Agilent ChemStation Plus

Instrument control, data analysis and data management

Topics

Contents

Overview

ChemStation

ChemStore

Security Pack

Method Validation Pack

ChemAccess

Summary

What is ChemStation Plus?

ChemStation

Core-product for instrument control,data acquisition, simple data review & reporting

+any of the following modules;ChemStore ChemStore ChemAccess ChemAccess Security Pack Security Pack Method Validation PackMethod Validation Pack

=ChemStation Plus

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Requirements

Speeding up the advanced second-pass data review • Including statistics, custom calculations, charting with control limits

and powerful reports

Hardware related performance data• performance of each module, column quality, system suitability

trends...

Security• Data storage (raw data and results) in ChemStation Plus is

compliant with the latest rules of the FDA (21 CFR part 11)

Long-term data storage and data management• Built-in automatic archiving and backup tools help in handling

large data amounts

Analytical method validation• Automated method validation from planning to overall validation

report

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ChemStation Plus offers...

ChemStation Easy-to-use graphical user interface and full level-4 instrument control for a wide variety of chromatographic instruments.

ChemStore Increases lab productivity by providing a tool for easy management of your chromatography data in a relational database.

Security Pack Full support of your compliance needs to pass audits easily.

Method Validation Pack Automated method validation according to USP, EP, ICH and FDA guidelines following the guidelines of 21 CFR part 11.

ChemAccess

for effective management and operation of a networked laboratory by providing remote system monitoring and control, plus centralized information storage.

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ChemStation

ChemStation – Easy-to-use graphical user interface and full level-4 instrument control for a wide variety of chromatographic instruments.

Chem

Statio

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Level-4 instrument control for multiple techniques

Level-4 instrument control for:

• LC• GC• LC-MS• CE*• CE-MS*• A/D-Converter

LAN and GP-IB interfacing

Chem

Statio

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Unique level-4 features

Column ID tags for identification of the analytical column

• Micro chip stores all important columns information including an injection counter

Storage of instrument firmware revisions and serial numbers

Needed to fulfill the needs of 21 CFR Part 11

Chem

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Powerful data analysis

Batch review for first-pass data review

3D data analysis with spectra evaluation, peak purity, spectra libraries and iso-plot

Chem

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Diagnostics and EMF

Maximising instrument up-time through:

• Automatic alerts for instrument maintenance

• Minimizes cost of ownership

• Advanced 1100 instrument diagnostics for fast and easy trouble- shooting

Chem

Statio

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Fast and reliable instrument qualification

Built-in verification package (OQ/PV) allows instrument qualification in less than an hour.

Tests like wavelength calibration document the specified and actual values on paper and on disk.

Chem

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Agilent ChemStore

Database solution for single-user or networked ChemStations

Increases lab productivity in the laboratory by providing a tool for easy management of your chromatography data in a relational database.

Chem

Store

Data organization

Data organization

• Data organized in studies

• Level of data storage defined per study

• Include your own custom fields in study to add supplemental data

Chem

Store

Study-based data access and security levels

The ChemStore study

• Highest organizational element

• On a study configurable data access for users

• Data security on a study level • separate “container” for Part 11

and non-Part 11 data

• Study-based archival of data

Chem

Store

Custom fields

Custom fields

• To add supplemental ChemStation data or non-chromatographic data

• Select from a pool of custom fields

• Define new fields of type• True/false• Selection list• Integer or Real number• Text• Date/Time

• Selection list allows to specify a collection of default values

Chem

Store

Result storage

• Data transfer is set up in the ChemStore menu

• Select destination study • Define custom field values• Use “After each analysis”

for automated transfer

• Automatic data transfer after each run in single run or sequence mode, or

• Manual data transfer from Data Analysis screen

• AIA Import of data from other vendor’s system

Note: with security pack, the transfer checkmark is set by default and can not be disabled!

Chem

Store

Data review

One query result for review, charting and reporting

Chem

Store

Switch between sample- and compound-focused view

Query and filter tool

Review, table or charting view

ChemStore report template creation tool

Filter for query builder

View studies

• allows users to query for data from all studies, or

• to restrict the data shown in the query dialog to data items only contained in a specific study

Chem

Store

Control charting of results

Define columns for table view and results to be charted at the same time

Define upper and lower warning limits and critical limits

Chem

Store

Statistical results review

Get summary or regression statistics, for example, for compounds

• Customize your table to display results of interest

• Get summary statistics such as mean value, SD, %RSD or regression statistics

• Print the results or export to MS Excel

• Sort with two mouse-clicks

Chem

Store

Custom calculations

The ChemStore custom calculator facilitates:

• Cross-compound calculations (relative retention times, relative area)

• Calculations across two runs (concentration ratio)

• Calculations based on (statistical) results (average from repetitive injections)

