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1APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
ISO Guide 34 Training
2APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Disclaimer
The information contained in this presentation is intended to help potential assessors of reference material producers seeking to attain or retain accreditation to the requirements of ISO Guide 34:2009.
It is not intended that this material should be used as an ‘accreditation manual’ or as a checklist of requirements for assessors to audit against.
September 2010
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3APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
REMCOREMCOSyllabusSyllabusDay 1
1. ISO REMCO Guides
2. ISO Guide 34:2009 Management Requirements
3. ISO Guide 34:2009 Technical Requirements
Day 2
3. ISO Guide 34:2009 Technical Requirements (cont’d)
Day 3
4. ISO Guide 34:2009 Annexes
5. Cross-walk between 2nd and 3rd Editions
6. Other ISO Guides that contain requirements for RMPs
7. Experience sharing, transition plan to the new edition, wrap-up
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4APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
REMCOREMCOAPLAC ISO Guide 34 TrainingAPLAC ISO Guide 34 Training
Session OneISO REMCO Overview
Introduction to Guide 34
September 2010
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5APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
WHY REFERENCE MATERIALS ARE WHY REFERENCE MATERIALS ARE ESSENTIAL ESSENTIAL
Accurate measurements are an essential feature both of everyday life and economic activity.
– Food safety
– Healthcare measurements
– Material composition and reliability
Such measurements can only be performed when the corresponding measurement instruments have been properly calibrated. This is the same procedure as used when the accuracy of a set of weighing scales is checked by using a known standard weight. Consequently, materials which can be used for instrument calibration – such as the kilogram standard –are required. These are known as “reference materials”.
Because vital decisions may depend on measurements such as the examples given above, there needs to be confidence in the measurement data. Therefore, the correct application of critical measurement procedures must also be controlled by using reference materials which are similar to the material to be tested, and for which the measured value is already known. In consequence, laboratories are able to verify their ability to measure accurately.
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6APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
ISO/REMCOISO/REMCOISO Committee on Reference MaterialsISO Committee on Reference Materials
Carries out and encourages a broad international effort for the harmonization and promotion of reference materials, their production and their application.
REMCO’s vision is to be the global centre of excellence with respect to issues relating to reference materials.
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7APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
REMCO ObjectivesREMCO Objectives
To establish definitions, concepts and classification of reference materials for use by ISO
To determine the basic characteristics of reference materials in dependence on their use
To formulate criteria for the selection of publications referenced in ISO documents
To propose, as far as necessary, actions on reference material issues required to support other ISO activities
To prepare guidelines for technical committees when dealing with reference material issues in ISO documents
To deal with matters within the competence of the Committee, in relation with other international organizations and to advise the ISO Technical Management Board (TMB) on actions to be taken
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8APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
StakeholdersStandardisation bodiesMetrology institutionsInternational and regional liaison partners
ClientsISO committees (horizontal advisory function)Users of reference materials (e.g. analytical laboratories)Producers of reference materialsAccreditation bodies (in particular for RM producers)
REMCO REMCO stakeholders and clientsstakeholders and clients
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9APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
REMCO StructureREMCO Structure
Chairman’s Advisory Group (CAG)Chair, Vice Chair, Past Chair,
SG and WG Conveners,CASCO Representative
ChairmanProf. Hendrik Emons
SecretaryStéphane Sauvage
Assistante : Leila Saber
Vice Chairman
Dr. Angelique Botha
SG1 International Coordination and Communication
Dr. Stephen Davies
WG 6 Information Services
John P. Hammond
SG 2 Technical Guidance
Dr. Aleš Fajgelj
WG 4 Transportation
Prof. Hendrik Emons
WG 8 Guidance on QCMs
Dr. Steve Wood
WG 10 Definitions, including review of ISO Guide 30
Dr. Robert Watters
WG 9 Revision of ISO Guide 33
Dr. Adriaan van der Veen
WG 13 RMs for qualitative analysis – Testing of nominal
properties
Dr. Stefanie Trapmann
WG 14 Revision of ISO Guide 31
Dr. Takeshi Saito
WG 15 Metrological Traceability (new)
Dr. Wolfram BremserB
10APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
REMCO PublicationsREMCO Publications
ISO Guide 30:1992/Amd 1:2008 – Revision of definitions for reference material and certified reference material.
ISO Guide 31:2000 – Reference material – Contents of certificates and labels.
ISO Guide 32:1997 – Calibration in analytical chemistry and use of certified reference materials.
ISO Guide 33:2000 – Uses of certified reference materials.
ISO Guide 34:2009 – General requirements for the competence of reference material producers.
ISO Guide 35:2006 – Reference materials – General and statistical principles for certification.
ISO/TR 10989:2009 – Reference materials – Guidance on, and keywords used for, RM categorization.
The role of reference materials in achieving quality in analytical chemistry (1997).
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11APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
The REMCO Family of GuidesThe REMCO Family of Guides
The reference for accreditationThe reference
for accreditation
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12APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Guide 34 Guide 34 –– the 2009 Versionthe 2009 Version
Same general organization
1. Scope
2. Normative references
3. Terms and definitions
4. Organization and management requirements
5. Technical and production requirements
Better alignment with ISO/IEC 17025:2005B
13APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
1 Scope1 Scope
For recognition of reference material producers’competence
– Quality management system
– Administrative operations
– Technical approach
Production of certified and non-certified reference materials
– Minimum requirements for non-certified RMs are specified
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14APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Question for DiscussionQuestion for Discussion
Our reference material producer, “North Pole RMs” produces an RM for classifying polar bears by color. The three classifications are:
The customer wishes to verify that these classifications meet the RGB specification:
– Almost White: Red 221; Green 221; Blue 221
– White: Red 234; Green 234; Blue 234
– Really White: Red 248; Green 248; Blue 248
Can Guide 34 be used for this purpose?
Almost White White Really White
B
15APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
2 Normative References2 Normative References
ISO Guide 30 , Terms and definitions used in connection with reference materials
ISO Guide 31 , Reference materials — Contents of certificates and labels
ISO Guide 35 , Reference materials — General and statistical principles for certification
ISO/IEC Guide 98-3 , Uncertainty of measurement — Part 3: Guide to the expression of uncertainty in measurement (GUM)
ISO/IEC Guide 99 , International vocabulary of metrology — Basic and general concepts and associated terms (VIM)
– Also known as JCGM 200:2008 with Corrigendum (May 2010)
ISO 9000, Quality management systems — Fundamentals and vocabulary
ISO 10012, Measurement management systems — Requirements for measurement processes and measuring equipment
ISO 15189, Medical laboratories — Particular requirements for quality and competence
ISO/IEC 17000, Conformity assessment — Vocabulary and general principles
ISO/IEC 17025, General requirements for the competence of testing and calibration laboratories
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16APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
ISO/TR 10989:2009 RM CategorisationISO/TR 10989:2009 RM Categorisation
Potentially useful for defining the scope of an RMP’s technical capability
General scheme:
– certified or reference property
– Field(s) of application
– Measurand(s) or analyte(s)
– Matrix or base material
17APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Categorization ExampleCategorization Example
18APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
ISO/TR 10989:2009 RM CategorisationISO/TR 10989:2009 RM Categorisation
certified or reference property
– Amount-of-substance fraction
Field(s) of application
– Environmental, green house gases, etc.
