User-Configurable OQ and RQ Suitable for Most Makes of LC

Designed to Meet These Rules and Enforcement Guidelines:

United States Pharmacopeia <1058>; EDQM Annex 1: Qualification of HPLC; ISO/

IEC 17025 Sections 5.5 & 5.6; GAMP for Laboratory Systems; United States FDA
Warning Letter FLA-09-20. 21 CFR Part 11 and European Commission Annex 11
for Electronic Records.

Review Protocol
Liquid Chromatography

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol
Liquid Chromatography

Summary of Test Results:

Operational Qualification Protocol

Summary of Test Results:

PerkinElmer
Summary Product Release
of Test Results: Product Number: 09360020 F

08 Mar 2017

Damien POSSOZ
Manager Global Compliance Services R&D
Summary of Test Results:
63 User Limit(s)
The configuration of this protocol is:
15 User Setpoint(s)
Summary of Test Results:
Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001
HPLC_TPW_BAO_001
Customer Name: TEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab

Address: Hungary
Summary of Test Results:
Customer Ink or Digital Signature Approvals
Name / Role
Summary of Test Results: Ink or digital signature Date

Click
Summary of Testto Results:
Approve and Lock this Protocol. Locked when file is next saved.

Reviewed and Approved by Names Above

1/21
PDF Locked and Saved: 13-Jul-2017 14:33:14

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 2/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Overview 3/21
Standard LC System Recommended Tests for GLP/GMP Compliance
Column Oven / Column Manager Temperature Test 4/21
Pump Flow Accuracy and Stability Test (all pump types) 4/21
Gradient Pump Performance (Binary or Quaternary) 4/21
Injection Precision 5/21
Injector Linearity 5/21
Injector Carry Over 5/21
Sample Tray Temperature Test 5/21
Sample Organizer / Compartment Temperature Test 5/21
UV Detector Wavelength Accuracy using caffeine (Monochromator or Diode Array) 6/21
UV Detector Linearity (Monochromator or Diode Array) 6/21
UV Detector Noise & Drift (TUV / VWD / Monochromator) 6/21
UV Detector Noise & Drift (PDA / DAD / MWD Diode Array) 6/21
Additional Modules (extra fees apply)
FLD Wavelength Accuracy using Raman Band of Water 7/21
FLR Wavelength Accuracy using Rayleigh Scattering of Water 7/21
FLD / FLR Detector Linearity 7/21
FLD / FLR Noise & Drift and Signal to Noise 7/21
Refractive Index Detector (RID) Linearity 7/21
RID Noise & Drift 7/21
Conductivity Detector Linearity 8/21
Conductivity Detector Noise & Drift 8/21
Evaporative Light Scattering Detector (ELSD) Reproducibility 8/21
ELSD Noise & Drift 8/21
Charged Aerosol Detector (CAD) Reproducibility 8/21
CAD Noise & Drift 8/21

Extra Test Set Points (extra fees apply)

Extra Sample and Oven Temperatures / Pump Flows 9/21
Extra UV Wavelengths / FLD Noise / Injector Precision Volumes 10/21
Test Procedures 11/21
Formulas and Chemical Standards Used in this OQ 18/21
Customer Comments and Instructions 20/21
Scope of the Protocol (Lab, Department, List of LC Systems...) 20/21

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 3/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Overview

Purpose The Protocol ID, User Setpoints and User Limits will
The purpose of this document is to provide a reviewer transfer to each report. Customer selected limits
with the list of tests, set points & limits included in this over-ride the recommended limits in reports.
OQ. This document allows a record of customer Extra tests can be selected (extra fees apply). Extra
pre-approval as required by cGMP, GLP and ISO testing requests must be communicated to PerkinElmer
17025 or a firm"s own SOPs. before OQ delivery.
Extra tests or 'Report Only' tests are turned on by
entering set points and limits over the 'N/A'. Any test
Scope with 'N/A' User Limit is turned off and will not be
This OQ is applicable to most makes and models of performed in the OQ.
analytical-scale, standard configuration LC with UV, If custom entries are made you must enter some
FLD, RID, ELSD or conductivity detector. It is designed custom text into the Protocol ID on page 1/21 like
for complete LC systems but can be used for "UOQ_LC_6.01_xyz123" to uniquely identify your
Re-Qualification (RQ) on individual modules. protocol.
Provide the locked approved pdf to your PerkinElmer
The approved OQ protocol can cover one or any representative and send to the automated email link by
number of LC systems for as long as required. All clicking any of the square OneSource icons in this
selected tests are to be run except where a given LC document.
system is absent the module or functionality (such as
oven, sample cooling, other detectors) in which case
Compliance
the tests are simply not run and not reported.
PerkinElmer trained engineer shall perform the test
The list of LC systems covered is usually kept methods and sequences using calibrated test tools
separately in a scheduling database. But page 21 at the and certified chemical standards and the customer"s
back of this document is provided to list the in-scope Chromatography Data System (CDS) connected to
LC systems if desired. The list page is not locked on the LC. The report is created with a validated, secure
approval to allow additions/deletions of in-scope LC ˆsmart pdf" report tool.
systems.
This report tool has built-in calculations, secure
date/time stamps and automated pass/fail reporting.
Customer Set Points and Limits and Extra Tests No calculators, Excel or other external software are
used to generate the final report.

Default set points and recommended limits are

The full original record of the OQ is either the ink
provided for most tests where applicable.
signed paper report with raw data, certificates and
The default set points should meet the typical user
training records appendices. Alternatively customer
range but can be configured if not suitable. The
may choose the paperless reporting option that uses
recommended limits match industry consensus limits
21 CFR Part11 compliant digital signatures on pdf
or (if no consensus) the most popular commercial OQ
reports. In either mode, an e-record copy of the report
limits and/or any regulatory and quality guidelines.
is automatically and confidentially uploaded to a
There are no direct pharmacopoeia specifications for
PerkinElmer database. The track & trace of OQ
OQ/PQ/RQ of LC systems at this date.
reports is required by ISO17025 and ISO13485.