Chem

Store

Second pass data review

Approval (A)• Records who approved results

and when• Only authorized users

Reject (R)• Records who and when results

rejected

Batch (B)• Runs to transfer back to

ChemStation

Controlled access for GLP

Chem

Store

Batch creation

Batch functions• Select runs for a batch• Select method• Assign to a person• Status of pending batches• Smooth integration with the ChemStation

Productivity gains• Faster review, reprocessing• Proper person performs the work• Easy to learn and use

Chem

Store

Report generation

Integrated tool for report creation

A variety of report templates already included

For example, full-featured report similar to ChemStation Sequence Summary Report

• Chromatogram and spectra in report• All calculations printed with report

Chem

Store

Automated archiving

Automated archiving

• Scheduled automatic archives

• Pre-defined queries andtime intervals

• Checksum-protected XML catalog file

• Bi-directional generic archive interface

List of defined archive queries

Chem

Store

External archive management system

Defining archive queries

Selected set of criteria: archive query equals combination of criteria

Archive name and file location

Archive query condition

Archive frequency

Chem

Store

XML archive catalog

Easy and fast retrieval of archives

Generic XML catalog file

• For indexing of archives in archive management system – simplifies retrieval

• Generated with each ChemStore archive unit

• Contains detailed information on the archive content:

• sample information (sample name, acquisition info)

• result information (results, approval status)

(or other external archive management system)

Managing ChemStore archives in Cerity ECM

Chem

Store

TOC

Security Pack

For full support of your compliance needs to pass audits easily

Your information

Reporting

Charting

Calculations and statistics

Security and compliance

Archiving and organization

Secur

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21 CFR Part 11

• Limit Access• Prevent data

modification

• Change control• Link Raw Data

and Results

• Who did what when and why?• Previous entries must not be obscured

Security Integrity

Traceability

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Part 11 Technical ControlsSecur

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• §11.10a Systems must be validated (P)

• §11.10b Accurate and complete copies (T)

• §11.10c Protection of records (P,T)

• §11.10d Access limited to authorized individuals (P,T)

• §11.10e Secure, computer-generated, time-stamped audit trail (T)

• §11.10f/g/h Checks (device, authority, system checks) (T)

• §11.50 Signature manifestations (T)

• §11.70 Signature/record linking (T)

• §11.100 Uniqueness of E-signature to individual (P,T)

• §11.200 E-signature components and controls (P,T)

• §11.300 Controls for identification codes and passwords (P,T)

P = Procedural controls (usually the responsibility of the pharmaceutical company to develop)T = Technical controls (usually the responsibility of the supplier to develop)

General rules for paperless record systems

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1. Appropriate control procedures for the laboratory (SOPs)

2. System that fulfills the FDA guidelines for electronic records and electronic signatures

1 + 2 = General rules for implementing a paperless record system

System Validation (§11.10a)Secur

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“The systems used for the creation and maintenance of the electronic records must be validated”

1. Validation by the vendor• Development qualification

2. Validation by the user• Formal acceptance testing

• Installation qualification

• Operational qualification (OQ/PV)

• Performance qualification

Users may outsource validation services to the vendor

System validationSecur

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Agilent validation services

• Installation Qualification (IQ)

• Operational Qualification (OQ)

• Procedures and documentation that meet the requirementsof GLP, ISO 9000 and other regulatory agencies

Limited system access (§11.10d)Secur

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“System access must be limited to authorized individuals”

1. Procedural controls (SOP‘s)

2. Automatic system controls

Managing access securitySecur

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What?• Accounts/groups?

• Password security?

• File security?

• Set inactivity timeout?

How?• Windows user management!

• Windows password policy!

• NTFS permissions!

• Time-based application lock!

User management

User management

• Mandatory login

• Complements NT security scheme

• Password policies with automated account lockout, expiry date and minimum length

• Users must be set up for access to the database

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Session locking

For periods of unattended operation security pack provides for:

• Explicit lock function• Private session locking when

leaving the session unattended such as during a break

• Non-private session locking such as for shift changes

• Configurable inactivity timeout

• Releasing requires authentication with both user ID and password

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Record protection (§11.10c)Secur

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“Records must be protected to enable accurate and ready retrieval throughout the record retention period”

Sign Secure Maintainintegrity

Retrieve

Linking and versioning

Data integrity is ensured by storing all results, raw and meta data (sequence, method, etc.) in a relational database

• Data can be buffered on acquisition PC

• Each version is added to the record - iterations are stored as revisions in the database

• Transfer is documented and checksum protected

No data is ever overwritten!

