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Agilent Solutions for achieving 21 CFR 11 Compliance on Atomic Spectroscopy Instrumentation Page 1 Jon Talbott, PhD Application Scientist
Agilent Solutions for achieving 21 CFR 11 Compliance on Atomic Spectroscopy Instrumentation
Page 1
Jon Talbott, PhDApplication Scientist
Spectroscopy Products currently supported with Compliance Solutions1. ICP-MSs (7800, 7900,
8900 and older units)
2. ICP-OES (5110)
3. GFAAs and Flame AAs(240Z, 480, 240FS)
Spectroscopy Products currently supported with Compliance Solutions - continued
4. Cary Win UV-Vis Spectrometers(8453 and Cary 60)
5. Dissolution InstrumentsUV DissolutionUV Fiber Optic
(Cary 60 w/ Multicell shown)
5. MicroLab
Agilent ICPMSs: 3 Features for « Pharma » Applications1) Matrix tolerance 2) Interferences removal 3) Wide Dynamic range
Ultra High Matrix Introduction System (UHMI)
Able to analyze high total dissolved solids (up to 25%)• Reduces sample prep time
and error• Better long-term stability
Octopole Reaction System (ORS3) – Helium Mode
He mode removes all polyatomic interferences• Easy to use - He collision
mode only • Effective for a wide range of
sample types
Wider Dynamic Range
11 orders of dynamic range• Simplifies method development• Easy sample prep. • Improves productivity
ICP-OES Agilent 5110: Benefits for USP <232> <233>
1) Matrix tolerance 2) Synchronous Axial and Radial Viewing
3) Interference removal
Vertical Torch
Able to analyze high total dissolved solids ( > 25%)
Background Correction and Interference Removal
FBC Fitted Background Correction FACT Spectral Deconvolution
Dichroic Spectral Combiner
Compliance for Elemental Impurities, Why Needed? USP Heavy Metal Chapters – Current and Planned
<2232>
Heavy Metals Limit Test
<233><232>
ElementalImpurities(Limits)
ElementalImpurities
(Procedures)
ElementalImpurities in
Dietary Supplements
Terminology changing:“Heavy Metals” “Elemental Impurities”
Is being replaced with:
Page 7September 26, 2017
Related method <2232> applies to dietary supplements only
<232> will eventually replace other “metals” General Chapters
<251>
<231>
Lead
<211>Arsenic
<261>Mercury
September 26, 2017
Confidentiality Label
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ICH Class Element Symbol ICH (ug/day) Oral PDE
Class 1 Arsenic As 15Cadmium Cd 5Mercury Hg 30
Lead Pb 5Class 2A Cobalt Co 50
Nickle Ni 200Vanadium V 100
Class 2B Silver Ag 150Gold Au 100
Iridium Ir 100Osmium Os 100
Palladium Pd 100Platinum Pt 100Rhodium Rh 100
Ruthenium Ru 100Thalium Tl 8
Selenium Se 150Class 3 Barium Ba 1400
Chromium Cr 11000Copper Cu 3000Lithium Li 550
Antimony Sb 1200Tin Sn 6000
Molybdenum Mo 3000
• PDE’s apply to final products• Drug Substances• Excipients
• Does not apply to vaccines• Does not apply to veterinary
products• Does not apply to dietary
supplements• Testing is based on risk-based
assessment• Compliance is required with all
the limits throughout the life of the product
USP/ICH Oral PDE Limits
PDE Limits depend upon Route of Entry
What is FDAs 21 CFR Part 11 Compliance Chptabout? It is just 4 pages of the Code of the Federal Register!
Regulations for Pharma, Food, CROs, anyone sending Sx data to the FDA
What is FDA 21 CFR Part 11 Compliance Chptabout? Legalese to address …
Electronic Records (Sample DATA in electronic format)• Their management, storage,
authenticity, integrity, confidentiality and retrieval
ValidationofSystems (Instrument IQ/OQ/PQ)Limiting Access to systems to authorized individuals (User Access Control)
Protection of Records (Data)Secure Time Stamped Audit TrailsRecords shall not obscure preciously recorded information (version control)
Authorized IndividualsElectronically signed DataSOPs, Training
FDA 21 CFR Part 11 Compliance Chpt: Summary of Four Key Categories of Criteria1. Instrument Qualification Procedures and Documentation
– Instrument design qualification (DQ), lifecycle management, Installation and Operational Qualification (IQ/OQ) for analytical instruments + Software and Performance Qualification (PQ)
2. Access control of instrument and data processing limited to authorized individuals, eSignature with audit trail of user log-on/log-off and actions– User Access Control (UAC) on Agilent ICP-MSs – Spectroscopy Configuration Manager (SCM) on ICP-OESs
3. Electronic records management, secure data storage, version control, archival and retrieval of data records– SDA (Spectroscopy Database Administrator) – Data Store– OpenLab ECM (Enterprise Content Manager)
4. Physical access control (e.g. lab access), standard operating procedures– Making the lab “compliant” is the responsibility of the user, using the
tools and software the vendor provides
Application software+ 4 Qs
Graphical Representation of Key Categories of Agilent Solutions for 21 CFR Part 11 Compliance
Data Management
Control the instrument for data acquisition and processing
ICPExpert or MassHunter
Administration of databases and data, records integrity, security and retention
SDA, OpenLab ECM
+ +
Access Control
Manage groups, projects, users and user profiles, e-sigs and Audit Trail
SCM or UAC
2nd Category 3rd Category1st Category
Agilent Solution for First Category of 21 CFR 11- 4 Qs: Design Qualification, Installation and Operational Qualification (IQ/OQ)
PQ is customer’s responsibility• Agilent’s compliance products and services includes Installation
Qualification and Operational Qualification for Hardware and Software,• Documentation of IQ/OQ
IQ/OQ (Installed correctly/ Work as expected)Hardware & Software
IQ checks if the system is installed correctly prior to initial utilization:• Operating environment• Physical connection• Safety• Functional parameters
OQ defines functional tests and compares them against Agilent specifications.
