lyomax 50 industrial freeze drying system

BOC EDWARDS BOC Edwards Pharmaceutical Systems

PSGA MTE1870 Lyomax 50 1/69

Maintenance Manual Rev. 1 (13-Dec-2004) SC473401.doc

Maintenance Manual

Lyomax 50 Industrial Freeze Drying System

Revision : 1 Revision Date : 13 December 2004

Note: Be sure that you have read the Operating Manual and are familiar with operation of the Lyomax 25 before performing maintenance. The Lyomax 25 Operating Manual provides details on the Maintenance and Device Mode screens that will be used during routine maintenance and troubleshooting.


2/69 MTE1870 Lyomax 50 PSGA

SC473401.doc Rev. 1 (13-Dec-2004) Maintenance Manual

VERSION DATE NAME DESCRIPTION 0 12/03/04 MV Initial Release 1 12/13/04 MV Incorporate FAT Comments

Copyright Notice

This manual contains confidential and proprietary information of BOC Edwards Pharmaceutical Systems and is provided in confidence and solely for use in conjunction with the Freeze Dryer indicated on the title page of this manual. The manual may not be reproduced or its contents disclosed to third parties without the prior written consent of BOC Edwards Pharmaceutical Systems. BOC Edwards Pharmaceutical Systems reserves the right to make additions, deletions, or modifications to the information at any time without prior notification.

Copyright © 2004, The BOC Group All rights reserved

BOC Edwards Pharmaceutical Systems is a trading name of The BOC Group Inc.




TABLE OF CONTENTS

1. SAFETY..................................................................................................................................... 7 1.1 Introduction ........................................................................................................................... 7 1.2 Safety Precautions................................................................................................................ 7 1.2.1 Health and Safety Aspects................................................................................................... 8 1.2.2 Qualification ......................................................................................................................... 8 1.2.3 Stoppering System............................................................................................................... 8 1.2.4 Sterilization .......................................................................................................................... 8 1.2.5 Cycle Optimization ............................................................................................................... 8 1.2.6 Computer Programs............................................................................................................. 9 1.2.7 Shipment.............................................................................................................................. 9 1.3 Maintenance Hazards ........................................................................................................... 9 1.4 Operating Hazards .............................................................................................................. 10

2. DESCRIPTION ........................................................................................................................ 12 2.1 Introduction ......................................................................................................................... 12 2.2 Basic Construction ............................................................................................................. 12 2.3 Component Parts ................................................................................................................ 12 2.3.1 Freeze Drying Chamber..................................................................................................... 12 2.3.2 Vacuum System................................................................................................................. 13 2.3.2.1 Vacuum Control .............................................................................................................. 14 2.3.2.2 Capacitance Pressure Gauge......................................................................................... 15 2.3.3 Refrigeration System ......................................................................................................... 15 2.3.4 Product Shelves................................................................................................................. 16 2.3.4.1 Shelf Temperature Control.............................................................................................. 17 2.3.5 Ice Condenser.................................................................................................................... 17 2.3.6 Control System .................................................................................................................. 18 2.3.6.1 Personal Computer (PC)................................................................................................. 18 2.3.6.2 Programmable Logic Controller (PLC) ............................................................................ 19 2.3.6.3 Screen Printer ................................................................................................................. 19 2.3.7 Manual Controls................................................................................................................. 19 2.3.7.1 Control and Power Panel ................................................................................................ 20 2.3.7.2 Remote Panels................................................................................................................ 20 2.3.7.3 Operator Interface - Manual Controls Screen ................................................................. 20 2.4 Functional Accessories...................................................................................................... 20 2.4.1 Hydraulic Stoppering System............................................................................................. 20 2.4.2 Steam Sterilization System (SIP) ....................................................................................... 21 2.4.3 Main Isolation Valve........................................................................................................... 22 2.4.4 Clean In Place System (CIP) ............................................................................................. 22 2.4.5 Calibrated Leak.................................................................................................................. 22 2.5 Automated Tests................................................................................................................. 23 2.6 Nitrogen Blanket for Silicone Oil Expansion Tank .......................................................... 23




3. COMMISSIONING AND TESTING.......................................................................................... 24 3.1 Service Connections .......................................................................................................... 24 3.1.1 Refrigerant Compressor Cooling Water ............................................................................. 24 3.1.2 Defrost ............................................................................................................................... 25 3.1.3 CIP Supply ......................................................................................................................... 25 3.1.4 Compressed Air Supply ..................................................................................................... 25 3.1.5 Vacuum Pump Exhaust ..................................................................................................... 25 3.1.6 Electrical Supply ................................................................................................................ 26 3.1.7 Sterile Air/Inert Gas............................................................................................................ 26 3.1.8 Steam Quench Water ........................................................................................................ 26 3.1.9 Main Drain.......................................................................................................................... 27 3.1.10 Filtering Hydraulic Fluid ..................................................................................................... 27 3.2 Preparing the Freeze Dryer for Operation ........................................................................ 27 3.2.1 Preparing the Refrigerant Compressor .............................................................................. 27 3.2.2 Dry Vacuum Pump Gear Box Oil Level.............................................................................. 27 3.2.3 Testing the Refrigeration Circuit ........................................................................................ 27 3.3 Functional Tests and Calibration ...................................................................................... 28 3.3.1 Start Up and Preliminary Tests .......................................................................................... 28 3.3.2 Calibrating Temperature Probes........................................................................................ 30 3.3.3 Partial Shut Down after Commissioning............................................................................. 30 3.3.4 Automated Tests................................................................................................................ 31 3.3.4.1 Ram Bellows Test ........................................................................................................... 31 3.3.4.2 Main Valve Bellows Test ................................................................................................. 31 3.3.4.3 Leak Test ........................................................................................................................ 31 3.3.4.4 Filter Integrity Test (FIT).................................................................................................. 31

4. ROUTINE MAINTENANCE ..................................................................................................... 32 4.1 Introduction ......................................................................................................................... 32 4.2 Cleaning the Chamber........................................................................................................ 32 4.3 Daily Maintenance............................................................................................................... 33 4.3.1 Refrigerant Compressors................................................................................................... 33 4.3.2 Compressed Air Supply ..................................................................................................... 34 4.3.3 Product Temperature Probes............................................................................................. 34 4.3.4 Dry Vacuum Pumps ........................................................................................................... 34 4.3.5 Silicone Oil Circuit .............................................................................................................. 35 4.3.6 Hydraulic Stoppering.......................................................................................................... 35 4.3.6.1 Checking and Replacing Seals ....................................................................................... 35 4.3.6.2 Replacing Hydraulic Oil Filters ........................................................................................ 35 4.3.7 Device Mode (Maintenance Only)...................................................................................... 36 4.4 Weekly Maintenance........................................................................................................... 37 4.5 Monthly Maintenance ......................................................................................................... 37 4.6 Semiannual Maintenance ................................................................................................... 37 4.7 Annual Maintenance ........................................................................................................... 39 4.8 Maintenance Summary....................................................................................................... 40




4.9 Service Contracts ............................................................................................................... 40

5. SPECIALIZED MAINTENANCE.............................................................................................. 41 5.1 Introduction ......................................................................................................................... 41 5.2 Silicone Oil Circuit .............................................................................................................. 41 5.2.1 Silicone System Leak Test................................................................................................. 41 5.2.2 Vacuum Filling ................................................................................................................... 42 5.2.3 Pump Filling ....................................................................................................................... 44 5.2.4 Silicone Oil Circuit Check................................................................................................... 45 5.3 Refrigeration System.......................................................................................................... 45 5.3.1 Refrigeration Circuit Pressure Safety Check ..................................................................... 45 5.3.2 Evacuating the Refrigeration System................................................................................. 47 5.3.3 Refrigerant Compressors - Cooling Water Supply ............................................................. 48 5.3.4 Charging Refrigeration System.......................................................................................... 49 5.3.4.1 Initial Charge of Refrigerant ............................................................................................ 49 5.3.4.2 Refrigeration System Problem Solving ........................................................................... 50 5.3.5 Recovery of Refrigerant ..................................................................................................... 51 5.3.6 Recovery of Refrigerant for Storage or Disposal ............................................................... 52 5.3.7 Refrigerant Compressors - Adding/Changing Oil............................................................... 53 5.3.8 Replacing the Dehydrator Filter and Anti-Acid Filter .......................................................... 53

6. GENERAL MAINTENANCE.................................................................................................... 54 6.1 Filling the Rotary Vacuum Pumps..................................................................................... 54 6.2 Hydraulic Stoppering.......................................................................................................... 54 6.2.1 Checking and Replacing Seals .......................................................................................... 54 6.2.2 Replacing Hydraulic Oil Filters........................................................................................... 54 6.2.3 Adding Hydraulic Fluid ....................................................................................................... 55 6.3 Adding Oil to the Refrigerant Compressor....................................................................... 55 6.3.1 Testing Crankcase Oil Acidity ............................................................................................ 56 6.4 Replacing the Dehydrator / Anti-Acid Filter ..................................................................... 57 6.5 Gasket Replacement/Tightening Bolted Joints ............................................................... 57 6.6 Changing Oil Header Tank Filter ....................................................................................... 58 6.7 Temperature Probe Inspection .......................................................................................... 59 6.7.1 Ice Water Bath Technique ................................................................................................. 59 6.7.2 Resistance/Temperature Technique.................................................................................. 59 6.8 Reverse Low Pressure Switch Adjustment (Specialist) .................................................. 60

7. FAULT FINDING ..................................................................................................................... 61 7.1 Introduction ......................................................................................................................... 61 7.2 Basic Procedures................................................................................................................ 61 7.2.1 Record Keeping ................................................................................................................. 61 7.2.2 Problem Identification ........................................................................................................ 61 7.3 Shelf Cooling....................................................................................................................... 62




7.3.1 Control and Regulation Difficulties..................................................................................... 62 7.3.2 Poor Performance.............................................................................................................. 62 7.3.3 Operational Failure ............................................................................................................ 63 7.4 Shelf Heating ....................................................................................................................... 64 7.4.1 Control and Regulation Difficulties..................................................................................... 64 7.4.2 Poor Performance.............................................................................................................. 64 7.4.3 Operational Failure ............................................................................................................ 65 7.5 Condenser Refrigeration.................................................................................................... 65 7.5.1 Control and Regulation Difficulties..................................................................................... 65 7.5.2 Poor Performance.............................................................................................................. 66 7.5.3 Operational Failure ............................................................................................................ 66 7.6 Vacuum System .................................................................................................................. 67 7.6.1 Control and Regulation Difficulties..................................................................................... 67 7.6.2 Poor Performance.............................................................................................................. 67 7.6.3 Operational Failure ............................................................................................................ 68 7.7 Vacuum Alarm..................................................................................................................... 68 7.8 Hydraulic Stoppering.......................................................................................................... 69 7.9 Calibrated Leak ................................................................................................................... 69

LIST OF ILLUSTRATIONS Figure Description 2.1 Example of Full Penetration Weld...................................................................................... 13 2.2 Circuit for Cooling Diathermic Fluid.................................................................................... 16 2.3 Shelf Structure ................................................................................................................... 17 2.4 Lyomaster Control System Block Diagram ........................................................................ 19 5.1 Pump Filling of Silicone Oil Circuit ..................................................................................... 44

LIST OF TABLES Table Description 4.1 Maintenance Summary ...................................................................................................... 40 6.1 Suction and Discharge Valve Settings............................................................................... 49 6.1 Torque Values for ANSI Flanges * ..................................................................................... 58




1. SAFETY

1.1 Introduction

This maintenance manual provides general guidelines for keeping the BOC Edwards Pharmaceutical Systems freeze dryer reliable and operating at the highest performance levels. We ask that you take the time to carefully read this manual and familiarize yourself with each task before conducting any maintenance.

The Lyomax freeze dryer design meets all normal industrial safety standards. The safety hazards associated with the Lyomax unit are, generally, those arising from incorrect use, or from a failure to follow correct procedures. This section attempts to highlight the main hazards that can occur when installing, commissioning, operating, or maintaining the unit.

1.2 Safety Precautions

Every effort was made to verify information and instructions in the manuals are accurate. Please notify the manufacturer before continuing if there is any doubt concerning the validity of information or instructions.

The terms Warning, Caution, and Note are used throughout this text to provide emphasis. A definition of each is given below:

WARNING: WARNINGS ALERT YOU TO POTENTIALLY

HAZARDOUS SITUATIONS WHICH, IF NOT AVOIDED, COULD RESULT IN DEATH OR SERIOUS INJURY.

Caution: Cautions alert you to potential hazards or unsafe

practices that may result in personal injury or damage to equipment or product.

Note: Notes emphasize an important piece of information.

Safe equipment operation is the responsibility of the user and user's staff. Before performing any operations, read and comply with all precautions included in this manual, the Product Documentation, and posted on the machine. Additionally, read and understand this manual, the operation manual, and all vendor manuals supplied in the Product Documentation provided with your freeze dryer.




Perform maintenance procedures at the specified intervals to ensure that the equipment remains in safe operating condition. Only qualified engineers or trade workers should perform the specialized maintenance in this manual.

1.2.1 Health and Safety Aspects

The customer is responsible for preventing equipment exposure to materials or substances that can result in direct or indirect hazardous conditions.

1.2.2 Qualification

BOC Edwards Pharmaceutical Systems standard freeze dryer configurations facilitate working to GMP requirements.

1.2.3 Stoppering System

The stoppering system meets normal stoppering design conditions and is fully workshop tested before delivery. Be sure to uniformly load freeze dryer shelves. BOC Edwards Pharmaceutical Systems strongly recommends the use of silicone treated stoppers. For stopper and container specifications, refer to specifications DIN 58359 and DIN 58366, respectively.