Measurand(s) or analyte(s)
– Carbon dioxide
Matrix or base material
– Nitrogen
19APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Natural Materials Natural Materials –– Organic ConstituentsOrganic Constituents
20APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
ISO/TR 10989:2009 RM CategorisationISO/TR 10989:2009 RM Categorisation
certified or reference property
– Mass fraction
Field(s) of application
– Environmental, food analysis
Measurand(s) or analyte(s)
– 65 analytes
Matrix or base material
– Freeze-Dried Mussel Tissue (Mytilus edulis)
21APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Application of TR 10989:2009Application of TR 10989:2009
Might be a convenient way to define scope, especially for RMPs with relatively simple RMs and CRMs (few measurands)
May be too restrictive to apply rigorously
– Accredited capability for SRM 2974a is PAHs, PCB congeners, chlorinated pesticides, and PBDE congeners in marine bivalve mollusk tissue and similar matrices
22APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
REMCOREMCOAPLAC ISO Guide 34 TrainingAPLAC ISO Guide 34 Training
Session TwoISO Guide 34: 2009
Management Requirements
September 2010
B
23APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
3 Terms and definitions3 Terms and definitions
Acknowledges the terms in ISO/IEC 17000, ISO/IEC 17025, ISO Guide 35, ISO 9000
Introduces 3 terms specifically for this Guide
Explicitly repeats terms from ISO Guide 30 and ISO/IEC Guide 99
– The definitions of RM and CRM rely on ISO Guide 30:1992/Amd 1:2008
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24APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Terms in Guide 34Terms in Guide 34
Term Guide 34 Guide 30 Guide 99
3.1 reference material producer ♦
3.2 Subcontractor ♦
3.3 production of a reference material ♦
3.4 reference material (RM) ♦
3.5 certified reference material (CRM) ♦
3.6 commutability of a reference material ♦
3.7 metrological traceability ♦
3.8 measurement uncertainty ♦
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25APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
3.2 Subcontractors3.2 Subcontractors
Can be a collaborator
Can do
– Processing
– Handling
– Homogeneity and stability assessment
– Characterization measurements
– storage and/or distribution
Can be either paid or non-paid
Cannot do
– Project planning
– Assignment and decision on property values and uncertainties
– Authorization of property values
– Issuing of certificates or other statements for RMs
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26APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
3.5 Reference Material (RM)3.5 Reference Material (RM)
material, sufficiently homogeneous and stable with respect to one or more specified properties, which has been established to be fit for its intended use in a measurement process
– NOTE 1 RM is a generic term.
– NOTE 2 Properties can be quantitative or qualitative (e.g. identity of substances or species).
– NOTE 3 Uses may include the calibration of a measurement system, assessment of a measurement procedure, assigning values to other materials, and quality control.
– NOTE 4 A single RM cannot be used for both calibration and validation of results in the same measurement procedure.
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27APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Question for DiscussionQuestion for Discussion
What is the principal difference between the VIM definition for RM and the Guide 30 definition?
– NOTE 5 VIM has an analogous definition (ISO/IEC Guide 99:2007, 5.13), but restricts the term “measurement” to apply to quantitative values and not to qualitative properties. However, Note 3 of ISO/IEC Guide 99:2007, 5.13, specifically includes the concept of qualitative attributes, called “nominal properties”.
B
28APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
3.5 Reference Material (RM)3.5 Reference Material (RM)
material, sufficiently homogeneous and stable with respect to one or more specified properties, which has been established to be fit for its intended use in a measurement process
– NOTE 1 RM is a generic term.
– NOTE 2 Properties can be quantitative or qualitative (e.g. identity of substances or species).
– NOTE 3 Uses may include the calibration of a measurement system, assessment of a measurement procedure, assigning values to other materials, and quality control.
– NOTE 4 A single RM cannot be used for both calibration and validation of results in the same measurement procedure.
– NOTE 5 VIM has an analogous definition (ISO/IEC Guide 99:2007, 5.13), but restricts the term “measurement” to apply to quantitative values and not to qualitative properties. However, Note 3 of ISO/IEC Guide 99:2007, 5.13, specifically includes theconcept of qualitative attributes, called “nominal properties”.
B
29APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
3.6 Certified Reference Material (CRM)3.6 Certified Reference Material (CRM)
reference material characterized by a metrologically valid procedure for one or more specified properties, accompanied by a certificate that provides the value of the specified property, its associated uncertainty, and a statement of metrological traceability
– NOTE 1 The concept of value includes qualitative attributes such as identity or sequence. Uncertainties for such attributes may be expressed as probabilities.
– NOTE 2 Metrologically valid procedures for the production and certification of reference materials are given in, among others, ISO Guides 34 and 35.
– NOTE 3 ISO Guide 31 gives guidance on the contents of certificates.
– NOTE 4 VIM has an analogous definition (ISO/IEC Guide 99:2007, 5.14).
B
30APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4 Organization and Management4 Organization and Management
4.1 Management system requirements
– 4.1.1 Documentation as to types of RMs, measured properties measures, their ranges, and uncertainties
In other words, the quality system needs a scope statement
– 4.1.2 Policy statement committing to quality of all aspects of RM production
Statement must come from top management
Produce RMs as defined in Guide 30
CRMs per Guide 35 and certificates per Guide 31
Testing and calibration per ISO/IEC 17025
All personnel are familiar with the quality documentation and that they implement it
Policy of continuous improvement
Audit hint: When you are nearly done with the audit,
check to see if everything you saw is included in the scope.
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31APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4 Organization and Management4 Organization and Management
4.1 Management system
– 4.1.2 Quality policy: The quality policy shall include but shall not be limited to the following commitments:
a) to produce reference materials which conform to the requirements of this Guide and to the definitions given in ISO Guide 30;
b) to produce, where applicable, certified reference materials according to the requirements of ISO Guide 35 and accompanied by certificates meeting the requirements of ISO Guide 31;
c) to conduct all testing and calibration in support of the production of reference materials in compliance with the requirements of ISO/IEC 17025;
– 4.1.3 document all policies, systems, programmes, procedures, instructions, findings, etc., to the extent necessary to enable the producer to ensure the quality of the reference materials produced
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32APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.1.3 Management System4.1.3 Management System
Material suitability
– type of material
– measurands
– concentration range
Required stability
Processing procedures
Design homogeneity specification
Assessment of the stability
Assessment of the material stability
commutability assessment (where appropriate)
Establishment of metrological traceability
Assignment of property values for the measurands
Certificate preparation (ISO Guide 31) where appropriate
Adequate storage facilities
inventory control, labeling and packaging
Packing and shipping
Adherence to relevant safety regulations
Customer service
Post-certification stability monitoring
Compliance with ISO Guide 30 and with appropriate sections of ISO Guides 31 and 35
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33APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.2 Organization and Management4.2 Organization and Management
Legally responsible entity
Control on-site or off-site locations
Personnel with adequate authority, resources and no conflict of interest
Organizational and quality management structure
Specify the details of responsibilities and authority lines
Technical manager
Quality manager
Deputies for back-upS
34APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.3 Document and Information Control4.3 Document and Information Control
Procedures to control quality system documents
– Approval and issue
– Availability of official version
– Periodic review
– Retirement and retention of obsolete versions
– Unique identification system
– Change management
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35APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.4 Request, Tender, and Contracts4.4 Request, Tender, and Contracts
Documented process for review to ensure:
– Requirements are adequately defined
– RM producer has capability and resources
– Differences between contract and tender get resolved
Records of such reviews, discussions or other communications are maintained and archived
Requirements extend to any subcontractors that are used
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36APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.5 Use of Subcontractors4.5 Use of Subcontractors
Policies and documented procedures to
– Select competent subcontractors
– Monitor compliance with design and performance specifications
– Ensure adherence to relevant sections of G34
Selection based on
– Technical competence (Section 5)
Measurement and testing covered by ISO/IEC 17025
– Quality system for relevant tasks
– Accreditation not required
Documentation of use and evaluated performance of subcontractors maintained
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37APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.6 Procurement of Services and Supplies4.6 Procurement of Services and Supplies
Policies and procedures for
– Selecting things that affect RM quality
– Using services and supplies that conform to specifications
– Verify and document quality of purchased services and supplies before use
– Maintain records of suppliers and subcontractors from whom services and supplies are obtained
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38APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.7 Customer Service and 4.8 Complaints4.7 Customer Service and 4.8 Complaints
Clarify customer's requests and questions
Seek feedback for service improvement
– Evaluate feedback
– Design and implement improvement steps
Resolve complaints and keep records
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39APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.9 Non4.9 Non --conformitiesconformities
Define and implement policy for responding to non-conformities
– Responsibilities and authorities are defined
– Actions to be taken are identified and implemented
– Significance is evaluated
– Effected RMs withheld if necessary
– Timely remediation
– Customer notification
– Authorization for re-releaseS
40APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.10 Corrective Actions4.10 Corrective Actions
Evidence of procedures for root-cause analysis from complaints or non-conformities
