EQUIPMENT QUALIFICATION PLAN (EQP) - Agilent Document... · Design Qualification (DQ) for commercial lab instruments is recommended by some, but not all, guidances and procedures

Qualification of GCMS SystemsAgilent 6890/6850 & 7890/7820 Series with Liquid or Headspace Samplers (including CTC) Connected to Agilent 597x Series MSD SQAgilent 7000 GC-QQQ Series and Agilent 7200 GC-QTOF SeriesAgilent 7890-based 220/240 Ion Trap Systems

REVIEW DOCUMENT NAME:Agilent_Recommended_EQP_GCMS

EQUIPMENT QUALIFICATION PLAN (EQP)

Agilent Enterprise Edition Compliance Services

Page 1 of 20

Page 2 of 20

Agilent_Recommended_EQP_GCMS

© Agilent Technologies, Inc. 2014

Document Released: April 2014

No reproduction, translation, or use without permission

Enterprise Edition Compliance Services

How to Use This DocumentThis 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 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 setpoints is possible to enable testing of chromatography system(s) over their intended range of use. All setpoint 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 several pdf file attachments included with this document: (i) Question and Answer document; (ii) 21 CFR Part11 Conformance Checklist for the Agilent Compliance Engine (ACE) - the Enterprise Edition delivery tool; (iii) EE 1.76 EQR comparison with other versions.

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 with scheduling and delivery.

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” later in this document; [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 SETPOINT VARIANCES.

For a full process description, click here to go to the EQP Record of Variances section.

Approval of EQPThe 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 Standard 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 form entries with Adobe Reader. 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.

Page 3 of 20






ContentsTo go to a section, click on one of the section titles below.

Sections Page

How Enterprise Edition Compliance Services Work ................................................................................................. 4

Design Qualification (DQ) .............................................................................................................................................. 5

Installation Qualification (IQ) Hardware ..................................................................................................................... 6

Operational Qualification (OQ) Hardware ................................................................................................................... 7

Standard OQ Test Specifications for GCMS Systems:

GC Modules ........................................................................................................................................................... 9

MSD ....................................................................................................................................................................... 9

OQ Test Design and Rationale for GCMS Systems ................................................................................................. 10

EQP Record of Variances to Setpoints from Standard OQ Specifications .............................................................. 17

Re-Qualification after Repair (RQ) Hardware ........................................................................................................... 18

Legal, Endorsement, and Revision History ............................................................................................................... 19

PDF file attachments to this electronic EQP (open the attachments folder for this document in Adobe):

Why Has Agilent Introduced the New Compliance Service, Called Enterprise Edition?IntroductionAgilent (then we were HP Analytical) introduced OQPV for our own LC and GC instruments in the early 1990’s and since then we have delivered well over 100,000 OQPV reports to customers around the world. Despite the undoubted success and acceptance of our old OQPV (now called Classic Edition to distinguish from the new Enterprise Edition service) times have changed. Expectations and requirements of an OQ have slightly shifted. The number and type of instruments and software used by our customers has increased. And of course we are truly in the new world of computers and electronic media.

So Agilent set out with a team of international experts 3 years ago to create an upgraded compliance service that would meet the new demands but crucially maintain the fundamental requirements:

• Always pass FDA and national agency audits without over-testing or under-testing;

• Challenge the LC or GC system with a scientifi cally sound methodology that provides valuable performance data.

• Meet the quality needs of customers and the spirit & intention of the GLP & GMP laws.

• Offer this service at a cost-effective price that makes it more than just worthwhile – we hope it is the simplest & best qualifi cation choice that a customer can make.

What Are The High Level Changes In Enterprise Edition And What Were The Drivers For These Changes?The fi rst big driver was the software environment. A greatly increased number of chromatography data system (CDS) products are available to control LC and GC systems. Agilent has ChemStation, Cerity, EZChrom, OpenLab and some specialist LCMS/GCMS software. Our customers also use Empower, Chromeleon, Atlas, Turbochrom and many others. Classic OQPV was built into ChemStation software. The Classic OQPV is a miracle of validated and almost fully automated OQ testing. But these benefi ts are therefore limited to Agilent instruments running on ChemStation. To provide all our customers, and customers of non-Agilent instruments, a single OQ solution as good as (or better than) OQPV – it was clear we had to develop an automation tool independent of ChemStation and any other CDS.

The Agilent Compliance Engine (ACE) is our new software tool that manages the workfl ow and protocols, calculates results and produces the reports. Naturally it is fully validated and tested. Our service engineers carry “ACE laptops” in the same way as they carry “ChemStation laptops”. Alternatively our contract customers can have the ACE software on their own laptops or installed with Agilent OpenLab networked CDS.

Table of contents: [click on title for fast navigation]

What Are The High Level Changes In Enterprise Edition And What Were The Drivers For These Changes?

Any Other Practical Or Process Changes In Enterprise Edition?

Let’s Dive Into The Details – How Do The Protocols And Tests In Enterprise Edition Compare To Classic Edition?

List Of Enterprise Edition OQ Tests Versus Classic OQPV Tests For LC:

What About The Reports, How Are These Different To OQPV Reports?

What Would I Have To Do If I Wanted To Move My Annual OQ Service From Classic To Enterprise Edition?

What Are The Main Risks To Migrating To Enterprise Edition And How To Avoid Them?

Finally, Can You Summarize The High Level Comparison Of Enterprise Edition Versus Classic Edition Compliance Services?

EE 1.76 Comparison Document

Q & A: Why Change? Part 11 Checklist (ACE)Signal to Noise Limits Table for MSD

Page 4 of 20






How Enterprise Edition Compliance Services WorkEnterprise 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 #123: Qualification of GCMS 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.

(v) In the traditional qualification methodology there is no convenient provision to record the actual workflow of the tests execution and results. In the event that a test is repeated during the Enterprise Edition delivery, ACE maintains a counter per test which is automatically incremented for GxP compliant work, and the engineer should generate a deviation note within the ACE report.

Figure 1:This EQP Review Document is the record of IQ checks and OQ / RQ tests, setpoints, and limits for GCMS systems. The tests already exist in the automation tool called ACE and are ready to run after the EQP is approved. ACE holds the test forms applicable to the full range of GCMS 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. The correct test forms are automatically selected by ACE from its internal catalog of test designs. Each test in the catalog has a blank results template form. The appropriate setpoints and limits for the individual GCMS 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 and then collated to make a single final report called an Equipment Qualification Report (EQR), which is provided in secure PDF format or optional CD disk – printable to paper and stored in a binder and/or customers’ network storage system.

.

Page 5 of 20






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, GCMS, UV-Vis and Dissolution 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 EQP 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.

Page 6 of 20






Installation Qualification (IQ) HardwareHardware 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.

Page 7 of 20






Operational Qualification (OQ) HardwareStandard OQ Test Specifications for GCMS Systems: GC Modules

Test Name Setpoints and Parameters Limits

System Inspection and BasicSafety and Operation

N/A Gases, chassis electric grounding, interlocks, hydrogen shutdown, and so on all correct.

GC Oven Temperature Accuracy and Stability

Temperature 1 = 230.0 °CTemperature 2 = 100.0 °C(Stability measured at Temperature 2)

Accuracy ≤ 1.0 % of setpoint (in °K)Stability ≤ 0.5 °C

Headspace Vent and Pressurization Valve Integrity

N/A Valve functions properly.

Headspace Heated Zones Temperature Accuracy

Zone 1: 100.0 °CZone 2: 110.0 °C

Accuracy ≤ 4.0 °C on G1888AAccuracy ≤ 6.0 °C on 7694 (Zone 1)Accuracy ≤ 2.0 °C on CTC

Vial Heater Temperature Accuracy Temperature 1: 60.0 °CSetpoints for temperature 2 and 3 arevariable.

Diff. from setpoint ≥ – 2.0 °C, ≤ 2.0 °C

Inlet Pressure Decay Inlet gas flow control Pressure change / 5 minutes ≥ –2.0 psi, ≤ 0.5 psi

Inlet Pressure Accuracy Inlet pressure = 25.0 psi Accuracy ≤ 1.2 psi

Detector Flow Accuracy Flow rate varies by detector type(Test is N/A for NPD)

Accuracy ≤ 10.0 % of setpoint (or 0.5 ml/minute, whichever is larger)

Signal Noise and Drift (FID) Inlet signal Initial signal ≤ 25 pANoise ≤ 0.10 pADrift ≤ 2.50 pA/hour

Signal Noise and Drift (TCD) Inlet signal Initial signal ≤ 35 DU (1 DU = 25 uV)Noise ≤ 0.15 DUDrift ≤ 2.20 DU/hour

Signal Noise and Drift (NPD) Initial signal(Test N/A to 5890)

Initial signal = 30-50 DU (1 DU = 1 pA)Noise ≤ 0.15 DUDrift ≤ 3.50 DU/hour

Signal Noise and Drift (ECD) Initial signal(Test N/A to 5890)

Initial signal ≤ 70 DU (1 DU = 5 Hz)Noise ≤ 0.15 DUDrift ≤ 1.00 DU/hour

Key: Fixed setpoints/limits Variance allowed for setpoint(s)

Page 8 of 20






Operational Qualification (OQ) Hardware (continued)Standard OQ Test Specifications for GCMS Systems: GC Modules (continued)


Signal Noise and Drift (uECD) Initial signal(Test N/A to 5890)

Initial signal ≤ 400 DU (1 DU = 1 Hz)Noise ≤ 3.00 DUDrift ≤ 15.00 DU/hour

Signal Noise and Drift (FPD new style)

Initial signalSulfur(Test N/A to 5890)

Initial signal ≤ 70 DU (1 DU = 150 pA)Noise ≤ 5.00 DUDrift ≤ 5.00 DU/hour

Signal Noise and Drift (FPD+) Initial signalSulfur(Test N/A to 5890)

Initial signal ≤ 70 DU (1 DU = 150 pA)Noise ≤ 4.00 DUDrift ≤ 3.00 DU

Signal Noise and Drift (FPD new style)

Initial signalPhosphorous(Test N/A to 5890)

Initial signal ≤ 80 DU (1 DU = 150 pA)Noise ≤ 5.00 DUDrift ≤ 5.00 DU/hour

Signal Noise and Drift (FPD+) Initial signalPhosphorous(Test N/A to 5890)

Initial signal ≤ 20 DU (1 DU = 150 pA)Noise ≤ 2.00 DUDrift ≤ 1.50 DU

Signal to Noise (FID/SS/ALS/MMI)

Signal height divided by ASTM baseline noise for known concentration and conditions.

