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1APLAC ISO Guide 34 Training20 September 2010

REMCO – ISO Committee on Reference Materials

ISO Guide 34 Training



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

B



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

B



REMCOREMCOAPLAC ISO Guide 34 TrainingAPLAC ISO Guide 34 Training

Session OneISO REMCO Overview

Introduction to Guide 34

September 2010

B



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.

B



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.

B



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

B



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

B



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



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).

B



The REMCO Family of GuidesThe REMCO Family of Guides

The reference for accreditationThe reference

for accreditation

B



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



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

B



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



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

B



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



Categorization ExampleCategorization Example




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



Natural Materials Natural Materials –– Organic ConstituentsOrganic Constituents




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)



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




Session TwoISO Guide 34: 2009

Management Requirements

September 2010

B



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

B



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 ♦

B



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

B



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.

B



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



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



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



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.

S



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

S



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

S



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



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

S



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

S



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

S



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

S



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

S



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



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

S



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



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

S




Session ThreeISO Guide 34: 2009

Technical Requirements

September 2010

B



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

B



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

B



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

B



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

B



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

B



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



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

B



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

B



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

S



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

S



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

S



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

S




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

S




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

S



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



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

S



Planning Exercise

Suggest an exercise on planning a simple RM project using the ERM project planning form as a template.

S



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



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

H



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]

H



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

H



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



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



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



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



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



5.12 Metrological Traceability5.12 Metrological Traceability5.12 Metrological Traceability

H



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




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




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




Imagine, you buy 250 g sausages at the local butcher. Upon weighing at home, you find only 200 g. Is there a problem?




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





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




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)




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




IdentityIdentity

Structurally defined

clearly defined molecule, physical property

independent of the method


Method defines the analyte

Size of this particle?




Two aspects of traceabilityTwo aspects of traceability

Traceability is split into

Identity (measurand)

Quantity value (number and unit)



SI reference

Artefact reference




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




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




IdentityIdentity


pure standard CRMs (retention time, mass/charge ratio, etc.)


the right method

at the right conditions

– Physical property CRMs: calibrated flasks, thermometers, balances, etc.




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.




comparison DON?

Quantity value Quantity value –– sample preparationsample preparation




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




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






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




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)




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).




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



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



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



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




0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

freq

uenc

y q3

*(x)

0

0.1

0.2

0.3

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0.9

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

0

0.05

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freq

uenc

y q3

*(x)

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0.95

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



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!


H



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


H




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




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



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


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



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



Evaluation HomogeneityEvaluation Homogeneity

ANOVA (Analysis of Variance)

Low “between”and low “within”

High “between”and low “within”

H



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



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



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



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



5.13, 35.13, 3--D mixingD mixing

Much smaller bench top 3-D-mixers are also available

BULKX

H



5.13 Cone mixer5.13 Cone mixer

BULKX

H



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



5.14 Accelerated stability studies?5.14 Accelerated stability studies?

H



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



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



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



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



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



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



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



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



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



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



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



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



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



5.14 Freeze drying / Oven drying5.14 Freeze drying / Oven drying

H



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



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



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




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




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




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




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




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




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




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.




Ideal characterisation studyIdeal characterisation study

many methods, many labs, all with uncertainties,all results agree within their expanded uncertainties

15

20

25

30

35

40

45

50

met

hod

1

met

hod

2

met

hod

3

met

hod

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met

hod

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met

hod

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met

hod

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met

hod

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met

hod

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met

hod

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met

hod

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met

hod

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met

hod

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met

hod

14

met

hod

15

met

hod

16

met

hod

17

met

hod

18

met

hod

19

met

hod

20




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 ++=




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)




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




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)




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!




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




Agreement of results (1)Agreement of results (1)

No eye-catching results (based on measurement uncertainty): use all data

0

2

4

6

8

10

12

14

16

18

20

HP

LC 1

HP

LC 2

HP

LC 3

GC

1

GC

2

CE

1

CE

2

CE

3

CE

4

IC 1

IC 2

anal

yte

cont

ent





Groups formed by one method each:

material not certified OR method specific values or one certified value, if difference is technically not significant

5

7

9

11

13

15

17

19

21

23

25

HP

LC 1

HP

LC 2

HP

LC 3

GC

1

GC

2

CE

1

CE

2

CE

3

CE

4

IC 1

IC 2

anal

yte

cont

ent





One outlying dataset with uncertainties comparable to the others

material might not be certified

5

7

9

11

13

15

17

19

21

23

25

HP

LC 1

HP

LC 2

HP

LC 3

GC

1

GC

2

CE

1

CE

2

CE

3

CE

4

IC 1

IC 2

anal

yte

cont

ent

general uncertainty budgets interlab comp. purity

Why?

H




One or more outlying datasets with higher uncertainties than the others

outlying set is removed and used as “confirmatory results”

5

7

9

11

13

15

17

19

21

23

25

HP

LC 1

HP

LC 2

HP

LC 3

GC

1

GC

2

CE

1

CE

2

CE

3

CE

4

IC 1

IC 2

anal

yte

cont

ent




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



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




Session FourISO Guide 34: 2009

Annexes

September 2010



Annexes

Two Annexes, both informative

Annex A

– Metrological traceability of certified property values of reference materials

Annex B

– Commutability of reference materials



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)



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



Standard method

01

23

46

5

01

23

46

78

910

5



China

BIPM

LAB A LAB B

UK

LAB DLAB C

International

National

Traceability



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.



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.



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.



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



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




Session Five

Cross-walk of 2nd and 3rd editions

September 2010



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



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



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



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



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.



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.



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.




Session SixOther ISO Guides that contain

requirements for RMPs

September 2010



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



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



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




Terms related to reference materials

– Reference material

– Certified reference material

– Primary standard

– Secondary standard

– Characterisation

– Homogeneity

– Stability

– Sample




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




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




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)




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




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




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




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?




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?




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




General and statistical principles for certification, 3rd edition, 2006




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



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



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



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



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.



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

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