boc edwards

boc edwards
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Operating Manual
Lyomax 50 Industrial Freeze Drying System
PSGA
Operating Manual
Revision
:
1
Revision Date
:
13 December 2004
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
1/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
REVISION HISTORY
Version
0
1
Date
12/03/04
12/13/04
Name
MV
MV
Description
Initial Release
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.
2/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
TABLE OF CONTENTS
1.
FREEZE DRYING...................................................................................................................... 9
1.1
History.................................................................................................................................... 9
1.2
Advantages of Freeze Drying .............................................................................................. 9
1.3
1.3.1
1.3.2
1.3.3
Freeze Drying Process ......................................................................................................... 9
Freezing ............................................................................................................................... 9
Primary Drying ................................................................................................................... 10
Secondary Drying .............................................................................................................. 10
1.4
1.4.1
1.4.2
1.4.3
The Effects of Freeze Drying on Materials ....................................................................... 11
Freezing ............................................................................................................................. 11
Primary Drying ................................................................................................................... 11
Secondary Drying .............................................................................................................. 11
1.5
1.5.1
1.5.2
1.5.3
1.5.4
Controlling Freeze Drying .................................................................................................. 11
General .............................................................................................................................. 11
Temperature ...................................................................................................................... 12
Pressure............................................................................................................................. 12
Freezing ............................................................................................................................. 12
1.6
1.6.1
1.6.2
1.6.3
Factors Affecting Freeze Drying........................................................................................ 12
Depth of Fill........................................................................................................................ 12
When Primary Drying Is Complete..................................................................................... 12
Drying Time........................................................................................................................ 12
1.7
Glossary of Freeze Drying Terminology........................................................................... 13
2.
SAFETY................................................................................................................................... 14
2.1
Introduction ......................................................................................................................... 14
2.2
Safety Precautions.............................................................................................................. 14
2.3
Operating Hazards .............................................................................................................. 15
3.
LYOMASTER PC CONTROL SYSTEM.................................................................................. 17
3.1
3.1.1
3.1.2
3.1.3
3.1.4
Introduction ......................................................................................................................... 17
PC Control System ............................................................................................................ 17
Personal Computer (PC).................................................................................................... 17
Programmable Logic Controller (PLC) ............................................................................... 18
Screen Printer .................................................................................................................... 18
3.2
3.2.1
3.2.2
3.2.3
Manual Controls.................................................................................................................. 18
Local Switches ................................................................................................................... 19
Process Room Slave Panel ............................................................................................... 22
Rear Access Door Panel View ........................................................................................... 24
3.3
PC Manual Controls............................................................................................................ 26
3.4
3.4.1
3.4.2
3.4.3
3.4.4
3.4.5
Automatic Controls............................................................................................................. 30
Header ............................................................................................................................... 30
Footer................................................................................................................................. 31
Login / Logout Dialog ......................................................................................................... 32
Navigate............................................................................................................................. 33
General Overview Screen .................................................................................................. 35
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
3/143
SC473501.doc
BOC EDWARDS
3.4.6
3.4.7
3.4.8
3.4.9
3.4.10
3.4.11
3.4.12
3.4.13
3.4.14
3.4.15
3.4.16
3.4.17
3.4.18
3.4.19
3.4.20
3.4.21
3.4.21.1
3.4.21.2
3.4.21.3
3.4.22
3.4.22.1
3.4.22.2
3.4.22.3
3.4.22.4
4.
BOC Edwards
Pharmaceutical Systems
Unit Graphic Screen........................................................................................................... 36
Freeze Drying Recipe Screen ............................................................................................ 38
Optional Cycle Recipe Screens ......................................................................................... 42
Engineering Parameter Screens ........................................................................................ 45
System Parameter Screen ................................................................................................. 48
Error Recovery Screen ...................................................................................................... 49
Manual Controls Screen .................................................................................................... 50
Alarm Screen ..................................................................................................................... 51
Historical Trending Screen................................................................................................. 58
Maintenance Screen .......................................................................................................... 59
Control Loops Screen ........................................................................................................ 61
Calibration Screen ............................................................................................................. 63
Shelf Positioning Screen.................................................................................................... 66
Digital Input Screen............................................................................................................ 68
Device Mode Screen.......................................................................................................... 72
Batch Record Screen......................................................................................................... 73
Batch Reports ................................................................................................................. 74
Freeze Drying Report...................................................................................................... 75
Optional Cycle Report ..................................................................................................... 78
Security Screen.................................................................................................................. 83
Privileges......................................................................................................................... 83
User Accounts................................................................................................................. 86
Secure Desktop............................................................................................................... 88
Electronic Signatures ...................................................................................................... 88
OPERATOR INTERFACE FUNCTIONS ................................................................................. 91
4.1
Login .................................................................................................................................... 91
4.2
4.2.1
4.2.2
4.2.3
4.2.3.1
Working with Recipes......................................................................................................... 91
Create Recipe .................................................................................................................... 91
Edit Recipe......................................................................................................................... 92
Save Recipe....................................................................................................................... 92
Batch Recipes ................................................................................................................. 93
4.3
4.3.1
4.3.1.1
4.3.2
4.3.3
4.3.4
4.3.5
4.3.6
4.3.7
4.3.8
4.3.9
4.3.9.1
Starting an Automatic Freeze Drying Cycle ..................................................................... 94
Loading .............................................................................................................................. 94
Load Product Step Error Recovery ................................................................................. 95
Freezing ............................................................................................................................. 95
Evacuation ......................................................................................................................... 96
Drying................................................................................................................................. 96
Pressure Rise Test (Moisture Test) ................................................................................... 97
Aeration.............................................................................................................................. 97
Stoppering.......................................................................................................................... 97
Aeration.............................................................................................................................. 98
Storage / Unloading ........................................................................................................... 98
Unload Product Step Error Recovery.............................................................................. 98
4.4
Starting an Optional Automatic Cycle .............................................................................. 99
4.5
4.5.1
4.5.2
Automatic Defrost Cycle .................................................................................................... 99
Condenser Aerate and Drain ........................................................................................... 100
Evacuate Condenser ....................................................................................................... 100
4/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
4.5.3
4.5.4
4.5.5
Steam Defrost .................................................................................................................. 100
Condenser Drying ............................................................................................................ 100
Condenser Aeration ......................................................................................................... 100
4.6
4.6.1
4.6.2
4.6.3
4.6.4
4.6.5
4.6.6
4.6.7
4.6.8
4.6.9
4.6.10
4.6.11
4.6.12
Automatic Clean-in-Place Cycle (CIP)............................................................................. 101
Lock Rear Access Door ................................................................................................... 101
Aerate Chamber and Condenser ..................................................................................... 101
Chamber Initial Rinse....................................................................................................... 101
Condenser Initial Rinse.................................................................................................... 102
Clean Condenser ............................................................................................................. 102
Clean Chamber................................................................................................................ 102
Drain Chamber and Condenser ....................................................................................... 102
Chamber Final Rinse ....................................................................................................... 103
Condenser Final Rinse .................................................................................................... 103
Final Drain........................................................................................................................ 103
System Drying and Unlock Door ...................................................................................... 103
Aerate Chamber and Condenser ..................................................................................... 103
4.7
4.7.1
4.7.2
4.7.3
4.7.4
4.7.5
4.7.6
4.7.7
4.7.8
4.7.9
4.7.10
4.7.11
4.7.12
Starting a Sterilization Cycle (SIP) .................................................................................. 103
First Evacuation and Lock Door ....................................................................................... 104
Chamber Jacket Heating ................................................................................................. 104
One Steam Purge ............................................................................................................ 104
Two Steam Purges .......................................................................................................... 105
Three Steam Purges ........................................................................................................ 105
Steam............................................................................................................................... 105
Steam Discharge ............................................................................................................. 106
Filter Drying...................................................................................................................... 106
System Drying.................................................................................................................. 106
Condenser Cooling .......................................................................................................... 107
Shelf and Chamber Jacket Cooling ................................................................................. 107
Aeration............................................................................................................................ 107
4.8
4.8.1
4.8.2
4.8.3
4.8.4
Leak Test ........................................................................................................................... 107
Evacuate Chamber & Condenser .................................................................................... 107
Dry System ...................................................................................................................... 108
Leak Test ......................................................................................................................... 108
Aeration............................................................................................................................ 108
4.9
4.9.1
4.9.2
4.9.3
Shelf Ram Bellows Test ................................................................................................... 108
Lower Shelf Stack and Evacuate Bellows........................................................................ 109
Bellows Test..................................................................................................................... 109
Raise Shelves and Vent Bellows ..................................................................................... 109
4.10
4.10.1
4.10.2
4.10.3
Main Isolation Valve Bellows Test................................................................................... 109
Evacuate Bellows............................................................................................................. 110
Bellows Test..................................................................................................................... 110
Vent Bellows .................................................................................................................... 110
4.11
4.11.1
4.11.2
4.11.3
4.11.4
Filter Integrity Test (FIT)................................................................................................... 110
Start of FIT ....................................................................................................................... 110
Pressurize Slot Door and Vent Chamber ......................................................................... 111
Fill WFI Water Tank ......................................................................................................... 111
Flood Filter ....................................................................................................................... 111
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
5/143
SC473501.doc
BOC EDWARDS
4.11.5
4.11.6
4.11.7
4.11.8
BOC Edwards
Pharmaceutical Systems
Perform Integrity Test ...................................................................................................... 111
Drain Filter Housing ......................................................................................................... 111
Filter Cartridge Drying ...................................................................................................... 111
Drain Tank ....................................................................................................................... 112
4.12
Device Mode (Maintenance Only) .................................................................................... 112
4.13
4.13.1
Security - Adding Users ................................................................................................... 113
Disabling Users ................................................................................................................ 115
4.14
iFIX System Backup.......................................................................................................... 115
4.14.1
Microsoft SQL Server Desktop Edition Audit Trail Backup .............................................. 117
4.14.1.1
Weekly Backup ............................................................................................................. 117
4.14.1.2
Manual Weekly Backup................................................................................................. 118
4.14.1.3
Daily Backup ................................................................................................................. 118
4.14.1.4
SQL Weekly Backup Schedule ..................................................................................... 119
4.14.1.5
Restoration of SQL Backups......................................................................................... 121
4.14.1.6
Backup Log Files and Job Histories.............................................................................. 122
4.14.2
PLC Program Backup ...................................................................................................... 125
4.15
4.15.1
4.15.2
SCADA System Backup ................................................................................................... 126
SCADA Backup................................................................................................................ 126
Create SCSI Driver Disk .................................................................................................. 126
4.16
4.16.1
4.16.2
4.16.3
4.16.4
System Restore................................................................................................................. 127
SCADA System Restore .................................................................................................. 127
iFIX System Restore ........................................................................................................ 128
Microsoft SQL Server Desktop Edition Restore ............................................................... 129
Data Accumulated on the PC Operator Interface............................................................. 129
5.
OPERATING PROCEDURES ............................................................................................... 130
5.1
Introduction ....................................................................................................................... 130
5.2
5.2.1
Pre-Start Requirements.................................................................................................... 130
Start-up Checks ............................................................................................................... 130
5.3
5.3.1
5.3.2
5.3.3
5.3.4
5.3.5
5.3.6
5.3.7
5.3.8
5.3.9
5.3.10
5.3.11
5.3.12
5.3.13
5.3.14
5.3.15
5.3.16
5.3.17
Operating Sequence ......................................................................................................... 131
Loading Shelves .............................................................................................................. 131
Guide Rail Removal for Incomplete Loads....................................................................... 132
Positioning Product Temperature Probes ........................................................................ 132
Closing the Chamber Door .............................................................................................. 133
Pre-Cycle Checks ............................................................................................................ 133
Shelf Cooling/Product Freezing ....................................................................................... 134
Condenser Cooling .......................................................................................................... 134
Vacuum Pump Down ....................................................................................................... 135
Shelf Heating ................................................................................................................... 137
Secondary Drying ............................................................................................................ 137
End of Cycle..................................................................................................................... 138
Hydraulic Stoppering........................................................................................................ 138
Chamber Aeration............................................................................................................ 139
Unloading......................................................................................................................... 140
Condenser Defrosting ...................................................................................................... 140
Cleaning the Chamber ..................................................................................................... 140
Partial and Total Shutdown .............................................................................................. 141
6/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
LIST OF ILLUSTRATIONS
Figure
1.1
1.2
3.1
3.2
3.3
3.4
3.5
3.6
3.7
3.8
3.9
3.10
3.11
3.12
3.13
3.14
3.15
3.16
3.17
3.18
3.19
3.20
3.21
3.22
3.23
3.24
3.25
3.26
3.27
3.28
3.29
4.1
4.2
4.3
4.4
4.5
4.6
4.7
5.1
5.2
Description
Phase Diagram for Water .................................................................................................. 10
Freeze Dried Material Showing Voids Remaining After Sublimation ................................. 11
Control System Block Diagram .......................................................................................... 18
Process Room Slave Panel ............................................................................................... 22
Rear Access Door Panel View Slave Panel....................................................................... 24
Screen Header................................................................................................................... 30
Footer................................................................................................................................. 31
Login/Logout Keypad ......................................................................................................... 32
General Overview Screen .................................................................................................. 35
Unit Graphic Screen........................................................................................................... 37
Example Freeze Drying Recipe Screen ............................................................................. 38
Typical Optional Cycle Recipe Screen............................................................................... 42
Typical Engineering Parameter Screen ............................................................................. 45
Example System Parameter Screen .................................................................................. 48
Error Recovery Screen ...................................................................................................... 49
Manual Controls Screen .................................................................................................... 51
Example Alarms Screen .................................................................................................... 52
Example Historical Trending Screen.................................................................................. 58
Maintenance Screen .......................................................................................................... 60
Example Control Loops Screen ......................................................................................... 62
Example Calibration Screen .............................................................................................. 63
Shelf Positioning Screen.................................................................................................... 67
Example Digital Input Screen............................................................................................. 68
Example Device Mode Screen........................................................................................... 73
Example Freeze Drying Recipe Start Report 1 .................................................................. 76
Example Freeze Drying Recipe Start Report 2 .................................................................. 77
Example Freeze Drying Step End Report .......................................................................... 78
Typical Optional Cycle Start Report ................................................................................... 82
Typical Optional Cycle End Report .................................................................................... 83
Example Perform Only Electronic Signature Screen ......................................................... 88
Example Perform and Verify Electronic Signature Screen................................................. 89
SQL Server Archive Job .................................................................................................. 120
SQL Server Archive Job Schedule .................................................................................. 120
SQL Server Archive Job Schedule Change ..................................................................... 121
Archive Backup Job History ............................................................................................. 123
SQL Server Logs ............................................................................................................. 124
Event Viewer Archive Database Failure Backup Tape Missing from Drive...................... 125
Event Viewer Archive Database Backup to Tape ............................................................ 125
Shelf Loading ................................................................................................................... 131
Positioning Temperature Probes. .................................................................................... 133
LIST OF TABLES
Table
1.1
3.1
Description
Typical Freeze Drying Conditions ...................................................................................... 13
Control Cabinet Switches................................................................................................... 19
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
7/143
SC473501.doc
BOC EDWARDS
3.2
3.3
3.4
3.5
3.6
3.7
3.8
3.9
3.10
3.11
3.12
3.13
3.14
3.15
3.16
3.17
3.18
3.19
3.20
3.21
3.22
3.23
3.24
3.25
3.26
3.27
3.28
3.29
3.30
3.31
3.32
3.33
3.34
3.35
3.36
3.37
3.38
3.39
3.40
3.41
3.42
3.43
3.44
3.45
4.1
4.2
BOC Edwards
Pharmaceutical Systems
Power Cabinet Switches .................................................................................................... 19
Process Room Slave Panel Functions............................................................................... 23
Rear Access Door PanelView Functions ........................................................................... 25
PC Pushbuttons and PC Manual Controls ......................................................................... 27
Manual Setpoint Functions ................................................................................................ 30
Main Menu Navigation Functions....................................................................................... 33
Recipe Sub-Menu Functions.............................................................................................. 33
Maintenance Sub-Menu Functions .................................................................................... 34
Engineering Parameters Sub-Menu Functions .................................................................. 34
Screen Color Assignments ................................................................................................ 36
Recipe Configuration ......................................................................................................... 41
General Recipe Parameters .............................................................................................. 41
Defrost Recipe Screen Parameters ................................................................................... 43
CIP Recipe Screen Parameters ......................................................................................... 43
SIP Recipe Screen Parameters ......................................................................................... 44
Leak Test Recipe Screen Parameters ............................................................................... 44
Shelf Ram Bellows Test Recipe Screen Parameters......................................................... 44
Main Isolation Valve Bellows Test Recipe Screen Parameters ......................................... 44
Filter Integrity Test Recipe Screen Parameters ................................................................. 44
Freeze Drying Engineering Parameters............................................................................. 46
Defrost Engineering Parameters........................................................................................ 46
CIP Engineering Parameters ............................................................................................. 46
SIP Engineering Parameters ............................................................................................. 47
Leak Test Engineering Parameters ................................................................................... 47
Shelf Ram Bellows Test Parameters ................................................................................. 47
Filter Integrity Test Engineering Parameters...................................................................... 48
Alarm/Message Color ........................................................................................................ 53
Alarms and Messages ....................................................................................................... 53
Analog Inputs and Outputs ................................................................................................ 64
Digital Inputs ...................................................................................................................... 69
Cycle Abbreviations ........................................................................................................... 74
Tab Naming Formats ......................................................................................................... 75
Freeze Drying Recipe Start Report Contents..................................................................... 76
Step End Report Contents ................................................................................................. 77
Defrost Report Contents .................................................................................................... 79
CIP Report Contents .......................................................................................................... 79
SIP Report Contents .......................................................................................................... 80
Leak Test Report Contents ................................................................................................ 80
Shelf Ram Bellows Test Report Contents.......................................................................... 81
Main Isolation Valve Bellows Test Report Contents .......................................................... 81
FIT Cycle Test Report Contents ........................................................................................ 81
Group Account Privileges .................................................................................................. 84
User Account Definitions.................................................................................................... 87
Electronic Signature Functions .......................................................................................... 90
Backup and Restore Options ........................................................................................... 115
Application Files............................................................................................................... 117
8/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
1.
FREEZE DRYING
1.1
History
Freeze drying can occur naturally. At the end of the 19th century, it was discovered that the
application of a vacuum could accelerate the freeze drying process. The second world war saw the
first commercial applications of freeze drying for the supply of dried blood plasma and penicillin to the
armed forces. Since then, the size, sophistication, and applications of freeze drying machinery have
grown significantly.
1.2
Advantages of Freeze Drying
Freeze drying easily stabilizes degradable materials. Its major advantages over alternative freezing
or drying forms of stabilization are:
1.
The retention of essential characteristics of the original material (appearance, size, shape, taste,
color, etc.)
2.
The ability to rapidly re-constitute the freeze dried material by adding liquid.
3.
The ease of storage and the long-term viability of the material.
4.
The production of high internal surface area can be useful (e.g., in catalysts).
5.
Friable, free flowing powders useful for further processing (e.g., ceramics).
1.3
Freeze Drying Process
The natural forms of freeze drying consist of removing liquid in a transition process of evaporation
from the liquid to the vapor phase, even if the product was originally in the solid state (i.e., frozen). In
commercial applications of freeze drying, a process referred to as sublimation accelerates the
evaporation process by removing liquid from a substance directly from the solid (frozen) state, under
vacuum, to the vapor state without passing through the liquid state.
The freeze drying cycle has three stages:
1.
Freezing (or pre-freezing).
2.
Primary drying to remove water ice.
3.
Secondary drying to remove 'bound' water molecules from the primary dried material.
1.3.1
Freezing
It may be necessary to subject the product to temperatures of -50°C or lower at atmospheric pressure
to ensure solid freezing below its triple or eutectic point (Figure 1.1). The rate of freezing has an
effect on freeze drying rates since a rapidly frozen product will dry more slowly forming smaller water
crystals that provide smaller vapor ducts when the product is subjected to the drying process.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
9/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Note:
When the product freezes, the temperature must not rise until establishing a
vacuum, or melting will occur.
WATER VAPOR
PRESSURE
(MBAR)
10
3
10
2
10
1
10
0
10
-1
10
-2
10
-3
10
-4
10
-5
LIQUID
Freezing
Melting
SOLID
Evaporation
-100
TRIPLE POINT
VAPOUR
Sublimation
-80
-60
-40
-20
-0
40
20
80
100
o
TEMPERATURE (C )
Figure 1.1: Phase Diagram for Water
1.3.2
Primary Drying
The sublimation process converts frozen liquid directly from solid to vapor. Conditions required are:
1.
Reduced pressure on the product to assist the vapor flow.
2.
Increased temperature required for primary drying to occur. The energy input rate affects the
rate of drying. This should be as high as possible to speed up the freeze drying process, but
not damage the product, melt or blow the dried product. Primary drying is finished when the ice
is removed.
Note:
1.3.3
For rapid freeze drying, the product is dried at the highest temperature below the
product eutectic point.
Secondary Drying
This part of the sublimation process desorbs remaining bound moisture (usually 2-5% by volume).
This process requires the addition of heat energy to break up the crystal lattice structure (formed
during freezing) to allow water molecules trapped within the lattice to escape. Secondary drying may
not be required, depending on the product.
10/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
1.4
The Effects of Freeze Drying on Materials
1.4.1
Freezing
During this stage, the liquid comes out of solution, forming ice crystals and locking the material into a
solid matrix (see Figure 1.2).
Figure 1.2: Freeze Dried Material Showing Voids Remaining After Sublimation
1.4.2
Primary Drying
This is a dynamic process, involving the transition of liquid from ice phase directly to vapor phase.
This leaves the solid matrix formed in the freezing phase without ice crystals. During drying, an
interface occurs that travels from the surface exposed to the vacuum system to the surface where the
heat source originates. At the interface point, freeze drying occurs.
1.4.3
Secondary Drying
Providing additional heat to the system removes “bound” liquid from the product. To remove bound
liquid, increase the temperature or slightly increase the gas pressure within the chamber to improve
the thermal contact between the product and heat source.
1.5
Controlling Freeze Drying
1.5.1
General
The Lyomaster PC Control System controls process variables to establish the required thermal
“balance.” To achieve the fastest rate of drying, this balance should be at the point where
temperature and pressure are as high as possible without damaging the product by melting or
scorching. This means controlling the process by accurately monitoring temperatures and pressures
within the system.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
11/143
SC473501.doc
BOC EDWARDS
1.5.2
BOC Edwards
Pharmaceutical Systems
Temperature
The shelf thermo-regulation system controls heat input, adjusting the shelf temperature to ±1.5°C at
steady state.
1.5.3
Pressure
Adjust or 'spoil' system pressure by admitting nitrogen into the system using a fine calibrated leak
when such an option is fitted.
1.5.4
Freezing
The rate of freezing has an effect upon the drying rate due to the size of the ice crystals that leave
vapor ducts after they have sublimed. The vapor ducts occur from the interface to the surface
exposed to vacuum allowing water vapor to escape from the interface.
1.6
Factors Affecting Freeze Drying
1.6.1
Depth of Fill
Sublimation requires heat energy that generally travels from the heat source to the interface where ice
converts to vapor. In addition, this vapor escapes from the product through the voids where the ice
sublimed. As material fill depth increases, the drying time increases and the danger of melting also
increases.
1.6.2
When Primary Drying Is Complete
The main methods used are:
1.
Pressure stability: during drying, pressure will decrease slowly, until it stabilizes at an 'ultimate'
low level, which remains constant for 1-2 hours.
2.
Product temperature rise: when heat energy is no longer required for sublimation, the overall
product temperature will rise until equal with, or close to, the shelf temperature. A product
temperature probe detects product temperature and its output displayed on an indicator (digital
or chart recorder).
3.
Pressure rise test: if an isolation valve is fitted, it will be possible to periodically isolate the drying
chamber. If the material is not dry then the pressure will rise quickly (due to the continued
sublimation of water vapor). If it is dry, little pressure rise will be detected.
1.6.3
Drying Time
Primary drying time is roughly proportional to thickness. While the time for unit thickness depends on
process variables, under typical conditions, the ice boundary recedes from the surface of the dry cake
at an average rate of 1 mm an hour. See Table 1-1 for typical product drying times.
12/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 1.1: Typical Freeze Drying Conditions
Material
(10 mm thickness)
Milk
Urea
Blood Plasma
Serum
1.7
Safe Temperature
(ºC)
-5
-7
-10 to -25
-25
Condenser
Temperature (ºC)
-40
-40
-40
-40
Typical Pressure
(mBar)
0.1
0.1
0.1
0.1
Typical Time
to Dry (hours)
10
10
16
18
Glossary of Freeze Drying Terminology
Bound Water -
Cake Condenser Eutectic -
Water remaining in the product once primary drying has been
completed (usually 2 to 5% by volume).
Dried mass left after freeze drying.
Unit used to trap water vapor originating from product sublimation.
The lowest freezing point.
Meltback -
Undesirable situation when ice in the product melts before changing
to vapor.
Primary Drying -
Initial stage of dehydrating a product under vacuum. Primary drying
is complete when further product sublimation is impossible at a
given 'safe' temperature and vacuum.
Product -
Substance to be freeze dried.
Secondary Drying -
Secondary stage of dehydrating a product under vacuum where
residual 'bound' water molecules are removed. Secondary drying is
achieved either by increasing the drying temperature or by
improving thermal contact between the heat source and product.
Sublimation -
Conversion of ice, in a product, to its vaporous state without passing
through the liquid state.
Triple Point -
The temperature and pressure at which solid, liquid, and gas phases
of a given substance are all present simultaneously.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
13/143
SC473501.doc
BOC EDWARDS
2.
SAFETY
2.1
Introduction
BOC Edwards
Pharmaceutical Systems
The Lyomax Freeze Dryer design meets normal industry safety standards. Safety hazards associated
with the Lyomax unit generally are those caused by incorrect use or failure to follow correct
procedures. This section lists the main hazards that can occur when operating the unit.
2.2
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:
Note:
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.
Notes emphasize an important piece of information.
Safe equipment operation is the responsibility of the user and user's staff. Comply with all safety
instructions and take appropriate actions to protect personnel and property from the hazards
associated with the freeze dryer's operation. Before performing any operations, read and comply with
all precautions included in this manual, the Product Documentation package, and posted on the
machine. Additionally, read and understand this manual, the maintenance manual, and all vendor
manuals supplied in the Product Documentation provided with your freeze dryer.
Perform all maintenance at the recommended intervals to maintain equipment in safe operating
condition. Only qualified engineers or trade workers should perform the specialized maintenance
described in the maintenance manual.
14/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
2.3
Operating Hazards
Observe the following points when operating the freeze dryer. For full details and specific
instructions, refer to the operating instructions contained in Sections 4 and 5 of this manual.
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:
CHECK PROCESS & INSTRUMENTATION DIAGRAMS
D-C47-19-01, D-C47-19-05, D-C47-19-06, C-C47-19-07,
C-C47-19-08, C-C47-19-09, D-C47-19-10, AND
D-C47-19-11 TO ENSURE ALL VENTS ARE CORRECTLY
INSTALLED AND RELEASE TO SAFE AREAS.
1.
Operators must read all instructions before starting any work on the unit.
2.
Read all safety information for fluids used in the system. Material Safety Data Sheets for these
fluids are provided in the Instruction Manual
3.
Ensure all incondensable materials (especially solvents) are removed from the system before
startup.
4.
Perform required pre-start and maintenance checks before startup.
5.
When taking instrument measurements, verify gauges indicate correct values and the values
are not confused by other operating conditions.
6.
Do not tamper with pressure switch settings or any hydraulic safety devices. Keep away from
the shelf stack when stoppering.
7.
The accumulation or use of dangerous cleaning agents will damage the freeze dryer and create
hazardous conditions. The freeze dryer is not flameproof.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
15/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
8.
When there are problems with the unit contact a BOC Edwards Pharmaceutical Systems
service technician before attempting any maintenance.
9.
Keep clear of door lock pistons.
10.
Do not tamper with door lock pistons.
16/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
3.
LYOMASTER PC CONTROL SYSTEM
3.1
Introduction
The freeze dryer has a dedicated programmable logic controller (PLC), slave panels, and field devices
(Figure 3.1). The PLC, slave panels, and a personal computer form the Control System. The
fundamental tasks of the Control System are to monitor, control, and display freeze drying process
parameters during a cycle, allowing the operator to view and modify the process.
The PC is the primary Operator Interface with the freeze dryer. Operator commands from the PC, the
slave panels, or from selector switches mounted on 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. An Operator enters data in the appropriate
screen using the keyboard and mouse.
3.1.1
PC Control System
The PC control system can be used to control every aspect of the freeze drying cycle. To achieve
this, each stage of the cycle is divided into steps. The control system requires that the operator enter
certain information for each step so that the cycle can be controlled. The information is fed into the
system during programming in the form of a table, called the recipe. The recipe is then processed on
a step-by-step basis utilizing information obtained from temperature sensors, pressure transducers,
operator instructions, etc. to achieve the desired drying cycle.
The freeze dryer control system can be divided into the following:
1.