WARNING: BOC EDWARDS PHARMACEUTICAL SYSTEMS IS NOT

RESPONSIBLE FOR DAMAGE TO EQUIPMENT OR INJURY TO PERSON(S) DUE TO INCORRECT STOPPERING USE.

1.2.4 Sterilization

Use an alternative form of sterilization if the freeze dryer is not designed for steam or gas sterilization.

WARNING: ANY ALTERNATIVE FORM OF STERILIZATION MUST

NOT, IN ANY WAY, JEOPARDIZE FREEZE DRYER SAFETY AND OPERATION.

1.2.5 Cycle Optimization

Cycle optimization may be necessary when transferring cycle data from another freeze dryer to the Lyomax Unit supplied. BOC Edwards Pharmaceutical Systems will be glad to help customers optimize or update cycle data.




1.2.6 Computer Programs

Obtain written approval from BOC Edwards Pharmaceutical Systems for computer software program changes that affect freeze dryer operation. Send a copy of all program changes to BOC Edwards Pharmaceutical Systems Engineering Department to enable updates to original files when necessary.

1.2.7 Shipment

BOC Edwards Pharmaceutical Systems standard procedure is to discharge all fluids from the freeze dryer unit and to ship the fluids in their respective containers. This procedure can change due to transportation requirements.

1.3 Maintenance Hazards

WARNING: DO NOT ENTER THE CHAMBER - SEVERE INJURY OR

DEATH MAY RESULT. IN SOME FREEZE DRYERS, IT MAY BE POSSIBLE FOR AN INDIVIDUAL TO ENTER THE AREA BENEATH THE SHELF STACK WHEN THE SHELVES ARE FULLY RAISED. UNDER NO CIRCUMSTANCES SHOULD ANYONE ENTER THE AREA UNDER THE RAISED SHELF STACK.

WARNING: VENTING A LARGE CHAMBER CONTAINING INERT GAS

INTO THE WORK PLACE ATMOSPHERE CAN DISPLACE OXYGEN AND CAUSE ASPHYXIA.

WARNING: FOLLOW PROCEDURES FOR CONFINED SPACE PRIOR

TO ENTERING OR PERFORMING MAINTENANCE ON CHAMBER. AN OXYGEN DEFICIENT ATMOSPHERE CAN EXIST WITHIN CHAMBER.

Observe the following when performing maintenance on the freeze dryer:

• Only qualified technicians should perform maintenance.

• Read all safety information for fluids used in the system. Material Safety Data Sheets for these fluids are provided in the Instruction Manual.

• The electrical supply is NOT automatically isolated when the service doors open. Always isolate the electrical supply before servicing or troubleshooting.




• When the electrical supply is connected, the automatic controls may pump down the refrigerant circuits even if cooling or heating functions are not selected (i.e., unit in the standby mode).

• There is no filtering system between the inlet nozzle and the chamber/condenser connection for connecting a sterile air/inert gas supply. Safety and pressure regulating device installation is the customer responsibility.

• Use care when routing service pipes to ensure supplies and exhausts are not obstructed.

• Be careful when performing common pipe work to prevent contamination and siphoning.

• Follow instructions when filling oil circuits and pumps. Do not overfill. Overfilling will damage the unit.

• Ensure that all services are available to the freeze dryer before commencing testing or commissioning.

• If any test or commissioning procedure fails to achieve the correct result, ascertain and correct the cause before proceeding with further work.

• Ensure that the correct shutdown procedure is followed after completion of testing or commissioning of the unit.

1.4 Operating Hazards

WARNING: VENTING A LARGE CHAMBER CONTAINING INERT GAS

INTO THE WORK PLACE ATMOSPHERE CAN DISPLACE OXYGEN AND CAUSE ASPHYXIA.

Be sure to observe the following points when operating the freeze dryer:

• Check the Process and Instrumentation Diagrams (C47-19-05 to C47-19-11) to verify all vents are correctly installed and release to a safe area.

• Operators read and understand all instructions pertinent to the operation of the freeze dryer before starting any work on the unit.

• Verify incondensable materials (especially solvents) are removed from the system before startup.

• Verify all pre-start and maintenance inspections are done before start-up.

• Use only approved materials to seal the chamber door.

• When taking readings, ensure that gauges are giving true results and that the values are not being influenced by other factors as explained in the relevant sections of the operator's instructions.

• Chamber pressure is adversely affected by even small amounts of solvents, such as alcohol, in the product.

• Avoid contact with operating fluids and sealants. Use personal protective equipment or clothing when handling fluids and sealants.




• The control and access panels are not electrically isolated when the panels are opened or removed.

• Always follow the correct shut down procedure when work on the freeze dryer has been completed. Failure to do so could result in dangerous pressures developing within the refrigeration system.




2. DESCRIPTION

2.1 Introduction

This section is a functional description of the Lyomax freeze dryer and its component parts.

2.2 Basic Construction

The freeze dryer is constructed around central support frames. The chamber, condenser, and refrigeration components are mounted on separate frames. The system components are mounted on the frames for maintenance access and servicing. The principle components of the freeze dryer are:

a. Freeze drying chamber

b. Vacuum system

c. Refrigeration system

d. Product shelves

e. Ice condenser

f. Control system

g. Hydraulic stoppering system

h. Steam sterilization system

i. Main isolation valve

j. Clean in place system

2.3 Component Parts

2.3.1 Freeze Drying Chamber

The freeze drying chamber is rectangular in shape and houses the product shelves. Two slot doors are provided for the automatic vial loading and unloading system (AV-LUS). A main access door is provided for maintenance purposes.

The chamber is constructed of stainless steel with ground and polished, full penetration welds (Figure 2.1). Welds are ground and polished to eliminate contamination traps and make it possible to thoroughly clean the chamber. A hydraulically operated mushroom valve isolates the freeze drying chamber from the ice condenser.

Illuminated sight glasses permit visual monitoring of the freeze drying process. A remotely illuminated sight glass is provided on the chamber door and a second illuminated sight glass is mounted on the side of the chamber.




Full Penetration WeldNon Penetration Weld

Figure 2.1: Example of Full Penetration Weld

The chamber and main access door incorporate a heating/cooling jacket. Silicone oil circulating through the jacket heats the chamber and chamber door before steam sterilization and cools them after steam sterilization.

Ports are provided for vacuum gauge heads, temperature sensors, and validation probes. The chamber is protected against dangerous over-pressure conditions by an automatic relief valve which opens as soon as the chamber pressure rises above a pre-set level.

2.3.2 Vacuum System

The vacuum system is used to evacuate the chamber and condenser. This reduces the pressure of permanent gases within the chamber, and is essential for the freeze drying process, because this aids in the sublimation of the frozen solvent portion of the product.

The vacuum system consists of two GV160 dry vacuum pumps, two EH1200 booster pumps, and a liquid ring pump (LRP). The freeze dryer uses the two vacuum pumps and booster pumps for evacuating the chamber and condenser. The vacuum pumps are multiple stage, rotary units with water cooling, dry air/nitrogen inlet purge gas and piping to vent exhaust to a safe location. The pumps are connected to the condenser via the main vacuum line (stainless steel piping and flexible bellows). An electro-pneumatically operated butterfly isolation valve separates the vacuum system from the condenser.

The vacuum and booster pumps are used during automatic freeze drying cycles, automatic bellows tests, and leak tests. Both vacuum pumps and booster pumps are used to evacuate the freeze dryer during an automatic cycle.

Five seconds after the vacuum pump(s) is enabled, the corresponding vacuum pump isolation valve opens. The booster pump starts after the vacuum pump isolation valve opens. The booster pump compresses air prior to the high vacuum pump, enabling the high vacuum pumps to operate more efficiently with a resulting increase in pumping speed. Using a booster pump reduces the time to evacuate the freeze dryer.

The vacuum system uses a Pirani gauge for measuring the vacuum system performance. When chamber pressure reaches the evacuation set point, one of the vacuum pumps de-energizes and is




used as a backup; if the evacuation set point is above 267 µBar (200 microns), the booster also de-energizes. The two vacuum pumps will alternate duty at the start of each automatic freeze drying cycle.

If a vacuum pump fails, the main vacuum valve closes and the corresponding vacuum pump isolation valve will close. The backup vacuum pump energizes and the main vacuum valve re-opens when the vacuum system Pirani gauge indicates that the vacuum pump system is at a pressure less than the chamber pressure or when the vacuum system has been evacuated for 5 minutes.

During the evacuation stage, condenser cooling also starts. The control system logic opens the main vacuum valve separating the vacuum pumping system from the condenser, ten minutes after the condenser temperature reaches -40°C. The condenser coil must be chilled prior to opening the main vacuum valve so that any water in the condenser or chamber will freeze on the condenser coils and not be drawn into and foul the high vacuum pumping system.

Regulating the vacuum in the drying chamber in a controlled manner improves heat transfer during primary and secondary drying and reduces product drying time. The calibrated leak system allows a precise measure of sterile air or nitrogen gas into the chamber to counteract and stabilize the vacuum created by the vacuum pump. A PID loop controls the amount of sterile air or nitrogen gas admitted to the chamber based on the chamber vacuum set point and the actual chamber vacuum as read by capacitance manometer.

The LRP is used during steam sterilization in place (SIP), clean in place (CIP), and steam defrost of the condenser. It is used to evacuate the chamber so that the chamber door can be locked. The LRP is also used to evacuate the chamber, the condenser, and the sterile filters, so that they will dry after being washed or steamed. The LRP is used in situations where the freeze dryer contains large quantities of water, water vapor, or steam that could contaminate the high vacuum pumping system.

2.3.2.1 Vacuum Control

The vacuum control function at the PC monitors and controls chamber and condenser vacuum and main bellows vacuum.

• A Pirani vacuum gauge head, located at the vacuum pump discharge provides analog input signals to the PLC where they are linearalized to provide both a pressure signal for display at the PC and maintain condenser vacuum control at a set point.

• A Pirani vacuum gauge head, located at the hydraulic cylinder, provides analog input signals to the PLC where they are linearalized to provide both a pressure signal for display at the PC and maintain bellows vacuum control at a set point.

The vacuum function at the PC monitors and controls the vacuum in the chamber and condenser.

• A vacuum gauge head, type MKS 621 capacitance manometer, is connected to the chamber. It provides analog input signals to the PLC where they are linearalized to provide a pressure signal for display at the PC and to maintain chamber vacuum control at a set point by modulating gas bleed valve FV66.




• A vacuum gauge head, type MKS 621 capacitance manometer, is connected to the condenser to provide analog input signals to the PLC where they are linearalized to provide a pressure signal for display at the PC and to maintain condenser vacuum control at a set point

2.3.2.2 Capacitance Pressure Gauge

Caution: The vacuum gauge head is heated to 125ºC to minimize

calibration drift. The heater should be on at all times. Should the power be turned off to the instrument, the head may require recalibration.

The capacitance pressure gauge allows the measurement of total pressures independent of the composition of the gas being measured. The gauge is an absolute pressure monitoring tool and is intended for precise and repeatable measurements throughout the freeze drying process. It consists of a pressure transducer or pressure sensing element and associated controller instrument.

The pressure sensing element is a high precision, stable capacitance manometer, the variable element of which is a thin, highly pre-stressed metal diaphragm. Positioned between fixed capacitor plates, the diaphragm forms the separation between two gas-tight enclosures which are connected to the external pressure ports. A pressure difference deflects the diaphragm and varies the relative capacitance of the diaphragm and the fixed capacitor plates.

The pressure transducer is electrically arranged in a 10k Hz carrier-excited bridge such that the capacitance variation resulting from deflection of the diaphragm unbalances the bridge and produces a 10k Hz voltage of amplitude proportional to the measured pressure.

The most significant factor for vacuum measurements provided by this method is the fact that the output signal is directly related to the total pressure of the gases present and is not affected by variations in gas composition.

The gauge is continually heated to 125ºC to ensure it remains stable during changes in ambient conditions and during sterilization.

2.3.3 Refrigeration System

The refrigeration system is composed of five independent cooling circuits. Each circuit includes a 50 HP Mycom variable speed compressor, separate flow cooler/plate heat exchanger circuits for the shelves, condenser, and chamber jacket, and mechanical expansion valves. Additionally, each circuit includes a combined sight-glass/wetness indicator, filter dryer, an oil separator, a pressure relief valve, pressure switches, pressure gauges, and all other necessary safety devices.

Each circuit can be used to cool the product shelves or the ice condenser. Four compressors are used during a freeze drying cycle. The fifth compressor serves as a backup. During the drying phase, one compressor will toggle between shelf cooling and condenser cooling as required to maintain the shelf temperature set point. The five compressors alternate primary and backup duty each time an automatic cycle is initiated.




Figure 2.2: Circuit for Cooling Diathermic Fluid

The product shelves and ice condenser are cooled using separate silicone oil flow cooling circuits. In a typical cooling circuit (Figure 2.2), high-pressure liquid refrigerant flows from the refrigerant condenser through a mechanical expansion valve. As the refrigerant flows through an orifice in the expansion valve, it flashes from a high-pressure liquid to a low-pressure gas and/or liquid. The low-pressure refrigerant flows through the evaporator (plate heat exchanger) where it removes heat from the silicone oil that is circulated through the shelves and the condenser. The compressor recovers the returning low-pressure, low-temperature refrigerant from the evaporator and pressurizes it, causing it to heat. The resulting high-pressure, high-temperature gas is discharged into the water-cooled refrigerant condenser that operates as a refrigerant gas liquefier and a refrigerant accumulator. The water cooling removes the heat extracted from the silicone oil and discharges the refrigerant as a high-pressure, low-temperature liquid, completing the loop. Two double circulation pump systems circulate the silicone oil through the shelf and condenser flow cooling circuits.

