Equipment Qualification Plan (EQP) : Agilent Enterprise Edition Compliance Services

Standard_EQP_UHPLCMS Document Released: October 2009 Enterprise Edition Compliance Services
Equipment Qualification Plan (EQP)

Agilent Enterprise Edition Compliance Services
Qualification of UHP_LCMS Systems
1290 Infinity UHPLC Series with 6000,6100, 6200, 6300, 6400,

and 6500 Series LCMS Systems
REVIEW DOCUMENT NAME:

Standard_EQP_UHPLCMS
Standard_EQP_LCMS Document Released: October 2009 Enterprise Edition Compliance Services
How to Use this Document

This document is an Equipment Qualification Plan (EQP). It covers Design Qualification (DQ), Installation Qualification (IQ),
Operational Qualification (OQ), scheduled repeat OQ, and Re-Qualification after Repair (RQ). It contains information on how
Enterprise Edition Compliance Services work, and also provides a full list of the tests and checks performed as part of Agilent’s
standard Enterprise Edition IQ and OQ services.
The hardware and software IQ and OQ procedures listed in this document include fixed tests and checks at Agilent recommended
criteria and limits.
All tests in this document exist in all Agilent delivery tools. However, customer-selectable variance to the standard hardware OQ set
points is possible to enable testing of chromatography system(s) over their intended range of use. All set point menu selections in the
Variance Section are with the validated range of Enterprise Edition.
The inventory of systems covered by the EQP will be maintained as a separate record.
To facilitate the EQP review and approval process, this document is best viewed on-screen using Adobe ®. Also, there are three pdf
file attachments included with this document: (i) Sample Hardware OQ Report (ii) Question and Answer document (iii) 21 CFR Part11
Conformance Checklist for the Agilent Compliance Engine (ACE) - the Enterprise Edition delivery tool.
To approve this EQP simply print to paper and sign. To add variances see instructions below. Keep copies for your own records.
Verbal confirmation of approval is sufficient for Agilent service to proceed.
To make variances to the standard hardware OQ setpoints:

[1] Use the pull-down button to select the alternative approval statement "shall follow...the standard specifications with VARIANCES to OQ setpoints...";
[2] Complete the "EQP Record of Variances to Setpoints from Standard OQ Specifications" Page 20; [3] Print EQP to paper and
[4] ENSURE THE VARIANCE REQUEST IS COMMUNICATED to Agilent service engineer BEFORE first OQ delivery starts. Do not e-mail/FAX/post
copies of your approved EQP to Agilent. BUT CUSTOMER MUST PROVIDE A COPY OF ANY EQP WITH VARIANCES TO AGILENT OPERATOR
ON-SITE TO ENSURE THE VARIANCES ARE ENTERED INTO DELIVERY TOOL. NO EXTRA FEE TO DELIVER SET POINT VARIANCES.
For a full process description, see the EQP Record of Variances to Setpoints section on page 20.
Approval of EQP
The undersigned person(s) approve the following:
[1] the use of Enterprise Edition Compliance Services and delivery of the IQ and/or OQ and/or RQ checks and tests
appropriate to the actual configuration, make, and model of those systems covered by the service;
[2] the specifications described in this Global EQP Review Document where the tests, setpoints, and limits shall follow ...
the STANDARD FIXED Agilent recommended specifications.

Name and Role Signature and Date
[You cannot save your form entries with Adobe Reader. But typed entries and menu selections are printed on your official paper copy when you print.]
DO NOT SEND AGILENT A COPY OF YOUR APPROVED EQP. THIS DOCUMENT IS YOUR OWN RECORD OF APPROVAL.
(C) Agilent Technologies Inc. 2005-2009 Page 2 of 22 No reproduction, translation or use without permission
Contents
Click a section title to move to that page.
Section Page
How Enterprise Edition Compliance Services Work 4
Design Qualification (DQ) 5
Installation Qualification (IQ) Hardware 7
Operational Qualification (OQ) Hardware 7
Standard OQ Test Specifications for Agilent UHP_LCMS Systems 7
Standard OQ Test Specifications for Agilent LCMS Systems: Single Quadrupole 9
Standard OQ Test Specifications for Agilent LCMS Systems: Triple Quadrupole 10
Standard OQ Test Specifications for Agilent LCMS Systems: Ion Trap 11
Standard OQ Test Specifications for Agilent LCMS Systems: Q-TOF 12
Standard OQ Test Specifications for Agilent LCMS Systems: TOF 13
OQ Test Design and Rationale for LCMS Systems 14
EQP Record of Variances to Setpoints from Standard OQ Specifications 20
Re-Qualification after Repair (RQ) Hardware 21
Legal, Endorsement, and Revision Notes 22
PDF File Attachments to this electronic EQP [open attachments folder of this document in Adobe]
Extracts of sample OQ Report Why Change? Q & A Part 11 Checklist (ACE)
How Enterprise Edition Compliance Services Work

Enterprise Edition is designed to fit the traditional quality systems used by firms and recognized by regulatory agencies worldwide.
How Enterprise Edition aligns with a traditional, paper-based methodology is described below:
[i] Policy documents dictate the need for validation & qualification of GMP/GLP systems and usually mention the DQ/IQ/OQ/PQ model.
The precise procedures for IQ & OQ for each type of equipment are prescribed in an approved SOP, perhaps called SOP #101:
Qualification of LCMS Systems. In Enterprise Edition, the EQP has the same role as the traditional Qualification SOP.
[ii] The traditional SOP provides lists of tests & limits for the range of system configurations found in the lab or department. The EQP
follows this concept. The inventory of systems covered by an SOP or EQP changes over time - so this is kept as a separate record.
[iii] The traditional Qualification SOP typically has blank results forms as attachments to be photocopied for each IQ or OQ event - the
results recorded in ink with manual calculations. In Enterprise Edition this execution process is streamlined and automated by use of
Adobe forms and the Agilent Compliance Engine (ACE) delivery tool. It provides reports with no hand-writing errors; validated
calculations; automated pass/fail report; traceability to raw data and a count of number of times a test was run. This automation
provides efficiency and enforces compliance to procedure.
[iv] The traditional Qualification SOP is approved and released only once - replacing need to author individual protocols for each
chromatography system. This is the same concept for the EQP. The appropriate tests for each individual configuration are automatically
selected by ACE from the list in the approved EQP - at time of delivery. The final reports are unique for each system and each
qualification event - but the single approved EQP can cover a lab, department or as wide a scope as desired.
ACE
Software
(a) (b) (c)
(d) (e) (f) (g)

