Waters

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Chromatography

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Systems
Qualification

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WorkbookEN
System
Qualification
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Overview
Part I: OV
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34 Maple Street
Milford, MA 01757

WAT530-04, Revision 3
May 2003
Waters Chromatography Systems Qualification Workbook

NOTICE

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Waters instruments, software, and technical documentation are under revision control. The information
contained in this document is appropriate for the revision level of the specified instruments, software, and
technical documentation. This document is believed to be complete and accurate at the time of publication.

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Waters Corporation assumes no responsibility for any errors that may appear in this document. In no event
shall Waters Corporation be liable for incidental or consequential damages in connection with or arising
from the use of this documentation.

 1998–2003 WATERS CORPORATION. PRINTED IN THE UNITED STATES OF AMERICA. ALL

RIGHTS RESERVED. THE PROTOCOLS AND FORMS IN THIS DOCUMENT HAVE REQUIRED
EXTENSIVE DEVELOPMENT, TESTING, AND REFINEMENT IN ORDER TO PROVIDE A

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QUALITY PRODUCT TO OUR CUSTOMERS. AS SUCH, THIS DOCUMENT IS REGARDED AS
INTELLECTUAL PROPERTY OF WATERS. EXCEPT WHERE INDICATED, THIS DOCUMENT OR
PARTS THEREOF MAY NOT BE REPRODUCED IN ANY FORM WITHOUT THE WRITTEN
PERMISSION OF THE PUBLISHER.

Waters Service Technicians are not authorized to make entries into unauthorized photocopied documents. To
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obtain additional documents, contact your Waters representative.

Waters is a registered trademark, and LAC/E is a trademark of Waters Corporation.

Rheodyne is a registered trademark of Rheodyne L. P.

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All other trademarks or registered trademarks are the sole property of their respective owners.
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 Part I: System Qualification Overview

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Caution: For continued protection against fire hazard, replace fuses with those of the same type and
rating.

Caution: Use caution when working with any polymer tubing under pressure.

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• Always wear eye protection when near pressurized polymer tubing.
• Extinguish all nearby flames.
• Do not use tubing that has been severely stressed or kinked.
• Do not use nonmetallic tubing with tetrahydrofuran (THF) or concentrated nitric or sulfuric
acid.
• Be aware that methylene chloride and dimethyl sulfoxide cause nonmetallic tubing to
swell and greatly reduce the rupture pressure of the tubing.

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Caution: If the equipment is used in a manner not specified in this document, the protection provided
by the equipment can be impaired.

Refer to the associated operator’s guide for further information and safety warnings.

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Caution: To avoid possible eye damage, always wear ultraviolet protective glasses when you work
with optics assemblies in detectors.
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Caution: Always observe safe laboratory practices when you use this equipment and when you work
with solvents and test solutions. Know the chemical and physical properties of the solvents and test
solutions. Refer to the Material Safety Data Sheet for each solvent and test solution in use.
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Attention: The Waters HPLC and LC/MS system includes highly sensitive instruments. When you
STOP use this equipment, follow generally accepted procedures for quality control and methods
development. Read the accompanying documentation before using the instruments.

If you observe a change in the retention of a particular compound, in the resolution between two
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compounds, or in peak shape, immediately determine the reason for the changes. Until you determine
the cause of a change, do not rely on the results of the separations.

Attention: Changes or modifications to this equipment not expressly approved by the party
STOP responsible for compliance could void your authority to operate the equipment.
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Attention: This equipment generates, uses, and can radiate radio frequency energy. If not installed
STOP and used strictly in accordance with the operator’s guide, this equipment can cause harmful radio
frequency interference to radio communications.
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Operation of this equipment in a residential area can cause radio frequency interference, in which
case the operator, at his or her expense, is required to correct the interference.