User Setpoints and User Limits can be entered

PerkinElmer controls and manages how its official OQ
directly into this pdf by typing in the appropriate cells.
documents are developed, validated, released and
The font changes to bold italic and message appears
updated by approved internal quality procedures.
on page 1/21 as indicators.
Summary of Test Results:
Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 4/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Standard LC System Recommended Tests for GLP/GMP Compliance

Column Oven Temperature Tests

Accuracy Default User Setpoint(s) Recommended User Limit(s)

Set Point (°C) 40 N/A

40 Limit (°C) < = 2 N/A
2.0
Set Point (°C) 60 N/A
80 Limit (°C) < = 3 N/A
3.0

Stability
Set Point (°C) 40 N/A
40 Limit (°C) < = 1 N/A
1.0
Set Point (°C) 60 N/A
80 Limit (°C) < = 1 N/A
1.0

Column Manager Temperature Tests

Accuracy Default User Setpoint(s) Recommended User Limit(s)

Set Point (°C) 40 N/A

40 Limit (°C) < = 2 N/A
2.0
Set Point (°C) 60 N/A
60 Limit (°C) < = 2 N/A
2.0

Stability
Set Point (°C) 40 N/A
40 Limit (°C) < = 0.5 N/A
0.5
Set Point (°C) 60 N/A
60 Limit (°C) < = 0.5 N/A
0.5
Summary of Test Results:

Pump Flow Accuracy and Stability Test (all pump types)

Accuracy Default User Setpoint(s) Recommended User Limit(s)

Set Point (mL/min) 0.5 N/A

0.2 Limit (%) <= 5 N/A
3.0

Set Point (mL/min) 2 N/A

1.0 Limit (%) <= 5 N/A
3.0
Stability
Set Point (mL/min) 0.5 N/A
0.2 Limit (%RSD) <= 0.5 N/A
0.5

Set Point (mL/min) 2 N/A

1.0 Limit (%RSD) <= 0.5 N/A
0.5
Summary of Test Results:

Gradient Pump Performance (Binary or Quaternary)

Accuracy Default User Setpoint(s) Recommended User Limit(s)

Set Point (abs%) 20 N/A

20 Limit (abs%) <= 2.00 N/A
2.00
Set Point (abs%) 40 N/A
40 Limit (abs%) <= 2.00 N/A
2.00
Set Point (abs%) 60 N/A
60 Limit (abs%) <= 2.00 N/A
2.00
Set Point (abs%) 80 N/A
80 Limit (abs%) <= 2.00 N/A
2.00
R2 of Regression Line Limit (R2) >= 0.995 N/A
0.995
Summary of Test Results:
Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:
Summary of Test Results:
15 User Setpoint(s) 63 User Limit(s)

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 5/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Standard LC System Recommended Tests for GLP/GMP Compliance

Injection Precision Volume: N/A

20 µL
Recommended User Limit(s)
Peak Areas Limit (%RSD) <= 1.00 N/A
0.85
Peak Heights Limit (%RSD) <= 2 N/A
2.00
Peak Times Limit (%RSD) <= 2 N/A
1.00
Summary of Test Results:
Injector Linearity
Default: 5, 10, 20, 40, 50% of Loop Size or User Setpoints (% or µL) below:

N/A
2 N/A
5 N/A
20 N/A
50 N/A
80 μL

+/-

+/-
Recommended User Limit(s)
R2 of Regression Line Limit (R2) >= 0.999 N/A
0.99900

Response Factor RSD Limit (%RSD) <= 5.0 N/A

5.0
Estimated Injection Accuracy (Intercept/slope) Limit (% Max inj Vol) <= 4.0 Report
1.0Only

Summary of Test Results:

Injector Carry Over
Recommended User Limit(s)

Peak Areas Limit (%) <= 0.20 N/A

0.1
Peak Heights Limit (%) <= 0.40 N/A
0.2
Summary of Test Results:

Sample Tray Temperature Test

Accuracy Default User Setpoint(s) Recommended User Limit(s)

Set Point (°C) 4 N/A

5.0 Lower Limit (°C) >= -3 N/A
-2.0
Upper Limit (°C) <= 3 N/A
3.0

Sample Organizer / Compartment Temperature Test

Accuracy Default User Setpoint(s) Recommended User Limit(s)

Set Point (°C) 4 N/A

5.0 Lower Limit (°C) >= -3 N/A
-2.0
Upper Limit (°C) <= 3 N/A
3.0

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:
Summary of Test Results:
15 User Setpoint(s) 63 User Limit(s)

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 6/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Standard LC System Recommended Tests for GLP/GMP Compliance

UV Detector Wavelength Accuracy using caffeine (Monochromator or Diode Array)

Accuracy Recommended User Limit(s)

Test Wavelength (nm) 205 Limit (nm) <= 2 N/A

2

Test Wavelength (nm) 273 Limit (nm) <= 2 N/A

2
Summary of Test Results:
UV Detector Linearity (Monochromator or Diode Array)
Recommended User Limit(s)

R2 of Regression Line Peak Limit (R2) >= 0.99900 N/A

0.99900
Response Factor RSD Areas Limit (%RSD) <= 5.0 N/A
5.0

R2 of Regression Line Peak Limit (R2) >= 0.9900 N/A

0.99000
Response Factor RSD Heights Limit (%RSD) <= 5.0 N/A
5.0

Linearity% (areas) Limit (%) <= 2 N/A

2.00
Summary of Test Results:
UV Detector Noise & Drift (TUV / VWD / Monochromator)
Baseline Noise Recommended User Limit(s)
Waters TUV Detectors Limit ( mAU )<= 0.06 N/A
0.06
Agilent VWD Detectors Limit ( mAU )<= 0.04 N/A
0.04
Other Variable UV Detectors Limit ( mAU )<= 0.1 N/A
0.06
Baseline Drift Recommended User Limit(s)
Waters TUV Detectors Limit ( mAU/h )<= 10 N/A
10.00
Agilent VWD Detectors Limit ( mAU/h )<= 0.5 N/A
0.50
Other Variable UV Detectors Limit ( mAU/h )<= 1 N/A
1.00