Signal to noise ≥ 300,000 (nitrogen makeup gas)Signal to noise ≥ 240,000 (helium makeup gas)

Signal to Noise (FID/SS/HSS/MMI)



Signal to Noise (FID/VI/HSS) Signal height divided by ASTM baseline noise for known concentration and conditions.


Signal to Noise(FID/non-SS/using 18710-60170)


Signal to noise ≥ 800 (nitrogen makeup gas)Signal to noise ≥ 600 (helium makeup gas)

Signal to Noise(FID/non-SS/using 5188-5372)


Signal to noise ≥ 300 (nitrogen makeup gas)Signal to noise ≥ 240 (helium makeup gas)

Signal to Noise (NPD) Signal height divided by ASTM baseline noise for known concentration and conditions.

Signal to noise ≥ 300

Signal to Noise (TCD/SS/MMI) Signal height divided by ASTM baseline noise for known concentration and conditions.

Signal to noise ≥ 5,000

Signal to Noise (TCD/non-SS) Signal height divided by ASTM baseline noise for known concentration and conditions.

Signal to noise ≥ 100

Signal to Noise (uECD) Signal height divided by ASTM baseline noise for known concentration and conditions.

Signal to noise ≥ 1,500


Page 9 of 20






Operational Qualification (OQ) Hardware (continued)Standard OQ Test Specifications for GCMS Systems: GC Modules (continued)


Signal to Noise (FPD new style) Signal height divided by ASTM baseline noise for known concentration and conditions.

Signal to noise ≥ 700 (sulfur)Signal to noise ≥ 1000 (phosphorous)

Signal to noise (FPD+) Signal height divided by ASTM baseline noise for known concentration and conditions.

Signal to noise ≥ 1,400 (sulfur)Signal to noise ≥ 2,400 (phosphorous)

Injection Precision Injection volume on column: 1/1000/250 ul(ALS/Agilent HSS/CTC HSS with split/splitless FID)Injection time: 0.2 minutes(pressure-balanced HSS only)

Retention time RSD ≤ 1.00 %Area RSD ≤ 3.00 % (ALS & Agilent HSS)Area RSD ≤ 4.00 % (CTC HSS)Area RSD ≤ 5.00 % (Packed Inlet & Special detectors)

Injection Carry Over Injection Volume on column: 1000/250 ul(Agilent HSS/CTC)

Area carry over ≤ 1.00%

Standard OQ Test Specifications for GCMS Systems: MSD

Log Amp Maximum abundance ≥ 20,000 counts

Radio Frequency Power Amplification (RFPA)

Amu = 1050 m/z (MSD 5975)Amu = 800 m/z (MSD 5973)

RFPA voltage ≤ 1,100 mVDrift in 5 minutes ≤ 100 mV

Tune Autotune function Tune report shows no errors.

Signal to Noise (MSD) Signal height is divided by rms baseline noise for known concentration and conditions.

Spedific to model, vacuum system, carrier gas.Same as Installation Checkout test. Limitsauto-configured by ACE. See PDF fileattachment for details.

Injection Precision (MSD) Injection volume on column:1.00/1000.00/250.00 ul (ALS/AgilentHSS/CTC HSS with split/splitless FID)

Retention time RSD ≤ 1.00 %Area RSD ≤ 5.00 %

Mass Ratio Precision Two ion masses compared during injection precision test

Mass ratio RSD ≤ 5.00 %

High Mass Tune* Amu 1049 m/z Amu offset diff. (suggested - current)= ± 5.00

Instrument Detection Limit (IDL) In combination with Injection Precision IDL = 16.8 for an injection amount of 100 fg of OFN, and an injection precision limit of 5 % RSD


* Only applicable when Option G3396A is included in the system configuration

End of Section - Standard OQ Test Specifications for Agilent GCMS Systems

Page 10 of 20






Operational Qualification (OQ) Hardware (continued)OQ Test Design and Rationale for GCMS Systems

Many GMP/GLP enforcement agency inspectors now ask firms to provide a risk assessment of their equipment and computer systems plus a science-based rationale for subsequent validation and qualification testing.

GENERAL RISK STATEMENT: Any LC, LCMS, UHPLC, UHPLC_MS, 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.

This section outlines the science-based rationale for each test in the Agilent hardware OQ plus a brief test design and procedure description.

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.

The OQ test design incorporates modular and holistic testing which is a proven and regulatory acceptable approach. Direct metrology is used to test the inlet integrity (pressure decay and pressure accuracy), detector flow accuracy and temperature accuracy of the GC (oven, oven ramp, inlet/detector) and headspace heated zones. Holistic chemical testing is used for the evaluation of the following critical instrument characteristics: precision, signal to noise, and carry over. Certified reference standards and calibrated traceable thermometers and manometers 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, that end 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 following OQ tests for GC Systems (with FID, ECD, TCD, NPD, FPD, but NOT MSD) will be performed as appropriate for the configuration of the individual GCMS system.

1. System Inspection and Basic Safety and Operation [core GC OQ test]

Rationale: System must be in safe and operational condition before starting the OQ tests.

Procedure: The instrument is given a general inspection and its basic safety features are challenged to ensure proper operation.

2. GC Oven Temperature Accuracy and Stability [core GC OQ test]

Rationale: Oven temperature accuracy is important for comparability between systems and transferring methods. Oven temperature stability is critical for qualitative and quantitative analysis.

Procedure: At two different temperatures, accuracy is measured using an external calibrated thermometer. At one of these, a statistically significant number of additional readings are taken during the total duration of the test to calculate the oven stability. Accuracy is the difference between found and setpoint values.

3. Headspace Vent and Pressurization Valve Integrity [core GC OQ test if headspace sampler is integral part of system]

Rationale: Proper operation of the valves is critical for repeatable peak areas and carry over.

Procedure: This test verifies that the valves operate properly: with no excessive leaks or restricted internal flow paths.

Page 11 of 20






Operational Qualification (OQ) Hardware (continued)OQ Test Design and Rationale for GCMS Systems (continued)

4. Headspace Heated Zones Temperature Accuracy [core GC OQ test if headspace sampler is integral part of system]

Rationale: Temperature accuracy of the heated zones is important for comparing systems and transferring methods. Oven accuracy is critical to quantitative headspace methods.

Procedure: The temperature is measured using an external calibrated thermometer with appropriate probe design. Accuracy is determined as the difference between found and setpoint values.

5. Inlet Pressure Decay [core GC OQ test]

Rationale: Pressure integrity of the inlet is critical for repeatable injection and retention times. The pressure decay and pressure accuracy tests combine to demonstrate pressure integrity.

Procedure: The inlet is capped, a pressure applied, and inlet flow is turned off. The pressure decay is recorded over a specified time range.

6. Inlet Pressure Accuracy [core GC OQ test]

Rationale: Pressure integrity of the inlet is critical for repeatable injection and retention times. The pressure decay and pressure accuracy tests combine to demonstrate pressure integrity. This test checks for accurate pressure to the head of the column. Column flow is achieved by maintaining a constant pressure against a known restriction. Because the restriction is a function of the column geometry, measuring pressure in the inlet is the most accurate way to determine flow.

Procedure: The inlet is capped, a pressure is applied and the inlet pressure is recorded using an external calibrated manometer connected to the inlet.

7. Detector Flow Accuracy [core GC OQ test]

Rationale: Detector flow accuracy is critical for a stable detector signal. Incorrect flows may have an impact on detector performance.

Procedure: Flow accuracy is determined by measuring the flows with a calibrated mass flowmeter and comparing them to the test setpoints and the values displayed by the GC.

8. Signal to Noise [core GC OQ test]

Rationale: Sensitivity of GC detection 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.

Procedure: A traceable standard is injected and signal to noise is calculated.

9. Injection Precision [core GC OQ test]

Rationale: System precision is critical for quantitative analysis.

Procedure: An initial stabilizing injection followed by six repeat injections of a traceable standard followed by a final blank injection is made. The %RSD of the six injections is calculated to provide precision statistics. There are separate dedicated instrument parameters and reference standards applicable to each inlet/detector combination. This test is performed with liquid and headspace sampler configurations.

Page 12 of 20







10. Carry Over [core OQ test for headspace but optional extra fee test for liquid samplers]

Rationale: Low carry over from a previous injection is critical for accuracy of quantitative and reliability of qualitative analysis. For headspace samplers, the engineering condition contributes to carry over performance, so this is a core OQ test for these samplers.

Procedure: The blank injection after the six repeat injections of the precision test is evaluated for carry over, and the result is expressed as a percentage.

11. Vial Heater Temperature Accuracy [core GC OQ test if sampler tray has the heater option installed]

Rationale: The 7693A vial heater option can be used during sample preparation. This test verifies that it heats accurately.

Procedure: The temperature of the heater (using an external thermometer) is recorded and accuracy is calculated as the difference between the recorded value and setpoint. A single temperature is tested by default, but it is possible to add two more setpoints.

12. Signal Noise and Drift [core GC OQ test]

Rationale: This test gives an indication of detector sensitivity and stability.

Procedure: The signal is monitored at specified conditions appropriate to the type of detector over a twenty-minute period. The signal noise is calculated based on ASTM E594-96 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. Detector type and the gases used all contribute to different performance and therefore different limits for each configuration.