Figure 1:
This EQP Review Document (a) is the record of IQ checks and OQ / RQ tests, setpoints, and limits for analytical scale LCMS systems.
The tests already exist in the automation tool called ACE (b) and are ready to run after the EQP is approved. ACE holds the test forms
applicable to the full range of LCMS configurations plus a validated calculation and report generator engine. At time of delivery, a
record of individual system configuration is made by the operator and entered into ACE (c). The correct test forms are automatically
selected by ACE from its internal catalog of test designs (d). Each test in the catalog has a blank results template form (e).
The appropriate setpoints and limits for the individual LCMS system are added by ACE to the forms according to the approved EQP.
When each test is run, the results are calculated and forms completed (f) and then collated to make a single final report called an
Equipment Qualification Report (EQR), which is provided in secure PDF format on CD disk – printable to paper and stored in a binder
and/or customers' network storage system (g).
Design Qualification (DQ)
Design Qualification (DQ) for commercial lab instruments is recommended by some, but not all, guidances and
procedures. Defintions of DQ found in guidances and firm-specific validation procedures vary widely around the world.
Some firms require nothing more than a record (such as certificate) from the instrument manufacturer demonstrating that
the lab system has been designed for purpose and manufactured to a quality standard. Others treat DQ as the
development of a user requirement specification document (URS) which can be matched to the IQ and OQ specifications
for a manufacturer. Other firms consider DQ as including the vendor selection activities.
USP Chapter <1058> pre-published in USP 31/Supplement defines DQ:
Design qualification (DQ) is the documented collection of activities that define the functional and operational
specifications of the instrument and criteria for selection of the vendor, based on the intended purpose of the instrument.
Design qualification (DQ) may be performed not only by the instrument developer or manufacturer but also may be
performed by the user. The manufacturer is generally responsible for robust design and maintaining information
describing how the analytical instrument is manufactured (design specifications, functional requirements, etc.) and tested
before shipment to users. Nonetheless, the user should ensure that commercial off-the-shelf (COTS) instruments are
suitable for their intended application and that the manufacturer has adopted a quality system that provides for reliable
equipment. Users should also determine capability of the manufacturer for support installation, services, and training.
For your reference, Agilent provides the following statements for DQ purposes:
1. All Agilent LC, LCMS, GC, and GCMS hardware and software laboratory products including the ACE software used to
deliver qualification services, are designed, manufactured, and tested according to Agilent internal Quality Life-Cycle
Development Procedures.
2. Certificates of Agilent testing, validation, and conformance to standards are provided with new Agilent instruments
and similar certification is provided for ACE software. These documents are checked and recorded in Enterprise Edition
Compliance Services IQ.
3. Agilent maintains information describing how products are manufactured and maintains a problem and bug reporting
program as required by international software quality guidelines.
4. The OQ specifications in this EQR can be used, as appropriate, by the user to prepare URS. The OQ specifications in
this EQP represent the levels of performance acceptable to regulatory agencies for the technique; conform to typical
specifications found in Validation literature; are equally suitable for OQ at installation and on-going OQ throughout
operational lifetime; are equivalent to the OQ specifications published in the legacy Agilent Classic OQPV protocols; and
are suitable for most user requirements.
5. Agilent Technologies is capable of installation, support, preventive maintenance, on-going qualification and
re-qualification after repair and user training worldwide.
Installation Qualification (IQ) Hardware

Hardware IQ checks and tests for Agilent software products include the following:
1. Purchase Order Documents:
Allows the customer to verify that the instrument being qualified matches their design requirements (if available) and
purchase order.
2. Preparation and Installation Documents:
Gathers and records information about preparation and installation documents.
3. System and Installation Documentation:
Gathers and records information about reference and user manuals for initial installations.
4. Product Quality Assurance Documents:
Collects and records certificates and other forms that verify that the vendor has developed and built the product
according to internal standards.
5. Start Up Test:
Verifies that all modules start up properly.
6. Instrument Check:
Demonstrates that all modules of the instrument are correctly installed and connected. It does not test instrument
performance as fully as OQ. This test is not necessary and therefore skipped if an OQ is to be performed by Agilent
operator at installation after IQ.
Operational Qualification (OQ) Hardware

