000 5% 25,224 2,954 <5,500 <5,500 3,500 3,500 PASS GPC 11/Feb/2020

t50-min 13:50 FT-002 25,000 5%

FT-004 3,000 5% 24,765 3,149 <5,500 <5,500 4,500 4,500 PASS GPC 11/Feb/2020

t55-min 13:55 FT-002 25,000 5%

FT-004 3,000 5% 24,459 3,005 <5,500 <5,500 5,500 5,500 PASS GPC 11/Feb/2020

t60-min 14:00 FT-002 25,000 5%

FT-004 3,000 5% 25,809 2,959 5,500 5% 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t65-min 14:05 FT-002 25,000 5%

FT-004 25,000 5% 24,924 24,924 5,500 5% 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t70-min 14:10 FT-002 25,000 5%

FT-004 25,000 5% 24,255 24,255 5,500 5% 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t75-min 14:15 FT-002 25,000 5%

FT-004 25,000 5% 25,245 25,245 5,500 5% 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t80-min 14:20 FT-002 25,000 5%

FT-004 25,000 5% 25,457 25,457 5,500 5% 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t85-min 14:25 FT-002 25,000 5%

FT-004 25,000 5% 25,189 25,189 5,500 5% 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

Comments:

Maria Kaluzna 15 FEB 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 16 FEB 24

Approved By (Quality Assurance) Date

16.3.3. Hot Detergent System Temperature ControlTest Step # Operational Test Step Description Expected Result Actual Result Pass / Fail Initials Date

(dd/mmm/yyyy)

1 Start heating up the recirculating water loop in the hot detergent system to a steady 80C 5C and confirm the temperature on TT-002 and TT-004. TT-002 = 80C5C

TT-004 = 80C5C TT-002 = 82C

TT-004 = 79C PASS GPC 11/Feb/2020

2 Open the transfer valves to reactors RE-119 and reactor RE-140, and transfer 5,500 litres into both reactors, noting the level on LT-119 and LT-140. Confirm that the temperature of the hot detergent system maintains 80C 5C during the transfer on TT-002 and TT-004 LT-119 > 5,500 Litres

LT-140 > 5,500 Litres

TT-002 = 80C5C

TT-004 = 80C5C LT-119 = 5,500L

LT-140 = 5,500L

TT-002 = 82C

TT-004 = 79C PASS GPC 11/Feb/2020

3 Following the transfer, maintain the hot detergent system in normal circulation mode for a further 30-minutes with no further drawdown. No drawdown No drawdown PASS GPC 11/Feb/2020

4 Print out the associated trends for temperature transmitters TT-002 and TT-004, and level-transmitters LT-119 and LT-140 during the test period and append to this test section. Trends attached Trends attached PASS GPC 11/Feb/2020

Aisling Field 17 MAR 24

Reviewed By (Validation Peer Review) Date

Laura Keating 19 MAR 24

Approved By (Quality Assurance) Date

In the following table, at successive 5-minute intervals record the online indicator values of, temperature transmitters TT-002 and TT-004, and level-transmitters LT-119 and LT-140. Ensure that during the time period the values are recorded correspond to the following:

The 30-minutes before the transfer from the hot detergent tank to the reactors RE-119 and RE-140 (starting at t0-min)

During the transfer to RE-119 and RE-140 to the full 5,500L charge to each reactor

The 30-minutes following the stopping of the transfer to RE-119 and RE-140

Time

minutes Time

HH/MM Expected

TT-002 and TT-004

TT-002

TT-004

LT-119

LT-140

(Litres) Actual LT-119

(Litres) Actual LT-140

(Litres) Pass / Fail Initials Date

(dd/mmm/yyyy)

t0-min 13:00 <80C 25C 25C 0 0 0 PASS GPC 11/Feb/2020

t5-min 13:05 <80C 40C 40C 0 0 0 PASS GPC 11/Feb/2020

t10-min 13:10 <80C 60C 60C 0 0 0 PASS GPC 11/Feb/2020

t15-min 13:15 <80C 75C 75C 0 0 0 PASS GPC 11/Feb/2020

t20-min 13:20 80C 5C 80C 80C 0 0 0 PASS GPC 11/Feb/2020

t25-min 13:25 80C 5C 81C 80C 0 0 0 PASS GPC 11/Feb/2020

t30-min 13:30 80C 5C 78C 83C 0 0 0 PASS GPC 11/Feb/2020

t35-min 13:35 80C 5C 80C 78C <5,500 1,000 1,000 PASS GPC 11/Feb/2020

t40-min 13:40 80C 5C 80C 78C <5,500 2,000 2,000 PASS GPC 11/Feb/2020

Aisling Field 19 MAR 24

Reviewed By (Validation Peer Review) Date

Laura Keating 19 MAR 24

Approved By (Quality Assurance) Date

Time

minutes Time

HH/MM Expected

TT-002

TT-004

TT-002

TT-004

LT-119

LT-140

(Litres) LT-119

(Litres) LT-140

(Litres) Pass / Fail Initials Date

(dd/mmm/yyyy)

t45-min 13:45 80C 5C 81C 82C <5,500 3,000 3,500 PASS GPC 11/Feb/2020

t50-min 13:50 80C 5C 79C 82C <5,500 4,000 4,000 PASS GPC 11/Feb/2020

t55-min 13:55 80C 5C 82C 80C <5,500 5,000 5,000 PASS GPC 11/Feb/2020

t60-min 14:00 80C 5C 81C 83C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t65-min 14:05 80C 5C 80C 78C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t70-min 14:10 80C 5C 80C 81C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t75-min 14:15 80C 5C 79C 85C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t80-min 14:20 80C 5C 80C 78C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t85-min 14:25 80C 5C 81C 80C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

Comments:

N/A AF 19 MAR 24

Aisling Field 19 MAR 24

Reviewed By (Validation Peer Review) Date

Laura Keating 19 MAR 24

Approved By (Quality Assurance) Date

Hot Detergent System Detergent Dosing ControlTest Step # Operational Test Step Description Expected Result Actual Result Pass / Fail Initials Date

(dd/mmm/yyyy)

1 Start up the hot detergent recirculation system.

Give the system time to warm up until it is recirculating water at 80C. TT-002 = 80C5C

TT-004 = 80C5C TT-002 = 81C

TT-004 = 80C PASS GPC 11/Feb/2020

2 Commence introducing detergent into the recirculation loop at time = (t0-min)

After 30 minutes, confirm the conductivity measurement CT-001 is reading 500 Scm-1 5%. CT-001 = 500 Scm-1 5% CT-001=505 Scm-1 PASS GPC 11/Feb/2020

3 At time = (t30-min) open the transfer valves to reactors RE-119 and reactor RE-140, and transfer 5,500 litres into each reactor, noting the level on LT-119 and LT-140. Confirm that the temperature reading of the hot detergent system maintains 80C 5C during the transfer on TT-002 and TT-004 and the conductivity reading remains at 500 Scm-1 5%. LT-119 > 5,500 Litres

