Using Empower SystemsQT Qualification Tool

for Waters Modular HPLC Systems

A summary of Empower SystemsQT

Qualification Tool features and
benefits, with emphasis on the
technical attributes of the
qualification tests.
G x P1 Com p lianc e Qualification data and records are still required for fully automated
Regulatory agencies continue to require documented evidence systems but qualification processes have needed to evolve to meet
(electronic and written) that responsible companies and persons these new challenges.
can consistently generate quality products with supporting
Throughout all the evolutionary changes to system qualification
analytical data.
processes, the roles of the involved participants have
Analytical systems have become more automated and generate remained constant.
analytical data that is managed by sophisticated software programs.
n Company (System owner) management is still responsible for
While automated analytical systems require less operator involve-
the overall use, operation and integrity of analytical systems
ment to produce data, it is worth noting that routine involvement
and generated analytical data. During the process of qualifying
of a designated responsible person(s) to ensure continued system
analytical systems for use in a GxP regulated environment,
performance is still required.
owner management (Approver) is responsible for designating
Regulated companies are constantly balancing expenses to a qualified company individual to oversee qualification
maximize shareholder value as well meeting product quality and processes (Reviewer) as well as approve qualification results
regulatory compliance requirements. The constant quest for reduced and the qualification Performer.
expenses may target analytical system qualification (performance
n The Reviewer is responsible for ensuring the Performer
verification) and maintenance as means to decrease laboratory
follows the company approved protocols and has completed
operating costs. Short cuts in such areas can result in erosion of
all maintenance, qualification testing, and documentation.
system performance with accompanying analysis and product errors
which may result in regulatory compliance problems and loss of n The Performer is a trained and owner management approved

corporate reputation. system maintenance and qualification services specialist who

can successfully complete all required qualification processes.
To assist customers in meeting their regulatory requirements as well as
meeting laboratory throughput and system uptime objectives, Waters
has created an extensive portfolio of regulatory compliance products Traditional Paper-Based Qualification Processes
and services. Empower Software system qualification (SystemsQT) Tied to the evolution of chromatographic systems, Waters qualifica-
tools, chemical test solutions kits, qualification workbooks, and Global tion services has kept pace with the production of Qualification
Services are all focused on ensuring customer success. Workbooks, chemical test kits, and software qualification tools.

Paper-based qualification processes, while being used successfully

for many years, share many of the same problems as do manual
The E volut ion of Ch romatog ra p h y
system control and data acquisition processes.
Syst em Qua lific at ion
As HPLC and now UPLC® and LCMS systems evolve into highly 1. Paper records present archival challenges: storage logistics,
automated, computer software controlled systems, so too is the record management, and record retrieval/access issues.
need to verify performance in an “as used” system configuration. 2. Risk of human error in testing, calculations, and documentation.
With the growing acceptance of Waters Empower Software as the 3. Metrology-type testing of modules in a non-“as-used”
preferred chromatography laboratory platform, adding systems configuration.
qualification capability extends its value and benefits to GxP
regulated laboratories.

When non-automated HPLC systems were comprised of individually

programmed and controlled modules, there was a need to verify the
performance of each individual component. Individual component
performance verification, in terms of accuracy and linearity is
called OQ or Operational Qualification. Following the successful
completion of module OQs, the total system performance is verified
in terms of precision as vendor Performance Qualification (PQ).

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Please Note Waters Empower SystemsQT Features and Benefits
While paper-based qualification processes have issues, there are 1. Built-in option to a validated chromatography control and
and will be instances when such processes are required to complete data system, which is switched on as required, not a third-
system qualification. With the addition of specialized detectors party program.
to UPLC and HPLC systems as well the continued requirement of 2. Eliminates most manual calculations and decisions to reduce
metrology-type testing of some physical parameters for automated human error opportunities as well as provide much faster
systems, a paper or electronic workbook-based process may be system testing.
required to supplement automated qualification processes. 3. Qualification processes can be managed as electronic records.
4. All system control, data collection (acquisition, processing,
Automated HPLC and UPLC Systems Qualification reporting, archiving) are auditable.
Older, automated HPLC systems can continue to utilize paper-based 5. Uses validated chromatographic methods to test and verify
qualification processes. But in light of today’s laboratory regulatory total system performance.
and efficiency challenges, automated system qualification tools are 6. Designed to provide means to integrate metrology-type test
receiving much more focus and acceptance. methods where required. The Waters Compliance Specialist
will transfer DVD-based manual test protocols to a customer’s
location of choice. Typically such manual tests are run
and documented before running the automated Empower
SystemsQT tests.
7. Waters Compliance Specialists are trained and certified to per-
form all system testing, maintenance, and documentation for
both traditional workbook-based processes and for Empower
SystemsQT automated qualification.