Operator Interface PC - Operator interface from which manual and automatic freeze drying
cycles may be initiated. The Lyomax PC operates using Windows Server 2000 and Intellution
FIX platforms. The operator interface uses multiple screens to present various freeze drying
operations and related process data collected from the PLC.
2.
Programmable Logic Controller (PLC) - Interfaced with the Lyomax PC to control freeze dryer
operation and interlocks. The PLC program resides in internal RAM and cannot be modified by
the operator.
3.1.2
Personal Computer (PC)
The computer system consists of the following components:
•
One IBM compatible Operator Interface PC with a 2.8GHz Pentium IV processor, 1GB RAM, three
36GB SCSI RAID 5 hard-drives, ENET, floppy disk drive, internal CD drive, internal DVD/CDRW,
internal tape drive, running Windows Server 2000 operating system
•
A 17-inch CRT Monitor for the Operator Interface PC.
•
A USB 4800 x 1200 dpi color screen printer (PRN1) for the Operator Interface PC.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
17/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
•
An 8 port Ethernet Hub for the Ethernet network.
ETHERNET
SWITCH
PLC
PLC
OPERATOR
INTERFACE PC
SCREEN PRINTER
SLAVE PANEL
PANELVIEW
1000
Figure 3.1: Control System Block Diagram
An Ethernet network facilitates communication between the Operator Interface PC, the slave panels,
the PLC Ethernet Communications Module, and the Loading / Unloading System.
3.1.3
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.
3.1.4
Screen Printer
The system includes a color printer for making hardcopies of screens displayed on the personal
computer and for printing reports.
3.2
Manual Controls
For manual operation and testing of the freeze dryer, the unit is equipped with a series of selector
switches located in the Power Cabinet, the Control Cabinet, the slave panel, and the PanelView 1000
terminal. 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.
18/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
3.2.1
Local Switches
Individual system components may be enabled or disabled using local selector switches located 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 and their functions are
shown in the following tables.
Table 3.1: Control Cabinet Switches
Control
Control Power
(HS1)
Mode
Auto &
Manual
Position
On
Function
Returns power to the safety relay and the control lines.
Off
Removes power from the safety relay interrupting
power to control lines. All valves, pumps, motors and
compressors are disabled.
Emergency
Switching Off
Control Power
(PB8)
Auto &
Manual
In
Push in to disable power to output devices.
Reset Control
Power(PB78)
Auto &
Manual
Note: If an automatic cycle is active and PB8 is
pushed-in and then pulled-out, the PLC logic will
attempt to reset and restore the control power.
This allows the auto cycle to resume.
Out
Normal Position. Power to output devices enabled.
Momentary
Pushbutton
If an automatic cycle is not active and PB8 has been
pressed, a “control power reset req’d @ control cab”
alarm will occur. To clear alarm and restore control
power, PB8 is pulled-out, then the reset pushbutton
PB78 is pressed.
Table 3.2: Power Cabinet Switches
Control
Compressor 1
Mode
Auto &
Manual
Position
Enable
Off
Compressor 2
Auto &
Manual
Enable
Off
Compressor 3
Auto &
Manual
Enable
Off
PSGA
Operating Manual
Function
Connects PLC output and power to compressor motor
and heater. Compressor can Start/Run.
Disconnects PLC output and power to compressor motor
and heater. Compressor cannot Start/Run.
Connects PLC output and power to compressor motor
and heater. Compressor can Start/Run.
Disconnects PLC output and power to compressor motor
and heater. Compressor cannot Start/Run.
Connects PLC output and power to compressor motor
and heater. Compressor can Start/Run.
Disconnects PLC output and power to compressor motor
and heater. Compressor cannot Start/Run.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
19/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.2: Power Cabinet Switches (continued)
Control
Compressor 4
Mode
Auto &
Manual
Position
Enable
Off
Compressor 5
Vacuum Pump 1
Auto &
Manual
Auto &
Manual
Enable
Auto &
Manual
Auto &
Manual
Enable
Connects PLC output and power to vacuum pump motor.
Pump can Start/Run.
Enable
Enable
Off
Booster Pump 2
Shelf Fluid
Circulation Pump
1
Auto &
Manual
Auto &
Manual
Enable
Auto &
Manual
Connects PLC output and power to vacuum pump motor.
Pump can Start/Run.
Disconnects PLC output and power to vacuum pump
motor. Pump cannot Start/Run.
Connects PLC output and power to booster pump motor.
Pump can Start/Run.
Disconnects PLC output and power to booster pump
motor. Pump cannot Start/Run.
Connects PLC output and power to booster pump motor.
Pump can Start/Run.
Disconnects PLC output and power to booster pump
motor. Pump cannot Start/Run.
Enable
Connects PLC output and power to circulation pump
motor. Pump can Start/Run.
Enable
Off
20/143
SC473501.doc
Disconnects PLC output and power to vacuum pump
motor. Pump cannot Start/Run.
Off
Off
Shelf Fluid
Circulation Pump
2
Connects PLC output and power to compressor motor
and heater. Compressor can Start/Run.
Disconnects PLC output and power to compressor motor
and heater. Compressor cannot Start/Run.
Off
Booster Pump 1
Disconnects PLC output and power to compressor motor
and heater. Compressor cannot Start/Run.
Off
Off
Vacuum Pump 2
Function
Connects PLC output and power to compressor motor
and heater. Compressor can Start/Run.
Disconnects PLC output and power to circulation pump
motor. Pump cannot Start/Run.
Connects PLC output and power to circulation pump
motor. Pump can Start/Run.
Disconnects PLC output and power to circulation pump
motor. Pump cannot Start/Run.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.2: Power Cabinet Switches (continued)
Control
Condenser Fluid
Circulation Pump
1
Mode
Auto &
Manual
Position
Enable
Off
Condenser Fluid
Circulation Pump
2
Auto &
Manual
Enable
Off
Jacket Fluid
Circulation Pump
Auto &
Manual
Enable
Off
Hydraulic Pump
Auto &
Manual
Enable
Off
Liquid Ring Pump
Auto &
Manual
Enable
Off
Shelf Heater 1
Auto &
Manual
Enable
Off
Shelf Heater 2
Auto &
Manual
Enable
Off
Jacket Heater
Auto &
Manual
Enable
Off
CIP Recirculation
Pump
Auto &
Manual
Enable
Off
PSGA
Operating Manual
Function
Connects PLC output and power to circulation pump
motor. Pump can Start/Run.
Disconnects PLC output and power to circulation pump
motor. Pump cannot Start/Run.
Connects PLC output and power to circulation pump
motor. Pump can Start/Run.
Disconnects PLC output and power to circulation pump
motor. Pump cannot Start/Run.
Connects PLC output and power to circulation pump
motor. Pump can Start/Run.
Disconnects PLC output and power to circulation pump
motor. Pump cannot Start/Run.
Connects PLC output and power to hydraulic pump.
Pump can Start/Run.
Disconnects PLC output and power to hydraulic pump.
Pump cannot Start/Run.
Connects PLC output and power to liquid ring pump
motor. Pump can Start/Run.
Disconnects PLC output and power to liquid ring pump
motor. Pump cannot Start/Run.
Connects PLC output and power to heater.
Disconnects PLC output and power to heater.
Connects PLC output and power to heater.
Disconnects PLC output and power to heater.
Connects PLC output and power to heater.
Disconnects PLC output and power to heater.
Connects PLC output and power to the CIP recirculation
pump. Pump can Start/Run.
Disconnects PLC output and power to the CIP
recirculation pump. Pump cannot Start/Run.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
21/143
SC473501.doc
BOC EDWARDS
3.2.2
BOC Edwards
Pharmaceutical Systems
Process Room Slave Panel
A slave panel, located near the loading/unloading slot door, is capable of controlling specific freeze
drying functions under limited and controlled conditions. The function of slave panel control switches
is described in the table below. Controls that indicate "Manual" in the mode column are only available
while the freeze dryer is in manual mode. While in manual mode, the operation of the slave panel
must be enabled from the PC manual control screen. Controls that have "Auto & Manual" in the mode
column are available during both manual mode and automatic freeze drying cycles, if permitted by the
PLC logic software
Figure 3.2: Process Room Slave Panel
22/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.3: Process Room Slave Panel Functions
Switch
Loading Door 1
Mode
Manual
Position
Open
Off
Loading Door 2
Manual
Normal switch position. No action.
Close
The loading door closes.
Open
The loading door opens.
Off
Normal switch position. No action.
Close
Stopper Index Shelf
#1
Stopper Index Shelf
#2
Manual
Manual
Description
The loading door opens.
The loading door closes.
Up
The hydraulic pump is turned on. The ram retracts, and
the shelves move up one shelf at a time. Shelves will
not move if the rear access door is open.
Off
Normal switch position. No action.
Down
The hydraulic pump is turned on. The ram extends and
the shelves move down one shelf at a time. Shelves
will not move if the rear access door is open.
Up
The hydraulic pump is turned on. The ram retracts, and
the shelves move up one shelf at a time. Shelves will
not move if the rear access door is open.
Off
Normal switch position. No action.
Down
The hydraulic pump is turned on. The ram extends and
the shelves move down one shelf at a time. Shelves
will not move if the rear access door is open.
Push
All shelf and loading door movement is immediately
stopped.
Stop shelf
Movement Slot
Door
Auto &
Manual
Reset Loading
Door and Shelf
Movement
Auto &
Manual
Push
Resets the loading door and shelf movement abort and
lets the shelf and loading door movement resume.
Chamber Aeration
Manual
Pre-aerate
Pre-aerates chamber to the set point entered on the
manual controls screen if main isolation valve is closed.
Twist To
Release
Off
Aerate
Light Curtain
Override
Auto &
Manual
PSGA
Operating Manual
Push
Releases the emergency stop button but action does
not resume.
Aeration and pre-aeration is deactivated.
Aerates or pre-aerates with process air or sterile
nitrogen as selected on the manual controls screen.
Press to test lamp.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
23/143
SC473501.doc
BOC EDWARDS
3.2.3
BOC Edwards
Pharmaceutical Systems
Rear Access Door Panel View
A touch screen Panel View, located near the rear access door, is capable of controlling specific freeze
drying functions under limited and controlled conditions. The function of panel control switches is
described in the table below. Controls that indicate "Manual" in the mode column are only available
while the freeze dryer is in manual mode. While in manual mode, the operation of the slave panel
must be enabled from the PC manual control screen. Controls that have "Auto & Manual" in the mode
column are available during both manual mode and automatic freeze drying cycles, if permitted by the
PLC logic software
Figure 3.3: Rear Access Door Panel View Slave Panel
24/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.4: Rear Access Door PanelView Functions
Switch
Chamber Sight
Glass Light
Mode
Manual
Position
Push
Description
Energizes chamber sight glass light for one (1) minute.
Chamber Aeration
Manual
Pre-aerate
Pre-aerates chamber to the set point entered on the
manual controls screen if main isolation valve is closed.
Off
Chamber Door
Manual
Aeration and pre-aeration is deactivated.
Aerate
Aerates or pre-aerates with process air or sterile nitrogen
as selected on the manual controls screen.
Open
If the chamber door is closed, the hydraulic pump starts
and the primary door pistons retract to unlatch the door.
Close
If the chamber door is unlatched and closed, the hydraulic
pump starts and the primary door pistons extend to latch
the door.
This function is inhibited if:
The main isolation valve is open.
The chamber is above atmospheric pressure.
The shelf stack is moving.
The slot door is not fully closed.
Chamber Door
Manual
Unlock
Off
Chamber door secondary locking pins are unlocked.
Normal switch position. No action.
Note: Switch must be returned to OFF position otherwise
all manual and automatic functions will be inhibited.
Lock
Shelf Ram 1
Index
Shelf Ram 1 Jog
Manual
Manual
PSGA
Operating Manual
Rear access door secondary locking pins are locked.
Chamber pressure remains at the evacuation set point.
Up
The hydraulic pump is turned on. The ram retracts, and
the shelves move up one shelf at a time. Shelves will not
move if the chamber door is open.
Down
The hydraulic pump is turned on. The ram extends and
the shelves move down one shelf at a time. Shelves will
not move if the chamber door is open.
Up
The hydraulic pump is turned on. The ram retracts, and
the shelves move up until switch is released. Shelves will
not move if the chamber door is open.
Down
The hydraulic pump is turned on. The ram extends and
the shelves move down until switch is released. Shelves
will not move if the chamber door is open.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
25/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.4: Rear Access Door PanelView Functions (continued)
Switch
Shelf Ram 2
Index
Shelf Ram 2 Jog
3.3
Mode
Manual
Manual
Position
Up
Description
The hydraulic pump is turned on. The ram retracts, and
the shelves move up one shelf at a time. Shelves will not
move if the chamber door is open.
Down
The hydraulic pump is turned on. The ram extends and
the shelves move down one shelf at a time. Shelves will
not move if the chamber door is open.
Up
The hydraulic pump is turned on. The ram retracts, and
the shelves move up until switch is released. Shelves will
not move if the chamber door is open.
Down
The hydraulic pump is turned on. The ram extends and
the shelves move down until switch is released. Shelves
will not move if the chamber door is open.
PC Manual Controls
Manual functions are accessed from the Operator Interface PC. Manual freeze dryer controls are
found on the Recipe screen (Figure 3.8) and the Manual Controls screen (Figure 3.13.) 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.
Note:
The mode of operation for a freeze dryer is selected at the Operator Interface PC.
The freeze dryer may be placed in "Manual" or "Automatic" modes using the
Control Select switch on the Manual Controls screen.
The following table lists the manual control and setpoint functions available from the Operator
Interface PC. Unless otherwise indicated, all functions listed are located on the Manual Controls
Screen. The Manual Controls screen provides operator interface for manual operation and testing of
the freeze dryer. Select the Manual Controls button from the Main Menu to view this screen.
26/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.5: PC Pushbuttons and PC Manual Controls
Pushbutton
Cycle Hold
(Freeze Drying
Recipe Screen)
Mode
Auto
Cycle Step
Advance
(Freeze Drying
Recipe Screen)
Auto
Control Select
Shelf
Temperature
Control
Position
Cycle Hold
Off
Auto &
Manual
Manual
Auto
Manual
Manual
Manual
Permits manual control of the freeze dryer using the
PC Manual Controls Screen or the slave panels.
Enable
Permits manual adjustment of the shelf temperature
setpoint.
Enable
Enable
Enable
Off
Vacuum Pump 1
Manual
Enable
Off
PSGA
Operating Manual
Permits automatic operation of the freeze dryer.
Manual
Off
Maintenance
Room Panel
View
Normal switch position. No action.
Forces PLC to reset all outputs and prevents both
manual and automatic operation of the freeze dryer.
Off
Process Room
Slave Panel
Advances the freeze drying cycle to the next step.
Off
Off
Condenser
Cooling Control
Normal switch position. No action.
Step Advance
Off
Description
Places the freeze drying cycle on hold.
Normal switch position. No action.
Permits manual adjustment of condenser coil
temperature setpoint if:
Chamber/Condenser drain is not active.
Condenser aeration is not active.
Condenser set point is entered on manual controls
screen.
Normal switch position. No action.
Enables the process room slave panel if the
maintenance room Panel View is inactive.
Disables the process room slave panel.
Enables the maintenance room Panel View if the
process room slave panel is inactive.
Disables the maintenance room Panel View.
Starts vacuum pump 1.
Stops vacuum pump 1 after completing automatic
cooling and purging.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
27/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.5: PC Pushbuttons and PC Manual Controls (continued)
Pushbutton
Vacuum Pump 1
Isolation Valve
Vacuum Pump 2
Mode
Manual
Manual
Position
Enable
Close
Normal switch position. No action.
Enable
Starts vacuum pump 2.
Off
Vacuum Pump 2
Isolation Valve
Booster Pump 1
Manual
Manual
Manual
Clean Dry
Process Air /
Sterile N2 Select
Main Vacuum
Valve
Main Isolation
Valve
Manual
Manual
28/143
SC473501.doc
Stops vacuum pump 2 after completing automatic
cooling and purging.
Enable
Opens isolation valve, following a five second delay,
when vacuum pump 2 is running.
Close
Normal switch position. No action.
Enable
Starts booster pump 1.
Off
Booster Pump 2
Description
Opens isolation valve, following a five second delay,
when vacuum pump 1 is running.
Enable
Normal switch position. No action.
Starts booster pump 2.
Off
Normal switch position. No action.
Off
Normal switch position. No action.
Sterile N2
Selects sterile nitrogen for gas bleed for functions
such as vacuum control, aeration, and pre-aeration.
Enable
Opens Main Vacuum valve if:
A vacuum pump is running and its isolation valve is
open.
Condenser cooling is active.
The rear access door is closed.
Chamber and/or condenser drain is not active.
Condenser aeration is not active.
Main Isolation valve is open.
Close
Closes Main Vacuum valve.
Enable
Opens Main Isolation valve if:
Rear access door is closed.
Chamber and/or condenser aeration or pre-aeration is
not active.
Chamber and condenser drains are not active.
Close
Closes Main Isolation valve.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.5: PC Pushbuttons and PC Manual Controls (continued)
Pushbutton
Chamber
Pre-aeration
Mode
Manual
Position
Pre-Aerate
Off
Chamber
Aeration
Manual
Aerate
Off
Condenser
Aeration
Manual
Enable
Off
Condenser Drain
Manual
Enable
Off
Description
Pre-aerates the chamber to the pre-aeration setpoint
entered on the Manual Control screen if:
Rear access door and slot door are closed.
Main Isolation valve is closed.
Chamber drain is not active.
Main Vacuum valve is closed.
De-activates pre-aeration.
Aerates chamber to the aeration setpoint and
continues until the aeration timer expires if:
Rear access door and slot door are closed.
Main Isolation valve is closed.
Chamber drain is not active.
Main vacuum valve is closed.
De-activates aeration.
Aerates condenser until the aeration timer expires.
Aeration only occurs if:
Main isolation valve is closed.
Main vacuum valve is closed.
Condenser drain is not active.
Condenser cooling is not active.
De-activates aeration.
Aerates condenser until the aeration timer expires.
Once aerated, the drain valve opens and remains
open until the function is deactivated. Condenser
drain only occurs if:
Main Isolation valve is closed.
Main Vacuum valve is closed.
Condenser aeration is not active.
Condenser cooling is not active.
De-activates condenser drain.
In addition to pushbutton controls, the Manual Controls screen provides an operator interface for
adjusting process setpoints. These functions are available only when automatic cycles are not in
progress. When an automatic cycle is active, the MANUAL select button on the menu is not visible
(indicating the selection is unavailable).
Use the Manual Controls screen to enter setpoints for various control functions as indicated in the
table below. To activate a specific function, position the cursor over the function and press the left
control button on the mouse. A virtual keypad will appear permitting entry of the required setpoints.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
29/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Table 3.6: Manual Setpoint Functions
Setpoint
Shelf Temperature
Setpoint
Mode
Manual
Description
When shelf temperature control is active, the shelves are
controlled to this set point. (-60°C to +70°C)
Chamber Vacuum
Setpoint
Manual
When vacuum control is active, the vacuum can be controlled to
an operator-specified set point. (0 to 1000 µBar)
Pre-Aeration Setpoint
Manual
Provides pre-aeration setpoint for manual and automatic preaeration cycles.
Stoppering Pressure
Setpoint
Manual
Provides stoppering pressure set point in an automatic
stoppering step. (0.0 to 98.0 kPa)
Condenser Temperature
Setpoint
Manual
When condenser temperature control is active, controls
condenser inlet coil temperature to this set point. (-50 to -75°C)
3.4
Automatic Controls
Automatic controls are a function of the Operator Interface program on the freeze dryer PC. The
program is divided into functionally related screens. Each screen is divided into three parts: header,
screen, and footer. The header and footer present status data, general information and on-screen
pushbuttons to aid with system navigation. Select a button for access to the desired control/function
area. To exit, select another option from the menu.
Note:
3.4.1
The user’s security level dictates which buttons are presented in the menu. Refer
to Security Screen for additional details.
Header
Figure 3.4: Screen Header
The top of each screen is divided into ten fields, grouped to form a header. Header fields are
described below:
•
Date and Time - Select this field to modify operating system date and time. The date and time
should only be modified when the system is idle (when data collection is not critical). After
modifying the date, iFIX must be shut down and then restarted in order for historical collection to
work properly.
•
Help - Select the Help button to open the help menu for the screen indicated in the screen title
field.
•
Print - Select the Print button to send the active screen to the printer.
30/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
The remaining fields in the header contain the following information:
•
BOC Logo Field.
•
PLC Status Indicator - This field is blank unless there is a PLC communication error or PLC fault
for the selected unit. The box is green when the PLC is communicating; FAULT appears on a red
background for PLC faults; COMM appears on a yellow background to indicate a PLC
communication failure.
•
Screen Title - This field identifies the screen being displayed.
•
Selected Unit - This field identifies the selected freeze dryer by name (for example, FD1) in
systems with more than one freeze dryer.
3.4.2
Footer
The bottom of each screen contains a footer. The footer contains alarm information, cycle status and
data, and buttons for navigation to other screens.
Figure 3.5: Footer
Functions available from the footer include:
•
Last Alarm in Queue - The last active alarm is displayed at the top of the footer. A new alarm
message will flash until the alarm is acknowledged from the Alarm screen. Selecting the alarm
message will call up the alarm screen.
•
Login/Logout - Select to open the Login dialog box.
•
Navigate - Select to view the Main Menu. The main menu can have up to 20 selections. Several
of these selections open submenus with additional choices. The button is disabled while the iFIX
database is loading, during critical scripts (for example, recipe loading), and during PLC
communication errors and faults.
•
Exit - Select to exit the Operator Interface program and return to the operating system.
The status area below the alarm message in the footer presents the following information:
•
Name - If a cycle is running on the selected freeze dryer, the name of the cycle (for example,
Freeze Drying Cycle) is displayed.
•
Message - When a cycle is running on the selected freeze dryer, the name of the step or phase in
progress is displayed.
•
Cycle Elapse Time - The cycle elapse time for the active cycle is displayed.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
31/143
SC473501.doc
BOC EDWARDS
•
BOC Edwards
Pharmaceutical Systems
Time Remaining - The time remaining for phases within the active cycle is displayed.
3.4.3
Login / Logout Dialog
Select the Login / Logout button in the footer to display the Login dialog box. If a user is currently
logged into the system, their name will appear in the name field. To continue logging in, the first user
must log out. Type your user name and password in the designated fields and click on the Login Key
to complete the function. The Login dialog box has the following functions / features:
•
Name - User name field. Displays name of current user. Place the cursor in this field and enter
your name using the keyboard.
•
Password - Password field. Place the cursor in this field to enter the password associated with
the user name. Disabled for current user.
•
Login - Place the cursor over the button and click to Login.
•
Logout - Place the cursor over the button and click to Logout.
•
Change Password - Permits password modification for the user currently logged in to the system.
•
Exit - Select exit to close the form.
Figure 3.6: Login/Logout Keypad
32/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
3.4.4
Navigate
Select the Navigate button to access the desired control/function area. Some functions in the main
menu provide access to multiple functions in the form of a sub-menu. Others immediately open the
associated function screen. To exit the current screen, select another option from the menu. The
following tables describe the function of each button in the menus.
Table 3.7: Main Menu Navigation Functions
Button
Function
Overview
Displays the General Overview screen.
Unit Graphic
Displays the Unit Graphic screen for the selected machine.
Recipe
Opens the Recipe submenu.
Error Recovery
Displays the Error Recovery screen for the selected machine.
Manual Controls
Displays the Manual Controls screen for the selected machine.
Alarms
Displays the Alarm screen for the system.
Trends
Displays the Historical Trending screen for the selected machine.
Maintenance
Opens the Maintenance submenu.
Batch Record
Display the Batcher screen for the system.
Engineering Parameters
Opens the Engineering Parameters submenu.
Security
Displays the iFIX security configuration utility.
Table 3.8: Recipe Sub-Menu Functions
Button
Function
Freeze Drying
Displays the freeze drying recipe screen for the selected freeze dryer.
Defrost
Displays the defrost recipe screen for the selected freeze dryer.
CIP
Displays the CIP recipe screen for the selected freeze dryer.
SIP
Displays the SIP recipe screen for the selected freeze dryer.
Leak Test
Displays the leak test recipe screen for the selected freeze dryer.
Shelf Ram Bellows Test
Displays shelf ram bellows test recipe screen for the selected freeze dryer.
Main Isolation Valve
Bellows Test
Displays main isolation valve bellows test recipe screen for the selected freeze
dryer.
Filter Integrity Test
Displays the filter integrity test recipe screen for the selected freeze dryer.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
33/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Table 3.9: Maintenance Sub-Menu Functions
Button
Function
Maintenance
Displays the maintenance screen for the selected freeze dryer.
Control Loops
Displays the control loops screen for the selected freeze dryer.
Calibration
Displays the calibration screen for the selected freeze dryer.
Shelf Positioning
Displays the shelf positioning screen for the selected freeze dryer.
Digital Input
Displays the digital input screen for the selected freeze dryer.
Table 3.10: Engineering Parameters Sub-Menu Functions
Button
Function
System Parameters
Displays the System Parameters screen for the selected freeze dryer.
Freeze Drying
Displays the freeze drying engineering parameters screen for the selected
freeze dryer.
Defrost
Displays defrost engineering parameters screen for the selected freeze dryer.
CIP
Displays the CIP engineering parameters screen for the selected freeze dryer.
SIP
Displays the SIP engineering parameters screen for the selected freeze dryer.
Leak Test
Displays the leak test engineering parameters screen for the selected freeze
dryer.
Shelf Ram Bellows Test
Displays the shelf ram bellows test engineering parameters screen for the
selected freeze dryer.
Filter Integrity Test
Displays the filter integrity test engineering parameters screen for the selected
freeze dryer.
34/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
3.4.5
General Overview Screen
Select the Overview button on the Main Menu screen to display the General Overview Screen. The
General Overview screen presents freeze dryer status information in a read-only format.
Figure 3.7: General Overview Screen
The following information is displayed on the General Overview Screen.
•
Freeze Dryer Mode - Indicates the freeze dryer operating mode: “Auto,” “Manual,” or “Off.”
•
PLC Comm. Status - Indicates the current communication status between the PC and PLC.
•
PLC Fault Status - Indicates PLC fault status.
•
Active Cycle - Indicates the name of the active cycle (for example, Freeze Drying Cycle).
•
Active Cycle Status - This is the status of the active cycle. If no cycle is active, the cycle status
will not be displayed.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
35/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
•
Active Cycle Phase Message - Indicates the name of the step or phase in progress when a cycle
is running. If no cycle is active, the phase message will not be displayed.
•
Active Recipe - This is the recipe name of the active cycle (only applicable to freeze drying). If
freeze drying is not active, the recipe name will not be displayed.
•
Active Batch Name - This is the batch name of the active cycle. If no cycle is active, the batch
name will not be displayed.
3.4.6
Unit Graphic Screen
Select the Unit Graphic button on the Main Menu screen to display the Unit Graphic Screen. The
screen is a graphic representation of freeze dryer system components including cycle status
information and critical process values. The Status Screen uses both numerical data and color to
indicate component status. Device identifiers appear for all valves, pumps, motors and other devices.
Table 3.11: Screen Color Assignments
Components /
Color
Cycles
Motors
Green
Gray
Red
Flashing Red
Valves
Green
Gray
Red
Flashing Red
Chamber Door White
Gray
Green
Flashing Red
Flashing Yellow
Yellow
Loading Door
White
Gray
Green
Flashing Blue
Red
Yellow
Lines and
Orange
Piping
Light Green
Magenta
Dark Blue
Light Blue
Medium Blue
36/143
SC473501.doc
Status Indication
Motor On
Motor Off
Active Acknowledged Alarm
Unacknowledged Alarm
Valve Open
Valve Closed
Active Acknowledged Alarm - Actuator shows current valve state
Unacknowledged Alarm
Door Open
Door Closed
Door Closed and Locked
Locked and Unlocked - Error state, limit switch failure
Neither Locked nor Unlocked - Warning, changing state
Door Open and Locked
Fully Open
Door Closed
Door Closed and Gasket Pressurized
Neither Open nor Closed - changing state
Fully Open and Closed
Fully Open / Not Closed and Gasket Pressurized - Warning
Indicates steam lines.
Indicates air and nitrogen lines.
Indicates silicone oil lines.
Indicates refrigerant lines.
Indicates cooling water lines.
Indicates water and condensate lines.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Buttons on the Unit Graphic screen open pop-up windows presenting additional information.
Depending on the configuration of the freeze dryer, any or all of the following buttons may be included
on the Unit Graphic.
•
Compressors Detail
•
Filter Detail
•
Drain Detail
•
Condenser Cooling Detail
Figure 3.8: Unit Graphic Screen
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
37/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
3.4.7
Freeze Drying Recipe Screen
Select the Recipe button from the Navigate menu to display the Recipe Screen. A recipe is
composed of values placed in the recipe step table, general parameter table, and information placed
in the Product Notes. If a recipe is already loaded, it will be displayed when Recipe is selected. A
displayed recipe is either on-line or off-line. A recipe that is on-line will be displayed on PC and
loaded into the PLC. If the recipe is off-line, it is loaded on the PC only. Recipes are initially created
off-line and saved using the Save Recipe button.