– Investigative procedures
– Analysis of findings
– Selection and implementation of corrective actions
Implement change management process from Section 4.3
– Continuous monitoring – possible re-audit
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41APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.11 Preventive Actions and 4.12 Improvement4.11 Preventive Actions and 4.12 Improvement
Improvement opportunities identified
Preventive actions planned and implemented
Process improvement measures documented
Continuous improvement via
– quality policy
– quality objectives
– audit results
– analysis of data
– corrective and preventive actions
– management reviewS
42APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.13 Records4.13 Records
Includes both quality system and technical records
Records shall be legible, stored safely for prescribed retention time
No erasures
Changes signed
Security and confidentiality maintained
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43APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
REMCOREMCOAPLAC ISO Guide 34 TrainingAPLAC ISO Guide 34 Training
Session ThreeISO Guide 34: 2009
Technical Requirements
September 2010
B
44APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5. Technical and production requirements
Guide covers both certified and non-certified RMs:
– Clarification which parts apply to non-certified/certified RMs
– Precision of different requirements for non-certified/certified RMs:
– homogeneity and traceability
– metrological traceability
– documentation
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45APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.1 General
General paragraph added
– to identify the minimum requirements for non-certified RMs
– the requirements which are specific for certified RMs
– which paragraphs apply for both types
– which paragraphs are specific for CRMs
Minimum requirements for non-certified RMs are specified with reference to specific paragraphs
=> Homogeneity and stability assessment always required
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46APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Non certified reference materials
The following may not be required:
– Designing interlaboratory exercises
– Assessing commutability
– Assigning property values and establishing uncertainty budgets
– Providing detailed information to users on homogeneity studies
– Providing detailed information to users on stability studies
– Characterization of the material
– Establishing metrological traceability
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47APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.2 Personnel
Aligned with ISO/IEC 17025 and uses same terminology
more details on:
– competence in production
– production of novel materials
– education and training
– technical knowledge and experience of staff
including:
– formulation of goals
– establishing policies
– establishing procedures for (re)training needs
– evaluation of effectiveness of received (re)training
Requirements are also valid for contracted work
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48APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.3 Subcontractors
Subcontractors shall execute their tasks in compliance with ISO/IEC 17025
see also 4.5
Evaluation of subcontractor’s competence:
– competence of its staff
– appropriateness of its accommodation
– environmental conditions
– instrumentation and
– measurement equipment
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49APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Subcontractor Activities
Activity Producer Subcontractor
Project planning ♦
Selection of subcontractors ♦
Processing ♦ ♦
Homogeneity and stability testing ♦ ♦
Characterization ♦ ♦
Handling, storage and distribution ♦ ♦
Assignment of and decision on property values ♦
Authorization of property values ♦
Issue of certificates/statements ♦
B
50APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.3 Clarification of subcontractor’s competence
Subcontractor does not need to be accredited
– responsibility of the producer to ensure compliance with ISO/IEC 17025
– producer must have sufficient staff with knowledge to evaluate the results of subcontracted activities and the compliance with ISO/IEC 17025
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51APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.3 Clarifications on evaluation of subcontractors’competence
How to evaluate subcontractor’s competence if not accredited ISO/IEC 17025?
– Successful participation in relevant proficiency testing schemes
– Production of acceptable results on well-characterized, similar materials
– On-site assessment
– On-site supervision of subcontracted work
– Analysis of similar materials (matrix, concentration levels) prior or together with candidate RM
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52APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.4 Production Planning
Production Steps
– Material specification
– Confirmation of identify
– Sourcing, preparation and sub-division
– Homogeneity assessment
– Stability assessment
– Characterisation of the assigned value(s)
– Calculation of the assigned value and its uncertainty
– Documentation and storage of the material
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53APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.5 Production Control
Producer shall
– Identify the verification procedures necessary to ensure the quality of each stage of production
– Shall assign adequate resources and personnel for the inspection, testing and monitoring of all stages of production
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54APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.6 Accommodation & Environmental Conditions
5.6.1 Lab facilities are fit for producing RMs within the scope
– Includes processing, packaging and measurement spaces as appropriate
– Start with documented technical requirements for protection from adverse environmental conditions
Contamination – dust, microbial, radiation
– Facility specifications and measured performance with respect to
energy sources
Lighting
Humidity
Temperature
Pressure
ventilation .
5.6.2 Employ appropriately calibrated environmental monitoring
5.6.3 Appropriate health, safety and environmental protection precautions shall also be implemented
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55APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.7 Material Handling & Storage
Avoid contamination
– During processing until distribution
Materials shall be appropriately packaged
– Choice of Container
moisture
contamination (e.g. by leaching of impurities)
light degradation
Volatility
Appropriate procedures for dispatch
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56APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.7 Material Handling & Storage
Regular checks on condition of materials to detect possible deterioration
Packaging and labelling
– To conform to safety and transport requirements
– Label to be securely attached and legible under defined storage conditions
– Label to
Identify material and producer
Batch and catalogue numbers
Any unique identifier (e.g. unit number linking unit to certificate)
Comply with relevant safety and risk regulations (symbols and risk phrases: http://www.hse.gov.uk/chip/phrases.htm)
R24 – toxic in contact with skin
R40 – limited evidence of carcinogenic effect
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57APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.7 Material Handling & Storage
Integrity of each unit to be maintained until seal is broken
– Producer cannot be held responsible for material once the seal has been broken
– Single use units may be appropriate
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58APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.8 Material Processing
Processes to be established to ensure item or material has undergone adequate processing for its intended use
– Verification of material type or identity
– Synthesis/purification/transformation to final form
– Homogenisation
– Protection from contamination
– Appropriate process control (particle size / moisture)
– Clean sample containers
– Stabilisation (irradiation, drying)
– Packaging (control of volatile components)
S
59APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Bottling trends - 40% alcohol by volume
948.02
948.03
948.04
948.05
948.06
948.07
948.08
0 200 400 600 800
Bottle Number
Den
sity
kg
/cub
ic m
eter
Homogeneity data used to assess bottling trends
Evaporation of alcohol over a bottling run of 800 units
Bottles analysed in random order
Results plotted in bottling order
Reject all units above No. 600
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60APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Planning Exercise
Suggest an exercise on planning a simple RM project using the ERM project planning form as a template.
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61APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.9 Measurement methods5.9 Measurement methods
International or national standard methods
Laboratory developed methods
Non-standard methods
– Validation plan
– Validation = “Confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled”
Effort must be reasonable and in relation to what is needed
A = Check execution of validation planH
62APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.9 Measurement methods5.9 Measurement methods
Calibration using reference standards (or reference materials)
Comparison of results achieved with other methods
Inter-laboratory comparisons
Systematic assessment of factors influencing the result
Assessment of the uncertainty of the results based on scientific understanding of the theoretical principles of the method and practical experience
– uncertainty; detection limit; limit of quantification; selectivity of the method; linearity; limit of repeatability and/or reproducibility; robustness and cross-sensitivity
A = Check understanding of uncertainty estimations
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63APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Reference to ISO/IEC 17025 in ISO Guide 34Reference to ISO/IEC 17025 in ISO Guide 34
4.1.2 Quality policy
4.5.3 Use of subcontractors
4.13.2 Records and reports
5.3.2 Subcontractors
5.3.3 Subcontractors
5.9.1 Measurement methods
5.9.2 Measurement methods
5.10.1 Measuring equipment
5.13.2 Assessment of homogeneity
5.14.2 Assessment of stability
5.15 Characterization
[Note: Section numbers refer to ISO Guide 34]
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64APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
4.1 Alignment with ISO/IEC 17025 4.1 Alignment with ISO/IEC 17025
4.1.2 Quality policy
New:
-Introduction of requirement to apply ISO/IEC 17025 for testing and calibration: “to conduct all testing and calibration in support of the production of reference materials in compliance with the requirements of ISO/IEC 17025 (…. ISO 15189 in medical field)”
- Requirement that personnel be familiar with quality documentation and implements the policies and procedures in the work
- Requirement that management improves effectiveness of management system
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65APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.10 Measurement equipment5.10 Measurement equipment
“Equipment and its software used for testing calibration and sampling shall be capable of achieving the accuracy required and shall comply with specifications relevant to the tests and or calibrations concerned.”