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Empower SystemsQT Qualification Tool versus Paper Workbook-Based Qualification Processes
Empower SystemsQT Processes Paper Workbook Processes

Responsible Person Owner management designated responsible ‘approver’. Same

Qualification Performer Trained, certified and owner management approved qualification and Same
system service expert.

Approval / sign-off process Electronic record or summary page print out sign-off. Performer initials and dates each results page.
Approver signs and dates summary page.

Qualification documents Empower / Empower 2 software validated projects. Waters Compliance Comprehensive workbook containing IQ, OQ, PQ and
Specialist (Performer) provides DVD-based projects and documents as maintenance instructions, procedures, results logs and
required for testing. Storage binder supplied for hard copy sign-off sheets. sign-off pages for each system module. Storage binder
supplied for workbook archiving.

Qualification test chemicals Ready-to-use, certified test chemicals in accordance with sample Ready-to-use, certified test chemicals to be manually
manager loading instructions. used in accordance with workbook instructions.

Calibrated test equipment As required, calibrated measurement devices provided by Waters As required, calibrated measurement devices provided
Compliance Specialist (Performer). by Waters Compliance Specialist (Performer).

New system Installation Empower / Empower 2 Acquisition Node provides system configuration for Performer written insertion of system configuration,
Qualification (IQ) inserting serial number, location, purchase information for either electronic serial numbers, location, purchase information with
record sign-off or print out for manual sign-off and binder insertion. initials and dates on workbook form pages.

Operational Qualification If required, (for specialized detector and physical parameter testing), load Performer follows workbook instructions and procedures
(OQ) and system Performance DVD-based protocols and follow instructions for manual procedures. for test chemical preparation, test equipment use,
Qualification (PQ) individual module testing, system preparation, and
For system testing, select Empower qualification project, follow system total system testing.
preparation instructions, load test chemicals in specified sample manager
locations and run automated qualification tests. Performer makes pass/fail decisions for all tests, signs
and dates all result forms, and has Reviewer approve
SystemsQT will analyze chromatographic results and, through the use of and signs-off completed document.
Boolean custom fields, provide a pass/fail decision for all test parameters.
Completed workbook chapters are inserted into
Reviewer approves qualification results. Performer and Reviewer sign-off storage binder.
either electronic record or hard copy of summary report.

Hard-copy sign-off sheets filed in supplied storage binder.

Failed Test Result Process SystemsQT will identify failed test. Performer will stop module /system testing when an
individual test fails.
Performer will then investigate system problem, either provide repair(s)
or, more likely, ensure system passes all performance diagnostics and Performer will then investigate system problem, either
re-run test injections and failed qualification test. provide repair(s) or, more likely, ensure system passes all
performance diagnostics and re-run failed qualification
Performer will log required maintenance. test. The performer will then continue qualification testing.

Pre-OQ & PQ Maintenance For existing systems, maintenance must be performed prior to running Performer will log required maintenance.
Processes system qualification.

Recommended maintenance procedures are DVD- based and are elec- For existing systems, maintenance must be performed
tronically transferred to owner’s management location of choice. prior to running system qualification.

Maintenance information report is inserted into qualification binder. Individual maintenance chapters are supplied with each
module’s qualification workbook.

Maintenance information report is inserted into

qualification binder.

Archiving System Qualification System qualification and maintenance records should be stored in a safe System qualification and maintenance records should be
& Maintenance Records place that makes them easily available for inspection. stored in a safe place that makes them easily available
for inspection.
SystemsQT records can be stored as electronic records or as hard copy
signed-off summary reports that can be stored in the supplied binder. Completed and signed-off workbooks can be stored in
the supplied binder.
Empower search capabilities can be used to locate records easily.