Standard OQ Test Specifications for Agilent UHP_LCMS Systems LC Modules
Test Name Setpoints and Parameters Limits
Pump Flow Accuracy and Flow Rate 1 = 0.500 ml/minute Accuracy <= 3.00% from setpoint
Precision Flow Rate 2 = 5.000 ml/minute Precision <= 0.50% RSD
Column Temperature Accuracy Temperature 1 = 80.0 C Accuracy <= 3.0 C from setpoint (above 60 C)
and Stability Temperature 2 = 40.0 C Accuracy <= 2.0 C from setpoint (up to 60 C)
[Stability measured at setpoint 2] Stability <= 1.0 C
Wavelength Accuracy (UV-Vis) Wavelength 1 = 205 nm [Maximum] Difference from set point <= 2 nm
Wavelength 2 = 245 nm [Minimum]
Wavelength 3 = 273 nm [Maximum]
Wavelength Accuracy (FLD) Wavelength 1 = 350 nm [Maximum] Difference from set point <= 3 nm
Wavelength 2 = 397 nm [Maximum]
Signal Noise and Drift (VWD) ASTM baseline noise Noise <= 0.04 mAU
Slope of regression fit for drift Drift <= 0.50 mAU/hour
Signal Noise and Drift (DAD, ASTM baseline noise DAD Noise <= 0.030 mAU
MWD) Slope of regression fit for drift DAD Drift between +/-3.0 mAU/hr
MWD Noise: <= 0.050 mAU
MWD Drift between +/- 5.0 mAU/hr
Signal Noise and Drift (RID) ASTM baseline noise Noise <= 10.000 nRIU
Slope of regression fit for drift Drift between +/- 400.000 nRIU/hour
Signal Noise and Drift (ELSD) ASTM baseline noise Noise <= 2.0 mV
Slope of regression fit for drift Drift between +/- 5.0 mV/hour
Signal to Noise (UV-Vis) Signal height is divided by ASTM baseline DAD Signal to noise >= 10,000
noise for known concentration and known Other UV-Vis Signal to noise >= 3,000
conditions.
Signal to Noise (RID) Signal height is divided by ASTM baseline Signal to noise >= 2000
noise for known concentration and known
conditions.
Signal to Noise (FLD) Signal height of Raman peak is divided by Signal to noise >= 400
noise at different wavelength in flat region
of emmision spectrum.
Fixed/Variance Key
UHPLC Fixed Fixed setpoints/ Variance allowed
setpoints/limits limits for setpoint(s)
Operational Qualification (OQ) Hardware (continued)

Standard OQ Test Specifications for Agilent UHP_LCMS Systems LC Modules
Injection Precision (UV-Vis, RID) UV-Vis: Injection volume: 10 ul Height RSD <= 2.00%
RID: Injection volume: 20 ul Area RSD <= 1.00%
Injection Precision (ELSD) Injection volume: 20 ul Height RSD <= 2.00%

Area RSD <= 2.00%
Injection Carry Over (UV-Vis and UV-Vis: Injection volume: 10 ul Height carry over <= 0.20%
RID) RID: Injection volume: 20 ul Area carry over <= 0.10%
Response Linearity (UV-Vis) 5 concentrations of certified reference Coefficient of determination (r2) >= 0.99900
standard R/F Precision <= 5.00% RSD
Response Linearity (RID) 5 concentrations of certified reference Coefficient of determination (r2) >= 0.99500
standard R/F precision <= 10.00% RSD
Gradient Composition Accuracy 20%, 40%, 60%, and 80% steps Accuracy <= 2% difference from each step setpoint
Gradient Composition Noise and 20%, 40%, 60%, and 80% steps ASTM noise <= 2.0% from each step setpoint
Gradient Composition Drift Drift between +/- 2.0% from each step setpoint
Gradient Linearity Linear Gradient from 100% to 0% Coefficient of determination (r2) >= 0.99900
(at start, middle, and end)
Sample Temperature Accuracy Temperature: 4C Diff. from setpoint = -2.0 to +5.0 C (setpoints < 10 C)
[Four vials of water in different tray Diff. from setpoint <= 3.0 C (setpoints > 9 C)
positions]
Fixed/Variance Key
Specifications for MSD Component of LCMS
Source Key
ES: API-ES MMES: Multimode API-ES mode; MMCI: Multimode AP-CI mode
CI: AP-CI DSES: Dual spray API-ES;
ES+AJST: AP-ESI with Agilent Jet Stream Technology
No set point variances available for MSD specific tests
Standard OQ Test Specifications for Agilent LCMS Systems: Single Quadrupole
Test Name Setpoints and Limits

Parameters
Vacuum Verification N/A High Vacuum Min.: 2E-6 torr (any source)
High Vacuum Max.: 2E-5 torr (any source)
Scan Verification Evaluated mass: 311 m/z All used masses: +/- 0.2 m/z (ES, CI, MMCI; N/A for MMES)
Injection volume: 5 ul
Response Linearity Evaluated mass: 311 m/z Coefficient of Determination (r2): >= 0.98000 (any source)
Injection Precision Evaluated mass: 311 m/z Area RSD: <= 10.00% (any source)
Injection volume: 5 ul Height RSD: <= 10.00% (any source)
Injection Carry Over Evaluated mass: 311 m/z Area <= 1.00% (any source)
Injection volume: 5 ul Height <= 1.00% (any source)
Signal to Noise Evaluated mass: 311 m/z Signal to Noise: >= 20 (any source)
Masses Used for Scan Verification
Known G2421A AP-ESI (for G2432A AP-CI (for G1969-85000 ESI-L G1969-85010 APCI-L
Mass models G6110A, models G6110A, API-ES and MM Source AP-CI (for model
G6120A, G6130A*) G6120A, G6130A) (for model G6140A) G6140A)
1: 118.09 121.05 118.09 121.05
2: 622.03 622.03 622.03 622.03
3: 922.01 922.01 922.01 922.01
4: 1521.97** 1521.97* 1221.99 1221.99
5: 2121.93** 2121.93* N/A N/A
* Also applies to G1946C, G1946D, G1956A, and G1956B models.

