GUIDE 34

General requirements for the competence of reference material

producers
ISO GUIDE 34:2009E!
"ontents
Page
#ore$ord %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%i&
Introduction%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%&
' Scope%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'
2 (ormati&e references%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'
3 )erms and definitions %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%2
4 Or*ani+ation and mana*ement requirements%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%4
4%' ,ana*ement s-stem requirements %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%4
4%2 Or*ani+ation and mana*ement%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%.
4%3 Document and information control %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%/
4%4 0equest1 tender and contract re&ie$s %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%2
4%3 Use of su4contractors %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%2
4%. 5rocurement of ser&ices and supplies %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%9
4%/ "ustomer ser&ice %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%9
4%2 "omplaints %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%9
4%9 "ontrol of non6conformin* $or7 and8or reference materials%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%9
4%'0 "orrecti&e actions %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'0
4%'' 5re&enti&e actions%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%''
4%'2 Impro&ement %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%''
4%'3 0ecords %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%''
4%'4 Internal audits %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'2
4%'3 ,ana*ement re&ie$s %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'3
3 )echnical and production requirements%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'3
3%' General %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'3
3%2 5ersonnel %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'4
3%3 Su4contractors %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'4
3%4 5roduction plannin*%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'3
3%3 5roduction control %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'.
3%. 9ccommodation and en&ironmental conditions%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'.
3%/ ,aterial handlin* and stora*e %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'/
3%2 ,aterial processin*%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'2
3%9 ,easurement methods %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'2
3%'0 ,easurin* equipment %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'2
3%'' Data e&aluation %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'9
3%'2 ,etrolo*ical tracea4ilit- %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%'9
3%'3 9ssessment of homo*eneit- %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%2'
3%'4 9ssessment of sta4ilit- %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%2'
3%'3 "haracteri+ation %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%22
3%'. 9ssi*nment of propert- &alues and their uncertainties%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%23
3%'/ "ertificates or documentation for users%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%23
3%'2 Distri4ution ser&ice %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%24
9nne: 9 (informative) ,etrolo*ical tracea4ilit- of certified propert- &alues of reference materials %%%%%%23
9nne: ; (informative) "ommuta4ilit- of reference materials %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%2/
9nne: " (informative) ISO8IE" '/0238ISO Guide 34 cross6reference ta4le %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%29
;i4lio*raph-%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%34
#ore$ord
ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies
(ISO member bodies). The work of preparing International Standards is normally carried ot throgh ISO
technical committees. !ach member body interested in a sb"ect for which a technical committee has been
established has the right to be represented on that committee. International organizations# governmental and
non$governmental# in liaison with ISO# also take part in the work. ISO collaborates closely with the
International !lectrotechnical %ommission (I!%) on all matters of electrotechnical standardization.
International Standards are drafted in accordance with the rles given in the ISO&I!% 'irectives# Part (.
'raft )ides adopted by the responsible %ommittee or )rop are circlated to the member bodies for voting.
Pblication as a )ide re*ires approval by at least +, - of the member bodies casting a vote.
.ttention is drawn to the possibility that some of the elements of this docment may be the sb"ect of patent
rights. ISO shall not be held responsible for identifying any or all sch patent rights.
ISO )ide /0 was prepared by the ISO Reference Materials Committee (1!2%O).
This third edition cancels and replaces the second edition (ISO )ide /03(444)# which has been technically
revised. It also incorporates the Technical %orrigendm ISO )ide /03(444&%or.53(44/.
Introduction
The se of reference materials enables the transfer of the vales of measred or assigned properties between
testing and measrement laboratories. Sch materials are widely sed# e.g. for the calibration of measring
e*ipment and for the evalation or validation of measrement procedres. In certain cases# they enable
properties to be e6pressed conveniently in arbitrary nits.
7OT! The concept 8reference material9 is inclded in the concept 8measrement standard9# both of which also
inclde physical reference materials sed for calibrating instrments in mechanical# non$destrctive and constrction
type$testing facilities.
There are an increasing nmber of reference material prodcers# and a demonstration of their scientific and
technical competence is nowadays a basic re*irement for ensring the *ality of reference materials. The
demand for new reference materials of higher *ality is increasing as a conse*ence of both the increased
precision of measring e*ipment and the re*irement for more accrate and reliable data in the scientific
and technological disciplines. Some previosly acceptable reference materials may not meet these more
stringent re*irements anymore. It is# therefore# not only necessary for reference material prodcers to
provide information abot their materials in the form of reports# certificates and statements# bt also to
demonstrate their competence in prodcing reference materials of appropriate *ality.
