QPS LLC

SYSTEM DESCRIPTION

The CIP system shall be provided for the cleaning of a lyophilizer.  The CIP System is designed as a one-tank system, in a fully validated, cGMP compliant fashion. The CIP system consists of the following fully integrated major components:

• CIP Solution Tank
• Centrifugal Supply Pump
• CIP Solution Heater (Steam)
• Control System with HMI including all related instrumentation

The system is pre-engineered and built for the addition of detergents.  Refer to the last section for description of the detergent wash components. 

PROCESS OVERVIEW

QPS shall design and build a one tank CIP system. The CIP system shall be designed and fabricated to meet all cGMP and ASME BPE standards.

QPS shall supply a pre-engineered, pre-piped, pre-wired and skid mounted system. System to include storage tank, pump, filters, instrumentation and controls, pressure safety devices, valves, control panels, electrical devices and any other necessary design components.

The CIP Solution Tank is for holding of ambient WFI for initial and final cleaning cycle rinses; it is also designed for holding / recirculation of CIP wash solutions used in the cleaning cycle. WFI shall be delivered to this tank at ambient conditions. When required by the cleaning cycle, it will be necessary to heat the water or wash solution to 176°F maximum, by recirculation through a QPS supplied steam heat exchanger.

Feed water to the CIP system will be provided by a recirculation loop (by others). CIP System shall send a pneumatic control signal from the QPS supplied local control system to the pneumatically controlled WFI feed water valve (by others) when there is a demand for CIP system water.

The CIP system will be used for the cleaning of a lyophilizer.  The CIP system shall be equipped with an independent control system and shall be capable of delivering WFI or re-circulated wash detergent solutions to the lyophilizer.

The lyophilizer cleaning cycle is controlled by the lyophilizer control system. The CIP system will deliver the following to the lyophilizer, as required:

• WFI at a temperature ranging from ambient to 176 °F; flowrate 40 gpm; 40 psig pressure at lyophilizer. Used to supply spray devices for once-through rinses. Total water used for cleaning one lyophilizer is approximately 300 gallons.

The length of piping from the CIP skid to the lyophilizer skid is approximately 10 feet; 2" diameter stainless steel tubing is planned.

The CIP system shall be controlled by an onboard PLC. The CIP control system shall be configured for cleaning at the lyophilizer using one step.

Lyophilizer CIP supply piping and associated flow divert valves from the CIP system to the equipment that will be cleaned will be supplied by the owner (or lyophilizer vendor)and shall not be included in the QPS's scope of supply.  The CIP loop supplied by QPS will bring water to the customer equipment.

EQUIPMENT

CIP Solution Tank

One stainless steel insulated atmospheric vessel shall be provided with level control/switches. The tank shall be completely self drainable. The tank shall be equipped with a u-bend vent line.

QPS to provide a vessel with a minimum working volume of 300 gallons.

The vessel shall be fabricated out of 316L stainless steel with welds ground smooth and with an internal electropolish finish. The external surface finish shall be 2B with welds ground smooth.

Tank will have removable spray ball assembly at WFI fill line.

CIP Liquid Steam Heater

The heater shall be of sanitary design and shall be capable of heating the WFI water and the re-circulating cleaning solution (maximum volume of 300 gallons, i.e. contents of CIP Solution Tank) within the skid boundary from 68°F to 185°F (20 to 85°C) in 30 minutes, prior to leaving the skid boundary and entering the lyophilizer CIP piping.

Owner shall include any required pressure reducing valves to reduce the steam pressure from the supply to the working pressure of the heater.

QPS shall provide all necessary relief devices for the steam heater.

Pump

The CIP supply pump shall be sanitary design, industry-accepted pump, sized to circulate at least 40 gallons per minute of solution at a discharge pressure determined by QPS to accomplish the identified piping runs.

The pump shall be complete with electric motor, wash down capability, casing drains and provisions for pneumatically operated diaphragm drain valve. The pump shall have a VFD controller. The pump controls/VFD shall be operated through the CIP control system.

Air Blow

Furnish sanitary isolation valve(s) for a filtered air-blow, on the discharge of the CIP heater.

The air-blow supply filter shall be a 5" sanitary code-7 style with a 316L SS housing and 0.2 μm PTFE filter cartridge.