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Empower SystemsQT Pass / Fail Processes CGMP / GLP validation as well as global pharmaceutical, cosmetic,
For automated system qualification, SystemsQT employs the and food regulatory compliance groups. Customers using Waters
appropriate sample sets in Empower Software to acquire data in regulatory compliance products (workbooks and SystemsQT) have
Run Samples. Appropriate statistical analysis is applied to the been achieving successful system audits for over fifteen years.
results to provide standard deviation, %RSD, R linearity etc.
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The portfolio of qualification tests utilized by Waters is designed to meet
results. Custom Boolean Fields are applied to the final results to
or exceed all regulatory agency requirements. Testing of parameters
determine test pass or fail.
that are connected to a specific analytical method and not the analytical
system are not included in Waters qualification processes.
Non-Standard System Qualification Tests and Processes
The development of Waters Global Compliance Services and Products If custom qualification tests and services are required, please
included reviews and input by key experts in the USA Department of contact your local Waters service management team or Global
Health and Human Services (US FDA) inspection branch, international Compliance Services Marketing.
Ministries of Health experts, internationally recognized experts in

Qualification of 1525/1525µ HPLC Pump and 2707 Autosampler Systems with 2489 or 2998 Detector using
Empower SystemsQT Qualification Tool

A 1525/2707 System includes:

A 1525 Binary HPLC pump or a 1525µ Micro Binary HPLC Pump with a 2707 temperature controlled autosampler plus detector option
which can be:

n A 2489 Tunable UV/Visible (TUV) Dual Wavelength Detector or a 2998 Photodiode Array (PDA) Detector

Plus other system options that can include:

n A 1500 series column heater

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Empower SystemsQT processes for qualifying a 1525 / 2707 HPLC System with a UV Detector are as follows:

Manual OQ Tests Performed OQ Tests From SystemsQT Projects/Documentation DVD OQ Test Methods
before running Automated
SystemsQT Tests 1. Temperature verified using calibrated temperature probe.
1. Autosampler Temperature Accuracy.

2 Column Heater Temperature Accuracy. 2. Temperature verified using calibrated temperature probe.

System Preparedness Test 1. Test Injections – These are not considered part of the 1. Replicate test sample injections to verify system is equilibrated and
qualification test suite. ready to commence.

1525, 2707 UV Automated OQ & PQ Tests Running Empower OQ & PQ Test Methods
OQ & PQ Tests Project Sample Sets

1. System Precision Test. 1. System precision (standard deviation and %RSD of peak retention
times, peak areas, and heights) is verified by making replicate injec-
tions of test sample.

2. (A) PDA detector wavelength accuracy test. 2. (A) Wavelength accuracy is determined by scanning spectra and
verifying lambda maximums of well characterized compound falls
within specifications.

(B) TUV detector wavelength accuracy test. (B) Wavelength accuracy is determined by the wavelength of
the highest peak from several injections of well characterized
compound.

3. Carryover test. 3. Sample carryover is determined by running blank injections follow-

ing an injection of a concentrated sample.

4. Detector linearity and sensitivity test. 4. Detector linearity is determined by using a fixed injection volume of
varying sample concentrations to generate a plot of peak height and
area versus sample amount.

Sensitivity is determined by dividing peak height and area by

sample amount.

Pass/fail is based on R2 of the plot and %RSD of sensitivity values.

5. Injector linearity and accuracy test. 5. Verifying a linear response from variable injection volumes of a
fixed sample concentration. Accuracy is determined from x intercept
of injection volume plot.

6. Flow rate linearity and accuracy test. 6. Flow rate linearity is determined by plotting the inverse of peak
retention time versus the flow rates. Flow rate accuracy is deter-
mined from the X intercept of the plot.

7. Sample positioning test. 7. Successful completion of all of the above tests signifies proper
sample positioning capabilities.