The first edition of ISO )ide /0 set ot specific gidelines on the interpretation of ISO&I!% )ide (, and the
International Standards prepared by ISO&T% 5+:5) in the conte6t of reference material prodction. The more
general re*irements of these International Standards were omitted. Since the first edition of ISO )ide /0
was pblished in 5;;:# the assessment of the competence of reference material prodcers has gained
considerable impets. The second edition of ISO )ide /0 set ot all the general re*irements in accordance
with which a reference material prodcer has to demonstrate that it operates. The present edition makes
these re*irements mandatory and in line with ISO&I!% 5+4(,3(44,&%or.53(44: in view of its se for the
assessment of the competence of reference material prodcers applying for accreditation. <or tests performed
in the medical field# ISO 5,5=; may be sed as the reference instead of ISO&I!% 5+4(,.
5) Inclding ISO ;444# ISO ;445 and ISO ;440.
General requirements for the competence of reference material
producers
' Scope
'%' This )ide specifies general re*irements in accordance with which a reference material prodcer has
to demonstrate that it operates# if it is to be recognized as competent to carry ot the prodction of reference
materials.
'%2 This )ide is intended for the se by reference material prodcers in the development and
implementation of their management system for *ality# administrative and technical operations. 1eference
material cstomers# reglatory athorities and accreditation bodies may also se it in confirming and
recognizing the competence of reference material prodcers.
7OT! This )ide is not intended to be sed as the basis for conformity assessment by certification bodies.
'%3 This )ide sets ot the management system re*irements in accordance with which reference
materials shall be prodced. It is intended to be sed as part of a reference material prodcer>s general *ality
assrance (?.) procedres.
'%4 This )ide covers the prodction of certified and non$certified reference materials. <or non$certified
reference materials# the prodction re*irements are less stringent than for certified reference materials. The
minimm re*irements for the prodction of non$certified reference materials are specified throghot the
)ide.
2 (ormati&e references
The following referenced docments are indispensable for the application of this docment. <or dated
references# only the edition cited applies. <or ndated references# the latest edition of the referenced
docment (inclding any amendments) applies.
ISO )ide /4# Terms and definitions used in connection with reference materials
ISO )ide /5# Reference materials Contents of certificates and labels
ISO )ide /,# Reference materials General and statistical principles for certification
ISO&I!% )ide ;=$/# Uncertainty of measurement Part 3: Guide to the expression of uncertainty in
measurement GUM!
ISO&I!% )ide ;;# "nternational #ocabulary of metrolo$y %asic and $eneral concepts and associated terms
&"M!
ISO ;444# 'uality mana$ement systems (undamentals and #ocabulary
ISO 5445(# Measurement mana$ement systems Re)uirements for measurement processes and
measurin$ e)uipment
ISO 5,5=;# Medical laboratories Particular re)uirements for )uality and competence
1
ISO&I!% 5+444# Conformity assessment &ocabulary and $eneral principles
ISO&I!% 5+4(,# General re)uirements for the competence of testin$ and calibration laboratories
3 )erms and definitions
<or the prposes of this docment# the terms and definitions given in ISO&I!% 5+444# ISO&I!% 5+4(,#
ISO )ides /4 and /,# ISO ;444# ISO&I!% )ide ;; and the following apply.
7OT! The definition of (certified) reference materials in this )ide is referenced to ISO )ide /4 (not
ISO&I!% )ide ;;).
@nless e6plicitly stated otherwise# the term 8certification9 is sed for the certification of reference materials and
shall not be confsed with prodct certification or certification of management systems.
3%'
reference material producer
body (organization or company# pblic or private) that is flly responsible for pro"ect planning and
management# assignment of and decision on property vales and relevant ncertainties# athorization of
property vales and isse of the certificate or other statements for the reference materials it prodces
3%2
su4contractor
body (organization or company# pblic or private) that ndertakes aspects of the processing# handling#
homogeneity and stability assessment# characterization# storage or distribtion of the reference material on
behalf of the reference material prodcer# on a contractal basis# either paid or non$paid (see ,./.5)
7OT! 5 Aey tasks&aspects of the reference material prodction process which cannot be performed by e6ternal parties
are pro"ect planning# assignment and decision on property vales and relevant ncertainties# athorization of property
vales and issing of certificates or other statements for the reference materials.