LT-140 > 5,500 Litres

TT-002 = 80C 5C

TT-004 = 80C 5C

CT-001 = 500 Scm-1 5% LT-119 = 5,500L

LT-140 = 5,500L

TT-002 = 81C

TT-004 = 80C

CT-001=505 Scm-1

PASS GPC 11/Feb/2020

4 Following the transfer, maintain the hot detergent system in normal circulation mode for a further 30-minutes with no further drawdown. No drawdown No drawdown PASS GPC 11/Feb/2020

5 Print out the associated trends for conductivity transmitter CT-001, temperature transmitters TT-002 and TT-004, and level-transmitters LT-119 and LT-140 during the test period and append to this test section. Trends attached Trends attached PASS GPC 11/Feb/2020

Aisling Field 20 MAR 24

Reviewed By (Validation Peer Review) Date

Laura Keating 29 MAR 24

Approved By (Quality Assurance) Date

In the following table, at successive 5-minute intervals record the online indicator values of conductivity measurement CT-001, temperature transmitters TT-002 and TT-004, and level-transmitters LT-119 and LT-140. Ensure that during the time period the values are recorded correspond to the following:

The 30-minutes before the transfer from the hot detergent tank to the reactors RE-119 and RE-140 (starting at t0-min)

During the transfer to RE-119 and RE-140 to the full 5,500L charge to each

The 30-minutes following the stopping of the transfer to RE-119 and RE-140

Time

minutes Time

HH/MM Expected

CT-001

Scm-1 Actual

CT-001

Scm-1 Expected

TT-002

TT-004

TT-002

TT-004

LT-119

LT-140

(Litres) LT-119

(Litres) LT-140

(Litres) Pass / Fail Initials Date

(dd/mmm/yyyy)

t0-min 13:00 <500 100 Scm-1 80C 5C 80C 80C 0 0 0 PASS GPC 11/Feb/2020

t5-min 13:05 <500 200 Scm-1 80C 5C 81C 80C 0 0 0 PASS GPC 11/Feb/2020

t10-min 13:10 <500 300 Scm-1 80C 5C 80C 80C 0 0 0 PASS GPC 11/Feb/2020

t15-min 13:15 <500 400 Scm-1 80C 5C 84C 82C 0 0 0 PASS GPC 11/Feb/2020

t20-min 13:20 500 Scm-1 5% 499 Scm-1 80C 5C 80C 79C 0 0 0 PASS GPC 11/Feb/2020

t25-min 13:25 500 Scm-1 5% 502 Scm-1 80C 5C 83C 80C 0 0 0 PASS GPC 11/Feb/2020

t30-min 13:30 500 Scm-1 5% 500 Scm-1 80C 5C 78C 83C 0 0 0 PASS GPC 11/Feb/2020

t35-min 13:35 500 Scm-1 5% 503 Scm-1 80C 5C 80C 78C <5,500 1000 1000 PASS GPC 11/Feb/2020

t40-min 13:40 500 Scm-1 5% 497 Scm-1 80C 5C 80C 79C <5,500 2000 2000 PASS GPC 11/Feb/2020

Aisling Field 20 MAR 24

Reviewed By (Validation Peer Review) Date

Laura Keating 29 MAR 24

Approved By (Quality Assurance) Date

Time

minutes Time

HH/MM Expected

CT-001

Scm-1 Actual

CT-001

Scm-1 Expected

TT-002/4

TT-002

TT-004

LT-119

LT-140

(Litres) Actual

LT-119

(Litres) Actual

LT-140

(Litres) Pass / Fail Initials Date

(dd/mmm/yyyy)

t45-min 13:45 500 Scm-1 5% 500 Scm-1 80C 5C 81C 80C <5,500 3,000 3,000 PASS GPC 11/Feb/2020

t50-min 13:50 500 Scm-1 5% 502 Scm-1 80C 5C 79C 82C <5,500 4,000 4,000 PASS GPC 11/Feb/2020

t55-min 13:55 500 Scm-1 5% 499 Scm-1 80C 5C 82C 80C <5,500 5,000 5,000 PASS GPC 11/Feb/2020

t60-min 14:00 500 Scm-1 5% 500 Scm-1 80C 5C 80C 81C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t65-min 14:05 500 Scm-1 5% 503 Scm-1 80C 5C 80C 78C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t70-min 14:10 500 Scm-1 5% 497 Scm-1 80C 5C 80C 81C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t75-min 14:15 500 Scm-1 5% 498 Scm-1 80C 5C 79C 82C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t80-min 14:20 500 Scm-1 5% 501 Scm-1 80C 5C 80C 80C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

t85-min 14:25 500 Scm-1 5% 500 Scm-1 80C 5C 81C 80C 5,500 5% 5,500 5,500 PASS GPC 11/Feb/2020

Comments: N/A AF 20 MAR 24

Aisling Field 20 MAR 24

Reviewed By (Validation Peer Review) Date

Laura Keating 29 MAR 24

Approved By (Quality Assurance) Date

Hot PUW System Level ControlTest Step # Operational Test Step Description Expected Result Actual Result Pass / Fail Initials Date (dd/mmm/yyyy)

1 Confirm the initial level in the Hot PUW2 tank LT-001 = 0 0 PASS MK 29/May/2024

2 Fill the hot PUW2 tank from the PUW1 water loop until it

stops filling automatically. LT-001 = 5775 litres 5% 5775 PASS MK 29/May/2024

3 Open the drain valve and the tank should automatically start

filling again from the PUW1 water loop to remain full. LT-001 = 5775 litres 5% 5775 PASS MK 29/May/2024

4 Close the drain valve and check that the level in the tank remains full in normal operation mode for a further 30-

minutes LT-001 = 5775 litres 5% 5775 PASS MK 29/May/2024

5 Print out the associated trends for level LT-001 the test

period and append to this test section. Trends attached Trends attached PASS MK 29/May/2024

Aisling Field 29 MAY 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 29 MAY 24

Approved By (Quality Assurance) Date

In the following table, at successive 5-minute intervals record the level in the Hot PUW2 tank of the level transmitter LT-001. Ensure that during the time period the values are recorded correspond to the following:

The 30-minutes for filling the hot PUW2 tank (starting at t0-min) [INSERT INFORMATION]

Automatic filling during the draining of the hot PUW2 tank

The 30-minutes following the closing of the valve

Time minutes Time HH/MM Expected

LT-001 (Litres)_ Actual

LT-001 (Litres) Pass / Fail Initials Date (dd/mmm/yyyy)

t0-min 13:00 0 0 Pass MK 26/May/2024

t5-min 13:05 <5,775 914 Pass MK 26/May/2024

t10-min 13:10 <5,775 1833 Pass MK 26/May/2024

t15-min 13:15 <5,775 2752 Pass MK 26/May/2024

t20-min 13:20 <5,775 3666 Pass MK 26/May/2024

t25-min 13:25 <5,775 4582 Pass MK 26/May/2024

t30-min 13:30 5,775 5% 5775 Pass MK 26/May/2024

t35-min 13:35 5,775 5% 5775 Pass MK 26/May/2024

t40-min 13:40 5,775 5% 5775 Pass MK 26/May/2024

Aisling Field 29 MAY 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 29 MAY 24