Installation qualification
Operation qualification
Authorized personnel
Up-to-date working instructions
Records: instrument log-book or dossier
A = Check records of IQ
A = Check records of OQ
A = Check training plan and authorizations
A = Check WIs
A = Check logbooks
H
66APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.9 Measurement methods5.9 Measurement methods5.10 Measurement equipment5.10 Measurement equipmentEnsure accurate performance through PT rounds and/or other types of laboratory intercomparisons and checks
– Use of CRMs/RMs
– Participate in PT rounds
– Replicate tests or calibrations same or different methods
– Retesting of retained items
– Correlation of results for different characteristics of an item
5.9.1 a-e in ISO17025
A = Check results /certificate, good leaflet on web
A = Check records of PT, z-scores, frequency
A = Check control charts
H
67APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.10 Measurement equipment5.10 Measurement equipment5.10 Measurement equipment
Control Chart SiC P600'06 for X50 using the CUVETTE and R5
25
25,2
25,4
25,6
25,8
26
26,2
26,4
26,6
26,8
27
27,2
27,4
27,6
27,8
28
okt-06 apr-07 nov-07 jun-08 dec-08 jul-09 jan-10
Time
Equ
ival
ent s
pher
e di
amet
er, µ
m
R5 X50
Mean± 2SD± 3SDCert.
H
68APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.10 Measurement equipment5.10 Measurement equipment
99 % of observations occur within 3 standard deviations of the mean
OUT-OF-CONTROL situations:
– 1 point above/below 3 sigma
– 2 of 3 points above/below 2 sigma ("early warning" of a process shift)
– 8 consecutive sample means on the same side of the centre line
– 6 or more points in a row steadily increasing or decreasing is also an "early warning" of something going wrongA = Check control-charts as part of IQ/OQ
H
69APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.11 Data Evaluation5.11 Data evaluation5.11 Data evaluation
Calculations and data transfers subjected to checks
Software that is developed in-house or modified off-the shelf software (macro in Excel) must be validated and adequate for use
Protection integrity of data and its manipulation (Title 21 CFR p 11)
Only authorized access to computer records, adequate back-up
A = Check procedures and checks for software and macrosH
70APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.12 Metrological Traceability5.12 Metrological Traceability5.12 Metrological Traceability
H
71APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.12 Metrological Traceability5.12 Metrological Traceability
Planning a holiday. Average temperature at the time of the holiday is 30 degrees. What to wear?
or ?
“Weigh 100 mg of plant powder in a 2 mL tube, add 1 mL of extraction buffer and 10 µL of RNase A, mix by shaking and incubate at 60 °C for 30 min; centrifuge for 10 min at 13000 rpm, then add the supernatant to 500 µL of chloroform, …”
H
72APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.12 Metrological Traceability5.12 Metrological Traceability
Traceability
What it is
Why we need it
To which references can it be achieved
How CRMs can be used to achieve it
– Identity
– Quantity values
Example of a traceability web
How to find on certificatesH
73APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.12 Metrological Traceability5.12 Metrological Traceability
ISO Guide 99:2007 International Vocabulary of Metrology (VIM)
“property of a measurement result whereby the result can be related to a reference through a documented unbroken chain of calibrations, each contributing to the measurement uncertainty”
Information on what the result means, and whyit really means what one says it means
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
74APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.12 Metrological Traceability5.12 Metrological Traceability
Imagine, you buy 250 g sausages at the local butcher. Upon weighing at home, you find only 200 g. Is there a problem?
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
75APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
primary referencemeasurement procedure
definition of(SI) unit
secondary referencemeasurement procedure
manufacturer’sproduct calibrator
end-user’s routinemeasurement procedureroutine sample
RESULT
manufacturer’sworking calibrator
primary calibrator
manufacturer’s standingmeasurement procedure
uncertainty
uncertainty
uncertainty
uncertainty
5.12 Metrological Traceability5.12 Metrological Traceability
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
76APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Metrological traceability: What forMetrological traceability: What for
Traceability is
Prerequisite for comparability of results
– results that are not traceable to a common reference are not comparable
The property that makes results meaningful
Hence, traceability written down in ISO 17025:
– 5.6 Measurement traceability
– 5.6.2.1 Calibration (RMs)
– 5.6.2.2 Testing (RMs)
– 5.6.3 Reference standards and reference materials (RMs)
definition need references use_of_CRMs traceability_web traceability_on_certificates
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
77APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Traceability Traceability –– final referencefinal reference
Important: traceability chain has to be linked to a Metrological reference:
– measurement unit
– measurement procedure
– reference material (“artefact”)
ISO/IEC Guide 99 (VIM)
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
78APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Two aspects of traceabilityTwo aspects of traceability
Traceability is split into
Structurallydefined
Operationally defined
Identity (measurand)
Quantity value (number and unit)
Cd mass fraction: 12 ± 2 mg/kg
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
79APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
IdentityIdentity
Structurally defined
clearly defined molecule, physical property
independent of the method
Operationally defined
Method defines the analyte
Size of this particle?
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
80APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Two aspects of traceabilityTwo aspects of traceability
Traceability is split into
Identity (measurand)
Quantity value (number and unit)
Operationally defined
Structurally defined
SI reference
Artefact reference
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
81APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Quantity valueQuantity value
SI (International System of Units)
Can link result really to SI
Arbitrary units
Final link is arbitrary standard
Traceability to institutes?
Not possible
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
82APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Achieving traceability of resultsAchieving traceability of results
To achieve traceability, one must
link the identity to a stated reference
link the quantity value to a stated reference
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
83APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
IdentityIdentity
Structurally defined
pure standard CRMs (retention time, mass/charge ratio, etc.)
Operationally defined
the right method
at the right conditions
– Physical property CRMs: calibrated flasks, thermometers, balances, etc.
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
84APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Quantity value (1)Quantity value (1)
Final quantification
pure standard CRMs
matrix CRMs: not recommended (too high uncertainty), but sometimes necessary
All relevant input factors (see fishbone diagram)
Physical property CRMs
– calibrated glassware
– balances
– thermometers
– etc.
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
85APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
comparison DON?
Quantity value Quantity value –– sample preparationsample preparation
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
86APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Quantity value Quantity value –– sample preparationsample preparation
balance calibration
calibrated glassware
pure standards
weigh the sample
extraction/digestion
clean-up
dilution to a certain volume
quantification
sample
Mat
rix C
RM
impossible to link sampleto final extract
X
X
Restoring the traceability chain
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
87APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Traceability web in practiceTraceability web in practice
Clean-up
Extraction
Grinding
Sample
Quantity value IdentityM
etho
d va
lidat
ion
Use
of
a C
RM
Con
trol
cha
rts
Sample chromatogram
signal
Multicongenerstandard
International System of Units
Single congener standard
? Purity?
signal
retention time,mass/charge ratio
retention time,mass/charge ratio
retention time,mass/charge ratio
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
88APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Traceability on certificatesTraceability on certificates
Only results comparable to same reference are comparable, therefore
need to know traceability of the assigned valuesof reference materials
On BCR, IRMM and ERM certificates: Footnotes
A = Check for correct understanding and statements on certificates
Problem: Guide 31 does not require this
as yet
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
89APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Certificates Certificates -- Version 2Version 2
• Footnote 1: Definition of identity
– only for operationally defined properties
• Footnote 2: Definition of assigned value; traceability of quantity value
• Footnote 3: Definition of uncertainty
BODY/MATRIXCertified quantity (e.g. Mass Fraction)
Certified value 2)
[unit]Uncertainty 3)
[unit]
Certified properties1)
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
90APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
CertificatesCertificates -- Version 2Version 2
1) As obtained, after extraction, by reversed phase chromatography with post column bromination and subsequent quantification by fluorescence detection.
2) Unweighted mean value of the means of accepted sets of data, each set being obtained in a different laboratory. The certified value and its uncertainty are traceable to the International System of Units (SI).
definition need references use_of_CRMs traceability_web traceability_on_certificatesH
91APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
SummarySummary
Pure standard CRMs for identification and to ensure correctness and traceability of final quantification
“Physical” CRMs to ensure correctness of measurement conditions
– operationally defined properties
– quantity value
Matrix CRMs in method validation prove correctness, absence of losses and interferences and link the final quantification to the sample
(C)RMs in control charts prove that the method has been applied as during validation
H
92APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.13 Homogeneity 5.13 Homogeneity --liquids and solidsliquids and solidsFrom solid
•Sample work-up more complicated•More equipment needed•Out-sourcing?