13. Log Amplifier [MSD-specific test]

Rationale: A linear output detector is critical for quantitative analysis. The log amplifier amplifies the output of the detector in proportion to the logarithm of the input current.

Procedure: This procedure determines the performance of the MSD system log amplifier. If verifies operation of the log amplifier and functionality of the main board, instrument control card, and ChemStation.

14. RFPA [MSD-specific test]

Rationale: The GCMS detector requires functioning radio frequency power amplification to ensure ion selection. This test verifies the stability of the optimized voltage by applying a combined direct current (DC) and radio frequency (RF) signal to two pairs of four hyperbolic surfaces. The magnitude of the RF voltage determines the mass-to-charge ratio of the ions that pass through the mass filter and reach the detector.

Procedure: The RFPA voltage is first minimized. After this, the RFPA voltage is ramped for a specified time at a high mass, and then the voltage drift is calculated.

Page 13 of 20







15. Tune [MSD-specific test]

Rationale: Calibration of mass range is critical in qualitative mass spectrometry.

Procedure [Agilent MS only]: The built-in Agilent autotune feature is performed. The masses used for the test are 69, 209, and 502 rough-rounded numbers. This determines the proper calibration of the MSD and ensures that the masses are correctly reported across the entire mass range of the instrument.

16. Signal to Noise [MSD-specific test]

Rationale: Sensitivity of MS detection 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.

Procedure: A traceable standard is injected and signal to noise is calculated.

17. Injection Precision [MSD-specific test]

Rationale: System precision is critical for accuracy of quantitation. Autosampler performance and MS ionization contribute to GCMS system precision.

Procedure: An initial stabilizing injection, followed by six repeat injections of a traceable standard, followed by a final blank injection are made. The %RSD of the six injections is calculated to provide precision statistics.

18. Mass Ratio Precision [MSD-specific test]

Rationale: Constant ionization is critical for accuracy of quantitation.

Procedure: Data for this test is collected during the injection precision test. From each run, two masses are extracted from the total ion chromatogram (TIC) and the ratio is calculated. The %RSD of the six injections is calculated to provide mass ratio precision.

19. High Mass Tune (EI) [MSD-specific test]

Rationale: Calibration of mass range is critical in qualitative mass spectrometry.

Procedure: A traceable checkout standard is used to determine the operation of the MSD in the high-mass range. Based on the result from the run, the tune parameters are updated to get optimum performance in the high-mass range.

20. Instrument Detection Limit (IDL) for GC-QQQ Systems.

Rationale: Replaces Signal-to-Noise test for ultra-low noise systems, where there are often no ions in the background and the noise is essentially zero.

Procedure: This test uses a traceable standard to determine injection precision and IDL. The mean, standard deviation, and % RSD of six standard injections are calculated. Using the area RSD and the known amount injected onto the column, the instrument detection limit is calculated. This amount returns a peak in the chromatogram which is detectable and distinguishable from the background with a 99% probability.

Page 14 of 20







The following tests are NOT INCLUDED in the standard OQ for GCMS but can be ordered as EXTRA COST TESTS.

Test Name Setpoints and Parameters Limits Include

Response Linearity(FID, TCD)

Certified reference standard with multiple peaks known concentration

Coefficient of determination (r2) = 0.99900R/F Precision ≤ 10.00 % RSD

GC Heated ZonesTemperatureAccuracy (uECD /MSD not supported)

Inlet temp. 1 = 200.0 °C / 250.0 °C (OC / all others)Detector temp. 1 = 200.0 °C / 300.0 °CSetpoints for temperature 2 are variable.

Inlet accuracy ≤ 15 °C / 10 °C (OC / all others)Detector accuracy ≤ 15 °C

GC Oven Temp.Ramp: Accuracy,Linearity, Precision

Initial temperature: 50.0 °CRamp 30.0 °C/minuteFinal temperature: 280.0 °C

Ramp accuray: ≤ 1.0 °C/minuteRamp linearity ≥ 0.99990Ramp precision ≤ 2.0 %

LTM Basic Operation N/A Self test completes w/o errorsRef. voltage = 794 ± 10 mVTransferlines 1, 2 = 794 ± 50 mVColumn temperature = 784 ± 10 mV

LTM OvenTemperature Acc.and Stability

Temperature 1 = 230.0 °CTemperature 2 = 100.0 °CStability measured at temperature 2

Diff. from setpoint ≤ 1.0 % of setpoint (in °K)Stability ≤ 0.5 °C

LTM Oven Temp.Ramp: Accuracy,Linearity, Precision

Initial temperature: 50 °CRamp 100 °C/minuteFinal temperature: 280 °C

Ramp accuray: ≤ 2.0 °C/minuteRamp linearity ≥ 0.9990Ramp precision ≤ 2.0 %

Injection Carry Over Injection volume on column: 1.0 ul(ALS split/splitless FID)

Area carry over ≤ 1.00 %

Key:

Fixed setpoints/limits Variance allowed for setpoint(s)

Extra Test 1. FID Response Linearity [NOT CORE OQ TEST: additional extra fee test]

Rationale: Response linearity is critical for quantitative analysis. It is often demonstrated in user applications and analytical methods typically using multi-level calibration standards and internal standards. Therefore, this is an optional extra fee OQ test. The FID response linearity test uses a certified chemical reference test mix that is validated to be challenging and representative of many applications.

Procedure: The response linearity test is executed using a single injection from a standard containing a number of n-alkanes with increasing concentrations. Response linearity can be calculated with just one injection of a standard for the following reasons.

• The difference in length of the n-alkanes (boiling-point increases) separates these components on the column.• The increasing concentration gives an increasing detector response.• GC theory states (and experiment confirms) that the response factors for these compounds are the same (within a very small

variance). Therefore, a single injection of this multi-component /multi-level concentration sample can be used to calculate the response linearity of the detector.

• The single injection test design eliminates the contribution of injector precision to the linearity statistics evaluation.

Page 15 of 20







Extra Test 2. GC Heated Zones Temperature Accuracy [NOT CORE OQ TEST: additional extra fee test]

Rationale: The precise temperature of the heated zones is not critical to quantitative or qualitative analysis. When the inlet zones are hot enough to vaporize but not so hot as to thermally decompose sample, this is adequate. When the detector zones are hot enough to evaporate sample and prevent condensation, this is adequate. Temperature accuracy of the heated zones may be important for comparing systems and transfer methods. Therefore, this is an optional test.

Procedure: This test demonstrates that the inlet and detector show an accurate temperature using proprietary novel design to overcome the inherent difficulties in gaining accurate and meaningful readings. The temperature is measured using an external thermometer. The probe is inserted as if it is a column with a pre-defined length above the column nut to get consistent measurements between different instruments. Two setpoints (high and low) are measured. (Note: Due to the possible risk of radioactive contamination, ECDs are excluded from this service).

Extra Test 3. GC Oven Temperature Ramp: Accuracy, Linearity, and Precision [NOT CORE OQ TEST: additional extra fee test]

Rationale: Most GC analyses use a temperature program instead of an isothermal oven temperature program to complete the separation of the compounds in the sample. For retention time reproducibility, it is important that the temperature program is always executed in the same way.

This test uses a calibrated digital thermometer to determine the accuracy, linearity, and precision of the GC oven temperature program. Linearity is defined as the coefficient of determination (r2) and uses data points that are part of the ramp. Ramp accuracy is defined as the slope of the linear curve fit through the same data points used for linearity calculations. Precision is calculated as the RSD over three temperatures in the slope over three different runs.

Procedure: In this test, a linear oven temperature profile is collected three times in a row using a digital thermometer and a data logger. For each run, the oven ramp accuracy and oven ramp linearity are calculated. After all three runs are completed, the oven ramp precision is calculated. The ramp in use is a steep slope that challenges the GC to deliver high power in a reproducible way.

Extra Test 4-6. LTM Tests [NOT CORE OQ TEST: additional extra fee test]

Rationale: The RTD is a column packed in a heating foil. Although columns are generally considered to be consumables and not part of a hardware qualification, in this case the “oven” includes the column so tests are required to evaluate its functionality.

A direct temperature measurement (vs. indirect) is preferred but not feasible in this case given the LTM design: adding a temperature sensor to the metal foil introduces a cold spot and adversely affects temperature, and inserting a probe into the RTD requires taking the column apart.

One indirect temperature measurement is a direct measurement of the return voltage from the RTD, which can be converted to temperature using a known equation.

Another indirect temperature measurement would be chemical tests. If the system is not able to heat up in a reproducible way, you might see a shift in retention times. Because this kind of measurement is used by Agilent (and many other vendors) to evaluate system performance, it would be difficult for LTM to rework the complete chemical test suite: especially detector-specific tests like Signal to Noise and Signal Noise and Drift. The RTD can be any column and noise, in particular, is influenced by the column type.

Page 16 of 20







Based on the above, the following qualification is executed when an LTM is installed:

1. A complete GC qualification without Injection Precision (IP) is run with standard oven procedures. An LTM Basic Operation test is scheduled to show the LTM is functional.

2. An LTM Oven Temperature Accuracy and Stability test is executed. This test is similar to the standard GC Oven Temperature Accuracy and Stability.

3. An LTM Oven Temperature Ramp test is executed, similar to the standard GC Oven Temperature Ramp test, but it uses a much higher ramp.

4. The IP test is run using the LTM module. Inlet, detector, and RTD modules are tested separately in steps 1-3, but this test verifies that all components work together. LTM runs in general are very short due to the high oven ramp and very fast cool down rate.

Procedure for LTM Basic Operation: After completing the self test, four different temperatures (voltages) are measured: reference voltage (setpoint), return voltage (column temperature), and both transfer lines. This assures that all zones are functional, correctly installed, and connected.