2.3.4 Product Shelves

The two product shelf stacks are inside the freeze drying chamber. Each shelf is manufactured with an upper and lower surface separated by baffles (Figure 2.3). The resulting space within the shelves provides a channel for the flow of silicone oil. The baffle arrangement ensures consistent oil flow through the shelf for optimum heat transfer and temperature uniformity.

Two pumps circulate chilled silicone oil through the shelves, where heat is transferred from the product to the oil. The oil then passes through the plate heat exchanger (evaporator) where heat is transferred to the refrigerant. The two pumps are connected in parallel. Only one pump is required to circulate the silicone oil through the system. The pumping duty is alternated between the two pumps




each time an automatic freeze drying cycle is initiated. In the event one pump fails, or there is a drop in operating pressure, that pump will turn off and the other pump will turn on.

Figure 2.3: Shelf Structure

The shelf fluid system also contains an immersible heater that is used to warm the fluid during the product drying phase. The surface temperature of the shelves can be controlled to ±1.0°C of the shelf temperature set point with no load (-60°C to +20°C). Shelves have an operating temperature range of -60°C to +70°C.

2.3.4.1 Shelf Temperature Control

The shelf temperature controller measures shelf temperature via a standard temperature sensor (TE201) fitted to the shelf oil inlet. The controller’s analog output is transmitted to the PLC where it is linearalized to maintain shelf temperature at a set point by cycling heater HTR-1 on and off. The controller is enclosed in a standard panel-mounted enclosure. The required temperature is selected manually via a keypad on the controller.

A manual digital temperature controller is provided to give a digital read-out of the fluid inlet temperature. The indicator is fitted with a large LED display that indicates temperature to one decimal point of accuracy.

2.3.5 Ice Condenser

The ice condenser is a vertically mounted, cylindrically shaped vessel containing the trapping coils. The refrigeration circuit, vacuum pumps and gauge head, temperature probes, and defrost line supply connect to the condenser. The ice condenser is attached to the freeze drying chamber by a vapor duct. A polished, hydraulically operated mushroom valve provides isolation between the chamber and ice condenser.

As water vapor leaves the product, it is attracted to the condenser where it forms an ice coating on the trapping coil. A manually illuminated sight glass mounted on the side of the condenser permits monitoring of the ice formation. At the end of freeze drying period, the condenser is defrosted by admitting steam to the vessel.




Two pumps circulate chilled silicone oil through the condenser trapping coil, a specially designed and manufactured, spiral, stainless steel coil, where heat is transferred from the condenser chamber to the oil. The oil then passes through the plate heat exchanger (evaporator) where heat is transferred to the refrigerant. The two pumps are connected in parallel. Only one pump is required to circulate the silicone oil through the system. The pumping duty is alternated between the two pumps each time an automatic freeze drying cycle is initiated. In the event one pump fails, or there is a drop in operating pressure, that pump will turn off and the other pump will turn on.

Additional connections to the condenser provide steam from the sterile filter system and purified water for the CIP circulation system. Ports for gauge heads and temperature probes are provided. A drain connection also provides for draining the condenser to either the CIP re-circulation system or the liquid ring pump and associated drain system.

A solenoid-operated valve permits venting of the condenser with air or inert gas, if required. An automatic relief valve prevents over-pressurization of the condenser. The relief valve opens, venting to a safe area if the chamber pressure rises above a pre-set level. A special ‘disk’ type relief valve maintains atmospheric equilibrium during machine inactivity or storage.

2.3.6 Control System

The Lyomaster PC Control System monitors, controls, and displays freeze drying process parameters during a cycle, allowing the operator to view and modify the process.

The control system (Figure 2.4) consists of a Programmable Logic Controller (PLC) and a Personal Computer (PC). The PC is the primary Operator Interface with the freeze dryer. Operator commands from the PC, the remote panels, and/or from selector switches mounted in the control-cabinets are input to the PLC. The PLC responds to these instructions and adjusts freeze dryer operations as necessary.

The operator initiates manual control or automatic cycle functions through the PC. The PC collects process data from the PLC and displays the information. Operators enter data in the appropriate screen using the keyboard and mouse.

2.3.6.1 Personal Computer (PC)

The computer system consists of an Operator Interface PC.

The Operator Interface PC includes a 2.8GHz Xeon processor, 1GB RAM, three 36GB SCSI RAID 5 hard drives, ENET port, floppy disk drive, internal CD drive, internal DVD/CDRW drive, internal tape drive, and the Windows 2000 operating system. The Operator Interface PC also includes a 17-inch Graphical Display Monitor, a USB 4800 x 1200 dpi color screen printer, and an eight-port Ethernet switch for the Ethernet network.

An Ethernet network facilitates communication between the Operator Interface PC, the PLC Ethernet Communications Module (ENET1), the remote panels, and the Loading / Unloading System.




2.3.6.2 Programmable Logic Controller (PLC)

The PLC is an Allen-Bradley Control Logix 5555 processor mounted in the control cabinet. The PLC monitors field devices such as temperature elements, pressure transducers, and manual controls. The PLC program and the recipe dictate the PLC response to these inputs. The PLC responds by routing output signals to control devices that adjust freeze dryer operations as necessary.

OPERATOR INTERFACE PC

SLAVE PANEL PANELVIEW 1000

PLC

ETHERNETSWITCH

PLC

SCREEN PRINTER

Figure 2.4: Lyomaster Control System Block Diagram

2.3.6.3 Screen Printer

The system includes a color printer for making hardcopies of screens displayed on the personal computer and for printing reports.

2.3.7 Manual Controls

For manual operation and testing of the freeze dryer, the unit is equipped with a series of selector switches located in the Control Cabinet, the Power Cabinet, and on remote panels. The Manual Controls screen on the PC also permits manual control of freeze dryer functions. For safety and interlocking purposes, the switches do not directly control the freeze dryer, but serve as inputs to the PLC. The PLC executes the selected operation when all conditions (interlocks) associated with the function or operation, are satisfied.




2.3.7.1 Control and Power Panel

Individual system components may be enabled or disabled using local selector switches mounted in and on control cabinets. Normally, these switches are configured to permit the PLC to operate the components during manual or automatic cycles. Be sure to return switches to the normal operating position to enable PLC control of the component. Local Control switches are found on both the Control Cabinet and Power Cabinet.

2.3.7.2 Remote Panels

The remote control system for the freeze dryer includes two remote panels; a slave panel, located at the process room slot door, and a Panel View touch screen, located at the maintenance room chamber door. The remote panels are capable of controlling specific freeze drying functions under limited and controlled conditions. The panels are enabled from the Manual Controls screen. Only one panel may be active at a time.

2.3.7.3 Operator Interface - Manual Controls Screen

Manual functions are accessed from the Operator Interface PC. Manual freeze dryer controls are found on the Freeze Drying Recipe screen and the Manual Controls screen. The freeze dryer may be placed in "Manual" or "Automatic" modes using the Control Select switch on the Manual Controls screen. The Recipe screen and Manual Controls screen use pushbutton graphics to represent manual functions. To activate and deactivate a specific function, position the cursor over the function and press the left control button on the mouse. Most functions are available only when automatic cycles are not in progress.

2.4 Functional Accessories

2.4.1 Hydraulic Stoppering System

The freeze drying chamber is fitted with a hydraulic stoppering system to enable vials and bottles to be stoppered without removing them from the chamber.

The stoppering system is controlled automatically using the Operator Interface PC. The PC control system incorporates a number of safety interlocks to ensure operator safety.

For automatic stoppering, the PLC commands the controller to move the shelves down until the stoppering pressure input is activated. When the shelves reach the stoppering position, the resistance to ram movement increases the hydraulic circuit oil pressure. This triggers the stoppering pressure input (detected by a pressure sensor), which signals the PLC that stoppering is complete. The PLC then signals the controller to return the shelf stack to the home position.




WARNING: KEEP CLEAR OF THE CHAMBER ENTRANCE WHEN

THE CHAMBER DOOR IS OPEN AND THE MANUAL STOPPERING SELECTOR SWITCH(ES) ON THE SLAVE PANEL ARE ACTIVE. UNEXPECTED SHELF MOVEMENT COULD RESULT IN PERSONAL INJURY.

WARNING: DO NOT TAMPER WITH PRESSURE SWITCH SETTINGS

OR ANY OF THE SAFETY DEVICES ON THE HYDRAULIC POWER SUPPLY. KEEP AWAY FROM THE SHELF STACK DURING STOPPERING.

Caution: An "over pressure" safety switch (PSH9) monitors

hydraulic pressure. The safety switch is set to trigger at 10 BarG above the maximum operating pressure. When triggered, the over pressure switch activates an alarm and the hydraulic pump will turn off. The Hydraulic pump will not restart until the alarm is reset and cleared on the alarm screen at the Operator Interface PC.

The stoppering system allows operators to stopper vials and bottles of product before removal from the freeze dryer, as well as index shelves for loading and unloading. Safety interlocks are built into the unit to ensure operator safety.

Caution: Partially or improperly filled shelves will damage shelf

stack during stoppering. When loading the shelves, ensure that the shelves to be used are full. Verify shelves are full before stoppering. Refer to the Operating Manual for loading procedures.

2.4.2 Steam Sterilization System (SIP)

Caution: Ensure that the shelf stacks are fully retracted before

beginning the Sterilization SIP Cycle.




The freeze dryer chamber and condenser are designed for sterilization with saturated steam, at temperatures up to 126°C. Steam from the clean steam generator passes through all pipe work, sterile filters, and valves that might be exposed to the product. The system is fitted with a mechanical pressure relief valve that opens to relieve steam pressure in the chamber/condenser should a malfunction occur. Interlocks on the chamber door prevent sterilization when chamber doors are open or unlocked.

Sterilization temperature is measured at two locations in the freeze dryer: the sterile filter drain and the condenser drain. Temperature is measured at these points because they are the last locations to heat-up and therefore the coldest. Once these locations reach the sterilization temperature set point, the rest of the freeze dryer is at or above the sterilization set point temperature. The freeze dryer will be held at the sterilization set point temperature for the time entered in the recipe. Once the sterilization timer has expired, the steam is discharged down the drain. The liquid ring pump is used to dry the sterile filter and then the rest of the freeze dryer including the aeration pipe works.

2.4.3 Main Isolation Valve

The main isolation valve is located between the freeze drying chamber and ice condenser. This hydraulic mushroom valve isolates the chamber and condenser, allowing the following:

• Decreases cross contamination between batches.

• Conducting a pressure rise test during a freeze drying cycle. This helps detect faults and allows operators to check product dryness.

• Eliminates the risk of chamber flooding during condenser defrosting.

The chamber isolation valve plate is made of stainless steel and may be steam sterilized. The status of the isolation valve is indicated on the status screen. When the associated indicator is green, the isolation valve is open; when red, the isolation valve is closed.

2.4.4 Clean In Place System (CIP)

The CIP system washes particulate matter and dried water-soluble residue from the interior of the chamber and condenser. The areas that are cleaned include the chamber, condenser, shelf hoses, shelves, ram bellows, main isolation valve bellows, drains, and all ports and sight glasses in the freeze dryer. A number of strategically placed wash nozzles within the chambers ensure complete coverage of interior surfaces. During the cleaning process, the shelves are cycled from the home position to the extended position several times to expose all shelf surfaces to the wash solution. A CIP cycle includes several wash and rinse steps followed by a drying step.

2.4.5 Calibrated Leak

Regulating the vacuum in the drying chamber in a controlled manner can increase heat transfer from shelf to product during primary and secondary drying. The calibrated leak system allows a precise measure of sterile air or inert gas into the chamber. The resulting increase in pressure speeds up product drying time. The system accurately controls the gas pressure from ultimate up to 1333 µBar (1000 microns).




2.5 Automated Tests

Automated tests confirm the integrity of various Freeze Dryer components. The Leak Test evaluates the integrity of the Freeze Dryer chamber, condenser, inlet piping, and sterile filters. Bellows tests evaluate the integrity of the Shelf Ram Bellows, the Main Isolation Valve Bellows. The Filter Integrity Test verifies that sterile filter cartridges were not damaged during normal operations.

2.6 Nitrogen Blanket for Silicone Oil Expansion Tank

Nitrogen gas is supplied to the silicone oil expansion tank as a safety precaution, to reduce the risk of fire. The silicone oil (used as the heat transfer medium for cooling) is flammable. To prevent combustion, pressurized nitrogen gas is pumped into the silicone oil expansion tank to displace air that may be present and thereby reduce the amount of oxygen present in the tank. Although oxygen is nonflammable, it supports and vigorously accelerates combustion of flammables such as silicone oil.

Customer supplied pressurized nitrogen gas flows through a pressure control valve, where it is regulated. A solenoid valve, controlled by the freeze dryer PLC, opens to allow the gas to enter the silicone oil expansion tank. A back-pressure control valve on the expansion tank ensures that the expansion tank never becomes over pressurized. A solenoid valve admits gas into the expansion tank whenever the freeze dryer is operating.

There are three (3) alarms associated with the nitrogen blanket and the silicone oil expansion tank: a nitrogen blanket low-pressure alarm, a nitrogen blanket high-pressure alarm, and a silicone oil level low alarm.

1. N2 Blanket Low Pressure Alarm - The low-pressure alarm activates when the nitrogen pressure in the silicone oil expansion tank is less than the Silicone Tank Low Pressure switch setting. If this pressure is less than the lower set point (0.13 BarG or 1.9 PSIG), the shelf fluid heater is disabled and an SIP cycle is disabled or aborted. The alarm is cleared when PSLH50 indicates the pressure in the silicone oil expansion tank is greater than the lower set point or the automatic cycle or manual function has been completed or aborted.