To powder or solid as such
Homogeneity?
From liquid
•Straightforward sample work-up•Rather simple equipment•Easy to prepare in house
To spiked liquid
Intrinsic homogeneity?H
93APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
It is essential that the content of the bottles is as similar as possible to each other i.e. the between-bottle homogeneity is very important
5.13 Homogeneity 5.13 Homogeneity -- many samples from the many samples from the same bulksame bulk
BULKX X X
XX
X
X
A = Check for process control steps & contamination control here H
94APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Which type of sample above gives the correct result for vitamin C in a fruit mixture?
1. 2. 3.
Homogeneity is achieved by milling and careful mixing of the material. The particle size and the target parameter must be controlled.
Problem: To measure vitamin C in a fruit mixture
5.13 Assessment of Homogeneity5.13 Assessment of Homogeneity
H
95APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.13 Assessment of Homogeneity5.13 Assessment of Homogeneity
0
0.1
0.2
0.3
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1.1
1.2
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uenc
y q3
*(x)
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1.0
1.1
1.2
dens
ity d
istr
ibut
ion
q3lg
(x)
0.5 1 5 10 50 100 500 1000
particle size / µm
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0.65
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0.75
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0.95
freq
uenc
y q3
*(x)
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freq
uenc
y q3
*(x)
0.5 1 5 10 50 100 500 1000
particle size / µm
Designator TRAP-01TRAP-02TRAP-03TRAP-04TRAP-05TRAP-06TRAP-07
H
96APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Within-unit heterogeneity: can be completely eliminated by the user by taking larger samples
needed: minimum sample intake
not a part of RM uncertainty!
Between-unit heterogeneity: user can do nothing about it
needed: quantification of variation between units (ubb), part of the uncertainty of reference value
All analytes to be certified must be measured!
5.13 Assessment of Homogeneity5.13 Assessment of Homogeneity
H
97APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Difficult to know the heterogeneity of an analyte in a material on beforehand.
Although it is possible to plan the study so that it is possible to detect a certain degree of heterogeneity
intended use
maximum heterogeneity
maximum uncertainty
study setup
5.13 Assessment of Homogeneity5.13 Assessment of Homogeneity
H
98APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.13 Assessment of Homogeneity5.13 Assessment of Homogeneity
Which type of materials? All materials, even true solutions (contamination / memory effects /carry over)
Which parameters? all parameters to be certified
Which methods? Validated methods
– selectivity, interferences, correctness
– working range, repeatability, robustness
– traceability!H
99APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.13 Assessment of Homogeneity5.13 Assessment of Homogeneity
Selection and number of samples?
selected over the whole batch i.e from unit 1 to 2000 if 2000 is the final number, preferably randomly selected
Number of samples?
Number of replicates?
– Dictated by the level of homogeneity to be achieved and the repeatability of the method
3 batch the in samples of number total≈N
A = Check for sample allocation and number
H
100APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
40
45
50
55
60
65
70
75
80
85
bottl
e 1
bottl
e 2
bottl
e 3
bottl
e 4
bottl
e 5
bottl
e 6
bottl
e 7
bottl
e 8
bottl
e 9
5.13 Assessment of Homogeneity5.13 Assessment of Homogeneity
40
45
50
55
60
65
70
bottl
e 1
bottl
e 2
bottl
e 3
bottl
e 4
bottl
e 5
bottl
e 6
bottl
e 7
bottl
e 8
bottl
e 9
maximum desired uncertainty
insufficiently precisestudy
sufficiently precise study
H
101APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
ANOVA ANOVA -- AssumptionsAssumptions
Data from each group are randomly selected
variances in each group are equal
Data in each group follow normal distribution
A = Check proof of normal distribution
However, N is almost never large enough for a reliable test of
any distribution
H
102APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Evaluation HomogeneityEvaluation Homogeneity
ANOVA (Analysis of Variance)
Low “between”and low “within”
High “between”and low “within”
H
103APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Randomise analysis orderRandomise analysis order
Replicate 1: 1 3 5 2 4
Replicate 2: 4 2 1 3 5
In this way possible instrumental drift can be discerned from a trend in fill-order
1 2 3 4 5out of 125 units
order of analysis
A = Check for proper implementation of ISO Guide 35
H
104APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
CalculateCalculate
Microsoft Excel Analysis Tool Pak contains ANOVA
Use Single factor ANOVA and set up the data
Average whole study 9.98 ng/g
Cdng/g
#1 #2 #3 #4 #5
Rep1 9.7 10.2 9.4 11.0 9.6
Rep2 9.9 10.1 9.6 10.9 9.4
H
105APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
What does Excel give?What does Excel give?
Average
nMSMSS Withinbetweenbb )/( −=
Average whole study 9.98 ng/g
n=2
Sbb = 4.2 %
Much more in ISO Guide 35!H
106APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Material Processing for Material Processing for reference material productionreference material production
5. Homogensiation
All kinds of flowing powdersmost kind of materials
WAB Schatz Turbula180 L capacity
Turbula mixing
All kinds of flowing powdersmost kind of materials
WAB Schatz Turbula1 L capacity
Turbula mixing
Presently mainly'GMO powders' maize, soya
Lödige LabomixerPropeller mixing
Lödige mixing
Mainly dirty materialsSoil, sediments, sewage slude
fly ash, etc
Alpine Cone mixer250 L capacity
bottling capability
Cone mixing
Homogenisation
Smaller equipment for homogenisationalso exists such as an ultrasonic sonication probe(Bioblock scientific). For homogenisation using slurries
H
107APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.13, 35.13, 3--D mixingD mixing
Much smaller bench top 3-D-mixers are also available
BULKX
H
108APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.13 Cone mixer5.13 Cone mixer
BULKX
H
109APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Assessment of Stability5.14 Assessment of Stability
Assessment of the chemical stability of the analyte during the time of use of the (C)RM is mandatory!
Need for stability studies
If dispatch is needed (in a large company or organization) a short-term stability study will tell you the dispatch conditions
Long term stability study will show the analyte behaviour upon long-term storage. Part of uncertainty of reference value
H
110APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Accelerated stability studies?5.14 Accelerated stability studies?
H
111APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Potential degradation plots5.14 Potential degradation plots
- 10 20 30 40 50 60 time
anal
yte
cont
ent
diffusion controlled analyte degradation
diffusion controlled matrix degradation
consumption of an antioxidant,; diffusion controlledautocatalyticelementary reaction
analyte creation by microbes
H
112APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Isochronous studies5.14 Isochronous studies
Variation of measurement results comprises
– repeatability
– intermediate precision (= day-to-day variation)
– heterogeneity
– degradation
Only interested in degradation, therefore eliminate as many effects as possible
Isochronous: intermediate precision is eliminated
H
113APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Isochronous studies5.14 Isochronous studies
Reference conditions: conditions, where we are pretty sure that the material is stable e.g. -70 °C
Test conditions: conditions where we believe that the material is stable
Result: conditions where we know that the material is stable
An isochronous study is NOT an accelerated stability / artificially ageing study
H
114APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Short5.14 Short --term stabilityterm stability --planning, STSplanning, STS
Stability during dispatch (up to 60 °C)
– relevant temperatures tested
Limited duration (at least 2, normally 4 weeks)
At least three time points
Suitable number of replicates
– At least 2 units per time
all critical analytes to be certified
suitable method (Procedure “Traceability”)
– validated: selectivity, interferences, correctness, working range, repeatability, traceability
H
115APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Long5.14 Long --term stabilityterm stability
Problem: must predict degradation
Therefore:
– as long as possible
– started as soon as possible
– rather one temperature too many than one too few
H
116APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Long5.14 Long --term stability planning, LTSterm stability planning, LTS
Want to know: Ults of the material
Temperatures: Relevant T (plus at least one below)
Duration: at least 1 year or for an LRM the planned life-time
Time points: At least 3, typically 4
– At least two units per time
Check all analytes to be certified
Method: Assess the repeatability of the method and the uncertainty to be achieved
H
117APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Isochronous stability study, STS5.14 Isochronous stability study, STS
+60 °C
-70 °CAdvantage: All samples are analysed the same day at the end of the study= increases significance of slope, betterPrecision not compromised by day-to-day variation
Ref. 1 w 2 w 3 w 4 w
3 w
4 w
1 w
2 w
t0
H
118APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Isochronous stability study, LTS5.14 Isochronous stability study, LTS
+20 °C
-70 °CAdvantage: All samples are analysed the same day at the end of the study= increases significance of slope, betterPrecision not compromised by day-to-day variation
Ref. 2 m 4 m 6 m 8 m
6 m
8 m
2 m
4 m
t0
H
119APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Evaluation, STS5.14 Evaluation, STS
R 1.00
R 1.05
R 0.95
Time, weeks1 2 3 4
+60 °C
Requirements on method given in 5.12.3.1, A = CheckH
120APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Evaluation, LTS5.14 Evaluation, LTS
R 1.00
R 1.05
R 0.95
Time, months1 2 6 12
+20 °C
Requirements on method given in 5.12.3.1 A = CheckH
121APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Estimation of U5.14 Estimation of U ltslts
98.5%
99.0%
99.5%
100.0%
100.5%
101.0%
101.5%
0 10 20 30 40 50 60
time [months]
reco
very
IRMM-IFCC-451
Requirements on method given in 5.12.3.1 A = CheckH
122APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Why dry biological samples?5.14 Why dry biological samples?