** Applies to SL and 6130 systems only.

Standard OQ Test Specifications for Agilent LCMS Systems: Triple Quadrupole

Parameters
Vacuum Verification N/A High Vacuum Min./Max.: 2.7E-5 torr/3.4E-5 torr (any source)
High Vacuum Min./Max.: 1.8E-5 torr/2.7E-5 torr (any source, QQQ Hotbox)
Scan Verification See table below for used All used masses: +/- 0.2 m/z (ES only, N/A for others)
masses.
Scan Verification (Additional See table below for used All used masses: +/- 0.2 m/z (ES only, N/A for others)
Filter) masses.
Response Linearity Evaluated mass: 156 m/z Coefficient of Determination (r2): >= 0.98000 (any source)
Injection volume: 5 ul (*)
Injection volume: 5 ul (*) Height RSD: N/A (any source)
Injection Carry Over Evaluated mass: 156 m/z Area <= 1.00% (any source)
Injection volume: 5 ul (*) Height <= 1.00% (any source)
Signal to Noise Evaluated mass: 156 m/z Signal to Noise: >= 20 (ES, MMES, MMCI. N/A for APCI)
(*) Injection volume: 1 ul for 6460 Series AP-ESI Source with Agilent Jet Stream Technology.
Masses Used for Scan Verification and Scan Verification (Additional Filter)
G1969-85000 ESI-L Tune Mix [Positive Mode]
Known 6410 6420 6460 6430

Mass
1: 118.09 118.09 118.1 118.1
2: 322.05 322.05 322.1 322.0
3: 622.03 622.03 622.0 622.0
4: 922.01 922.01 922.0 922.0
5: 1221.99 1221.99 1522.0 1222.0
6: 1521.97 1821.95 2121.9 1822.0

Standard OQ Test Specifications for Agilent LCMS Systems: Ion Trap

Parameters
Scan Verification See table below for used All used masses: +/- 0.2 m/z (ES only, N/A for others)
masses.
Response Linearity Eval. mass: 156/218/245 m/z* Coefficient of Determination (r2): >= 0.98000 (any source)
Injection volume: 5 ul**
Injection Precision Eval. mass: 156/218/245 m/z* Area RSD: <= 10.00% (any source)
Injection volume: 5 ul** Height RSD: N/A (any source)
Injection Carry Over Eval. mass: 156/218/245 m/z* Area <= 1.00% (any source)
Injection volume: 5 ul** Height <= 1.00% (any source)
* Use the most abundant ion.

** For CI source, use 20 ul.
Known G2431A Ion Trap ESI

Mass Tune Mix
1: 118.09
2: 322.05
3: 622.03
4: 922.01
5: 1521.97
6: 2121.93

Standard OQ Test Specifications for Agilent LCMS Systems: Q-TOF

Parameters
(Additional Zone) High Vacuum Max.: 5E-7 torr (any source)
Scan Verification See table below for used All used masses: +/- 0.2 m/z (DSES, ES+AJST, N/A for others)
masses.
Scan Verification (Additional See table below for used All used masses: +/- 3.0 ppm (DSES, ES+AJST, N/A for others)
Filter) masses.
Response Linearity Evaluated mass: 156 m/z Coefficient of Determination (r2): >= 0.98000 (DSES, ES+AJST; N/A for
Injection volume: 20 ul (*) others)
Injection volume: 20 ul (*) Height RSD: Not applicable (any source)
Injection Carry Over Evaluated mass: 156 m/z Area <= 1.00% (DSES, ES+AJST; N/A for others)
Injection volume: 20 ul (*) Height <= 1.00% (DSES, ES+AJST; N/A for others)
Signal to Noise Evaluated mass: 156 m/z Signal to Noise: >= 10 (DSES, ES+AJST, N/A for others)
Masses Used for Scan Verification and Scan Verification (Additional Filter)
Known G1969-85000 ESI-L Tune Mix

Mass
Scan Verification Scan Verification (Additional Filter)
1: 118.09 118.086255
2: 322.05 322.048121
3: 622.03 622.028960
4: 922.01 922.009798
5: 1221.99 1221.990637
6: 1521.97 1521.971475
7: 1821.95 1821.952313
8: 2121.93 2121.933152
9: 2421.92 2421.913990
10: 2721.90 2721.894829

Standard OQ Test Specifications for Agilent LCMS Systems: TOF

Parameters
Scan Verification See table below for used All used masses: +/- 3.0 ppm (CI, MMCI, DSES, ES+AJST; N/A for MMES)
masses.
Response Linearity Eval. mass: 311.08 m/z Coefficient of Determination (r2): >= 0.98000 (DSES, ES+AJST; N/A for
Injection volume: 20 ul others)
Injection Precision Eval. mass: 311.08 m/z Area RSD: <= 10.00% (any source)
Injection volume: 20 ul Height RSD: N/A (any source)
Injection Carry Over Eval. mass: 311.08 m/z Area & Height <= 1.00% (DSES, ES+AJST; N/A for others)
Signal to Noise Eval. mass: 311.08 m/z Signal to Noise: >= 20 (DSES, ES+AJST; N/A for others)
Known G1969-85000 ESI-L G1969-85010 APCI-L G1969-85020 MMI-L

Mass Tune Mix Tune Mix Tune Mix
1: 118.086255 121.050873 121.050873
2: 322.048121 322.048121 322.048121
3: 622.028960 622.028960 622.028960
4: 922.009798 922.009798 922.009798
5: 1221.990637 1221.990637 1221.990637
6: 1521.971475 1521.971475 1521.971475
7: 1821.952313 1821.952313 1821.952313
8: 2121.933152 2121.933152 2121.933152
9: 2421.913990 N/A 2421.913990
10: 2721.894829 N/A 2721.894829
End of Section - Standard OQ Test Specifications for Agilent analytical-scale LCMS Systems.
EXTRA INFORMATION SECTION