UV Detector Noise & Drift (PDA / DAD / MWD Diode Array)

Baseline Noise Recommended User Limit(s)
Waters PDA Detectors Limit ( mAU )<= 0.08 N/A
0.08
Agilent DAD / MWD Detectors Limit ( mAU )<= 0.05 N/A
0.05
Other DAD / MWD Detectors Limit ( mAU )<= 0.1 N/A
0.08
Baseline Drift Recommended User Limit(s)
Waters PDA Detectors Limit ( mAU/h )<= 10 N/A
10.00
Agilent DAD / MWD Detectors Limit ( mAU/h )<= 5 N/A
5.00
Other DAD / MWD Detectors Limit ( mAU/h )<= 5 N/A
1.20
Summary of Test Results:
Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:
Summary of Test Results:
15 User Setpoint(s) 63 User Limit(s)

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 7/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Additional Modules (extra fees apply)

FLD Wavelength Accuracy using Raman Band of Water

Accuracy Recommended User Limit(s)

Test Wavelength (nm) 350 Limit (nm) <= 3 N/A

Test Wavelength (nm) 397 Limit (nm) <= 3 N/A

FLR Wavelength Accuracy using Rayleigh Scattering of Water

Accuracy Recommended User Limit(s)

Test Wavelength (nm) 365 Limit (nm) <= 3 N/A

Test Wavelength (nm) 730 Limit (nm) <= 5 N/A

FLD / FLR Detector Linearity

Recommended User Limit(s)
R2 of Regression Line Limit (R2) >= 0.995 N/A

Response Factor RSD Limit (%RSD) <= 10 N/A

Linearity% (areas) Limit (%) <= 2 N/A

Signal-to-Noise

Agilent Fluorescence Detectors Limit ( % Full Scale )>= 400 N/A

Waters Fluorescence Detectors Limit ( % Full Scale )>= 800 N/A

300 N/A
Summary
Other Variableof Test Results:
Fluorescence Detectors Limit ( % Full Scale )>=

Refractive Index Detector (RID) Linearity

Recommended User Limit(s)
R2 of Regression Line Limit (R2) >= 0.995 N/A

Response Factor RSD Limit (%RSD) <= 10 N/A

Linearity% (areas) Limit (%) <= 2 N/A

RID Noise & Drift

Recommended User Limit(s)
Baseline Noise Limit ( nRIU )<= 10 N/A

Baseline
SummaryDrift
of Test Results: Limit ( nRIU/h )<= 400 N/A

Gravimetric Injection Accuracy Test

Injection Accuracy Limit (%) <= 2.0 N/A

Injection Precision Limit (%RSD) <= 2.0 N/A

Summary of Test Results:
Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:
Summary of Test Results:
15 User Setpoint(s) 63 User Limit(s)

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 8/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Additional Modules (extra fees apply)

Conductivity Detector Linearity

Recommended User Limit(s)

R2 of Regression Line Limit (R2) >= 0.995 N/A

Response Factor RSD Limit (%RSD) <= 10 N/A

Linearity% (areas) Limit (%) <= 2 N/A

Conductivity Detector Noise & Drift

Baseline Noise Limit ( uV )<= N/A N/A

Baseline
Summary Drift
of Test Results:
Limit ( uV/h )<= N/A N/A

Evaporative Light Scattering Detector (ELSD) Reproducibility

Peak Areas Limit (%RSD) <= 10 N/A

Peak Heights Limit (%RSD) <= 10 N/A

ELSD Noise & Drift

Baseline Noise Limit ( mV )<= 5 N/A

Baseline Drift Limit ( mV/h )<= 5 N/A

Summary of Test Results:
Charged Aerosol Detector (CAD) Reproducibility
Peak Areas Limit (%RSD) <= 10 N/A

Peak Heights Limit (%RSD) <= 10 N/A

CAD Noise & Drift

Baseline Noise Limit ( % Full Scale )<= 5 N/A

Baseline
Summary Drift
of Test Results:
Limit ( % Full Scale/h )<= 5 N/A

Extra Test Set Points (extra fees apply)

Gradient Stability, Noise and Drift (Extra Tests) Turn ON this extra test

Stability of each gradient step expressed as %RSD

of 6 heights along the plateau Limit (%RSD) <= 5.0 N/A

Noise of each gradient step expressed as Max-Min

of 6 heights reported as % of the 100% step Limit (%Noise) <= 2.0 N/A

Drift of each gradient step expressed as End-Start

of plateau as % of the 100% step Limit (%Drift) <= 2.0 N/A

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001
Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:
Summary of Test Results:
15 User Setpoint(s) 63 User Limit(s)

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 9/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Extra Test Set Points (extra fees apply)

Sample Tray Temperature Test

Accuracy Recommended User Limit(s)

Set Point #2 (°C) N/A

15 Limit (°C) < = 3 N/A
3.0
Set Point #3 (°C) N/A Limit (°C) < = 3 N/A

Sample Organizer / Compartment Temperature Test

Accuracy Recommended User Limit(s)

Set Point #2 (°C) N/A

15 Limit (°C) < = 3 N/A
3.0
Set Point #3 (°C) N/A Limit (°C) < = 3 N/A

Summary of Test Results:

Column Oven Temperature Extra Tests

Accuracy Recommended User Limit(s)

Set Point #3 (°C) N/A

15 Limit (°C) < = 2 N/A
2.0

Comments: For column oven with cooling option only.