QPS shall include a filter/regulator and pressure gauge for the air-blow compressed air supply.

MECHANICAL DETAILS

General

All exposed moving parts shall be enclosed with OSHA approved guards.

Equipment shall comply with the Current Good Manufacturing Practices of the Department of Health, Education and Welfare; Food and Drug Administration and the Department of Health and Social Services.

Design shall include provisions for ease of maintenance of all components.

All pressure rated vessels shall be designed, fabricated, inspected and tested in accordance with ASME Code Section VIII, Division 1. National Board (NB) registration and U stamp.

Relief valves shall be provided for the process and utility sides of heat exchangers as required by codes.

As a minimum, the valves shall be sized for conditions of thermal expansion, failed open regulators / control valves, blocked outlet with continued heating, and fire scenario.

QPS to provide field NIST calibration of all Instrumentation.

All engineered wiring systems and their components shall be assembled in accordance with UL 508A standards. 

Materials and Finishes

Tubing will be manufactured of Type 316L stainless steel using TIG (Tungsten Inert Gas) welding methods without the addition of filler metal to produce pharmaceutical grade tubing conforming to ASTM A269 and A270. Tubing will be fully annealed after welding. Tubing wall thickness will be as follows:  1/4" OD 0.035"; 3/8" OD 0.035"; 1/2" through 3" OD 0.065"; 4" 0.083"

Fittings: Tube fittings will be suitable for fabrication into the system by automatic welding or sanitary clamped connections. Fittings will be of material, wall thickness, and finish specified for tubing.

Joints: Only automatic machine butt-welded and tri-clamp type joints will be provided. Tri-clamp type joints will be used when connecting to equipment and accessories with tri-clamp type ends; otherwise, joints will be automatic machine butt-welded.

Support frame fabricated using 304 stainless steel square tubing. All welds ground and polished suitable for washdown cleaning.

Valves

Sanitary piping shall use diaphragm valves with tri-clamp or butt weld endings to match ferrules to which they are attached and Teflon faced EPDM gaskets.

Interior finish shall be electro-polish over multi-pass mechanical polish to 32 micro-inch Ra.

Exterior finish will be standard mill finish.

All elastomers shall be either PTFE or EPDM and be CFR 21 Part 177 compliant.

All internal surfaces shall be designed to allow free drainage.

Actuators will be provided with limit switches tied to the CIP control system to indicate status of the valve.

Assembly

All pipe work shall be seamless and shall be designed and constructed to be adequately sloped (minimum of 1/8" per foot) to allow free self-drainage to a common drain. Size reductions in horizontal pipe will be made with eccentric reducers only and be positioned to allow for self-drainage.

Branch valves, gauges, and control devices will be located within six pipe diameters of branch pipe measured from axis of piping main.

All pipe work and tubing shall be designed and constructed to drain freely and be free from all deadlegs.

Threaded fittings shall not be used for any piped service connection supplying product contact utilities.

Only continuous pipe runs, welded piping (orbital or butt) or sanitary (tri-clamp) fittings / connections shall be used. Threaded / flanged fittings will be used for non-product contact utility (i.e. plant steam, vacuum, refrigerant, etc.)

Painting and Insulation

All non-insulated, non-stainless steel components shall be painted per QPS standards with epoxy paint that is resistant to water, ethanol, acetone and isopropyl alcohol.

All potentially hot piping will be insulated with chloride free insulation.

All surfaces to be insulated will be cleaned to remove dirt, grease, or other foreign matter prior to application of insulation materials.

All openings for nozzles, nameplates, etc., will be cut as close as possible to achieve a tight fit without interfering with make up connections.

Nameplates and Code stamps will be left uncovered and readable.

Certification

Stainless steel valve, tube and fitting certification will indicate mill heat number from which they were manufactured. Chemical analysis will be furnished for each mill heat number.

Weld and Passivation certificates shall be provided for all sanitary piping and tubing including the following as a minimum:

• Weld Log
• Weld Map
• Material Certifications including Heat Numbers
• Welding Procedures
• Welder Qualifications
• Boroscope of all welds (where boroscope access is possible), with 10% of those welds being videotaped

CONTROLS SYSTEM

Description

The main control panel will have an operator interface mounted to the front of the control panel.  The operator interface is an Allen Bradley Panelview Plus screen with an Ethernet communication port.  The OIT will communicate with the PLC via the Ethernet port using an Ethernet protocol.  The OIT will allow the users to view process data, enter setpoints and change control states.