Many GMP/GLP enforcement agency inspectors now ask firms to provide a risk assessment of their equipment &
computer systems plus a science-based rationale for subsequent validation & qualification testing.
GENERAL RISK STATEMENT: Any LC, LCMS, GC or GCMS system used for raw material testing or final drug
product / medical device testing in GMP or used in formal GLP studies will likely fall into a HIGH RISK category. This
risk assessment will imply the need for IQ & OQ & on-going qualification. ANY USER SPECIFIC RISK ANALYSIS
SUPERCEDES THIS GENERAL RISK STATEMENT.
The following section outlines the science-based rationale for each test in the Agilent hardware OQ plus a brief test
design & procedure description.
OQ Test Design and Rationale for LCMS Systems
The recommended set of hardware OQ tests described in this EQP derives from Agilent's intepretation of FDA, USP, and GAMP4
guidelines and other authoritative expert literature.
OQ test design incorporates both modular and holistic testing, which is a proven and regulatory acceptable approach. Direct
metrology is used to test pump flow rates and thermal-controlled column compartment and autosampler modules. Holistic chemical
testing is used for the evaluation of the following critical instrument characteristics: linearity, precision, signal to noise, and carry over.
Certified reference standards and calibrated traceable thermometers and digital flowmeters are used.
Considering the number of setpoints, parameters, and conditions of each recommended OQ test, the proven concepts of worst case,
range, and representative have been applied. If a property or characteristic is known to have its worst performance at one end of a
range of use, this is the setpoint that should be tested and other setpoints are not required. If a property or characteristic has no
known worst case, testing at the high and low points of the range of use is required. If there are too many possible use cases and
conditions to realistically test (and none is a worst case), a representative sample for test is the best approach.
The test design for LC systems covers UV absorbance, fluorescence, evaporative light scattering, and refractive index detectors;
isocratic, binary, tertiary, and quaternary pumps; most autosampler models; and fraction collectors.
Tests for LC Systems (Non-MSD)
1. Pump Flow Accuracy and Precision
Rationale: Accuracy of flow is important for comparability between systems and transferring methods. Flow precision is critical for
repeatability of peak height and area.
Procedure: A calibrated digital flowmeter is attached to the waste line of the system flowing pure water at representative back
pressure provided by a small guard column. Six readings are taken at each setpoint to determine the flow accuracy and precision.
Flow accuracy is calculated as the absolute % difference of the mean of the six flow readings against the setpoint. The precision is
calculated as the %RSD of the six flow readings. The two default set points (0.5ml/min and 5.0 ml/min) are evaluated in the core test.
Extra setpoints and flexible test range are only available in customer-configured EQPs for flow, temperature, and some other tests.
The repeat measurements of flow in the flow precision test eliminate the need for measurement of retention time precision (which is an
indirect approach to determining flow precision).
OQ Test Design and Rationale for LCMS Systems (continued)
2. Column Temperature Accuracy and Stability
Rationale: The thermostat accuracy is important for comparability between systems and transferring methods. Column temperature
stability is critical for repeatability of peak height and area.
Procedure: A calibrated digital temperature meter and a proprietary probe are used to measure the temperature of the flowing eluent.
With the use of a T-piece, the temperature probe is positioned to be in contact with the heated eluent. A typical column compartment
temperature range of use is tested. At the high end of the range, after stabilization, the temperature accuracy is calculated as the
absolute difference between what was measured and the setpoint. After completing this measurement at the low end of the range, six
readings are taken every four minutes and temperature stability is calculated as the absolute difference between the highest and
lowest measured temperatures. The temperature accuracy is calculated as the average of the six readings compared to the setpoint.
All readings are reported in Celsius. Both sides of the Agilent column compartment are tested at the same time.
3. Wavelength Accuracy
Rationale: Wavelength accuracy is critical for accuracy of quantitative and qualitative analysis. Wavelength accuracy is also important
for comparability between systems and transferring methods.
Procedure for UV absorbance detector (UV, VWD, DAD, PDA, etc.): A traceable caffeine standard is used to determine the
wavelength accuracy. In one procedure, for certain models, the caffeine is trapped in the flow cell and a programmable timetable is
used to determine the wavelength maxima (205 and 273 nm) and minimum (245 nm). For other models (for example, DAD and PDA),
a caffeine injection is made and a spectrum is acquired. The spectral maxima and minimum are determined directly from the scan or
the table of scan results. The wavelength accuracy is determined as the absolute difference between the measured and certified
wavelength values.
Procedure for fluorescence detector: The detector cell is filled with pure water. Using a programmable timetable, the excitation (350
nm) and Raman band emission (397 nm) wavelengths are determined. The wavelength accuracy is determined as the absolute
difference between the measured and theoretical peaks of Raman scattering (in nm).
4. Signal Noise and Drift
Rationale: This test gives an indication of detector sensitivity and stability.
Procedure for UV absorbance detectors: Pumping water at 1 ml/min, the signal is monitored at a specified wavelength over a twenty
minute period. The signal noise is calculated based on ASTM E685-93 as the average peak-to-peak noise in a number of signal
segments. The drift is calculated as the slope of the linear regression for the signal.
Procedure for evaporative light scattering detectors: With no flow and the inlet to the detector capped, the signal is monitored over a
twenty minute period. The signal noise is calculated based on ASTM E685-93 as the average peak-to-peak noise in a number of
signal segments. The drift is calculated as the slope of the linear regression for the signal.
Procedure for refractive index detectors: Pumping water at 1 ml/min, the signal is monitored over a twenty minute period. The signal
noise is calculated based on ASTM E685-93 as the average peak-to-peak noise in a number of signal segments. The drift is
calculated as the slope of the linear regression for the signal.
5. Injection Precision
Rationale: System precision is critical for accuracy of quantitation. Autosampler performance contributes to system precision.
Procedure: A short column is used to separate the evaluation standard from the void volume. Using a traceable standard, six
injections from the same standard are made and the height, area, average height, average area, %RSD of height and %RSD of area
are determined and calculated.
6. Injection Carry Over
Rationale: Low carry over from a previous injection is critical for accuracy of quantitative and reliability of qualitative analysis. This test
challenges the injector system in the LC system.
Procedure: Following the six-injection precision test, a blank injection is made. The carry over result is calculated as a ratio of the area
of any residual peak found in the blank injection to the average peak area of the previous six injections (expressed as a percentage).
7. Signal to Noise
Rationale: Sensitivity is a critical performance feature in quantitative and qualitative analysis. A signal-to-noise value of a
representative compound at known concentration provides sensitivity statistics. This
measurement is especially critical to establish level of detection.
Procedure for UV absorbance detector and refractive index detector: An evaluation standard is injected and the calculated height,
divided by the ASTM noise monitored over a specified range, provides the signal-to- noise result.
Procedure for fluorescence detector: Using pure water in the flow cell, the signal is monitored at the emission maximum wavelength of
the Raman band of water and then, using a timetable, switched to a no emission wavelength where the noise is monitored. Signal to
noise is calculated as the height of the Raman band peak divided by the monitored noise in a spectral region where no scattering is