Approved By (Quality Assurance) Date

Time minutes Time HH/MM Expected

LT-001 (Litres)_ Actual

LT-001 (Litres) Pass / Fail Initials Date (dd/mmm/yyyy)

t45-min 13:45 5,775 5% 5775 Pass MK 29/May/2024

t50-min 13:50 5,775 5% 5775 Pass MK 29/May/2024

t55-min 13:55 5,775 5% 5775 Pass MK 29/May/2024

t60-min 14:00 5,775 5% 5775 Pass MK 29/May/2024

t65-min 14:05 5,775 5% 5775 Pass MK 29/May/2024

t70-min 14:10 5,775 5% 5775 Pass MK 29/May/2024

t75-min 14:15 5,775 5% 5775 Pass MK 29/May/2024

t80-min 14:20 5,775 5% 5775 Pass MK 29/May/2024

t85-min 14:25 5,775 5% 5775 Pass MK 29/May/2024

Comments: N/A MK 26 MAY 24

Aisling Field 29 MAY 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 29 MAY 24

Approved By (Quality Assurance) Date

Hot PUW System Flow ControlTest Step # Operational Test Step Description Expected Result Actual Result Pass / Fail Initials Date (dd/mmm/yyyy)

1 Start the hot PUW2 pump circulating FT-001 = 25,000 litres/hr 5% FT-003 = 25,000 litres/hr 5C FT-002 = 25,000

litres/hr

FT-004 = 25,000

litres/hr Pass AF 30/May/24

2 Confirm the initial flow reading of FT-002 and FT-004 FT-001 = 25,000 litres/hr 5%

FT-003 = 25,000 litres/hr 5% FT-002 = 25,000

litres/hr

FT-004 = 25,000

litres/hr Pass AF 30/May/24

3 Open the transfer valves to RE-119 and RE-140 and transfer 5,500 litres into each vessel, confirming the level reading on LT-119 and LT-140 (this will take approximately 30-minutes).

Confirm the flow readings FT-001 and FT-003 LT-119 = 5,500 Litres LT-140 = 5,500 Litres

FT-001 = 25,000 litres/hr 5%

FT-003 = 3,000 litres/hr 5% LT-119 = 5,500 litres LT-140 = 5,500 litres

FT-002 = 25,000

litres/hr

FT-004 = 3,000 litres/hr Pass AF 30/May/24

4 After the transfer stops, maintain the hot detergent system in normal recirculation mode for a further 30-minutes with no further drawdown. FT-001 = 25,000 litres/hr 5%

FT-003 = 25,000 litres/hr 5% FT-002 = 25,000

litres/hr 5%

FT-004 = 25,000

litres/hr 5% Pass AF 30/May/24

5 Print out the associated trends for level LT-119 and LT-140, flow FT-001 and FT-003 during the test period and append to this test

section. Trends attached Trends attached Pass AF 30/May/24

Maria Kaluzna 30 MAY 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 30 MAY 24

Approved By (Quality Assurance) Date

In the following table, at successive 5-minute intervals record the online indicator values of of flow transmitters FT-001 and FT-003 and Level transmitters LT-119 and LT-140. [INSERT INFORMATION].

Ensure that during the time period the values are recorded correspond to the following:

The 30-minutes before the transfer from the hot PUW2 tank to the reactors RE-119 and RE-140 (starting at t0-min)

During the transfer to RE-119 and RE-140 to the full 5,500L charge to each reactor

The 30-minutes following the stopping of the transfer to RE-119 and RE-140.

Time minutes Time HH/MM Expected

FT-001 / FT-003

Litres/hr Actual FT-001

Litres/ hr Actual FT-003

Litres/hr Expected LT-119

(Litres) Expected LT-140

(Litres) Actual LT- 119

(Litres) Actual LT- 140

(Litres) Pass / Fail Initials Date (dd/mmm/yy yy)

t0-min 14:00 FT-002 25,000 5%

FT-004 25,000 5% 25,491 25,491 0 0 0 0 Pass AF O2/Jun/2024

t5-min 14:05 FT-002 25,000 5%

FT-004 25,000 5% 24,967 24,967 0 0 0 0 Pass AF O2/Jun/2024

t10-min 14:10 FT-002 25,000 5%

FT-004 25,000 5% 25,020 25,020 0 0 0 0 Pass AF O2/Jun/2024

t15-min 14:15 FT-002 25,000 5%

FT-004 25,000 5% 24,700 24,700 0 0 0 0 Pass AF O2/Jun/2024

t20-min 14:20 FT-002 25,000 5%

FT-004 25,000 5% 25,244 25,244 0 0 0 0 Pass AF O2/Jun/2024

t25-min 14:25 FT-002 25,000 5%

FT-004 25,000 5% 24,698 24,698 0 0 0 0 Pass AF O2/Jun/2024

t30-min 14:30 FT-002 25,000 5%

FT-004 25,000 5% 25,243 25,243 0 0 0 0 Pass AF O2/Jun/2024

t35-min 14:35 FT-002 25,000 5%

FT-004 3,000 5% 24,446 2,919 <5,500 <5,500 1,000 1,000 Pass AF O2/Jun/2024

t40-min 14:40 FT-002 25,000 5%

FT-004 3,000 5% 25,009 3,111 <5,500 <5,500 2,000 2,000 Pass AF O2/Jun/2024

Maria Kaluzna 03 JUN 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 03 JUN 24

Approved By (Quality Assurance) Date

Time minutes Time HH/ MM Expected

FT-001 / FT-003

Litres/hr Actual FT-001

Litres/hr Actual FT-003

Litres/hr Expected LT-119

(Litres) Expected LT-140

(Litres) Actual LT-119

(Litres) Actual LT-140

(Litres) Pass / Fail Initials Date (dd/mm/yyyy)

t45-min 14:45 FT-002 25,000 5%

FT-004 3,000 5% 25,224 2,954 <5,500 <5,500 3,500 3,500 Pass AF O2/Jun/2024

t50-min 14:50 FT-002 25,000 5%

FT-004 3,000 5% 24,765 3,149 <5,500 <5,500 4,500 4,500 Pass AF O2/Jun/2024

t55-min 14:55 FT-002 25,000 5%

FT-004 3,000 5% 24,459 3,005 <5,500 <5,500 5,500 5,500 Pass AF O2/Jun/2024

t60-min 15:00 FT-002 25,000 5%

FT-004 3,000 5% 25,809 2,959 5,500 5% 5,500

5% 5,500 5,500 Pass AF O2/Jun/2024

t65-min 15:05 FT-002 25,000 5%

FT-004 25,000 5% 24,924 24,924 5,500 5% 5,500

5% 5,500 5,500 Pass AF O2/Jun/2024

t70-min 15:10 FT-002 25,000 5%

FT-004 25,000 5% 24,255 24,255 5,500 5% 5,500

5% 5,500 5,500 Pass AF O2/Jun/2024

t75-min 15:15 FT-002 25,000 5%

FT-004 25,000 5% 25,245 25,245 5,500 5% 5,500

5% 5,500 5,500 Pass AF O2/Jun/2024

t80-min 15:20 FT-002 25,000 5%

FT-004 25,000 5% 25,457 25,457 5,500 5% 5,500

5% 5,500 5,500 Pass AF O2/Jun/2024

t85-min 15:25 FT-002 25,000 5%

FT-004 25,000 5% 25,189 25,189 5,500 5% 5,500

5% 5,500 5,500 Pass AF O2/Jun/2024

Comments: N/A AF 03 JUN 24

Maria Kaluzna 03 JUN 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 05 JUN 24