2. N2 Blanket High Pressure Alarm - The high pressure alarm activates when the nitrogen pressure in the silicone oil expansion tank is greater than the high pressure setting of the Silicone Tank High Pressure switch. If this pressure is greater than the high pressure setting (0.48 BarG or 7.0 PSIG) the Nitrogen Supply valve closes until the alarm is cleared. The alarm clears when the Silicone Tank High Pressure switch indicates the pressure in the silicone oil expansion tank is less than the high pressure setting.

3. Silicone Oil Level Low Alarm - The low level alarm activates when the level sensor in the silicone oil tank indicates that the minimum necessary oil level is not present. If the Silicone Expansion Tank Low Level sensor indicates a low level, the shelf fluid heater and circulation pumps are disabled, until the alarm clears. The alarm clears when the level sensor indicates the level in the silicone oil expansion tank is greater than the minimum required level or the automatic cycle or manual function has been completed or aborted.




3. COMMISSIONING AND TESTING

This section contains procedures for preparing and testing the freeze dryer prior to operation. Refer to the control system operating manual as required for operating procedures. Verify that all daily maintenance tasks were performed before starting test and calibration procedures. Comply with each of the following instructions when commissioning and testing the freeze dryer:

• Verify all services are connected and available before testing or commissioning.

• Determine the exact cause of any failure occurring during the testing and commissioning process. Correct the problem before proceeding to the next step or procedure.

• Use the shutdown procedure after completing testing or commissioning.

3.1 Service Connections

The following paragraphs detail how each service is connected and, where appropriate, explains the function of each service. Connect the services as indicated in the Piping and Instrumentation (P & I) Diagrams provided with your freeze dryer. Ensure that the service is connected to the correct inlets and outlets and that they are NOT reversed.

Caution: Use good engineering principles when inter-connecting

skids or when connecting skids to site services, i.e., water supply, steam supply, etc., to ensure that all piping is adequately supported.

3.1.1 Refrigerant Compressor Cooling Water

The refrigerant compressor cooling water cools the refrigerant receivers and the compressed refrigerant. Cooling water supply must be clean and filtered. Refrigerant compressor performance depends on the cooling water supply. The water supply pressure should not exceed 3-4 BarG (43.5-58.0 PSIG).

WARNING: THE COOLING WATER SUPPLY MUST BE CONNECTED

AND AVAILABLE BEFORE CHARGING THE REFRIGERANT CIRCUITS AND SWITCHING ON THE MAINS SUPPLY.

The refrigerant circuit can become dangerously over-pressurized when the cooling water supply is cut off or restricted during operation.




The cooling water inlet and outlet are two separate lines that must NOT be reversed when installing the freeze dryer. Install the inlet and outlet pipes carefully to prevent water flow restriction from pinching and kinking.

3.1.2 Defrost

Ice accumulating on the ice condenser coil is removed by flushing with defrost steam at a supply pressure of 1.8 BarG (26 PSIG). Steam enters through the defrost nozzle, passes through the defrost inlet valve, and enters the condenser chamber. Water leaves the condenser through the condenser drain.

3.1.3 CIP Supply

The CIP system uses 2-3 BarG (29-43.5 PSIG) water pressure through a 1 ½ inch connection.

Caution: To prevent damage to the shelves, remove guide rails

from all shelves before running a CIP cycle.

3.1.4 Compressed Air Supply

The instrument air supply is compressed air with a supply pressure of approximately 5.5-6.5 BarG (79.8-94.3 PSIG). The supply must be dry and filtered. Lubrication is acceptable, if desired.

3.1.5 Vacuum Pump Exhaust

WARNING: THROTTLING CAUSES DANGEROUS OVER-PRESSURE

IN THE PUMP BODY.

1. Connect the vacuum pump exhaust pipe outside of the building or a well ventilated area to avoid

polluting the work area.

2. Install a catch pot and drain in the exhaust line and at the base of long, vertical runs. This prevents fluid condensing in the pipe and returning to the vacuum pump.

3. Connect the vacuum pump exhaust outlet nozzle to the discharge line with a corrugated transparent plastic hose or stainless steel (steel is acceptable) rigid piping.

4. Secure the hose to the outlet nozzle using a suitable hose clip. Do not use copper or any “heavy metal” material.




5. Follow the same precautions when installing the exhaust hose as with the cooling water supply lines.

3.1.6 Electrical Supply

WARNING: ONLY QUALIFIED ELECTRICIANS SHOULD MAKE

ELECTRICAL CONNECTIONS ON THE FREEZE DRYER. THE ELECTRICAL SUPPLY TO THE UNIT IS NOT AUTOMATICALLY ISOLATED WHEN THE SERVICE DOORS ARE OPENED - ALWAYS ISOLATE THE SUPPLY MANUALLY BEFORE PROCEEDING WITH SERVICE OR TROUBLESHOOTING OPERATIONS.

The electrical supply to the freeze dryer as well as all electrical fittings used must comply with the rules set out in the National Electric Code or applicable local codes. Always ensure that the available electrical supply matches that specified for the unit, as detailed on the electrical main supply label, before connecting.

WARNING: DO NOT CLOSE THE ELECTRICAL SUPPLY UNTIL THE

CHAMBER, CONDENSER, SHELF COOLING CIRCUITS, AND ASSOCIATED REFRIGERATION SYSTEM ARE OPERATING.

Isolate the main supply using the Main Isolator switch on the freeze dryer. BOC Edwards Pharmaceutical Systems recommends installing an additional electrical isolator between the power supply and the freeze dryer. This isolator must comply with applicable regulations and be suitably rated for the unit.

3.1.7 Sterile Air/Inert Gas

The freeze dryer has a 1-inch flange for purging with sterile air or an inert gas such as nitrogen. Any supply connected to the unit should be pressure regulated and must be fitted with all necessary safety devices as detailed on the P & I Diagram.

Connect the supply using suitable material compatible with the pressure and service required. Be sure all connections secured.

3.1.8 Steam Quench Water

Connect a potable water supply to the liquid ring pump and/or main drain. The supply details are provided on the P & I Diagram.




3.1.9 Main Drain

Connect the main drain through the air break to a suitable floor drain. Comply with local regulations regarding effluent drains.

3.1.10 Filtering Hydraulic Fluid

Use an industry approved strainer/cart to filter the hydraulic fluid before filling the hydraulic system.

3.2 Preparing the Freeze Dryer for Operation

WARNING: BEFORE COMMISSIONING, TIGHTEN ALL FLARE

FITTINGS IN THE REFRIGERATION SYSTEM TO ELIMINATE REFRIGERANT LEAKS. LOOSE FLARE FITTINGS CAN BE CAUSED BY TEMPERATURE CHANGES WHEN THE EQUIPMENT WAS NOT OPERATING. RETIGHTEN THE FLARE FITTINGS FOLLOWING COMPLETION OF THE COMMISSIONING AND TEST PROCEDURES.

3.2.1 Preparing the Refrigerant Compressor

Refer to the manufacturer's instructions included in the Component Information Section of the Product documentation to prepare compressors for operation.

3.2.2 Dry Vacuum Pump Gear Box Oil Level

Refer to the manufacturer's instructions for checking the gear box oil-level. The manufacturer’s instructions are supplied with the Component Information in the Product Documentation for the freeze dryer.

3.2.3 Testing the Refrigeration Circuit

Refer to the manufacture's instructions included in Component Information Section of the Product documentation for additional information while performing these tests. Check operation of the refrigeration system as follows:

1. Check that the cooling water flow rate is correct and at operating temperature. See the Refrigeration P & I Diagrams for details. The cooling water temperature can be read from the high pressure gauge.

2. Check standing head pressure to verify that it corresponds to the expected pressure indicated in the Refrigerant Pressure/Temperature Charts for the refrigerant being used.




3. Check humidity indicator in sight glass to confirm "dry" indication.

4. Select shelf cooling (or condenser cooling depending on circuit being checked) and check for correct operation.

5. Allow refrigeration circuits to run under normal load with a test batch on the shelf stack.

6. Verify operating pressures and temperatures are in accordance with Refrigerant Pressure/Temperature Charts for the refrigerant being used as well as the manufacturer's specifications.

7. Verify liquid line sight glasses are full of refrigerant.

3.3 Functional Tests and Calibration

This section describes testing and setup of the freeze dryer for normal operation. Before starting test and calibration procedures, carry out the Daily Maintenance procedures outlined in the Routine Maintenance section of this manual. Be sure to read the appropriate sections of the Operating Manual provided with your control system. Verify daily maintenance has been performed and that the person performing the tasks is familiar with the controls of the freeze drying unit.

3.3.1 Start Up and Preliminary Tests

The following steps detail the procedure for starting up and testing the freeze dryer’s primary functions:

1. Ensure that all control functions are OFF and that the chamber door is closed and the condenser is defrosted and drained.

2. Switch ON the electrical supply at the local isolator and at the unit's main isolator.

Note: The refrigerant compressors may start - this is normal, indicating dispersed gas in the refrigeration circuit is being pumped into the refrigerant receiver.

3. Set Control Enable Switch HS1 to ENABLE.

4. Close the Main Isolation valve.

5. Close the Chamber and Condenser Inlet valves.

6. Establish Shelf Temperature Control at the desired set point. The circulation pump and the shelf cooling refrigeration circuit should become operational under PLC control. Monitor shelf cooling and ensure constant cooling is in progress.

7. Carefully monitor the fall in shelf oil temperature on the temperature indicator. Typical times for the shelf temperature to reach specified tolerances (from room temperature) are 1.25 to 1.5 hours. The shelf temperatures are measured on the Shelf Oil Inlet probe.




8. With the oil temperature steady at the desired tolerance, ensure that the shelf oil level in the header tank is visible. The shelf temperature control system should now control the shelf oil temperature within tolerance with the heating and cooling functions operating at their set points:

a. Shelf cooling ON - at tolerance.

b. Shelf heating ON - if the oil temperature falls below tolerance.

c. Shelf cooling ON - if the oil temperature rises above tolerance.

9. Enable Condenser Cooling and set to the desired set point. Condenser cooling should become operational under PLC control. Monitor condenser cooling and ensure constant cooling is in progress.

10. Carefully monitor the fall in condenser temperature on the temperature indicator

11. When the shelf oil temperature reaches the desired tolerance and the condenser temperature reads the desired value (or lower) for a predetermined interval, open the Main Isolation valve.

12. Open the Main Vacuum valve and check that the vacuum pressure pulls the chamber door tight. If the condenser temperature has not been below the desired value for a predetermined time, the valve will not open.

13. The chamber pressure will slowly decrease. Under perfectly clean system conditions, the vacuum pump pressure will always be lower than the chamber pressure.

14. Allow the freeze dryer to remain in this condition for a few hours to out gas the system and check overall vacuum performance. Generally, the chamber pressure should be allowed to fall below a desired low tolerance at the end of this test. Ensure that the chamber pressure has stabilized below the tolerance value before proceeding with the next step.

15. Set the shelf heating temperature to the desired tolerance value and enable shelf temperature control. Ensure that the refrigeration circuit is isolated from shelf cooling to prevent the refrigeration circuit from attempting to cool the shelf oil.

16. Monitor the rise in shelf oil temperature. The shelf oil temperature control system should now control the shelf oil temperature at the desired tolerance value with the heating and cooling functions operating at the their desired set points:

a. Shelf heating on up to the tolerance value

b. Shelf cooling on if the shelf oil temperature rises above the tolerance value

c. Shelf heating on if the shelf oil temperature falls below the tolerance value

17. With the shelf fluid at the desired tolerance value, adjust the Heater Safety thermostat below the tolerance value and confirm that the heater turns off. If it operates correctly, reset the switch to a maximum tolerance value as noted on the Piping and Instrumentation Diagram.




WARNING: POTENTIAL FIRE HAZARD! DO NOT PROCEED WITH

TESTING UNTIL YOU CONFIRM THAT THE HEATER SAFETY THERMOSTAT IS FUNCTIONING PROPERLY.

18. Leave the freeze dryer in this condition for a few hours or, preferably, overnight; this will ensure

that system is further out-gassed and the operation of the shelf oil heating system is verified.

3.3.2 Calibrating Temperature Probes

Check the calibration of temperature probes to verify temperature readings are accurate. Confirm calibration before using the probes, and check the probes every month. See General Maintenance Tasks for additional details.

3.3.3 Partial Shut Down after Commissioning

When all tests have been completed satisfactorily, the freeze dryer should be shut down to the standby state, ready for further operation. The following procedure should be adopted for shutting down the unit at all times.

1. Switch off the following PLC functions:

a. Shelf Temperature Control

b. Condenser Cooling

c. Vacuum valve

d. Gas Bleed

e. Main Valve

2. Open the chamber air admittance (vent) valve and the condenser air admittance (vent) valve. Air will now be drawn into the system via the vent valves. When the chamber pressure reaches atmospheric pressure the chamber door can be opened.

3. Inspect the inside of the chamber and the shelf stack for signs of damage.

4. With the condenser at atmospheric pressure, defrost the condenser by enabling the "defrost" from the PC control system.

5. If additional draining is needed, reset drain time.

6. Water should now flow out of the condenser drain. If water does not flow, either the drain is blocked or the condenser is not at atmospheric pressure. Close the defrost water valve and ascertain the cause of the problem before proceeding.




7. Once the freeze dryer is commissioned, leave the main electrical supply on to allow the refrigeration circuits to pump back the dispersed refrigerant into the receivers. Failure to do this causes a dangerous build up of pressure in the refrigeration circuits.