Procedure for LTM Oven Temperature Accuracy and Stability: This test uses a calibrated voltmeter to determine temperature accuracy and stability of the LTM oven. (Voltages are measured and then converted to temperatures using a known relation. The converted temperatures are used in all calculations and limit comparisons.)

Procedure for LTM Oven Temperature Ramp: This test uses a calibrated voltmeter to determine the accuracy, linearity, and precision of the LTM oven temperature program. (Temperatures cannot be measured directly for LTM ovens, so voltages are measured and then converted to temperatures using a known relation. The converted temperatures are used in all calculations and limit comparisons.) Linearity is defined as the coefficient of determination (r2) and uses data points that are part of the ramp. Ramp accuracy is defined as the slope of the linear curve fit through the same data points used for linearity calculations. Precision is calculated as the RSD over three temperatures in the slope over three different runs.

Extra Test 7. Carry Over [NOT CORE TEST: additional extra fee test for liquid samplers]

Rationale: For liquid samplers, carry over performance is contingent on many variable factors independent of the engineering condition of the GC system. Many different syringe wash programs are available that can eliminate carry over. These are user selectable and may be application specific. The condition of the injection syringe is the only controllable engineering factor.

Procedure: The blank injection after the six repeat injections of the precision test is evaluated for carry over, and the result is expressed as a percentage. For liquid samplers, carry over performance is contingent on many variable factors independent of the engineering condition of the GC system.

Page 17 of 20






Operational Qualification (OQ) Hardware (continued)EQP Record of Variances to Setpoints from Standard OQ Specifications

IGNORE THIS SECTION IF YOU ACCEPT AND APPROVE THE FIXED STANDARD QUALIFICATION TESTS AND SETPOINTS RECORDED IN THE PRECEDING PAGES OF THIS STANDARD EQP.

-EQP with Variance Approval Process: Customer Actions: (1) View in Adobe ®; select required setpoint variances below; 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 and 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 and 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 UnitsGC Heated Zones Temperature Accuracy(Inlet temp. default varies by OC/others; detector temp. default varies by FPD/others except MSD and uECD [test does not apply])

Inlet temp. 1 200.0/250.0 °CInlet temp. 2 Not applicable °CDetector temp. 1 200.0/300.0 °CDetector temp. 2 Not applicable °C

GC Oven Temperature Accuracy and Stability Temperature 1 230.0 °CTemperature 2 100.0 °C

Headspace Heated Zones Temperature Accuracy Zone 1 temperature 100.0 °C**Zone 2 temperature 110.0 °C**Zone 3 Temperature (7697) 110.0 °C

Vial Heater Temperature Accuracy Temperature 1 60.0 °CTemperature 2 Not applicable °CTemperature 3 Not applicable °C

Injection Precision, Injection Carry Over (ALS) Injection volume on column 1.0 ulInjection Precision, Injection Carry Over (Agilent HSS) Injection volume on column 1000 ulInjection Precision, Injection Carry Over (HSS*) Injection time* 0.02 minutesGC Oven Temperature Ramp: Accuracy, Linearity, and Precision

Initial temperature 50.0 °CRamp 30.0 °C/minuteFinal temperature 280.0 °C

LTM Oven Temperature Accuracy and Stability Temperature 1 230.0 °CTemperature 2 100.0 °C

LTM Oven Temperature Ramp: Accuracy, Linearity, and Precision

Initial temperature 50.0 °CRamp 100.0 °C/minuteFinal temperature 280.0 °C

* Pressure-balanced HSS** Temperatures over 150 °C only applicable to 7697 HSS

For a fully tailored operational qualification program using all the flexibility of Enterprise Edition, contact your local Agilent representative and/or e-mail [email protected] with your OQ test specification requirements. Fees may apply.

Agilent Operator (verifies variances are entered into ACE):

Name:

Signature, Date:

Customer:

Name:

Signature, Date:

Page 18 of 20






18

Re-Qualification after Repair (RQ) HardwareIn 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. Part of an example form is shown below.

Re-Qualification After Repair

Mainframe Strategies

Repair/Replace Strategy OQ/PV Testing

Main board System Insp. & Basic Safety & Op.GC Oven Temp. Acc. & StabilityInlet Pressure AccuracyDetector Flow AccuracyGC Oven Temp. Ramp

Keyboard System Insp. & Basic Safety & Op.

EPC board Inlet Pressure AccuracyDetector Flow Accuracy

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).

Dual-Acceptance LimitsWithin the Equipment Qualification Plan (EQP) of the Agilent Enterprise Edition, each of the tests final result can be compared against two different limits if required. This allows customer-configured OQ to report against a User Limit (limit1) and the Agilent Recommended Limit (limit2) simultaneously.

The Standard_EQP documents have both Limit1 & Limit2 values set the same – effectively de-activating this feature. Custom_EQP’s can also be prepared on request, making effective use of the Two-Limit feature of the Agilent Compliance Engine (ACE). In those cases, “Limit2” will always be the Agilent Recommended limit, and “Limit1” will be the limit requested by the user. Agilent will not be under any obligation regarding the OQ testing results against User-requested limits that are more stringent than the Agilent Recommended ones.

Page 19 of 20






Legal, Endorsement, and Revision HistoryEnterprise 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: April 2014

Services R&D Manager: Michael F. Pope. Santa Clara, California USAServices Quality Manager: Julio Hector. Santa Clara, California USA

Enterprise Edition is endorsed by Dr. Ludwig Huber on behalf of labcompliance.com.

ACE software is patented. 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 GCMS Enterprise Edition Protocols.

A.01.83 April 2014 Added support for (1) Agilent 7200A Q-TOF; Agilent 7000C GC-QQQ; TCD with hydrogen or nitrogen as carrier/makeup.

A.01.82 September 2013 Area RSD limit in the Injection Precision test updated to 5% for packed inlets combined with special detectors (ECD, uECD, NPD, FPD, FPD+, DFPD+)

A.01.81 April 2013 Added support for (1) Agilent 5977 GCMS and 7890B Series GC; (2) Agilent 7890 FPD+ and DFPD+ detectors. Enhanced flexibility in set-points and limits with individual settings per inlet and detector type. Corrected discrepancy in reported number of decimal places in RPFA test. No regulatory impact for previously approved EQP’s.

A.01.80. December 2012 Instrument Detection Limit (IDL): new test replaces Signal to Noise test for GC QQQ. Enhanced scheduling of response Linearity test for independent FID and TCD testing if both are present. Added Injection Carry Over Optional test for liquid injectors (ALS).

A.01.79. July 2012 Added support for Agilent 7650A sampler. Corrected standards listed for PCI Tune test. Updated ASTM noise algorithm for the Signal-to-Noise and Noise & Drift calculations. Enhanced graphical representation. Enhanced integration and compatibility with HSS for the FID Response Linearity test.

A.01.78. April 2012 Added support for (1) Varian 320 QQQ GCMS. (2) PTV inlet in Inlet Temperature Accuracy test. No regulatory impact for previously approved EQP’s.

A.01.77. February 2012 Added support for Varian GC models 430 and 450. No regulatory impact for previously approved EQP documents.

A.01.76. August 2011 No changes for GCMS. Protocol revision made independent from ACE revisions. No regulatory impact for previously-approved EQP’s.

A.01.75. March 2011 No changes for GCMS.A.01.74. September 2010 No changes for GCMS.A.01.73. June 2010 (1) Updated Signal-to-Noise MSD limits (see attachment); (2) Added selcetion boxes for Optional Tests.A.01.72. January 2010 Added G7000B GCMSD QQQ support.A.01.71. October 2009 Added E-signature fields (No regulatory impact).A.01.70. May 2009 Added G7000A QQQ support.A.01.60. May 2008 (1) Added 5975C Enhanced GCMS support; (2) added forms: Certificate of System Qualification at end

of EQR, Chromatography Report after each applicable test, Errors and Corrections for operator and customer to record any corrections to EQR, Data Transfer Audit Log for complete traceability.

A.01.53. August 2007 Added kPa units for pressure tests.A.01.50. March 2007 Added GCMS support.A.01.40. December 2006 Initial GC - Operational Qualification

End of EQP Review Document

Information, descriptions and specifications in this publication are subject to change without notice.

© Agilent Technologies, Inc. 2014Published in USA, April 22, 2014

www.agilent.com/chem/enterprise

Page 20 of 20

Agilent Enterprise Edition — Review DocumentRisk Assessment and Conformance to FDA 21 CFR Part 11 ChecklistAgilent Compliance Engine – Main Rev. A.01.20, 01.30, 01.40, 01.50, 01.60, 01.70, 02.00, A.02.10, A.02.20

Conformance Checklist

Software ProductAgilentAutomatedComplianceEngineRevisions A.01.20 1.30 1.40 1.50 1.601.70, A.02.00, A.02.10, and A.02.20.The software enabling tool of the Enterprise Edition compliance service for for LC, GC, MS, SW, UV, and Disso.

DescriptionProprietary commercial software developed by Agilent Technologies Inc. The software is used to manage the procedures, collect data, calculate derived data and results and generate final reports of equipment qualification testing. The reports are electronic records.

Intended Use and Regulatory Environment

Agilent Compliance Engine is intended as a tool for delivering Equipment Qualification services on laboratory instruments such as chromatography systems. The predicate rules affecting this software and intended use are: all the FDA and equivalent international predicate laws (including national GMP’s and GLP’s) that relate to equipment qualification, calibration and system validation.

Risk Assessment: MEDIUM

Risk assessment of a computer system, according to latest FDA guidance and GAMP guidance, depends on the definition and intended use of the electronic records handled by the system. The Agilent Compliance Engine software handles equipment qualification records / calibration records. These records are secondary data - not directly related to either drug product quality or patient safety or confidentiality.

Record Retention Period

GMP: Typically less than 10 yearsGLP: Typically more than 10 years

The retention periods for the equipment qualification records / calibration records produced by Agilent Compliance Engine should be defined by customer policies & procedures. These corporate rules

are in turn interpretations of GMP or GLP regulations. For GMP regulated labs, the retention period must ensure availability of calibration records for relevant lab test equipment up to the date of disposal of the last drug batch record that referenced the lab test equipment.