Approved By (Quality Assurance) Date

Hot PUW System Temperature ControlTest Step # Operational Test Step Description Expected Result Actual Result Pass / Fail Initials Date (dd/mmm/yyyy)

1 Start heating up the recirculating water loop in the hot TT-001 = 80C5C TT-001 = 73C Fail MK 05/Jun/24

PUW2 system to a steady 80C 5C and confirm the TT-003 = 71C temperature on TT-001 and TT-003. TT-003 = 80C5C 2 Open the transfer valves to reactors RE-119 and reactor LT-119 > 5,500 Litres LT-119 = 5,500L Pass MK 05/Jun/24

RE-140, and transfer 5,500 litres into both reactors, LT-140 > 5,500 Litres LT-140 = 5,500L noting the level on LT-119 and LT-140. Confirm that TT-001 = 80C5C TT-001 = 81C the temperature of the hot detergent system maintains TT-003 = 80C5C TT-003 = 78C 80C 5C during the transfer on TT-001 and TT-003 3 Following the transfer, maintain the hot detergent

system in normal circulation mode for a further 30- minutes with no further drawdown. No drawdown No drawdown Pass MK 05/Jun/24

4 Print out the associated trends for temperature transmitters TT-001 and TT-003, and level-transmitters LT-119 and LT-140 during the test period and append

to this test section. Trends attached Trends attached Pass MK 05/Jun/24

Daniel Crandol 05 JUN 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 05 JUN 24

Approved By (Quality Assurance) Date

In the following table, at successive 5-minute intervals record the online indicator values of temperature transmitters TT-001 and TT-003, and level- transmitters LT-119 and LT-140 [INSERT INFORMATION].

The 30-minutes before the transfer from the hot PUW2 tank to the reactors RE-119 and RE-140 (starting at t0-min)

During the transfer to RE-119 and RE-140 to the full 5,500L charge to each reactor

The 30-minutes following the stopping of the transfer to RE-119 and RE-140.

Time minutes Time HH/MM Expected

TT-001TT- 003

(Litres) Actual LT-119

(Litres) Actual LT-140

(Litres) Pass / Fail Initials Date (dd/mmm/yyyy)

t0-min 14:30 80C 5C 81C 82C <5,500 3,000 3,500 Pass MK 11/Jun/2024

t5-min 14:35 80C 5C 79C 82C <5,500 4,000 4,000 Pass MK 11/Jun/2024

t10-min 14:40 80C 5C 82C 80C <5,500 5,000 5,000 Pass MK 11/Jun/2024

t15-min 14:45 80C 5C 81C 83C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

t20-min 14:50 80C 5C 80C 78C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

t25-min 14:55 80C 5C 80C 81C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

t30-min 15:00 80C 5C 79C 85C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

t35-min 15:05 80C 5C 80C 78C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

t40-min 15:10 80C 5C 81C 80C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

Brian Roche 21 JUN 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 21 JUN 24

Approved By (Quality Assurance) Date

Time

minutes Time

HH/MM Expected

TT-001

TT-003

TT-001

TT-003

LT-119

LT-140

(Litres) LT-119

(Litres) LT-140

(Litres) Pass / Fail Initials Date

(dd/mmm/yyyy)

t45-min 11:45 80C 5C 82C 80C <5,500 3,000 3,000 Pass MK 11/Jun/2024

t50-min 11:50 80C 5C 82C 80C <5,500 4,000 4,000 Pass MK 11/Jun/2024

t55-min 11:55 80C 5C 82C 80C <5,500 5,000 5,000 Pass MK 11/Jun/2024

t60-min 12:00 80C 5C 82C 80C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

t65-min 12:05 80C 5C 82C 80C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

t70-min 12:10 80C 5C 82C 80C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

t75-min 12:15 80C 5C 82C 80C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

t80-min 12:20 80C 5C 82C 80C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

t85-min 12:25 80C 5C 82C 80C 5,500 5% 5,500 5,500 Pass MK 11/Jun/2024

Comments: N/A MK 11 JUN 24

Brian Roche 21 JUN 24

Reviewed By (Validation Peer Review) Date

Calvin Moore 21 JUN 24

Approved By (Quality Assurance) Date

Approved SOP VerificationPage _ 1__ of _ 2__

Standard Operating Procedure Verification Form

No. Description Verified By / Date

1 Title: Operation of the Hot detergent system AF 15 MAR 24

SOP #: 11302 Revision #: 1 Date: 15 MAR 24 2 Title: Operation of the Hot PUW2 system MK 03 FEB 24

SOP #: 11303 Revision #: 0 Date: 03 FEB 24 3 Title Cleaning the Hot PUW2 and Hot Detergent system MK 16 FEB 24

SOP #: 11304 Revision #: 0 Date: 16 FEB 24 4 Title: Examine the attachments and connections on the Hot detergent and hot PUW generation and distribution skid.

AF 08 APR 24

SOP #: 11325 Revision #: 2 Date: 08 APR 24 5 Title: Assembling and disassembling the Hot detergent and hot PUW generation and distribution skid

AF 20 APR 24

SOP #: 11330 Revision #: 3 Date: 20 APR 24 6 Title: Operation and maintenance of CIP wash tanks MK 12 JAN 24

SOP #: SOP-235 Revision #: 12 Date: 12 JAN 24 7 Title: CIP procedures for bioreactors MK 08 JAN 24

Page _2_ of __2_

SOP #: SOP-157 Revision #: 4.3 Date: 08 JAN 24 8 Title: Operation and maintenance of steam supply line MK 30 APR 24

SOP #: SOP-1002 Revision #: 6.7 Date: 30 APR 24 9 Title: Operational maintenance of hot detergent line FR 22 JAN 24

SOP #: SOP-645 Revision #: 15.6 Date: 22 JAN 24 10 Title: Operational maintenance of PUW1 supply line FR 17 APR 24

SOP #: SOP-880 Revision #: 3.9 Date: 17 APR 24 11 Title: Operation and maintenance of pumps in generation and distribution system MK 20 APR 24

SOP #: SOP-184 Revision #: 1.7 Date: 30 APR 24 Comments:

Reviewed By:

Validation Daniel Crandol Date: 14 JUN 24

Approved By:

(QA) Calvin Moore_ Date: 18 JUN 24

Appendix D:Deviation logDeviation # Deviation Summary Statement Deviation Resolved

(YES / No) Date Verified Date Approved Related Change #

(if applicable)

1 The PUW2 system is not achieving the stated temperature of 80C 5C, instead it only reaches a recirculation temperature of 72C to 73C.

Yes 25MAR24 27MAR24 1

2 The GPC Validation engineer failed to provide their signature in the protocol's signature log.

Yes 29 MAY 24 06 JUN 24 N/A

CAPA-corrective and preventative method- additional training

3 There is no existing documentation/ record for LT-002. Error in the specific test steps.

Yes 10 JUN 24 10 JUN 24 N/A

Repeated tests taken in consideration.