IQ/OQ performed jointly with customer representative
Example OQ Tests for ICP-MS
Example OQ Tests for ICP-OES
Agilent Solution for First Category of 21 CFR 11- Design Qualification, Installation and Operational Qualification (IQ/OQ)
• Agilent’s compliance products and services includes Installation Qualification and Operational Qualification for Hardware and Software,
• Documentation of IQ/OQ
Application software
21 CFR Part 11 – 2nd Category of CriteriaUser Access Control & Electronic Signatures
Data Management
Control the instrument for data acquisition and processing
ICPExpert or MassHunter
Administration of databases and data, records integrity, security and retention
SDA, DS or OpenLab
+ +
Access Control
Manage groups, projects, users and user profiles, esigs and Audit Trail
UAC or SCM
User Access Control SW on ICP-MSs for 21CFR11 Compliance - Access Control of Instrument/SW, eSignature and Audit Trail
MassHunter User Access Control (UAC) functionality provides:• Password protection for user access to ICP-MS MassHunter• Flexible, multi-level configurable access to MassHunter functions (defined by user
levels, Admin, ECM Mgr, SDAAdmin, SDAApprover, Mgr and Operator)• Audit trail - Record of user(s) logon/logoff to operating system (supported OS
function) and MassHunter logon; audit trail also records user actions as defined in ATM (Audit Trail Map)
ICP-MS MassHunter User Access Control for Audit Trail and some of eSignature
ICP-MS MassHunter Audit Trail
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User Access Control with OpenLab ECM on ICPMSs – A Second level of UAC exists Systems with OpenLab ECM
ECM is the most comprehensive solution for protecting, storing and accessing your dataNot only is there MassHunter User Access Control (UAC) Users and their access roles/privileges are also set up in OpenLab ECM
• Users must log on to ECM AND UAC foraccess to ICP-MS MassHunter
• Different User roles/Privileges/Access rights are also set up in ECM
Note Network Domain
Application software
21 CFR Part 11 - 2nd Category for OESs, UV-VisUser Access Control & Electronic Signatures
Data Management
Control the instrument for data acquisition and processing
ICPExpert or MassHunter
Administration of databases and data, records integrity, security and retention
SDA, DS or OpenLab
+ +
Access Control
Manage groups, projects, users and user profiles, esigs and Audit Trail
UAC or SCM
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Spectroscopy Configuration Manager What is it?
1. User Access Control Manager for all other Spectroscopy instrumentation (OES, AA, UV, Dissolution)
click
2. Allows set up Groups, Programs, Users, User Profiles (access rights) and even Stations
3. Network capable/scalable
4. Audit trail contained within
Potential SCM Configurations Network configurable and Scalable
There are 5 Scenarios (configurations) for Compliance SCM software. • Configuration depends upon customer wishes at installation.
Scenario 5Scenario 1
ApplicationSDASCM
Scenario 2
Application
SDA
SCM
Scenario 3
SCM
Application
SDA
Application
Scenario 4
SDA
SCM SDAApplication
SCM
In contrast, UAC SW for ICPMS is not configurable as a network (Client/Server) and is not scalable
Spectroscopy Configuration Manager (SCM)User Profile set up and are similar to Audit Trail Map access rights (Actions) in UACProfile capabilities different depending upon the Instrument
• Select the applications which a User can access by adding ‘x’ next to each application.
• Note: For Cary WinUVsoftware the Color, Fabric Protection and Sunglasses Applications are not 21 CFR 11 compliant.