Recipes are presented in a tabular format on the screen. From here, an operator may add, change,
or delete steps in the recipe. Functions that may be added to the recipe include:
•
Loading
•
Pressure Rise Test (Moisture Test)
•
Freezing
•
Aeration and Pre-aeration
•
Evacuation
•
Stoppering
•
Drying
•
Storage / Unloading
Figure 3.9: Example Freeze Drying Recipe Screen
38/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
The following steps are independent cycles and cannot be inserted in, or attached to, a standard
freeze drying cycle:
•
Clean in Place (CIP)
•
Shelf Ram Bellows Test
•
Sterilization (SIP)
•
Defrost
•
Main Isolation Valve Bellows Test
•
Leak Test
•
Filter Integrity Test
The following functions may be accessed from the Freeze Drying Recipe screen. Some functions
require an electronic signature before being implemented. Refer to Electronic Signatures for more
information.
•
Go Offline/Online - When “Go Offline” is selected, the text above the recipe table changes to
“Offline” and the recipe in view is offline (values are read from / written to the hard drive). When
Go Offline is selected for the first time, the recipe table is cleared out and the general recipe
parameters are set to their default values. Use caution when selecting Go Offline from a view
node (if applicable). Entering offline mode from the view node (if applicable) can wipe out an
unsaved recipe on the SCADA node. When “Go Online” is selected, the text above the recipe
table changes to “Online” and the recipe in view is online (values are read from / written to the
PLC). Online mode is the default mode when entering the freeze drying recipe screen.
•
Product Notes - Selecting the “Product Notes” button will display the Product Notes pop-up
window.
•
Start Cycle - This selection will start the cycle as long as the batch name is not blank and no
cycle interlocks exist. Examples of cycle interlocks are: incorrect device states, active alarms, no
recipe downloaded (if applicable), and setup parameters not confirmed (if applicable). The user
will be prompted for cycle start confirmation.
•
Abort Cycle - This selection will abort the active cycle. The system prompts for confirmation of
this action prior to initiating the abort.
•
Setup Param. - Select to display the Freeze Drying Setup Parameters screen.
•
New Recipe - When “New Recipe” is selected, the recipe table is cleared. The user will be
warned that the current recipe values will be erased. This selection is only available in offline
mode.
•
Save Recipe – When “Save recipe” is selected, the current recipe is checked for step type
restrictions and, if properly constructed, saved to the hard drive.
•
Save Recipe As - When “Save Recipe As..” is selected, the current recipe is checked for step
type restrictions and, if the recipe is constructed properly, the recipe will be saved to the hard drive
under a new name. The user will be prompted for the recipe name. If the recipe already exists,
the user will be prompted to overwrite the existing recipe. After the recipe save attempt is
complete, the results will be displayed to the user. “Save Recipe As..” cannot be selected when a
freeze drying cycle is active because the original downloaded recipe name would be overwritten..
•
Load Recipe - This selection will call up a list of recipes to load. The user will be warned that the
current recipe values will be erased. After loading the recipe, the recipe builder will perform a
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
39/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
verification test to ensure that the recipe has been properly loaded. After the recipe load attempt
is complete, the results will be displayed to the user
•
Delete Recipe - This selection presents a list of recipes that may be selected for deletion.
•
Backup Recipe – This selection opens the Backup Recipe User Form pop-up window. The user
can select a recipe to copy.
•
Parameter modification - Edit the step parameters / general recipe parameters. Note that if any
parameters for the active step are changed the step starts over.
•
Scroll buttons - Scroll the recipe step table right / left and up / down to view up to 50 steps with a
maximum of 15 parameters each. Scroll the general recipe parameter table right / left to view up
to 20 parameters.
•
Select/Deselect Hold - Place cycle in hold or release a cycle from hold.
•
Step Advance - Advance the cycle to the next step.
Other functions available from the Freeze Drying Recipe screen include:
•
“+” Key – Use this button to add or modify a recipe step. When pressed, the Recipe Step
Selection pop-up window opens. This selection is only available in offline mode.
•
“-” Key – Select this key to delete a recipe step. This selection is only available in offline mode.
•
“>” Key – Select this key to insert a blank recipe step. This selection is only available in offline
mode.
The following information is presented on the Recipe screen:
•
Recipe Name - This is the name of the current recipe.
•
Cycle Status - The cycle status message (Ready, Running, Held, Done, Interlocked, or Aborted) is
displayed on the recipe screen. The status of the cycle is only visible in online mode.
•
Downloading to PLC – This message appears when the recipe is being loaded.
•
Reload Recipe - This message is visible when a recipe has not been downloaded to the PLC. The
message is only visible in online mode.
•
Batch Name - The batch name of the cycle is only visible in online mode. The batch name can be
edited. The batch name can be any combination of alphabetic or numeric characters (no spaces,
punctuation, or special characters are permitted).
•
Online / Offline Status - Indicates mode for the recipe being viewed.
•
Highlight Active Step – The box containing the active step in the table is highlighted in green.
Recipes for the freeze dryer are stored in the PC where they are created. Recipes may be edited
using the Recipe Screen and related functions. Columns in the recipe table permit entry of STEP,
TEMP., PRES., and TIME. Recipe parameters and associated limits and default values are shown in
the following tables.
40/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.12: Recipe Configuration
Step Type Name
Loading
Freezing
Evacuation
Drying
Pressure Rise Test
Aeration
Stoppering
Storage/Unloading
Step #
1
2 to 9
10 to 15
1
2
3
4 to 7
8 to 15
1
2
3
4
5 to 8
9 to 15
1
2
3
4
5 to 9
10 to 15
1
2
3
4
5 to 15
1
2
3
4
5 to 15
1
2
3
4 to 15
1
2 to 3
4 to 15
Parameters
Shelf temperature
Reserved
Not used
Shelf temperature
Not used
Step time
Reserved
Not used
Shelf temperature
Chamber vacuum
Reserved
Condenser temperature
Reserved
Not used
Shelf temperature
Chamber vacuum
Step time
Condenser temperature
Reserved
Not used
Pressure rise
Test time
Test repeat time
Reserved
Not used
Gas (0 = nitrogen, 1=air)
Pressure
Aeration time
Reserved
Not used
Ram pressure
Reserved
Stoppering dwell time
Not used
Shelf temperature
Reserved
Not used
Low
-60.0
High
70.0
Default
-60.0
Units
°C
-60.0
70.0
-60.0
°C
00:00
99:59
00:01
HH:MM
-60.0
1
70.0
1000
-60.0
1
°C
µBar
-72.0
-50.0
-50.0
°C
-60
1
00:00
-72.0
70
1000
99:59
-50.0
-60
1
00:01
-50.0
°C
µBar
HH:MM
°C
1
1
1
100
30
99
1
1
1
µBar
sec
min
0
0.0
0
1
1.07
300
1
1.01
0
BarA
sec
17.0
97.0
52.0
BarG
1
60
30
sec
-60.0
70.0
22.0
°C
Units
µBar
µBar
Table 3.13: General Recipe Parameters
Par #
1
2
3
4
Parameter
Pressure deviation sp.
Product protection alm. Sp.
Reserved
Vac. cntr. (0 = N2; 1 = Air)
PSGA
Operating Manual
Low
1
1
High
500
1000
Default
50
500
0
1
0
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
41/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
3.4.8
Optional Cycle Recipe Screens
Select the Recipe button from the Main menu to display the Recipe sub menu and the following
optional cycle recipes:
•
Defrost
•
Leak Test
•
Defrost Decontamination
•
Shelf Ram Bellows Test
•
CIP
•
Main Isolation Valve Bellows Test
•
SIP
•
Filter Integrity Test
Figure 3.10: Typical Optional Cycle Recipe Screen
The following functions may be accessed from a typical Optional Cycle Recipe screen. Some
functions require an electronic signature before being implemented. Refer to Electronic Signatures for
more information.
•
Start Cycle - This selection will start the cycle as long as the batch name is not blank and no
cycle interlocks exist. Examples of cycle interlocks are: incorrect device states, active alarms,
42/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
cycle reset not selected, and setup parameters not confirmed (if applicable). The user will be
prompted for cycle start confirmation
•
Abort Cycle - This selection aborts the active cycle. The user is prompted for confirmation.
•
Cycle status - This is the status of the cycle.
•
Batch name - The batch name can be edited by the user. Selecting this field displays the
alphanumeric entry keypad. The batch name cannot contain any of the following characters:
space, exclamation mark (!), @, $, asterisk (*), (, ), [, ], {, }, |, \, colon (:), semi-colon (;),doublequotes ("), single-quotes ('), comma (,), <, period (.), >, /, ?.
•
Cycle Reset - Resets the done / aborted cycle status to ready / interlocked.
•
Recipe Parameters – Refer to the following tables for cycle-specific parameters.
•
Setup Parameters (Analog / Alphanumeric Values) - Use this function to enter pre-cycle start
values (non-recipe values).
•
Setup Parameters (Check Boxes) - Use this function to complete a pre-cycle start checklist.
When an item is selected (checked), a message is sent to the audit trail.
•
Confirm Setup Parameters - Select this check box when the all of the setup parameters have
been entered and the pre-cycle start checklist has been completed.
•
Retry – Leak Test Only. Restarts leak test if test fails.
Refer to the following tables for specific recipe screen parameters.
Table 3.14: Defrost Recipe Screen Parameters
Par #
1
2
3 to 5
6
7and 8
9 to 100
Parameter
Low
High
Default
Units
1
60
10
min
Units
sec
sec
Reserved
Defrost time
Reserved
Not used
Reserved
Not used
Table 3.15: CIP Recipe Screen Parameters
Par #
1
2
3 and 4
5
6
7 and 8
9
10 to 15
16
17 to 20
21 to 100
Parameter
Chamber wash time
Cond. wash time
Reserved
Wash cycles
Shelf ram cycles
Reserved
Dry time
Reserved
CIP fluid type (0 = WFI; 1 = Det.)
Reserved
Not used
PSGA
Operating Manual
Low
30
0
High
600
600
Default
120
30
1
1
10
3
1
1
0
120
30
0
1
0
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
min
43/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.16: SIP Recipe Screen Parameters
Par #
1
2
3
4
5 to 11
12
13 to 19
20 to 100
Parameter
Reserved
Steriliz. Exposure time
Sterilization temperature
Sterilization pressure
Reserved
Not used
Reserved
Not used
Low
High
Default
Units
30
110.0
2.00
120
127.0
2.70
30
121.0
2.34
min
°C
BarA
Table 3.17: Leak Test Recipe Screen Parameters
Par #
1
2 and 3
4
5 to 7
8 to 100
Parameter
Leak pressure
Reserved
Leak test time
Reserved
Not used
Low
1
High
100
Default
100
Units
µBar
0
480
60
min
Table 3.18: Shelf Ram Bellows Test Recipe Screen Parameters
Par #
1
2
3
4 to 100
Parameter
Test pressure
Pumpdown time
Reserved
Not used
Low
0
1
High
200
60
Default
100
10
Units
µBar
min
Table 3.19: Main Isolation Valve Bellows Test Recipe Screen Parameters
Par #
1
2
3 to 100
Parameter
Test pressure (µBar)
Pumpdown time (min)
Not used
Low
0
1
High
200
60
Default
100
10
Units
µBar
min
Table 3.20: Filter Integrity Test Recipe Screen Parameters
Par #
1
2
3
4
5 to 6
7
8
9
10 to 12
13
14 to 15
16 to 100
Parameter
Filter test (1=F1,2=F2)
Filter drying time
Not used
Filter flood time
Reserved
Not used
Reserved
Not used
Reserved
Not used
Reserved
Not used
44/143
SC473501.doc
Low
1
0
High
2
120
Default
1
15
Units
10
60
30
sec
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
min
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
3.4.9
Engineering Parameter Screens
Select the Engineering Parameters button from the Main menu to display the Engineering Parameters
sub menu and the following functions:
•
Freeze Drying
•
SIP
•
Defrost
•
Leak Test
•
Defrost Decontamination
•
Shelf Ram Bellows test
•
CIP
•
Filter Integrity Test
Figure 3.11: Typical Engineering Parameter Screen
Engineering Parameter screens permit modification of set points for specific cycles on the selected
freeze dryer. See the following tables for a complete list of cycles and associated parameters. The
following information is presented on the Engineering Parameters screen.
•
Parameter Name - Each screen contains a list of associated parameters.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
45/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
•
Parameter Set Point - Parameter set points are listed following each parameter.
Point and click on a parameter set point to open the Data Entry pop-up window. The Data Entry
window presents the set point and high / low limits for the selected parameter. Clear the existing
value and enter a new value for the set point or select cancel to return to the Engineering Parameters
screen without changing the set point.
Table 3.21: Freeze Drying Engineering Parameters
Par #
1
2
3
4
5
6
7
8
9 to 14
15
16
17
18 to 100
Parameter
Max. ramping shelf temp. dev.
Max. step end shelf temp. dev.
Reserved
Max. cond. Temp deviation
Max. time to reach cond. tmp.
Step end low vacuum dev.
Step end high vacuum dev.
Max. time to reach evac. Prs.
Reserved
Product protection temperature
Low vacuum alarm deviation
Shelf ram to load/unload first
Not used
Low
1.0
1.0
High
10.0
5.0
Default
4.0
1.0
Units
°C
°C
5.0
10
5
5
10
25.0
120
500
500
120
10.0
30
50
20
30
°C
min
µBar
µBar
min
-70.0
5
1
60.0
500
2
-70.0
150
1
°C
µBar
Table 3.22: Defrost Engineering Parameters
Par #
1
2
3
4
5
6
7
8
9 to 100
Parameter
Defrost temperature
Reserved
Drying time
Defrost override time
Defrost drain time
Not used
Steam pressure high limit
Steam pressure low limit
Not used
Low
30.0
High
90.0
Default
50.0
Units
°C
0
20
0
120
120
20
30
90
5
min
min
min
0.99
0.90
1.10
0.99
1.05
0.99
BarA
BarA
Table 3.23: CIP Engineering Parameters
Par #
1 to 11
12
13
14
15
16
17
18 to 20
21
22 to 100
Parameter
Not used
Shelf ram position 1
Shelf ram position 2
Drain time between manifolds
Final drain time
Reserved
Fill level
Reserved
Clean dry air purge time
[Not used
46/143
SC473501.doc
Low
High
Default
Units
0
0
0
0
3276.7
3276.7
600
10
1550.0
1550.0
30
5
mm
mm
sec
min
0
120
60
IWC
0
300
60
sec
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.24: SIP Engineering Parameters
Par #
1
2 to 4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23 to 100
Parameter
Accum. Lethality setpoint.
Reserved
Number of purges
Pre-evacuation pressure
Steam discharge pressure
Steam purge pressure
Max. time to reach evac. sp.
Max. time to reach temp. sp.
Maximum time below setpoint
Not used
Sterilization override time
Condenser cooling time
Reserved
Shelf cooling time
Shelf cooling temp. setpoint
Filter drying time
System drying time
Not used
Chamber jacket heat temp.
Chamber jacket cool temp.
Not used
Low
30
High
120
Default
30
Units
min
1
0.1
0.98
0.98
10
20
0
5
0.5
1.4
1.4
120
120
1800
3
0.20
1.05
1.05
30
60
900
Bar
BarA
BarA
min
min
sec
20
10
120
120
60
10
min
min
10
0.0
10
20
120
30.0
120
120
10
15.0
10
30
min
°C
min
min
50.0
10.0
65.0
20.0
55.0
15.0
°C
°C
Table 3.25: Leak Test Engineering Parameters
Par #
1
2
3
4 to 5
6
7
8 to 100
Parameter
Reserved
Drying pressure
Drying time
Reserved
Allow repeat test on fail
Max. time to reach dry. Pres.
Not used
Low
High
Default
Units
0
0
1000
120
100
60
µBar
0
20
10
120
3
60
repeats
min
Table 3.26: Shelf Ram Bellows Test Parameters
Par #
1
2
3
3
5 to 100
Parameter
Reserved
Reserved
Shelf ram 1 test position
Shelf ram 2 test position
Not used
PSGA
Operating Manual
Low
High
Default
Units
0.0
0.0
3276.7
3276.7
1550.0
1550.0
mm
mm
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
47/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.27: Filter Integrity Test Engineering Parameters
Par #
1 to 4
5
6
7
8
9
10
11
12
13
14
15
16 to 100
3.4.10
Parameter
Reserved
Stabilization time
Drain time
Not used
Filter test time
Not used
WFI water temperature
Maximum test pressure
Available pressure drop
Not used
WFI tank drain time
Drying medium (0 = N2; 1 = Air)
Not used
Low
High
Default
Units
10
1
15
30
12
60
min
min
5
10
7
19.0
0.0
0.0
25.0
2.5
2.5
20.0
1.5
1.5
°C
BarG
BarG
10
0
30
1
15
1
min
System Parameter Screen
Figure 3.12: Example System Parameter Screen
48/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
The following table contains the engineering parameter configuration for this control system.
Par #
1
2
3
4
5
6
Parameter and units
Chamber aeration setpoint
Chamber aeration time
Condenser aeration setpoint
Condenser aeration time
Condenser freeze time
Condenser freeze temperature
Low
0.90
0
0.90
0
0
-70.0
High
1.05
300
1.05
300
30
-40.0
Default
0.98
60
0.98
60
10
-40.0
Units
BarA
sec
BarA
sec
min
°C
Note: Parameters 7 to 100 are either Reserved or Not used, or can be modified by BOC Edwards
Pharmaceutical Systems only.
3.4.11
Error Recovery Screen
This screen lists loading and unloading system errors, and the operator actions for resetting or
clearing the conditions. In the event that an error occurs during automatic loading and unloading
steps, operator intervention will be required.
Figure 3.13: Error Recovery Screen
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
49/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
The following functions may be accessed from the Error Recovery screen. Some functions require an
electronic signature before being implemented. Refer to Electronic Signatures for more information.
•
Load / Unload Hold - Use this function to place loading / unloading in hold following a load or
unload step error. Loading / unloading must be on hold before any error recovery function can be
performed.
•
Load / Unload Step Restart - Use this function to take loading / unloading out of hold mode.
•
Number of Shelves to Load - The screen displays the current setpoint for the number of freeze
dryer shelves to be loaded.
•
Number of Shelves to Load / Apply - Use this function to change the number of shelves to be
loaded (minimum = 1 shelf; maximum and default = 8 (for 120 mm inter-distance) and 16 (for 240
mm inter-distance). Select “Apply“ to enter and use the new value.
•
Force Load / Unload Complete - Use this function to set the number of shelves to load / unload
to the current number of shelves loaded in the freeze dryer.
•
Shelf Index Incomplete - Use this function to reposition the current shelf by re-indexing the shelf
ram to the shelf setpoint.
•
Index Shelf Up / Down - Use this function to index the shelves to the next loading / unloading
position.
•
Open / Close Loading Door - Use this function to open / close the loading door during error
recovery.
The following information is presented on the Error Recovery screen.
•
Number of Shelves Loaded / Unloaded - The screen presents data on the current number of
shelves loaded / unloaded.
•
Current Shelf Position - The current shelf position is displayed.
•
Loading Door Fully Open / Closed Messages - When the loading door is fully open or closed, a
message will be displayed on the right-hand side of the screen.
3.4.12
Manual Controls Screen
The Manual Controls screen permits manual control of freeze dryer components and functions
including setting and adjusting setpoints. Refer to PC Manual Controls in Section 3.3 for a description
of functions and setpoints.
Note:
This screen permits operation of freeze dryer components without using a recipe
for control.
50/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Figure 3.14: Manual Controls Screen
3.4.13
Alarm Screen
The system continuously monitors those freeze dryer parameters for which alarm setpoints are
defined. When one of these parameters falls outside designated limits (setpoints), an alarm message
is displayed on the Alarm screen.
Under normal or non-alarm conditions, the screen displays no alarms. When an alarm occurs, date,
time, value, tag name, alarm status (OK or ALARM) and description appears on a line. A new or
unacknowledged alarm will flash in the alarm summary display. This alerts the operator that a new
alarm occurred and must be acknowledged. The alarm indicator then flashes again when a new
alarm condition occurs. Alarms are only acknowledged on the Alarm Screen.
The following functions may be accessed from the Alarm screen.
•
Priority Filter – Use this function to filter alarms/messages by priority (for example, messages low priority, alarms - high priority)
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
51/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
•
Acknowledge One - Use this function to acknowledge the selected alarm/message in the alarm
summary display.
•
Acknowledge Page - Use this function to acknowledge all alarms/messages in the view.
•
Sort - Use this function to sort alarms/messages by the date or tag name column headings on the
alarm summary display.
•
Delete Alarms - Use this function to open the alarm/message table pop-up window. Select an
alarm table to delete from the list presented in the pop-up. To delete alarms only during a
specified period, select the tab and define the start and end dates. The system prompts for
confirmation prior to deleting the table.
•
Alarm buttons - The buttons on the bottom of the alarm screen enable pump resets and other
auxiliary functions. The buttons become enabled (selectable) when the process allows and/or
requires selection.
Figure 3.15: Example Alarms Screen
The following information is presented on the Alarm screen.
52/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
•
Alarm Summary - The alarm/message summary presents the date, time, value, tag name,
alarm/message status, acknowledgement status and description of the all active/unacknowledged
alarms/messages. Unacknowledged alarms/messages will blink in the alarm summary display.
An alarm/message is removed from the alarm summary display when it is acknowledged and the
status of the alarm is OK. Alarms/messages can be individually acknowledged by selecting the
alarm/message, then clicking the Acknowledge One button. Color is used in the display to
indicate status as shown in the table below.
Table 3.28: Alarm/Message Color
Color
White Text
Blue Text
Green Text
Gray Background
Light Blue Background
Red Background
Status
Unacknowledged Alarm / Message
Communication Alarm / Message
Unacknowledged Alarm / Message is OK
Low Priority Alarm/Message (cycle passed / aborted / held / step advanced /
step complete, maintenance messages)
Medium Priority Alarm / Message (device failures)
High Priority Alarm / Message (process / safety alarms)
Table 3.29: Alarms and Messages
Description
Alarm Enable Turned Off
Auto Cycle Abort
Booster Pump #1 Fail
Booster Pump #2 Fail
Chamber CIP Manifold Valve #1 Failed To Open
Chamber CIP Manifold Valve#2 Failed To Open
Chamber Not Sterile
Chamber Press >= Maximum Safety
Chamber Pressure Probe Fail
Chamber Vacuum Back Up Probe Fail.
Chamber Vacuum Probe Fail
CIP Circulation Pump Fail
CIP Pump Drain Valve Failed To Open
CIP Recirculation Level Transmitter Fail
CIP Return Valve Failed To Open
CIP Return/Drain Valve Failed To Open
CIP Water Supply Pressure Low
CIP Water Supply Valve Failed To Open
Clean Dry Process Air Supply Valve Failed To
Open
Clean Dry Process Air/Gas Isolation Valve Failed
To Open
Clean In Place Failed
Communication Failure Between PC And PLC
PSGA
Operating Manual
Cause
Alarm horn disabled.
Abort button selected while recipe is running
Booster pump over current
Booster pump over current
Valve failed to open/close in 10 seconds.
Valve failed to open in 10 seconds.
Time interval between the completion of SIP cycle and
the next Freeze Drying cycle is longer than the
specified time limit.
Chamber pressure > 2.75 BarA.
Probe failed.
Chamber vacuum back up probe.
Chamber Vacuum probe.
CIP circulation pump over-current.
Valve failed to open in 10 seconds.
The level transmitter to monitor the CIP recirculation
water level failed.
Valve failed to open in 10 seconds.
Valve failed to open in 10 seconds.
Low CIP water pressure.
Valve failed to open in 10 seconds.
Valve failed to open in 10 seconds.
Valve failed to open in 10 seconds.
Did not complete all the wash and rinse cycles.
Communication between PC and PLC failed to occur.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
53/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.29: Alarms and Messages (continued)
Description
Communication With AV-LUS Failed
Compressed Air Low Pressure
Compressor #1 Fail
Compressor #1 High Pressure
Compressor #1 High Temperature
Compressor #1 Motor Cooling Water Fail
Compressor #2 Fail
Compressor #2 High Pressure
Compressor #2 High Temperature
Compressor #2 Motor Cooling Water Fail
Compressor #3 Fail
Compressor #3 High Pressure
Compressor #3 High Temperature
Compressor #3 Motor Cooling Water Fail
Compressor #4 Fail
Compressor #4 High Temperature
Compressor #4 Motor Cooling Water Fail
Compressor #4high Pressure
Compressor #5 Fail
Compressor #5 High Temperature
Compressor #5 Motor Cooling Water Fail
Compressor #5high Pressure
Condenser Circulation Pump #1 Fail
Condenser Circulation Pump #2 Fail
Condenser Drain Temperature Probe Fail
Condenser Drain Valve Failed To Open
Condenser Inlet Temperature Probe Fail
Condenser Inlet Valve Failed To Open
Condenser Press >= Maximum Safety
Condenser Pressure Probe Fail
Condenser Steam Valve Failed To Open
Control Power Reset Req’d @ Control Cabinet
Cooling Water Fail
Cycle Hold
Cycle Step Advance
Defrost Cycle Failed
Defrost Time Excessive
Emergency Stop Active.
Expansion Tank Blanket N2 Pressure High
Expansion Tank Blanket Sterile N2 Pressure Low
Expansion Tank Oil Level Low
54/143
SC473501.doc
Cause
Electrical/mechanical problems.
Air supply to skid is< 4 BarG.
Compressor PLC output on, but the input is NOT on.
The discharge pressure is >19.6 BarA.
Compressor windings over heated.
Compressor motor cooling water flow is not detecting
minimum required water flow after 30 seconds.
Compressor PLC output on, but the input is NOT on.
The discharge pressure is >19.6 BarA.
Compressor windings over heated.
Compressor motor cooling water flow is not detecting
minimum required water flow after 30 seconds.
Compressor PLC output on, but the input is NOT on.
The discharge pressure is >19.6 BarA.
Compressor windings over heated
Compressor motor cooling water flow is not detecting
minimum required water flow after 30 seconds.
Compressor PLC output on, but the input is NOT on.
Compressor windings over heated.
Compressor motor cooling water flow is not detecting
minimum required water flow after 30 seconds.
The discharge pressure is >19.6 BarA.
Compressor PLC output on, but the input is NOT on.
Compressor windings over heated.
Compressor motor cooling water flow is not detecting
minimum required water flow after 30 seconds.
The discharge pressure is >19.6 BarA.
Circulation pump over current.
Circulation pump over current.
RTD probe shorted or open circuit.
Valve failed to open in 10 seconds.
RTD probe shorted or open circuited.
Valve failed to open in 10 seconds.
Condenser pressure > 2.75 BarA.
Probe failed.
Valve failed to open in 10 seconds.
If an automatic cycle is not active and the push button
has been pushed in.
Cooling water pressure is < 1.75 BarG.
Cycle hold button selected by the operator at the PC
Step advance button selected by operator at the PC
Did not complete the steaming phase.
If the accumulated defrost time exceeds 90 minutes.
One of the emergency stops is pushed in.
Pressure more than the higher set point.
Pressure less than the lower set point.
Expansion tank level switch fail.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.29: Alarms and Messages (continued)
Description
Failed To Reach Evacuation Set Point
Filter integrity test, Filter #1 Passed.
Filter integrity test, Filter #2 Passed.
Gas Bleed Bypass Valve Failed To Open
Heater #1 Fail
Heater #2 Fail
Hydraulic Pump Fail
Hydraulic Pump Outlet Filter High Diff. Pressure
Invalid Batch Name
Jacket Circulation Pump Fail
Jacket Heater Fail.
Leak Test Failed
Leak Test Passed.
Liquid Ring Pump Evacuation Valve Failed To
Open
Liquid Ring Pump Fail
Liquid Ring Pump Low Water Supply
Liquid Ring Pump Over Temperature
Low Differential Pressure (Condenser Circulation
Pump #1)
Low Differential Pressure (Condenser Circulation
Pump#2)
Low Differential Pressure (Jacket Circulation).
Low Differential Pressure (Shelf Circulation Pump
#1)
Low Differential Pressure (Shelf Circulation Pump
#2)
Low Oil Temperature Compressor #2
Low Oil Temperature Compressor #3
Low Oil Temperature Compressor #4
Low Oil Temperature Compressor #5
Low Oil Temperature Compressor 1
Main Drain Bypass Valve Failed To Open
Main Drain Valve Failed To Open
Main Isolation Valve Bellows Pirani Gauge Fail
Main Isolation Valve Failed To Close
Main Isolation Valve Failed To Open
Main Vacuum Valve Failed To Open
Main Valve Bellows Test Failed
PSGA
Operating Manual
Cause
During SIP, if the evacuation set point has not been
reached within 30 minutes, during door locking or pre
purging evacuation.
Sterile Filter #1 passed the water intrusion test.
Sterile Filter #2 passed the water intrusion test.
Valve failed to open in 10 seconds.
Heater contactor failed to activate.
Heater contactor failed to activate.
Hydraulic pump over current.
Indicates that the pressure line filter is dirty and
should be replaced.
Number of characters more than allowed or previously
used batch name/number.