Comments: N/A MK 12 JUN 24

Reviewed By:

(Validation) Daniel Crandol Date: 25 MAY 24

*Reviewed By:

(QA) Calvin Moore Date: 27 MAY 24

*Must be approved by QA if any deviations are deemed a Direct Impact SystemWhat are the many forms of deviation in the pharmaceutical industry? A deviation refers to an undesirable occurrence that deviates from the authorised methods, procedures, instructions, specifications, or established norms. Deviation may arise at various stages of drug product production, including manufacture, packing, sampling, and testing. There exist three categories of deviations: crucial, significant, and minor.

Appendix E:Deviation FormDeviation Details Deviation# 1

Building / Area Drug Product Equipment / System Hot detergent & hot PUW2

Protocol Section # 2

16.3.7 Protocol Test Descriptor Operational testing

Deviation Category

(Please Circle) 1 3 *4 *5

DEVIATION DESCRIPTION

Upon initial operation, the hot PUW2 system only achieves a recirculation temperature ranging from 72C to 73C after 30 minutes, instead of the specified range of 80C 5C.

2. Impact Assessment of Deviation

System GMP Category

*Direct

(Please Circle) Component GMP Category

(Please Circle)

Indirect No Impact Critical Non-Critical

Affected Items Yes/No Affected Items Yes/No

User Requirement No Functional or Detailed Design Specifications No

Testing Already Completed No System Documentation No

Testing Protocols No Drawings No

Validation Plan No Standard Operating Procedures No

Training No Other No

Details of Affected Items: N/A

REFERENCES (AFFECTED ITEMS)

Document # Revision

MK 25/MAR/24 3. Resolution Description

See change control #1

4. Resolution Verification

Verified By: (Originator) Maria Kaluzna Date: 25MAR24

Approved By: (Validation) Daniel Crandol Date: 25MAR24

*Approved By: (QA) Calvin Moore Date: 27MAR24

*Must be approved by QA only if a Direct Impact System

Deviation Details Deviation# 2

Building / Area BDS Equipment / System Hot Detergent System

Protocol Section # 13.2.6.3 Protocol Test Descriptor Hot Detergent System Flow Control. Expected results and Actual results.

Deviation Category

(Please Circle) 1

2 3 *4 *5

DEVIATION DESCRIPTION

GPC Validation engineer did not sign signature log of protocol upon completion of test.

2. Impact Assessment of Deviation

System GMP Category

No Impact

(Please Circle) Component GMP Category

Non-Critical

(Please Circle)

*Direct Indirect Critical Affected Items Yes/No Affected Items Yes/No

User Requirement No Functional or Detailed Design Specifications No

Testing Already Completed No System Documentation No

Testing Protocols No Drawings No

Validation Plan No Standard Operating Procedures No

Training No Other Yes

Details of Affected Items: Signature log not completed unable to identify initials. (Potential problems for audit). Affected item-documentations.

REFERENCES (AFFECTED ITEMS)

Document # Title / Description Revision

5555 The system involves the production and distribution of hot detergent and hot PUW2.

3. Resolution Description

Company reached out to the vendor in order to ascertain the identity of the validation engineer who will be responsible for finalising the signature log. Other comparable test results used- optionally.

4. Resolution Verification

Verified By: (Originator) Frank Roche Date: 07 JUN 24

Approved By: (Validation) Daniel Crandol Date: 08 JUN 24

*Approved By: (QA) Calvin Moore Date: 09 JUN 24

*Must be approved by QA only if a Direct Impact System

Deviation Details Deviation# 2

Building / Area BDS Equipment / System Hot detergent tank

Protocol Section # 13.2.5.6, 13.3.5.1, 13.4.5.1 Protocol Test Descriptor Hot Detergent System Flow Control. Detergent Dosing Control- Temperature Control. Specific Test Steps.

Deviation Category

(Please Circle) 1

2 3 *4 *5

DEVIATION DESCRIPTION

There is no existing documentation/record of LT-002. The specific test protocols indicate that the level in the hot detergent tank must be maintained at 5775 litres during the transfer process. Hydrostatic Pressure type level Transmitter.

2. Impact Assessment of Deviation

System GMP Category

*Direct

(Please Circle) Component GMP Category

(Please Circle)

Indirect No Impact Critical Non-Critical

Affected Items Yes/No Affected Items Yes/No

User Requirement No Functional or Detailed Design Specifications No

Testing Already Completed No System Documentation No

Testing Protocols Yes Drawings No

Validation Plan No Standard Operating Procedures No

Training No Other No

Details of Affected Items: The testing technique is erroneous, needs to be revised as it requires confirmation that the level in the hot detergent tank must be maintained at 5775 litres. Testing protocol incorrect as it asks to confirm that level in hot detergent tank must maintain at 5775 litres.

REFERENCES (AFFECTED ITEMS)

Document # Title / Description Revision

2222 The system involves the generation and distribution of hot detergent and hot PUW2.

3. Resolution Description

Maybe check what are the possibilities when the manufacturer and senior engineer what happens when the level is lower and higher than 5775L in tank. . eventually use other comparable tests.

4. Resolution Verification

Verified By: (Originator) Nick Walsh Date: 12 JUN 24

Approved By: (Validation) Daniel Crandol Date: 15 JUN 24

*Approved By: (QA) Laura Keating Date: 16 JUN 24

*Must be approved by QA only if a Direct Impact System

Deviation Details Deviation# Building / Area Equipment / System Protocol Section # Protocol Test Descriptor Deviation Category

(Please Circle) 1 2 3 *4 *5

DEVIATION DESCRIPTION

2. Impact Assessment of Deviation

System GMP Category

(Please Circle) Component GMP Category

(Please Circle)

*Direct Indirect No Impact Critical Non-Critical

Affected Items Yes/No Affected Items Yes/No

User Requirement Functional or Detailed Design Specifications Testing Already Completed System Documentation Testing Protocols Drawings Validation Plan Standard Operating Procedures Training Other Details of Affected Items:

REFERENCES (AFFECTED ITEMS)

Document # Title / Description Revision

3. Resolution Description

4. Resolution Verification

Verified By: (Originator) Date: Approved By: (Validation) Date: *Approved By: (QA Date: Appendix F:Change Control LogChange Control # P&ID / System # Summary Description of change Direct / Indirect /

No-Impact Date Raised

(dd/mmm/yyyy) Pre-Approval Date

(dd/mmm/yyyy) Post-Approval Date

(dd/mmm/yyyy)

1 Hot Detergent & Hot PUW2 The Plate Heat Exchangers HX211 and HX-411 are both to be replaced with units that have a rating of 650KW.

Direct 20/MAR/2024 25/MAR/2024 21/JUN/2024

2. CC-10389 P&ID-227 Additional equipment has been incorporated/added into the hot detergent and hot PUW2 generation and distribution system.