The main control panel will provide the operator the capability to select desired recipe, and to skip and / or repeat any of the steps in the pre-programmed sequences. The panel will be provided with an emergency stop button and the ability to cancel a recipe in mid cycle. The panel will indicate the system status and availability of the system to execute a CIP cycle.

Data display and input for operation of the CIP System shall be accomplished via the OIT mounted in a control panel on the skid.

The control system will control the operation of the one CIP Supply valve (owner furnished - as depicted in the overall system schematic). Connection of pneumatic lines from the valve shall be furnished by others.

The OIT screens will provide for operations monitoring, operator interface, alarm monitoring and alarm summary, and system diagnostics. The operations screen shall indicate "Ready" when all parameters have been satisfied and the equipment can be run. Operator interface screens shall enable the operator to operate the equipment via programmable function keys and input selected numeric data. The diagnostics screen(s) shall provide status of critical inputs and outputs.

Operators will have the ability to set timers, change timers, control and change flow rates and controller set points, and select recipes from the main control panel. 

The system will include continuous alarm monitoring. Critical alarms will result in a safety interlock requiring operator action. The operator will be required to acknowledge the alarm before the alarm can be reset and the system restarted. All alarms will be displayed on the alarm summary page. When any alarm is reported, the PLC will generate a signal to an audible device on the control panel. Audible alarms will be silenced on the OIT.

The operator interface will be provided a Restart button to restart the equipment for operation after alarm clearance. Cleaning sequence will restart from the point of alarm.

The control system will be fully 21 CFR Part 11 compliant. Software automation shall be deployed to achieve Part 11 compliance wherever practical.   Compliance validation is a customer responsibility.

The equipment will be provided with an Emergency Stop button. The Emergency Stop button will be highly visible and readily accessed without obstruction. When activated, the hard-wired Emergency Stop button disables all mechanical operations immediately.

The equipment will automatically stop after designated faults and an audio / visual alarm will sound. The restart of the equipment after this event will be manually initiated.

Security

Access to certain screens will require entry of a numeric password.  If a password-protected screen is accessed, a pop up will appear requesting log in.  If the correct password is entered, access will be granted.  If an incorrect password is entered, access will be denied and the OIT will return to the previous screen. Log out is automatic when the screen saver activates on the OIT.  Screen saver activation is user adjustable.  Password protection is provided at two (2) levels:  Administrator and Operator 1. These passwords can be modified on the Administrator screen.

OIT Screens

The following are proposed Control Panel OIT Screens.  Final screens may vary. 

Screen Number	Description	Comment
NA	Alarm Banner	Pop up display when an alarm occurs
1	Main	Main Screen
2	Navigator	System Navigation Screen
3	System Overview	System Overview Screen
4	Heat Exchanger & Utility Status	Displays detailed information about the heat exchanger and utilities
5	Tank Status	Displays detailed information on the Tank
6	Active Alarm	Displays active alarms
7	Alarm History	Displays alarm history
8	Operator	Operator control screen
9	Admin	Administrator control screen
10	Control Setpoint	Control setpoint adjustment screen
11	Alarm Setup	Alarm setup adjustment screen
12	Output Override	Output override screen
13	PID Loop Tuning	PID Loop tuning screen
14	Alarm Delay	Alarm delay adjustment screen.

Analog Inputs

The CIP Control System will interface with field-mounted sensors that are connected to the PLC analog inputs.  This data will be scaled and used for control within the PLC and indicated on the OIT.

Analog Outputs

The CIP Control System will interface with field-mounted controls that are connected to the PLC analog outputs.  This output will be used for control and indicated on the OIT.

Discrete Inputs

The CIP Control System will interface with field-mounted sensors that are connected to the PLC discrete inputs.  This data will be used for control within the PLC and indicated on the OIT.

Discrete Outputs

The CIP Control System will interface with field-mounted controls that are connected to the PLC discrete outputs.  This output will be used for control and indicated on the OIT.

 Interface with Other Systems

The CIP Control System will be interfaced to the Lyophilizer Control system.  QPS will provide a "Ready" bit and require a return "Status" bit from the Lyophilizer.  The CIP Control System will control a user supplied fill valve.  A set of common dry contacts is provided as a general remote alarm interface.