Set Point #4 (°C) N/A Limit (°C) < = 2 N/A

Comments:

Stability
Set Point #3 (°C) N/A
15 Limit (°C) < = 1 N/A
1.0

Set Point #4 (°C) N/A Limit (°C) < = 1 N/A

Column Manager Temperature Extra Tests

Accuracy Recommended User Limit(s)

Set Point #3 (°C) N/A

15 Limit (°C) < = 2 N/A
2.0

Comments: N/A

Set Point #4 (°C) N/A Limit (°C) < = 2 N/A

Comments: N/A

Stability
Set Point #3 (°C) N/A
15 Limit (°C) < = 1 N/A
1.0

Set Point #4 (°C) N/A Limit (°C) < = 1 N/A

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:
Summary of Test Results:
15 User Setpoint(s) 63 User Limit(s)

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 10/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Extra Test Set Points (extra fees apply)

Extra UV Detector Wavelengths (Scanning Monochromator or Diode Array)

Accuracy Recommended User Limit(s)

Test Wavelength (nm) N/A Limit (nm) <= 2 N/A

Test Wavelength (nm) N/A Limit (nm) <= 2 N/A

Test Wavelength (nm) N/A Limit (nm) <= 2 N/A

Test Wavelength (nm) N/A Limit (nm) <= 2 N/A

Test Wavelength (nm) N/A Limit (nm) <= 2 N/A

Extra wavelength tests only possible for scanning UV detectors using the main peaks of Holmium. NOTE: the wavelength
range for UV detectors is limited by the light source energy in the visible region. 190 - 600nm is a typical range.
Summary of Test Results:

Extra Pump Flow Accuracy and Stability Tests (all pump types)
Accuracy Recommended User Limit(s)

Set Point #3 (mL/min) N/A

1.0 Limit (%) <= 5 N/A
3.0
Set Point #4 (mL/min) N/A Limit (%) <= 5 N/A

Stability
Set Point #3 (mL/min) N/A
1.0 Limit (%RSD) <= 0.5 N/A
0.5
Set Point #4 (mL/min) N/A Limit (%RSD) <= 0.5 N/A
Summary of Test Results:

FLD / FLR Noise & Drift and Signal to Noise

Recommended User Limit(s)

Baseline Noise Limit (% of Full-Scale) <= 5 N/A

Baseline Drift Limit (% of Full-Scale/hr) <= 5 N/A

Summary of Test Results:
Additional Tests for the 2nd injection Vol Accuracy Volume: N/A µL
Recommended User Limit(s)
Peak Areas Limit (%RSD) <= 1.00 N/A

Peak Heights Limit (%RSD) <= 2 N/A

Peak Times Limit (%RSD) <= 2 N/A

Additional Tests for the 3rd injection Vol Accuracy Volume: N/A µL
Peak Areas Limit (%RSD) <= 1.00 N/A

Peak Heights Limit (%RSD) <= 2 N/A

Peak Timesof Test Results:

Summary Limit (%RSD) <= 2 N/A

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:
Summary of Test Results:
15 User Setpoint(s) 63 User Limit(s)

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 11/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Test Procedures

Column Oven / Column Manager Temperature Test

This test uses a calibrated digital thermometer to determine the accuracy and stability of column oven temperature.
The temperature accuracy is reported as the absolute difference between the average of 6 measured temperatures
and the set point. The temperature stability is reported as absolute difference between the highest and lowest
measured temperatures.

Notes: For Agilent column compartments with left and right sides: both sides are set to same temperature, left side
tested for accuracy and stability and right side tested for accuracy and closeness to left side with a single measurement.
(Or vice versa if requested - right side for accuracy and stability and left side accuracy only)

Method

Column oven turned on and stabilized. Digital thermometer is turned on with thermocouple placed in column oven
at test point(s). Channel A of the degasser and pump is purged with HPLC-grade water. Stainless steel restriction
capillary column installed.
Set column oven to the set points prescribed in the approved version of this protocol and allow to stabilize.
Record six temperature readings at a minimum of 2 minute intervals.

Pump Flow Accuracy and Stability Test (all pump types)

The test uses a calibrated digital flow meter to determine the accuracy and stability of pump flow. The tests use
HPLC-grade water as mobile phase. Flow Accuracy is reported as the absolute % difference of the average of 6 flow
readings to the set point. Flow Stability is reported as the %RSD of the six flow readings. The pump pressure at time
of test is also recorded.

Notes: For binary pumps both A and B pump mechanisms are tested at the same set points and against the same limits.
Isocratic and Quaternary pumps have only one pump mechanism.

Method
LC pump turned on and flow stabilized with HPLC-grade water at first prescribed set point. Stainless steel restriction
capillary column installed providing at least 300 psi back pressure. Column oven (if installed) set to 40 °C. Digital
flow meter connected after the restriction capillary column. Allow the flow meter to perform 6 flow rate measurements
at the set points prescribed in the approved version of this protocol.

Gradient Pump Performance (Binary or Quaternary)

The test uses two mobile phases to step the pump through a series of compositions. Accuracy is calculated as the
absolute difference between the found composition and the nominal step composition. Gradient linearity is based on the
heights (adjusted for the starting baseline) for steps 1, 2, 3, and 4 and 100% step.

Notes: Binary pumps channel A versus B is tested . Quaternary two runs are made - A/B then C/D as default but different combinations can be
instructed - type custom options in the protocol instructions page.

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 12/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Test Procedures

Gradient Pump Performance (Binary or Quaternary) continued...

Method
LC pump turned on and flow stabilized with HPLC-grade water at 0% step. Stainless steel restriction capillary column installed. Column oven (if installed) set to 40 °C.
Channel A/C of the degasser and pump purged with HPLC-grade water. Channel B/D of the degasser and pump purged with the 20 µg/mL caffeine in water standard.
Flow rate 2 mL/min. Create a gradient timetable equivalent to the example table below.

Note : Alternative "tracer" solution adapted to the detector type can be used such as :
UV/PDA Detectors: 10 to 30µg/ml of Caffeine in Water or 0.4 to 0.6% of Acetone in Water (V/V).
RI Detectors: Sucrose in water 1g/l.
FLD/FLR Detectors: Quinine sulfate 5 mMol/l.