Qualification of1525/1525µ HPLC Pump and 2707 Autosampler Systems with a 2414, 2410, 410 or 2475
Detector using Empower SystemsQT Qualification Tool

A 1525/2707 System includes:

A 1525 Binary HPLC pump or a 1525µ Micro Binary HPLC Pump with a 2707 temperature controlled autosampler plus detector option
which can be:

n A 2414, 2410, or 410 Refractive Index (RI) Detector or a 2475 Fluorescence (FL) Detector

Plus other system option that can include:

n A 1500 series Column Heater

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Empower SystemsQT processes for qualifying a 1525 / 2707 HPLC System with a RI or FL Detector are as follows:

Manual OQ Tests OQ Tests From SystemsQT Projects/ OQ Test Methods

Performed before Documentation DVD
running Automated
SystemsQT Tests 1. Flow rate accuracy (1525/ 2475 systems). 1. Flow rate accuracy verified by timing collection of fixed volume.
2. Autosampler temperature accuracy. 2. Temperature verified using calibrated thermometer.
3. Column heater temperature accuracy. 3. Temperature verified using calibrated thermometer.
4. Wavelength calibration (2475 only). 4. Calibrates detector wavelengths to internal erbium filter wavelengths.
5. Emission units normalization (2475 only). 5. Sets a common detector sensitivity based on Raman water band energy.
6. Raman signal-to-noise (2475 only). 6. Uses Raman water band light scattering reading to verify signal-to-noise is within
specifications.

System Start Up 1. Sample set that purges injector and RI 1. Purges and equilibrates system.
(RI Detector Only) detector and equilibrates system.

System 1. Test Injections – These are not considered 1. Replicate test sample injections to verify system is equilibrated and ready to commence.
Preparedness Test part of the qualification test suite.
1525, 2707 RI Automated OQ & PQ Tests Running OQ & PQ Test Methods
OQ & PQ Tests Empower Project Sample Sets
1. System Precision Test. 1. System precision (standard deviation and %RSD of peak retention times, peak areas and
heights) is verified by making replicate injections of test sample.
2. RI detector sensitivity test. 2. Sensitivity is determined by injecting fixed injection volumes at different sensitivity settings
and dividing the peak area by the sensitivity setting.
3. RI detector linearity and plate 3. Determines that response is linear within the specified range. Fixed injection volumes of
positioning test. different concentrations of test sample, provides the coefficient (r2) of detector response
versus sample amount. Proper function of autosampler plate positioning is verified during
linearity test by injecting from vials in different plate locations.
4. Injector linearity and accuracy tests. 4. Verifying a linear response from variable injection volumes of a fixed sample concentration.
Accuracy is determined from x intercept of injection volume plot.
5. Flow rate linearity and accuracy test. 5. Flow rate linearity is determined by plotting the inverse of peak retention time versus the flow
rates. Flow rate accuracy is determined from the X intercept of the plot.

1525, 2707 FL Automated OQ & PQ Tests Running OQ & PQ Test Methods

OQ & PQ Tests Empower Project Sample Sets
1. System Precision Test 1. System precision (standard deviation and %RSD of peak retention times, peak areas and
heights) is verified by making replicate injections of test sample.
2. Emission wavelength accuracy test. 2. Emission wavelength accuracy, is verified by determining that the lambda maximum of test
sample peak falls within specifications.
3. Excitation wavelength accuracy test. 3. Excitation wavelength accuracy, is verified by determining that the lambda maximum of test
sample peak falls within specifications.
4. Carryover test. 4. Sample carryover is determined by running blank injections following an injection of a
concentrated sample.
5. Linearity, sensitivity, and plate 5. Detector linearity is determined by using a fixed injection volume of varying sample
positioning test. concentrations to generate a plot of peak height and area versus sample amount. Sensitivity
is determined by dividing peak height and area by sample amount. Pass/fail is based on R2 of
the plot and %RSD of sensitivity values. Proper function of autosampler plate positioning is
verified during linearity test by injecting from vials in different plate locations.
6. Gain linearity test. 6. To verify detector gain linearity performance, replicate injections of fixed volume and concentra-
tions are run at different gain settings and plotted. Gain sensitivity is determined by dividing
peak area/height by the gain amount. Pass/fail is based on %RSD of gain sensitivity values.

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References
1. GxP refers to all government required good laboratory operating prac-
tices including, Current Good Laboratory Practices (CGLP), Current Good
Manufacturing Practices (CGMP), Current Good Automated Laboratory Practices
(CGALP), Current Good Clinical Practices (CGCP) as well as other regulatory
agency required practices.

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