System Architecture

The CIP Control System will consist of (1) Allen Bradley Micrologix PLC and (1) PanelView Plus Operator Interface Terminals.

The PLC and PanelView will communicate over an Ethernet cable internal to the main CIP Control System cabinet. 

The PLC and PanelView will be programmed and communicate using Panelbuilder 32 Rev 3.82, RSLogix500 Rev #7.00.00, and RSLinx #2.50.00 or newer versions.

Power Loss

In the event of a power loss the system will return to the state prior to power loss.  The Panelview will return to the Main screen. 

Power Up

The Process PLC is operational upon the application of power.  The program will execute, based on inputs and operator interface settings, on the application of power.

The PanelView terminals are operational upon the application of power.  The main screen is the start up screen.

Power Down

The PanelView consoles and PLC processor have battery-backed memory which will maintain the programming when power is removed.

Redundancy

The PLC's processors and OIT's have battery backed RAM which will retain the contents of user memory through extended power outages. Should a hardware failure result in a loss of program software the PLC & Panel View software must be restored from backup into the repaired hardware.  There is no hardware redundancy in the PLC control system.  A hardware failure may cause the system to become inoperable or may cause unexpected results.

Manual Control Operations

Manual operations can only be initiated from the password protected PLC Output Override and PID Loop Tuning Screen.  A PLC output can be turned off or turned on.  In the case of analog outputs, these can be turned off (0%) or turned on.  When an analog output is turned on, it will be set to the analog override % set from the override screen.  Only PLC outputs controlled by the Local PLC rack are available for override. 

The normal operating mode of all PLC outputs is Automatic.  All outputs should be set to Auto from the PLC Output Override Screen and PID Loop Tuning Screen.  If any of the outputs are not in automatic, the Override Indicator will appear on all screens.

 

Automatic Operator Control Functions

Operator control functions are initiated from the password protected Operator screen. When selected, these functions will enable the automatic control sequence associated with that function. The operator-initiated functions will have associated prerequisites and permissives.

The control system uses multiple sequence steps.  Each step will have a unique indentifying initiating condition, any action conditions and setpoints, step number, and the state of the system outputs and valves

ELECTRICAL

The system shall be provided complete, with all necessary motor starters, step-up and step-down transformers, and transfer switches premounted by the QPS.

All motor starting equipment and transfer switches shall be separated from the control panel devices in a manner to prevent interference with these devices.  A separate motor starting panel may be provided if necessary.

Stop switches shall be provided and shall be mounted adjacent to each motor.

Analog and digital wiring will be insulated and shielded and connected to devices and routed directly through bulkheads in the panel.

High voltage wiring will be contained in suitable conduit.

PHYSICAL CONSTRAINTS

QPS estimates the CIP System requires 4' x 8' of floor space.  Final dimensions including elevations will be submitted upon receipt of purchase order.

UTILITIES

Power: 480 Volt / 3 Phase / 60 Hertz (or owner specific voltage); 110V / 1 Phase / 60 Hertz - QPS to receive two electrical feeds to distribute power at system voltage/phase as required.

Compressed Air: 80 psig - 16-20 scfm

Steam: Saturated and dry, available at 100 psig, 338°F - 507 lbs / hr

Water For Injection (WFI): Available at 40 psig @ 65°F +/- 10°F - Quantity of 300 gallons + additional for CIP rinses (up to 1200 gallons)

Drain: No temperature or chemical treatment is provided. Customer may need to dilute effluent from their equipment prior to introducing it to a PVC drain.

FACTORY ACCEPTANCE TESTING (FAT)

General

In advance of the FAT, QPS shall undertake the following as a minimum:

• Verification that the equipment is mechanically and electrically complete; satisfying the User Requirements Specification.

• 100% P&ID Verification
• 100% Electrical / Wiring Diagram Verification
• 100% Input / Output Verification (digital and analog)
• 100% Alarms / Interlocks Verification

The intent of the FAT is for the owner to confirm specification compliance. The FAT will not be used to trouble shoot the equipment. Troubleshooting / commissioning of the equipment shall be done by QPS prior to the owner's witnessing of the FAT.

Factory Testing

QPS shall develop Factory Acceptance Test (FAT) documents. QPS shall submit the FAT documents, for review, by the owner.