Channel A (or C) Channel B (or D)

Time Water Tracer

Step (mins) Solution
(%) (%)
0.00 100 0
0% B (D)
2.00 100 0
2.01 For LC 80.0 20.0
#1 B (D) systems
4.00 80.0 20.0
4.01
with large 60.0 40.0
#2 B (D) delay
6.00 60.0 40.0
6.01 volume the 40.0 60.0
#3 B (D)
8.00 step times 40.0 60.0
#4 B (D)
8.01 may be 20.0 80.0
10.00 extended to 20.0 80.0
10.01 3 or 4 or 5 0 100
100% B (D)
12.00 minutes 0 100
12.01 100 0
0% B (D)
14.00 100 0

Run a gradient timetable equivalent to the example table above.

[Different Chromatography Data Systems (CDS) may have different ways to program the step time intervals]

Injection Precision
This test is used to determine the repeatability over multiple injections. A sequence of 6 injections of the same
volume of caffeine standard is run with preferable UV detector. The precision is reported as the relative standard
deviation, which is the standard deviation divided by the average of the peak areas, heights and times. An estimated
injection accuracy value is also reported - the calculation is the intercept divided by the slope of the response curve.

Notes: The default test injection is Caffeine standard 20 µg/mL for 20 µL injection with 1cm path length UV detection but some
custom choices of injection volume may be too high or low or non-UV detector sensitivity too low for for suitable peaks using this
concentration standard. In those cases, one of the weaker or stronger standards must be used to obtain suitable peak heights.

Method

UV Detector turned on and stabilized at wavelength 273 nm. Run time not less than 0.5 min with HPLC-grade water
flow rate 0.5 mL/min. Stainless steel restriction capillary column installed (or C18 column if customer requests).
Column oven (if installed) set to 40 °C. Create injection sequence of 6 replicates of the 20 µg/mL caffeine standard
at set points prescribed in the approved version of this protocol.

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 13/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Test Procedures

Injector Linearity
This standard test uses caffeine standard at increasing injection volumes. The peak areas are used to calculate
linearity by two different statistical methods: The R squared of the best-fit regression line and relative standard
deviation of the response factors. Response factor is the signal divided by the nominal injection volume. In addition,
the intercept divided the slope of the regression line provides an indirect estimate of injector accuracy.

Notes: The default is standard is Caffeine 20 µg/mL at approx. 5, 10, 20, 40 and 50% of the loop size but some custom choices
of injection volume may be too high or low or non-UV detector sensitivity too low for for suitable peaks using this concentration
standard. In those cases, one of the weaker or stronger standards must be used to obtain suitable peak heights.

Method

UV Detector turned on and stabilized at wavelength 273 nm. Run time not less than 0.5 min with HPLC-grade water
flow rate 0.5 mL/min. Stainless steel restriction capillary column installed (or C18 column if customer requests).
Column oven (if installed) set to 40 °C. Create single injection sequence of 20 µg/mL caffeine standard at 5, 10, 20,
40 and 50% of the loop size or as prescribed in the approved version of this protocol.

Injector Carry Over

In most cases this test immediately follows the sequence of 5 injections of the UV Detector Linearity test where a
water test blank is injected after the highest concentration 40 µg/mL caffeine standard injection. For standalone
autosamplers (for instance front-end of MS systems or Re-Qualification of injector after repair) it is only necessary
to make a single 40 µg/mL caffeine standard injection before the test blank. Any observed carry over is reported
as the percentage of the peak area and height found in test blank compared to the previous caffeine injection.

Notes: Two confirmation pure water injections are made before and after the test. The average value of the the 2 confirmation
blanks is subtracted from the test blank to eliminate any false peak interference.

Method
All conditions same as the Injector Precision and Linearity tests.
Sample Tray / Organizer / Compartment Temperature Test
This test uses a calibrated digital thermometer with thin K-type thermocouple to determine the temperature control
accuracy of any installed sample tray, sample organizer or similar thermostatically controlled sample compartment
modules. 5 water vials are placed in positions across the sample tray. Temperature accuracy is reported as the
difference of each measured vial temperature from the set point.

Notes: The five uncapped vials of water are placed in appropriate positions around the tray or compartment to ensure any hot or cold spots are
detected. Typically placed in corners and middle of a flat tray or evenly spread around multi tray compartments.

Method
Set the sample tray temperature at the set point(s) prescribed in the approved version of this protocol. Vials filled with water
(uncapped) are placed in recommended positions or positions requested by customer. Allow at least 60 minutes for vials to
equilibrate or leave the vials in the tray until near the end of the OQ process. Remove the vials from closed compartments
or measure in situ if open tray by Inserting the thermocouple into the water and quickly make the reading for each test vial.

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 14/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Test Procedures

UV Detector Wavelength Accuracy (Monochromator or Diode Array)

The standard test uses the UV wavelength maxima of certified caffeine at 205 nm and 273 nm. The test solution may be
introduced into the detector flow cell through injection, flow-filled manually or by pump during gradient test or some
detectors allow test cuvettes to be inserted. Extra wavelengths may optionally be tested in the same way but using
certified Holmium solution. (See Extra Test Set Points page).

Notes: The default is standard is Caffeine 20 µg/mL but some custom choices of injection volume may be too high or
low or non-UV detector sensitivity too low for for suitable peaks using this concentration standard. In those cases, one of
the weaker or stronger standards must be used to obtain suitable peak heights.

Method
Option 1: Manual or software driven scanning or timed wavelength method:
20 µg/mL caffeine filled into the flow cell. If a gradient test is performed the cell is filled with the caffeine solution
when at the 100% gradient step. Run spectral scan with software or, if not possible, create one run method with
timed wavelength changes starting at 201 nm in 1 nm steps to 209 nm, and a second run method starting at 269
nm in 1 nm steps to 277 nm. Record the absorbance at each step.

Option 2: Individual injections method. (Only required if detector has no spectral scanning and timed or manual
wavelength changes are not possible):
Create a sequence to run 18 injections of 20 µg/mL caffeine standard. Program a single wavelength for each
injection at 201, 202, 203, 204, 205, 206, 207, 208, 209 nm and 269, 270, 271, 272, 273, 274, 275, 276, 277 nm.
The wavelength setting per injection is randomized across the sequence to eliminate hysteresis. The injection
with highest signal demonstrates the wavelength maximum.
All instrument conditions same as the Injector Precision and Linearity tests.
Extra wavelengths using Holmium or Erbium: Only Option 1 (with scanning detectors) is applicable.