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Data integrity

Data integrity equates to secure, version-controlled, unbreakably linked and centrally stored data

• No data is ever overwritten

• All calculated results are stored as individual revisions in the database

• All revisions are automatically linked to original injection run

• No deletion of single run versions possible – either all versions or none

• Audit-trail documents all versions with timestamp and operator ID

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ChemStore spooler

The ChemStore spooler works like a printer spooler:

• Prepares the background data transfer

• Buffers the data if a transfer problem occurs

• Can be paused and resumed

• Removes the buffered data from local drive after successful transfer

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Audit trail (§11.10e)Secur

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“Secure, computer-generated, time-stamped audit trails must be used”

Who did what, when and why?

Results audit trail

PrintableIncludes manual integration details

Includes change history Time-stamped (local time zone information)

Computer-generated & user-independent

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Database logbook

Executing user and time stamp of activities

Event Affected user Application and client details

Query for specific events

Access to event details

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Logbook documents application-related activities that are relevant to security and data integrity. For example, the administrator removed access restrictions for the guest account.

Check for data access status: detailed modification of permission rights

Database logbook event details

Query all entries for the relevant setting:the time interval, the user and affected user plus the reason for the entry

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Run information screen

Injection information

Processing information

Data storage

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Direct access to audit-trail, instrument and column configuration

Restore raw and meta data to a human-readable format

Checks (§11.10 f/g/h)Secur

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Checks

• Limit system access to authorized users

• Check permitted sequence of steps

• Check authorization of users

• Written policies to hold users accountable for their actions and signatures

Authority checks (§11.10g)

Logon to the application:

• User must exist as a system user

• Requires valid user-name/password combination

• Access level determined by individual permissions

• Logon is independent of user who logged on to the operating system

• Independent sessions can have individual users

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Authority checks (§11.10g)

Setting up new users

Use standard profiles template, or define individual user profiles

Define ChemStation access level and command line access

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Define which database actions the user is authorized to do

System checks (§11.10g)

Formal result review/approval

For approval,user must provide:

• User-ID

• password

• mandatory signature meaning

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Device checks (§11.10g)

Links instrument with data acquisition PC

“… determine (…) the validity of the source of data input or operational instruction.”

Traceability of instrument configuration

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Accurate and complete copies (§11.10b)Secur

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“The system must allow the creation of accurate and complete copies of the electronic record in human readable as well as electronic format for inspection and review by the FDA”

The system should support standard file formats that allow inspection of the data on another system.

Accurate and complete copies

… of an e-record in both human readable and electronic format:

• Archive/restore for long-term storage in electronic format

• Printouts on paper, screen or to file as human-readable copy

• Checksum protection of exported data to ensure data integrity

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Archive and restore

Archive and restore

• Only authorized users can archive, restore, or delete data

• The data of each analysis data is archived as one unit including all result versions

• Use standard queries to define the archive contents

• Archive log is maintained

• Password reentry control for archive, dearchive, or delete

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Data export

Export to clipboard (for graphics) or xls format

Database reports on paper or to file (htm, csv)

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Electronic signature

§ 11.200(i)

“When an individual executes a series of signings during a single, continuous period of controlled system access, the first signing shall be executed using all electronic signature components”

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Security violations

§11.30(d)

“Instant notification on unauthorized access to the central database from any ChemStation Plus client”

Email notification of account lockout!

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Signature and record linking (§11.70)Secur

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“Electronic signatures … shall be linked to their respective electronics records to ensure that (they) cannot be excised, copied, … to falsify an electronic record by ordinary means”

• Design ensures referential integrity between raw and meta data and result versions

• Audit trail and signature information cannot be manipulated

• Strict revision control of all records maintained by the system

Unique electronic signatures (§11.100)Secur

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“Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else”

• Requires procedural controls in the organization

• Is typically handled by HR and IT departments

• IT policies ensure that combinations of user ID and passwords are unique and periodically revised

Components and controls (§11.200)

The rule requires stringent controls to prevent impersonation

• Logon is mandatory (User ID and password)

• Session can be locked interactively

• After a defined inactivity period, sessions are locked automatically

• User ID and password are required to release a locked session

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Method Validation Pack

ChemStation Plus Method Validation Pack for automated method validation according to USP, EP, ICH and FDA guidelines, including 21 CFR part 11

MVP

The ChemStation Plus design

Method Validation Pack

• A ChemStation Plus module

• Based on ChemStore relational Oracle database

• Delivered with built-in support of FDA requirements (21 CFR Part 11)*

For detailed information on features and configuration see ChemStation Plus specifications (Pub No. 5988-8606EN)

* Requires ChemStation Plus Security Pack

MVP

Strategy for method validation

Document validation

experiments and results

SST AQC

SOPs Prelim. Tests

Materials TrainingDefine Purpose

Validation Plan

Iterative Process

MVP

Method validation requirements

Method validation requires:

• Cross instrument and cross-technique data management

• Full validation of tools and result creation

• An iterative process of definition/design, execution, result creation

• Flexibility to address different guidelines such as published by the USP, ICH, FDA

Method validation pack provides:

• Full integration of data acquisition and analysis for all instruments*

• Convenient import capabilities for data from other sources**

• A fully validation solutionfrom Agilent

• One software for validation planning, data acquisition, review and reporting

• Built-in statistics and preconfigured tests based on regulatory guidelines from the USP, ICH, FDA (including 21 CFR Part 11)

* controlled by ChemStation** not controlled by ChemStation

MVP

Method validation requirements

Method validation requires:

• All validation data stored in a central location

• One overall validation report

• 21 CFR Part 11 compliance

Method validation pack provides:

• Central data management of all validation data in a hierarchical, compound-centric structure

• A single detailed, customizable validation report for all data included with the validation

• In combination with ChemStation Plus Security Pack full support of all 21 CFR Part 11 requirements

* controlled by ChemStation** not controlled by ChemStation

MVP

Method Validation Pack workflow

ChemStationMethod

ValidationPack

ChemStore Database

Dynamic study creation and update

Compliantstorage of raw and meta data

Integrated sequence generation

Createvalidationreport fromdatabase

3

1Createvalidationtemplate

2Run sequenceto acquire data

MVP

Regulations and guidelines for method validation

Method Validation Pack supports

• ICH Q2A/Q2B• Selectivity / Specificity• Precision• Accuracy • Linearity• Limit of Detection / Quantification• Robustness / Ruggedness• Stability (short-term)

• ICH Q1A • Stability (long-term)

• FDA’s 21 CFR Part 11*

• Various DIN/ISO guidelines• Lab Capability• Calibration Function• Ring Experiment

* Only in conjunction with ChemStation Plus Security Pack

MVP

ChemAccess

For effective management and operation of a networked laboratory by providing remote system monitoring and control, plus centralized information storage.

Chem

Acces

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Windows 2000 Server

Data analysis ChemStation (offline)

MS ChemStation

GC/LC/CE/LC-MS ChemStation

Overview

PC-anywhere for the analytical lab

• Remote instrument status

• Remote real time plot

• Remote instrument method and sequence control

Centralized data storage

• Data file organization on the server

• Remote data review

• Centralized data backup

Chem

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User interface

Graphical view organized by:

• Group• Used to logically separate laboratory organization

• WorkStation• Represents ChemStation

• Instrument• Displays online instruments interfaced to

workStation

• Menus accessed by right mouse button

WorkStation status

• View name & selectable status• Disk space, memory, resources,

Windows/ChemStation versions

• Full panel includes network ID

• User access security defined for each workstation

Chem

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Instrument status

Individual instrument status information:Individual instrument status information:

• View name & two selectable status lines

– ChemStation/Method Status, Runtime, Current Sequence/ Method, Data File

• Instrument status depicted by colors

• GreenGreen for Ready

• YellowYellow for Not Ready

• RedRed for Error

• PurplePurple for Pre-Injection

• BlueBlue for Running

• Remote real-time plot

• Detailed instrument status panels available from this menu

Chem

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Instrument status screensChem

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Remote real-time plot

User may remotely monitor available signals delivered by the selected instrument

Function supported by both stage 1 & 2 instruments

Security access defined at instrument signal source

Chem

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Remote single-run control

Load Method – Lists the methods found in the ChemStation’s default directory

Start Method – Starts the instrument with the currently loaded method

Stop Method – Stops the current run

Chem

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Remote sequence control

Load Sequence

• Lists the Sequences found in the ChemStation’s default directory.

Available Sequence Controls

• Start, Stop, Pause and Resume

Chem

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Data transfer properties

Administrator configures file transfer properties for each instrument

Properties are viewable, but not editable by users

• Keep Versions maintains data integrity when re-analyzed

• Delete File after Copy keeps local drive clean & available

• Write Protect File secures original data from accidental deletion

• Copy Method/Sequence to Data Directory maintains instrument conditions & method parameters with data, results and reports

Chem

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Server data storage

Administrator configures server storage for each instrument

Master path configuration defined on server

• Administrator sets fixed path components

• Client user can set path components which are enabled and not fixed

• Client user can set new path components that are creatable and not fixed

Chem

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Summary

ChemStation Easy-to-use graphical user interface and full level-4 instrument control for a wide variety of chromatographic instruments.

ChemStore Increases lab productivity by providing a tool for easy management of your chromatography data in a relational database.

Security Pack Full support of your compliance needs to pass audits easily.

Method Validation Pack Automated method validation according to USP, EP, ICH and FDA guidelines following the guidelines of 21 CFR part 11.

ChemAccess

for effective management and operation of a networked laboratory by providing remote system monitoring and control, plus centralized information storage.

Summ

ary