Circulation pump over current.
Heater contactor failed to activate.
When it fails to reach 100 microbars in 1 hour.
The system passed the leak test followed by an SIP
cycle.
Valve failed to open in 10 seconds.
Liquid ring pump over current
LRP #1 does not have an adequate water supply
LRP windings over heated
Low differential pressure when a circulation pump is
running.
Low differential pressure when a circulation pump is
running.
Low differential pressure when a circulation pump is
running.
Low differential pressure when a circulation pump is
running.
Low differential pressure when a circulation pump is
running.
Oil discharge temperature is below 40°C.
Oil discharge temperature is below 40°C.
Oil discharge temperature is below 40°C.
Oil discharge temperature is below 40°C.
Oil discharge temperature is below 40°C.
Valve failed to open in 10 seconds.
Valve failed to open in 10 seconds.
The Pirani gauge is sending a signal to the PLC of <
1.5 VDC.
Valve failed to close in 10 seconds.
Valve failed to open in 10 seconds.
Valve failed to open in 10 seconds.
Bellows vacuum failed to reach set point
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
55/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.29: Alarms and Messages (continued)
Description
Main Valve Bellows Test Passed
Over Pressure Hydraulic Pump
Pressure Rise Test Failed
Pressure Rise Test Passed
Process Room Hydraulic/ Slot Door Abort
Selected
Rear Access Door Closed Failure
Rear Access Door Lock Failure
Shelf Circulation Pump #1 Fail
Shelf Circulation Pump #2 Fail
Shelf Failed To Reach Position.
Shelf Fluid In Temperature Probe Fail
Shelf Fluid Temperature > Safety Set Point
Shelf Fluid Temperature Deviation Alarm
Shelf Ram Bellows Pirani Gauge Fail
Shelf Ram Bellows Test Failed
Shelf Ram Bellows Test Passed
Slot Door Failed To Close
Slot Door Failed To Open
Slot Door Gasket Failed
Steam Supply Valve Failed To Open
Steam/ CIP Isolation Valve Failed To Open
Steaming Time Is Excessive
Step End Temperature Fail
56/143
SC473501.doc
Cause
The main valve ram bellows passed the pumpdown
test.
Hydraulic pump over pressure.
Pressure rise failed
When the pressure rise test was passed during a
automatic freeze drying cycle.
The hydraulic / slot door abort button on the Process
room Slave Panel was pushed, by the operator.
The rear access door closed proximity switch
indicates the door is open
During locking, the output is on, but the input has not
been received for 10 seconds. Or, the door locked
input is lost during automatic cycle,
Circulation pump over current
Circulation pump over current
Shelf does not reach the desired position within
maximum allowable time.
RTD probe shorted or open circuit.
Shelf fluid temperature exceeded 70°C
Shelf fluid temperature is not within +HD/−LD from the
set point, (typically 4°C)
The Pirani gauge is sending a signal to the PLC of <
1.5 VDC.
Bellows vacuum failed to reach set point
The shelf ram bellows passed the pumpdown test.
- The closed slot door input signal is lost during
CIP/SIP.
- The close slot door output is energized and the
closed inputs are not received within a predetermined period of time.
- The slot door error check performed while opening
the door to ensure that the proximity switches have
not failed closed.
- The slot door open and the slot door closed input
signals are lost at the same time.
- The open slot door output is energized and the fully
opened input signal is not received within a predetermined period of time.
- The slot door open and the slot door closed input
signals are lost at the same time.
Gasket failed to pressurize or de-pressurize within 10
seconds of opening/closing.
Valve failed to open in 10 seconds.
Valve failed to open in 10 seconds.
Total steaming time is greater than the time specified
on the Engineering Parameter screen.
Shelf temp. not ± temp. High limit/low limit of set point
at end of step, (typically 1°C).
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.29: Alarms and Messages (continued)
Description
Step End Vacuum Failure
Cause
Vacuum not within vacuum high limit/vacuum low limit
of set point at end of step, as measured by chamber
vacuum transducer.
Valve failed to open in 10 seconds.
Sterile Filter Drain Steam Trap Bypass Valve
Failed To Open
Sterile Filter Drain Temp. Probe Fail
Sterile Filter Drain Valve #2 Failed To Open
Sterile Filter Drain Valve #3 Failed To Open
Sterile Filter Drain Valve Failed To Open
Sterile Filter Drain Valve Failed To Open
Sterile N2 Supply Valve Failed To Open
Sterility Monitoring Terminated
Sterility Override
Sterilization Failed
Sterilization Temperature Below Set Point
Sterilization Temperature Failed To Reach Set
Point
Vacuum Fail
Vacuum Fail – Below Set Point
Vacuum Pump #1 Fail
Vacuum Pump #2 Fail
Vacuum Pump Isolation Valve Failed To Open
Vacuum Pump Isolation Valve Failed To
Open/Close
Vacuum System Pirani Gauge Fail
Vacuum Warning
Water Supply Valve To Drain HX Failed To Open
PSGA
Operating Manual
RTD probe shorted or open circuit.
Valve failed to open in 10 seconds.
Valve failed to open in 10 seconds.
Valve failed to open in 10 seconds.
Valve failed to open in 10 seconds.
Valve failed to open in 10 seconds.
Functionality to monitor the sterility of the chamber
after an SIP cycle is terminated.
Chamber not sterile alarm override.
Did not complete the steaming phase.
Once steam temperature set point is achieved,
temperature falls below set point for 15 consecutive
minutes.
Steam temperature failed to reach set point within 2
hours.
Vacuum above product protection set point.
The low vacuum alarm activates if the chamber
pressure is ≤ the difference of the current ramping
vacuum set point and 20 microbars.
Vacuum pump over current
Vacuum pump over current
Valve failed to open in 10 seconds.
Valve failed to open/close in 10 seconds.
The Pirani gauge is sending a signal to the PLC of <
1.5 VDC.
Vacuum above product deviation set point.
Valve failed to open in 10 seconds.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
57/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
3.4.14
Historical Trending Screen
The Historical Trending screen permits viewing historical process data in graphical form. Select the
Trends button from the menu to view the following chart categories.
•
Plant Pressures
•
Sterilization Values
•
Shelf Fluid Temperatures
•
Lyophilization Values
Figure 3.16: Example Historical Trending Screen
The following functions may be accessed from the Trend screen.
•
The Chart – Point and click on a pen in the chart legend to display pen units. High and low EGUs
and the pen description will be displayed in the selected pen box.
•
Select Chart - This selection presents a pop-up window containing a list of pre-configured charts.
Select a chart for viewing from the list.
58/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
•
Restore Defaults - This selection will restore the default configuration for the selected chart.
•
Export Data - This selection will export the data currently displayed in the chart to a database
"csv" file. The user will be prompted to enter a file name and path for the exported file.
•
Enable/ Disable Auto Update Hist. - When Enabled, historical data in the chart will be updated
periodically. When Disabled, updates to historical data in the chart are discontinued.
•
Reset Zoom - This section restores pen limits to the original ranges.
•
Toggle Y-axes - Select this function to enable/disable the display of all Y-axes. If this is not
enabled, click on the desired tag description below the chart to change the Y-axis.
•
Toggle X-axes – Use this function to enable/disable the display of all X-axes. This selection will
only work on charts with 6 pens or less. For charts that contain more than 6 pens, the user can
remove the applicable number of pens to allow the button to become operational.
•
Set to Current Time - This selection sets the X-axis to the current date and time to obtain new
data.
•
Backup Trend Files - Selecting the “Backup Trends” button opens the Copy Trend File pop-up
window. Select a trend file to copy from the drop-down list. Each time this feature is used, a
message is sent to the audit trail indicating the name of the copied trend file and the destination to
which it was copied.
•
Delete Trend Files - This selection presents a pop-up window containing a list of trend files.
Select a trend file to delete from the list. Following trend selection, the system prompts for
confirmation of the selection. Each time this feature is used, a message is sent to the audit trail
indicating the name of the deleted trend file
•
Start Date / Time - Use this function to enter a new start date and time for the active chart.
•
Scroll Buttons - Use this function to scroll backwards and forwards by 25% and 50% of the chart
time.
•
Vertical / Horizontal Gridlines - Use this function to enter the number of vertical / horizontal
gridlines displayed in the active chart.
•
Duration - Use this function to set the chart duration in hours.
•
Add Pen - This selection will add the selected pen to the active chart.
•
Delete Pen - This selection will remove the selected pen from the active chart.
•
Low / High Limits for Selected Pen - Use this function to enter high / low limits for the selected
pen (a method of zooming)
3.4.15
Maintenance Screen
This screen presents running time data on system components such as compressors, circulation
pumps, vacuum pumps, hydraulic pump, and fluid heater. Critical operating information includes
accumulated runtime, maintenance schedule time, and time running without maintenance.
This screen assists management planning for periodic pump maintenance. Reset the Time Since
Last Maintenance following pump maintenance.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
59/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
The following functions may be accessed from the Maintenance screen. Some functions require an
electronic signature before being implemented. Refer to Electronic Signatures for more information.
•
Maintenance Interval - Use this function to enter the maintenance interval for each device.
•
Reset - Use this function to reset the run time and the time since last maintenance to zero.
•
Override Sterility - Maintenance button. Use this function to override the Sterility alarm loading
door interlock. The alarm remains active (until SIP is completed) but the loading door gasket may
be deflated and the loading door opened.
•
Terminate Sterility Monitoring - Maintenance button. Use this function to deactivate Sterility
Monitoring.
•
Device Mode - Maintenance button. Use this function to place the freeze dryer 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 manual or automatic functions
active and the freeze dryer is placed in Manual mode.
Figure 3.17: Maintenance Screen
60/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
The following information is presented on the Maintenance screen:
•
Device List - Listing of all compressors, circulation pumps, vacuum pumps, hydraulic pumps, and
fluid heaters associated with the freeze dryer.
•
Run Time - This value is the length of time the device has been used. This value may be
manually reset or will reset automatically after 32,760 hours (1365 days) of operation.
•
Time Since Last Maintenance - This value is the amount of time since the device was serviced.
This value should be manually reset each time maintenance is performed on the device. If not
manually reset, the value will automatically reset after 32,760 hours (1365 days) of operation.
3.4.16
Control Loops Screen
Select Control Loops in the Maintenance submenu. The Control Loops screen permits tuning of the
following control loops:
•
Chamber Vacuum Control
•
Condenser Cooling Control
•
Shelf Cooling PID Control
•
Sterilization Pressure Control
•
Shelf Heating PID Control
The following functions may be accessed from the Control Loops screen.
•
Select Chart - This selection presents a pop-up window containing a list of pre-configured charts.
Select a chart for viewing from the list. Each chart presents process variable, setpoint, and the
control variable for the loop. Some loops will display only general parameters such as PC1 and
HYS1. These valves use ON/OFF control versus modulating control.
•
Restore Defaults - This selection will restore the default configuration for the selected chart.
•
Enable / Disable Auto Update Real Time - When Enable is selected, data in the chart will be
updated each second. When Disable is selected, updates to the chart are discontinued.
•
Reset Zoom - This section restores pen limits to the original ranges.
•
Toggle Y-axes - This selection enables/disables the display of all Y-axes. If not enabled, click on
the desired tag description below the chart to change the Y-axis.
•
Toggle X-axes - This selection enables/disables the display of all X-axes.
•
Low / High Limits for Selected Pen - Use this function to enter high / low limits for the selected
pen (a method of zooming).
•
Vertical / Horizontal Gridlines - Use this function to enter the number of vertical / horizontal
gridlines displayed in the active chart.
•
Duration - Use this function to set the chart duration.
•
Setpoint - When Control Mode is set to Local, use this function to enter a setpoint for the loop. If
the Control Mode is set to PLC, data entry field will not be visible, indicating the value is read-only.
•
Control Variable - This is the percentage output of the PID loop. Use this function to enter a
value for the control variable when the PID loop is in manual mode. If the PID Mode is set to Auto,
the data entry field will not be visible, indicating the value is read-only.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
61/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
•
PID Parameters - Use this function to enter PID parameters for loop tuning.
•
PID Reset - Select PID reset after changing PID parameters (only for Siemens PLCs)
•
PID Mode - Use this function to place the PID loop in auto or manual mode. In auto mode, the
Control Variable cannot be changed. In manual mode, the control variable may be changed. The
system prompts for confirmation of the mode change.
•
Setpoint Control Mode - Use this function to select local mode to override the active setpoint
values. PLC mode does not allow changes to the setpoint from the PC. The system prompts for
confirmation of the change.
•
Scroll Buttons - Use the scroll buttons to view the shelf heating and shelf cooling loop data
without repopulating the chart and losing the plotted curve.
Figure 3.18: Example Control Loops Screen
62/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
The following information is presented on the Control Loops screen.
•
Process Variable - This parameter is monitored and controlled by the control loop.
•
Current Control Loop - Identifies loop parameters being displayed below the chart when two loops
are combined in a single chart, e.g., when viewing shelf heating and shelf cooling in the chart.
3.4.17
Calibration Screen
This screen presents analog inputs and outputs to the system. Each I/O is identified by description
and the actual input or output value is displayed for each.
Figure 3.19: Example Calibration Screen
The following functions may be accessed from the Calibration screen.
•
Analog Inputs - Selects analog inputs for display.
•
Analog Outputs - Selects analog outputs for display.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
63/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
•
Scroll buttons - Permits review of additional pages of analog inputs / outputs.
•
Enable / Disable - The Enable / Disable button (for analog inputs) are for BOC Edwards
Pharmaceutical Systems personnel only and are only visible when a BOC Edwards
Pharmaceutical Systems administrator is logged in. They are used to disable the current analog
input and allow the user to enter a value in the forced column to be used to control. The PLC will
copy the actual value to the forced value when the Disable button is selected.
The following information is presented on the Calibration screen.
•
Actual Value - The actual value of the parameter being measured by the field instrument.
•
Forced Value - A user entered value for an analog output to be used for control or calibration.
•
Analog Inputs / Outputs - Description of each analog inputs and outputs parameter being
measured. Refer to the following table for a complete list.
Table 3.30: Analog Inputs and Outputs
Group
AIM1-0 COM1
AIM1-1 COM1
AIM1-2 COM1
AIM1-3 COM1
AIM1-4 COM1
AIM1-5 COM1
AIM1-6 to AIM1-7
AIM2-0
AIM2-1
AIM2-2
AIM2-3
AIM2-4
AIM2-5
AIM2-6 to AIM2-7
AIM3-0
AIM3-1
AIM3-2
AIM3-3
AIM3-4
AIM3-5
AIM3-6 to AIM3-7
AIM4-0
AIM4-1
AIM4-2
AIM4-3
AIM4-4
AIM4-5
AIM4-6 to AIM4-7
AIM5-0
AIM5-1
AIM5-2
AIM5-3
AIM5-4
AIM5-5
AIM5-6
Description
Discharge pressure PT401
Discharge pressure redundant PT401A
Suction pressure PT409
Interstage pressure PT417
Oil pressure after filter PT425
Condenser coil outlet pressure PT438
Spare
COM2 discharge pressure PT402
COM2 discharge pressure redundant PT402A
COM2 suction pressure PT410
COM2 interstage pressure PT418
COM2 oil pressure after filter PT426
COM2 condenser coil outlet pressure PT439
Spare
COM3 discharge pressure PT403
COM3 discharge pressure redundant PT403A
COM3 suction pressure PT411
COM3 interstage pressure PT419
COM3 oil pressure after filter PT427
COM3 condenser coil outlet pressure PT440
Spare
COM4 discharge pressure PT404
COM4 discharge pressure redundant PT404A
COM4 suction pressure PT412
COM4 interstage pressure PT420
COM4 oil pressure after filter PT428
COM4 condenser coil outlet pressure PT441
Spare
FIT pressure filter # 1 PT904
FIT pressure filter # 2 PT905
Sterile filter drain temp TE238
WFI tank drain temp TE903
CIP fill level PT500)
Condenser drain conductivity CI1
Condenser vacuum PT201
64/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
Range
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 12.76 BarG
4 to 20 mA / -1.01 to 12.76 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 12.76 BarG
4 to 20 mA / -1.01 to 12.76 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 12.76 BarG
4 to 20 mA / -1.01 to 12.76 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 12.76 BarG
4 to 20 mA / -1.01 to 12.76 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / 0.00 to 4.00 BarG
4 to 20 mA / 0.00 to 4.00 BarG
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / 0.0 to 120.0 IWC
4 to 20 mA / 0 to 5.00 µS
4 to 20 mA / 0 to 1000 µBar
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.30: Analog Inputs and Outputs (continued)
Group
AIM5-7
AIM6-0
AIM6-1
AIM6-2
AIM6-3
AIM6-4
AIM6-5
AIM6-6
AIM6-7
AIM7-0
AIM7-1
AIM7-2
AIM7-3
AIM7-4 to AIM7-7
AIM8-0
AIM8-1
AIM8-2
AIM8-3
AIM8-4
AIM8-5
AIM8-6
AIM8-7
AIM9-0
AIM9-1
AIM9-2
AIM9-3 to AIM9-4
AIM9-5
AIM9-6
AIM9-7
AIM10-0
AIM10-1
AIM10-2
AIM10-3 to AIM10-4
AIM10-5
AIM10-6
AIM10-7
AIM11-0 to AIM11-7
AIM12-0
AIM12-1
AIM12-2
AIM12-3
AIM12-4
AIM12-5
AIM12-6 to AIM12-7
RTD1-0
RTD1-1
RTD1-2
RTD1-3
RTD1-4 to RTD1-5
RTD2-0
RTD2-1
RTD2-2 to RTD2-5
AOM1-0
Description
Condenser fluid inlet temp TE246
Condenser pressure PT203
Condenser coil temp TE203
Condenser drain temp TE213
Condenser fluid inlet temp redundant TE246A
Condenser fluid outlet temp TE247
Main valve bellows vacuum PT307
Vacuum pump 1 vacuum PT301
Vacuum pump 2 vacuum PT302
Sterile filter drain temp redundant TE238A
WFI tank drain temp redundant TE903A
Condenser drain temp redundant TE213A
CIP recirculation flow FM7
Spare
Hydraulic stoppering press 1 PT306
Shelf ram position ZT1
Chamber vacuum PT101
Shelf ram 1 bellows vacuum PT304
Spare
Shelf fluid inlet temp TE201
Shelf fluid outlet temp TE202
Slot door 1 drain temp TE298
Chamber vacuum PT102
Chamber pressure PT105
Shelf fluid inlet temp redundant TE201A
Spare
Slot door 1 drain temp redundant TE298A
Spare
Shelf fluid outlet temp redundant TE202A
Shelf ram 2 position ZT1A
Shelf ram 2 bellows vacuum PT304A
Hydraulic stoppering press 2 PT306A
Spare
Spare
Slot door 2 drain temp TE298B
Slot door 2 drain temp redundant TE298C
Spare
Spare
COM5 discharge pressure PT405
COM5 discharge pressure redundant PT405A
COM5 suction pressure PT413
COM5 interstage pressure PT421
COM5 oil pressure after filter PT429
COM5 condenser coil outlet pressure PT442
Spare
WFI tank temp TE1007
FIT # 1 temp TE1001
FIT # 2 temp TE1002
Drain HX CW temperature TE910
Spare
Chamber jacket inlet temp TE1010
Chamber jacket outlet temp TE1011
Spare
Compressor 1 VFD output
PSGA
Operating Manual
Range
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / 0.00 to 4.00 BarA
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -100.0 to +150.0 °C
3.00 to 7.48 VDC / 1 to 30,200 µBar
3.00 to 7.48 VDC / 1 to 30,200 µBar
3.00 to 7.48 VDC / 1 to 30,200 µBar
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / 0.0 to 150.0 GPM
4 to 20 mA / 17 to 97 BarG
4 to 20 mA / 0.0 to 2350.0 mm
4 to 20 mA / 0 to 1000 µBar
3.00 to 7.48 VDC / 1 to 30,200 µBar
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / 0 to 1000 µBar
4 to 20 mA / 0.00 to 4.00 BarA
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / 0.0 to 2350.0 mm
3.00 to 7.48 VDC / 1 to 30,200 µBar
4 to 20 mA / 17 to 97 BarG
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -100.0 to +150.0 °C
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 12.76 BarG
4 to 20 mA / -1.01 to 12.76 BarG
4 to 20 mA / -1.01 to 33.45 BarG
4 to 20 mA / -1.01 to 33.45 BarG
PT100 RTD / -100.0 to +150.0 °C
PT100 RTD / -100.0 to +150.0 °C
PT100 RTD / -100.0 to +150.0 °C
PT100 RTD / -100.0 to +150.0 °C
PT100 RTD / -100.0 to +150.0 °C
PT100 RTD / -100.0 to +150.0 °C
0 to 100% / 4 to 20 mA
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
65/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Table 3.30: Analog Inputs and Outputs (continued)
Group
AOM1-1
AOM1-2
AOM1-3
AOM1-4
AOM1-5
AOM2-0
AOM2-1
AOM2-2
AOM2-3
AOM2-4
AOM2-5
AOM3-0
AOM3-1
AOM3-2 to AOM3-5
AOM4-0
AOM4-1
AOM4-2
AOM4-3 to AOM4-5
AOM5-0
AOM5-1
AOM5-2
AOM5-3 to AOM5-5
AOM6-0
AOM6-1 to AOM6-5
3.4.18
Description
Compressor 3 VFD output
Shelf circ. Pump 1 VFD output
Heater 1 drive level HTR1A
Heater 3 drive level HTR3A
Heater 2 drive level HTR2B
Compressor 2 VFD output
Compressor 4 VFD output
Shelf circ. Pump 2 VFD output
Heater 2 drive level HTR2A
Heater 3 drive level HTR3B
Heater 1 drive level HTR1B
Steam modulating valve FV38% output
Gas bleed modulating valve FV66 % output
Spare
Hydraulic stoppering control valve 1 fv86 % output
Spare
Hydraulic stoppering control valve 2 fv86a % output
Spare
Shelf ram 1 proportional valve FV214 % output
Spare
Shelf ram 2 proportional valve FV214A % output
Spare
Compressor 5 VFD output
Spare
Range
0 to 100% / 4 to 20 mA
0 to 100% / 4 to 20 mA
0 to 50% / 4 to 20 mA
0 to 50% / 4 to 20 mA
51 to 100% / 4 to 20 mA
0 to 100% / 4 to 20 mA
0 to 100% / 4 to 20 mA
0 to 100% / 4 to 20 mA
0 to 50% / 4 to 20 mA
51 to 100% / 4 to 20 mA
51 to 100% / 4 to 20 mA
4 to 20 mA/ 0 to 100%
4 to 20 mA/ 0 to 100%
4 to 20 mA/ 0 to 100%
4 to 20 mA/ 0 to 100%
4 to 20 mA/ 0 to 100%
4 to 20 mA/ 0 to 100%
0 to 100% / 4 to 20 mA
Shelf Positioning Screen
The Shelf Positioning screen permits the review and adjustment of shelf loading position parameters.
Select Shelf Positioning in the Maintenance submenu.
The following functions may be accessed from the Shelf Positioning screen.
•
Shelf Ram Number - Use this function to select a shelf ram. Data for the selected shelf ram is
presented on the screen. Data includes: process variable, loading positions, unloading positions
and setpoints. For single ram systems, only one selection is available.
•
Inter-distance - Use this function to select an alternate shelf inter-distance if more than one interdistance is possible. When selected, the loading and unloading positions associated with that
inter-distance are loaded in the PLC.
•
Loading / Unloading Positions - Use this function to enter the loading and unloading positions
for each shelf for each inter-distance.
•
Copy PV - Use this function to copy the current process variable to the loading / unloading
position listed to the left of the button.
•
Home Position Setpoint - Use this function to enter a value for the fully retracted position.
•
Stoppering Position Setpoint - Use this function to enter a value for the stoppering position. Set
value greater than the fully extended position of the shelf ram to allow the hydraulic system to
build pressure during the stoppering step of the freeze drying cycle when no shelves are loaded.
66/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Figure 3.20: Shelf Positioning Screen
The following information is presented on the Shelf Positioning screen.
•
Process Variable - This is the current shelf position.
•
Current Setpoint - This is the current setpoint for the shelf ram position.
•
Previous Setpoint - This is the previous setpoint for the shelf ram position.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
67/143
SC473501.doc
BOC EDWARDS
3.4.19
BOC Edwards
Pharmaceutical Systems
Digital Input Screen
This screen presents digital inputs to the system. Each digital input is identified by description and the
actual input value (on or off) for each.
The following functions may be accessed from the Calibration screen.
•
Scroll buttons - Permits review of additional pages of digital inputs.
The following information is presented on the Calibration screen:
•
Actual Value - Displays the condition of the digital input, indicating whether it is On or Off.