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 Part I: System Qualification Overview

Table of Contents

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1.1 System Qualification Process ....................................................................................... 7
1.2 Chromatography System Qualification Criteria ........................................................... 13

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1.3 Chromatography System Qualification Workbook Structure ........................................ 14
1.4 Verification Forms..................................................................................................... 15
1.5 Chromatography System Qualification Protocol Approval ........................................... 18

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Waters Chromatography Systems Qualification Workbook

Forms

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Form 1-1 Chromatography System Qualification Protocol Approval...............................................18

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 Part I: System Qualification Overview

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Chromatography Systems
Qualification Overview

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This overview describes the Waters® chromatography system qualification process and the Waters
Chromatography Systems Qualification Workbook.

Purpose of the Qualification Process

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Use the system qualification process to properly install, verify the proper operation of, and maintain the
components of a Waters chromatography system in a GLP-, CGMP-, and/or GALP-regulated environment
and/or an ISO 9000-series registered facility. Record the information obtained during the qualification process in
the Waters Chromatography Systems Qualification Workbook to provide industry regulators with evidence that:
• The instruments of your chromatography system individually and collectively perform as intended.
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• Your chromatography system software is properly installed.
• The data produced from your chromatography system meets specified performance criteria.
The purpose of qualification is to provide a high degree of assurance that the module or system functions, or
continues to function, as designed by the vendor in terms of accuracy, linearity, and precision where practical. It
is not a complete test of all specifications, but is a comprehensive test of basic functionality. Qualification tests
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do not ensure that a system is suitable for a specific analysis. That is accomplished by system suitability tests
associated with the specific assay. Qualification tests are designed to meet the requirements of 21 CFR Ch. 1,
211.68 and 211.160 with regard to calibration of automatic, mechanical, or electronic equipment.
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Purpose of the Qualification Workbook

The individual workbooks (Parts I through V) that make up the Waters Chromatography Systems Qualification
Workbook provide an organized set of chromatography system qualification procedures and the forms in which
the results of the procedures can be recorded. The workbooks enable the owner of the chromatography system to
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record the following:

• Identity and credentials of personnel performing and reviewing the qualification protocols
• Identity of the instruments, system, and documents involved in the qualification process
• Qualification procedures performed and the results obtained

1.1 System Qualification Process

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System qualification is performed under either of the following conditions:

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• Pre-use qualification – At the time of hardware and/or software installation

• Post-use qualification – After maintenance or major component replacement, and
at regular intervals
This qualification process varies depending on whether you perform pre-use or post-use qualification.

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The qualification workbook binder is designed to contain the Installation Qualification, Maintenance Procedures,

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and Operational Qualification documents (Parts II, III, and IV) or Advanced Qualification Technology (AQT)

1 printouts specific to your chromatography modules. Additionally, this binder is also designed to contain the
Performance Qualification (Part V) documents applicable to your chromatography system.

Pre-Use Qualification

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To perform pre-use qualification of a Waters chromatography system, follow the steps in Figure 1-1.

Overview
Read and understand the
Chromatography Systems Qualification Overview,
Part I: OV.

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Installation Qualification
For each instrument in the chromatography

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system, perform the procedures and complete the
forms in the corresponding Recommended
Procedures for Installation Qualification, Part II: IQ.

Maintenance Procedures
Although maintenance procedures are not
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performed during the pre-use qualification
process, the Recommended Maintenance
Procedures, Part III: MP is retained in the binder
for future post-qualification use to:
• Provide the Maintenance Log for recording
all maintenance performed after startup
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• Meet the requirements for having standard

operating procedures for maintenance

Operational Qualification
For each instrument in the chromatography
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system, perform procedures and complete forms

in the corresponding Recommended Procedures
for Operational Qualification, Part IV: OQ.

Performance Qualification
For your complete chromatography system,
perform procedures and complete forms in the
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Recommended Procedures for Performance

Qualification, Part V: PQ.
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Figure 1-1 Pre-Use Qualification Process

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 Part I: System Qualification Overview

Post-Use Qualification

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To perform post-use qualification of a Waters chromatography system, follow the steps in Figure 1-2.