The retention period for a given record maybe as little as 1 year or as much as 10 years. GMP rules on retention periods of qualification / calibration records vary between country and region.

The retention period guidelines for qualification / calibration records of test equipment used in GLP studies can vary widely from country and region.

Some corporate interpretations of FDA and OECD GLP rules infer an indefinite retention period for all GLP study data including related secondary data such as lab equipment qualification / calibration records.

Raw Data / Original Record Definition

The raw data (GMP terminology) or original records (GLP terminology) for Agilent Compliance Engine are here defined as the electronic records generated as Acrobat pdf documents.

Paper prints of the Acrobat documents are copies. The paper prints represent true and accurate copies of the electronic documents.

Page 1 of 5 © Agilent Technologies, Inc. 2013Issued Oct 13 - Revision 0.9 (added ACE version 2.20)

Page 2 of 5 © Agilent Technologies, Inc. 2013

Agilent Enterprise Edition — ReviewDocumentRisk Assessment and Conformance to FDA 21 CFR Part 11 ChecklistAgilent Compliance Engine - Main Rev. A.01.20, 01.30, 01.40, 01.50, 01.60, 01.70, 02.00, A.02.10, A.02.20

Issued Oct 13 - Revision 0.9 (added ACE version 2.20)


FDA 21 CFR Part 11 Assessment

Reference: 21 CFR Part 11 Part B Electronic Records 11.10 Controls for Closed Systems

a. Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records.

Intermediate detector signal electronic data are in human readable form when viewed using Agilent Compliance Engine, EZChrom, Cerity ECM software products or a number of other commercially available viewers in Electronic Document Managements Systems. Paper print copies can be made of the raw data if necessary.

Access to Agilent Compliance Engine machines is limited by operating system security managed by Agilent IT policies.

Agilent Compliance Engine software is validated by the developer (Agilent Technologies Inc.) as part of the Enterprise Edition compliance service R1668A. See “Declaration of Compliance Product Validation Revision Date 9 September 2013”.

Each individual instance of Agilent Compliance Engine software is qualified by automated IQ at installation. In addition all installations on the Agilent engineer’s production laptops are qualified by automated software IQ and semi-automated OQ plus a manufacturer’s A/D connection calibration check.

b. The ability to generate accurate and complete copies of records in both human readable and electronic form suitable for inspection, review, and copying by the agency.

All the report records and associated information (such as supporting certificates, training data) handled by Agilent Compliance Engine are in Adobe Acrobat pdf.

Copies are complete, accurate and in human readable form in both paper-printed and electronic formats.

c. Protection of records to enable their accurate and ready retrieval throughout the records retention period.

Agilent Compliance Engine protects work-in-progress records by use of software access control and access control to the Agilent Compliance Engine machines. Final records are secured by Adobe Acrobat 7 digital signature and secure burning on to ISO 9660 format CD-ROM. The lifetime of the CD media is 100 years.

These electronic records may in turn then be copied onto secure centralized electronic document management systems (EDMS).

Accuracy and completeness of each report record is ensured by the secure file format.

d. Limiting system access to authorized individuals.

Agilent Compliance Engine software access is limited by a log-in with password rights assigned only to trained and certified operators.

e. Use of secure, computergenerated, time-stamped audit trails to independently record the date and time of operator entries and actions that create, modify, or delete electronic records. Record changes shall not obscure previously recorded information. Such audit trail documentation shall be retained for a period at least as long as that required for the subject electronic records and shall be available for agency review and copying.

The report records generated by Agilent Compliance Engine have system generated time stamps automatically inserted into the footer of each page of the reports.

Qualification Report records, once completed and saved, cannot be altered, therefore no audit trail of changes is necessary or appropriate.

f. Use of operational system checks to enforce permitted sequencing of steps and events, as appropriate.

Agilent Compliance Engine software enforces all the sequences and steps that are critical to quality and data integrity during execution of an equipment qualification protocol.





h. Use of device (e.g., terminal) checks to determine the validity of the source of data input or operational instruction, as appropriate.

11.30 Controls for open systems. Procedures and controls to ensure authenticity, integrity, and as appropriate, confidentiality. Include additional measures beyond 11.10 requirements such as document encryption and use of digital signature standards.

have the education, training, and experience to perform their assigned tasks. Only trained and certified engineer/operators have access to Agilent Compliance Engine machines and software for the purposes of executing instrument qualification.

g. Use of authority checks to ensure that only authorized individuals can use the system, electronically sign a record, access the operation or computer system input or output device, alter a record, or perform the operation at hand.

Agilent Compliance Engine software access is limited by a log-in with password rights assigned only to trained and certified operators.

Access to Agilent Compliance Engine machines is limited by operating system security to authorized individuals.

Individually assigned Agilent Digital certificates are used in any Acrobat digital signatures.

Device checking between Agilent Compliance Engine machines and the Analog Digital Converter is assured by the software driver design and the calibration & OQ check of Agilent Compliance Engine machines. This is the only appropriate device check requirement.

i. Determination that persons who develop, maintain, or use electronic record/electronic signature systems have the education, training, and experience to perform their assigned tasks.

All members of the R&D and product support teams involved in the development of the software

j. The establishment of, and adherence to, written policies that hold individuals accountable and responsible for actions initiated under their electronic signatures, in order to deter record and signature falsification.

The official training modules in Training@Agilent for GXP compliance and operator training courses for Agilent Compliance Engine software covers the above requirements.

k. Use of appropriate controls over systems documentation including: (1) Adequate controls over the distribution of, access to, and use of documentation for system operation and maintenance. (2) Revision and change control procedures to maintain an audit trail that documents time-sequenced development and modification of systems documentation.

Agilent’s product life-cycle documentation system meets these requirements.

Agilent Compliance Engine is a closed system.

However, electronic distribution and sharing of the records produced by the system is envisaged. Acrobat 7 Digital certification may be applied to ensure authenticity and integrity of the records when outside of Agilent Compliance Engine or outside a validated EDMS. This digital signature technology meets the legal requirements for digital signatures in all USA State laws and relevant European Directives.

Part C Electronic Signatures 11.100 General requirements.

Approval of the records by compliant electronic signature can be performed during ‘checkin’ to customers’ own validated EDMS.

SAFE technology electronic signature approval is offered with Enterprise Edition qualification services when Agilent Compliance Engine is combined with Cerity ECM system. The SAFE technology e-signature is technically fully compliant to the electronic signature requirements of 21 CFR Part 11 and ensures a very high degree of security.

Alternatively use of a compliant ‘hybrid’ hand-written ink signature procedure is made possible by the secure e-records with unique identification on every page and document pagination.





11.300 Controls for identification codes/passwords.

a. Maintaining the uniqueness of each combined identification code and password, such that no two individuals have the same combination of identification code and password.

Conclusionc. Following loss management procedures to electronically deauthorize lost, stolen, missing, or otherwise potentially compromised tokens, cards, and other devices that bear or generate identification code or password information, and to issue temporary or permanent replacements using suitable, rigorous controls.Uniqueness of password/

username combination is ensured by use of Windows NT log-on for the Agilent Compliance Engine machine and enforcement of full email address as username for the Agilent Compliance Engine software login. In both cases the username is unique and therefore the combination is unique.

b. Ensuring that identification code and password issuances are periodically checked, recalled, or revised (e.g., to cover such events as password aging).

Passwords/usernames for Agilent Compliance Engine software access are managed by the Agilent Product Support Engineer and will be recalled or revised periodically and for cause. Passwords for Agilent Compliance Engine machines (using Windows log-on) have enforced annual changes.

No tokens, cards or devices are currently used in the Agilent Compliance Engine system.

d. Use of transaction safeguards to prevent unauthorized use of passwords and/or identification codes, and to detect and report in an immediate and urgent manner any attempts at their unauthorized use to the system security unit, and, as appropriate, to organizational management.

Password issuance is at time of operator training and certification. Sharing of passwords is prohibited. Unauthorized use of Agilent Compliance Engine is detectable at delivery of reports generated by Agilent Compliance Engine.

e. Initial and periodic testing of devices, such as tokens or cards, that bear or generate identification code or password information to ensure that they function properly and have not been altered in an unauthorized manner.

No tokens, cards or devices are currently used in the Agilent Compliance Engine system.

Agilent Compliance Engine is a medium risk, commercial-off-the-shelf (COTS) software with adequate controls and electronic records/electronic signatures compliance for its intended use.

Information, descriptions and specifications in thispublication are subject to change without notice.

© Agilent Technologies, Inc. 2013Published in USA, October 30, 2013


AgilentEnterprise Edition Compliance

Technical Overview

Differences between revision A.01.76 Enterprise Edition (EE) qualification products and previous revisions

Enterprise Edition revision A.01.76 is a result of seven years of evolution of a

fl exible service delivery system based on the Agilent Automated Compliance

Engine (ACE). During that time the qualifi cation protocol underwent its own

evolution, resulting in the highly successful A.01.7x series of products. A.01.76

is the result of the migration of the A.01.75 product to the enhanced delivery

platform. In that process the thoroughly tested suite of tests were ported intact.

This means that moving from A.01.7x to this new revision will result in the same

approved test coverage, set points, and limits.

A comparison of revision A.01.76 of the Agilent Enterprise Edition Equipment Qualification Report (EQR) with previous versions of this protocol

2

Enhancements to the A.01.76 Equipment Qualification Report (EQR)

Agilent improved the effectiveness of

the Equipment Qualifi cation Plan (EQP)

process and improved the structure

and clarity of the EQR. The effect is a

substantial gain in overall quality and

effectiveness.

1. The electronic version of the EQP

establishes set point and limit

conditions. The report includes the

name and signature information

attributed to the EQR.