Cooling water must circulate when the freeze dryer is not in use or when the main electrical supply is switched off. This prevents over-pressure conditions from developing in the refrigeration circuit.

WARNING: IN THE EVENT OF PARTIAL OR TOTAL PLANT SHUT

DOWN, THE MAIN ELECTRICITY SUPPLY AND COOLING WATER MUST BE RECONNECTED AS SOON AS POSSIBLE UNLESS THE REFRIGERANT IS REMOVED.

3.3.4 Automated Tests

Automated system testing is a function of control system programming. Several different tests may be available including those briefly described below. Refer to the Operating Manual for information concerning these and other software controlled tests.

3.3.4.1 Ram Bellows Test

This test evaluates the integrity of each shelf stack ram bellows, ensuring there are no leaks. Refer to the control system Operating Manual for instructions. This test fully extends the shelf ram, evacuates the bellows, and determines the amount of time required to achieve the evacuation set point. When the test is complete, the shelf ram retracts and the chamber bellows aerates.

3.3.4.2 Main Valve Bellows Test

This test evaluates the integrity of the Main Isolation valve bellows, ensuring there are no leaks. Refer to the control system Operating Manual for instructions. This test fully extends the Main Isolation valve, evacuates the bellows, and determines the amount of time required to achieve the evacuation set point. When the test is completed, the Main Isolation valve bellows aerates.

3.3.4.3 Leak Test

Perform a Leak Test, also called a Leak-up Test, to check the leak rate of the system (chamber, condenser, inlet piping, and sterile filters) to determine if freeze dryer integrity is intact. Refer to the control system Operating Manual for instructions.

3.3.4.4 Filter Integrity Test (FIT)

This test evaluates the integrity of the sterile filter. The filter is tested using the Water Intrusion Test (WIT) method. In a two filter arrangement, the integrity test is done after a CIP cycle but prior to a SIP cycle. The PLC performs the required steps of the integrity test. The operator has the option to perform WIT on one of the filters or both depending on the selection in the recipe.




4. ROUTINE MAINTENANCE

4.1 Introduction

This section lists the routine maintenance required to keep the freeze dryer in proper working order. Some tasks depend on the use and frequency of unit operations. The periods quoted are a guide. BOC Edwards Pharmaceutical Systems recommends maintaining records of all tasks performed and the quantity of materials used, such as oil. This will aid in planning and stocking of consumed materials.

Procedures are divided into daily, weekly, monthly, semiannual, and annual functions.

Note: BOC Edwards Pharmaceutical Systems offers a comprehensive preventive maintenance service that covers all semiannual and annual maintenance of the freeze dryer. Qualified service engineers perform all work. Contact BOC Edwards Pharmaceutical Systems for additional information.

4.2 Cleaning the Chamber

The rules governing medicinal products in the European Union, Volume 4, Medicinal Products for Human and Veterinary Use: Good Manufacturing Practices (1998 Edition) recommends cleaning equipment before starting any new production cycle. In the United States, 21 CFR Parts 210 and 211, Feb. 4, 2002 recommends establishing a regular cleaning and sanitation schedule appropriate to prevent malfunctions or contamination that would alter safety, identity, strength, quality, or purity of the drug product beyond official or established requirements. The cleaning methods used depend on the equipment and the product being processed by the equipment. The following information is provided as a guideline to assist in establishing procedures and specifications for cleaning the freeze dryer.

WARNING: THE USE OF INAPPROPRIATE CLEANING AGENTS CAN

CAUSE INJURY TO PERSONNEL OR DAMAGE TO EQUIPMENT:

• THE FREEZE DRYER IS NOT EXPLOSION-PROOF. DO NOT USE CLEANING AGENTS THAT PRODUCE EXPLOSIVE VAPORS.

• NEVER USE CHLORIDE BASED CLEANERS.

• DO NOT USE PRODUCTS CONTAINING AZIDES OR THOSE THAT CAN PRODUCE AZIDES.




WARNING: DO NOT ENTER CHAMBER WITH SHELF STACK

RAISED.

1. Use a vacuum cleaner to remove debris (broken vials, stoppers, etc.) from inside the chamber.

2. Use a cleaning agent approved for use by your Quality Department for this equipment, process, and environment. Wash the chamber, shelves, and interior door surface.

Caution: Only use cleaning agents that will not damage stainless

steel, EPDM (O-rings), Teflon, or silicone.

3. Use de-ionized water to rinse away cleaning agents from the chamber.

4. Allow chamber door to remain open to facilitate chamber drying and permit cleaning vapors to escape.

5. To complete drying of the chamber, close the chamber door, place the chamber under vacuum, and heating the shelf stack to +50°C for several hours.

4.3 Daily Maintenance

Visually check the freeze dryer for damage, deterioration, and overheating. Check individual components as follows.

4.3.1 Refrigerant Compressors

The refrigeration compressor motor is cooled by water running through a cooling jacket. Cooling water is supplied to the jacket via a cooling circuit connected to the plant water service. Be certain that this water supply is unrestricted or fully open after performing any maintenance on the machine. Compressor damage will result if the cooling water supply is cut-off or otherwise restricted.

Caution: Restricting or cutting off the cooling water supply to the

refrigeration compressor will result in damage to the compressor motor. Be certain that this water supply is unrestricted or fully open after performing any maintenance on the refrigeration compressor or freeze dryer.




Check each refrigerant compressor cooling water supply, and record the inlet and outlet temperatures, the flow rate and supply pressure. The freeze dryer does not have sensors to record this information. Records with this information help diagnosis problems with the unit.

Perform the following before starting a freeze drying process:

1. Check pressure gauge readings.

2. Check refrigerant compressor crankcase oil level.

3. Check color and condition of the compressor crankcase oil.

4. Check operation of the reverse low pressure switch.

4.3.2 Compressed Air Supply

The compressed air must be filtered, pressure regulated, dry, and lubricated. Verify the following to ensure the supply is usable:

1. Check the line pressure and pressure regulator.

2. Check the pressure after the regulator (read from the pressure regulator gauge).

4.3.3 Product Temperature Probes

Carefully examine the probes and electrical connections for signs of damage or deterioration. Oxidation on the electrical contacts causes incorrect product temperature readings. Product temperature probes can be sterilized at +121°C.

Check the calibration of temperature probes to verify temperature readings are accurate. Confirm calibration before using the probes, and check the probes every month. See General Maintenance Tasks for additional details.

4.3.4 Dry Vacuum Pumps

Caution: If the pump shuts down or is manually shut down for

maintenance, the pump alarm reset pushbutton on the Alarms screen must be reset to clear the alarm condition(s). This enables pump restart after corrective action and/or maintenance is performed.

Check the vacuum pump gearbox oil level before starting the pump. The gearbox oil-level should be at the MAX mark on the bezel of the oil-level sight glass. If the oil-level is below the MAX mark, add the correct grade of oil using the procedure specified in the manufacturer’s instructions supplied with the Component Information in the Product Documentation for the freeze dryer.




4.3.5 Silicone Oil Circuit

Check the condition of the silicone oil circuit, including:

1. The shelf flexible hoses and all pipe work. Verify there are no leaks.

2. Starting the circulating pump and verifying pump runs smoothly.

3. Check circuit pressure is between 0.5 and 0.7 Bar (7.25 and 10 PSI) when the pump is running.

4. Check the header tank oil level is between the high and low sight glass level.

4.3.6 Hydraulic Stoppering

Check the condition of the hydraulic stoppering system, including:

1. Verify there is adequate hydraulic oil.

2. Verify the hydraulic oil pressure is within limits. Reading is zero when the circuit is not under pressure (not in use). Refer to the Hydraulic Piping and Instrumentation Drawing for pressures and gauge locations.

3. Verify the hydraulic unit motor runs smoothly.

4. Verify setting of the Over-Pressure Safety switch (PSH9) to ensure unit shuts down for excessive pressure.

4.3.6.1 Checking and Replacing Seals

Each hydraulic stoppering cylinder is supplied with a set of seals on the rod end. A visual flow indicator (FI13) is provided to monitor the condition of the seals. If hydraulic oil is visible in FI13, then the cylinder should be scheduled for maintenance to replace the cylinder seals. This condition usually means that the cylinder seals are wearing. Refer to the cylinder manufacturer's instructions for replacing the seals. If the seals are not replaced and become badly worn, then hydraulic oil can leak into the bellows and end up in the vacuum pump during bellows integrity testing.

Caution: Replace worn cylinder seals when they are found.

Hydraulic oil leaking into the bellows because of badly worn seals may cause damage to vacuum pumps during bellows leak (integrity) testing.

4.3.6.2 Replacing Hydraulic Oil Filters

The dirty filter alarm will indicate when the differential pressure across the filter is 2.4 Bar (35 PSI) or greater. When the differential pressure reaches 3.5 Bar (50 PSI), the oil bypasses the filter element.




At this point the oil is no longer filtered and could contain potentially harmful contaminants that will spread through the hydraulic circuit and damage the power unit.

When the filter alarm indicates, change the filter element after the cycle has completed.

4.3.7 Device Mode (Maintenance Only)

The Operator Interface PC permits the freeze dryer to be placed in “device” mode. Using “Device” mode, maintenance personal can operate valves and motors on the selected freeze dryer. Device mode of operation is only possible when there are no active manual or automatic functions and the freeze dryer is placed in Manual mode.

Individuals with proper security (Maintenance access) can enable device mode from the Maintenance screen. Once enabled, all major devices can be selectively controlled with minimal interlocks imposed by the software. Use the mouse to position the cursor on the image of a valve or motor on the Unit Graphic screen and click on the desired function to activate or de-activated the device. For example, all discrete output devices may be turned on and off (e.g., valves may be opened/closed, compressors may be started/stopped), and analog output devices may be varied 0 – 100 % (e.g., shelf fluid heater output may be set to 0-100%, gas bleed valve FV66 output may be set to 0-100% open). The only analog output device that cannot be accessed in device mode is stoppering pressure.

WARNING: MINIMAL INTERLOCKS ARE IMPOSED BY THE

SOFTWARE DURING DEVICE MODE. THE PERSON INITIATING MAINTENANCE MODE OPERATION ASSUMES RESPONSIBILITY OF PROTECTING BOTH PERSONNEL AND THE FREEZE DRYER BEFORE AND DURING ACTIVATION OF ANY DEVICES.

In Device Mode, many of the operational/safety interlocks for the freeze dryer are disabled to allow flexibility during machine troubleshooting and maintenance. However, the following interlocks will be active during Device Mode to maintain a minimal measure of protection for personnel and equipment:

• All hardwired interlocks will remain operational.

• Steam Supply valve is hardwired not to open unless the chamber and maintenance doors are locked and if the loading slot door is not closed.

• There will be no provision for shelf ram movement in Maintenance Mode.

• The shelf fluid heater cannot be started unless one shelf fluid circulation pump is already running.

• Steam Defrost valve cannot be opened unless the main isolation valve and the Main Vacuum valve are closed.

• The Main Isolation valve between the chamber and condenser cannot be opened if the Steam Defrost valve is open.

• The Main Vacuum valve cannot be opened if the Steam Defrost valve is open.




• If a compressor or vacuum pump is started in Device Mode, then any corresponding cooling valves will be automatically opened to cool the device while it is running.

• Silicone N2 Supply valve cannot be opened if a high pressure condition exists in the silicone expansion tank.

• There will be no provision for activation of the shelf and condenser cooling valves. Chamber door lock/unlock solenoids will not energize to extend/retract primary/secondary pistons unless the chamber door is open and the hydraulic pump is running.

Note: All devices return to their de-activated state after exiting Device Mode.

4.4 Weekly Maintenance

Perform all daily maintenance procedures before proceeding with weekly maintenance.

1. Check vacuum pump gearbox oil level and fill as necessary with the correct grade of oil.

2. Inspect the silicone oil circuit header tank air filter; the dehumidifying agent that it contains is silica gel. The silica gel is navy blue when fresh and pink when saturated. Replace the filter before saturation. Instructions on changing the filter are contained in the General Maintenance section.

4.5 Monthly Maintenance

Perform the daily and weekly maintenance before starting the monthly maintenance tasks.

Caution: After the first 100 hours of operation, replace vacuum

pump oil (regardless of condition) and clean the internal vacuum pump oil filter and inlet strainer.

BOC Edwards Pharmaceutical Systems recommends performing a monthly test on the unit with an expendable product batch. Record performance figures and compare results with the previous monthly test.

Perform the following tasks:

1. Check the product probe calibration in accordance with the instructions under General Maintenance.

2. Change the oil mist filter odor element, if supplied.

4.6 Semiannual Maintenance

Perform the daily, weekly and monthly maintenance before starting semiannual tasks:




1. Service the vacuum pump as directed by the manufacturer instructions supplied with the Component Information Section of the Product Documentation.

WARNING: HAVE A QUALIFIED INDIVIDUAL PERFORM THE

FOLLOWING TASKS.

2. Change the refrigerant compressor oil:

a. Use a test kit and check acidity in the oil. A test kit should be suitable for Freon refrigerants.

b. If the pH is high there could be a refrigerant leak or other contamination. Take corrective actions to repair leak.

c. Change contaminated circuit filter dryers as required.

d. Change the silicone oil circuit header tank air filter.