Direct 22 JUN 24 23 JUN 24 In progress

MK 21/JUN/24 COMMENTS: N/A

Reviewed By:

(Validation Engineering) Daniel Crandol Date: 10JUN24

Appendix G:Change Control FormChange Control Form

Project Title: Reactor cleaning CHANGE #: 1

Project No: 24-RC-0001 P&ID / System: Hot detergent & Hot PUW2

Attachments (Yes/No): Yes Date: 26 MAR 24

SECTION 1: OBSERVATIONS AND PROPOSED CHANGE (to be completed by 1Project Engineer)

ORIGINAL DESIGN: PROPOSED CHANGE:

Plate Heat Exchangers HX-211 and HX411 rated 569.4KW

Both Plate Heat Exchangers, HX-211 and HX-411, are scheduled for replacement with units rated at 650KW.

2HAZOP TO BE UPDATED (Yes / No) No

SECTION 2: IMPACT ASSESSMENT (to be completed by 1Engineering Validation)

AFFECTED APPROVED ITEMS Yes/No AFFECTED APPROVED ITEMS Yes/No

3Validation Plan No 3Project URS No

3System Level URS No 3System Impact Assessment No

3Component Impact Assessment No 3, 4Qualification Protocol(s) Yes

4Commissioning Protocol(s) Yes 4Other Yes

3, 5DIRECT 5INDIRECT 5NO IMPACT

3SYSTEM IMPACT Yes (/ No) Yes /( No) (Yes /) No

How to Troubleshoot a Plate Heat Exchanger?

How to tell if a plate heat exchanger is bad?

The most common symptoms are the following:

Increased pressure drop from inlet to outlet.

Loss of heat transfer efficiency.

Loss of flow and performance.

Process fluid leakage.

HYPERLINK "https://academy.paulmueller.com.

" https://academy.paulmueller.com.

SECTION 2 (Continued): IMPACT ASSESSMENT (to be completed by 1Engineering Validation)

3, 5OPER. CRITICAL 3, 5PRODUCT CONTACT 5NON CRITICAL

3COMPONENT IMPACT No Yes No

5CONSTRUCTION 5COMMISSIONING 3, 5QUALIFICATION

PROJECT PHASE No No Yes

SECTION 3: TESTING REQUIRED (to be completed by 1Engineering Validation)

4TESTING REQUIRED

A. Create a nw/fresh test script, attach it, and save it in the file along with this change control.

B. End the current qualification protocol's tests and grant approval for the remaining ones.

C. Using this change control as a reference, close out deviations for the failed tests. 4DOCUMENT UPDATES REQUIRED

A. Commissioning Protocol

B. Qualification Protocol

C. Equipment Specification

D. P&ID for Hot Detergent & Hot PUW2

Number of Test Pages Attached SECTION 4: COST CALCULATIONS AND SCHEDULE (to be completed by 1Project Engineer)

6COST OF CHANGE 4,262.15 6IMPACT ON SCHEDULE (time) 3 months

SECTION 5: PRE-APPROVALS

PROJECT DISCIPLINE PRINT NAME SIGNATURE DATE

PROJECT ENGINEER FRANK ROCHE Frank Roche 07JUN24

PROJECT MANAGER JOHN ROBERTS John Roberts 14JUN24

EHS KATHY MC DONALD Kathy McDonald 14JUN24

VALIDATION DANIEL CRANDOL Daniel Crandol 10JUN24

QA CALVIN MOORE Calvin Moore 12JUN24

SECTION 6: REJECT CHANGE

PRINT NAME SIGNATURE DATE

CHANGE REJECTED BY N/A N/A N/A

REASON FOR REJECTING CHANGE

N/A MK08JUN24

SECTION 7: DOCUMENT UPDATES (to be completed by 1Engineering Validation)

DOCUMENT UPDATED Yes/No/

N/A DOCUMENT UPDATED Yes/No/

N/A

3Commissioning and Qualification Plan N/A 3Project URS N/A

3System Level URS N/A 3System Impact Assessment N/A

3Component Impact Assessment N/A 3, 4Qualification Protocol(s) Yes

4Commissioning Protocol(s) Yes 4Other Yes

2HAZOP UPDATED (Yes / No) Yes

SECTION 8: 4POST-CHANGE TESTING SUCCESSFUL EXECUTED AND COMPLETED

PRINT NAME SIGNATURE DATE

VERIFIED BY MARIA KALUZNA Maria Kaluzna 07JUN4

SECTION 9: POST-CHANGE APPROVALS

PROJECT DISCIPLINE PRINT NAME SIGNATURE DATE

PROJECT ENGINEER FRANK ROCHE Frank Roche 07JUN24

PROJECT MANAGER JOHN ROBERTS John Roberts 14JUN24

EHS KATHY MC DONALD Kathy McDonald 14JUN24

VALIDATION DANIEL CRANDOL Daniel Crandol 10JUN24

QA CALVIN MOORE Calvin Moore 12JUN24

ADDITIONAL COMMENTS

N/A

1 Enter name and signatures details in approval section; 2 If Yes EHS must approve change; 3 If Yes QA must approve change; 4 Attach list accordingly; 5 Circle correct entry; 6 Attach additional cost breakdown, and if applicable details on updated schedule

Change Control Form

Project Title: New equipment added to the hot detergent and hot PUW2 generation and distribution system CHANGE #: CC-10389

Project No: 1 P&ID / System: P&ID 227

Attachments (Yes/No): No Date: 18 APR 24

SECTION 1: OBSERVATIONS AND PROPOSED CHANGE (to be completed by 1Project Engineer)

ORIGINAL DESIGN: PROPOSED CHANGE:

No Hot detergent and hot PUW2 generation and distribution system onsite The suggested modification involves the installation of a hot detergent and hot PUW2 generating and distribution system in accordance with P&ID-227.

2HAZOP TO BE UPDATED (Yes / No) Yes

SECTION 2: IMPACT ASSESSMENT (to be completed by 1Engineering Validation)

AFFECTED APPROVED ITEMS Yes/No AFFECTED APPROVED ITEMS Yes/No

3Validation Plan Yes 3Project URS Yes

3System Level URS Yes 3System Impact Assessment Yes

3Component Impact Assessment Yes 3, 4Qualification Protocol(s) Yes

4Commissioning Protocol(s) Yes 4Other N/A

3, 5DIRECT 5INDIRECT 5NO IMPACT

3SYSTEM IMPACT Yes No No

SECTION 2 (Continued): IMPACT ASSESSMENT (to be completed by 1Engineering Validation)

3COMPONENT IMPACT 3, 5OPER. CRITICAL 3, 5PRODUCT CONTACT 5NON CRITICAL

Yes Yes No

PROJECT PHASE 5CONSTRUCTION 5COMMISSIONING 3, 5QUALIFICATION

Yes Yes Yes

SECTION 3: TESTING REQUIRED (to be completed by 1Engineering Validation)

4TESTING REQUIRED

Hot detergent system Level control Hot detergent system Flow control

Hot detergent system Temperature control Hot detergent system Detergent control PUW2 Level control

PUW2 Flow control

PUW2 Temperature control PUW2 Detergent control 4DOCUMENT UPDATES REQUIRED

SOP #: 11302 Operation of the Hot detergent system Revision 1

SOP #: 11303 Operation of the Hot PUW2 system Rev/0

SOP #: 11304 Cleaning the Hot PUW2 and Hot Detergent system Rev.0

SOP #: 11325 Examine the attachments and connections on the Hot detergent and hot PUW generation and distribution skid. Rev.2