7OT! ( The concept 8sbcontractor9 is e*ivalent to the concept 8collaborator9.
7OT! / .dvisors# who cold be asked for recommendations# bt who are not involved in decision making or the
e6ection of any aspects mentioned in the definition above# are not considered as sbcontractors.
3%3
production of a reference material
all necessary activities and tasks leading to a reference material (certified or non$certified) spplied to
cstomers
7OT! Prodction of a reference material incldes prodction planning# prodction control# material handling and
storage# material processing (also referred to as 8manfactring9 or 8preparation9)# assessment of homogeneity and
stability# isse of statements and post$distribtion service of the reference materials. It can inclde characterization#
assignment of property vales and their ncertainties# athorization and isse of certificates for certified reference
materials.
3%4
reference material
0,
material# sfficiently homogeneos and stable with respect to one or more specified properties# which has
been established to be fit for its intended se in a measrement process
7OT! 5 12 is a generic term.
7OT! ( Properties can be *antitative or *alitative (e.g. identity of sbstances or species).
7OT! / @ses may inclde the calibration of a measrement system# assessment of a measrement procedre#
assigning vales to other materials# and *ality control.
2
7OT! 0 . single 12 cannot be sed for both calibration and validation of reslts in the same measrement procedre.
7OT! , BI2 has an analogos definition (ISO&I!% )ide ;;3(44+# ,.5/)# bt restricts the term 8measrement9 to apply
to *antitative vales and not to *alitative properties. Cowever# 7ote / of ISO&I!% )ide ;;3(44+# ,.5/# specifically
incldes the concept of *alitative attribtes# called 8nominal properties9.
DISO )ide /435;;(&.md.53(44=# definition (.5E
3%3
certified reference material
"0,
reference material characterized by a metrologically valid procedre for one or more specified properties#
accompanied by a certificate that provides the vale of the specified property# its associated ncertainty# and
a statement of metrological traceability
7OT! 5 The concept of vale incldes *alitative attribtes sch as identity or se*ence. @ncertainties for sch
attribtes may be e6pressed as probabilities.
7OT! ( 2etrologically valid procedres for the prodction and certification of reference materials are given in# among
others# ISO )ides /0 and /,.
7OT! / ISO )ide /5 gives gidance on the contents of certificates.
7OT! 0 BI2 has an analogos definition (ISO&I!% )ide ;;3(44+# ,.50).
DISO )ide /435;;(&.md.53(44=# definition (.(E
3%.
commuta4ilit- of a reference material
property of a reference material# demonstrated by the closeness of agreement between the relation among
the measrement reslts for a stated *antity in this material# obtained according to two given measrement
procedres# and the relation obtained among the measrement reslts for other specified materials
7OT! 5 The reference material in *estion is normally a calibrator and the other specified materials are sally rotine
samples.
7OT! ( The measrement procedres referred to in the definition are the one preceding and the one following the
reference material (calibrator) in *estion in a calibration hierarchy.
7OT! / The stability of commtable reference materials is monitored reglarly.
DISO&I!% )ide ;;3(44+# definition ,.5,E
3%/
metrolo*ical tracea4ilit-
property of a measrement reslt whereby the reslt can be related to a reference throgh a docmented
nbroken chain of calibrations# each contribting to the measrement ncertainty
7OT! 5 <or this definition# a 8reference9 can be a definition of a measrement nit throgh its practical realization# or a
measrement procedre inclding the measrement nit for a non$ordinal *antity# or a measrement standard.
7OT! ( 2etrological traceability re*ires an established calibration hierarchy.
7OT! / Specification of the reference mst inclde the time at which this reference was sed in establishing the
calibration hierarchy# along with any other relevant metrological information abot the reference# sch as when the first
calibration in the calibration hierarchy was performed.
7OT! 0 <or measrements with more than one inpt *antity in the measrement model# each of the inpt *antity
vales shold itself be metrologically traceable and the calibration hierarchy involved may form a branched strctre or a
network. The effort involved in establishing metrological traceability for each inpt *antity vale shold be commensrate
with its relative contribtion to the measrement reslt.