Application software
21 CFR Part 11 – 3rd Category of CriteriaElectronic Records Mgmt, Storage & Security
Data Management
Control the instrument for data acquisition and processing
ICPExpert or MassHunter
Administration of databases and data, records integrity, security, retention and retrieval
SDA, DS or OpenLab
+ +
Access Control
Manage groups, projects, users and user profiles, esigs and Audit Trail
UAC or SCM
Agilent Compliance Products for ICPOES & ICP-MS
Large/global Pharma
MidRegulated(CRO)
Small Regulated
All MS DB options need UAC
OpenLab Data Store
SDA
OpenLab ECM
ICP-MS MassHunter Compliance SolutionsPage 29
OpenLAB ECM 3.5• Supports 7800, 7900 ICP-MS, and 8900
ICP-QQQ• Accepts data files from 5110 with
Scheduler but still not compliant (versioning missing)
OpenLAB Data Store A.01.03• Supports 7800, 7900 ICP-MS, and 8900
ICP-QQQSpectroscopy Database Administrator A.01.02• Supports 7800, 7900 ICP-MS, and 8900
ICP-QQQ• Supports 5110 ICP-OES (different SDA)
Recommended for:
Database provides secure storage of DataSDA and ECM Provide Database Management functions:• Creation/ Attaching / Detaching / Archiving / Retrieval of a database
• An “attached” database is “online” and • a “detached” database is “offline” and cannot be accessed by users
• Version Control on file save/upload• Includes Database Viewer• Audit Trail for databases• Batch approval in SDA• Database backup/upload• Admin functions
• Control of database access rights• SDA log
•SDA Database Management pane
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Agilent Solution for 3rd Category of 21CFR11 Compliance – Electronic Records Management, eSig, Version, Archive
SDA Database Viewer for more eSignature
ICP-MS MassHunter with SDA includes a Database viewer for data management. Batch data is secured using ssizip checksum protected file
ICP-MS SDA Database Viewer for batch approval, upload, etc.. Version numbers can be seen
Batch Properties, Audit and Approval logs are available
April 11, 2013Page 32
SDA Database Viewer showing Versioning, Secure Data Storage
ICP-MS SDA Database Viewer for batch approval, upload, etc.. 13 Versions of the DA Method Post processed shown here
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Sitting on this batch
OpenLAB ECM Provides Secure Content Management for all files from all InstrumentsECM maintains all electronic data regardless of source:
• Analytical data from mulitple techniques and suppliers
• Chromatographic result data• Master methods, and
sequence and report templates
• Pictures and graphic images • PDF documents und
formulars• Email• Microsoft Office files• Electronic reports
Search function is really cool
OpenLAB Data Store Compliance FunctionsServer-based solution for ICP–MS Compliance
Efficient Data Storage and Retrieval Centralized Storage for ICP–MS MassHunter (rev B.01.03) Efficient search and retrieval of files Local Language Support (English, Chinese & Japanese)
Security Comprehensive data security Access for registered users with roles Integration to OpenLAB Shared Services/Control Panel
Data Integrity and Traceability Maintain file revision and history Comprehensive Audit Trails
Trail of who has what item Trail of when an item was received
21 CFR Part 11 Compliant Built to support FDA regulations
Data Integrity and Traceability Electronic Signatures Archival Capabilities
ServerOpenLAB Data StoreOpenLAB Shared Services2 MS instrument connections
Agilent Compliance Products for ICP-MS• Functional Comparison
OpenLAB ECM Data Store for MS SDA for ICP - MSGeneral Specs International Language support (From A.01.02)
Multi – Vendor Support
Integrated Search & Retrieve
# of Instruments supported No limit Up to 15 1Server Required (Enhanced Security)
Automated Uploads
Integrated (free) Database
Compliance e-Signature
PDF Signature
Audit Trails
File Revisions
Integration OpenLAB CDS (From A.02.01)
MassHunter (Before A.02.01,
only ICP–MS) (ICP–MS)
OpenLAB ELN
Third-party LIMS and ELN
ECM SDA
Summary of 21 CFR Part 11 Compliance Solutions
1. Software and hardware design validation – Agilent excels in IQ/OQ for both hardware and software – Agilent consistently ranked #1 for compliance services
2. User Access Control – ICP-MS add-on– User Access Control for ICP-MS MassHunter OR SCM for all other Atomic line
and Spectroscopy products provides fully flexible solution, with configurable access levels
3. Electronic records Mgmt – 3 DB options: SDA, Data Store or OpenLabECM (Enterprise Content Manager)
4. ICP-MS MassHunter User Access Control add-on functionality and SDA/Data Store/OpenLAB ECM software provides full compliance with 21 CFR Part 11
– Electronic records and version management done by SDA/OpenLAB ECM– Data security is ensured through use of secure (encrypted, non-editable) files– Databatch information (raw data and reports) is secured and versioned– All back-up and archival functions are performed in SDA/OpenLAB ECM
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