SOP #: 11330 Assembling and disassembling the Hot detergent and hot PUW generation and distribution skid Rev.3

SOP-235 Operation and maintenance of CIP wash tanks Revision.12

SOP-157 CIP procedures for bioreactors Rev.4.3

SOP-1002 Operation and maintenance of steam supply line Rev.6.7

SOP-645 Operational maintenance of hot detergent line Rev. 15.6

SOP-880 Operational maintenance of PUW1 supply line Rev. 3.9

SOP-184 Operation and maintenance of pumps in generation and distribution system Rev. 1.7

Number of Test Pages Attached 98

SECTION 4: COST CALCULATIONS AND SCHEDULE (to be completed by 1Project Engineer)

6COST OF CHANGE 5000 6IMPACT ON SCHEDULE (time) 4 months

SECTION 5: PRE-APPROVALS

PROJECT DISCIPLINE PRINT NAME SIGNATURE DATE

PROJECT ENGINEER DANIEL CRANDOL Daniel Crandol 03 MAY 24

PROJECT MANAGER FRANK ROCHE Frank Roche 10 MAY 24

EHS KATHY MC DONALD Kathy McDonald 11 MAY 24

VALIDATION AISLING FIELD Aisling Field 12 MAY 24

QA LAURA KEATING Laura Keating 13 MAY 24

SECTION 6: REJECT CHANGE

PRINT NAME SIGNATURE DATE

CHANGE REJECTED BY REASON FOR REJECTING CHANGE: N/A

SECTION 7: DOCUMENT UPDATES (to be completed by 1Engineering Validation)

DOCUMENT UPDATED Yes/No/ N/A DOCUMENT UPDATED Yes/No/ N/A

3Commissioning and Qualification Plan Yes 3Project URS Yes

3System Level URS Yes 3System Impact Assessment Yes

3Component Impact Assessment Yes 3, 4Qualification Protocol(s) Yes

4Commissioning Protocol(s) Yes 4Other N/A

2HAZOP UPDATED (Yes / No) Yes

SECTION 8: 4POST-CHANGE TESTING SUCCESSFUL EXECUTED AND COMPLETED

VERIFIED BY PRINT NAME SIGNATURE DATE

DANIEL CRANDOL Daniel Crandol 15 MAY 24

SECTION 9: POST-CHANGE APPROVALS

PROJECT DISCIPLINE PRINT NAME SIGNATURE DATE

PROJECT ENGINEER DANIEL CRANDO Daniel Crandol 15-May-24

PROJECT MANAGER FRANK ROCHE Frank Roche 15-May-24

EHS KATHY MC DONALD Kathy McDonald 20 MAY 24

VALIDATION JONATHAN WALSH Jonathan Walsh 15-May-24

QA CALVIN MOORE Calvin Moore 24-May-22

ADDITIONAL COMMENTS: N/A

Appendix H:Component Impact AssessmentEquipment Components

Critical Non-Critical

Tag Description Operational Critical Product Contact Critical T-211 Hot Detergent Tank No Yes No

T-411 Hot PUW2 Tank No Yes No

P-207 Detergent Centrifugal Transfer Pump Yes Yes No

P-209 Detergent Centrifugal Transfer Pump Yes Yes No

P-415 PUW2 Centrifugal Transfer Pump Yes Yes No

P-417 PUW2 Centrifugal Transfer Pump Yes Yes No

P-223 Detergent Metering Pump Yes Yes No

HX-211 Detergent Plate Heat Exchanger Yes Yes No

HX-411 PUW2 Plate Heat Exchanger No Yes No

FL-399 Detergent Cartridge Filter No Yes No

FL-401 PUW2 Cartridge Filter No Yes No

PSV-001 PUW2 Sanitary Pressure Relief Valve No Yes No

PSV-002 Detergent Sanitary Pressure Relief Valve No Yes No

Instrument Components

Critical Non-Critical

Tag Description Operational Critical Product Contact Critical TCV-005 Steam Temperature control valve Yes No No

TCV-006 Steam Temperature control valve Yes No No

TT-001 3 wire RTD Temperature transmitters Yes Yes No

TT-002 3 wire RTD Temperature transmitters Yes Yes No

TT-003 3 wire RTD Temperature transmitters Yes Yes No

TT-004 3 wire RTD Temperature transmitters Yes Yes No

PT-001 Sanitary Diaphragm type Pressure Indicating transmitters No No Yes

PT-002 Sanitary Diaphragm type Pressure Indicating transmitters Yes No No

PI-007 Local pressure indicators c/w bourdon type gauges No No Yes

FT-001 Magnetic flow Transmitter Yes Yes No

FT-002 Magnetic flow Transmitter Yes Yes No

FT-003 Magnetic flow Transmitter Yes Yes No

FT-004 Magnetic flow Transmitter Yes Yes No

FS-005 Low Flow switch Yes No No

CT-001 Conductivity transmitter Yes Yes No

PI-003 Diaphragm type pressure indicator Yes No No

PI-004 Diaphragm type pressure indicator Yes No No

PI-005 Diaphragm type pressure indicator No No Yes

PI-006 Diaphragm type pressure indicator Yes No No

PI-008 Diaphragm type pressure indicator Yes No No

TI-007 Bimetalic Temperature indicator Yes Yes Yes

TI-008 Bimetalic Temperature indicator Yes No No

TI-009 Bimetalic Temperature indicator Yes No No

TI-010 Bimetalic Temperature indicator Yes No No

LS-003 Low Level Switch (Tuning fork type) Yes Yes No

LS-004 Low Level Switch (Tuning fork type) Yes Yes No

LS-005 High Level Switch (Tuning fork type) Yes Yes No

LS-006 High Level Switch (Tuning fork type) Yes Yes No

LT-001 Hydrostatic Pressure type level Transmitter Yes No No

LT-002 Hydrostatic Pressure type level Transmitter Yes No No

XV-003 Actuated Sanitary Butterfly Valve No Yes No

XV-004 Actuated Sanitary Butterfly Valve No Yes No

XV-008 Actuated Sanitary Ball Valve No Yes No

XV-009 Actuated Sanitary Ball Valve No Yes No

XV-001 Actuated Tuchenhagen Multiport divert Valves. No Yes No

XV-002 Actuated Tuchenhagen Multiport divert Valves. No Yes No

XV-005 Actuated Tuchenhagen Multiport divert Valves. No Yes No

XV-006 Actuated Tuchenhagen Multiport divert Valves. No Yes No

XV-007 Actuated Tuchenhagen Multiport divert Valves. No Yes No

PRV-001 Back Pressure Regulating Valve No Yes No

PRV-002 Back Pressure Regulating Valve No Yes No

Piping Components

Critical Non-Critical

Tag Description Operational Critical Product Contact Critical 50-PUW1-S6-147-IH From LN-486 To T-211 No Yes No

50-PUW1-S6-148-IH From LN-486 To T-411 No Yes No

80-DETERGENT-S6-149-IH From T-211 To FL-399 No Yes No

80-DETERGENT-S6-150-IH From FL-399 To P-207 No Yes No

80-DETERGENT-S6-151-IH From LN-150 To P-209 No Yes No

65-DETERGENT-S6-152-IH From P-209 To LN-153 No Yes No

65-DETERGENT-S6-153-IH From P-207 To HX-211 No Yes No

65-DETERGENT-SS1-154-IH From HX-211 To XV-021 @ DETERGENT change-over valves No Yes No