3
7OT! , 2etrological traceability of a measrement reslt does not ensre that the measrement ncertainty is
ade*ate for a given prpose or that there is an absence of mistakes.
7OT! : . comparison between two measrement standards may be viewed as a calibration if the comparison is sed
to check and# if necessary# correct the *antity vale and measrement ncertainty attribted to one of the measrement
standards.
7OT! + The IF.% considers the elements for confirming metrological traceability to be an nbroken metrological
traceability chain to an international measrement standard or a national measrement standard# a docmented
measrement ncertainty# a docmented measrement procedre# accredited technical competence# metrological
traceability to the SI# and calibration intervals (see IF.%$P543(44(D;E).
7OT! = The abbreviated term 8traceability9 is sometimes sed to mean 8metrological traceability9 as well as other
concepts# sch as 8sample traceability9 or 8docment traceability9 or 8instrment traceability9 or 8material traceability9#
where the history (8trace9) of an item is meant. Therefore# the fll term of 8metrological traceability9 is preferred if there is
any risk of confsion.
DISO&I!% )ide ;;3(44+# definition (.05E
3%2
measurement uncertaint-
non$negative parameter characterizing the dispersion of the *antity vales being attribted to a measrand#
based on the information sed
7OT! 5 2easrement ncertainty incldes components arising from systematic effects# sch as components
associated with corrections and the assigned *antity vales of measrement standards# as well as the definitional
ncertainty. Sometimes estimated systematic effects are not corrected for bt# instead# associated measrement
ncertainty components are incorporated.
7OT! ( The parameter may be# for e6ample# a standard deviation called standard measrement ncertainty (or a
specified mltiple of it)# or the half$width of an interval# having a stated coverage probability.
7OT! / 2easrement ncertainty comprises# in general# many components. Some of these may be evalated by
Type . evalation of measrement ncertainty from the statistical distribtion of the *antity vales from series of
measrements and can be characterized by standard deviations. The other components# which may be evalated by
Type G evalation of measrement ncertainty# can also be characterized by standard deviations# evalated from
probability density fnctions based on e6perience or other information.
7OT! 0 In general# for a given set of information# it is nderstood that the measrement ncertainty is associated with
a stated *antity vale attribted to the measrand. . modification of this vale reslts in a modification of the associated
ncertainty.
DISO&I!% )ide ;;3(44+# definition (.(:E
4 Or*ani+ation and mana*ement requirements
4%' ,ana*ement s-stem requirements
4%'%' General
The reference material prodcer shall establish# implement and maintain a docmented management system
appropriate to the scope of its activities# inclding the type# range and volme of the reference material
prodction it ndertakes.
It shall be recognized that a reference material property needs to be characterized mainly to the level of
accracy re*ired for its intended prpose (i.e. appropriate measrement ncertainty for a property vale of a
certified reference material). The reference material prodcer shall describe the procedre for establishing the
*ality of materials as a component of the management system.
4
1eference material prodcers shall define their scope of activities in terms of the types of reference materials
(inclding the sample matrices# if applicable)# the properties to be certified and the ranges of assigned vales
(and their ncertainties) of the reference materials they prodce# and their involvement in the performance of
testing# calibration and measrements in relation to homogeneity# stability and characterization assessments
and their se of sbcontractors in these tasks.
4%'%2 <ualit- polic-
The reference material prodcer shall define and docment its policy# ob"ectives and commitment to ensring
and maintaining the *ality of all aspects of reference material prodction# inclding material *ality (e.g.
homogeneity and stability with respect to specified properties)# characterization (e.g. e*ipment calibration
and measrement method validation)# assignment of property vales (e.g. se of appropriate statistical
procedres for data evalation) and material handling# storage and transport procedres.
The reference material prodcer>s management system policies related to *ality# inclding a *ality policy
statement# shall be docmented in a *ality manal (however named). It shall be issed nder the athority of
the top management.
The *ality policy shall inclde bt shall not be limited to the following commitments3
a) to prodce reference materials which conform to the re*irements of this )ide and to the definitions
given in ISO )ide /4H
b) to prodce# where applicable# certified reference materials according to the re*irements of ISO )ide /,
and accompanied by certificates meeting the re*irements of ISO )ide /5H
c) to condct all testing and calibration in spport of the prodction of reference materials in compliance with
the re*irements of ISO&I!% 5+4(,()H
d) to re*ire that all personnel concerned with the *ality of any aspect of reference material prodction
activities familiarize themselves with the *ality docmentation and implement the policies and
procedres in their workH
e) for the management to continally improve the effectiveness of the management system and to be
committed to good professional practice and to the *ality of its reference materials.