Overview
Read and understand the

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Chromatography Systems Qualification Overview,
Part I: OV.

Installation Qualification
The Recommended Procedures for Installation
Qualification, Part II: IQs are not used for post-use
qualification and should be discarded.

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Maintenance Procedures
For each instrument in the chromatography system,
perform the procedures and complete the forms in
the corresponding Recommended Maintenance
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Procedures, Part III: MP.

Operational Qualification
For each instrument in the chromatography system,
perform the procedures and complete the forms in
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the corresponding Recommended Procedures for
Operational Qualification, Part IV: OQ.
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Performance Qualification
For the entire chromatography system, perform the
procedures and complete the forms in the
Recommended Procedures for Performance
Qualification, Part V: PQ.
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Figure 1-2 Post-Use Qualification Process

Requalification Guidelines
Waters recommends that you use the following guidelines on when to requalify your Waters chromatography
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system:
• Requalify your chromatography system 12 to 15 months after installation and at regular periods thereafter
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as described in Figure 1-2.

Note: Use discretion when you decide to perform the requalification procedures. Your
chromatography system may need to be requalified more or less often than recommended,
depending on the frequency of use.

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• Requalify the affected chromatography module each time any major instrument component is changed.

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Document the repair in the Maintenance Log and the requalification in the Operational Qualification Log.

1 • Requalify your chromatography system when you make major repairs. While it is not necessary to
requalify your chromatography system when you replace parts for minor repairs, routine maintenance, or
normal wear, some type of test to verify the repair or replacement should be performed. Table 1-1 lists
typical major and minor repairs.

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– Major repair: A major repair item has the ability to affect accuracy, linearity, or precision of the
system in a manner that is not readily apparent. An example of a major repair item is a pump CPU
board. Since the CPU board controls the pump motor drivers that determine proper flow rates, a CPU
board’s proper functionality is best determined by performing a complete operational qualification
(OQ) of the pump to verify flow rate accuracy and then system performance qualification (PQ) to
verify proper pump precision.
Major repairs should be documented in the maintenance log for the module and in the OQ test log or
other suitable log as appropriate.

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– Minor repair: A minor repair item is a repair that is unlikely to affect proper operation of the device
in an unexpected manner. An example of a minor repair is the installation of a new pump seal. If a

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new pump seal is installed incorrectly and is leaking, it can indeed cause an error in flow rate
accuracy, but this problem can easily be diagnosed by the visual leak and/or the results of an easily
performed ramp and decay test. Therefore, this would not be considered a major repair since it is not
necessary to perform a complete operational qualification to determine if the repair was performed
correctly. If the ramp and decay test passes, it is not necessary to verify flow rate accuracy of the
pump because we have a high degree of assurance that flow rate accuracy has not been affected.
Performing system suitability analysis before running any unknowns further verifies proper
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completion of the task.
In general, when a minor repair is performed, you need not requalify the entire instrument. However,
inspect and/or test the repaired or replaced part to be sure it functions properly. Record the test
performed and the test results in the Maintenance Log. For example, a suitable test after replacing a
pump seal, plunger, or check valve is a ramp and decay test. A lamp, photodiode, or cell window
replacement can be verified by using the internal detector calibration diagnostics. Replacing a minor
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injector component such as a valve seal can be verified by using internal test diagnostics. Proper
functionality of a replaced fan can be a simple visual check. The important point is to document
whatever you do. After you test the replaced component, perform system suitability analysis as the
final step to verify proper operation.
– Software changes: Software reloads or upgrades to the Chromatography Data System (CDS) are
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considered major repairs, but for data systems this may not require a PQ. Important criteria for
qualification of proper software functionality includes verification of the revision and the correct
files associated with that revision, proper computational capability, and system control functionality.
An IQ should be performed whenever loading new software, reloading software (such as after a hard
drive failure), adding service packs to the operating system, or upgrading software to verify that the
proper files are present. An OQ should then be performed to verify accuracy of the CDS’s
computational capability. System suitability should be the final step to verify proper system control
functionality. If it is time to requalify the entire system, then a PQ should also be performed before
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system suitability, but this is not necessary to merely verify system control functionality. Adding
service packs to CDS software can be major or minor depending on the specific changes they make.
Always refer to the change notes and other appropriate documentation to determine what is affected.
Minimally, an OQ and system suitability should be performed after any software changes.
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• Table 1-1 is intended as a general guide for determining what constitutes major and minor repairs. There
may be exceptions to the guidelines, depending on instrument usage and applications. Use a practical
approach when determining what to requalify after a major repair. For example, replacing an injector
component on an integrated module does not affect flow rate accuracy. Therefore, you need to requalify
only the injector portion of the integrated module.