Removal of water lowers the biological activity and renders much better stability to the sample!
H
123APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Material Processing for 5.14 Material Processing for reference material productionreference material production
2. Drying
Animal tissuesPlant materials
Body fluids
Epsilon 2-85D Martin Christ
Freeze drying
Plant materialsFeeding stuff
Epsilon 2-85D Martin Christ
Vacuum drying
Sedimentssoil
ash, sludgeores, plant materials
Elbanton cabinet, Heraeus cabinet
Oven drying
Soilsediments etc
No special equipment
Air drying
Drying
H
124APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Freeze drying / Oven drying5.14 Freeze drying / Oven drying
H
125APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Other 5.14 Other ““ stabilisersstabilisers ””
Thermal sterilization at 121 °C
γ-irradiation is another possibility
This is also a necessary approach if the sample contains pathogens
H
126APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.14 Beware of5.14 Beware of ……H2OH2O
Determination of residual water after drying!
– Oven drying -
– Desiccators 0
– Karl Fischer +
• Impact on analytical result, • Proper dry mass correction• Hygroscopic materials (do
not over-dry)
H
127APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.15 Characterisation5.15 Characterisation
“For CRMs the producer shall use and document technically valid procedures to characterise its reference materials, The chracterisation shall comply with the requirements of ISO Guide 35 and ISO 17025 for testing, calibration and related activities”
a. A single (primary) method in a single laboratory
b. Two or more independent reference methods in one or several laboratories
c. One or more methods of demonstrable accuracy, performed by a network of competent laboratories
d. An approach providing method-specific, operationally defined property values using a network of competent laboratories
A = Check if a, b c or d is applied H
128APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.15 Characterisation5.15 Characterisation
Characterisation: process of determining the certified values
Laboratory: entity providing one set of results
independent results: same measurement protocols, separate subsamples, separate sample preparations, separate calibrations
general uncertainty budgets interlab comp. purity
Requirements on method given in 5.12.3.2 A = Check
H
129APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.15 Characterisation5.15 Characterisation
stsltsbbcharCRM ccccc δδδ +++=
Goal:
Obtaining the best estimate of the “true value”of the batch of the material
within the scope of the intended traceability
“batch” can be one unit
Outcome:
average value of the batch and its uncertainty
Model:
general uncertainty budgets interlab comp. purityH
130APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
5.15 Characterisation5.15 Characterisation
Approaches:
gravimetric preparations
analytical measurements
– SI: at least two independent methods or primary method and confirmation
– method dependent: all the same method
A = Remember traceability
general uncertainty budgets interlab comp. purityH
131APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Uncertainty evaluationUncertainty evaluation
Uncertainty must include all relevant uncertainty contributions
– relatively trivial for gravimetric preparation
– difficult evaluation if full uncertainty budgets are submitted
– so far only approximations for results without uncertainty budget
conceptual problems for purity
– agreement that approximations are acceptable
A = Check for proper uncertainty estimations
general uncertainty budgets interlab comp. purityH
132APLAC ISO Guide 34 Training20 September 2010
REMCO – ISO Committee on Reference Materials
Measurement methodMeasurement method
Must give relevant information about the “true” value
traceable to a useful reference
– traceable to the SI
– traceability to a method
– traceability to an artefact
therefore:
method must be fully validated in a way that an uncertainty statement can be drawn up
all requirements of ISO 17025 must be fulfilled
general uncertainty budgets interlab comp. purityH
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MethodMethod --defined measurandsdefined measurands
All participants use the same method therefore,
method must be fully described
– method can also be “over-described”
– every information/instruction given to the participants will (in theory) show up somewhere in the traceability statement
participants must be able to apply the method
– introduce checks: old CRMs, other CRMs etc.
Should be used for
ALL certification
designs
general uncertainty budgets interlab comp. purityH
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Structurally defined measurandsStructurally defined measurands
ideally, completely different measurement principles should be applied
for chromatography, at least different detectors must be used
sample preparation must be varied as much as possible
A = Check for sample preparation (different solvents, digestions) separation principles, detectors etc.
general uncertainty budgets interlab comp. purityH
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Ideal characterisation studyIdeal characterisation study
many methods, many labs, all with uncertainties,all results agree within their expanded uncertainties
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Combination of uncert. budgetsCombination of uncert. budgets
Idea : l labs in a total of g groups. Some contributions are completely lab specific u(I)
– influence is smaller for more labs
common to all laboratories u(II)
– stays the same no matter how many labs
common to groups of laboratories u(III)
– influence goes down with the number of groups g222 )()()( IIIuIIuIuuchar ++=
general uncertainty budgets interlab comp. purityH
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Looks easy, butLooks easy, but ……
Problems:
splitting uncertainty budgets into u(I), u(II), u(III)
quantification of u(III)
– e.g: uncertainty specific to a certain sample preparation
results do not agree within the uncertainties
– Pauwels et al. suggest to add the standard error of lab. means as additional uncertainty component (AQUAL 3:180-184)
– Levenson et al. suggest to model differences as rectangular distribution (J.Res. NIST 105:571-579)
general uncertainty budgets interlab comp. purityH
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Interlaboratory comparisonInterlaboratory comparison
Rationale: randomisation of bias to make up for missing uncertainties
Assumptions:
All laboratories measure equally well
– otherwise unweighted average would not make sense
Results from different labs are independent
– problem if several results from one lab
(No significant method bias)
– otherwise would have to take averages per method
general uncertainty budgets interlab comp. purityH
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Selection of labs/methodsSelection of labs/methods
As many different principles as possible
– active contacting of people by phone, fax, letter, email etc.
Labs of proven performance
– Accreditation, proficiency tests etc.
About the same number for each principle
Sufficient documentation (ISO 17025)
– Must be able to repeat the measurement:
send SOP (may be done in retrospective)
or be accredited (short description sufficient)
general uncertainty budgets interlab comp. purityH
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Study setStudy set --upup
at least two units of the material (depending on heterogeneity)
– selected over whole batch
analyses spread over at least two days
– conditions of intermediate precision
sufficient number of analyses (about 6)
independent calibrations for each result
– means 6 calibrations or more
set up clear measurement protocol stating all these facts
– also include dry mass!
general uncertainty budgets interlab comp. purityH
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Sample selection and dispatchSample selection and dispatch
selection: “random stratified”, if possible
– possibility to get estimation of homogeneity
samples must be spread over whole batch
Shipment conditions as found in the short-term stability study
A = Check dispatch procedures
general uncertainty budgets interlab comp. purityH
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Agreement of results (1)Agreement of results (1)
No eye-catching results (based on measurement uncertainty): use all data
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IC 2
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ent
general uncertainty budgets interlab comp. purityH
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Agreement of results (2)Agreement of results (2)
Groups formed by one method each:
material not certified OR method specific values or one certified value, if difference is technically not significant
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Agreement of results (3)Agreement of results (3)
One outlying dataset with uncertainties comparable to the others
material might not be certified
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Why?