Figure 3.21: Example Digital Input Screen
68/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.31: Digital Inputs
Group
IM1-0
IM1-1
IM1-2
IM1-3
IM1-4
IM1-5 to IM1-31
IM2-0
IM2-1
IM2-2
IM2-3
IM2-4
IM2-5
IM2-6
IM2-7
IM2-8
IM2-9
IM2-10
IM2-11
IM2-12
IM2-13
IM2-14
IM2-15
IM2-16
IM2-17
IM2-18
IM2-19
IM2-20
IM2-21
IM2-22
IM2-23
IM2-24
IM2-25
IM2-26
IM2-27
IM2-28
IM2-29
IM2-30
IM2-31
IM3-0
IM3-1
IM3-2
IM3-3
IM3-4
IM3-5
IM3-6
IM3-7
PSGA
Operating Manual
Description
EM switching off control power PB8
Control power available
Spare
UPS battery ok
UPS line power present
Spare
COM1 not over temperature TSH1/TSH51
COM1 overcurrent
COM1 running
COM1 oil temperature not low TSL1
COM1 cooling water flow FSL10
COM4 not over temperature TSH10/TSH54
COM4 overcurrent
COM4 running
COM4 oil temperature not low TSL4
COM4 cooling water flow FSL13
Shelf circulation pump #1 overcurrent
Shelf circulation pump #1 running
Condenser circulation pump #3 overcurrent
Condenser circulation pump #3 running
Liquid ring pump overcurrent
Liquid ring pump running
Chamber cooling jacket valve open FV27
Recirculation pump overcurrent
Recirculation pump running
Heater 1 isolation valve open FV1143
Heater 2 isolation valve open FV1144
Heater 3 isolation valve open FV1148
Cooling water pressure switch PSL35
Shelf circulation pumps differential pressure not low DPS1
Condenser circulation pumps differential pressure not low DPS1A
Jacket fluid circulation pumps differential pressure not low DPS12
COM5 not over temperature TSH13/TSH55
COM5 overcurrent
COM5 running
COM5 oil temperature not low TSL5
COM5 cooling water flow FSL14
Spare
COM2 not over temperature TSH4/TSH52
COM2 overcurrent
COM2 running
COM2 oil temperature not low TSL2
COM2 cooling water flow FSL11
Vacuum pump #1 overcurrent
Vacuum pump #1 not over temperature TSH27
Vacuum pump #1 running
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
69/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Table 3.31: Digital Inputs (continued)
Group
IM3-8
IM3-9
IM3-10
IM3-11
IM3-12
IM3-13
IM3-14
IM3-15
IM3-16
IM3-17
IM3-18
IM3-19 to IM3-31
IM4-0
IM4-1
IM4-2
IM4-3
IM4-4
IM4-5
IM4-6
IM4-7
IM4-8
IM4-9
IM4-10
IM4-11
IM4-12
IM4-13
IM4-14
IM4-15
IM4-16
IM4-17 to IM4-31
IM5-0
IM5-1
IM5-2
IM5-3
IM5-4
IM5-5
IM5-6
IM5-7
IM5-8
IM5-9
IM5-10
IM5-11
IM5-12
IM5-13
IM5-14
IM5-15
IM5-16
IM5-17
70/143
SC473501.doc
Description
Booster pump #1 overcurrent
Booster pump #1 running
Shelf circulation pump #2 overcurrent
Shelf circulation pump #2 running
Condenser circulation pump #4 overcurrent
Condenser circulation pump #4 running
Heater 1 not over temperature TSH25/TSH25A
Heater 1 running
Chamber jacket circulation pump #5 overcurrent
Chamber jacket circulation pump #5 running
Control power on HS1
Spare
COM3 not over temperature TSH7/TSH53
COM3 overcurrent
COM3 running
COM3 oil temperature not low TSL3
COM3 cooling water flow FSL12
Vacuum pump #2 overcurrent
Vacuum pump #2 not over temperature TSH28
Vacuum pump #2 running
Booster pump #2 overcurrent
Booster pump #2 running
Hydraulic pump overcurrent
Hydraulic pump overpressure PSH9
Hydraulic pump running
Heater 2 not over temperature TSH26/TSH26A
Heater 2 running
Heater 3 not over temperature TSH61/TSH61A
Heater 3 running
Spare
Sterile air/nitrogen isolate valve open FV4
Open gas bleed bypass valve open FV5
Nitrogen supply valve open FV6
Sterile air supply valve open FV7
Sterile filter drain valve #1 open FV21
Sterile filter drain valve #2 open FV44
Sterile filter bypass valve #1 open FV45
Sterile filter steam trap bypass valve closed FV49
Sterile filter drain valve #3 open FV53
Sterile filter bypass valve #2 open FV56
Sterile filter 1 FIT air supply valve open FV88
Sterile filter 1 FIT vent valve open FV90
Sterile filter 1 FIT vent valve open FV90A
Sterile filter 2 FIT vent valve open FV91
Sterile filter 2 FIT vent valve open FV91A
Filter isolation integrity test valve open FV92
Filter isolation integrity test valve open FV94
Sterile filter 1 FIT water supply valve open FV96
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.31: Digital Inputs (continued)
Group
IM5-18
IM5-19
IM5-20
IM5-21
IM5-22
IM5-23
IM5-24
IM5-25
IM5-26
IM5-27
IM5-28
IM5-29
IM5-30
IM5-31
IM6-0
IM6-1
IM6-2
IM6-3
IM6-4
IM6-5
IM6-6
IM6-7
IM6-8
IM6-9
IM6-10
IM6-11
IM6-12
IM6-13
IM6-14
IM6-15
IM6-16
IM6-17
IM6-18
IM6-19
IM6-20
IM6-21
IM6-22
IM6-23
IM6-24
IM6-25 to IM6-31
IM7-0
IM7-1
IM7-2
IM7-3
IM7-4
IM7-5
IM7-6
IM7-7
PSGA
Operating Manual
Description
Sterile filter 2 FIT water supply valve open FV97
Steam inlet to CIP HX valve open FV1072
Sterile steam isolation valve open fv1117
WFI tank drain valve open FV1130
WFI tank isolation valve open FV1131
WFI tank cooling valve open FV1133
WFI tank vent valve open FV1134
Spare
Sterile filter 1 sterile air valve open FV1141
Sterile filter 2 sterile air valve open FV1142
Steam supply valve closed FV38
WFI tank level hi LSH5
WFI tank level lo LSL5
LRP water flow not low FS1
Main vacuum valve open FV2
Condenser inlet valve open FV8
Condenser drain valve open FV9
Vacuum pump #1 isolation valve open FV11
Vacuum pump #2 isolation valve open FV12
Condenser drain steam trap bypass valve closed FV14
Liquid ring pump vacuum valve open FV15
Main drain valve closed FV16
Condenser steam defrost valve open FV20
CIP supply isolation valve open FV19
Main isolation valve open FV1
Steam / CIP isolation valve open FV25
CIP solvent drain valve open FV41
Main drain bypass valve open FV48
CIP recirculation pump drain open FV230
Condenser inlet valve open FV33
CIP pump outlet valve open FV67
CIP pump condenser drain isolation valve open FV401
Condenser vent valve open FV1012
Drain HX water supply valve open FV1043
Compressed air pressure switch PSL36
CIP water pressure switch PLS38
Drain HX water flow not low FS6
CIP recirculation water flow not low FS4
Steam isolation valve open FV81
Spare
Silicone oil level not low PSHL50
Silicone oil level not high PSHL50
Silicone expansion tank level not low LSL1
Main isolation valve closed FV1
Hydraulic filter differential pressure DPS11
Slot door 2 drain valve open FV1050A
Slot door 2 steam trap bypass valve closed FV1061a
CIP manifold #1 valve open FV29
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
71/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Table 3.31: Digital Inputs (continued)
Group
IM7-8
IM7-9
IM7-10
IM7-11
IM7-12 to IM7-14
IM7-15
IM7-16 to IM7-17
IM7-18
IM7-19
IM7-20
IM7-21
IM7-22
IM7-23
IM7-24
IM7-25 to IM7-26
IM7-27
IM7-28
IM7-29
IM7-30
IM7-31
IM8-0
IM8-1
IM8-2
IM8-3
IM8-4
IM8-5
IM8-6
IM8-7
IM8-8
IM8-9
IM8-10
IM8-11
IM8-12
IM8-13
IM8-14
IM8-15
IM8-16
IM8-17
IM8-18
IM8-19
IM8-20 to IM8-31
3.4.20
Description
CIP manifold #2 valve open FV30
CIP manifold #3 valve open FV31
Spare
Slot door 1 drain valve open FV1050
Spare
Slot door 1 steam trap bypass valve closed FV1061
Spare
Slot door 1 not closed XS153, XS178, XS179
Spare
Slot door 1 not fully open XS152
Spare
E-stop reset PB72
Slave panel e-stop not selected SR2/PB73
Light curtain not breached
Spare
Chamber door closed XS140
Chamber door unlocked ZS120-123
Chamber door locked ZS100-107
Chamber not overpressure PSH11
Slot doors gasket pressurized PSL37
Chamber jacket cooling isolation valve open FV705
Slave panel chamber door unlock select HS226
Slave panel chamber door lock select HS226
Slave panel chamber pre-aeration select HS31
Slave panel chamber aeration select HS31
Slave panel slot door 1 open select HS45
Slave panel slot door 1 close select HS45
Slave panel index/jog shelf 1 up select HS72
Slave panel index /jog shelf 1 down select HS72
Slave panel slot door 2 open select HS45a
Slave panel slot door 2 close select HS45a
CIP manifold #5 valve open FV34
CIP manifold #6 valve open FV35
CIP manifold #7 valve open FV36
Spare
Slot door 2 not closed XS153A, XS178A, XS179A
Spare
Slot door 2 not fully open XS152A
Slave panel index/jog shelf 2 up select HS72a
Slave panel index/jog shelf 2 down select HS72a
Spare
Device Mode Screen
Select the Device Mode button on the Maintenance Screen to place the freeze dryer in device mode
and allow maintenance personnel to manually operate valves and motors. Device Mode of operation
is only possible when there are no active manual or automatic functions and the freeze dryer is in
72/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Manual mode. Proper security (Maintenance access) is required to enable device mode from the
Maintenance screen.
Figure 3.22: Example Device Mode Screen
The following functions may be accessed from the Device Mode screen.
•
Auto / Manual – Select to toggle the control mode for the device. Devices in manual mode can
be controlled in device mode.
•
Enable / Disable - Select these buttons to toggle the state of a device. The text for these buttons
may also be “Open” and “Close” if a valve is selected.
•
Control Variable – Select to enter a % output for an analog device. This function is only visible
for devices requiring control loops.
•
Close - Closes the screen.
The following information is presented on the Device Mode screen.
•
Device description - A description of the selected device including the tag name is displayed.
3.4.21
Batch Record Screen
The function of the Batch program is to collect data, security logs, and alarm logs during an automatic
freeze drying cycle and generate a printout when the cycle ends. The Batch Record screen permits
an individual with appropriate security privileges to define, view, print, copy, and archive batch files.
The following functions may be accessed from the Batch Report screen. Some functions require an
electronic signature before being implemented. Refer to Electronic Signatures for more information.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
73/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
•
View / Print Report - Select to open View Report pop-up window. Select the batch for viewing or
printing from the list of completed batches.
•
Delete Report - Select to open Delete Report pop-up window. Select a batch from the list to
delete and select Delete the Files. When delete is selected, a message is sent to the audit trail
indicating which files were deleted.
•
Copy Report - Select to open the copy file pop-up window. Select a source file (batch) and a
destination. Hold the shift key while selecting files to choose more than one file for copying.
Select a destination directory and click on the copy button to complete the action. A message is
sent to the audit trail indicating which files were copied and the destination.
3.4.21.1
Batch Reports
The PC uses Sytech XLReporter and Microsoft Excel to create batch reports in Portable Document
Format (“.pdf” format). Batch report information is saved on the PC in the following directories:
•
Template files - Dynamics\App\Reports\Template
•
Temporary Excel Files - Dynamics\App\Reports\Temp
•
PDF Reports - Dynamics\App\Reports\PDF Reports
•
XLReporter scheduler - Dynamics\App\Reports\Template
The system generates one report for each cycle type in a batch. The name of the batch report file is
[batch name]_[unitname]_[cycle type abbreviation].pdf. For example, the Clean in Place cycle for
batch name 123 on Freeze Dryer 2 would have the report file name 123_FD2_CIP.pdf. Thereafter
every Clean in Place cycle for batch name 123 on Freeze Dryer 2 is added to the file. Should the
Clean in Place fail and need to be rerun, this feature allows the next Clean in Place Cycle to have the
same batch name. The cycle abbreviations used for the batch file names are listed in the following
table.
Table 3.32: Cycle Abbreviations
Cycle
Freeze drying
Defrost
Clean in place
Sterilization
Leak test
Shelf ram 1 bellows test
Main isolation valve bellows test
Filter integrity test
Abbreviation
FD
Def
CIP
SIP
LT
Ram1BT
MIVBT
FIT
The XLReporter Scheduler monitors the control system’s progress through a cycle. Each time a new
cycle starts XLReporter copies the appropriate template file to a new batch report file using the
appropriate file name format (described above).
74/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
A Recipe Start Report is printed at the start of each cycle. At the end of the cycle, additional reports
are generated, including a Recipe End Report, an alarm report containing all events that occurred
during the cycle, and graphs and / or tables of critical process values that are plotted during the cycle.
Graph intervals are based on the number of data points and the range of data. The interval used for
tables is 1 minute. Each of these reports within the batch file is named according to the cycle type,
type of report, and date/time stamp of when that cycle began. For example, if the Clean in Place
cycle for batch 123 began on December 2, 2003 at 9:12 am and ended at December 2, 2003 at 11:12
am, the recipe start report tab in the batch file would be named CIPrecStart 12_02_03_09_12 and the
recipe end report would be named CIPrecEnd 12_02_03_11_12. If a second Clean in Place cycle is
run for the same batch at 1:32 pm that day and ends at 3:32 that day, the recipe start report tab would
be named CIPrecStart 12_02_03_13_32 and the recipe end report would be CIPrecEnd
12_02_03_15_32. All of these reports, and any other CIP cycles that are run for batch 123 on Freeze
Dryer 2, would be included in the Batch Report file 123_FD2_CIP.PDF. The tab naming formats used
within the report are indicated in the following table.
Table 3.33: Tab Naming Formats
Report
Recipe start report
Step end report (Freeze drying only)
Recipe end report
Alarm / event report
Data table
Graphs
Tab name
[cycle abbreviation]recStart [date time]
[cycle abbreviation]step[step number]End [date time]
[cycle abbreviation]recEnd [date time]
[cycle abbreviation]almEvt [date time]
[cycle abbreviation]dataTable date time]
[cycle abbreviation]graph[graph number] [date time]
Every page of the batch report provides an “Approved by” line, a “Date” line, batch file name, and tab
name in the footer.
3.4.21.2
Freeze Drying Report
The Freeze Drying report is composed of multiple parts, a Recipe Start Report (Figure 3.23) part 1,
Recipe Start Report (Figure 3.24) part 2, and a Step End Report (Figure 3.25) for each completed
step of the recipe. The reports contain the following information:
•
Report Header including batch name, unit identification, cycle identification, product name, recipe
name, report time, author’s name, plant number.
•
Product notes.
•
Listing of all process alarms that occurred during the cycle.
•
Data table listing applicable parameters and values during the cycle.
•
Graphs of process data collected during the cycle.
•
Applicable set points and pass/fail status of the cycle.
•
Report Footer including an “approved by” signature line.
•
The Step End report - Information is saved at the end of each freeze drying step.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
75/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Parameters, process data, and set points for each report are listed in the following tables. All items
are printed at the end of the cycle.
Table 3.34: Freeze Drying Recipe Start Report Contents
Data Table Contents
Process Data Graph 1
Process Data Graph 2
Process Data Graph 3
Process Data Graph 4
Start Report Set points and Status
Chamber vacuum (current ramping set point) (µBar)
Chamber vacuum(µBar)
Shelf fluid inlet temperature (current ramping set point) (ºC)
Shelf fluid inlet temperature (ºC)
Condenser coil temperatures (ºC)
Chamber vacuum (current ramping set point) (µBar)
Chamber vacuum (µBar)
Shelf fluid inlet temperature (current ramping set point) (ºC)
Shelf fluid inlet temperature (ºC)
Condenser coil temperatures (ºC)
Condenser coil temperatures (ºC)
Chamber vacuum (current ramping set point) (µBar)
Chamber vacuum (µBar)
Shelf fluid inlet temperature (current ramping set point) (ºC)
Shelf fluid inlet temperature (ºC)
Number of shelves to load per ram
Interdistance
Pressure deviation set point (µBar)
Product protection alarm set point (µBar)
Vacuum control gas type (N2/air)
Recipe steps and associated parameters and set points
Freeze Drying Recipe Start Report 1
Batch:123
Unit:FD1
Cycle: Freeze Drying
Product Name: XYZ
Recipe name: 111
Report time: 11/7/02 5:19 PM
Operator’s Name: Joe
Verifying Operator’s Name: John
Plant Number: 1
Stopper Type:
Overseal Type:
Product Notes
1
2
3
4
Number of shelves to load
Vial Type
Pressure Deviation Setpoint (Microns)
Product Protection alarm setpoint (Microns)
Vacuum control gas type (0=N2, 1=air)
Approved By ____________________
13
1
50
200
0
Date ________________________
Figure 3.23: Example Freeze Drying Recipe Start Report 1
76/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Freeze Drying Recipe Start Report 2
Step Type
Parameter 1
1
2
3
4
5
6
Loading
Freezing
Evacuation
Drying
Pres. Rise Test
Aeration
7
Stoppering
8
Aeration
9
Storage / Unloading
Temperature
Temperature
Temperature
Temperature
Pressure Rise
Gas type
(0=N2, 1=air)
Stoppering with
aeration
(0=no,1=yes)
Stoppering pressure
Gas type
(0=N2, 1=air)
Temperature
Approved By ____________________
Parameter 2
20
30
30
40
100
0
°C
°C
°C
°C
Microns
0
870
0
PSIG
20
°C
Parameter 3
Time
0:20
HH:MM
Time
Test Repeat Time
Aeration Time
1:30
10
0
HH:MM
MM
sec
Chamber vacuum
Chamber vacuum
Test Time
Pressure
500
400
200
13.0
Microns
Microns
sec
PSIA
Aeration pressure
13.5
PSIA
Gas type
(0=N2, 1=air)
Pressure
14.7
PSIA
Aeration Time
1
60
sec
Date ________________________
Figure 3.24: Example Freeze Drying Recipe Start Report 2
Table 3.35: Step End Report Contents
Data Table Contents
End Report Set points and Status
(Pressures)
End Report Set points and Status
(Temperatures)
PSGA
Operating Manual
Step type
Step number
Cycle elapsed time (hh:mm)
Step time (set point) (hh:mm)
Step elapsed time (hh:mm)
Step end deadband (high/low) (µBar)
Step end set point (µBar)
Process variable (µBar)
Pressure readings (min/max) (µBar)
Step end deadband (ºC)
Shelf fluid in (step end set point and actual) (ºC)
Shelf fluid out (actual) (ºC)
Temperature (min/max) (ºC)
Condenser coil temperatures (ºC)
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
77/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Figure 3.25: Example Freeze Drying Step End Report
3.4.21.3
Optional Cycle Report
Reports may be generated for each of the following cycles:
•
Defrost
•
Shelf Ram Bellows Test
•
CIP
•
Main Isolation Valve Bellows Test
•
SIP
•
FIT Cycle
•
Leak Test
The report for each optional cycle is composed of two parts, a Recipe Start Report (Figure 3.26) and a
Recipe End Report (Figure 3.27). The reports contain the following information.
1.
Report Header including report name, batch identification, unit identification, cycle name, report
date and time.
2.
Listing of all process alarms that occurred during the cycle
3.
Data table listing applicable parameters and values during the cycle.
4.
Graph of process data collected during the cycle.
5.
Applicable set points and pass/fail status of the cycle.
6.
Report Footer including an “approved by” signature line.
78/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Parameters, process data, and set points for each report are listed in the following tables. All items
are printed at the end of the cycle.
Table 3.36: Defrost Report Contents
Data Table Contents
Process Data Graphs
Start Report Set points and Status
End Report Set points and Status
Condenser coil temperatures (ºC)
Condenser drain temperatures (ºC)
Condenser Pressure (BarA)
Condenser coil temperatures (ºC)
Condenser drain temperatures (ºC)
Condenser Pressure (BarA)
Defrost Time (min)
Defrost Time (min)
Defrost Successful (yes/no)
Table 3.37: CIP Report Contents
Data Table Contents
Process Data Graph 1
Process Data Graph 2
Start Report Set points and Status
End Report Set points and Status
PSGA
Operating Manual
Chamber pressure (BarA)
Condenser pressure (BarA)
Condenser drain temperature (ºC)
Conductivity (µS)
Recirculation flow (GPM)
Condenser drain temperature (ºC)
Chamber pressure (BarA)
Condenser pressure (BarA)
Chamber wash time (sec)
Condenser wash time (sec)
Number of wash cycles
Number of shelf ram cycles per ram
CIP drying time (min)
CIP fluid type (WFI/Det.)
Chamber wash time (sec)
Condenser wash time (sec)
Number of wash cycles
Number of shelf ram cycles per ram
CIP drying time (min)
CIP fluid type (WFI/Det.)
CIP successful (yes/no)
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
79/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Table 3.38: SIP Report Contents
Data Table Contents
Process Data Graph 1
Process Data Graph 2
Start Report Set points and Status
End Report Set points and Status
Chamber pressure (BarA)
Condenser pressure (BarA)
Condenser drain temperature (ºC)
Sterile filter drain temperature (ºC)
Slot door 1 drain temperature (ºC)
Slot door 2 drain temperature (ºC)
WFI tank drain temp ((ºC)
SIP F(0) (min)
Condenser drain temperature (ºC)
Sterile filter drain temperature (ºC)
Slot door 1 drain temperature (ºC)
Slot door 2 drain temperature (ºC)
WFI tank drain temp ((ºC)
SIP F(0) (min)
Chamber pressure (BarA)
Condenser pressure (BarA)
Sterilization exposure time (min)
Sterilization temperature (ºC)
Sterilization pressure (BarA)
Sterilization exposure time (min)
Sterilization temperature (ºC)
Sterilization pressure (BarA)
SIP successful (yes/no)
Table 3.39: Leak Test Report Contents
Data Table Contents
Process Data Graph 1
Process Data Graph 2
Start Report Set points and Status
End Report Set points and Status
80/143
SC473501.doc
Chamber pressure (BarA)
Condenser pressure (BarA)
Chamber vacuum (µBar)
Condenser vacuum (µBar)
Chamber vacuum (µBar)
Condenser vacuum (µBar)
Chamber pressure (BarA)
Condenser pressure (BarA)
Leak pressure ()
Leak test time (min)
Leak pressure (BarA)
Leak test time (min)
Leak rate (µBar/sec)
Leak test successful (yes/no)
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.40: Shelf Ram Bellows Test Report Contents
Data Table Contents
Process Data Graph
Start Report Set points and Status
End Report Set points and Status
Chamber pressure (BarA)
Shelf ram 1 bellows vacuum (µBar)
Shelf ram 2 bellows vacuum (µBar)
Chamber pressure (BarA)
Shelf ram 1 bellows vacuum (µBar)
Shelf ram 2 bellows vacuum (µBar)
Shelf ram bellows test pressure (µBar)
Shelf ram bellows pumpdown time (min)
Shelf ram to test first
Shelf ram bellows test pressure (µBar)
Shelf ram bellows pumpdown time (min)
Shelf ram 1 bellows test successful (yes/no)
Shelf ram 2 bellows test successful (yes/no)
Table 3.41: Main Isolation Valve Bellows Test Report Contents
Data Table Contents
Process Data Graph
Start Report Set points and Status
End Report Set points and Status
Condenser pressure (BarA)
Main isolation valve bellows vacuum (µBar)
Condenser pressure (BarA)
Main isolation valve bellows vacuum (µBar)
Main valve bellows test pressure (µBar)
Main valve bellows pumpdown time (min)
Main valve bellows test pressure (µBar)
Main valve bellows pumpdown time (min)
Main valve bellows test successful (yes/no)
Table 3.42: FIT Cycle Test Report Contents
Data Table Contents
Process Data Graph 1
Process Data Graph 2
Start Report Set points and Status
PSGA
Operating Manual
Filter 1 integrity test pressure (BarG)
Filter 2 integrity test pressure (BarG)
Sterile filter 1 upstream temp (°C)
Sterile filter 2 upstream temp (°C)
WFI tank drain temp (°C)
Sterile filter 1 upstream temp (°C)
Sterile filter 2 upstream temp (°C)
WFI tank drain temp °C)
Filter 1 integrity test pressure (BarG)
Filter 2 integrity test pressure (BarG)
Filter number to test first (1/2)
Filter drying time (min)
Filter flood time (sec)
Stabilization time (min)
Drain time (min)
Filter test time (min)
WFI water temperature (°C)
Max. test pressure (BarG)
Allowable pressure drop (BarG)
WFI tank drain time (min)
Drying medium (N2/Air)
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
81/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Table 3.42: FIT Cycle Test Report Contents (continued)
End Report Set points and Status
Filter number to test first (1/2)
Filter drying time (min)
Filter flood time (sec)
Stabilization time (min)
Drain time (min)
Filter test time (min)
WFI water temperature (°C)
Max. test pressure (BarG)
Allowable pressure drop (BarG)
WFI tank drain time (min)
Drying medium (N2/Air)
Filter no. 1 test successful (yes/no)
Filter no. 2 test successful (yes/no)
Figure 3.26: Typical Optional Cycle Start Report
82/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Figure 3.27: Typical Optional Cycle End Report
3.4.22
Security Screen
Selecting the Security button will call up the security configuration.
3.4.22.1
Privileges
The software has pre-defined security levels each with specific privileges. There are seven access
levels: Public, Operator, Supervisor, Engineering, Maintenance, Administrator (highest customer
access), and Developer. These security groups are tied into the configuration of the Operator
Interface (iFIX) screens and database, and should never be deleted. The privileges for each security
level are shown in the following table.
Users can log in to iFIX by selecting the LOGIN button, which is located on the footer.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
83/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.43: Group Account Privileges
Screen/Category
Privileges
Alarms
Screen access
Alarm acknowledge one
Alarm acknowledge page
Pump reset, loading door reposition
selections
Delete alarm files
Batch record screen
Screen access
View batch
Print batch
Delete/Copy batch
Calibration screen
Screen access
Forcing analog outputs
Forcing analog inputs
CIP engineering parameter Screen access
screen
Modify engineering parameters
CIP recipe screen
Screen access
Modify recipe
Run cycle: edit batch name, edit setup parameters, start/abort auto cycle
Control loop screen
Screen access
Modify PID parameters, PID reset, /
general parameters
Modify CV, PID mode
Modify setpoint, control mode (Local /
PLC)
Defrost engineering
Screen access
parameter screen
Modify engineering parameters
Defrost recipe screen
Screen access
Modify recipe
Run cycle: edit batch name, edit setup parameters, start/abort auto cycle
Digital inputs
Screen access
Error recovery
Screen access
Error recovery functions
Filter integrity test engine. Screen access
parameter screen
Modify engineering parameters
Filter integrity test recipe
Screen access
screen
Modify recipe
Run cycle: edit batch name, edit setup parameters, start/abort auto cycle
Footer
Exit
84/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
Security Access Level
(D) Developer, (A) Administrator,
(M1) Maint. Level 1,
(M2) Maint. Level 2, (S) Supervisor,
(O) Operator, (P) Public
D
A M2 M1 S
O
P
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
PSGA
Operating Manual
√
√
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.43: Group Account Privileges (continued)
Screen/Category
Privileges
Freeze dryer shelf
positioning screen
Freeze drying engineering
parameter screen
Freeze drying recipe
screen
Screen access
Screen functions
Screen access
Modify engineering parameters
Screen access
Go offline and edit / create a recipe,
Modify online recipe
Run cycle: load recipe to the PLC, edit
batch name, edit set-up parameters,
start/abort auto cycle
Copy/delete recipe
Hold cycle / step advance
Screen access
Device mode screen access (option)
Device mode functions (option)
Screen access
Modify system date and time
Print screen
Screen access
Export data
Delete / backup trend
Screen access
Modify engineering parameters
Screen access
Modify recipe
Run cycle: edit batch name, edit setup parameters, start/abort auto cycle
Retry selection
Screen access
Modify recipe
Run cycle: edit batch name, edit setup parameters, start/abort auto cycle
Retry selection
Screen access
Edit maintenance interval, reset run
time, time since last maintenance
Override sterility, terminate sterility
monitoring, device mode (option)
Screen access
Manual functions
Screen access
Modify engineering parameters
Freeze drying unit graphic
General overview
Header
Historical trending
Leak test engineering
parameter screen
Leak test recipe screen
Main isolation valve
bellows test recipe screen
Maintenance screen
Manual controls
Shelf ram bellows test
engine. parameter screen
PSGA
Operating Manual
Security Access Level
(D) Developer, (A) Administrator,
(M1) Maint. Level 1,
(M2) Maint. Level 2, (S) Supervisor,
(O) Operator, (P) Public
D
A M2 M1 S
O
P
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
85/143
SC473501.doc
√
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.43: Group Account Privileges (continued)
Screen/Category
Privileges
Shelf ram bellows test
recipe screen
Screen access
Modify recipe
Run cycle: edit batch name, edit setup parameters, start/abort auto cycle
SIP engineering parameter Screen access
screen
Modify engineering parameters
SIP recipe screen
Screen access
Modify recipe
Run cycle: edit batch name, edit setup parameters, start/abort auto cycle
Security
Add new users, modify user
passwords to iFIX
Add new users, modify user
passwords to Windows
Configure Secure Desktop
System Engineering
Screen access
parameters
Modify engineering parameters
Modify engineering parameters (BOC
only)
3.4.22.2
Security Access Level
(D) Developer, (A) Administrator,
(M1) Maint. Level 1,
(M2) Maint. Level 2, (S) Supervisor,
(O) Operator, (P) Public
D
A M2 M1 S
O
P
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
User Accounts
The software has pre-defined user accounts. The privileges associated with each account are shown
in the following table. The security level can be configured to give extra privileges to a user. Users
can login or logout anytime, as desired, to change access. Using the security configuration program,
users can be assigned a login name and password.
Note:
All user accounts, with the exception of the System Administrator account, use
Windows security. The System Administrator account exists so that, in the
unlikely event that Windows security or iFIX security becomes corrupt, the System
Administrator can edit the iFIX security configuration, or exit the iFIX environment
to allow the Administrator or BOC user account to troubleshoot the Windows
security configuration.
The MNT1, MNT2, OP, and SUP accounts are examples of user accounts -- use these accounts as
templates for creating personalized user accounts for maintenance, operator, and supervisor
personnel. Once personalized accounts have been created, delete the template user account, or
change the passwords for these accounts to prevent unauthorized access to the PC Operator
Interface. Additionally, change the Administrator user account password to prevent unauthorized
access to the PC Operator Interface.
86/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Note:
BOC and Administrator user accounts have unlimited access to all iFIX application
features – only BOC and Administrator users can add new users to the Windows
XP/Intellution iFIX security configuration. However, the iFIX Administrator user
account and users with Supervisor security privileges can edit iFIX user
privileges. Also the Recipe, BOC, and iFIX Administrator accounts should never
be deleted.
When the PC Operator Interface boots up, the AU (public) user account is automatically logged in to
Windows XP. “No User” (idle user) is automatically logged in to iFIX.
All user accounts will be locked out for one hour after three successive failed logins. The password
age for TestUser only is 60 days. Other passwords will not expire.
Table 3.44: User Account Definitions
User
Account
AU (Public)
MNT1 (Maintenance level 1)
MNT2 (Maintenance level 2)
OP (Operator)
SUP (Supervisor)
Recipe 2)
Administrator
BOC
(BOC EPS Personnel Developer)
System Administrator
Group
Membership
Public
Public
Maintenance1
Public
Maintenance2
Public
Operator
Public
Operator
Supervisor
Public
Operator
Supervisor
Public
Maintenance1
Maintenance2
Operator
Supervisor
Administrator
Public
Maintenance1
Maintenance2
Operator
Supervisor
Developer
None
Login
Name
AU
MNT1
Login
Password
AU
MNT1
Inactivity
Timeout 1)
None
After 5 min
MNT2
MNT2
After 5 min
OP
OP
After 5 min
SUP
SUP
After 5 min
3)
3)
After 5 min
ADMINISTRATOR
None
After 5 min
3)
3)
After 5 min
3)
3)
After 5 min
1)
Functionality provided by iFIX screen saver.
2)
The Recipe user account is required by iFIX to allow the recipe upload/download functions to operate correctly.
The user never logs in to this account, but the iFIX application uses this account during recipe upload/download.
3)
These login names and passwords are known only to BOC EPS and are not required for normal daily operation of
the freeze dryer.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
87/143
SC473501.doc
BOC EDWARDS
3.4.22.3
BOC Edwards
Pharmaceutical Systems
Secure Desktop
Secure desktop provides access to the iFIX program group, Windows Explorer, and the Administrative
tools via passwords. Only an administrator in the operating system can change this configuration.
3.4.22.4
Electronic Signatures
Selections requiring electronic signatures are noted in the individual screen / user form sections of the
document. Note that items not listed in the tables cannot be configured for electronic signatures.
