Welcome to our E-Seminar:

Automation Tools for Efficient Result Review According to GMP

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Overview

Chapter Page

OverviewThe sample lifecycle 6

Chromatographic data system and the sample life cycle 7

IntroductionFrom sample to result 8-9

Requirements for good quality results 10

Review stepsHow to acquire “good quality” final results 10-13

Productivity enhancements 14

Impact 15-17

Automation Network monitoring and level 4 18-20

Custom calculation and limit checks 21-22

Result review and approval 23-25

Compliance 26-29Summary 30

The sample “lifecycle”

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QC SampleAnalysis Results

Historical DataQuality Data

Certificate of Analysis

f o r

LoginNamingAttribute entryAnalysis scheduling

Result GenerationWork acceptance Analysis results

ReviewSampleRelated results

ApprovalSample

ArchiveCopy forbackup

DeleteRemovesample fromdatabase

ReopenReopen asample foradditional tests

De-archiveMove samplesback to database

opt. custom calculations

LIMS ID

SAP - QM

Overview: Where will a CDS interfere

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• CDS ( Chromatographic Data System) will focus on analyzes, and result creation, final result calculation and batch release

• CDS must be integrated in higher level corporate Data Handling solutions such as LIMS, ERP and data archiving systems

• A fully flavored CDS covers ~80% of the tasks from sample logging to final result release

• Significant productivity benefits can be reached if the user’s routine tasks are integrated into the CDS

Introduction: Routine Tasks from sample to result

Introd

uctio

n

From sample to result

22%

17%

27%

11%

17%

6%

1 Samplepreparation

2 Analyzingsample

3 Calculate finalresults

4 documentation

5 Review andrelease

6 Archive

CDS can cover steps 2-5 plus parts of 1 and 6

Introduction: Tasks from sample to result

Introd

uctio

n

• Sample preparation: Logging, assigning procedure, analytical preparation ( extraction dissolution/dilution/derivatization), scheduling

• Sample analyzes: Evaluate system suitability, prepare standards, setup batch, run batch, review analytical results ( e.g. integration,purity, identification)

• Calculate final results: calculate compound results, apply advanced calculations, compare with given limits, create final report

• Review and release: present final results to first-pass and peer reviewer, sign-off, release

• Archive: Copy/move data to external storage devices, provide and monitor archive catalogue

Requirements for „Compliant results“

• Evaluate system suitability before analysis

• Have and follow SOP for analysis

• Analyze sample and document all acquisition data

• Ensure error-free execution of analytical data acquisition

• Calculate final results

• Evaluate results and sign-off

• Document all steps from analysis to result

Introd

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n

Steps to acquire analytical raw data

Review

step

s

Analyzes

Manually evaluate hardware performance (QC samples, maintenance…)

Equilibrate system

If pass sys suit run sample batch

Manually review equilibration status

Run system suitability samples

Manually check for sys. Suit pass/fail

Have good quality analytical

raw data

Have good quality analytical

raw data

Steps to acquire final analytical results

Review

step

s

Results

Manually confirm compounds with a reference

Transfer results to calculation module

Review chromatogram

Confirm identification results

Manually review integration settings

Review data analysis results

Manually check compound identification

Complete sample-based

review

Complete sample-based

review

Execute cross sample calculations

Manually compare with limits and map to analytical results

Get good quality final results

Get good quality final results

Results – Review and Release

Document release

Analyst: Review final reports

Release batchPeer Review final reports

(Manually) add second signature

Final review

(Manually) sign reports

Lock data and move to archive Lock data and

move to archive

Review

step

s

Final sign-off of sequence

Final sign-off of sequence

Impa

ct

Productivity Enhancements

• Key to enhancing productivity is automation of manual steps

• Integrate ALL steps from analysis to final sign-off in one application

• Eliminate as much manual review steps as possible through automation

• Have system-generated documentation on all steps

• Ensure unattended operation can be monitored with system tools

These requirements do have a significant impact on the system architecture !

Overview modular software architecture

Impa

ct

Using modular software architecture and standards based technology is the basics for an integrated data system

• COM/DCOM based architecture allows for easy integration of powerful tools for special applications

• Example: Custom Calculation module integrated into Cerity

• Modular design offers combination of focussed modules to a powerful overall solution

• Communication based onTCP-IP allows ongoing system monitoring during unattended operation

Break Number 1

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Automation of result creation

Automated creation of “Good quality” data is the key to fast and efficient result review

• Automate acquisition of “good quality” analytical raw data through• Usage of network technology for ongoing system monitoring during acquisition• Benefit from level 4 instrument control for secure unattended instrument operation

• Automate “good quality” final results creation through• Combination of spreadsheet calculations for system suit and result limits with a clear result

representation• Automation compound identification based on RT and UV-Spectrum• Clear graphical coded result representation