UV Detector Linearity (Monochromator or Diode Array)

This test uses a sequence of injections of 5 identical volumes of caffeine standards of increasing concentrations, the highest is
near 1.50 AU for a standard 1 cm path cell with Injection volume 20 µL. Peak areas and heights are reported. The peak areas
(or optionally heights) are used to calculate linearity by three statistical methods: The R squared of the best-fit regression line;
relative standard deviation of the response factors; difference between found slope and theoretical slope from the highest peak
expressed in %. Response factor is the peak area divided by the certified concentration.
In addition, the correct picking of vials is proved by the correct sequence of increasing signal to the increasing concentrations
injected.

Method
HPLC grade water in vial position 1;
Caffeine standard 1/16 [2.5 µg/mL] in vial position 2;
Caffeine standard 1/8 [5.0 µg/mL] in vial position 3;
Caffeine standard 1/4 [10.0 µg/mL] in vial position 4;
Caffeine standard 1/2 [20.0 µg/mL] in vial position 5;
Caffeine standard 1/1 [40.0 µg/mL] in vial position 6;
HPLC grade water in vial positions 7 and 8.

Injection volume: 20 µL (HPLC) 10 µL (UHPLC). All other instrument conditions same as the Injector Precision and Linearity tests.

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 15/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Test Procedures

Detector Noise & Drift

The test uses a zero injection run to measure the baseline. Where automated noise and drift reports can be programmed in the
CDS these are used. If not possible a manual method is performed.

Method
Option 1: The Noise and Drift is measured and reported by the Chromatography Data System (CDS) connected to the
LC system using the ASTM noise report.

Option 2: (To be used for systems where it is not possible to use automated method Option 1 above).
Generate a printed report with suitable scaling to see the baseline noise. Draw a pair of parallel lines peak to trough in
minute segments, the slope is visually estimated by a best-fit center line. The vertical distance between the parallel lines
is the noise value for each 1 minute segment. The average of the 10 segment values is the final noise result.
Segment 1 starts between 2 to 5 minutes into the 15 minute run. (The first few minutes of the chromatogram is ignored
to ensure the injection pressure artifact or solvent baseline disturbance has finished).
The drift is the difference between the start of first segment and end of last segment multiplied by 6 to convert drift over
10 minutes to a per hour value. (See figure below).

Conditions:
Column oven (if installed): 40 °C. Detector optical unit switched on for at least 1 hour. Run time 15 min. Channel A of the
degasser and pump purged with HPLC-grade water. Flow rate: 1.0 mL/min. Stainless steel restriction capillary column
installed. Injection Volume: 0 or minimum injection volume.

CDS data rate: Between the equivalent of 1Hz and 20Hz (some CDS use peak width as the unit). For automated noise
and drift report: start data acquisition of the baseline at 5 minutes for a period of 10 minutes in 1 minute segments.

Notes: Signal-to-Noise values for UV Detectors are also reported with no acceptance limits.
The average height from the injection precision test is divided by the noise result from the above test to give a raw
signal-to-noise result. This raw value is then multiplied by 20 and divided by actual injection volume to give the signal-to-noise
normalized to a 20uL injection volume to allow comparison across systems regardless of the injection volume used in the test.
Signal-to-Noise values for FL Detectors are also reported using the automated test routine provided for each model and CDS.
The test method varies considerably between manufacturers usually using the Raman band height at 397nm found in the
wavelength accuracy test versus noise theoretically below this peak or noise in the baseline at higher wavelength than the
peak. There are numerous way to calculate the noise resulting in varied specifications for Signal-to-Noise that usually cannot be
compared from one model to another.
Summary of Test Results:
Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 16/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Test Procedures
FLD Wavelength Accuracy using Raman Band of Water
For wavelength determination in Xenon source lamp FLD: This test measures the Raman band of pure water at nominal
excitation EX 350nm and emission EM 397nm wavelength. Accuracy is calculated as the absolute difference between
the found maximum and the nominal wavelengths.

Method
Flow cell filled with pure HPLC-grade water. EX at 350 nm and EM wavelengths scanned for the Raman peak
using a method of timed EM wavelength changes starting at 393 nm in 1 nm steps per minute to 401nm. PMT
maximized to detect Raman band. Perform a repeat run with EM at 397nm and timed EX wavelengths changes
starting at 346nm in 1 nm steps per minute to 354nm. Record the heights for each step. Alternatively perform full
scan analysis of both excitation and emission if the hardware and software allows.

Notes: The above test is impossible with fluorescence detectors that use a mercury-xenon source lamp due to the strong
mercury elemental emission band at 365nm. These are often called FLR instead of FLD. In these cases use the method below.

FLR Wavelength Accuracy using Rayleigh Scattering of Water

For wavelength determination in Mercury-Xenon source lamp FLR: This test measures the found wavelength for the
mercury band of the source lamp at 365nm and the Rayleigh scattering peak at nominal 730 nm wavelength. Accuracy
is calculated as the absolute difference between the found maximum and the nominal wavelengths.

Method
Flow cell filled with pure HPLC-grade water. EX at 365nm and EM wavelengths are scanned using a method of
timed EM wavelength changes starting at 726nm in 1 nm steps per minute to 734nm at PMT gain sufficient to
detect the band. Perform a repeat run with EM at 730nm and timed EX wavelengths changes starting at 361nm in
1 nm steps per minute to 369nm. Record the heights for each step. Alternatively perform full scan analysis of both
excitation and emission if the hardware and software allows.