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Table 1-1 Examples of Major and Minor Repairs

Device Major Repair Minor Repair

Solvent delivery CPU/control printed circuit boards (PCBs) Front panels

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systems/pumps Driver PCBs Power suppliesa
Motors Check valves
Gears Check valve cartridges
Castings Column heaterb
Gradient proportioning valves Column heater/coolerb
Pump control modules Plungers

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Automated gradient controllers Seals
Piston drives Pressure transducer
Fans
Fuses
Miscellaneous

Sample management
systems/injectors
CPU/control PCBs
Driver PCBs
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Power suppliesa
Complete injector assemblies Sample positioning drivesc
Complete valve assemblies Pressure transducers
Fluid packs Seal pack and needled
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Valve seals
Sample heater/coolerb
Column heaterb
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Column heater/coolerb
Fans
Fuses
Miscellaneous
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Table 1-1 Examples of Major and Minor Repairs (Continued)

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1 Device Major Repair Minor Repair

Detectors Cell assemblies Front panels

CPU/control PCBs Power suppliesa

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Analog PCBs Lamps
Preamp PCBs Cell windows
Photodiodes Fans
Optics benches Fuses
Gratings Air filters
Grating drive devices Miscellaneous

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Mirrors
Beam splitters
Photodiode arrays

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Photomultiplier tubes
Optical slits
Filter wheel replacement

Data systems Transputer data acquisition transfer (TDAT) Network card

PCB busLAC/E™ card
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CPU PCBs General purpose interface
Hard drives bus (GPIB) board
Reformatting hard disks Displays
Loading software Power suppliesa
Reloading software Keyboards
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Upgrading operating system service packs Printers

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Upgrading data system service packs Removable media drives
RAM SIMM modules
Upgrading data system
service packse
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Analog-to-Digital (A/D) A/D PCBs System interface module

Devices (SIM) injector printed
circuit boards (PCBs)f
SIM pump driver PCBsf
Fans
Fuses
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Miscellaneous
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Table 1-1 Examples of Major and Minor Repairs (Continued)

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Device Major Repair Minor Repair

Mass detectors Embedded PC PCB External connections PCB

Analog PCB Flow controllers

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Transputer processing card (TPC) PCB Stainless steel (SS)
High voltage direct current capillary (ESI Probe)
(DC) supplies Fused silica capillary
Low voltage DC supplies (APCI Probe)
Quadrupole Probe assemblies (ESI and
APCI)
Detector assembly
Probe adjustment assembly

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Headamp PCB
Rheodyne® injector valveg
Radio frequency (RF) feedthroughs
Heaters
A/D PCB
Syringe drive PCB
Digital PCB
Turbo pump
RF generator assembly
Turbo controller
RF DC PCB EN Roughing pump
Hexapole
Filters
Source assembly components
Fuses
Ion tunnels
Vacuum pump oil
Vacuum hose/fittings/
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clamps
Solenoid valves
Pirani gauge
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Relays/switches
DC power tray
Cables
O-Rings/seals
Fans
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a. Test power supplies to ensure that they produce proper voltages.

b. Test the sample heater/cooler, column heater, or column heater/cooler to verify that it properly controls temperature.
c. Verify proper sample positioning for injection.
d. Verify injection accuracy.
e. Refer to the Service Pack release notes for specific information.
f. Test SIM Injector PCBs and SIM Pump Driver PCBs by performing system suitability.
g. Verify proper operation of the rheodyne injector valve after any repair was performed on it.
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1.2 Chromatography System Qualification Criteria

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Chromatography system qualification protocols are based on:

• Recommended reference documents.
• Recommended chromatography system configuration components.