2. Enhanced support for complex

system confi gurations allows a

single comprehensive confi guration

description without need for

attachments or appendix.

3. Chromatographic plots can be

displayed along with meta-data

within each test. Where appropriate,

meta-data are also displayed in

graphical form.

4. All set points for a given test are

contained within the test, for a result

that is easier to review. A single fi nal

Pass/Fail assessment can be made

for all set points within a test.

5. Individual report sections now can

be ordered and confi gured to your

specifi c needs.

6. The summary “Certifi cate of System

Qualifi cation” can be issued as a

standalone document.

7. Independent data analysis removes

any perception of self-justifi ed

acceptance, and eliminates reliance

on other product validations.

8. Handling of attachments is

enhanced to manage all supporting

documentation despite disparate

sources and document types.

Equipment calibration and personnel

qualifi cation records, certifi cates

of analysis for samples used, and

time-stamped comments and

deviation records are managed in

separate sections of the Attachment

appendix. Users are prompted to

validate attachments to ensure

consistency of the fi nal report.

9. Supporting information for the EQR

is optimized for electronic review

and storage. Sections required to

make an acceptable printed version

are added to the document only

when a printed report is requested.

These graphics, taken from example

reports, illustrate improvements made

to the A.01.76 EQR.

Response Linearity : Detector Module 1,

G1314C, UV or UV-Vis: Response Linearity 112000

9000

6000

3000

0

0 70 140 210 280

Are

a

Peak area values

response_linearity002




response_linearity006Regression values

Injection Precision MS : Dectector Module 2,

G6130A - AP-ESI Source: Source Mode 1480000

450000

420000

390000

3600001 2 3 4 5 6

Are

a

Area

Average Area: 414467.7

Low Limit: 373020.9High Limit: 455914.4

Figure 1. Concentration results from Response Linearity test.

Figure 2. Reproducibility of the Injection Precision test.

Figure 3. Session vital constants documented on the front cover and footer of each page of the report,

including system ID and service and creation date/time stamps.

Service Date:System ID:

Friday, July 08, 2011 Creation Date: July 08, 2011 2:16:37 PM6130_RRLC_RA

Page 53 / 85

3

Figures 4 and 5. Graphical representation of the channel composition steps fi rst and second derivative,

for enhanced event-detection reliability in identifi cation and reporting.

Figure 6. Audit log test details, showing data path and host name for traceability.

Impact of differences between EQR revisions

1. No changes to test defi nitions or

testing methodology. The Enterprise

Edition procedural approach is

based on a balanced combination of

metrology and chromatography data,

not based on inference, and without

second-level data. This yields a

system characterization that is free

from risk.

2. Changes to the integration

algorithm: EQR’s generated in

revision A.01.76 use a self-contained

data reduction engine to ensure

independence from the measured

system, and guarantee compatibility

with the native data system.

Suitability of the new calculation

engine is described in the certifi cate

of validation of the delivery tool ACE

2.0. This software application is

designed as a Commercial-Off-the-

Shelf (COTS) product following a

strict life-cycle quality system.

3. Information that does not add value

to the report is eliminated. One-time

information is removed from

pre-approval archival documentation

to eliminate redundancy in service-

specifi c reports.

4. Some logging information moved

to test-specifi c section. Examples

include the “Data Audit Log”,

now integrated into each test,

where it is relevant to the results

and now easier to review. This

follows enhancements made in

automation and traceability, and

more fl exible support for use-cases.

This eliminates the need to copy

data from the system controller

(chromatography data system, or

CDS) to the qualifi cation engine

(ACE 2.0) – now integrated into the

same logical unit.

5. Some sections have a slightly

modifi ed structure to support the

primary use of the A.01.76 EQP as an

electronic document – yet it remains

completely compatible with paper-

based record retention policies. For

instance, the EQR paper signature is

moved to the attachments section.

ACE A.01.7x Name ACE 1.76 EQR Status Regulatory Impact

1 Report Cover Has new graphics Default None

2 Printed Signature Moved to Attachments section Optional None

3 Disclaimer & Warranty Now included on the signature page Default None

4 Table of Contents No changes Default None

5 Test Summary No changes Default None

6 Report Details Superseded now that sections and their sequence order are confi gurable Removed None

7 Concise Revision History Name Changed to “Protocol Details”. Lists revisions per individual test Default None

8 Detailed Revision History Available as external document Removed None

9 Scope & Purpose Not part of the qualifi cation report Removed None

10 Glossary No major Changes. Eliminates non-service related terms. Optional None

11 Qualifi cation Details. Renamed “Service Details”. No other changes. Default None

12 Instrument Details No Changes Default None

13 Protocol, Materials & Calibrated Tools Moved to independent sections Default None

14 General Procedure & Data Export Not part of the qualifi cation results. Removed None

15 Calculation Formulas No changes. Optional None

16 Declaration of Change Control No formal changes Default None

17 Tests Reports No formal changes. New calculation engine. Default Under COTS

18 Digital Data transfer log Removed as independent section. Data is interleaved into each specifi c test. Removed None

19 EQR Electronic Attachments Superseded by the new Attachments section Default None

20 EQR Reference Documentation Superseded by the new Attachments section Default None

21 Electronic Signature No major changes Default None

22 Certifi cate of System Qualifi cation No changes. Optional placement in front or end of report. Can also be issued as stand-alone document

Default None

Information, descriptions and specifi cations in thispublication are subject to change without notice.

© Agilent Technologies, Inc. 2011Published in USA, December 8, 2011

5990-9518EN


Page-by-page comparison of A.01.75 and A.01.76 reports, with assessment of individual impacts

ACE A.01.76 has the same level of

report detail as A.01.75. The report

format aggregates test and related

sections, is easier to review, while

enhancing overall data quality and

information richness of the service.

The report is supported by extensive

graphical elements and corroborated by

auxiliary documents to assure a self-

contained, audit-ready fi nal document.

The following table itemizes the

individual sections within the EQR,

denoting their differences from

previous revisions and assessment of

its regulatory impact to the service.

Note that without exception there

are no modifi cations made beyond

a layout and document structure

re-arrangement, all immaterial to

the signifi cance of the regulatory

information provided by the service.

Signal to Noise Limits for GCMS system typesRefer to the following table for the appropriate limit applicable to the specific GC-MS system type.

GCMS System Type Setpoint Model Limit (*)

For MSD-EI and with ALS or manual injection

Set all parameters listed in the configuration-specific Working Instructions: Instrument Parameters document.

5973A 10

5973N 20

5973 Inert 60

5975A 80

5975B (diffusion pump) 60

5975B (turbo pump) 140

5975C (diffusion pump, He) 80

5975C (turbo pump, He) 160

5975C Enh. (turbo pump, He) 320

7000A QQQ (turbo pump, He) 80

7000B QQQ (turbo pump, He) 400

220/240 Ion Trap (Internal) 20

240 Ion Trap (External) 30

For MSD-PCI using CH4 with an ALS or manual injection


5973A 75

5973N 75

5973 Inert 75

5975A 125



5975C Enh. (turbo pump, He) 125

7000B QQQ (turbo pump, He) 40000

220/240 Ion Trap (CI Internal) 50

240 Ion Trap (PCI External) 10

GCMS HARDWARE OPERATIONAL QUALIFICATION

Agilent Enterprise Edition Compliance Services


© Agilent Technologies, Inc. 2012Published in USA, July 17, 2012


GCMS System Type Setpoint Model Limit (*)

For MSD-NCI using CH4 with an ALS or manual injection


5973A 500

5973N 500

5973 Inert 500

5975A 300



240 Ion Trap (NCI External) 50

(*) On the table above the limits are expressed in counts. Because both the signal and noise values are affected by the same unit scaling factor, said unit of measurement has no impact in the Pass/Fail assessment.

Migrating to Agilent Enterprise Edition: Enabling Significant Instrument Qualification ImprovementsIntroductionAgilent (at the time, HP Analytical) introduced Operational Qualification/ Performance Verification (OQPV) for our own LC and GC instruments in the early 1990’s. Since then we have delivered well over 100,000 OQPV reports to customers around the world. Despite the undoubted success and acceptance of our original OQPV (called Classic Edition to distinguish from the new Enterprise Edition service) times have changed. Expectations and requirements of an OQ have shifted. The number and type of instruments and software used by our customers have increased. And of course we are immersed in the new world of computers and electronic media.

So Agilent set out with a team of international experts to create an upgraded compliance service that would meet the new demands while maintaining the critical requirements:

• Always pass US Food and Drug Administration (FDA) and national agency audits without over-testing or under-testing

• Challenge the analytical system with a scientifically sound methodology that provides valuable performance data

• Meet the quality needs of customers and the spirit and intention of the GLP & GMP laws

• Offer this service at a cost-effective price that makes it more than just worthwhile – it is the simplest and best qualification choice that a customer can make

What are the high-level changes in Enterprise Edition and what were the drivers for these changes?The first big driver was the software environment. Many more chromatography data system (CDS) products now are available to control LC and GC systems. Agilent has OpenLAB CDS ChemStation and EZChrom Editions, MassHunter, and other specialist software. Our customers also use Empower, Chromeleon, Atlas, Turbochrom and many others. The Classic OQPV was a wonder of validated and almost fully automated OQ testing, but because it was built into the software these benefits were limited to Agilent instruments running on ChemStation. To provide all our customers – and customers of non-Agilent instruments – a single OQ solution as good or better than OQPV – it was clear we had to develop an automation tool independent of ChemStation and any other CDS.

The Agilent Automated Compliance Engine (ACE) is our new software tool that manages the workflow and protocols, calculates results and produces the reports. Naturally it is fully validated and tested. Authorized Service representatives carry “ACE laptops” in the same way that they carried “ChemStation laptops.” Alternatively contract customers can have ACE software installed on their own laptops or with Agilent OpenLab networked CDS.