Figure 3.28: Example Perform Only Electronic Signature Screen
The Electronic Signature option of iFIX contains the following functions / features:
•
Perform Only - Enter user name and password and click OK. The signature is validated, a value
is written to the database, and the Electronic Signature dialog box closes.
•
Perform and Verify - After the "Performed By" signature is validated, the "Verified By" section
activates. Once the user who verifies the signature enters his user name and password in the
Verified By section and then clicks OK, the signature is validated, the value is written to the
database, and the Electronic Signature dialog box closes.
88/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
•
Allow Continuous Use - By default, continuous use is enabled for all tags in the "pdb" database
that require an electronic signature. This option permits repeated signing for successive actions
by supplying only a password. A continuous use period starts when the user successfully signs
for an action. The user name is recorded as the continuous user. While the continuous use
period is in effect, the user name displays in the Performed By section in each subsequent
Electronic Signature dialog box displayed for this tag. This feature saves the user the time
required to repeatedly type the user name. Continuous use applies only to the user performing an
action and does not affect the person verifying an action. A continuous use period ends when the
iFIX Screen Saver activates due to a period of keyboard or mouse inactivity, or when another user
enters his user name in the Perform By section of the Electronic Signature dialog box. The
application developer configures the duration of the inactive period and must also enable the
Reset Electronic Signature Continuous User option for the Screen Saver. When the continuous
use period ends, the Performed By user name is cleared in the Electronic Signature dialog box.
When a valid signature is entered, another continuous use period begins.
•
Log Out of iFIX (iFIX Screensaver) - The iFIX screensaver will be enabled after 5 minutes of
inactivity. When the iFIX screensaver starts, the current user will be logged out, and a login
prompt will appear.
•
Reset Electronic Signature Continuous User - This must be selected to allow for continuous
use.
Figure 3.29: Example Perform and Verify Electronic Signature Screen
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
89/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Table 3.45: Electronic Signature Functions
Screen
Freeze Drying Recipe
Optional Cycle Recipe
Maintenance
Batch Report
Error Recovery
90/143
SC473501.doc
Function
Start cycle
Abort cycle
Modification of all ONLINE recipe step
parameters and general recipe parameters
Select Hold
Step Advance
Start cycle
Abort cycle
Modification of all recipe parameters
Override sterility
Delete report
Apply selection
Force load / unload complete selection
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
Perform
Only
Perform
and
Verify
X
X
X
X
X
X
X
X
X
X
X
X
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
4.
OPERATOR INTERFACE FUNCTIONS
4.1
Login
Perform the following login procedure to enable access to Operator Interface functions:
1.
Select the Login/Logout button in the footer.
2.
Enter the Login Name.
3.
Enter the Login Password.
The operator interface provides access to all the control functions by selecting the applicable function
from the Navigate menu. At any time, operators can access the Help function for the current screen
by selecting the Help button in the screen header.
4.2
Working with Recipes
4.2.1
Create Recipe
Individuals with proper security can set up a recipe as follows:
1.
Point and click on the Navigate button in the footer of the screen to open the Main Menu.
2.
Select Recipe to open the Recipe submenu and choose the Freeze Drying recipe from the list.
The screen reformats to present the freeze drying recipe screen.
3.
Select Go Offline button at the top of screen. When offline is selected, the text above the
recipe table changes to “Offline status” and the recipe in view is offline (values are read from /
written to the hard drive).
4.
Select New Recipe. The system prompts that the current recipe values will be erased. Click on
Yes if current recipe is not in use.
5.
Press the “+” key to open the Add/Modify Recipe Step Window.
6.
Select a step that is pre-assigned an operation from the displayed list. The list outlines the
steps required for an automatic cycle.
7.
Define step parameters. The table below the step list permits entry of temperature, pressure, or
time required for the selected step.
Note:
8.
If a selected step requires only one or two inputs, data not required appears in
gray to alert an operator that the data is not applicable to the step type.
When the recipe is complete, select Product Notes from the menu bar along the top of the
recipe screen.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
91/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
9.
Enter desired cycle data, such as Plant Number, Product Name, Programmer’s name, and
product notes in the pop-up window.
10.
Select Close to enter the data.
4.2.2
Edit Recipe
Individuals with proper security can edit a recipe as follows:
1.
Login as required.
2.
Point and click on the Navigate button in the footer of the screen to open the Main Menu.
3.
Select Recipe to open the Recipe submenu and choose the Freeze Drying recipe from the list.
The screen reformats to present the freeze drying recipe screen.
4.
Select Go Offline button at the top of screen. When offline is selected, the text above the
recipe table changes to “Offline status” and the recipe in view is offline (values are read from /
written to the hard drive).
5.
Select Load Recipe button to open the recipe select pop-up window.
6.
Select the desired recipe from the list in the pop-up window then click on Load Recipe.
7.
Select Yes button to acknowledge that the selected recipe will replace the current recipe being
displayed.
8.
Add, insert, or delete steps from the recipe using the following keys:
4.2.3
a.
Press the “+” key to open the Add/Modify Recipe Step window. Select a step from the list
and press Accept.
b.
Press the “-” key to delete a recipe step.
c.
Press the “>” key to insert a blank recipe step.
Save Recipe
Individuals with proper security can save a recipe as follows:
1.
Select Save Recipe from the menu bar at the top of the Recipe screen to save a new recipe or
save over a recipe with the same name. Select Save Recipe As to save a modified recipe with
a new name to prevent overwriting the original recipe.
2.
Enter the desired file name at the prompt and press Accept. If the recipe already exists, the
system prompts for confirmation that overwriting the existing file is acceptable.
3.
Select Yes to continue saving the file or No to cancel the save function. A Save/Load Bar
appears indicating percentage of task completion.
92/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Note:
4.2.3.1
When saving the recipe to the hard drive, the recipe is validated. If the recipe is
not validated, it cannot be saved. If an error occurs during validation, a message
describing the error appears on the screen.
Batch Recipes
Apply the following rules when writing recipes to ensure the recipe follows the proper sequence of
operation.
•
The recipe can contain up to 50 steps.
•
Each freeze drying step will contain a maximum of 15 parameters. Examples of step parameters
are: temperature, pressure, time, vacuum cycling profile, operator acknowledge required to
continue, etc.
•
A freeze drying recipe can also contain a maximum of 10 text fields for product notes and a
maximum of 30 “non-step” type parameters and recipe name.
•
Use only one loading step, but it is an option that is not required for starting a recipe.
•
There must be at least one freezing step. The number of freezing steps required in a recipe
depends on the application; more may be added as necessary.
•
There is only one evacuation step, and it must follow a loading or freezing step and occur
immediately before a drying step.
•
There is at least one drying step. The number of drying steps required in a recipe depends on the
application; more may be added as necessary.
•
The pressure rise test is optional and is not required; but if it is used it must follow a drying step.
•
Pre-aeration is an optional step that may be used only once per recipe. Pre-aeration raises the
chamber pressure to stoppering pressure.
•
The stoppering option may be used only once in a freeze drying cycle. It is used for stoppering
product in vials and occurs after the product is dry. Never use a stoppering step when bulk
product trays are in use.
•
Aeration is used only once in a recipe. Aeration raises the chamber and condenser pressure to
atmospheric pressure in preparation for product removal.
•
Storage is an option that is used only once in a recipe. It is used after the product is dry, to keep
the product at a specific temperature, until the product may be removed from the chamber.
•
The Defrost, CIP, SIP, Leak Test, Bellows Tests, and the Filter Integrity Test cycles can not be
inserted into a freeze drying recipe. Each of these cycles must be treated as individual recipes.
•
The Leak Test and Bellows Tests are typically run following an SIP cycle and prior to starting the
next automatic freeze drying recipe.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
93/143
SC473501.doc
BOC EDWARDS
4.3
BOC Edwards
Pharmaceutical Systems
Starting an Automatic Freeze Drying Cycle
Individuals with proper security can start a Freeze Drying cycle as follows.
Note:
In order for the cycle to operate in auto mode, all valves must initially be in their
normal no cycle active state and all doors must be closed.
Note:
The system will perform an immediate shutdown any time the ABORT button is
activated at the PC. The Abort feature is password protected - only those
operators or supervisors who are logged into the system can abort the cycle.
1.
Login as required.
2.
Point and click on the Navigate button in the footer of the screen to open the Main Menu.
3.
Select Recipe to open the Recipe submenu and choose the Freeze Drying function from the
list. The screen reformats to present the freeze drying recipe screen.
4.
Verify the unit is Online. When Go Online is selected, the text above the recipe table changes
to “Online status” and the recipe in view is online (values are read from / written to the PLC).
When Go Offline is selected, the text above the recipe table changes to “Offline status” and the
recipe in view is offline (values are read from / written to the hard drive).
5.
Select Load Recipe button to open the recipe select pop-up window.
6.
Select the desired recipe from the list and click on Load Recipe.
7.
Select Start Cycle button at the top of screen to download the recipe and start the automatic
cycle.
8.
Select Yes button to run the selected cycle.
The freeze dryer operates according to the step functions in the recipe. Details on valve operation,
interlocks, and controls for each step are found in the Functional Specifications. The following text
briefly describes the steps in an automatic freeze drying cycle.
4.3.1
Loading
This is the first step in a freeze drying cycle. When shelf temperature reaches the recipe setpoint,
shelf loading is enabled, and the TCAR can then transfer vials from the loading accumulator table
(LAT) to the freeze dryer. The freeze dryer is loaded as follows:
94/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Caution:
The shelves must be fully loaded or completely empty and
clear of all foreign objects. Failure to do so will result in
damage to the shelves and the shelf stack assembly. See
Loading Shelves in Section 5 for Details.
If the product shelf is only half loaded with product, the
other half must be loaded with empty vials with stoppers.
1.
The hydraulic ram moves shelf 1 to the loading position.
2.
The freeze dryer signals the loading system that it is ready for loading.
3.
When the shelf is in position and the shelf temperature is within 2.0°C of the setpoint, the slot
door opens.
4.
The TCAR advances, transfers a load of vials to the shelf, and then retracts.
5.
When TCAR retraction is confirmed, the slot door closes, and the TCAR collects vials for the
next shelf.
6.
Steps 1 to 5 are repeated until all shelves are loaded.
7.
When all shelves are loaded, the freeze dryer signals the TCAR that loading is complete,
placing the TCAR in the normal state, and the cycle then advances to Freezing.
4.3.1.1
Load Product Step Error Recovery
Errors may occur during the loading phase. These errors require operator intervention in order to
resume or complete the freeze dryer load product step and continue the freeze drying cycle. Refer to
the TCAR Functional Specification for a description of the intervention procedure to correct the errors.
The errors include:
•
Operator Phase Hold - Insufficient Vials
•
Operator Phase Hold - Vial Count Change
•
Freeze Dryer Shelf Index Incomplete Alarm
•
The “slot door open” sensor fails to confirm the “open” status between successive shelf loadings.
4.3.2
Freezing
The freezing step continues lowering the shelf temperature to the setpoint. The recipe can be written
so that the product is gradually frozen in a series of freezing steps or frozen as quickly as possible.
Product must be frozen before evacuation to prevent condensate from entering and fouling the
vacuum pumps. Once the setpoint temperature is achieved the step advances.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
95/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
When the shelf fluid inlet temperature is within the deviation from setpoint specified in the engineering
parameters (+temp high limit / -temp low limit, typically ±1.0°C), the recipe automatically advances to
the next step. The next step can be another freezing step if the product is to be held at the same
temperature for a period of time.
4.3.3
Evacuation
This step quickly evacuates the chamber to the vacuum setpoint while maintaining the shelf
temperature at the freezing step setpoint.
During evacuation, the condenser begins cooling and the vacuum and booster pumps start. When
the condenser coil temperature is less than -40°C for the duration of the condenser freeze time (which
is specified on the Engineering Parameters screen, typically 10 minutes), the vacuum pump isolation
valves, main isolation valve, main vacuum valve, CIP manifold valve, steam/CIP isolation valve, and
air/nitrogen isolation valves open and draw a vacuum on the chamber.
Note:
The PLC logic must confirm that the main isolation valve is open prior to opening
the main vacuum valve.
When the vacuum is within the deviation from setpoint specified in the engineering parameters
(+vacuum high limit / -vacuum low limit, typically +50/-20 µBar), the recipe automatically advances to
the next step.
4.3.4
Drying
The drying step begins to heat the product while the very cold condenser coil draws moisture away
from the product. When the vacuum pressure and shelf temperature are within the deviation from set
points specified in the engineering parameters (typically +50/-20 µBar and ±1°C), the recipe
automatically advances to the next step. The drying step may be repeated as necessary to satisfy
product requirements.
There are three fixed vacuum alarm set points programmed for all drying steps. The Vacuum
Warning and Vacuum Fail – Product Protection alarms are disabled for 30 minutes after the Main
valve and Main Vacuum valve open during drying, allowing time for the system to reach the ramping
vacuum set point. The Vacuum Fail – Below Setpoint Alarm is enabled throughout the drying phase.
If a Vacuum Warning or Vacuum Fail – Product Protection alarm is triggered, the secondary vacuum
system is enabled. Both vacuum systems are used to evacuate the freeze dryer until the chamber
vacuum set point is reached and then the secondary vacuum system is de-energized.
1.
The Vacuum Warning alarm activates when the chamber vacuum is greater than the pressure
deviation set point. If the shelf temperature set point is > 20°C, the shelf fluid circulation pump
stops, the heater is disabled and the cycle timer holds. The Gas Bleed valve is closed. A
Vacuum Warning alarm is triggered and remains active until the chamber vacuum is below the
setpoint. If the shelf set point temperature is < 20°C, the shelf temperature control continues as
normal, the cycle timer holds, and the Gas Bleed valve is closed. A Vacuum Warning alarm is
triggered and remains active until the chamber vacuum is below the setpoint. In automatic
96/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
mode, the step timer continues when the chamber vacuum is equal to the vacuum set point and
normal temperature control is resumed.
2.
The Vacuum Fail – Product Protection alarm activates when the chamber vacuum is greater
than the product protection alarm set point. The PLC enters product protection mode, freezes
the product, and the cycle timer holds. The shelf fluid circulation pump is restarted, the heater
is disabled, and the Gas Bleed valve is closed. Compressor #1 is dedicated to shelf cooling
and compressor #2 is toggled between shelf and condenser cooling. The Vacuum Fail –
Product Protection alarm is annunciated at the PC and remains active until the chamber
vacuum reaches the vacuum set point. In automatic mode, the step timer continues when the
chamber vacuum is equal to the vacuum set point and normal temperature control is resumed.
3.
The Vacuum Fail - Below Setpoint alarm activates if the chamber pressure is ≤ the difference of
the current ramping vacuum set point and 20 µBar. The alarm remains active until the chamber
pressure rises above the difference of the current ramping vacuum set point and 20 µBar.
4.3.5
Pressure Rise Test (Moisture Test)
The pressure rise step indicates if moisture remains in the product. During this step, the chamber is
isolated from the condenser. If the chamber pressure rises above the calculated test pressure, the
test fails. The step automatically repeats until the test passes or the operator advances the step.
Note:
4.3.6
The vacuum warning and vacuum fail alarms are active during the pressure rise
test. If a vacuum alarms occurs during the test, the Main valve and main vacuum
valve must be re-opened to evacuate the freeze dryer to the last vacuum set point.
The shelf temperature is controlled to the same set point as in the previous step.
Aeration
This step aerates the chamber and condenser to the pre-aeration setpoint while maintaining the shelf
temperature at the set point established in the previous step. Once the Main Isolation valve closes,
the aeration valves open and aeration begins. When the chamber aeration set point is achieved, the
aeration timer starts. When the timer expires, the aeration valves close and the cycle advances to the
next step.
4.3.7
Stoppering
The rear access door and slot door must be closed for stoppering to be activated. This step collapses
the shelves (this is referred to as extending the shelf ram) to seal the vials. After the appropriate
stoppering pressure has been achieved, the shelf ram is held in position for the duration of the
stoppering timer (typically 10 seconds). If stoppering with aeration was selected as a recipe
parameter, the cycle advances to aeration without retracting the shelves. The shelf temperature is
controlled to the same set point as in the previous step.
If stoppering without aeration is selected in the engineering parameters, when the timer expires, the
shelves are retracted to the home position. When the stopper up timer expires, the cycle advances to
aeration. The shelf temperature is controlled to the same set point as in the previous step.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
97/143
SC473501.doc
BOC EDWARDS
4.3.8
BOC Edwards
Pharmaceutical Systems
Aeration
This step increases the chamber and condenser pressure to setpoint so that the chamber door can be
opened. The shelf temperature is controlled to the same setpoint as in the previous step. The Main
valve closes to isolate the chamber from the condenser. Isolating the chamber and condenser makes
it possible for the operator to remove vials from the shelves at the end of the cycle while the
condenser defrosts. When the Main valve closes, the aeration valves open and aeration begins.
When the chamber aeration set point is achieved, the aeration timer starts. After expiration of the
timer, the aeration valves close and the cycle advances to the next step.
4.3.9
Storage / Unloading
WARNING:
VENTING A LARGE CHAMBER CONTAINING INERT GAS
INTO THE WORK PLACE ATMOSPHERE CAN DISPLACE
OXYGEN AND CAUSE ASPHYXIA.
This step allows the vials to be removed from the freeze dryer. Shelf temperature is maintained at the
temperature setpoint for the duration of the step. The freeze dryer is unloaded as follows:
1.
The hydraulic ram moves the last-loaded shelf to the unloading position.
2.
The freeze dryer signals the TCAR that it is ready for unloading.
3.
When the shelf is in position and the shelf inlet temperature is within ±1.5°C of the setpoint, the
slot door opens.
4.
The TCAR advances to dock with the shelf, transfers a load of vials, and then retracts.
5.
When TCAR retraction is confirmed, the slot door closes.
6.
The TCAR moves to the UAT to unload vials and then returns to the freeze dryer to unload the
next shelf.
7.
Steps 1 to 6 are repeated until all shelves are unloaded.
8.
When all the shelves are unloaded, the freeze dryer signals the TCAR that unloading is
complete. The TCAR is placed in the normal state, and the Freeze Drying cycle is complete.
4.3.9.1
Unload Product Step Error Recovery
Errors may occur during the unloading phase. These errors require operator intervention in order to
resume or complete the freeze dryer unloading product step and continue the freeze drying cycle.
Refer to the TCAR Functional Specification for a description of the intervention procedure to correct
the errors. The errors include:
•
Operator Phase Hold – No More Shelves to be Unloaded
98/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
•
Freeze Dryer Shelf Index Incomplete Alarm
•
The “slot door open” sensor fails to confirm the “open” status between successive shelf unloading.
4.4
Starting an Optional Automatic Cycle
The optional automatic cycles are used to clean and sterilize the freeze dryer in preparation for a new
freeze drying cycle or to test freeze dryer components following a freeze drying and cleaning
sequence. The cycles must be run independently and can not be inserted into a freeze drying recipe.
The Defrost, CIP, and SIP cycles can be linked to form a cleaning recipe if desired. The Leak Test,
Bellows Tests, and FIT cycles are typically run after a SIP cycle.
The optional automatic cycles include:
•
Defrost
•
Shelf Ram Bellows Test
•
CIP
•
Main Valve Bellows Test
•
SIP
•
FIT
•
Leak Test
Individuals with the proper security can start an automatic optional cycle as follows.
1.
Login as required.
2.
Point and click on the Navigate button in the screen footer to open the Main Menu.
3.
Select Recipe to open the Recipe submenu and choose the desired cycle recipe from the list.
The screen reformats to present the selected cycle recipe screen.
4.
Modify recipe parameters and/or setup parameters as required.
5.
Select Start Cycle button at the top of screen to download the recipe and start the automatic
cycle.
6.
Select Yes button to confirm Start Cycle.
The freeze dryer operates according to step functions in a recipe. Details on valve operation,
interlocks, and controls for each step are found in the Functional Specification.
The following paragraphs briefly describe the steps in each optional automatic cycle and list the cycle
recipe and engineering parameters associated with each cycle.
4.5
Automatic Defrost Cycle
The automatic defrost cycle facilitates condenser defrost after a freeze drying cycle. The defrost cycle
admits steam into the condenser to defrost the coils.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
99/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Note:
In order for the cycle to operate in auto mode, all valves must initially be in their
normal no cycle active state and all doors must be closed.
Note:
The system will perform an immediate shutdown any time the ABORT button is
activated at the PC. The Abort feature is password protected - only those
operators or supervisors who are logged into the system can abort the cycle.
The following text briefly describes the steps in an automatic Defrost cycle.
4.5.1
Condenser Aerate and Drain
This step aerates the condenser to the aeration setpoint. When condenser pressure equals or
exceeds the aeration setpoint, the condenser drain valves open and the drain timer starts. When the
drain timer expires (typically 5 minutes), the condenser aeration and drain valves close and the cycle
advances.
4.5.2
Evacuate Condenser
This step uses the LRP to evacuate the condenser. The Main Drain valve closes, the LRP starts, and
the Condenser Drain valve opens. When the condenser pressure reaches the evacuation setpoint
specified in the engineering parameters, the cycle advances to the next step.
4.5.3
Steam Defrost
In this phase, ice is removed from the condenser coils by admitting steam into the condenser. The
temperature of the condenser drain is monitored to determine when the condenser coil is defrosted.
The control system monitors condenser pressure as steam is admitted. When the condenser
pressure reaches the steam pressure high limit set point, the Steam Defrost Supply valve closes. The
valve remains closed until condenser pressure falls below the set point, then the valve reopens. This
safety feature prevents contaminants from being drawn into the drain when the steam is dumped as a
result of pressure transducer failure.
The cycle advances when the condenser drain temperature is > 50°C for the defrost time specified in
the recipe parameter.
4.5.4
Condenser Drying
When the steam defrost phase ends, the LRP evacuates the condenser to remove moisture. The
cycle advances to the next step when the condenser drying timer expires.
4.5.5
Condenser Aeration
The condenser aeration valves open and aerate the condenser to the condenser aeration set point
specified in the system parameters. When the condenser pressure ≥ to the set point, the condenser
aeration timer starts and continues for the time specified in the system parameters. When the timer
100/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
expires, the condenser aeration valves close and the main drain valve opens. The Defrost cycle is
complete.
4.6
Automatic Clean-in-Place Cycle (CIP)
The CIP cycle washes particulate matter, and dried water-soluble residue from the interior of the
chamber and condenser. The CIP system cleans the chamber, condenser, shelf hoses, shelves, ram
bellows, Main valve bellows, and all ports and sight glasses in the freeze dryer. A sampling port
enables the collection of water samples for testing.
Note:
In order for the cycle to operate in auto mode, all valves must initially be in their
normal no cycle active state and all doors must be closed.
Note:
The system will perform an immediate shutdown any time the ABORT button is
activated at the PC. The Abort feature is password protected - only those
operators or supervisors who are logged into the system can abort the cycle.
The following text briefly describes the steps in an automatic CIP cycle.
4.6.1
Lock Rear Access Door
Prior to evacuation, the PLC checks that all doors are closed and retracts the shelves to the home
position. The PLC then pressurizes the loading door gasket. If the chamber door is locked, the cycle
advances to the next step. If the chamber door is unlocked, the LRP evacuates the chamber and the
door is locked. The LRP generates the vacuum necessary to compress the door gasket and align the
door locking pins with the door locking brackets. When the door is locked, the cycle advances to the
next step.
4.6.2
Aerate Chamber and Condenser
This step aerates the chamber and condenser to the pressure setpoint. The cycle advances after
reaching the setpoint and the timer expires.
4.6.3
Chamber Initial Rinse
The Main valve, Main Drain valve, and Condenser Drain valve open.
The CIP Skid WFI valve opens followed by the CIP Water Supply valve and, after 5 seconds, the
Steam/CIP Isolation valve. The CIP Manifold 1 valve opens to rinse the chamber interior. During this
process, the shelf ram extends to a pre-determined position then retracts to the home position
whereupon the CIP Skid WFI valve and then the CIP Water Supply valve close. The chamber is
drained for 30 seconds with the process air vent valves open for venting. When draining is complete,
the process air-vent valves and the CIP Manifold 1 valve close and the step advances to the next
manifold.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
101/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
The above sequence is repeated as written for CIP Manifolds 2 and 3. For the CIP Manifold 4
sequence only, the shelf ram remains in the home position and is not extended. When the CIP
Manifold 4 sequence is completed, the cycle advances to the next step.
4.6.4
Condenser Initial Rinse
The CIP Water Supply valve opens followed by the skid WFI valve. The Condenser Inlet valve opens
to rinse the condenser with water for 30 seconds (or as specified in the engineering parameters)
whereupon the CIP Water Supply valve closes. The chamber is drained for 30 seconds with the
process air vent valves open for venting. When draining is complete, the process air vent valves, the
Condenser Inlet valve, and the Condenser Drain valve close and the cycle advances to the next step.
4.6.5
Clean Condenser
In this phase, the condenser is filled to a specified level. The cleaning solution will be either WFI only
or WFI/base/acid/detergent depending on the recipe selection.
If the WFI only option is selected, the condenser vent valve, CIP water supply valve, condenser drain
valve and CIP recirculation pump inlet valve open and admit WFI into the condenser. The CIP
overflow vent valve opens followed by the CIP water supply valve, condenser drain valve, CIP
return/drain valve, and condenser inlet valve. The WFI loop valve opens to admit WFI water to the
condenser. When water has entered the drain lines, the CIP return valve and chamber drain valve
open for a specified time to allow the drain lines to completely fill with water. When the condenser is
filled to the specified level, the CIP water supply valve closes and the CIP Recirculation Pump starts
and washes the condenser. When the wash timer expires, the cycle advances to the next step.
If the WFI/base/acid/detergent option is selected, the prepared cleaning solution from the solution
tank is pumped into the condenser and re-circulated. When the wash timer expires, the cycle
advances to the next step.
4.6.6
Clean Chamber
The CIP Recirculation Pump remains on and the CIP Manifold 1 valve opens. As water is pumped
through CIP Manifold 1, the shelf ram is moved down and up for the number of cycles entered in the
recipe parameters. When the number of shelf ram cycles equals the recipe parameter, the shelf ram
retracts to the home position. The CIP manifold 1 valve closes and the step advances to the next
manifold.
The above sequence is repeated as written for CIP Manifolds 2 and 3. For the CIP Manifold 4
sequence only, the shelf ram remains in the home position and is not extended. When the CIP
Manifold 4 sequence is completed, the CIP Recirculation Pump shuts down and the cycle advances to
the next step.
4.6.7
Drain Chamber and Condenser
The CIP Recirculation Pump Drain valve opens to drain water in the recirculation line for the time
specified in the engineering parameters (typically 10 minutes).. The Condenser Drain valve and
Chamber Drain valve open for the time specified in the engineering parameters (typically 5 minutes)
102/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
and drain water from the chamber and condenser. The process air vent valves, Condenser Inlet
valve, and chamber CIP Manifold 1 valve open to provide a vent during draining. When draining is
complete, the valves close and the cycle advances to the next step.
4.6.8
Chamber Final Rinse
Refer to Chamber Initial Rinse for this procedure then advance to Condenser Final Rinse.
4.6.9
Condenser Final Rinse
Refer to Condenser Initial Rinse for this procedure then advance to Final Drain.
4.6.10
Final Drain
The Condenser Drain valve, Chamber Drain valve, Main Drain valve, Condenser Inlet valve, CIP
Return valve, CIP Manifold valves, CIP Recirculation valve, and process room air valves open to vent
and drain the chamber and condenser for the time specified in the engineering parameters. When the
timer expires, the valves close and the cycle advances to the next step.
4.6.11
System Drying and Unlock Door
Drying time is selected at the start of the CIP cycle. If a drying time of 0 minutes is selected, the
system drying phase is deactivated and the CIP cycle will end with the chamber door locked and
valves set to their normal no cycle state. If the drying time selected is > 0, the system drying phase is
activated. The LRP is started and, when the pressure is ≤ 0.15 BarA, the drying timer starts, the slot
door gasket vent valve opens, and the slot door gasket is deflated. When the timer expires, the door
is unlocked and the LRP shuts down. The Main valve, CIP Recirculation valves, Condenser Drain
valve, Condenser Inlet valve, and CIP Manifold valves close and the cycle advances to the next step.
4.6.12
Aerate Chamber and Condenser
The Main Valve Bellows is evacuated for five minutes or until the pressure < 1000 µBar. The Main
Isolation valve closes and the aeration valves open to aerate the chamber and condenser. When the
chamber pressure is ≥ the engineering parameter set point, a one-minute timer starts. When the
timer expires, the aeration valves close and the Main Drain valve opens. The CIP cycle is now
complete and all valves have returned to their normal de-energized conditions.
4.7
Note:
Starting a Sterilization Cycle (SIP)
Before starting a SIP cycle, remove any residual vials and stoppers from the
chamber.
The freeze drying chamber and ice condenser can be sterilized with saturated steam up to 126°C and
2 BarG. Saturated steam passes through the pipe work, sterile filters, and valves exposed to the
product. During sterilization, temperature is measured in three locations: the chamber drain, the
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
103/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
condenser drain, and the sterile filter drain. These locations are furthest from the steam source and
will be the last locations to heat up. When drain temperatures reach the sterilization temperature set
point, the freeze dryer is at, or above, the required sterilization temperature. The freeze dryer is held
at the sterilization set point temperature for a recipe-specified time. When sterilization is complete,
steam discharges down the drain. The LRP then dries the sterile filter, freeze dryer, and aeration
piping.