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Recommended Reference Documents

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1 Waters recommends that the performer use the Waters Chromatography Systems Qualification Workbook with
the corresponding installation and maintenance guides, operator’s guides, user’s guides, and startup kits to
qualify each system component and the system as a whole.

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1.3 Chromatography System Qualification Workbook
Structure
Table 1-2 summarizes the organization and content of the Waters Chromatography Systems Qualification
Workbook.

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Note: Most instruments in a Waters chromatography system have their own Part II (IQ), Part III (MP),
and Part IV (OQ) workbooks for inclusion in the Waters Chromatography Systems Qualification
Workbook. If you use the Advanced Qualification Technology (AQT) tool, reports for the IQ,

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Maintenance Log, and OQ are printed and can be added to the appropriate section of the workbook.
Note that there are some exceptions where some instruments only have IQ, MP, and OQ, or only a
PQ.

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Table 1-2 Waters Chromatography Systems Qualification Workbook Contents

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Workbook Content

Part I: OV, • Describes the qualification process.

Systems Qualification • Summarizes the contents of the Waters Chromatography Systems
Overview Qualification Workbook.
• Describes form completion requirements.
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Part II: IQ, • Describes the scope of the recommended installation

Recommended Procedures qualification process.
for Installation Qualification • Provides forms for documenting purchase order compliance.
• Provides instructions for installing the instrument and the forms
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for certifying that the instrument meets all installation

qualification requirements.

Part III: MP, • Describes the scope of the recommended maintenance process.
Recommended Maintenance • Provides recommended maintenance procedures and the forms for
Procedures recording their results.
• Provides logs for recording module maintenance.
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Part IV: OQ, • Describes the scope of the recommended operational qualification
Recommended Procedures process.
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for Operational Qualification

• Provides instructions for performing an instrument operational
qualification and the forms for verifying that the instrument meets all
operational qualification requirements.
• Provides logs for recording operational qualification.

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Table 1-2 Waters Chromatography Systems Qualification Workbook Contents (Continued)

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Workbook Content

Part V: PQ, • Identifies the system components and describes the scope of the
Recommended Procedures recommended system performance qualification process.

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for Performance
• Provides procedures to prepare for chromatography system
Qualification
performance qualification tests.
• Provides instructions for running and verifying chromatography
system performance qualification tests. Also provides the PQ project
diskette and forms for final approval of system performance
qualification.
Note: This is a vendor PQ that is designed to verify proper

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system operation. It is not designed to validate the system for any
specific use.

1.4 Verification Forms

Purpose of Forms
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The qualification process requires that performers and reviewers complete forms in the Waters Chromatography
Systems Qualification Workbook or forms printed from the Advanced Qualification Technology (AQT) tool. The
forms serve one or more of the following functions:
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• Identify and verify the credentials of the performers and reviewers who qualify the chromatography
system
• Verify that the performers and reviewers understand certain information
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• Identify the system components being qualified

• Record data and test results
• Verify the successful completion of a procedure
• Verify approval of qualification procedures by the owner or owner-designated personnel
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Form Completion Requirements

To complete qualification verification forms, performers and reviewers must:
• Make all entries in permanent black ink.
• Complete all items on a form, except the optional Comments section.
• Initial and/or sign and date the form based on standard operating procedures to verify the performance of
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each applicable procedure in the qualification process.

Note: If an item is not applicable, enter N/A where indicated. (See Marking Elements That Are
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Not Required, below.)