The overall ob"ectives shall be reviewed dring the management review.
4%'%3 ,ana*ement s-stem
The reference material prodcer shall docment all of its policies# systems# programmes# procedres#
instrctions# findings# etc.# to the e6tent necessary to enable the prodcer to ensre the *ality of the
reference materials prodced. 'ocmentation sed in this management system shall be commnicated to#
nderstood by# available to and implemented by all personnel concerned. In particlar# the prodcer shall
have a management system that covers the following3
a) arrangements for ensring the sitable choice (e.g. type of material# concentration range# etc.) of the
candidate reference materialsH
b) processing procedresH
c) assessment of the re*ired degree of homogeneity of the reference materialH
d) assessment of the stability of the reference material and determination of the period of validity of the
certificate or statementH
() <or tests performed in the medical field# ISO 5,5=; may be sed as a reference instead of ISO&I!% 5+4(,.
5
e) procedres for ndertaking characterization (if applicable)H
f) assessment of commtability (where appropriate)H
g) practical realization of metrological traceability of measrement reslts to a stated referenceH
h) assignment of property vales# inclding preparation of certificates or statements in accordance with
ISO )ide /5 when appropriateH
i) arrangements for ensring ade*ate storage facilitiesH
") arrangements for sitable identification# labelling and packaging facilities# packing and delivery
procedres in compliance with international safety reglations# and cstomer serviceH
k) assessment of post$certification stability monitoring as re*ired for the e6tension of the assigned period of
validity of the reference material certificate (if applicable)H
l) compliance with ISO )ide /4 and with appropriate sections of ISO )ides /5 and /,.
The docmented management system shall specify which activities are ndertaken by the reference material
prodcer and# where relevant# which activities are ndertaken by sbcontractors. It shall inclde policies and
procedres sed by the prodcer to ensre that all activities condcted by sbcontractors comply with the
relevant clases of this )ide.
The docmented management system shall define the roles and responsibilities of the technical management
and the *ality manager (however named)# inclding their responsibilities for ensring compliance with this
)ide.
4%2 Or*ani+ation and mana*ement
4%2%' The reference material prodcer# or the organization of which it is part# shall be an entity that can be
held legally responsible.
4%2%2 The reference material prodcer shall be organized and shall operate in sch a way that it meets all
the applicable re*irements of this )ide# whether carrying ot work at its permanent facilities or at sites
(inclding associated temporary or mobile facilities) away from its permanent facilities.
4%2%3 The reference material prodcer shall
a) have managerial personnel# spported by technical personnel# with the athority and resorces needed to
discharge their dties and to identify the occrrence of departres from the management system or the
procedres for the prodction of reference materials and to initiate actions to prevent or minimize sch
departresH
b) have arrangements to ensre that its management and personnel are free from any nde internal and
e6ternal commercial# financial and other pressres and inflences that may adversely affect the *ality of
their workH
c) have policies and procedres to ensre the protection of its cstomer>s confidential information and
proprietary rightsH
d) have policies and procedres to avoid involvement in any activities that might diminish confidence in its
competence# impartiality# "dgement or operational integrityH
e) define# with the aid of organizational charts# the organization and management strctre of the reference
material prodcer# its place in any parent organization# and the relations between management# technical
operations# spport services# sbcontractors and the *ality management systemH
6
f) specify the responsibility# athority and interrelationships of all personnel who manage# perform or verify
work affecting the *ality of reference materials prodcedH
g) have technical management# inclding a technical manager# who has overall responsibility for the
technical operations and the provision of the resorces needed to ensre the re*ired *ality of each
operation which forms part of the reference material prodctionH
h) appoint a member of staff as *ality manager (however named) who# irrespective of other dties and
responsibilities# shall have defined responsibility and athority for ensring that the re*irements of this
)ide are implemented and followed at all timesH the *ality manager shall have direct access to the
highest level of management at which decisions are taken on prodction policy or resorcesH
i) appoint depties for key managerial personnel sch as the technical and *ality managers.