H
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Agreement of results (4)Agreement of results (4)
One or more outlying datasets with higher uncertainties than the others
outlying set is removed and used as “confirmatory results”
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general uncertainty budgets interlab comp. purityH
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Major pitfalls in 5.9Major pitfalls in 5.9 --5.15?5.15?
5.9 Proper validation?
5.10 Combination of equipment and user?
5.11 An undetected “bug” –complacency?
5.12 Incorrect traceability statements?
5.13 Not checking homogeneity for all analytes?
5.14 Bad control over ovens and cooling units (calibration and alarms) Consequences?
5.15 Erroneous assumption that the majority must be right?
S
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Major pitfalls in 5.9Major pitfalls in 5.9 --5.15?5.15?
5.13 Point contamination anywhere in the chain
– (use inert materials where appropriate)
5.13 Segregation of already mixed materials?
5.14 Too wet materials?
OTHERS??? Your Opinion please, as we would like to discuss these items with you
S
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REMCOREMCOAPLAC ISO Guide 34 TrainingAPLAC ISO Guide 34 Training
Session FourISO Guide 34: 2009
Annexes
September 2010
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Annexes
Two Annexes, both informative
Annex A
– Metrological traceability of certified property values of reference materials
Annex B
– Commutability of reference materials
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Annex A
A1 - Metrological traceability of certified property values of reference materials
What is metrological traceability?
– ‘property of a measurement result whereby the result can be related to a reference through a documented unbroken chain of calibrations, each contributing to the measurement uncertainty’
ISO/IEC Guide 99:2007, 2.41 (VIM)
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Traceability in practice
A measurement exercise
Will consist of:
– a round of product ‘analysis’
– an intercomparison
– a calibration exercise
– a final round of ‘analysis’
– a thought experiment
152APLAC ISO Guide 34 Training20 September 2010
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Standard method
01
23
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5
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China
BIPM
LAB A LAB B
UK
LAB DLAB C
International
National
Traceability
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Reference
Achieving metrological traceability in chemical and bioanalytical measurement
Vicki Barwick and Steve Wood
J. Anal. At. Spectrom., 2010, DOI: 10.1039/B919885G
A tutorial article which provides practical advice to analysts and laboratory managers on how to establish metrological traceability of their results to reliable and appropriate measurement standards.
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A.2 Assignment of property values
Permitted characterization procedures include
– Single (primary) method – preferably supported by independent determinations
– Interlaboratory comparison – where data are assessed on technical basis (statistical treatment not to predominate)
Metrological traceability of property values ranges from
– Rigorous chain of calibrations back to SI base units, to
– Use of a well defined reference method
In all cases, the certificate must contain a statement of metrological traceability indicating the principles and procedures on which the property values (and uncertainties) are based.
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Annex B - Commutability
ISO/IEC Guide 99:2007, 5.15 (VIM)
– A material is commutable when equivalent mathematical ratios are observed for the results for a stated measurand obtained from the application of different measurement procedures both to the material and to a set of routine test samples containing the measurand.
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Why establish commutability?
Important where measurement procedures in routine use are based on different physical or chemical principles compared to the reference method used to assign property values for the reference material
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Assessment of commutability
Assessment of commutability requires:
– Comparison of the relationship between the property values assigned to a reference material and to standard test samples using both a higher order reference measurement procedure and one or more routine measurement procedures
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REMCOREMCOAPLAC ISO Guide 34 TrainingAPLAC ISO Guide 34 Training
Session Five
Cross-walk of 2nd and 3rd editions
September 2010
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CHANGES TO ISO GUIDE 34 FOR 2009 VERSIONCHANGES TO ISO GUIDE 34 FOR 2009 VERSION
Clause Change
2 Normative References: •New reference to ISO 9000•Reference to VIM 1993 updated to ISO/IEC Guide 99•New reference to ISO/IEC 17000•New reference to ISO/IEC 17025
3 Terms and Definitions•New NOTE 1 re definition of (certified) reference materials•New NOTE 2 re term “certification” only relating to certification of reference materials
3.2 Collaborator•2 New NOTES giving further details of role of collaborators and highlighting that collaborator is equivalent to sub-contractor in ISO/IEC 1025
3.3 Production of a Reference Material•New clause and notes covering activities involved in reference material production
3.4 Reference Material RM•New clause and notes defining RM and its uses
3.5 Certified Reference Material CRM•New clause and notes defining CRM
3.6 Commutability of a reference material•New clause and notes defining commutability
3.7 Metrological Traceability•New clause and notes defining metrological traceability
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Section 4Section 4
Clause Change
4.1 Management System – previously quality system
4.1.1 Management System Requirements •3rd paragraph more detailed
4.1.2 Quality policy•Redrafted by use of sub-headings
4.1.3 Management System•2 new sub-headings covering commutability and assessment of post-certification monitoring
4.4.1 Request, tender and Contract review•Brief paragraph on how to conduct contract review following sub-headings a) to c) deleted
4.5 Use of Collaborators•Clause 4.5.1 on policies and procedures has been reworded•New clause 4.5.3 on collaborators, specifications set for them and assessment of their competence
4.7 Customer Service•New section regarding service to customers, policy for resolving complaints/issues from customers, and seeking of feedback
4.8 Complaints•Previously named 4.7 Client feedback
4.9 Control of non-conforming work and/or reference materials•Previously named 4.8 Control of non-conforming (poor quality) reference materials •New clause after sub-headings a) to g) referring to decision on recall of reference materials
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Section 4 Section 4 -- continuedcontinued
Clause Change
4.10.2 Cause analysis• New sentence detailing root cause analysis must cover in-house production and work carried out by collaborators
4.10.3 Selection and Implementation of Corrective Actions• Clause enhanced by more detail
4.10.5 Additional audits• New clause highlighting need to audit following identification of non-conformities
4.11.1 Preventive actions• Clause reworded
4.12 Improvement• New clause on continual improvement (in line with ISO/IEC 17025)
4.13 Records• 4.13.1.3 New clause on correcting mistakes in records, in line with ISO/IEC 17025• 4.13.2 Records and reports. 2nd para reworded to include reference to ISO/IEC 17025
4.14 Internal audits• New clause 4.14.4 on follow-up activities to record the implementation and effectiveness of corrective actions
4.15 Management Reviews• Clause 4.15.1 redrafted with more detail added
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Section 5Section 5
Clause Change
5.1 Technical and production requirements• New section covering what is not required for non-certified reference materials, and subsequent renumbering of sections
5.2 Management, staffing and training• Clauses 5.2.1 (experience of producer) and 5.2.3 (education and training of staff) reworded.• New clause 5.2.5 on use of staff employed or under contract to the producer• New clause 5.2.6 on authorisation of staff to carry out particular tasks and assessment /updating of competence
5.3 Collaborators• Section restructured and expanded to give more weight to role of collaborators and establishing evidence of their
competence (accreditation, PT participation, etc) and responsibility of the producer to have the expertise to check compliance of outsourced activities and evaluate results of these.
5.4 Production Planning• Clause 5.4.1 expanded to highlight use of procedures from technical standards for production of reference materials• Clause 5.4.2 reworded but no change in sense• Clause 5.4.3 expanded significantly from 14 to 20 sub-headings covering commutability, metrological traceability, storage
conditions, post-certification stability monitoring, certificates, labelling, transportation, etc
5.6 Accommodation and environmental conditions• Section renamed from “Environment”• Clause 5.6.1 on accommodation and precautions against contamination expanded and a note added giving examples of
potential sources of contamination
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Section 5 continuedSection 5 continued
Clause Change
5.7 Material handling and storage• Clause 5.7.5 on labelling expanded to include safety labelling and what to do when the unit size limits the amount of
information on label.• Section 5.7 (Post distribution service) from 2000 version deleted. This is covered now by 4.7 Customer service.