3. Check the operation of the following components:

a. Motor cut outs

b. Earth connections and continuity

c. Pressure switches

d. Door limit switch

e. Valve position switches

f. Alarms

g. Oil heater safety thermostat

h. Fail-safe devices

4. Clean the electrical cabinet air circulating fan. The fan is on the top panel above the electrical system.

5. Change the oil mist filter cleaning element if installed on the machine.

6. Verify heater safety thermostat operation:

a. Switch freeze dryer to manual mode.

b. Enable Shelf Temperature Control.

c. Enter shelf temperature set point to 20°C.




d. Adjust heater thermostat to 40°C after reaching 20°C.

e. Adjust the shelf temperature set point to 50°C.

f. Verify the heater shuts down at approximately 40°C.

g. When heating does not shut down at approximately 40°C, replace the thermostat and repeat steps a - f.

h. When test is complete, reset heater thermostat to 80°C.

i. Shut down the shelf temperature control.

4.7 Annual Maintenance

Perform all daily, weekly, monthly and semiannual maintenance tasks before starting the annual tasks. Refer to manufacturer instructions included with the Product Documentation for any overhaul tasks. Following the manufacturer instructions, perform annual maintenance on the following components:

• The refrigerant compressors

• The vacuum system

• The hydraulic system

• The silicone oil circuits.

• Drain valves (replace seals as necessary)

Check, clean, and test the following services:

• Compressed air supply.

• Electric supply, including connections and line safety devices.

• Drain system.

• Defrost water supply.

• Sterile air/inert gas supply

• Refrigerant cooling water

• Exhaust systems

• Cooling water supplies for pumps, hydraulic unit and jacket cooling

Finally, perform a freeze drying cycle at maximum loading. Verify performance values are correct.




4.8 Maintenance Summary

Table 4.1: Maintenance Summary

Frequency Daily Weekly Monthly Semiannual Annual Compressor M M MI MI O Vacuum Pump MI MI MI MI O Silicone Oil Circuit MI MI MI MI O Hydraulics MI V I MI O Instrumentation MI V I MI O Services MI V I MI O Heater thermostat --- --- --- I I Key: I = Inspect: check operation-calibration or observe in use. M = Measure or take measurement. V = Visually check. O = Overhaul: strip down and replace all worn parts.

4.9 Service Contracts

It is important that qualified and experienced personnel perform the semiannual and yearly maintenance procedures. BOC Edwards Pharmaceutical Systems accepts no responsibility for equipment failures or injuries caused by improper servicing or maintenance of the freeze dryer. For the best equipment performance, BOC Edwards Pharmaceutical Systems strongly recommends a service contract. BOC Edwards Pharmaceutical Systems can provide worldwide service by fully trained and qualified engineers. The name and address of your nearest BOC Edwards Pharmaceutical Systems office is printed on the cover of the Product Documentation. In case of problems, please contact the Customer Support Department in the United States at the following address:

BOC Edwards Pharmaceutical Systems 2175 Military Road Tonawanda, New York 14150 USA Telephone: (716) 695-6354 Facsimile: (716) 695-6367




5. SPECIALIZED MAINTENANCE

5.1 Introduction

The maintenance procedures in this section are for specific equipment. BOC Edwards Pharmaceutical Systems strongly recommends that only specialists or trained engineers perform these procedures. If work is performed by non-specialist engineers, BOC Edwards Pharmaceutical Systems cannot be responsible for damage or injury.

5.2 Silicone Oil Circuit

The silicone oil circuit is drained before the freeze dryer leaves BOC Edwards Pharmaceutical Systems and the oil is supplied separately in drums. There are two ways that the silicone oil circuit can be refilled: vacuum filling or pump filling. Regardless of the filling method, always be sure that the expansion tank is situated at the highest point of the complete silicone oil system, and the heater is connected in a manner that prevents air pockets at the top of the heater housing.

Caution: When Pressure Checking the System, do not use more

than 3.4 BarG (49.3 PSIG).

5.2.1 Silicone System Leak Test

Prior to filling the silicone oil circuit with silicone oil, perform the following procedure to ensure there are no leaks.

1. Visually inspect entire system to be sure all valves, fittings, flanges, etc. are in place and tightened properly.

2. Cap all drain valves with plugs or caps to prevent accidental discharge of pressure.

3. Make sure all valves in silicone circuit are open prior to pressurizing.

4. Charge system with 30 PSI (2.0 Bar) of dry nitrogen. Use a pressure gauge with a minimum range of 0 - 50 PSI (0 to 4 Bar) to monitor the pressure.

5. Use an electronic surface thermometer to check temperature of silicone line.

6. Close the supply valve and disconnect pressure supply source.

7. Use a soap and water solution to check all potential leak areas e.g., threaded fittings, valve stems, flanges, welds, etc.

8. Keep the 30 PSI (2.0 Bar) charge in for a period of 24 hours. Check both temperature and pressure of the silicone line. If no pressure has been lost during the 24-hour period, the system




is considered leak tight. Use the following equation to compensate for any temperature change from the initial reading in step 5.

P1 x P2 P2 = T1

Where P1 = Initial Pressure P2 = Expected Pressure T1 = Initial Temperature (º Kelvin) T2 = Final Temperature (º Kelvin) º K = ºC + 273

Note: P2 must be within 0.25 PSI of the final recorded pressure

9. If a leak is suspected, charge the system to 30 PSI (2.0 Bar) using 15% R-22 and 85% nitrogen.

Check for the leak with an electronic leak detector until the leak or leaks are found.

10. Find and repair all leaks and repeat steps 4 -7 (for the repaired joint) and step 8.

5.2.2 Vacuum Filling

Use the following procedure to fill the silicone oil circuit:

1. Verify that the silicone system leak test has been performed.

2. Verify all ball valves (drains) and packed angle valves (bleeders) on silicone lines and system are closed:

a. Ball valves (drains) are usually located at low points on the silicone system (for example, heater housing, flow cooler assembly, silicone lines entering and exiting the chamber, or any trapped sections of the silicone system).

b. Packed angle valves are located at the high points in the silicone system (e.g., top of flow cooler assembly and high silicone lines).

c. Ensure the manual butterfly valves on each side of the circulation pumps are in the open position.

3. Vacuum pump hookup:

a. Use an Edwards E2M80 or similarly sized pump.

b. Check vacuum pump oil level. Change oil when there is water in the oil.

c. Connect cooling water to the vacuum pump. Verify cooling (chilled) water is at 20ºC and circulating through the vacuum pump without leaks.




d. Remove the expansion tank filter dryer and connect the silicone expansion line to the expansion tank.

e. Fasten the proper fitting to the top of the expansion tank and the vacuum pump. Use NW25 x 3/4 NPT connection with a vacuum hose. Connect a vacuum gauge to a suitable fitting on the fluid circuit, preferably the furthest point from the vacuum source.

f. Verify remaining expansion tank ports are plugged.

g. Run vacuum exhaust line from the vacuum pump to the exhaust manifold on the back wall of the freeze dryer.

h. Turn on the vacuum pump and run for at least 24 hours. If frost appears on the shelves, continue pulling vacuum until all frost is removed.

4. Silicone Charging:

a. Weigh a 55-gallon drum (or equivalent) of silicone oil and document weight for record keeping.

b. Isolate the vacuum gauge installed during step 3.

c. Connect silicone oil filling hose to the lowest valve on the silicone system and verify other end of fill hose is at the bottom of the silicone oil drum. Open the fill valve half way.

d. Verify the fill hose does not draw air from an empty drum.

e. Fill system to two thirds (2/3) as indicated at the sight glass on the silicone oil expansion tank.

f. Shut off the fill valve and turn off the vacuum pump.

g. Aerate system and allow silicone oil to settle.

h. Draw a vacuum again and fill to three-fourths (3/4) the sight glass level. Repeat this procedure until the oil level is 1/2 of the sight glass with no vacuum on the system.

i. Run the silicone oil circulation pumps and check the oil level on the sight glass is maintained.

j. Remove all filling components.

k. Install filter dryer and remove plugs and caps from the drain valves.

l. Weigh oil drum and record on available inventory sheets the number of pounds charged into the freezer according to the work order number.




The silicone oil circuit is now filled and ready for use.

5.2.3 Pump Filling

This method is when there is no lifting gear available or there is insufficient room to raise the drum above the freeze drying chamber. An auxiliary pump suitable for use with the silicone oil is required to artificially create the pressure head. The procedure is as follows:

1. Verify that the silicone system leak test has been performed.

2. Verify all ball valves (drains) and packed angle valves (bleeders) on silicone lines and system are closed:

a. Ball valves (drains) are usually located at low points on the silicone system (e.g., heater housing, flow cooler, assembly, silicone lines entering and exiting the chamber, or any trapped sections of the silicone system).

b. Packed angle valves are located at the high points in the silicone system (e.g., top of flow cooler assembly and high silicone lines).

c. Ensure the manual butterfly valves on each side of the circulation pumps are in the open position.

3. Prepare the silicone oil.

4. Attach hose clips to each end of two lengths of corrugated transparent plastic hose (two to five meters long).

5. Using the plastic hoses, connect the auxiliary pump into circuit as shown in Figure 5.1.

Figure 5.1: Pump Filling of Silicone Oil Circuit

6. Silicone Charging:




a. Weigh a 55-gallon drum (or equivalent) of silicone oil and document weight before charging for record keeping.

b. Verify the fill hose does not draw air from an empty drum.

c. Open fill valve half way and turn on pump.

d. Fill system to two thirds (2/3) as indicated at the sight glass on the silicone oil expansion tank.

e. Shut off the fill valve and turn off pump.

f. Aerate system and allow silicone oil settle.

g. Repeat this procedure until the oil level is 1/2 of the sight glass with the pump turned off and fill valve closed.

h. Remove all filling components.

i. Install filter dryer and remove plugs and caps from the drain valves.

j. Weigh oil drum and record on available inventory sheets the number of pounds charged into the freezer according to the work order number.

The silicone oil circuit is now filled and ready for use.

5.2.4 Silicone Oil Circuit Check

After filling the silicone oil circuit, perform the following checks:

1. Check the oil level with freeze dryer at room temperature (around +20°C). The oil level should be half way between the high and low sight glass levels.

2. As required, replace the header tank desiccant filter. The filter is dark blue when fresh and light pink when saturated with water.

3. Check the silicone oil circuit for leaks.

4. Turn on the shelf oil circulating system by selecting shelf heating. Verify that the shelf oil circuit pressure gauge reads between 7-10 PSIG (0.5-0.7 BarG) when the oil at +20°C.

5.3 Refrigeration System

5.3.1 Refrigeration Circuit Pressure Safety Check

Before charging the refrigeration system, perform a pressure check as follows:

1. Examine the refrigeration skid and verify the Schraeder valves fit tightly and are capped on compressors.




2. Examine for “back seating” of all packed line/angle valves, verifying the packing is tight. Also examine the Rotolocks are back seated, and packing is tight as well.

3. Ensure that all solenoid valves on the condenser and shelf cooling systems are functional and open during the leak test.

4. Remove check valve parts on condenser and shelf cooling suction lines to equalize the systems.

5. Verify system is leak tight:

a. Add Nitrogen at any service port (filters, packed angle valve ports, discharge and suction Rotolock ports, etc.) to all systems up to 50 PSIG (3.45 BarG) for each compressor installed.

b. Search for leaks (check valves, loosened flare nuts, unsoldered joints, etc.) and repair as required.

c. Repeat steps 5a and 5b as required until there are no leaks.

6. Increase system pressure to 100 PSIG (6.89 BarG) and verify system pressure remains unchanged for 10 minutes. If pressure drops:

a. Apply aqueous soap solution on joints and unions.

b. Repair any leaks that are found.

7. Increase pressure to 200 PSIG (13.79 BarG).

Caution: Do not exceed 200 PSIG (13.79 BarG) or low pressure

gauges on panels will be destroyed. Transducers can withstand 11/2 times the posted pressure rating.

8. Allow 1/2 hour for equalization, then record the refrigeration circuit pressure and temperature.

9. Maintain the refrigeration circuit at 200 PSIG (13.79 BarG) for 24 hours, then record the pressure and temperature readings.

Note: Use the temperature pressure formula below, then compare the expected pressure to the actual pressure. If there is no pressure drop, system passes and evacuation can proceed.

Initial Pressure x Temperature 2

Expected Pressure = Temperature 1




10. If a soap and bubble test does not locate the leak, perform a refrigerant test as follows:

a. Release pressure.

b. Pressurize system to 180 PSIG (12.41 BarG) exactly as follows:

- Add 30 PSIG (2.07 BarG) of R-22

- Add 150 PSIG (10.34 BarG) nitrogen.

c. Check for leak with an electronic leak detector.

d. Repair any leaks then evacuate the system for 30 - 60 minutes to remove residual refrigerant.

e. Repeat procedure.

11. Reinstall the check valve parts.

5.3.2 Evacuating the Refrigeration System

Evacuate the refrigeration system before charging as follows:

1. Manifold the circuits and connect a vacuum pump to the liquid and suction filter packed angle valve ports of each circuit.

2. Connect a vacuum gauge and meter to the manifold using a shut off valve between the vacuum pump and the refrigeration system. This allows vacuum pump isolation while taking vacuum readings.

3. Verify the following:

a. All valves connected to the manifold are open.

b. Check valve parts are installed.

c. Solenoid valves are operating.

Note: Turning on the compressor crankcase heater during evacuation (for a short period of time) will aid in the evacuation process.

4. Begin evacuating the refrigeration system:

a. Start the vacuum pump.

b. Slowly open the shut off valve between vacuum pump and refrigeration system.




c. Periodically check the vacuum by closing shutoff valve, then allowing the vacuum to stabilize before recording the reading.

d. Continue until vacuum gauge indicates less than 1000 microns (1333 µBar).