80-PUW2-S6-156-IH From FL-401 To P-415 No Yes No

80-PUW2-S6-157-IH From LN-156 To P-417 No Yes No

65-PUW2-S6-158-IH- From P-417 To LN-159 No Yes No

65-PUW2-S6-159-IH- From P-415 To HX-411 No Yes No

65-PUW2-SS1-160-IH- From HX-411 To XV-016 @ PUW2 change-over valves No Yes No

25-PROCESS-S6-161-NI From Conc. Detergent Dosing System To P-223 No Yes No

25-PROCESS-S6-162-NI From P-223 To LN-149 No Yes No

65-DETERGENT-SS1/S6-163-IH From XV-018 @ DETERGENT change-over valves To T-211 No Yes No

65-PUW2-SS1/S6-164-IH From XV-013 @ PUW2 change-over valves To T-411 No Yes No

100-VENT-S6-166-NI From T-211 To Safe Area No No Yes

25-DRAIN-S6-167-NI From LN-166 To LN-176 No No Yes

100-VENT-S6-168-NI From T-411 To Safe Area No No Yes

25-DRAIN-S6-169-NI From LN-168 To LN-176 No No Yes

50-DRAIN-S6-170-NI From XV-002 @ T-211 outlet to LN-176 No No Yes

50-DRAIN-S6-171-NI From XV-001 @ T-411 outlet to LN-176 No No Yes

25-VENT-S6-172-NI From PSV-002 To LN-176 No No Yes

25-VENT-S6-173-NI From PSV-001 To LN-176 No No Yes

50-DRAIN-S6-174-NI From XV-006 @ T-211 inlet to LN-176 No No Yes

50-DRAIN-S6-175-NI From XV-005 @ T-411 inlet to LN-176 No No Yes

80-DRAIN-SS1-176-NI From Drain Lines to Drain Header No No Yes

15-DRAIN-S6-177-NI From P-207 To Drain No No Yes

15-DRAIN-S6-178-NI From P-209 To Drain No No Yes

15-DRAIN-S6-179-NI From P-415 To Drain No No Yes

15-DRAIN-S6-180-NI From P-417 To Drain No No Yes

50-DRAIN-SS1-181-NI From T-411 Pump Discharge To Drain No No Yes

50-DRAIN-SS1-182-NI From T-211 Pump Discharge To Drain No No Yes

65-PLANT STEAM-CS5-183-IH From LN-241 To HX-211 / HX-411 No No Yes

15-PLANT STEAM-CS5-184-IH From LN-241 To LN-185 No No Yes

20-CONDENSATE-CS5-185-IH From LN-184 To LN-242 No No Yes

40-CONDENSATE-CS5-186-IH From HX-211 To LN-242 No No Yes

40-CONDENSATE-CS5-187-IH From HX-411 To LN-242 No No Yes

100-PLANT STEAM-CS5-241-IH From Existing Steam Header Level 2 To Cleaning generation Skid No No Yes

80-CONDENSATE-CS5-242-IH From Cleaning Generation Skid To Existing Condensate Header Level 4 No No Yes

40-COMPRESSED AIR-SS1-502-NI From V-39 To Pneumatic Control No No Yes

Appendix I:Traceability MatrixTesting Traceability Matrix

Hot Detergent and Hot PUW Generation and Distribution

Plant Throughputs for Hot Detergent and Hot PUW Generation System

URS Item Number User Requirement Description Testing Comment

1.1 The Hot Detergent system shall be capable of achieving and maintaining defined flowrates, at steady state conditions, e.g. maximum flow of 25,000 kg/hr 5%, minimum flow of 3,000 kg/hr 5% etc. Operational / Functional Test Hot Detergent System - Flow Control

Procedure section 13.2 &13.3 [Insert #]

Check sheet 16.3.2 &16.3.3 Conduct test during simultaneous maximum Hot Detergent drawdown into reactor RE-119 and reactor RE-140

1.2 The Hot PUW system shall be capable of achieving and maintaining defined flowrates, at steady state conditions, e.g. maximum flow of 25,000 kg/hr 5%, minimum flow of 3,000 kg/hr 5% etc. Operational / Functional Test - Hot PUW System Flow Control

Procedure Section 13.6 &13.3

Check sheet 16.3.6 &16.3.3 Conduct test during simultaneous maximum Hot PUW drawdown into reactor RE-119 and reactor RE-140

2Skid Configuration

URS Item Number User Requirement Description Testing Comment

2.1 The Skid shall consist of the following equipment items. The detailed design specifications for these equipment items are outlined in Appendix 1.

Process water tank1

Detergent solution tank1

Centrifugal recirculation pumps4

Detergent dosing pump1

Heat exchangers2

Equipment Installation Test

Procedure 11.2

Checksheet 16.2.2 &

16.2.2.1 to Checksheet 16.2.2.13

Piping Installation Test

Procedure 11.4 &11.1

Checksheet 16.2.4&16.2.1 Conduct a P&ID walkdown and Equipment and Piping Installation Tests for the CIP Skid.

2.2 Instrumentation as illustrated on the P&ID-227 shall be supplied with the skid.

Instrument Installation Test

Procedure 11.3

Checksheet 16.2.4 &

16.2.3.1 to Checksheet 16.2.3.12 Conduct a P&ID walkdown and Instrumentation Installation Test for the CIP SKID

3Hot Detergent Solution Operation

URS Item Number User Requirement Description Testing Comment

3.1 The Hot Detergent Tank shall be fed directly from the 25C PUW1 water loop and shall maintain the level in the tank during maximum drawdown into the reactors being washed.

Operational / Functional Test - Hot Detergent System Level Control

Procedure section 13.1 & 13.4

Checksheet 16.3.1 & 16.3.4

Conduct test during simultaneous maximum Hot Detergent drawdown into reactor RE-119 and reactor RE-140

3.5 The system shall have the facility to automatically dose concentrated detergent to the required concentration (2% 0.05%) during drawdown into the 2 reactors.

Online conductivity measurement shall be provided to verify the detergent concentration. Operational / Functional Test - Detergent Dosing Control

Procedure 13.4 &13.1

Checksheet 16.3.4 &16.3.1

Conduct test during simultaneous maximum Hot Detergent drawdown into reactor RE-119 and reactor RE-140

4Hot PUW Solution Operation

URS Item Number User Requirement Description Testing Comment

4.4 The Hot PUW supply temperature shall be maintained by a closed loop control system, which modulates steam flow to the heat exchanger.

The control system shall be capable of controlling the supply temperature to within 5C of the setpoint (80C) during maximum drawdown of the Hot PUW for the 2 reactors. Operational / Functional Test - Hot PUW System Temperature Control

Procedure13.7 &13.5

Checksheet 16.3.7 & 16.3.5

Conduct test during simultaneous maximum Hot PUW drawdown into reactor RE-119 and reactor RE-140

PUW Generation PW and WFI storage and distribution systems. The pharmaceutical water distribution system

https://cm-systems.pl/en/products-and-services/storage-distribution-systems

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