QPS shall submit the testing procedures for review two weeks prior to the start of testing.

In general, the FAT is intended to confirm compliance to the equipment specification. The FAT will provide testing of all operations that are required by the equipment. These tests shall be developed to simulate normal operating conditions to the extent possible. The overall FAT testing will include, functional testing, documentation confirmation, alarm, and interlock testing. As a minimum, documentation confirmations shall include dimensional checks; alarm lists; sequence of operation; calibration, spare parts list; material certification reviews; and welding including visual inspection of all welds, flushing, cleaning and passivation documentation reviews.

The QPS shall be responsible for the development and the execution of the FAT document. The owner shall be given the opportunity to witness and/or participate in the FAT execution at their discretion. A schedule of FAT execution activities shall be developed and maintained by QPS.

During the execution of the FAT, QPS shall conform to good documentation practices. This includes, but is not limited to, using indelible ink for data recording, signing and dating all data entries at the time they are recorded, using a single line strike out that is initialed and dated for all data entry errors, and providing explanation for line-outs that do not have an obvious reason. It is the intent of this project that some testing conducted and documented in the FAT may not be repeated once the system is installed at the owner site.

A formal deviation recording process will be described in the FAT document. The deviation process will describe what actions and sequences take place when data is recorded that does not conform to the acceptance criteria or expected results. The process of recording deviations, informing the appropriate personnel, determining corrective actions, determining dispositions, closing out, and final approval will be described.

Calibrated instrumentation traceable to the National Institute of Standards and Technology (NIST) will be used. Copies of all calibration certificates shall be turned over with the completed FAT document.

At the conclusion of the FAT, the originally approved document, the completed data sheets, and all referenced documentation and attachments shall be submitted to the owner's designated agent for their acceptance.

SITE ACCEPTANCE TESTING (SAT)

At the owner's discretion, all or some of the tests performed during the FAT will be repeated at the jobsite.

QPS shall demonstrate the complete functional integration of all of the components of the CIP System.

GUARANTEES/WARRANTIES

QPS guarantees the equipment, materials, and workmanship for period of twelve (12) months from date of start-up or eighteen (18) months from date of shipment, whichever comes first. During this period, QPS shall promptly provide travel time, labor, material, equipment, and services necessary to correct defects that may occur all at no cost to the buyer.

OPTIONAL DETERGENT WASH SYSTEM

SYSTEM DESCRIPTION

The system is pre-engineered and built for the addition of detergents.  The optional detergent system requires additional control components, a software upgrade, valving, and chemical delivery system and will include the following major components:

• Chemical Delivery System
• Conductivity Meters
• Control System and HMI software upgrade
• Actuated Drain Valves with Limit Switches

PROCESS OVERVIEW

The optional detergent wash system will deliver the following to the lyophilizer, as required:

• WFI at a temperature ranging from ambient to 176 °F; flowrate 40 gpm; 40 psig pressure at lyophilizer. Used to supply spray devices for once-through rinses. Total water used for cleaning one lyophilizer is approximately 300 gallons.
• Cleaning solution at a temperature ranging from ambient to 176 °F; flowrate approximately 40 gpm; pressure required at lyophilizer is less than 40 psig. Used to fill lyophilizer with cleaning solution. Total cleaning solution (WFI and detergent) used for cleaning one lyophilizer is approximately 300 gallons.

The control system upgrade for the system will provide up to four steps: pre-rinse, wash, post-rinse and final rinse.

EQUIPMENT

Chemical Delivery System

The chemical delivery system shall consist of a polyethylene reservoir with chemical feed pump and chemical supply piping manifold. The system shall be designed to deliver cleaning chemicals during a cleaning cycle. The delivery pump shall be controlled by the CIP control system. QPS shall provide a standard feed pump constructed of material compatible with cleaning solutions containing potassium hydroxide, sodium hydroxide, phosphoric acid, or citric acid in varying concentrations.

QPS shall include low level probe for reservoir, for the CIP detergent.

Level switch shall trigger an alarm and/or status message based on the level probe.

Conductivity Meter

Furnish fully assembled conductivity meter and transmitter, sanitary design, for conductivity measurement on CIP solution supply and at the chemical addition port.  Sensors are high range toroidal style.  Chemical addition will be adjusted using these sensors.