Note:
In order for the cycle to operate in auto mode, all valves must initially be in their
normal no cycle active state and all doors must be closed.
Note:
The system will perform an immediate shutdown any time the ABORT button is
activated at the PC. The Abort feature is password protected - only those
operators or supervisors who are logged into the system can abort the cycle.
The following text briefly describes the steps in an automatic SIP cycle.
4.7.1
First Evacuation and Lock Door
During this step of the SIP cycle, the shelf stack is placed in the home position and all valves exposed
to product during the freeze drying cycle open.
The LRP starts and evacuates the chamber and condenser to the door locking set point or preevacuation set point, whichever is lower. When the chamber vacuum reaches the set point, the
chamber door is locked. The LRP stops and the cycle advances to the next step
Note:
4.7.2
If the evacuation setpoint is not reached (during door locking or pre-purging
evacuation) within 30 minutes, then a “Failed to Reach Evacuation Setpoint” alarm
is activated at the PC. Evacuation continues until the evacuation setpoint is
achieved.
Chamber Jacket Heating
The chamber jacket is heated before starting a SIP cycle. The jacket circulation pump starts and
circulates heated silicone oil through the freeze dryer jacket. When the jacket is heated to set point,
the jacket coolant circulation pump stops, and the cycle advances to the next step.
4.7.3
One Steam Purge
The Steam Supply valve admits steam until the chamber or condenser pressure ≥ the steam pressure
set point specified in the engineering parameters. When the chamber or condenser pressure ≥ steam
discharge pressure specified in the engineering parameters, the steam trap bypass valves close, the
Main Drain Bypass valve and Steam Quench valve open, and the cycle advances to Steam.
104/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
4.7.4
Two Steam Purges
In the first steam purge, steam is admitted into the chamber and condenser until the pressure ≥ the
steam discharge pressure setpoint. When the setpoint is reached, steam is discharged by opening
the Main Drain valve and Steam Quench valve for 30 seconds or until the chamber or condenser
pressure ≤ steam post-purge pressure. The Main Drain valve closes and the LRP evacuates the
chamber and condenser to the pre-evacuation pressure set point. When the setpoint is reached, LRP
evacuation stops and the step advances to the second steam purge.
In the second steam purge, steam is again admitted into the chamber and condenser until the
pressure ≥ the steam pressure set point specified in the engineering parameters. When the chamber
or condenser pressure ≥ steam discharge pressure specified in the engineering parameters, the
steam trap bypass valves close, the Main Drain Bypass valve and Steam Quench valve open, and the
cycle advances to Steam.
4.7.5
Three Steam Purges
In the first steam purge, steam is admitted into the chamber and condenser until the pressure ≥ the
steam discharge pressure setpoint. When the setpoint is reached, steam is discharged by opening
the Main Drain valve and Steam Quench valve for 30 seconds or until the chamber or condenser
pressure ≤ steam post-purge pressure. The Main Drain valve closes and the LRP evacuates the
chamber and condenser to the pre-evacuation pressure set point. When the setpoint is reached, LRP
evacuation stops and the step advances to the second steam purge.
In the second steam purge, steam is again admitted into the chamber and condenser until the
pressure ≥ the steam discharge pressure setpoint. When the setpoint is reached, steam is
discharged by opening the Main Drain valve and Steam Quench valve for 30 seconds or until the
chamber or condenser pressure ≤ steam post-purge pressure. The Main Drain valve closes and the
LRP evacuates the chamber and condenser to the pre-evacuation pressure set point. When the
setpoint is reached, LRP evacuation stops and the step advances to the third steam purge.
In the third steam purge, steam is again admitted into the chamber and condenser until the pressure ≥
the steam pressure set point specified in the engineering parameters. When the chamber or
condenser pressure ≥ steam discharge pressure specified in the engineering parameters, the steam
trap bypass valves close, the Main Drain Bypass valve and Steam Quench valve open, and the cycle
advances to Steam.
4.7.6
Steam
Sterilization of the freeze dryer occurs during the Steam phase. The freeze dryer is pressurized with
steam so that the desired sterilization temperatures can be reached at the drains. The sterilization
timer advances when the temperature of each drain equals or exceeds the sterilization set point. The
interval between the last steam purge and the start of the sterilization timer is called heat-up.
The steam sterilization cycle is not controlled by the drain temperatures but by the steam pressure
required to reach sterilization temperature setpoint at the drains. The SIP recipe defines the pressure
range that must be maintained to ensure that sterilization temperatures are achieved at the drains.
The Steam Supply valve controls the amount of steam admitted to the freeze dryer based on current
chamber or condenser pressure measurements and the sterilization pressure setpoint.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
105/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
The sterilization timer starts when the condenser drain and sterile filter drain temperatures equal the
sterilization temperature setpoint. Steaming continues for the duration of the timer. When the timer
expires, the cycle advances to the next step.
There are three alarms programmed for the steaming sequence:
1.
“Sterilization Temperature Failed to Reach Setpoint” alarm occurs when the chamber,
condenser, or sterile filter drain temperatures do not reach the sterilization temperature setpoint
within the period specified on the Engineering Parameters screen. The cycle will advance to
Steam Discharge.
2.
“Sterilization Temperature Below Setpoint” alarm occurs when the chamber, condenser, or
sterile filter drain temperatures fall below the sterilization temperature setpoint for the period
specified on the Engineering Parameters screen. The sterilization timer pauses until the drain
temperatures again reach the sterilization setpoint. When the timer expires, the cycle advances
to Steam Discharge.
3.
“Steaming Time is Excessive” alarm occurs when the total sterilization time (the sum of the
sterilization time and any time elapsed due to a “Sterilization Temperature Below Setpoint”
alarm) exceeds the period specified on the Engineering Parameters screen. The cycle then
advances to Steam Discharge.
4.7.7
Steam Discharge
This step occurs when steaming is complete or there has been an error that stops the steaming
process. The Steam Supply valve closes. The Main Drain valve closes and the Main Drain Bypass
valve and Steam Quench valve open. The Main Drain is a three-inch valve and would discharge
steam too quickly. Instead, steam is discharged slowly through the one-inch Main Drain Bypass valve
and quenched with water, cooling and collapsing the steam.
Steam is discharged down the drain until the chamber pressure is ≤ the steam discharge pressure set
point specified in the engineering parameters. At this point, the Main Drain Bypass valve and Steam
Quench valve close and the cycle advances to the next step.
4.7.8
Filter Drying
The sterile filter valves open. The LRP starts and dries the sterilization filter for the filter drying time
specified in the engineering parameters (typically 15 minutes). When the timer expires, the sterile
filter valves close and the cycle advances to the next step.
4.7.9
System Drying
The sterile piping valves and Condenser Drain valve open. The LRP evacuates the chamber and
condenser. When the chamber pressure reaches the pre-evacuation pressure set point specified in
the engineering parameters, the Sterile Filter valves open and the system drying timer starts. The
LRP maintains the chamber pressure for the time specified in the engineering parameters (typically 60
minutes). When the timer expires, the cycle advances to the next step.
106/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
4.7.10
Condenser Cooling
Condenser cooling is initiated. The condenser cooling circulation pumps starts and circulates chilled
silicone oil through the condenser coils. When the condenser temperature falls below -40°C, the
condenser cooling timer starts. When the timer expires, the main isolation valve and sterile line
valves close, and the cycle advances to Shelf Cooling.
4.7.11
Shelf and Chamber Jacket Cooling
The shelf cooling and jacket cooling circulation pumps start and circulate chilled silicone oil through
the shelves and freeze dryer jacket. The temperature is controlled to the setpoint (typically 15°C) for
the time specified in the engineering parameters. When the timer expires, the cycle advances.
4.7.12
Aeration
The primary vacuum system is enabled. The Main Valve Bellows is evacuated for 5 minutes, or until
the pressure reaches 100 mTorr or less. The Main valve closes and then the chamber and condenser
are aerated. When the chamber pressure reaches the aeration set point, the aeration timer starts.
When the timer expires, the aeration valves close and the Main Drain valve opens. The SIP cycle is
complete.
4.8
Leak Test
The Leak Test confirms that the system leak rate is within the allowable rate. In this test, the system
is defined as the chamber, condenser, inlet piping, and sterile filters. The test is usually performed
following a SIP cycle as the wide range of temperatures and pressures associated with SIP can cause
bolts, fittings, or clamps to loosen up, creating a vacuum leak. A “virtual” vacuum leak can also occur
if the filters or system are not completely dry and water is out-gassed.
Note:
In order for the cycle to operate in auto mode, all valves must initially be in their
normal no cycle state and all doors must be closed.
Note:
The system will perform an immediate shutdown any time the ABORT button is
activated at the PC. The Abort feature is password protected - only those
operators or supervisors who are logged into the system can abort the cycle.
The following text briefly describes the steps in an automatic leak test cycle.
4.8.1
Evacuate Chamber & Condenser
Before evacuation, the shelf ram is automatically retracted to the home position. Condenser cooling
is enabled and the condenser coil is cooled to −40°C or below. The condenser is cooled so that any
water or water vapor in the freeze dryer will be collected on the condenser coils. This prevents water
damage to the vacuum pumping system.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
107/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
As the condenser cools to set point, the vacuum pumps are enabled. When the condenser
temperature has been at or below −40°C for 10 minutes, the Main Isolation valve opens. The Main
Vacuum valve opens and the vacuum pumps evacuate the chamber and condenser to 100 µBar. The
chamber and condenser CIP valves, the Sterile Filter valves, and aeration valves also open so that
the entire sterile aeration pathway is leak tested.
Caution:
4.8.2
During the automatic leak test do not evacuate the
bellows (chamber or condenser). The bellows should be
vented to atmosphere. Evacuating the bellows during a
leak test will hide a potential bellows leak.
Dry System
When the chamber vacuum equals the engineering parameter set point, the system continues drying
for the time specified in the engineering parameters (typically 60 minutes). When the timer expires,
the cycle advances to the next step.
4.8.3
Leak Test
The Main Vacuum valve closes and chamber vacuum is recorded. A selectable pressure rise value is
added to the recorded chamber vacuum, resulting in the test pressure. If the chamber vacuum rises
above the test pressure within the test time, an alarm displays “Leak Test Failed” at the alarm screen.
Activating the “Retry” button at the PC restarts the test at the Dry System step. If the chamber
vacuum does not rise above the test pressure within the test time, the test passes, the message “Leak
Test Passed” is displayed, and the cycle advances to the next step.
4.8.4
Aeration
The Main Isolation valve closes, condenser cooling stops, and the vacuum system is turned off. The
chamber and condenser are aerated until chamber pressure equals the aeration set point, starting a
timer. When the aeration timer expires, the leak test is complete and all valves return to their normal
state. The Leak Test is complete.
4.9
Shelf Ram Bellows Test
This test evaluates the integrity of the shelf stack ram bellows, ensuring there are no leaks. The test
involves evacuating the bellows and confirming that the vacuum setpoint is achieved within a
specified period.
Note:
In order for the cycle to operate in auto mode, all valves must initially be in their
normal no cycle active state and all doors must be closed.
108/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Note:
The system will perform an immediate shutdown any time the ABORT button is
activated at the PC. The Abort feature is password protected - only those
operators or supervisors who are logged into the system can abort the cycle.
The following text briefly describes the steps in an automatic shelf ram bellows test cycle.
4.9.1
Lower Shelf Stack and Evacuate Bellows
The chamber is automatically aerated with process air to the aeration set point, starting a timer.
When the aeration timer expires, the vacuum pumps start. The shelf stack extends to a
predetermined position and the bellows is evacuated. The shelf stack is extended to expand the
bellows volume and expose the greatest possible surface area to the pressure differential between
the chamber and the vacuum inside the bellows.
4.9.2
Bellows Test
A test timer starts (time from recipe) and the bellows pressure is compared to the recipe set point. If
the pressure is less than or equal to the set point within the test time, the test is complete and “Ram
Bellows Test Passed” is displayed on the screen. If the test timer expires and the set point is not
reached, an alarm sounds, and the message “Ram Bellows Test Failed” is displayed. The cycle
advances to the next step.
4.9.3
Raise Shelves and Vent Bellows
The shelf stack retracts to the home position. The vacuum pumps stop, and the bellows vent valve
opens. When all valves return to their de-energized state, the Shelf Ram Bellows Test is complete.
4.10
Main Isolation Valve Bellows Test
This test evaluates the integrity of the Main Isolation valve bellows, ensuring there are no leaks. The
test involves evacuating the bellows and confirming that the vacuum setpoint is achieved within a
specified period.
Note:
In order for the cycle to operate in auto mode, all valves must initially be in their
normal no cycle active state and all doors must be closed.
Note:
The system will perform an immediate shutdown any time the ABORT button is
activated at the PC. The Abort feature is password protected - only those
operators or supervisors who are logged into the system can abort the cycle.
The following text briefly describes the steps in an automatic Main Isolation Valve Bellows Test cycle.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
109/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
4.10.1
Evacuate Bellows
The condenser is automatically aerated with process air to the aeration setpoint, starting a timer.
When the aeration timer expires, the vacuum pumps start and the Main Isolation valve closes. The
cycle advances to the next step.
4.10.2
Bellows Test
A test timer starts (time from recipe) and the bellows pressure is compared to the recipe set point. If
the pressure is less than or equal to the set point within the test time, the test is complete and “Main
Valve Bellows Test Passed” is displayed on the screen. If the test timer expires and the set point is
not reached, an alarm sounds, and the message “Main Valve Bellows Test Failed” is displayed. The
cycle advances to the next step.
4.10.3
Vent Bellows
The vacuum pumps stop and the bellows vent valve opens. When all valves return to their deenergized state, the Main Isolation Valve Bellows Test is complete.
4.11
Filter Integrity Test (FIT)
The integrity of the sterile 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 the FIT on one of the
filters or both depending on the selection in the recipe.
4.11.1
Start of FIT
The FIT is initiated at the SCADA PC and proceeds according to the following steps. During the
cycle, the following integrity test specific alarms can be generated:
•
Lack of steam
•
Test pressure too high
•
WIT water temperature too high
•
Test pressure drop too high
•
WIT water temperature too low
•
WIT water level too low in tank
•
Test pressure not built up
•
WIT test failed
When an alarm or combination of alarms indicates before the test starts, a “WIT Not Started”
message will be displayed. Correct the alarm condition(s) before restarting the test.
Note:
In order for the cycle to operate in auto mode, all valves must initially be in their
normal no cycle active state and all doors must be closed.
Note:
The system will perform an immediate shutdown any time the ABORT button is
activated at the PC. The Abort feature is password protected - only those
operators or supervisors who are logged into the system can abort the cycle.
110/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
The following text briefly describes the steps in an automatic filter integrity test cycle.
4.11.2
Pressurize Slot Door and Vent Chamber
During this step, the slot door is pressurized and the chamber is vented.
4.11.3
Fill WFI Water Tank
The water required for the WIT test is created by condensing steam in the WFI water tank. Cooling
water is circulated during this step. Steam is admitted into the WFI water tank and condensed until
the tank is filled to a specified level. Cooling water circulation continues until the water is cooled to
the WFI water temperature setpoint. During this phase, the chamber is aerated to the pre-aeration
setpoint specified in the engineering parameters.
4.11.4
Flood Filter
The filter is aerated for one minute and is then flooded with water from the WFI water tank. The water
temperature stabilizes for the time specified in the engineering parameters and then the water
temperature is checked. If the water temperature in the filter > the temperature specified in the
engineering parameters, the filter is drained and re-filled with water from the WFI water tank. If the
water temperature is within allowable limits, the cycle advances to the next step.
4.11.5
Perform Integrity Test
The pressure drop across the filter element is monitored for the time period specified in the
engineering parameters. If the pressure drop is within allowable limits, the test passes, and the step
automatically advances to drain filter housing. If the test fails, the following options can be selected at
the Operator Interface PC:
•
Test unsuccessful but to be repeated immediately. Do not proceed with the drain operation.
•
Test unsuccessful and not to be repeated immediately. Proceed with the drain operation. Skip
filter drying.
4.11.6
Drain Filter Housing
The filter is drained for the time period specified in the engineering parameters. If the test failed, the
FIT Cycle ends when the drain timer expires. If the test passed, the cycle advances to the next step.
4.11.7
Filter Cartridge Drying
The filter cartridge is dried, using the LRP, for the time specified in the recipe parameters. When the
timer expires, the cycle advances. If two filters were selected for testing, the preceding steps repeat,
starting with Flood Filter, to test the integrity of the second filter, otherwise the cycle advances to the
next step.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
111/143
SC473501.doc
BOC EDWARDS
4.11.8
BOC Edwards
Pharmaceutical Systems
Drain Tank
The WFI tank is drained and aerated for the time specified in the engineering parameters. When the
timer expires, the FIT Cycle is complete.
4.12
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) 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 the desired function to activate or deactivate 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 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 is 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
and the differential pressure across the pump is above the minimum pressure required.
•
Steam Defrost valve cannot be opened unless Main valve and Main Vacuum valve are closed.
•
Main valve between chamber and condenser cannot be opened if Steam Defrost valve is open.
•
The Main Vacuum valve cannot be opened if the Steam Defrost valve is open.
•
If a compressor, vacuum pump, or booster pump is started in Device Mode, then any
corresponding cooling valves will be automatically opened to cool the device while it is running.
112/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
•
Silicone N2 Supply valve cannot be opened if a high pressure condition exists at PSHL50 for the
silicone expansion tank.
•
There is no provision for activation of the shelf and condenser cooling valves.
•
Rear access door lock/unlock solenoids will not energize to extend/retract primary/secondary
pistons unless the rear access door is open and the hydraulic pump is running.
Note:
All devices return to their de-activated state after exiting Device Mode.
4.13
Security - Adding Users
New users must first be added to the Windows XP User Manager because each iFIX security account
will be synchronized with a corresponding Windows XP account. Then an Administrator or Developer
level user adds a new user from the Security Configuration screen. Enter the full name, domain, login
timeout, and group membership when adding a new user. The password is entered in the Windows
XP User Manager only.
Adding New Users to iFIX and Windows XP:
1.
Shutdown all programs
2.
Log-off:
a.
Shutdown iFIX.
b.
Select Start / Shutdown.
c.
Log off the current user.
3.
Press CTRL-ALT-DEL twice to open Log-on Window.
4.
Log on as an administrator. User name: Administrator, Password: none (just hit enter).
5.
Access User Management functions:
6.
a.
Select All Programs / Administrative Tools.
b.
Select Computer Management / System Tools.
c.
Select Local Users and Groups / Users.
Enter new user information:
a.
Decide if the new user will be an administrator, supervisor, maintenance user (if
applicable), operator, or public user.
b.
Right-Click the Users and select New User.
c.
Enter user name, full name, and password fields.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
113/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
d.
Right-Click the New User in right-hand window and select Properties.
e.
Select Add under the “Member of” tab.
f.
Select Advanced and Find Now.
g.
Select Group.
Note:
The group must match the group name configured in iFIX security for new user.
Valid group names are Operator, Supervisor, Maintenance Level 1, and
Maintenance Level 2. Refer to User Privileges for additional information.
h.
Click OK to accept the selected group and close the window.
i.
Click OK to close the window and return to the user Properties window.
j.
Select Apply then click OK to close the user Properties window.
7.
Repeat step 6 for each new user.
8.
Close Computer Management by clicking on the 'X' in the upper right-hand corner of the
window.
Caution:
All new users added to iFIX must exist in Windows XP.
Do NOT alter the iFIX BOC or Administrator accounts or
pre-configured group accounts. Do NOT alter the
Windows XP BOC account or pre-configured group
accounts. The administrator account (user name
Administrator) can be modified.
9.
Select Start / Programs / Intellution FIX / System Configuration.
10.
Select Configure and then Security from the root menu.
11.
Select Edit and then User Accounts from the root menu.
12.
Select Add and select the NT security checkbox.
13.
Enter Full name. The Full name must match the user name in Windows XP exactly.
14.
Enter the Login timeout:
a.
For administrators, enter 00:00:00.
b.
For supervisors, enter 00:30:00.
114/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
15.
c.
For operators, enter 00:05:00.
d.
Select the Modify button under Group Membership.
e.
Highlight the desired group under Available and select Add.
f.
Click OK twice.
Repeat step 14 for each new user.
4.13.1
Disabling Users
To disable a user in IFIX and Windows XP:
1.
The user must be logged on as BOC developer or Administrator.
2.
Click on the Start button in the Microsoft Windows taskbar to open the Start Menu and select:
a.
All Programs
b.
Administrative Tools
c.
Computer Management / System Tools
d.
Open Local Users and Groups / Users
3.
Select the desired user to display properties for that user.
4.
Check the box labeled “Account is disabled.”
4.14
iFIX System Backup
The iFIX Backup & Restore Wizard is used to perform a system backup. To backup all custom
configuration data, the user must select the “Backup the entire system” checkbox displayed on the
Wizard dialog.
The following table contains the options displayed on the Wizard dialog along with a description of
each option in case the user requires a partial backup or restore.
Table 4.1: Backup and Restore Options
Description
Alarm Files
Extension
*.ALM
Application Files
*.*
Chart Group Wizard Files
Database ASCII Files
Database Files
Database/Driver CSV Files
*.CSV
*.GDB
*.PDB,*.AAD
*.CSV
PSGA
Operating Manual
Comments
Created by Alarm file service, printout using text
editor
Application specific files, see Application File Table
in this section
NOT USED1
NOT USED1
Process database configuration
Exported driver configuration files
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
115/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Description
Driver Config. Binary Files
Event Schedule files
Global Definition Files
Historical Config. Files
Historical Data Files
Extension
*.*
*.EVS
*.FXG
*.CFG,*.HGP,*.DAT
*.H*
Master Recipe Files
*.RCM
Picture files
*.GRF,*.FDS,
*.FTB,*.LST
Recipe Control files
SCU files
Security files
*.RCC
*.SCU,*.INI,*.CFG
*.UTL,*.^TL,*.AUT,*
.RPT,*.DOV
*.TGD,*.TGS,
*.TGE
Tag group files
Comments
E.g. NODE0.ABR, NODE0.SIX, NODE0.IDS
Schedule1.EVS
E.g. User.fxg, ExpertGlobals.fxg
Tag configuration for historical collection groups
Historical data collected while the system is running,
can be printed by printing Historical Trending Screen
Used for freeze drying recipe screen, can be printed
by printing recipe screen
GRF = Picture files
FDS = Dynamo sets (DEFAULT2)
FTB = Color table files (DEFAULT2)
LST = The Tables.LST file is an ASCII file that
contains the names of the color tables (DEFAULT2)
NOT USED1
System configuration files
Security configuration files
TGD = Picture Tag Group files
TGS = Optimized tag group storage files
TGE = Legacy tag group files for use with the recipe
builder application
Toolbar files
*.TBX,*.TBC
TBX = toolbar files (DEFAULT2)
TBC = toolbar button category files (DEFAULT2)
1
NOT USED - This file type may not exist on the system because this iFIX feature is not used.
2
DEFAULT - These files are configurable and are required by the system. These files have not been
modified. They are the default files that are installed with iFIX. Also, additional files of this type have not
been created.
116/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
The APP directory is a repository for custom files, such as reports and other non-iFIX configuration
files. The iFIX Backup and Restore Utility does a recursive backup of all files and directories stored in
the APP directory. The files stored in the app directory include the following:
Table 4.2: Application Files
Description
Report Templates and
XLReporter scheduler [option]
Temporary Excel Files[option]
Report output files [option]
Full Path
Dynamics\App\Reports\Templates
\*.*
Dynamics\App\Reports\Temp\*.*
Dynamics\App\Reports\PDF
Reports\*.pdf
Universal Datalink Files
Picture Configuration
information
CSV format file
Dynamics\App\PicConfig\*.udl
Dynamics\App\PicConfig\*.csv
Log files
AIS block
Master recipe template for the
Freeze Drying recipe
4.14.1
Dynamics\App\PicConfig\
schema.ini
Dynamics\App\*.csv
Dynamics\App\AIS\*.*
Dynamics\App\MasterRecipes\
Frzdry.rcm
Comments
Template for batch reports
Required for creating batch reports
Completed batch reports - can be
viewed, printed from Batch Report
Screen
SQL Audit trail connection
Dynamic data configuration for
pictures
Required for retrieving information
from csv files
VBA errors log
Required for analog input scaling
Template for creating new recipes
Microsoft SQL Server Desktop Edition Audit Trail Backup
Microsoft SQL Server Desktop Edition will be configured to perform the following:
1
Weekly full backups of the audit trail (Lyo and Archive databases) to tape.
2
Daily incremental backups of the audit trail to tape.
Backups of the SQL databases are performed automatically by the system, using the automated Jobs
feature resident in SQL Enterprise Manager. A tape needs to be in the drive every night by midnight,
otherwise the backups will fail.
It is important to note that the backup procedures themselves are not resident inside the Lyo or
Archive Database. They are management tools in SQL. Because of this, the backup routines will not
be backed up as part of a SQL database backup. This can be done using the standard Windows
Backup feature to CD-RW.
4.14.1.1
Weekly Backup
A SQL scheduled job, Weekly Backup, performs weekly backups. This job is located in SQL
Enterprise Manager \ console root \ Microsoft SQL servers \ SQL server Group\ (local) (Windows NT)
Management\ Jobs. The Weekly Backup job comprises 2 steps, Backup Lyo, and Backup Archive.
The job is scheduled to run automatically once a week starting on Sunday night at 00:00 hours. Once
the job starts, the Backup Lyo and then Backup Archive steps run in sequence to back up the Lyo and
Archive databases.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
117/143
SC473501.doc
BOC EDWARDS
Note:
BOC Edwards
Pharmaceutical Systems
On system initialization or when a new tape is inserted, a weekly backup must be
performed before a daily backup. Daily backups append to an existing database
and without one weekly backup on the tape, no database will reside on the tape.
There are 2 options: 1) manually start the “Weekly Backup” Job after inserting the
new tape, or 2) Insert the new tape before the weekly backup starts but after the
last daily backup completed.
The tape must be physically labeled for the time period of the backup as decided by the system
administrator.
4.14.1.2
Manual Weekly Backup
1.
Ensure an 8mm DAT Tape is in the tape drive.
2.
Start SQL Enterprise manager.
3.
Under console Root, double-click “Microsoft SQL Servers”.
4.
Double-click “SQL Server Group”.
5.
Expand “(local) (Windows NT)” by clicking on the + next to it.
6.
Select “Management\Jobs”.
7.
Right-click the required Job, “Weekly Backup” and select “Start Job”.
8.
Check the Log File (see log file section).
4.14.1.3
Daily Backup
A SQL scheduled Job, “Daily Backup”, performs daily backups (changes over the past 24 hours). This
Job is located in SQL Enterprise Manager \ console root \ Microsoft SQL servers \ SQL server Group\
(local) (Windows NT) Management\ Jobs. The “Daily Backup” contains 2 steps: 1) Backup Lyo, and
2) Backup Archive. “Daily Backup” is scheduled to run automatically every 24 hours starting at
11:45:00 hours (HH:MM:SS). Once the Job starts, the “Backup Lyo” and then “Backup Archive” steps
run in sequence to back up the Lyo and Archive databases.
Note:
On system initialization or when a new tape is inserted, a weekly backup must be
performed before a daily backup. Daily backups append to an existing database
and without one weekly backup on the tape, no database will reside on the tape.
SQL Weekly Backup Schedule
118/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
4.14.1.4
SQL Weekly Backup Schedule
The procedure below describes how to view and change the backup Job schedule. This is strictly an
administrator function.
1.
Start SQL Enterprise Manager.
2.
Under Console Root, double-click “Microsoft SQL Servers.”
3.
Double-click “SQL Server Group”.
4.
Expand “(local) (Windows NT)” by clicking on the + next to it.
5.
Expand Management selection by clicking + next to it.
6.
Expand SQL Server Agent by clicking + next to it.
7.
Select “Jobs”.
8.
In the window on the right, right-click the desired job and select Properties.
9.
Select the “Schedules” Tab.
10.
Double-click the schedule.
11,
Select the Change… button.
12.
Change the desired settings.
13.
Select OK to save.
Figures 4.1, 4.2 and 4.3 illustrate the SQL Server Enterprise Manager scheduled job modification
process.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
119/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Figure 4.1: SQL Server Archive Job
Figure 4.2: SQL Server Archive Job Schedule
120/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Figure 4.3: SQL Server Archive Job Schedule Change
4.14.1.5
Restoration of SQL Backups
Restoration should be performed by the SQL Administrator only when a catastrophic event occurs. If
a database is restored, all audit trail data in the current database will be overwritten and all database
entries that occurred after the last backup will be lost. To restore a database:
1.
Insert the backup tape in the tape drive.
2.
Start SQL Enterprise manager.
3.
Under console Root, double-click “Microsoft SQL Servers”.
4.
Double-click SQL Server Group.
5.