4%3 Document and information control
4%3%' General
The reference material prodcer shall establish and maintain procedres to control all docments (both
internally generated and from e6ternal sorces) and other information that form part of its management
system. These may inclde docments of e6ternal origin# sch as standards# gides# test and&or calibration
methods# as well as specifications# instrctions and manals related to the reference material nder
prodction.
7OT! In this conte6t# 8docment9 means any information or instrction inclding policy statements# te6t books#
procedres# specifications# calibration tables# charts# software# etc. These may be on varios media# whether in hard copy
or electronic# and they may be in digital# analoge# photographic or written form.
4%3%2 Document appro&al and issue
4%3%2%' .ll docments issed to personnel as part of the management system shall be sitably controlled.
This shall inclde review and approval for se by athorized personnel prior to isse. . master list or
e*ivalent# identifying the crrent revision stats of docments in the management system# shall be
established and be readily available to preclde the se of invalid and&or obsolete docments.
4%3%2%2 The procedres adopted shall also ensre that
a) athorized editions of appropriate docments are available at all locations where operations essential to
the effective prodction of reference materials are performedH
b) docments are periodically reviewed and# where necessary# revised to ensre contining sitability and
compliance with applicable re*irementsH
c) invalid or obsolete docments are promptly removed from all points of isse or se# or otherwise assred
against nintended seH
d) obsolete docments retained for either legal or information preservation prposes are sitably marked.
4%3%2%3 2anagement system docments generated by the reference material prodcer shall be ni*ely
identified. Sch identification shall inclde the date of isse and&or revision nmber# page nmbering# the total
nmber of pages or a mark to signify the end of the docment# and the issing athority(ies).
4%3%3 Document chan*es
4%3%3%' %hanges to docments shall be reviewed and approved by designated personnel performing the
same fnction as that condcted for the original review and approval nless specifically decided otherwise.
The designated personnel shall have access to pertinent backgrond information pon which to base their
review and approval.
7
4%3%3%2 Ihere practicable# the natre of the change shall be identified in the docment or appropriate
attachments.
4%3%3%3 If the reference material prodcer>s docment control system allows for the amendment of
docments by hand# pending the re$isse of the docments# the procedres and athorities for sch
amendments shall be defined. .mendments shall be clearly marked# initialled and dated. . revised docment
shall be formally re$issed as soon as practicable.
4%3%3%4 Procedres shall be established to describe how changes in docments maintained in
compterized systems are made and controlled.
4%4 0equest1 tender and contract re&ie$s
4%4%' !ach re*est# tender or contract concerning the prodction of a reference material shall be reviewed#
following docmented policies and procedres# established by the reference material prodcer to ensre that
a) the re*irements are ade*ately defined# docmented and nderstoodH
b) the reference material prodcer has the capability and resorces to meet the re*irementsH
c) in the case of contracts# any differences between the contract or order re*irements and those in a tender
are resolved to the satisfaction of the reference material prodcer and the cstomer.
7OT! 5 %apability means that the reference material prodcer has access to# for e6ample# the necessary e*ipment#
intellectal and information resorces and that its personnel have the skills and e6pertise necessary for the prodction of
those reference materials in *estion. The review of the capability can inclde an assessment of previos reference
material prodctions and&or the organization of interlaboratory characterization programmes sing samples of similar
composition to the reference materials to be prodced.
7OT! ( . contract can be any written or verbal agreement to provide a cstomer with reference materials from stock
or cstom$prodced.
4%4%2 1ecords of sch reviews# inclding any changes# shall be maintained. 1ecords shall also be
maintained of pertinent discssions with a cstomer relating to the cstomer>s re*irements or the reslts of
the work dring the period of e6ection of the contract or re*est.
4%4%3 The review shall inclde any work that has to be contracted by the reference material prodcer.
4%3 Use of su4contractors
4%3%' The reference material prodcer shall have policies and se docmented procedres to select
competent sbcontractors and shall establish and maintain procedres to ensre that all tasks performed by
sbcontractors comply with specifications set by the reference material prodcer for sch tasks. The reference
material prodcer shall also ensre that sbcontractors comply with any clases of this )ide relevant to the
tasks performed by them for the reference material prodcer.
4%3%2 The reference material prodcer shall select sbcontractors on the basis of their ability to meet the
re*irements stiplated by the reference material prodcer in terms of both their technical competence and
any specific *ality management system re*irements relevant to their tasks. The technical re*irements that
the sbcontractors shall meet shall be e*ivalent to either all# or the applicable# technical re*irements
specified in %lase , of this )ide.