• Use embedded calculation tools for final result calculation (e.g. content uniformity or total amount of unknowns) eliminating the need for result export/re-import

• Apply electronic signatures to all sign-off steps like in your lab notebook

Data Acquisition: Automated Instrument Failure Notification

LaboratoryOffice

Computer room

WAN

ApplicationServer

MailServer

FileServer Data

Base Hub

LAN

GCHPLC HPLC

Agilent Advisor Notified

Aut

ion

omat

• Configure maintenance limits for the system

• Integrate EMF information with each run

• EMF violations documented in instrument logbook

• Documentation of all acquisition events in the logbook

Data acquisition: Benefit from level4 instrument control

Automati

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Documentation of all instrument events in the logbook

• Online/offline information

• Communication errors

• Instrument changes

• System information such as “bottles are empty”

Data acquisition: Benefit from level4 instrument control

Automati

on

Result creation: Custom calculator

Automati

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Extra power through built-in spreadsheet calculations

• Part 11 compliance

• Full versioning of all calculation results and modifications

• Properties tab for existing columns: header and display can be modified without deleting the column

• Insert columns into an existing spreadsheet and keep all formulae

Combine the calculation power of a true spreadsheet with the compliance power of Agilent Cerity

Automati

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Result creation: Limit checks

Automation off limit checks according to your SOP with spreadsheet-based calculation tool – benefit:

•Final results are available immediately after acquisition and

•Result notifications can be reported in “eye-catching” format (free configurable)

Applied to all samples with a given marker or to a predefined subset

Automated notification

Automated user actions

SOP says:

RSD of multiple injections for comp XYZ must be below 1%

Applied to individual compounds, a group of compounds or all compounds

Result creation: Spectral compound confirmation

Automati

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Automated manual compound confirmation during initial result calculation

• Compound confirmation integrated into method-based peak identification

• Takes full benefit of DAD

• Speeds up result review

• Confirmation is optional

• Prevents manual errors and undocumented modifications

• Identifies peak based on RT AND confirms peak based on UV spectrum

• Peaks not confirmed will not be quantified

Result creation: Final result for review

Automati

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Cerity delivers results in a user friendly format ready for immediate decision

• Graphical representation of results• Color coding for quick visual result inspection• Review of overlaid and residual spectra • No interactive modification

Automati

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Result review

• Use your data system as electronic lab notebook:

• Configure e-sig to all review tasks as you do it in manual form

• Provide a reason as requested

• Sign-off analytical final results with a maximum of 3 levels

• Lock results after final approval

• Configure LIMS upload or archive depending on sign-off

Automati

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Automated Result review

•Key steps for fast and efficient result review: Automation of manual steps

Check for equilibration and sys. Suit pass/fail

Automated limit checks

Manual monitoring of system performance Automated system monitoring with level 4 instrument control incl. EMF and network system monitoring

Review of integration Remains manual Review of identification and compound confirmation

Automated compound purity and confirmation

Manual result transfer to calculations module

Not required, automated spreadsheet calculations available in the data system

Manual Execution of calculations with manual limit checks

Automated calculations and limit checks

Manual result check for pass/fail Automated clearly colour coded pass/fail display

Manual sign off after review Integrated 3 level sign off compliant with part 11

Key tools:

• Network and system monitoring systems

• Upfront maintenance and powerful diagnostics tools

• Built-in spreadsheet calculation tools…

•… combined with advanced automation “engine” and limits configuration tool

• UV spectra evaluation tools for identification and confirmation

• MS standard tools for system administration

• Integrated database archiving routines with full audit-trail

compli

ance

Audit-trail documentation

• Sign-off audit-trail

• Calculation audit-trail

Any tool is only as good as its documentation!

compli

ance

Audit-trail documentation

Any tool is only as good as its documentation!

• Instrument logbook = Acquisition audit-trail

• Results audit-trail including discarded changes

compli

ance

Long-term data Management

• Data archiving must be an integral part of the application including

• Locking and restore routine

• Full audit-trail documentation of all activities

• Tools for conflict resolution in case of duplicated records

• Allowing for linking sign-off, archive and result transfer e.g. To LIMS/ERP

Data archiving is required for compliance and for data management reasons

Summary

Summary

• Get final “good quality” results two times faster than anybody else

• Support for a paperless laboratory

• Less validation costs and highest security because of integration of latest IT technology

• Most reliable and cost-effective system: 1100 hardware and Cerity architecture reduce operation costs because they are designed for unattended 24 7/7 days operations

Using a set of advanced tools in Agilent Cerity combined with inclusion of latest technology into system design offers the quickest path from measurement to result with the following benefits