Table of contents: [click on title for fast navigation]

What are the high-level changes in Enterprise Edition and what were the drivers for these changes?

Are there any other practical or process changes in Enterprise Edition?

Diving into the details – how do the protocols and tests in Enterprise Edition compare to Classic?

List of Enterprise Edition OQ tests for 1100/1200 LC versus Classic OQPV tests for 1100 LC

How are Equipment Qualification Reports (EQR) different from OQPV Reports?

What should I do if I want to move my annual OQ Service from Classic to Enterprise Edition?

What are the main risks of migrating to Enterprise Edition and how can they be avoided?

Summary of high-level differences between Enterprise Edition versus Classic Edition Compliance services?

Page 2 of 8© Agilent Technologies, Inc. 2013 Document Release Date: November 2013

What are the high-level changes in Enterprise Edition and what were the drivers for these changes? (continued)Another driver, somewhat related to the first, was the demand that Agilent perform the analytical instrument qualification using the customer CDS as controller. Theory and good practice in validation implies testing in the everyday operating conditions and using the full computer and instrument system in a ‘holistic’ manner. Classic OQPV did not allow this, but Enterprise Edition does. Additionally, our customers demanded the exact same OQ on their non-Agilent instruments. Sometimes called ‘multi-vendor compliance,’ this capability is fully realized in Enterprise Edition by virtue of:

• The independence of Agilent ACE software• Extensive R&D to make test protocols that work on

Agilent and non-Agilent systems as robust and reliable as old OQPV

• Training for our service engineers on both the hardware & software of the main non-Agilent systems

The third driver comes from shifts in typical instrument usage and the greater regulatory enforcement. Qualification today is a fairly mature subject. No longer are customers simply asked “do you perform qualification and calibration?” FDA and EU inspectors increasingly look deeper and check that an annual OQ adequately (within reason and practicality) tests the range of operational use of the systems. GMP and GLP guidelines have always stated this. There is no change in the regulations. It is the range of use that has shifted with regulatory enforcement.

For example, Classic OQPV tested HPLC pump flow rate performance at 1 and 2 ml/min set points (1.5ml/min flow rate is found in hundreds of analytical methods around the world.) Today customers run much lower flow rates and much higher flow rates and LC methods with elevated column temperatures. OQPV tested only at 40 °C. Most of the metrology tests in Enterprise Edition now allow a wider range of testing.

Our HPLC pump flow test in Enterprise Edition now defaults at the recommended 0.500 and 5.000 ml/min. The column compartment is tested at 40 °C and 80 °C.

The fourth driver follows from the third. One-size OQ may not fit all needs. Enterprise Edition services allow customers to have an OQ protocol made especially for their set points and add extra tests not in OQPV. Agilent provides a standard

protocol – the Agilent-recommended Equipment Qualification Plan (EQP) – which is the simplest choice and should meet most requirements. But now it is possible for customers to make set point changes in a Variance to Standard EQP, a selection page in the Standard EQP Review Document. For changes deeper than set points (such as extra tests, limit changes, custom forms etc.) a customer-configured EQP can be produced on demand. Customers simply make change requests through their Agilent representative or email: [email protected]

Are there any other practical or process changes in Enterprise Edition?Yes. Approval of the protocol (called EQP) before execution of the OQ is greatly simplified, regardless of the complexity and type of analytical equipment. Customers need only sign a single recommended EQP that can cover all systems and configurations of analytical instruments in their lab. There is no need for individual protocols to be created before each scheduled OQ or sent by mail as a paper document for approval. The same simple process is followed for all major chromatography and spectroscopy techniques, including LC, GC, MS, UV-Vis, Dissolution, SFC, AA, and ICP-MS. Approval of the Global EQP also covers the hardware installation qualification (IQ) protocol and any software IQ and OQ ordered at time of new instrument purchase. All the tests & checks in our standard hardware and software IQ & OQ are listed in the Agilent-recommended EQP for each technique – or you may have a single EQP that includes them all under a single set of signatures.

Approval of the reports, called Equipment Qualification Reports (EQR), is the biggest change. The standard deliverable is a CD disk with links to the IQ and/or OQ report(s) plus raw data and other supporting information. The EQR is a secure Adobe Acrobat document with a single page for customer approval signatures. Compare this to over 80 pages in OQPV that needed both the service engineer and customer to sign and date at the bottom of each page. This is all made possible by the technology of secure and active Adobe Acrobat forms – fully proven electronic media that are 100% acceptable to the FDA and national agencies, 21 CFR Part 11 compliant records that may be printed as paper copies if desired.

This design meets the Agilent commitment to follow FDA GMPs for the 21st Century initiative, world-wide environmental concerns over excessive paper usage and many customer strategies to move towards paperless laboratories.


Changes:• Now called OQ not OQPV to align with literature and

current guidance nomenclature for GMP/GLP.• Wander was a unique Agilent proprietary algorithm.

It was removed to align with literature and other comparable protocols.

• The holmium oxide internal test was considered a pre-OQ diagnostic or calibration check and is not reported in Enterprise Edition OQ. This check is performed in Agilent Preventive Maintenance (PM) service prior to the OQ.

• All precision tests (flow precision, injection precision and temperature stability over time) use six readings to align with the latest literature & guidance and allow statistically comparable RSD results.

None of the changes affect the regulatory compliance status.

Enhancements and Additions:• The Gradient Performance test has been re-designed and

enhanced. A different gradient slope is used that tests and challenges more aspects of gradient performance and provides some additional, very useful information.

• The Column Compartment Temperature test now uses a special T-piece that allows measurement of the temperature of the water flowing out of the thermal exchange blocks.

• A Signal-to-Noise test has been added to ensure cell cleanliness (in LC), replace absolute area check (in GC), harmonize with MS qualifications that require signal-to-noise checks, provide comparable sensitivity results and thereby provide more system performance data.

• The response linearity test now adds Response Factor (R/F) Precision aligned with current literature and provides a more sensitive measure of linearity.

• For labs that run non-Agilent CDS such as Waters Empower, we can control the instrument during OQ, collect the digital signal data, and calculate the results in ACE. This provides a full ‘holistic’ OQ that simultaneously qualifies the instrument hardware and the Empower control and data acquisition functions.

• Two-Limit feature: each test’s final result can be calculated against two limits if required. This allows the customer-configured OQ to report against a User Limit (limit1) and the Agilent-recommended Limit (limit2) simultaneously. Or, as is common in process instrument calibration, a Warning Limit and Action Limit may be applied. Lab workers are familiar with Upper and Lower Limits in their control chart procedures, but Two-Limit reporting is new to LC and GC qualification. The Agilent-recommended EQPs have both limit1 & limit2 values set the same – effectively de-activating this feature.

Diving into the details – how do the protocols and tests in Enterprise Edition compare to Classic?The answer is multi-dimensional. We already mentioned single protocols, pdf reports, customer-selectable set points, functionality on non-Agilent instruments and software as well as enhancements. It is also worth noting that Agilent carried out a full analysis of our OQ test design for LC, GC and MS systems. The goal was an ideal OQ – avoid over-testing or under-testing; to align with current literature and international norms but without significantly deviating from the Classic OQPV given its international gold-standard status. Agilent hired internationally recognized experts into the development team and used the input of independent advisors (including customers and agency representatives) to assess what changes and additions should be made to Classic OQPV.

Concepts that have not changed include:• Always perform direct metrology for temperature and

flow using the best calibrated test equipment. Indirect measurement of flow and temperature found in competitor protocols were considered susceptible to error caused by variation in columns, ambient conditions, etc. Regardless of purported design elegance, the inferred final results can never be as absolute or comparable as direct metrology.

• In LC tests, avoid the variable contribution to system performance of the analytical column, by eliminating a test column. OQ aims to test only the hardware, not hardware plus an arbitrary choice of analytical column.

• Caffeine is still used as the chemical reference standard for LC precision, carry-over, linearity and UV detector wavelength accuracy tests. It is a representative sample, has continuity with OQPV, and matches international standards and published literature. It is accepted by auditors, is safe, stable, easy to use, low-cost, and readily available in accurate, pre-made solutions. And the fact that caffeine has a nice spectral maximum at 205 nm makes it the best choice for low UV verification.

The names of the tests are similar or identical to OQPV.• All the calculation formulas remain the same where the

test design is unchanged.• The standard OQ suite of tests for GC is kept the same in

terms of operator procedure and limits.• All service engineers must be trained and certified before

they can deliver the service.• The software tool and the test designs are fully validated

and maintained for quality by a large support team following Agilent ISO-approved life-cycle methodology.

IQ checks are the same in Enterprise Edition as in Classic.


List of Enterprise Edition OQ tests for 1100/1200 LC versus Classic OQPV tests for 1100 LC

Test Name in Enterprise Edition

Set Point / Parameter in Enterprise Edition for 1100/1200 series LC

Limits in Enterprise Edition A.01.60 Difference from Classic OQPV

Pump Flow Accuracy and Precision

Flow rate 1 = 0.500 ml/minute Accuracy ≤ 5.00% Same limits.

Flow rate 2 = 5.000 ml/minute Precision ≤ 0.50% Set points widened from previous 1ml/min and 2ml/min

Column Temperature Accuracy and Stability

Temperature 1 = 80.0 °C* Accuracy ≤ 3.0 °C Same limit for the 40 °C set point as OQPV. Stability was only measured at 40 °C with 0.5 °C limit in OQPV.Temperature 2 = 40.0 °C Accuracy ≤ 2.0 °C

For any temperature Stability ≤ 1.0 °C

Test design is enhanced to measure flow temperature in Enterprise Edition whereas OQPV tested the thermal block temperature.