Expand “(local) (Windows NT)” by clicking on the + next to it.
6.
Expand “Databases” by clicking + next to it.
7.
Right-click ((local) (Windows NT)) and select pause (not stop).
8.
Right-click the database requiring restoration.
9.
Select all tasks.
10.
Select database restore.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
121/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
11.
Select restoration method and file.
12.
Ensure the correct tape is in the drive corresponding to the backup set date.
13.
Select OK to continue.
4.14.1.6
Backup Log Files and Job Histories
Log files and Job History files record all automatic and manual backups. These files record events
associated with the backup procedures such as backup failure and backup success entries. The files
exist in 2 locations depending on the type of backup.
For SQL Jobs and automatic database backups:
1.
Start SQL Enterprise manager.
2.
Under console Root, double-click “Microsoft SQL Servers”.
3.
Double-click SQL Server Group.
4.
Expand “(local) (Windows NT)” by clicking on the + next to it.
5.
Expand “Management” by clicking on the + next to it.
6.
Select “Jobs”.
7.
Right-click the desired Job and select “View Job History” to view successful and failed Jobs.
Figure 4.4 illustrates a SQL job log.
122/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Figure 4.4: Archive Backup Job History
For automatic and manual database backups:
1.
Start SQL Enterprise manager.
2.
Under console Root, double-click “Microsoft SQL Servers”.
3.
Double-click SQL Server Group.
4.
Expand “(local) (Windows NT)” by clicking on the + next to it.
5.
Expand “Management” by clicking on the + next to it.
6.
Select SQL Server Logs.
7.
Choose the log with the appropriate date (normally 1 Archive log for each day) e.g. Archive # 5
– 03/02/2004 (10744 Byte) (note MM/DD/YY).
Figure 4.5 illustrates a tape backup failure.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
123/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Figure 4.5: SQL Server Logs
The Windows Event Viewer also contains information on SQL Server tasks. To view the Event
Viewer:
1.
Select “Start”, then “Programs”, then “Administrative Tools”.
2.
Select Event Viewer.
3.
Select Application
4.
The window on the right contains recent application tasks.
5.
Double-click on an entry to see more information.
Figure 4.6 illustrates an event viewer error resulting from a tape missing from the tape drive. Figure
4.7 illustrates an event viewer message resulting from a successful tape backup.
124/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Figure 4.6: Event Viewer Archive Database Failure Backup Tape Missing from Drive
Figure 4.7: Event Viewer Archive Database Backup to Tape
4.14.2
PLC Program Backup
The PLC program should be backed up when no recipe is loaded into the PLC (e.g. after an auto
cycle has ended) and no manual or automatic functions are active. Note that all PLC program data
files must be backed up because they contain PID control/tuning values, non freeze drying recipe
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
125/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
parameters, engineering parameters, and system parameters. A hard copy of the PLC program can
be generated using RSLogix 5000.
4.15
SCADA System Backup
The following paragraphs present the SCADA System backup procedure using the Symantec V2i
Protector.
4.15.1
SCADA Backup
1.
From the Windows Start Menu, navigate to V2i Protector and start the application.
2.
On the right menu sidebar, under Backup Tasks, select “Back Up Drive”.
3.
When the Drive Backup Wizard starts, select “Next”.
4.
Highlight the drive to be backed up (for example, C:\) then select “Next”.
5.
When the Backup Location screen appears, click the CD-RW/DVD-RW radial button selection
on the left of the panel. Enter a filename for the backup or accept the default. Select “Next”.
6.
When the options screen appears, select the compression level desired and check “Verify
backup image after creation” and then select “Next”.
7.
When the Command Files screen appears, select “Next”.
8.
A review screen will appear with all the options selected. If another option is desired, select
“Back” to add it, otherwise select “Next” to begin the backup.
Note:
9.
The application will automatically span multiple CD’s. Be sure to label each CD
with the appropriate number in the backup set as the set is being created (i.e.
BACKUP CD #1).
When the backup set is complete, select “Close”.
4.15.2
Create SCSI Driver Disk
1.
Insert the HP Server tc2120 Startup CD into the CDROM drive.
2.
When the startup.htm page opens in Internet Explorer, select the “drivers” link for number 4: hp
server tc2120 drivers for Video, SCSI Rain, IDE Raid, Tape, Modem.
3.
Insert a disk into the floppy drive, then select “Click here to create driver diskettes”.
4.
Select “Click here to create hp tc2120 Windows 2000 SCSI Raid drivers diskette”.
5.
When the “File Download” dialog appears, select “Run”.
126/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
6.
When the “WinZip Self-Extractor – w2k_scsiraid.exe” window appears, set “Unzip to folder” to
A:\ then select “Unzip”.
7.
When the “15 file(s) unzipped successfully” message appears select “OK”. Label the disk SCSI
Disk and store along with the backup CD set created in above.
4.16
System Restore
System restoration is required in the following situations:
•
Major recovery - The PC’s hard drive has failed and a full restoration of the operating system, iFIX,
Microsoft SQL Server Desktop Edition, and all other applications is required. During a major
recovery, there are some items that are not in any backup files (e.g. driver installation, loadable
PDB blocks, Windows User account configuration). Refer to SCADA System Restore below.
•
Minor recovery - Files are missing, corrupted, or wrongly changed. During a minor recovery, only
partial restoration of files is required. Refer to iFIX System Restore and Microsoft SQL Server
Desktop Edition Restore below for minor recovery procedures.
4.16.1
SCADA System Restore
Caution:
This procedure will re-image the hard drive and completely
replace all of the existing data with the saved backup
configuration stored on the CD’s.
1.
Reboot the server using the Symantec V2i Protector CD. This will automatically launch the
restore application.
2.
When the “Starting Powerquest Recovery Environment” status bar appears on the screen,
quickly press “F6” to load the SCSI drivers for the raid configuration. Press “S” to specify an
additional device when the setup screen appears.
3.
Insert the SCSI Disk created during system backup into the floppy drive and press “Enter”.
4.
Select “Adaptec I20 Raid Host Adapters for Windows 2000” and press “Enter”. Press “S” when
asked to confirm then press “Enter” to continue.
5.
Accept the default network configuration.
6.
When the Recovery Environment screen appears, select “time zone” then select “System
Restore”.
7.
When the System Restore Wizard starts, select “Restore Drives” then “Next”.
8.
When the Restore Type screen appears, select “Single Drive” then “Next”.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
127/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
9.
When the Backup Image to Restore screen appears, remove the V2i Protector CD and insert
the first CD of the backup image set into the CD drive. Select “Browse”.
10.
Select the backup image from the CD and then select “Open”. Follow the prompts to insert the
first and last CDs of the backup set. When the “Backup image details display” dialogue shows
the backup information, select “Next”.
11.
When the Restore Destination screen appears, select the “NTFS” allocation (for example, C:\),
then select “Next”.
12.
When the Restore Options screen appears, uncheck the “Verify backup image before restore”
checkbox and then check the following checkboxes:
-
“Restore original disk signature”
-
“Restore MBR”
-
“Set drive active”
-
“Resize drive to fill unallocated space” (only if target drive is lager than backed up drive)
-
“Check for file system errors”
When the boxes above are checked, select “Next”.
13.
A review screen will appear with all the options selected. Check the “Reboot after finish
checkbox” and then select “Next” to begin the restore operation. Follow the screen prompts and
insert the proper backup disks during the restore process.
14.
When system restore is complete, the SCADA will reboot to the restored backup configuration.
4.16.2
iFIX System Restore
In order to restore the iFIX configuration, the following steps must be performed:
1.
Shut down iFIX.
2.
If Secure Desktop is enabled, select the iFIX Backup & Restore Wizard from the Intellution
Group. If Secure Desktop is not enabled select the Windows Start button and then select “All
Programs”, then “iFIX”, then “Backup & Restore Wizard”.
3.
Refer to Table 4.4.1, Backup and Restore Options for a list of restore options and descriptions.
4.
Select from the list of options and then select “Finish”. During the restore process, the
application will prompt before overwriting files or creating subdirectories. If the archive contains
a directory or subdirectory, the restore will recursively go through all of the subdirectories, not
just one level.
128/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Note:
The driver configuration files for the PLC / Chart Recorder (if applicable) are
restored in the above procedure. However, restoring a driver may require reinstallation of the driver software. Refer to Install ABR Driver in Appendix B of the
Software Design Specification included in the Product Documentation.
Note:
Analog values unknown - AIS loadable blocks for the PDB may need to be
restored. Refer to Install iFIX AIS Block in Appendix B of the Software Design
Specification included in the Product Documentation. The application files must
be restored using the Backup & Restore Wizard before this procedure can be
performed.
4.16.3
Microsoft SQL Server Desktop Edition Restore
The SQL Server Enterprise manager will be used to restore any SQL data to recover from an audit
trail loss or SQL catastrophic failure. SQL is configured to back up the schema and data only. Refer
to 4.14.1, Microsoft SQL Server Desktop Edition Audit Trail Backup. Stored procedures and jobs will
have to be added after the database restore.
4.16.4
Data Accumulated on the PC Operator Interface
The following data is stored on the hard drive of the PC Operator Interface or the SQL database.
Description
iFIX alarm file tables; secured by SQL
iFIX alarm text files; secured by operating system security
Trend files created by iFIX; secured by operating system
security
Freeze drying recipe files; created by iFIX, secured by
operating system security
Batch files; created with XLReporter
File / location
SQL database
Dynamics\alm\*.alm
Dynamics\htrdata\node0\*.H*
Dynamics\rcm\fd\*.rcm
Dynamics\App\Reports\PDF Reports\*.pdf
The entire dynamics directory is configured to be hidden for non-administrators.
Data files are not automatically deleted. They must be manually deleted from the PC
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
129/143
SC473501.doc
BOC EDWARDS
5.
OPERATING PROCEDURES
5.1
Introduction
BOC Edwards
Pharmaceutical Systems
The following instructions guide the operator using the Manual Control System through the steps or
stages of a freeze drying cycle.
Read the entire manual before using the freeze dryer. Carefully note all warnings and cautions, as
well as the final shutdown procedure. Failure to follow the shutdown procedure can leave the freeze
dryer in a dangerous condition.
5.2
Pre-Start Requirements
5.2.1
Start-up Checks
WARNING:
CHECK PROCESS & INSTRUMENTATION DIAGRAMS
D-C47-19-01, D-C47-19-05, D-C47-19-06, C-C47-19-07,
C-C47-19-08, C-C47-19-09, D-C47-19-10, AND
D-C47-19-11 TO VERIFY ALL VENTS ARE CORRECTLY
INSTALLED AND RELEASE TO SAFE AREAS.
Caution:
Incondensable materials, such as solvent, degrade
vacuum performance.
Start the Lyomax before initiating a freeze drying cycle:
1.
Complete required daily maintenance procedures as defined in the Maintenance Manual.
2.
Verify drying chamber is clean of broken vials, old stoppers, product deposits, and other
contaminants. When using a solvent to clean the chamber, remove solvent by out-gassing
(pumping down) the system.
3.
Verify condenser coil is defrosted, and condenser drained.
4.
Verify chamber/condenser isolation valves are closed.
130/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
5.3
Operating Sequence
5.3.1
Loading Shelves
Caution:
Before collapsing the shelves, be sure they are correctly
loaded or completely empty and clear of all foreign
objects.
Failure to do so will result in damage to the shelves and
the shelf stack assembly.
Load shelves as follows:
1.
Verify shelves are evenly loaded as shown below:
Figure 5.1: Shelf Loading
2.
Place vials with stoppers on shelf as required to fill shelf for stoppering.
3.
Use the same cycle parameters and load conditions for each batch, when batch production
operations are needed.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
131/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
4.
Use a suitable buffer material (one having the same thermal characteristics) when a small batch
is processed. This ensures consistent results.
5.
Keep cycle parameters and load conditions the same, if possible, when freeze drying different
product materials.
5.3.2
Guide Rail Removal for Incomplete Loads
Remove rails when freeze drying an incomplete load. An incomplete load is any load in which
shelves are empty. Remove rails from all empty shelves or insert spacers prior to stoppering.
Partially filled shelves should be loaded with empty vials with stoppers. Failure to remove the rails
can result in damage to the shelves.
Each rail is fastened to the shelf by a single screw located on the slot door end and must be removed
or installed through the slot door. The back of the rail contains a hook that fits into a mating slot on
the back of the shelf.
5.3.3
Positioning Product Temperature Probes
The product temperature probes determine operating points and maintain product quality. The probe
sensing area is approximately 2 mm from the tip. This part of the sensor must be as close to the
center of the load as possible.
1.
Verify probe does not touch tray bottom when bulk drying in trays.
2.
Position probe as shown in figure below for ampoules and vials:
a.
Through the vial wall; in this case the vial will have to be prepared by drilling a suitable
hole in its wall.
b.
Through the vial neck.
c.
Through the stopper; in this case a channel must be cut in the side of the stopper.
Note:
Only option (b) is practical for ampoules because the glass used for
manufacturing ampoules is usually too thin to drill and they are invariably sealed,
not stoppered, as detailed in option c.
132/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
Figure 5.2: Positioning Temperature Probes.
3.
Verify depth of fill sufficiently covers the sensing part of the probe when using any container.
4.
Place the temperature probe(s) at the bottom of a bulk tray and at least 100mm (4 inches) from
the edges when freeze drying in bulk trays.
5.3.4
Closing the Chamber Door
1.
Check that the door seal and chamber mating surface are clean before closing the chamber
door.
2.
Use a damp cloth to remove any deposits as required. Do not use any sharp tools to clean the
seal.
3.
Carefully close the chamber door, verifying the temperature probe wires are clear of all door
mechanisms.
5.3.5
Pre-Cycle Checks
Perform the following before starting the freeze drying cycle:
1.
Verify the Control Enable key switch is in the ON position.
2.
Verify no alarms are present on the Status or Alarm Screen. Clear all alarm conditions.
3.
Check the Status Screen and verify the chamber vacuum control displays the chamber
pressure.
4.
Select Shelf Temperature Control on the Manual Controls Screen and activate the shelf
temperature control function.
5.
Change the shelf temperature set point.
6.
Verify Status Screen displays the operational shelf temperature.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
133/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
5.3.6
Shelf Cooling/Product Freezing
Activate the shelf cooling system as follows:
1.
Perform the following at the Status Screen:
a.
Verify the chamber/condenser isolation valve is closed
b.
Verify the chamber vent valve is closed.
2.
Set the shelf cooling temperature to the required value, e.g., -50°C.
3.
Select Shelf Temperature Control on the Manual Control Screen to activate the shelf
temperature control function. Verify the Status Screen displays circulating pump and
compressor operating status. If the pressure in the compressor suction line is greater than 1.38
BarG (20 PSIG), the compressor will perform a pump down prior to open the cooling valves.
4.
Verify the Status Screen shows the cooling solenoid valve open. Refrigerant starts expanding
in the flow cooler when the refrigerant passes through the expansion valve.
Note:
After refrigerant starts expanding, the cooling solenoid valves close when suction
pressure is greater than 1.03 BarG (15 PSIG). The compressor then pumps down
the suction line until suction line pressure is less than or equal to 344.7 mBarG (5
PSIG). This is a normal condition indicating the refrigerant circuit control system
is supervising the suction pressure correctly.
5.
Monitor the shelf temperature.
6.
Closely monitor the refrigerant compressor performance via the pressure gauges, if equipped.
Product freezing takes 3 to 5 hours. In some circumstances, freezing takes longer. The following
factors affect freezing time:
•
Product type and thermal characteristics.
•
Product depth of fill.
•
Shelf temperature control setting.
•
Quantity of product.
•
The selected freeze drying cycle.
•
Type of container.
•
Method used to load containers on shelves.
•
Freeze dryer performance.
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
5.3.7
Condenser Cooling
Start the condenser cooling sequence as follows:
1.
Verify condenser defrost steam valve is closed.
2.
Verify condenser inlet valve is closed.
134/143
SC473501.doc
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
3.
Verify main isolation valve is closed.
4.
Select Condenser Cooling button on the Manual Controls Screen and enable condenser
cooling.
5.
Select the Recorder button on the Manual Controls screen. A continuous readout of the
condenser temperature is also available on the Chart Recorder and Status Screen.
Condenser temperature is detected by a thermocouple or temperature probe attached to the
condenser coil wall near the inlet. The temperature measured is the inlet temperature. Differences
may occur in the condenser temperature at different pressures. Generally, the condenser
temperature decreases proportionally with system pressure. Temperatures quoted in the specification
assume the system is in vacuum. Fluctuations in the condenser temperature also occur depending
on the expansion valve setting and the system load conditions. The fluctuations, due to load,
decrease as the load conditions approach maximum.
The condenser temperature should fall from 20°C to -40°C within 30 minutes; leave the condenser in
this condition for 10 minutes before proceeding with vacuum pump down.
5.3.8
Vacuum Pump Down
Product must be at correct temperature before starting vacuum pump down. This is measured by the
product temperature probe(s) that provide the temperature at a given point in the product. Allowances
are then made to compensate for component tolerances and accuracy. The following points must be
considered:
•
The definition of 'frozen' is any temperature lower than the eutectic point of the product.
•
The product temperature measured by a probe represents the temperature of a very small portion
of the total load, some of which may be at a different temperature.
Since it is not possible to measure the temperature of every product container, it is necessary to build
a safety factor to ensure the entire load is frozen. The general rule for this factor is the lowest product
temperature maintained for sixty minutes. For example: if the product temperature required is -40°C
and the freeze dryer takes three hours to reach this temperature, the whole freezing phase will take
four hours. These temperatures and times refer to the drying chamber at atmospheric pressure.
Observe product appearance as an indication of readiness for pump down. Appearance indications
include:
•
The color of the frozen product.
•
The crystal structure of the product, especially uniformity.
•
The hardness of the product surface. The product surface is hard and difficult to penetrate when
poked with a sharp needle.
After the product is thoroughly frozen and the condenser temperature is at -40°C or lower, the system
is ready for pump down (the lower the temperature the faster the pump down phase will be). Pump
down procedure is as follows:
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
135/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
1.
Verify that all of the chamber and condenser valves are closed.
2.
Ensure associated Unit Graphic Screen functions are clear.
3.
Ensure that the Gas Ballast Valve is set in accordance with manufacturer's instructions.
4.
Select Vacuum Pump(s) on the Manual Controls Screen to start the vacuum pump(s) in a
'warm-up' mode while the vacuum valve is kept closed.
5.
Select gas ballast from the Manual Control screen. Pumping system pressure should fall below
10 microns in approximately 5 minutes depending on the pump condition, the oil, the gas ballast
valve setting and the pump setup.
Note:
With a manually operated gas ballast valve, the valve is normally set half open, but
is fully open when pumping solvents or condensable vapors. Refer to the
manufacturer pump manual for detailed information.
6.
Select the Vacuum Set Point field on the Manual Controls screen then enter the vacuum set
point.
7.
When the condenser coil is -40°C or below (check on the recorder screen display) and 10
minutes has passed since the start of condenser cooling, perform the following at the Manual
Controls screen:
8.
a.
Open Vacuum Pump Isolation Valves.
b.
Open Main Isolation Valve.
c.
Open the Vacuum Valve.
d.
Enable vacuum valve control.
Verify the Status Screen shows the following:
a.
Main valve open
b.
Vacuum valve open
c.
Vacuum pump(s) running.
d.
Vacuum pump isolation valves are open.
9.
Verify the chamber door pulls tight from chamber vacuum.
10.
Observe the decrease in chamber pressure at the vacuum display.
136/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
5.3.9
Shelf Heating
Sublimation (or drying) during vacuum pump down is extremely slow. To speed this step of the
sublimation process (known as 'primary drying') the shelves are heated.
The amount of heat energy input and not the shelf temperature is the important consideration for shelf
temperature setting. For example: if two similar loads with identical quantities of the same product are
processed in different sized vials (e.g., 2 ml for one batch and 5 ml for another) heat input is critical in
the smaller vial as opposed to the larger vial. Too much heat input results in product 'meltback' a
situation where the fluid content melts, returning to the liquid form before evaporating.
1.
Set the required shelf heating temperature at the Manual Controls Screen display.
2.
Verify the chamber pressure is at the Vacuum Set point.
Note:
Chamber pressure can be affected by the presence of solvents, such as alcohol,
giving abnormally high readings even in small traces.
3.
Observe rise in shelf oil temperature and product temperature.
4.
Observe product appearance.
Note:
Generally, product color changes during sublimation. Some substances may
show two distinct rings. Usually, the lighter colored ring is dried product.
5.
Verify the control system maintains the shelf oil temperature within the alarm limit (usually ±4°C
from set point).
6.
Determine when primary drying is complete by observing the following conditions:
a.
The product temperature is approaching shelf temperature.
b.
The condenser temperature has returned to its 'off-load' performance, i.e., near to its
lowest working temperature of -60°C to -70°C.
c.
The cake or lyophile is uniform in color.
5.3.10
Secondary Drying
Generally, the less water (ice) in the product, the lower the thermal conductivity. This requires greater
heat input to remove remaining bonded water (or residual moisture).
Use one of the following methods to increase heat input:
1.
Increase the shelf temperature:
a.
Set a higher value temperature set point at the Manual Controls Screen display.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
137/143
SC473501.doc
BOC EDWARDS
Note:
Do not exceed maximum heat temperature for product, causing meltback.
b.
2.
BOC Edwards
Pharmaceutical Systems
Continue drying process after product temperature stabilizes at new set point. Secondary
drying time depends on the product type, temperature pressure, etc.
Improve heat transfer between the heat source (shelf) and product by introducing a small
(calibrated) leak into the chamber. A leak increases chamber pressure thereby improving heat
transfer.
5.3.11
End of Cycle
Test product by performing a chamber pressure rise test as follows:
1.
Close the main isolation valve at the Manual Controls Screen display.
2.
Observe rise in chamber pressure. The rise in chamber pressure is proportional to the dryness
or residual moisture present in the product. The higher the rise rate, the higher the residual
moisture.
Note:
3.
An experienced operator can relate a rise in pressure to the product dryness. A
pressure rise test is only effective when the system is clean, free of solvents and
leak tight. A typical leak rate for a Lyomax freeze dryer is 1x10-2 mBar liter/second.
Observe one or more of the following conditions to determine when the secondary drying cycle
is finished:
a.
The condenser temperature returns to the 'off-load' performance, i.e., near to the lowest
working temperature of -60°C to -70°C.
b.
The cycle length is equal to or longer than previous cycles. This is only applicable when
this is a repeat cycle on an identical batch of product.
c.
Product has uniform color.
5.3.12
Hydraulic Stoppering
WARNING:
DO NOT TAMPER WITH PRESSURE SWITCH SETTINGS
OR ANY OF THE SAFETY DEVICES ON THE HYDRAULICS.
KEEP WELL AWAY FROM THE SHELF STACK DURING
STOPPERING.
Observe the following points for safe operation of the stoppering system:
•
Use properly sized, silicone-treated stoppers.
•
Partial loading of any shelf can lead to permanent shelf damage.
138/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
•
Remove all obstacles such as probe wires, probes, vials, etc., before stacking shelves.
Caution:
Improperly loaded shelves can be damaged during
stoppering. BOC Edwards Pharmaceutical Systems
recommends that shelves be fully loaded or completely
empty.
Stoppering can be carried out using sterile air (or nitrogen gas) in the drying chamber. The product
must be completely dry and ready for sealing. It is recommended that a pressure rise test be carried
out before stoppering. The sequence is covered below:
1.
Enable the slave panel at the Manual Controls screen.
2.
Check for shelf obstructions, tilted or tipped vials, etc.
3.
The chamber door and main valve both must be closed.
4.
Place Chamber Aeration selector switch on the slave panel in the Pre-Aeration position. The
chamber automatically aerates to the pre-aeration set point.
5.
To stop chamber pre-aeration (or aeration) at a lower pressure, select the Chamber PreAeration (or Chamber Aeration) button on the Manual Controls screen. The chamber pressure
can be monitored on the Status Display screen.
Caution:
Before collapsing the shelves, be sure they are correctly
loaded or completely empty and clear of foreign objects.
Failure to do so will result in damage to the shelves and
the shelf stack assembly.
6.
Place the Hydraulic Select switch on the Slave Panel in the Stopper position.
7.
Place the Shelf Movement switch on the Slave Panel in the Down position to stopper.
8.
Place the Shelf Movement switch on the Slave Panel in the UP position.
9.
Visually check that stoppering is satisfactory and that the shelf stack returns to its rest position.
10.
At the end of the stoppering phase, check that all vials have been completely stoppered.
5.3.13
Chamber Aeration
Select Chamber Aeration to aerate the chamber with clean room air from the Manual Controls screen.
If chamber aeration is to be controlled from the clean room, select the Slave Panel button on the
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
139/143
SC473501.doc
BOC EDWARDS
BOC Edwards
Pharmaceutical Systems
Manual Controls screen, then set the Chamber Aeration selector switch on the slave panel to Aerate
position. The chamber automatically aerates to atmospheric pressure. The aeration valves will
remain open for one minute after the aeration set points are reached.
Note:
5.3.14
Set the Aeration switch on the slave panel to Off to de-activate the aeration
function.
Unloading
WARNING:
VENTING A LARGE CHAMBER CONTAINING INERT GAS
INTO THE WORK PLACE ATMOSPHERE CAN DISPLACE
OXYGEN AND CAUSE ASPHYXIA.
1.
When the chamber is at atmospheric pressure open the chamber door and unload the shelves.
2.
Inspect inside the chamber and clean as necessary.
5.3.15
Condenser Defrosting
The accumulation of ice on the condenser coil must be removed after every cycle in order that the
next cycle can be carried out under identical conditions to the previous one. The ice is removed by
introducing steam into the condenser. Defrosting also has the effect of removing all other deposits
which can accumulate such as solvents and corrosive substances which can easily corrode seals,
gaskets, valve seats and even stainless steel.
Defrost is an automatic cycle that is downloaded by selecting the Recipe button on the Menu bar and
selecting the Defrost cycle. Refer to Starting a Defrost Cycle under Operator Interface Functions in
Chapter 4 for more information. Defrost can also be done manually from the Manual Controls screen.
5.3.16
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.
140/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
WARNING:
DO NOT ENTER CHAMBER WITH SHELF STACK RAISED.
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.
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.
5.3.17
Partial and Total Shutdown
Refrigerant circuits develop dangerous pressure when cooling water and electricity supplies are
disconnected for a length of time. When shutting down the unit:
1.
Maintain circulating cooling water.
2.
Maintain electric supply to the Unit so that refrigerant can be pumped back into the receiver.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
141/143
SC473501.doc
BOC EDWARDS
3.
BOC Edwards
Pharmaceutical Systems
Pump down refrigerant circuits and isolate refrigerant in receivers when cooling water and
electric supply are disconnected for a prolonged period.
142/143
SC473501.doc
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
PSGA
Operating Manual
BOC Edwards
Pharmaceutical Systems
BOC EDWARDS
BOC EPS Interpretation of FDA 21 CFR Part 11
All BOC EPS control systems are closed and only allow authorized individuals to access them. The
application programs are stored in the memory of a programmable logic controller. The integrity of
the program and data is assured by our software configuration management system. The software
can only be modified through the programming port of the PLC, which is located in a locked electrical
cabinet to prevent unauthorized access.
PLCs and industrial computer systems in combination with a textual HMI control all BOC EPS filling
systems (Washing & Sterilizing Equipment, Filling Machines, capping machines and tray loaders)
The filling line equipment can be equipped with a printer to print the batch records. 21 CFR Part 11
does not apply to this data because these records are not stored in the HMI or PLC, but sent directly
to the printer.
The memory of the PLC contains the production recipes. The production recipes contain a set of
recipe parameters that are necessary to set-up the system for a specific product. The production
recipes can be accessed and modified via a password-protected menu on the HMI. To make the
control systems 21 CFR Part 11 compliant, the HMI gives all production personnel the possibility to
check the contents of the selected recipe prior to starting a production run against a standard recipe.
This means that the integrity of the production recipes is secured through this procedure. Machines
that are equipped with a printer will print the recipe at the start of production.
PLCs in combination with a personal computer running Intellution iFIX software under a Windows XP
environment control all BOC EPS freeze dryers, loading systems and unloading systems
No data requiring modification is stored in the PLC. Upon modification of any data stored in the PC,
such as production recipes, the date of the action, time and name of the operator logged into the
system are written to the alarm log file.
The system generates copies of all records in both human readable and electronic form. Records
include alarm logs, security logs, recipes and trended data. The records are copied to a directory on
the PC that is secured by Windows XP security. Windows XP security maintains the uniqueness of
the identification code and password combination for each user. The records in the secure directory
cannot be edited or overwritten. The records will remain on the hard drive of the PC until a user with
a high level of security deletes them. If these secured records are created, copied or deleted, the
date of the action, time and name of the operator logged into the system are written to the above
mentioned alarm log file.
Based on the above, BOC EPS considers their equipment to be compliant with 21 CFR Part 11.
PSGA
Operating Manual
MTE1870 Lyomax 50
Rev. 1 (13-Dec-2004)
143/143
SC473501.doc
Was this manual useful for you? yes no
Thank you for your participation!

* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project

Download PDF

advertising