FLD / FLR and RID and Conductivity Detector Linearity

This test uses either: a sequence of injections of 5 identical volumes of standards of increasing concentrations or: uses
the gradient pump to fill the cell with 5 concentrations of solution created by the gradient pump.
The detector linearity is calculated by three statistical methods: The R squared of the best-fit regression line; relative
standard deviation of the response factors; difference between found slope and theoretical slope from the highest peak
expressed in %. Response factor is the peak area divided by the certified concentration (or gradient step composition).

For FLD/FLR the standard solution is Quinine Sulfate EX at 347.5 nm EM at 450 nm.
For RID the standard solution is Sucrose.
For Conductivity Detector the standard solution is a proprietary certified conductivity salt solution.

Method
The same sequence design as the UV Detector Linearity tests. If peak shape or detector sensitivity is poor the
gradient method must be used. Stainless steel restriction capillary column installed (or C18 column if customer
requests). Specific parameters for each type and model of FLD/FLR/RID and Conductivity Detector are provided to
the delivery engineer.
Summary of Test Results:
Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 17/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Test Procedures

ELSD and CAD Detector Reproducibility and Noise & Drift

Notes: ELSD and CAD usually exhibit non-linear response curves versus amount of sample and the response curve
can be specific to the sample and LC conditions. Quantification therefore requires analytical methods with multi-level
calibration curves of external standards. Instrument qualification tests are reproducibility and noise & drift.

A sequence of 6 injections of the same volume of caffeine standard is run. The detector reproducibility is reported as the
relative standard deviation, which is the standard deviation divided by the average of the peak areas and heights.

Method
Same design as the Injector Precision test. Specific parameters for each type and model of ELSD and CAD are provided to the
delivery engineer.

Gravimetric Injection Accuracy Test

The purpose of this test is to verify the injection volume accuracy of the HPLC using a gravimetric method.
The following materials will be required to perform the test: 1) HPLC Sample Vials, 2) Deionized (DI) Water, 3) A calibrated analytical balance.

Note: Water is used for this test because its density, 0.99923 g/mL at 20°C and 0.99707 g/mL at 25°C,
introduces less than 0.3% error when volume is assumed to equal to weight (grams water X 1000 = µL).
Method

1. Equip the HPLC system with a restriction capillary, purge the HPLC system with DI
water, set the flow rate at 1.0 mL/min (using DI water as mobile phase), and program the
autosampler to make full loop injections depending on installed loop same size.
2. Fill 6 HPLC sample vials with DI water and seal the vials with a septum cap. Label the
vials with the numbers 1-6.
3. Accurately weigh each sample vial and record the original weight (W1) in the results
table below. Obtain a print-out of each weighing and attach as Raw Data.
4. Place the sample vials in the autosampler and program a sequence in which one full
loop injection is taken from each vial.
5. After the sequence, reweigh each vial, and record the new weight (W2) in the result
table below. Obtain a print-out of each weighing and attach as Raw Data.

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 18/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Formulas and Chemical Standards Used in this OQ

Standard Deviation Column Oven Accuracy and Stability (°C)

∑ –
= Accuracy = abs ( ave – set)

SD = Standard deviation (same as STDEV in Excel)

ave = Average of n=6
ave = Average of n=6 set = Set point
= Value ith of measurement from n
Stability = ( – low)
Summary of Test Results: high

% Relative Standard Deviation (%RSD) high = Low temperature value

Summary of Test Results:

= High temperature value
low

% RSD =
Sample Tray Temperature Accuracy (°C)

ave = Average of n=6 Accuracy = abs ( pos – set)

SD = Standard deviation (same as STDEV in Excel)

Summary of Test Results: pos = Vial temperature at a given position
set = Set point
Squared Correlation Coefficient Summary of Test Results:

∆x = ∑ – ∑ Flow Rate Accuracy & Precision (mL/min)

∆y = ∑ – ∑ Accuracy % = abs ( ave – set) *100

set
∑ ∑ ∑
= ave = Average of n=6
∆ ∆
2 set = Set point
=
r2 = The Pearson product-moment correlation coefficient squared Precision = 100
Summary of Test Results:
of concentration vs. peak area values. [n=5]

ave = Average of n=6

Estimated Injection Accuracy (Intercept/slope) SD = Standard deviation (same as STDEV in Excel)
Summary of Test Results:
Estimated Injection Accuracy = intercept / slope
(of the best-fit regression line through the injection Detector Noise & Drift
linearity data)
Baseline NoiseNoise
= 1 + X2 + X3 ... to X10

The result is an estimate of the overall error of the

injection volume across the range reported in uL = Peak-to-trough value of noise in segment
= Number of 1 min noise segments (10)
Linearity% (areas)
Linearity% = (slope of the best-fit regression line through the 5
Baseline Drift = 1 10

data points - response factor of the highest data point) * 100

mv1 = Signal value at last segment center value
This effectively compares the found slope versus the mv10 = Signal value at first segment center value
theoretical slope drawn from the highest data point. Linearity%
is a statistic used in LabMetrix OQs.

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 19/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Formulas and Chemical Standards Used in this OQ

Detector Wavelength Accuracy (nm) Autosampler Injection Precision

Accuracy = abs ( max – set) Precision = 100

ave = Average of n=6

max = Wavelength at absorbance maximum
SD = Standard deviation (same as STDEV in Excel)
Summary
= Set point of Test Results:
set Summary of Test Results:

Detector Linearity & Carryover Autosampler Injection Linearity

Precision = 100 Precision = 100

ave = Average value of response factors (peak area / ave = Average value of response factors (peak area /
concentration). [n=5] volume). [n=5]

SD = Standard deviation (same as STDEV in Excel) SD = Standard deviation (same as STDEV in Excel)

Coefficient of determination (r2) Coefficient of determination (r2)

r2 = The Pearson product-moment correlation coefficient squared r2 = The Pearson product-moment correlation coefficient squared
of volume vs. peak area values. [n=5]
of concentration vs. peak area values. [n=5] Summary of Test Results:
All calculations and pass/fail algorithms in UOQ_LC
% Carryover (area) = 100 reports are validated. The total UOQ program is
developed, managed, validated and released
following an audited quality system. All chemical
5 = Peak area for highest concentration of caffeine (inj. 5) standards are certified. Digital temperature and flow
test devices are calibrated and certified.
6 = Peak area for blank water (injection 6)