Wavelength Accuracy (UV-Vis)

Wavelength 1 =205 nm [Maximum] Wavelength 2 =245 nm [Minimum] Wavelength 3 =273 nm [Maximum]

≤ 2 nm Same limit and set point

Wavelength Accuracy (FLD) Wavelength 1=350 nm [Maximum] Wavelength 2=397 nm [Maximum] ≤ 3 nm Same limit and set point

Signal Noise and Drift (UV-Vis)

Noise Noise VWD (0.04), DAD/MWD (0.05). Same limits (mAU and mAU/hr)

Drift Drift VWD (0.5), DAD/MWD (5.0)

The proprietary and unique Wander calculation in OQPV is removed.

Signal Noise and Drift (RID)Noise ≤ 10.000 nRIU Same limit and set point

Drift ≤ 400.000 nRIU/hour Same limit and set point

Signal to Noise (UV-Vis) Signal to Noise ≥ 3000 New test

Signal to Noise (RID) Signal to Noise ≥ 2000 New test

Signal to Noise (FLD) Signal to Noise ≥ 400 New test

Injection Precision (UV and RID)

Height RSD ≤ 2.00 % Same limit and set point

Area RSD ≤ 1.00 % Same limit and set point

Injection Carry Over (UV-Vis and RID)

Height Carry Over ≤ 0.40 % Same limit and set point

Area Carry Over ≤ 0.20 % Same limit and set point

Response Linearity (UV-Vis)Coefficient of Determination (r2) ≥ 0.99900 Same limit and set poin

R/F Precision ≤ 5.00 % New parameter and limit

Response Linearity (RID)Coefficient of Determination (r2) ≥ 0.99500 OQPV limit is 0.9990. Injection volume

was 2 uL in OQPV; this is now 5 uL

R/F Precision ≤ 10.00 % New parameter and limit


Test Name in Enterprise Edition

Set Point / Parameter in Enterprise Edition for 1100/1200 series LC

Limits in Enterprise Edition A.01.60 Difference from Classic OQPV

Gradient Composition

Composition Accuracy, Composition Noise, Composition Drift ≤ 2.00 % New test design, new parameters.

High Coefficient of Determination (r2) ≥ 0.99900 New parameter and limit. This tests linearity at start of gradient.

Mid Coefficient of Determination (r2) ≥ 0.99900 New parameter and limit. This tests linearity at the 50:50 zone.

Low Coefficient of Determination (r2) ≥ 0.99900 New parameter and limit. This tests linearity at end of gradient.

Sample Temperature Accuracy

Set point 4 °C ≥ –2.0 °C to ≤ 5.0 °C Same limit and set point

Additional Set point is Selectable ± 3.0 °C setpoints >10 °C Choice not available in OQPV

Injection Linearity (UV-Vis only)

Coefficient of Determination (r2) ≥ 0.999000 New optional extra test – choice not available in OQPVR/F Precision ≤ 5.00 %

Injection Response (UV-Vis)For a known injection vol. / conc. / path length, the peak area is predictable (within a range.)

≥ 1,200,000 to ≤ 1,800,000 counts (std cell path length)

This is a new semi-quantitative test of Injection Accuracy - choice not available in OQPV

*For routine qualification of installed base 1050, 1090 LC systems the column temperature set point recommendation is 60 °C limit ± 3 °CThe new instruments – LCMS, ELSD, CTC etc. never were covered by Classic OQPV so are not listed here.

Injection Linearity and Injection Response are only available with a Custom EQP.

For GC there are no significant changes to set points and limits in the core OQ tests. The main changes are:• The signal-to-noise test replaces the old absolute area test and oven temperature now is measured directly with

calibrated probe and meter.• The harmonized look and feel of the reports (EQR) is an improved and cleaner presentation of the Classic reports which

were different for different GC models.• The thermal qualification and response linearity tests that were separate services now are simply optional extra tests in

Enterprise Edition. This further harmonizes the look and feel of GC reports.

How are Equipment Qualification Reports (EQR) different from OQPV Reports?The easiest way to check is simply to look at the extract of a sample hardware OQ report provided in an EQP attachment. The main differences are:• A report (plus all raw data) is delivered to a customer as a single, secure pdf on a dedicated CD disk. View it on your

computer using the freely available program, Acrobat Reader™.• It has a color front page and one click to the back page shows a summary of results that can be used as your Qualification

Certificate. Print only these 4 or 5 pages for your paper copy to save paper, while providing all the summary information required. You may keep the pdf records on the disk and/or on your own network storage system for fully auditable electronic records.

List of Enterprise Edition OQ tests for 1100/1200 LC versus Classic OQPV tests for 1100 LC (continued)


• The major sections of the Equipment Qualification Report (EQR) include: ◦ All the details and descriptions of the tests and the system being tested ◦ A detailed test summary section that shows pass/fail per test, the number of times each test was run and overall OQ status ◦ The raw values and calculated results for each test run plus pass/fail status and chromatograms ◦ Data integrity and audit log pages to ensure trustworthiness and allow easy traceability to raw data ◦ Copies of certificates for the equipment, chemical standards and service engineer training ◦ Sections with general information, glossary, list of formulas, etc. You can request that these not be included in future EQRs to

receive shorter reports if multiple OQs are delivered.

Certificate of System Qualification – at customer-selected location

Cover page and Signatures page


What should I do if I want to move my annual OQ service from Classic to Enterprise Edition?The simplest answer is – just download and approve one of the published Agilent-recommended EQPs for the appropriate techniques, and order the service contract as usual. However, some customers have situations that require slightly more complex actions.

If a lab has a calibration/qualification that references the Agilent OQPV by name or even copies out the OQPV tests and limits — we need to ensure the new service does not conflict with the SOP. Check carefully the words in your SOP for any exception phrases such as “…or approved alternative” or “… or following Agilent’s current recommended procedures.” Many customers have simply made their old SOP obsolete– the EQP approval substitutes for an SOP.

Some firms have an efficient SOP deviation process where the QA Manager/Director can issue a simple form that states that the Agilent Enterprise Edition service and the signed EQP(s) are an approved alternative to the current local Qualification SOP. This allows instant use of Enterprise Edition and provides you time to consider whether or how to make a new SOP.

For thorough QA review and approval we provide a description of the service in the EQP Review Documents (with more information on the Agilent web site under the Compliance Services section), a Part 11 Conformance document, and other examples as attachments to each EQP and this document.

If a vendor audit is deemed appropriate by your QA department, Agilent can provide a Validation binder with Agilent’s lifecycle documentation showing the full testing and validation of Enterprise Edition and ACE. An electronic copy of the Validation binder is available to QA auditors upon receipt of a signed confidential disclosure agreement. These electronic documents have saved firms the expense of on-site audit visits to our offices in Delaware, USA or Waldbronn, Germany.

What are the main risks of migrating to Enterprise Edition and how can they be avoided?We do not believe that there are any regulatory compliance risks in using Enterprise Edition – in fact we are confident that it is the safest, most sustainable and convenient option for firms large and small. However, the previous section mentioned the need to ensure that your own SOPs align with (or at least do not conflict with) the Enterprise Edition protocols. Keeping a copy of the signed approval of your EQP(s) is an expectation. Keeping copies of the reports and your approvals is essential. The CD and report format make that easier and more convenient than paper reports when searching for past records and performance data. Ink signatures on the print-out of the secure pdf report and/or on the EQR CD disk are both 21 CFR Part 11 compliant “hybrid ink on paper signatures linked to an electronic record.”

As you may see, there are some first-time preparation steps to complete prior to the first ACE delivery. After that the automated Enterprise Edition OQ typically takes less time to deliver than Classic OQPV. A pre-approved EQP is essential to ensure an expeditious and efficient delivery of the service without last-minute adjustments. Pre-approval of the EQP is therefore checked by our schedulers when they call to arrange a time for the PM and OQ service. To ensure that any Agilent service engineer scheduled to arrive on-site will execute the customer-configured EQP you approved, keep a CD copy handy in the lab, just in case your regular engineer, who is familiar with your requirements and has your EQP in his ACE laptop, is not available. Agilent engineers save a copy of the approved EQP on every report CD – so once the first one is completed there is always a copy for any other Agilent service engineer to access.

Once the first couple of OQ deliveries are completed in a lab contract and you gain familiarity with the new report style, the benefits and efficiency gains are fully enjoyed. We can reduce the size of reports by turning off the repetitive text sections. The first time you need to electronically forward a copy of an OQ report for remote review (because the usual approver is out of office) or have to search and compare instrument performance data across multiple makes of LCs in your lab, or have an external audit of your lab qualification system – you’ll appreciate that your organization has invested in Agilent Enterprise Edition compliance services.



© Agilent Technologies, Inc. 2013Published in USA, November 20, 2013

5991-3662EN

Summary of high-level differences between Enterprise and Classic Edition Compliance Services

Table: List of Characteristics of an Analytical Instrument Qualification (AIQ) Program and comparison between Enterprise and Classic Edition OQ services

Characteristic Enterprise Edition OQ Classic Edition OQPV

Meets the letter, spirit and intent of cGMP and GLP regarding Equipment Qualification Yes Yes

Acceptable to (and used by the Labs of) International Agency auditors Yes Yes

QA-approved system in major Pharmaceutical firms Yes Yes

Compatible with Agilent LC, LC/MS and GC, GC/MS instruments Yes Yes

Compatible with leading non-Agilent LC and GC instruments and suitable for use as an Enterprise-wide program Yes No

Compatible with Agilent ChemStation CDS Yes Yes

Compatible with all Agilent CDS and most non-Agilent CDS (for example, OpenLab, EZChrom, MassHunter, Empower) Yes No

Adequate for compliance without delivering “over-testing” Yes Yes

Provides a protocol with fixed recommended tests and limits Yes Yes

Provides customer selectable setpoints and then a fixed protocol for future use that contains these tests and limits Yes No

Comprehensive final report with automated results calculation and pass/fail status reporting Yes Yes

Flexible-sized final report in secure pdf format that can be printed to paper in full, or in part (to save paper) Yes No

Final report in secure pdf format with a single signature Yes No

Reports with searchable electronic data and results Yes No

Page 8 of 8