• Document any deviation from defined protocols and expected results. Approval of protocol deviations by
an owner-designated responsible person (reviewer) must be documented before final approval signatures
are obtained in the applicable Part V: Performance Qualification workbook(s).

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• Write additional comments on an addendum page when there is not enough space on a form to

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accommodate all comments. Then:

1 1. Number the page alphanumerically (for example, 16A, 16B).

2. Initial and date the additions.
3. Insert the addendum page behind the original page.

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Correcting Entries
If you need to make corrections on forms, use the following procedures.

Correcting Short Entries

To correct a short entry (such as a single word or test result) on a form:
1. Draw a diagonal line, bottom-left to upper-right corner, through the misentered or incorrect information.

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2. Write the correction to the upper right of the original entry.
3. Initial and date the change.

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Correcting Long Entries
To correct a long entry or information block on a form:
1. Draw a diagonal line, bottom-left to upper-right corner, through the misentered or incorrect information.
2. Write the correction on a separate addendum page.
3. Number the page alphanumerically (for example, 16A, 16B).
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4. Initial and date the changes.
5. Place the addendum page behind the original page.

Marking Elements That Are Not Required

Some elements included in a qualification process may not apply to your chromatography system configuration.
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The elements that are not required may be a procedure or part of a procedure and/or part of a form. Mark each
such element carefully according to either of the following instructions to make it clear that the element is
unnecessary and that you have not skipped or forgotten it:
• Draw a diagonal line, bottom-left to upper-right corner, through the element that is not required. Waters
recommends that you initial and date the deletion. Include comments above the line or on the form to
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record why the element is not required.

• Write N/A (Not Applicable) where indicated. If necessary, you can include comments above the line or on
the form to record why the element is not required.

Note: The performer and reviewer must sign and date all forms, even when part of the form or
procedure is marked N/A. An unused line for an additional performer, reviewer, or manager, for
example, can be indicated as such by placing N/A on the line.
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Test Failures
When a test fails, it is important to determine if the instrument is not operating properly or if the failure is due to
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operator error or improper test preparation. If you determine the cause of the failure, enter an explanation of the
cause (such as lack of proper degassing) in the Comments section of the form. If you can correct the problem,
rerun the test. Enter results from the repeated test and initial and date the results next to the original failed results
on the form (if there is enough space), or on an addendum sheet that you insert in the workbook.

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If you cannot determine the cause of the test failure, review the test procedures thoroughly and repeat the test

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preparations. Be sure that test preparations, such as system equilibration, are complete before starting the
qualification process. This minimizes difficulties and reduces the time to complete the test by avoiding the
necessity of rerunning tests. Repeat the test twice. Enter the test results from both reruns, then initial and date the
results on the form or on an added addendum sheet. Keep all results, including the failed test results, in the
workbook.

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If the rerun test does not pass both times, contact your local Waters representative for a demand or contract
service visit.

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1.5 Chromatography System Qualification Protocol Approval

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1 To approve all protocols to be used to qualify the installation, operation, and maintenance of the chromatography
system and to qualify system performance, the owner’s management must:
1. Review all qualification protocols in this qualification workbook.

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2. Complete Form 1-1. If this form is duplicated in the other Parts of the workbook, you may write
“Signatures in Part I” in the Comments section and line out the signature section as described in
Section 1.4, Verification Forms, the “Marking Elements That Are Not Required” discussion.

Form 1-1 Chromatography System Qualification Protocol Approval

The undersigned owner’s management approve the procedures in Parts I through V of the workbook to be used to qualify

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the installation, maintenance, and operation of the chromatography system components and to qualify total system
performance.
Comments

Manager
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Name (printed) Signature

Title Date
Owner-designated responsible person

Manager
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Name (printed) Signature

Title Date
Owner-designated responsible person

Manager
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Name (printed) Signature

Title Date
Owner-designated responsible person

 2003 Waters Corporation

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