5. When the system reaches 1000 microns (1333 µBar), open the shut off valve and add POE oil to the compressor(s):

• Copeland ¾ gallon (2.85 liter)

• Mycom 30 hp 5 gallon (19 liter)

• Bitzer ¾ gallon (2.85 liter) or full sight glass on compressor

• Mycom 50 hp 6 gallon (22.8 liter)

6. Close shutoff valve and fill with dry nitrogen to atmospheric pressure (760 Torr or 1 Bar).

7. Evacuate again until pressure reads below 500 microns (667 µBar).

8. Fill again with dry nitrogen to atmospheric pressure (760 Torr or 1 Bar).

9. Evacuate again until pressure reads below 250 microns (330 µBar).

10. Fill to atmospheric pressure with correct refrigerant.

11. Return all valves to the “normal” position.

5.3.3 Refrigerant Compressors - Cooling Water Supply

The refrigeration compressor motor is cooled by water running through a cooling jacket. Cooling water is supplied to the jacket via a cooling circuit connected to the plant water service. Manual ball valves are placed in the cooling water supply circuit to isolate the jacket should it fail. The ball valves (refer to drawing D-C47-19-05) are supplied without handles to prevent accidental closure. Be certain that these valves are fully open after performing any maintenance on the machine. Compressor damage will result if the cooling water supply is cut off or otherwise restricted.

Caution: Restricting or cutting off the cooling water supply to the

refrigeration compressor will result in damage to the compressor motor. Be certain that isolation ball valves are fully open after performing any maintenance on the refrigeration compressor or freeze dryer.

Have a refrigeration specialist check each refrigerant compressor cooling water supply and record the inlet and outlet temperatures, the flow rate, and supply pressure. The freeze dryer does not have sensors to record this information. Records of this information may help diagnose problems with the unit.




5.3.4 Charging Refrigeration System

Caution: Refer to the manufacturer's instructions included in the

Component Information Section of the Product Documentation to charge the refrigeration system.

The correct refrigerant is indicated on the tag at the water cooled condenser rotolock, and found in the Utilities Consumption Sheet in the Product Documentation.

5.3.4.1 Initial Charge of Refrigerant

Caution: Only qualified individuals are allowed to charge

refrigeration circuits. Consult with applicable governing agencies for details on qualification.

The refrigerant charge is performed from the refrigerant charge valve (service valve). The end connection is a ¼” flare joint. Before charging with refrigerant, adjust the compressor discharge stop & check valve as specified below.

Table 6.1: Suction and Discharge Valve Settings

1290SSC* Model Valve size Operating position

Suction valve

50A (2”) Open by six (6) turns from the completely closed position.

Discharge valve

25A (1”) Open by six (6) turns from the completely closed position.

* This information also noted on the ring-shaped nameplate on the neck of the valve.

Adjusting the valve as indicated in the table causes the valve to function as a check valve, and refrigerant will not enter the compressor even if it enters the condenser.

Caution: Be sure that cooling water is flowing through condenser

before charging with refrigerant.




Refilling of the refrigerant is done through the liquid supply valve (service valve) of the liquid outlet of the condenser while the compressor is operating. To refill the refrigerant:

1. Prepare the refrigerant.

2. Connect the refrigerant cylinder and the refrigerant charge valve on the filter drier with a ¼” charging hose.

3. Fully close the liquid supply valve and open the refrigerant charge valve.

4. When the liquid supply valve of the refrigerant cylinder is opened, the refrigerant is refilled.

Caution: Be careful not to charge beyond the allowable refrigerant

holding volume of the condenser.

5. Refill the necessary volume while referring to the level eye of the condenser.

6. When refilling is finished, close the source valve of the cylinder and refrigerant charge valve, disconnect the charging hose, and then open the liquid supply valve.

5.3.4.2 Refrigeration System Problem Solving

This procedure aids in identifying problems in the refrigeration system, including:

• Chilled water not cold enough. Must be lower than ambient air temperature for refrigerant to condense.

• No flow from chilled water system. This allows water and ambient air temperature to be the same, equalizing the cylinder and condenser pressure.

Use the procedure to identify and correct problems during and after refrigerant charging:

1. Use a strap-on heater for the cylinder to raise the pressure.

WARNING:

DO NOT LEAVE CYLINDER WITH HEATER UNATTENDED. FAILURE TO MONITOR THE PRESSURE CAN CAUSE AN EXPLOSION.

2. Continue charging refrigerant.

3. Immediately close the cylinder valve and remove the heater when finished charging.




4. Close the outlet hose valve on refrigeration manifold assembly.

5. Back seat condenser outlet Rotolock and remove the filling hose.

6. Re-attach equalization or capillary line and return Rotolock to front seated position.

7. Attach inlet hose on refrigeration gauge manifold assembly to refrigerant cylinder on liquid side.

8. Attach high pressure outlet hose on compressor suction Rotolock service port. Verify valve is back seated before removing cap off port.

9. Verify all Rotolocks are back seated.

10. Turn the Rotolock on the water cooled condenser 1½ turns to the front seated position. This allows equalization line or capillary line to function for water regulating valve.

11. Purge all hoses.

12. Continue charging the system:

a. Start the compressor.

b. Open suction Rotolock 1½ full turn to the front seated position.

c. Carefully open gauge manifold until gauge indicates approximately 20 PSIG (1.38 BarG).

d. Allow refrigerant charging until the correct amount is charged.

e. Close gauge manifold.

f. Close suction valve (back seat valve) and turn off compressor.

g. Back seat outlet Rotolock, then turn 1½ turns to the front seated position. This allows equalization line or capillary line to function for water regulating valve

5.3.5 Recovery of Refrigerant

Refrigerant must be pumped into the receiver as a liquid before removing from the system. Perform the following to liquefy the refrigerant:

1. Verify cooling water is flowing through the receiver, then close the refrigerant delivery valve.

2. Energize the compressor refrigeration solenoid valve by turning ‘on’ shelf cooling or condenser cooling. This will start the refrigerant compressor and open the evaporator solenoid.

3. Run the system for 10 minutes then close the suction valve and turn off the refrigerant compressor.

4. Close the compressor discharge valve




5. Close the oil return line valve. The refrigerant is now in the receiver and in the liquid state.

6. Electrically isolate the freeze dryer mains supply and refrigerant compressor motor.

7. Place a safety notice near the place of work and on the mains isolator switch warning that the refrigeration circuits have been drained and stored in appropriate cylinders. Always use 'dry' cylinders corresponding to the refrigerant stored (see Recovery of Refrigerant for Storage or Disposal).

5.3.6 Recovery of Refrigerant for Storage or Disposal

Refrigerant must be in liquid form for storage and transportation.

WARNING: DO NOT OVERFILL CYLINDERS. OVERFILLING CAN

CAUSE AN EXPLOSION. USE ONLY CYLINDERS DESIGNED FOR REFRIGERANT SERVICE AND EQUIPPED WITH PRESSURE DEVICES.

1. Connect the correct cylinder to the discharge valve (either the lower valve on the receiver or the

refrigerant delivery valve on top of the receiver) using a suitable hose. Record the empty cylinder weight for transfer calculation.

2. Purge the connecting pipes:

a. Loosen the piping at the cylinder end and open the discharge valve for a few seconds.

b. Reconnect the pipe and tighten the joint.

c. Close the valve.

3. Place the cylinder in a container and cool the cylinder with a water spray. This keeps refrigerant in liquid state.

Note: Cooling water in the receiver increases refrigerant transfer time.

4. Shut off cooling water supply to the receiver and remove as much water as possible.

5. Open the discharge and cylinder valves and transfer refrigerant. Warm the receiver body to help evaporate the liquid refrigerant.

6. Periodically check the cylinder weight to determine amount of refrigerant transferred.

7. When the cylinder is full, close the discharge valve on the receiver and then close the cylinder valve. Disconnect the full cylinder and connect an empty one as explained in Step 1.




8. Purge the connecting piping as explained in Step 2, then continue refrigerant recovery until the freeze dryer is completely drained of refrigerant. Tightly shut valves when unit is drained.

9. Electrically isolate the freeze dryer main electrical supply and the refrigerant compressor's motor.

10. Place a safety notice near unit and on the main electrical isolator switch warning personnel that refrigeration circuits are drained.

5.3.7 Refrigerant Compressors - Adding/Changing Oil

Refer to the manufacture's instructions included in the Component Information Section of the Product Documentation, to add oil to, or change the oil of the refrigerant compressors.

5.3.8 Replacing the Dehydrator Filter and Anti-Acid Filter

The filter dryer in the refrigerant circuit is to the rear of the freeze dryer, near the floor.

1. Manually operate the refrigerant circuit low pressure switch by moving the toggle switch.

2. Verify the delivery valve is closed then energize the compressor refrigeration solenoid valve (shelf cooling or condenser cooling). This will start the refrigerant compressor and open the evaporator solenoid.

3. Close suction valve on the refrigerant compressor.

4. Remove the access cover on top of the housing.

5. Remove and discard old filters.

6. Install new filters.

7. Evacuate filter housing through access port on top of the housing.

8. Open suction valves on the refrigerant compressor.




6. GENERAL MAINTENANCE

6.1 Filling the Rotary Vacuum Pumps

Fill the vacuum and booster pumps with the appropriate grade oil as specified in the manufacturer's instructions included in the Component Information Section of the Product Documentation.

1. Shut down the vacuum pump and allow the pump to cool.

2. Change oil as directed by the manufacturer's instructions located in Component Information.

3. When filling the pump, remove the filler cap on the top of the rotary pump and fill with oil as shown in the pump instruction manual.

4. Allow oil to settle then check the sight glass. The correct level, for a pump not running and at +20°C, is the MAX level on the sight glass.

5. After filling the pump, refit the filler cap and hand tighten.

6.2 Hydraulic Stoppering

Perform daily maintenance inspections on the hydraulic stoppering system before continuing.

6.2.1 Checking and Replacing Seals

Check hydraulic stoppering cylinder for fluid leakage. The stoppering cylinder (CYL1) is supplied with a set of seals on the rod end. A visual flow indicator (FI13) is provided to monitor the condition of the seals. If hydraulic oil is visible in FI13, the cylinder seals are wearing and must be replaced. To replace the seals, refer to the cylinder manufacturer's instructions included with the hydraulic power unit maintenance documentation.

Caution: If the seals are not replaced and become badly worn,

then hydraulic oil can leak into the bellows and end up in the vacuum pump during bellows integrity testing.

6.2.2 Replacing Hydraulic Oil Filters

The dirty filter alarm will indicate when the differential pressure across the filter is 35 PSI (2 Bar) or greater. When the differential pressure reaches 50 PSI (3.5 Bar), the oil bypasses the filter element. At this point the oil is no longer filtered and could contain potentially harmful contaminants that will spread through the hydraulic circuit and damage the power unit.

When the filter alarm indicates, change the filter element after the cycle has completed.




6.2.3 Adding Hydraulic Fluid

Hydraulic fluid attracts atmospheric moisture when exposed to air. BOC Edwards Pharmaceutical Systems does not recommend re-using hydraulic fluid removed from the system.

1. Verify there are no loose hoses or connections. Repair or replace as required.

2. Determine the correct grade and quantity of hydraulic fluid required. Reference the Fluid Inventory sheet located in the Product Documentation.

3. Strain the new fluid in an industry approved strainer/cart.

4. Fill the system as required.

6.3 Adding Oil to the Refrigerant Compressor

The refrigerant compressors require oil at regular intervals. Use only oil specially formulated for use in refrigeration applications.

Caution: Use only oil specially formulated for use in refrigeration

applications. Refer to the Fluid Inventory sheet in the Product Documentation for the correct oil for this compressor.

To add oil to the refrigerant compressors:

1. Check the crankcase oil level. The correct level is indicated on a label next to the oil sight glass.

2. Connect a rigid 1/4 inch copper pipe to the isolation valve on the crankcase. This valve leads to the oil pressure switch and oil separator.

3. Place the other end of the copper pipe into the container of new oil.

4. Bleed air from the copper pipe by opening the crankcase isolation valve.

5. Close the crankcase isolation valve.

6. Energize the low-pressure switch and pump down the compressor crankcase.

7. Open the crankcase isolation valve. The vacuum in the crankcase draws oil into the crankcase.

8. Close the isolation valve and disconnect the copper pipe when filling is complete.

Changing the Refrigerant Compressors Crankcase Oil




Caution: Place a safety notice near unit and on the electrical supply

isolation switch to warn of work on the refrigerant compressor.

Caution: Lockout/tagout the compressor(s) as required before

proceeding.

Use the following procedure to change crank case oil:

1. Close the compressor high and low side valves.

2. Verify the refrigerant compressor is electrically isolated.

WARNING: RELIEVE PRESSURE IN THE CRANKCASE BEFORE

REMOVING THE DRAIN PLUG.

3. Remove the refrigerant compressor crankcase drain plug. If this is not accessible then remove

the crankcase heater and drain the oil from this point.

4. Verify crankcase is drained.

5. Inspect the oil removed from the crankcase. Oil condition can indicate mechanical problems within the refrigeration circuit.

6. Fill the crankcase as directed in the procedure Adding Oil to the Refrigerant Compressor.

7. Remove lockout/tagout as required.

6.3.1 Testing Crankcase Oil Acidity

Acid testing determines the condition of the refrigeration circuit. Various test kits are available depending on the type of refrigerant used. Specific instructions for testing are supplied with each kit.

If a sample of oil has not been taken from the crankcase, continue as follows:

1. Close the crankcase isolation valve connected to the oil separator.

2. Wait two to three minutes for pressure to build up in the connecting pipe.

3. Loosen the connection at the isolation valve and take an oil sample.




4. Re-tighten the pipe and open the crankcase isolation valve.

5. Test the oil. Test kit should be suitable for the refrigerant type.

Note: High pH can indicate a refrigerant leak or other contamination. Take corrective actions to repair leak.