5.8 Material Processing• Section renamed – previously Material preparation• Sub-heading b) expanded• New sub-heading c) on homogenization• New sub-heading e) on measurements for process control• Sub-heading g) on stabilization of material expanded
5.9 Measurement methods• Renumbered – previously 5.10. Old section 5.10 on homogeneity and stability measurements deleted• Section reworded to reference ISO/IEC 17025 and to highlight method validation
5.10 Measuring equipment• Clause 5.10.1 reworded to include reference to ISO/IEC 17025.
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Section 5 continuedSection 5 continued
Clause Change
5.12 Metrological Traceability• Renamed (previously Traceability and Validation)• Section considerably expanded to include details and definitions in line with ISO/IEC Guide 99
5.13 Assessment of Homogeneity• New section - from part of previous section 5.9 (homogeneity and stability)• Expanded to include references to, and consistency with ISO/IEC 17025
5.14 Assessment of Stability• New section - from part of previous section 5.9 (homogeneity and stability)• Expanded to include references to, and consistency with ISO/IEC 17025, stability under transport conditions
5.16 Characterization• 5.16.1: Sub-headings c) and d) reworded – no change of sense or coverage• 5.16.2 (Uncertainties): Rewritten to emphasis importance of estimating uncertainties, but no change of sense.
5.17 Certificates:• Much expanded section, with new Note and more detail. No change in sense or coverage.
5.18 Distribution – new section. • Covers the need to ensure materials do not deteriorate during distribution, and what documentation is required for
customs purposes to reduce delays.
5.19 Post Distribution Service• New location for this topic. This has been reworded and expanded.• New clause 5.19.1 requiring the producer to maintain an up-to-date record of all distribution and sales.
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AnnexesAnnexes
Clause Change
Annex A Metrological Traceability of Certified Property Values of Reference Materials (informative)• Section A.1 has been redrafted• Section A.2 on Property value assignment of reference materials and the procedures used for this replaces previous
section A.2 on Certification of reference materials.• The annex is significantly shorter and now contains no examples of different types of RM.
Annex B Commutability of Reference Materials (informative)• This is a new section which will require producers to consider commutability of reference materials
Annex C ISO/IEC 17025 / ISO Guide 34 Cross-reference table (informative)• New annex which shows the relationship between clauses in ISO Guide 34 and ISO/IEC 17025. This highlights that the
major changes to the Guide are in bringing it in line more formally with ISO/IEC 17025.
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REMCOREMCOAPLAC ISO Guide 34 TrainingAPLAC ISO Guide 34 Training
Session SixOther ISO Guides that contain
requirements for RMPs
September 2010
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OverviewOverview
ISO Guide 30
– Terms and definitions
ISO Guide 31
– Certificates and labels
ISO Guide 35
– General and statistical principles for certification
ISO Guide 98 – 3
– Uncertainty of measurement
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ISO REMCO document revision programmeISO REMCO document revision programme
Under revision
– ISO Guide 30
Revised text June 2010, followed by CD enquiry
– ISO Guide 31
Revised text for July 2011
– ISO Guide 35
Revision due
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ISO Guide 30, 2nd Edition, 1992
– Terms and definitions used in connection with reference materials
ISO Guide 30/Amd.1, 2008
– Revision of definitions for reference material and certified reference material
ISO Guide 30ISO Guide 30
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ISO Guide 30ISO Guide 30
Terms related to reference materials
– Reference material
– Certified reference material
– Primary standard
– Secondary standard
– Characterisation
– Homogeneity
– Stability
– Sample
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ISO Guide 30ISO Guide 30
Terms related to measurement and testing
– Certified value
– Uncertified value
– Consensus value
– Uncertainty of a certified value
– Precision
– Accuracy
– Accepted reference value
– Traceability
– Interlaboratory test
– Reference method
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ISO Guide 30ISO Guide 30
Terms related to certification and issuance of reference materials
– Certification of a reference material
– Reference material certificate
– Certification report
– Certifying body
– Certified reference material producer
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ISO Guide 30ISO Guide 30
Additional terms
– (production) batch
– Value (of a quantity)
– True value (of a quantity)
– Systematic error
– Random error
– Level of confidence
– Repeatability (of results of measurements)
– Reproducibility (of results of measurements)
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ISO Guide 31ISO Guide 31
Reference materials – Contents of certificates and labels, 2nd Edition, 2000
– To help producers prepare clear and concise certificates to accompany certified reference material.
– To help provide a summary of the information needed by the user of the reference material
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ISO Guide 31ISO Guide 31
Terms and Definitions
– Certificate
Document containing all the information essential to the use of a CRM [Note: a CRM and certificate should never be parted]
– Intended use
Use of a product, process or service in accordance with information provided by the supplier
– Hazardous situation
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ISO Guide 31ISO Guide 31
4. General
– Certificate
Amount of information included in a certificate depends on the ready availability of a certification report
Details given in a certificate and certification report may permit the user to make a judgement on the quality and integrity of the CRM
– Label
Information provided on the label should identify the CRM and belimited to the name of the producer, the name of the material, the producers code for the material, the batch number and relevant health and safety warnings
Recommended that certified property values are not included on the label – WHY?
to prevent the material being used without the certificate beingstudied
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ISO Guide 31ISO Guide 31
5 Certificate headings
– 5.1 General
– 5.2 Name and address of certifying body
– 5.3 Title of document
– 5.4 Name of material
– 5.5 Reference material code and batch number
– 5.6 Description of the CRM
– 5.7 Intended use
– 5.8 Instructions for use
– 5.9 Hazardous situation
– 5.10 Level of homogeneity
Exercise: - What would you expect on a certificate?
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ISO Guide 31ISO Guide 31
5 Certificate headings (cont.)
– 5.11 Certified values and their uncertianties
– 5.12 Traceability
– 5.13 Other values
Different laboratories or methods
– 5.14 Uncertified values
– 5.15 Date of certification
– 5.16 Period of validity
– 5.17 Further information
– 5.18 Names and signatures of certifying officers
What would you expect on a certificate?
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ISO Guide 31ISO Guide 31
6 Summary of essential information of a certificate
– Name of material
– Producer and producer’s code for the material
– General description of the material
– Intended use
– Instructions for proper use
– Instructions for appropriate conditions of storage
– Certified property values and uncertainties
– Methods used to obtain property values
– Period of validity
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ISO Guide 35ISO Guide 35
General and statistical principles for certification, 3rd edition, 2006
182APLAC ISO Guide 34 Training20 September 2010
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ISO Guide 35ISO Guide 35
Contents
– 5. Design of certification project
– 6. Evaluating measurement uncertainty
– 7. Homogeneity study
– 8. Stability study
– 9. Determination of property values
– 10. Data and uncertainty evaluation
– 11. Certification
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Guide to Uncertainty in MeasurementGuide to Uncertainty in Measurement
ISO/IEC Guide 98-1:2009
– Part 1 : Introduction to the GUM
– Also outlines documents intended to extend the application to broader categories and fields of practical problems.
ISO/IEC Guide 98-2
– Part 2 : Concepts and basic principles
– In preparation
ISO/IEC Guide 98-3:2008/Suppl 1:2008/Cor 1:2009
– Part 3 : reissue of the 1995 version of the GUM, with minor corrections
– Also available from BIPM as JCGM 100:2008
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ISO/IEC Guide 98ISO/IEC Guide 98 --3:2008 3:2008 –– what is it?what is it?
Uncertainty of measurement - Part 3: Guide to the expression of uncertainty in measurement (GUM:1995),
– a reissue of the 1995 version of the Guide to the Expression of Uncertainty in Measurement (GUM), with minor corrections.
Also available from BIPM as
– JCGM 100:2008
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How did it evolve?How did it evolve?
The basis of the Guide is Recommendation 1 (CI-1981) of the Comité International des Poids et Mesures (CIPM) and Recommendation INC-1 (1980) of the Working Group on the Statement of Uncertainties.
The Working Group was convened by the Bureau International des Poids et Mesures (BIPM) in response to a request of the CIPM.
The ClPM recommendation is the only recommendation concerning the expression of uncertainty in measurement adopted by an intergovernmental organization
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What does it do?What does it do?
The principles of this Guide are intended to be applicable to a broad spectrum of measurements, including those required for:
– Maintaining quality control and quality assurance in production;
– complying with and enforcing laws and regulations;
– conducting basic research, and applied research and development, in science and engineering;
– calibrating standards and instruments and performing tests throughout a national measurement system in order to achieve traceability to national standards;
– developing, maintaining, and comparing international and national physical reference standards, including reference materials.
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AlsoAlso …………..
JCGM 101:2008
– Evaluation of measurement data — Supplement 1 to the “Guide to the expression of uncertainty in measurement” — Propagation of distributions using a Monte Carlo method
JCGM 104:2009
– Evaluation of measurement data — An introduction to the “Guide to the expression of uncertainty in measurement” and related documents