expected.
8. Response Linearity
Rationale: The linearity of a detector is a critical parameter to establish for reliable and accurate quantitative results and is important
for comparability between systems and transferring methods.
Procedure: A series of five traceable standards which represent typical concentrations range are injected and evaluated. The response
linearity is calculated by determining the coefficient of determination (r2) of the peak areas versus concentration. It is now recognized
that regression statistics alone are insufficient and non-sensitive indicators of linearity. Therefore, the %RSD of the response factors
for all five peaks is also calculated. In addtion, as an optional extra linearity statistic, ratios of peak areas in the set of five injections
can be reported. For example, up to two ratios such as Peak 2 to Peak 1 and Peak 5 to Peak 2 can be selected in the Global EQP with
Variance section.
9. Gradient Composition
Rationale: Accuracy and stability of solvent mixing online is critical for consistent and accurate quantitative analysis. Gradient
composition is also important for comparability between systems and transferring methods.
Procedure: [Pre-requisite: UV detector is connected to the system.] An acetone tracer is used to determine the solvent gradient
composition accuracy, stability, and linearity. The test challenges the system by making compositional changes from 0% to 100% in
20% increments. In addition, a linear ramp down from 100% to 0% is performed where the composition accuracy is determined at 95,
75, and 25%. All composition accuracies are calculated as the absolute difference between the mean composition at each setpoint
and the theoretical composition. Stability is the slope of the linear regression of all compositions versus time points in each
composition step. Linearity is calculated from 95% to 5% in the linear portion of the gradient.
10. Sample Temperature Accuracy
Rationale: The thermostat accuracy is important for comparability between systems and transferring methods.
Procedure: Four vials are filled with water and allowed to equilibrate to the temperature setpoint. Similar to the column compartment,
the temperature of the water is measured using a traceable digital temperature meter and proprietary probe. Accuracy is determined
as the difference between the measured
temperature and the setpoint.
11. Fraction Collection (only applicable if collector is installed)
Rationale: It is important to demonstrate that a fraction collector is capable of collecting fractions based on peak detection or time.
Procedure: Two injections of a traceable standard are made and fractions are collected in peak-based or time-based mode. This is a
qualitative test in which the collected fractions are re-injected to demonstrate that they are fractions of the traceable standard.
The Following Tests are NOT INCLUDED in the Standard OQ but can be ordered as EXTRA COST TESTS
Injector Linearity Any choice of 5 injection volumes. Constant Coefficient of determination (r2) >= 0.99900
(must have UV detector) concentration std: 5ug/ml caffeine R/F precision <= 5.00% RSD
Injector Response Set point is same as set point chosen for Tolerance window varies depending on cell path
(must have UV detector) Injection Precision test length and injection volume. For std cell at 20ul limit
is 1,200,000 to 1,800,000 counts.
Custom 1. Injection Linearity (optional extra test available in custom-configured EQP)
Rationale: Injection linearity of variable volume LC injector systems is normally not critical to quantitative or qualitative analysis. Most
LC analytical methods use fixed and only nominal injection volumes and do not use variable volume injections within a single analysis.
However, some users may wish to use variable volume injection if the linearity is demonstrated.
Procedure: Five injections of increasing volumes of the same traceable caffeine standard are made. Injection linearity is calculated
from the coefficient of determination (r2) of the peak areas versus injection volume. In addition, the %RSD of the response factor for all
five peaks is calculated.
Custom 2. Injection Response (optional extra test available in custom-configured EQP)
Rationale: The accuracy of the injected volume is normally not critical to quantitative or qualitative analysis. Most LC analytical
methods use fixed and only nominal injection volumes and results are not affected by even moderate inaccuracy in actual injected
volume. However, it may be important for comparability between systems and transferring methods, and it is useful as a diagnostic for
establishing that the correct injection syringe/loop/device is installed.
Procedure: A known traceable caffeine standard is injected six times (in the precision tests) and the average response is calculated.
The injection response is the mean of the average areas corrected for sample concentration, cell path length, and attenuation, and the
response within an acceptance window indicates correct volume injected.
Fixed/Variance Key
Tests for Mass Spectrometer Detectors of LCMS:
MSD 1. Vacuum Verification
Rationale: A stable, high vacuum is required for high-sensitivity mass spectrometry.
Procedure: Multiple readings of the vacuum system are taken and an automated comparison of these values to the known acceptable
values is made. Passing this test is a pre-requisite for the following tests.
MSD 2. Scan Verification
Rationale: Calibration of mass range is critical in qualitative mass spectrometry.
Procedure: [Agilent MS only] The built-in Agilent autotune feature is performed. This determines the proper calibration of the MSD and
ensures that masses are correctly reported across the entire mass range of the instrument. [Non-Agilent LCMS systems] A manual
tune is made where applicable.
MSD 3. Response Linearity
Rationale: Knowledge of the response curve is critical for quantitative analysis.
Procedure: A sulfa drug mix standard of four sulfonamide drugs is injected into the system at five concentrations representing a wide
range for LCMS. The ions monitored are appropriate to the system type. The calculated RSQ best-fit regression line and plot of the
response curve provides the statistics required to evaluate the instrument’s overall response curve. This allows users to set
appropriate calibration ranges and limits in their quantitative application methods.
MSD 4. Injection Precision
Rationale: System precision is critical for accuracy of quantitation. Autosampler performance and MS ionization contribute to LCMS
system precision. Autosampler precision is challenged in the standard LC module tests using a UV detector. A repeat precision test in
MS mode further challenges the precision of source ionization and MS detection.
Procedure: A blank injection followed by six repeat injections of the sulfa drug mix followed by a final blank injection are made. The %
RSD of the six injections is calculated to provide precision statistics.
MSD 5. Carry Over
Rationale: Low carry over from a previous injection is critical for accuracy of quantitative and reliability of qualitative analysis.
Autosampler performance and MS detector condition contribute to LCMS carry over. Autosampler carry over is challenged in the
standard LC module tests using a UV detector. A repeat carry over test in MS mode further challenges the full LCMS system carry
over performance.
Procedure: A blank injection followed by single injection of the highest concentration standard followed by a blank injection. The last
blank injection is evaluated for carry over and the result expressed as a percentage of the value for the standard injection.
MSD 6. Signal to Noise
Rationale: Sensitivity of MS detection is an important performance feature in quantitative and qualitative analysis. A signal-to-noise
value of representative compounds and appropriate ions at known concentration provides sensitivity statistics.
Procedure: For all newly installed Agilent LCMS systems, a reserpine chemical standard is injected as part of the instrument check-out
test to provide a starting sensitivity reading. The reserpine signal-to-noise result is provided separately to the OQ report but can be
attached to the OQ report if required. For OQ at installation and ongoing OQ/re-calibration, the signal-to-noise value of the sulfa drug
mix is reported at the ion of interest. System performance over time can be evaluated by repeating this OQ test at suitable intervals.
(Signal to noise is only evaluated using the ESI source except for single quad. Ion Trap does not have signal to noise OQ test).
EQP Record of Variances to Setpoints from Standard OQ Specifications