Summary of Test Results:

Gradient Composition Accuracy and Linearity

( - X0)
% Calculated Composition = ( - X0)

= Height for the ith step. X0 = Baseline height at 0%

100 = Height at 100%

Accuracy = abs ( calc – set)

th
calc= Calculated
Calculatedcomposition
compositionfor
forthe
thei ith
step
step Standards Part Numbers:
set = Set point
UV / ELSD / CAD S-KT-0975-250 & S-KT-1975-250

Coefficient of determination (r2)

FLD S-KT-0972-250

r2 = The Pearson product-moment correlation coefficient squared of

nominal steps vs. calculated steps [n=5] RID S-KT-0973-250

COND S-KT-0400-050
Summary of Test Results:
Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 Review Protocol: OQ for LC 20/21
Summary of Test Results: 13-Jul-2017 14:33:14

Table of Contents

Customer Comments and Instructions

None.

Scope of the Protocol (Lab, Department, List of LC Systems...)

Not specified here. See separate list.

Summary of Test Results:

Protocol ID: UOQ_LC_6.07_HPLC_TPW_BAO_001

Customer
Summary Name:
of TestTEVA Pharmaceutical Works Plc.; R&D, Bioanalytical Lab
Results:

Protocol Version: UOQ LC PROTOCOL Version 6.07

 21/21

SIMPLE
ACCURATE
COMPLIANT
This back page with tag line and Revision History is in English in all language versions...

Revision History
Product Number: 09360020 A July 2011. First release UOQ-STD-LC-1.00 Product Number: 09360020 B.
UOQ-STD-LC-2.0: Released March 2012. Changes:
1. Usability and clarity improvements: Made gradient program table on page 8 of 17 a dynamic table so that any custom
changes to steps are reflected in the table. [GMP impact: None] 2. Default limit change by customer demand: Changed the default limits for carry-over to match
limits in Agilent EQP. The previous limits were set for UHPLC and twice as stringent. GMP Impact: For customers with approved Review Protocol
UOQ-STD-LC-1.00 - simply continue to use the approved protocol, engineer will import into the report engine - no change. For new customers - no impact, accept
the new default limits or use custom limit function if desired. For customers with existing approved version 1.00 review protocols who want to add other UOQ
protocols to the organization - check for consistency between labs and adjust as necessary by converting all to version 2.0 or using the custom limit function.
Product Number: 09360020 C. UOQ-STD-LC-3.0: Released May 2012. Changes:
1. Improved protocol lock function to be one-time lock cannot be re-opened. Changed due to customer demand. 2. Widened the limits for Response Linearity for
FLD and RID. Limits based on analysis of performance data of multi-vendor detectors in the field. 3. Added Response Linearity Test for Conductivity Detectors.
Product Number: 09360020 D. UOQ-STD-LC-4.0: Released Aug 2012. Changes:
1. Removed Conductivity Detectors (to be offered in separate protocol) 2. Corrected text and clarified language 3. Added noise and drift test for RID and included
reporting of automated noise & drift by CDS.
Product Number: 09360020 E. UOQ-STD-LC-5.0 Released Dec 2013 Changes:
Added page for extra set points and tests. Added Conductivity detector. Default Limit for column oven above 60C automatically adjusts to 3C (to match Agilent
specs). Improvements in test procedure descriptions made following customer inputs. Injection volume set points can be custom selected. Dynamic text in the
procedures changes to match any custom set point selections made in the specifications pages. Added standard procedures for deviations/out-of-tolerance/RQ
as pdf file attachments. UOQ-STD-LC-5.1 Released 09 Jan 2014: Added different test for FLD with mercury-xenon lamp. UOQ-STD-LC-5.2 Released 04 Feb
2014: Added noise & drift limits from latest Waters SQT. Updated page 2 text. Added a local PerkinElmer sign-off on page 1 to approve customer selections.
Product Number: 09360020 F.
UOQ-STD-LC-6.0 Released Jan 2015
UOQ-STD-LC-6.01 Released Feb 2015 Changes: added heights/areas for UV linearity test to match Waters Acquity specs; added separate specs section for
column manager devices; improved sample tray test to use 5 vials; corrected chemical std part number typo.
UOQ-STD-LC-6.02 Released Mar 2015 Changes: added caffeine @ 245nm to the extra wavelength dropdown and included all 14 nominal holmium wavelengths.
UOQ-STD-LC-6.03 Released Mar 2015 Changes: added 'MWD' to the diode-array noise list. Added 'The pump pressure is also recorded' to pump text.
UOQ LC PROTOCOL Version 6.04 Released Feb 2016 Changes: Gravimetric Injection Accuracy Test added.
UOQ LC PROTOCOL Version 6.05 Released May 2016 Changes: Updated language translation for French and Portuguese.
UOQ LC PROTOCOL Version 6.06 Released Oct 2016 Changes: FLD/FLR signal to noise typo correction.
UOQ LC PROTOCOL Version 6.07 Released Mar 2017 Changes: Gradient method description, Gravimetric Injection Accuracy Test moved to Extra test section
and Oven temperature max limitation removed.

Quality Assurance Statement:

This UOQ service product (comprising review protocol.pdf and report engine.pdf) was developed at PerkinElmer site (ISO9000 Registration Number: 19.4452).
All the calculations in the report engine validated at PerkinElmer R&D site during following a GAMP style Validation Program and the site Quality System. (This
site holds ISO17025 Accreditation No.2-5723 for temperature calibration). Adobe Acrobat is a Commercial Off-The Shelf (COTS) software available on all
Windows and IOS computers. Validation documents are available for review by customer QA Auditors and regulatory agencies at our Shelton CN or Paris,
France offices.

009179_01 Copyright ©2010-2015, PerkinElmer, Inc. All rights reserved. PerkinElmer® is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners.

Protocol Version: UOQ LC PROTOCOL Version 6.07