6. Repeat procedure as required for remaining refrigeration compressors.

6.4 Replacing the Dehydrator / Anti-Acid Filter

The filter dryer in the refrigerant circuit is to the rear of the freeze dryer, near the floor. Use the following procedure to change the filters:

1. Manually operate the refrigerant circuit low pressure switch.

2. Verify the delivery valve is closed.

3. Energize the compressor refrigeration solenoid valve, (shelf cooling or condenser cooling). This will cause the refrigerant compressor to start and the evaporator solenoid to open.

4. Close suction valve on the refrigerant compressor.

5. Remove access cover on top of the housing.

6. Remove and discard old filters.

7. Install new filters.

8. Evacuate filter housing through access port on top of the housing.

9. Open suction valves on the refrigerant compressor.

10. Repeat procedure as required for remaining refrigeration compressors.

6.5 Gasket Replacement/Tightening Bolted Joints

Torque loss is inherent with any bolted joint. The combined effects of bolt relaxation (approximately 10% during the first 24 hours after installation), gasket creep, vibration in the system, thermal expansion and elastic interaction during bolt tightening contribute to torque loss. When torque loss reaches an extreme, the internal pressure exceeds the compressive force holding the gasket in place and a leak or blow-out occurs.

Even when the installation is ideal, where bolt stress is uniformly applied to each bolt, and the gasket is properly compressed, problems can still arise. Inherently with time, loosening will occur due to the factors already mentioned. If other factors such as cycling, thermal upsets, water hammer, or an inadequately supported piping system are present, periodic re-torquing might be necessary. A key to reducing these effects is proper gasket installation.




When installing a gasket, remember to:

1. Bring the flanges together slowly and parallel,

2. Take multiple bolt passes, and

3. Follow the correct bolt tightening sequence.

Following these guidelines will reduce maintenance costs and increase safety.

Table 6.1: Torque Values for ANSI Flanges *

ANSI Flange Size (inches)

1st Tightening Pass (ft.-lbs.) **

2nd Tightening Pass (ft.-lbs.) **

Final Tightening Pass (ft.-lbs.) **

1 6 - 12 1.25 6 12 18 1.5 8 16 24 2 16 32 48-49 2.5 19 39 56-61 3 28 56 81-86 4 21 42 58-68 5 32 64 86-108 6 40 80 109-138 8 50 100 147-155 * Torque values based on using lubricated bolts ** To convert from foot-pound to Newton-meter, multiply by 1.356

6.6 Changing Oil Header Tank Filter

The header tank air filter contains silica gel that requires changing when the color turns blue. High humidity near the unit may require frequent changes. To change the filter:

1. Unscrew the plastic cover protecting the filter.

2. Remove the filter element.

3. Replace the old filter with a new filter.

4. Replace the plastic cover, verifying cover is screwed firmly into position.




6.7 Temperature Probe Inspection

Temperature probes can not be calibrated, but accuracy can be verified by measuring a known temperature with the probes (ice water bath technique) or by substituting known resistance in place of the probe and comparing the values (Resistance/Temperature Technique).

6.7.1 Ice Water Bath Technique

To check the zero centigrade point:

1. Immerse the probe in a container holding crushed ice and water.

2. Check remaining probes as required when reading is 0° Celsius.

3. Check connector pins for oxidization when the probe does not indicate 0°C.

4. Repair/replace oxidized connector pin and repeat test.

6.7.2 Resistance/Temperature Technique

A more accurate method for checking calibration is to substitute a known resistance, in place of the temperature probe. A 100-ohm precision resistance fitted in place of the probe corresponds to a temperature of 0°C. When using this substitution method, pay attention to the ambient temperature. Calibration resistance is only accurate at the stated temperature (usually +20°C).

Note: This procedure does not check the probe itself but instead confirms that the probe can be accurately read by the PC and recorded by the multi-channel recorder.

1. Use a decade resistance box to check a range of temperatures; the relationship between temperature and resistance in platinum resistance (PT100) probes is:

-100°C = 60.25 ohm +10°C = 103.90 ohm -90°C = 64.30 ohm +20°C = 107.79 ohm -80°C = 68.33 ohm +30°C = 111.67 ohm -70°C = 72.33 ohm +40°C = 115.54 ohm -60°C = 76.33 ohm +50°C = 119.40 ohm -50°C = 80.31 ohm +60°C = 123.24 ohm -40°C = 84.27 ohm +70°C = 127.07 ohm -30°C = 88.22 ohm +80°C = 130.89 ohm -20°C = 92.16 ohm +90°C = 134.70 ohm -10°C = 96.09 ohm +100°C = 138.50 ohm

0°C = 100 ohm 2. Check connector pins for oxidization when the recording device shows inaccuracies.

3. Repair/replace oxidized connector pin and repeat test.

4. Replace inaccurate probes.




6.8 Reverse Low Pressure Switch Adjustment (Specialist)

The reverse low pressure switch setting is set by measuring the refrigerant compressor’s load using a clamp type ammeter on one phase of the motor winding. The current measured must not exceed the motor winding rating specified on the motor data plate. It is advised that this operation only be performed by BOC Edwards Pharmaceutical Systems to prevent irreparable damage to the compressor.




7. FAULT FINDING

7.1 Introduction

This section provides operators and service engineers with a guide to freeze dryer problems. The content is divided into three categories:

1. Control and Regulation Difficulties - where the freeze dryer or a component appears to operate but does not respond correctly to the control instructions.

2. Poor Performance - where the freeze dryer or a component responds to the control instructions but, fails to reach set points or does so only after a prolonged period.

3. Operational Failure - where a sub component in the freeze dryer fails.

Note: The lists are not complete, as unforeseen problems develop in the future.

7.2 Basic Procedures

The basic principle of troubleshooting is "Isolate and Identify." This method requires good record keeping and documentation of problems and corrective actions.

7.2.1 Record Keeping

Record keeping is the most important part of the troubleshooting procedure. Keep a maintenance and troubleshooting log.

7.2.2 Problem Identification

Use the following steps for troubleshooting:

1. Record the problem:

It is important that you take the time to document the problem. First, record the symptoms and possible causes. When the problem has been corrected, record the solution.

2. Isolate and Identify:

Narrow the possibilities and isolate the problem. Eliminate unlikely possibilities. Then perform specific tests to eliminate the remaining possibilities.




7.3 Shelf Cooling

7.3.1 Control and Regulation Difficulties

Problem Possible Cause Solution

Faulty temperature controller Change the controller

Faulty temperature probe or poor probe contact

Check probe calibration. Check all probe electrical connections

Faulty expansion valve or valve incorrectly set

Check setting

Temperature will not adjust to set point

Faulty thyristor pack temperature control system

Call service engineer

Refrigerant circuit dirty or moisture holding expansion valve open.

Check “wetness” sight glasses: dry out and recharge circuit if necessary

Air in shelf oil circuit Check for leaks in the shelf oil circuit

Water in shelf oil circuit Check dehydration filter in header tank

Cooling water temperature fluctuation

Stabilize cooling water temperature

Operation erratic

Low shelf oil level Check for leaks in shelf oil circuit

7.3.2 Poor Performance


Leak in refrigerant circuit Check for leaks and repair

Incorrect expansion valve Check setting

Faulty expansion valve setting Check valve operation and replace if necessary

High cooling water temperature Chill cooling water supply

Insufficient cooling water flow Boost supply flow rate

Restricted shelf oil circuit pipe Check oil level and add if required. Check for leaks


Low shelf oil level Add oil as required - check for shelf oil leaks

Poor response time or failure to reach set point

Refrigerant receiver restricted by Call service engineer




contamination

7.3.3 Operational Failure


Compressor fuses blown Ascertain cause then change fuses

Compressor motor protector tripped

Reset trip

High pressure switch open Check compressor

Electronic protection for motor winding tripped

Reset trip

Oil pressure switch open Check oil pressure

No cooling water Check cooling water supply

Motor faulty Test motor

Cooling water pressure switch faulty

Check switch operation

Refrigerant compressor failed

Reverse low pressure switch faulty Check switch setting (see General Maintenance)

Shelf oil pump stopped Check motor trip. Check motor oil level

Temperature incorrectly set Check setting

Shelf cooling not selected Select shelf cooling

Electrical wiring fault Test wiring and correct fault

Electrical supply fault Check supply

PLC waiting for input or event Check program

PLC faulty Check operation of relays

Refrigerant compressor running but temperature not being controlled

PLC not programmed Check that memory has not been lost




7.4 Shelf Heating



Faulty thyristor pack temperature control system


Faulty temperature probe Check temperature probe calibration and electrical connection

Air in shelf oil circuit Check shelf oil level, top-up if necessary

Temperature will not adjust to set point

Low shelf oil level Check shelf oil level and top-up



Oil heater faulty Check heater - replace element if necessary

Faulty temperature probe or poor electrical contact

Check probe calibration and electrical connections

Air in shelf oil circuit Check shelf oil level


Vacuum alarm operated Check operating parameters

Shelf oil pump worn Test pump and replace if necessary

Poor response time or failure to reach setpoint

Low shelf oil level Add oil as required






Fuse for oil heater circuit blown Ascertain cause and replace

Oil heater safety thermostat open Check oil temperature and replace if necessary

No heating available - shelf oil circulating

Thyristor pack failed Replace

Vacuum alarm operated Check operating parameters

Oil pump failure Check oil pump fuses and oil level

Electrical wiring fault Check wiring and repair

Electrical supply fault Check electrical supply

PLC waiting for input or event Check operating parameters

PLC failure Test PLC

No heating available - shelf oil not circulating

No program loaded on PLC Check Recipe Display on PC

7.5 Condenser Refrigeration



False temperature readout caused by sensor fault

Check probe and electrical connections

Expansion valve faulty or incorrectly set


Refrigerant circuit dirty or moisture holding expansion valve open

Check “wetness” sight glass. Dry out and recharge circuit if necessary

Condenser temperature will not stabilize


Check cooling water and stabilize temperature






Leak in refrigeration circuit Check for leaks: repair and recharge refrigeration circuit

Expansion valve faulty or incorrectly set


Refrigerant circuit dirty or moisture holding expansion valve open

Check “wetness” sight glass. Dry and recharge circuit if necessary

Circuit fails to reach set point within time limit


Check cooling water supply and stabilize temperature



Refrigerant compressor fuse blown Ascertain cause and replace

Compressor motor protection tripped

Reset trip

High pressure switch open Check operating parameters

Oil pressure switch open Check oil pressure and level

No cooling water flow Check cooling water supply and drain pipes for obstructions

Motor contactor faulty Test and replace if necessary

Cooling water pressure switch faulty

Check switch and replace if necessary

Condenser cooling not selected Check control settings

Electrical wiring fault Check all wiring for signs of overheating. Check electrical connections

Electrical supply failure Check electrical supply



Compressor fails to start

No program loaded on PLC Check the respective recipe screen.




7.6 Vacuum System



Dirty chamber or system Check chamber for contamination. Check vacuum pump oil condition

Contaminated vacuum pump oil Change pump oil

Low vacuum pump oil level Top-up as required

Vacuum pump worn Check pump performance and replace if necessary

Vacuum system leak Check all interconnecting pipes and seals

Condenser not correctly defrosted Check condenser coil and restart defrost cycle

Vacuum gauge faulty Check calibration

System pressure will not stabilize

Vacuum gauge head dirty Clean head and check calibration



Leak on vacuum system circuit Check all interconnecting pipes and seals

Low vacuum pump oil level Check for leaks and add oil as required

Isolation valve partially closed Check operation of valve - check for cleanliness

Vacuum pump worn Check pump performance and replace if necessary

Ice condenser performance poor Check condenser system defrosting function

Excessive water load Check operating parameters

Air vent valve open Close air vent valve

System fails to achieve vacuum in required time or fails to reach setpoint

Vacuum gauge faulty or out of calibration

Check against gauge of known accuracy






Vacuum pump fuses blown Ascertain cause and replace

Vacuum pump motor protector tripped

Reset trip

Motor contactor faulty Test contactor and replace

Electrical wiring fault Check all wiring for signs of overheating. Check all electrical connections

Electrical supply failure Check electrical supply and correct fault



No program loaded on PLC Check Recipe Display on the PC

Vacuum gauge faulty or out of calibration

Check gauge and replace if necessary

Vacuum pump fails to start

Vacuum valves closed Check valve setting

7.7 Vacuum Alarm


Faulty vacuum gauge Call service engineer

Faulty gauge head Change head

Incorrect vacuum alarm pressure setting

Reset

Calibrated leak pressure settings wrong

Reset

Erroneous operation of vacuum alarm

Vacuum leak Check seals and vent valves for leakage




7.8 Hydraulic Stoppering


Fuses blown to hydraulic pump Ascertain cause and replace Stoppering not functioning

Hydraulic unit motor tripped Reset trip

Solenoid valve faulty Check solenoid valve operation and replace if necessary

Air in the hydraulic system Bleed system and check for leaks

Hydraulic oil leak Check for leaks and repair

Faulty regulator valve Test operation of valve

Motor runs but stoppering erratic or ineffective

Blocked filter Replace filter

7.9 Calibrated Leak


Valve FV66 closed or faulty Check valve setting

Solenoid valve faulty Check operation

Vacuum gauge faulty Check vacuum gauge and replace if necessary

Pressure setting incorrect Check and correct setting

Gas flow excessive Check gas supply pressure setting

Poor Vacuum control

Pressure controller faulty (optional equipment)

Check output signal from controller

lyomax 50 industrial freeze drying system

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