Operational Qualification (OQ) Hardware
(IGNORE THIS SECTION IF YOU ACCEPT AND APPROVE THE FIXED STANDARD QUALIFICATION TESTS AND
SET POINTS RECORDED IN THE PRECEDING PAGES OF THIS GLOBAL EQP.)
EQP with Variance Approval Process: Customer Actions:

1. View in Adobe ®. Select any required setpoint variances using the pull-down menus below and select the alternative
approval statement on Page 2.
2. Print to paper to save the selections. Sign page 2 of this EQP.
3. Ensure the approved EQP with Variances is provided to Agilent operator on the day of the first delivery before start of
OQ. Counter-sign & date the Agilent operator signature on this page.
[End of EQP with Variance approval process. Next step: wait for your qualification reports]
Agilent Operator Actions:

1. Enter and save the customer change requests on this page into the ACE tool.
2. Sign & date this page on the customer copy to verify that you made the changes in ACE. Return signed copy to
customer for counter-signature.
3. Deliver the qualification by following this EQP and any setpoint variances.
Note:
Once the EQP Variances are entered into ACE these are saved for all future OQ/RQ events where applicable.
Test Name Setpoint Standard Value Variance Units
Pump Flow Accuracy and Flow Rate 1 0.500 No variance ml/minute

Precision
Flow Rate 2 5.000 No variance ml/minute
Column Temperature Temperature 1 80.0 No variance C

Accuracy and Stability
Temperature 2 40.0 No variance C
Injection Precision, Injection Injection Volume on Column 20 No variance ul

Carry Over (UV-Vis, RID)
Sample Temperature Temperature 4.0 No variance C

Accuracy
Response Linearity (UV-Vis, 1st peak area ratio Not applicable No variance
RID optional extra statistic)
2nd peak area ratio Not applicable No variance
Customer Signature: Agilent Operator verifies variances are entered into ACE:
Name: Name:
Signature & Date: Signature & Date:
For a fully tailored operational qualificatiion program using all the flexibility of Enterprise Edition, contact your local Agilent
representative and/or e-mail Enterprise_edition@agilent.com with your OQ test specification requirements. Fees may apply.
Re-Qualification after Repair (RQ) Hardware

In the event of a hardware breakdown followed by an engineering repair of a qualified instrument, it is necessary to
re-qualify the system to an appropriate level before release back into operational use.
Agilent offers a service contract to repair and re-qualify an instrument during the period between scheduled annual OQs.
The level of re-testing is prescribed in the RQ section of ACE: a form is displayed for the operator showing all types of
repair possible and the re-testing required. An example form is shown below.
Re-Qualification After Repair
Pump Strategies
Repair/Replace Strategy Modules Repeat OQ Testing
Internal pump head parts, active inlet valve (or AIV cartridge), Any pump Flow Accuracy & Precision
(parts of) check valves, reference valves, inlet manifold or pump
drive, or taking pump head apart to clean (versus repair)
Pulse damper, pressure transducer Any pump Flow Accuracy & Precision
Multi-channel gradient valve Quaternary Flow Accuracy & Precision

Gradient Composition
The full list of repair and re-test guidance is available for review by customers of the RQ service.
The RQ form in ACE prescribes which tests the operator must perform for each repair circumstance. The test procedure,
setpoints, and limits will be an exact repeat of the previous OQ test (a so called regression testing strategy).
Legal, Endorsement, and Revision Notes
Enterprise Edition and its primary components (ACE software tool, procedures, test design, metrology tools, chemical
reference standards, operator training materials) has been designed, developed, tested, validated, and released for
commercial use following Agilent's Life-Cycle Development Quality Assurance methodology.
Date: May 2009
Services R&D Manager: Dr. Jonathan Gray. Santa Clara, California USA.
Services Quality Manager: Doug McDougall. Wilmington, Delaware USA.
Enterprise Edition is endorsed by Dr. Ludwig Huber on behalf of labcompliance.com

_________________________________________________________________________________________________________________________
ACE software is patent pending. Copyright is claimed by this statement for all original work comprising Enterprise Edition. Any
unauthorized use, reproduction, or translation will be prosecuted to the maximum extent possible by law.
All customer copies of EQP approval, final qualification reports, and raw data provided to customer at delivery of the service become
the property of the customer.
_________________________________________________________________________________________________________________________
Revision History of Enterprise Edition
A.01.71, October 2009 Added e-Signature fields. Changed nomenclature used to list limits. Regulatory impact: None.
A.01.70, May 2009 (1) Added Capillary Scale support; (2) Internal/External Valves support; (3) Reprocess plot for tests,
Injection Precision, Carry over, Response Linearity and Gradient Composition; (4) Condensed forms in
EQR; (5) New Noise and Drift Calculator REGULATORY IMPACT: None.
A.01.60, May 2008 One Test Specification Change: Noise & Drift limits for DAD/MWD and VWD re-set to same as Classic
OQPV limits. REGULATORY IMPACT: None.
GENERAL ADDITIONS/ENHANCEMENTS: (1) Made changes to simplify forms, make calculations
more flexible, and improve usability; (2) added support for a second UV detector; (3) added support for
the ELSD; (4) added the following forms: Certificate of System Qualification at end of EQR,
Chromatography Report automatically added after each test, Errors and Corrections for operator and
customer to record any corrections to EQR, Data Transfer Audit Log for complete traceability.
A.01.54, January 2008 Added e-Signature fields. Changed nomenclature used to list limits. Regulatory impact: None.
A.01.53, August 2007 (1) Added Q-TOF support; (2) added kPa units for pressure tests; (3) fixed typographical errors.
A.01.52, June 2007 Made cosmetic formatting changes to avoid truncation in Japanese version.
(1) Added support for fraction collectors; (2) added support for LCMS-MS; (3) added full IQ, OQ, RQ
A.01.50, March 2007 support for GC and GCMS.
A.01.40, December 2006 Added support for LCMS and limited GC support.
A.01.30, July 2006 (1) Added FLD and RID (initial release included UV/UV-Vis only); (2) added Signal to Noise test.
A.01.20, March 2006 Added support for rapid resolution.
A.01.10, November 2005 Initial HPLC - Analytical Scale - Operational Qualification.
_________________________________________________________________________________________________________________________
End of EQP Review Document

Equipment Qualification Plan (EQP) : Agilent Enterprise Edition Compliance Services

Uploaded by

Copyright:

Available Formats

Equipment Qualification Plan (EQP) : Agilent Enterprise Edition Compliance Services

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Equipment Qualification Plan (EQP) : Agilent Enterprise Edition Compliance Services

Uploaded by

Copyright:

Available Formats

What is the purpose of this document?

What is the purpose of this document?

What does IQ, OQ and RQ refer to?

What does IQ, OQ and RQ refer to?

Standard_EQP_UHPLCMS Document Released: October 2009 Enterprise Edition Compliance Services

Equipment Qualification Plan (EQP)

Qualification of UHP_LCMS Systems

1290 Infinity UHPLC Series with 6000,6100, 6200, 6300, 6400,

REVIEW DOCUMENT NAME:

How to Use this Document

To make variances to the standard hardware OQ setpoints:

the STANDARD FIXED Agilent recommended specifications.

How Enterprise Edition Compliance Services Work 4

Design Qualification (DQ) 5

Installation Qualification (IQ) Hardware 7

Operational Qualification (OQ) Hardware 7

Standard OQ Test Specifications for Agilent UHP_LCMS Systems 7

Standard OQ Test Specifications for Agilent LCMS Systems: Single Quadrupole 9

Standard OQ Test Specifications for Agilent LCMS Systems: Triple Quadrupole 10

Standard OQ Test Specifications for Agilent LCMS Systems: Ion Trap 11

Standard OQ Test Specifications for Agilent LCMS Systems: Q-TOF 12

Standard OQ Test Specifications for Agilent LCMS Systems: TOF 13

OQ Test Design and Rationale for LCMS Systems 14

EQP Record of Variances to Setpoints from Standard OQ Specifications 20

Re-Qualification after Repair (RQ) Hardware 21

Legal, Endorsement, and Revision Notes 22

How Enterprise Edition Compliance Services Work

(a) (b) (c)

(d) (e) (f) (g)

Design Qualification (DQ)

USP Chapter <1058> pre-published in USP 31/Supplement defines DQ:

Installation Qualification (IQ) Hardware

1. Purchase Order Documents:

2. Preparation and Installation Documents:

Gathers and records information about preparation and installation documents.

3. System and Installation Documentation:

4. Product Quality Assurance Documents:

Verifies that all modules start up properly.

Operational Qualification (OQ) Hardware

Test Name Setpoints and Parameters Limits

Operational Qualification (OQ) Hardware (continued)

Test Name Setpoints and Parameters Limits

Injection Precision (ELSD) Injection volume: 20 ul Height RSD <= 2.00%

Operational Qualification (OQ) Hardware (continued)

Specifications for MSD Component of LCMS

No set point variances available for MSD specific tests

Standard OQ Test Specifications for Agilent LCMS Systems: Single Quadrupole

Test Name Setpoints and Limits

Masses Used for Scan Verification

1: 118.09 121.05 118.09 121.05

2: 622.03 622.03 622.03 622.03

3: 922.01 922.01 922.01 922.01

4: 1521.97** 1521.97* 1221.99 1221.99

5: 2121.93** 2121.93* N/A N/A

* Also applies to G1946C, G1946D, G1956A, and G1956B models.

Operational Qualification (OQ) Hardware (continued)

Test Name Setpoints and Limits

G1969-85000 ESI-L Tune Mix [Positive Mode]

Known 6410 6420 6460 6430