4%3%3 Iork carried ot by sbcontractors shall be performed according to the specifications set by the
reference material prodcer. Sbcontractors can be paid or non$paidH in all cases# a protocol shall specify the
re*irements for e6ecting their tasks. <or sbcontractors e6ecting measrements or testing# the
specifications shall inclde re*irements as described in ISO&I!% 5+4(,. Prodcers shall ensre that they are
provided by the sbcontractors with the information to ensre compliance with the re*irements of
ISO&I!% 5+4(,.
8
The reference material prodcer shall assess the competence of the sbcontractors by appropriate means.
Ihilst it is encoraged that sbcontractors e6ecting measrements and testing be accredited to
ISO&I!% 5+4(,# this is not a mandatory re*irement. There are other ways to assess sbcontractor
competence# e.g. adit# performance on *ality control materials# historical performance on inter$laboratory
comparisons (see also ,./.().
4%3%4 The reference material prodcer shall maintain a register of all sbcontractors sed and inclde a
record of any assessments made of their abilities to carry ot contracted tasks according to the re*irements
of this )ide. These records shall inclde any *ality assrance approval the sbcontractor holds.
4%. 5rocurement of ser&ices and supplies
4%.%' The reference material prodcer shall have policies and procedres in place for the selection of
services and spplies that affect the *ality of its reference materials.
4%.%2 The reference material prodcer shall se only those services and spplies that comply with specified
re*irements to ensre the *ality of the reference materials it prodces.
4%.%3 Ihen no formal approval of the *ality of services and spplies is available# the reference material
prodcer shall have procedres to ensre that prchased spplies and services comply with specified
re*irements# and records of actions taken shall be maintained.
4%.%4 The reference material prodcer shall ensre that prchased e*ipment and consmable materials
are not sed ntil they have been inspected# calibrated or otherwise verified as complying with the
specifications or re*irements defined in specifications for prodction# characterization and certification of the
reference materials it prodces.
4%.%3 The reference material prodcer shall maintain records of the sppliers and sbcontractors from
whom it obtains services and spplies. These records shall inclde any *ality assrance approval the
sppliers and&or sbcontractors hold.
4%/ "ustomer ser&ice
4%/%' The reference material prodcer shall be willing to cooperate with cstomers or their representatives
in clarifying the cstomer>s re*ests and *estions.
4%/%2 The reference material prodcer shall seek feedback# both positive and negative# from its cstomers.
The feedback shall be sed and analysed to improve the management system# reference material prodction
activities and cstomer service.
4%2 "omplaints
The reference material prodcer shall have a policy and procedre for the resoltion of complaints received
from cstomers or other parties. 1ecords shall be maintained of all complaints and of the investigations and
corrective actions taken by the reference material prodcer (see also 0.54).
4%9 "ontrol of non6conformin* $or7 and8or reference materials
4%9%' The reference material prodcer shall have a policy and procedres that shall be implemented when it
establishes that any aspect of its prodction activities does not conform to its own specified prodction
procedres or the agreed re*irements of the cstomer.
The policy and procedres shall ensre that
a) responsibilities and athorities for the management of non$conforming work are designatedH
b) the actions# which shall be taken when any non$conforming work and&or reference materials are identified#
are defined# together with a system which ensres that they are effectively implementedH
9
c) an evalation of the significance of the non$conforming work is madeH
d) where necessary# work is halted and# if appropriate# isse of the affected reference material and its
certificates (and statements) withheldH
e) remedial actions are taken within a defined time$frameH
f) where necessary# the cstomers who# within an appropriate period# have prchased the reference
material are notified of the possible effects identified and# where necessary# non$conforming reference
materials and&or their certificates&statements already distribted# are recalledH
g) the responsibility for athorization of the resmption of work is defined.
The decision on recall of reference materials shold be taken in a timely manner to limit the se of
non$conforming reference materials by cstomers.
The identification of non$conforming reference materials or problems with the management system or with
certification activities can occr at varios places within the management system# sch as cstomer
complaints# *ality control# checking of consmable materials# staff observations or spervision# certificate
checking# management reviews and internal or e6ternal adits.
4%9%2 Ihere the evalation indicates that the non$conforming work and&or reference materials cold recr
or that there is dobt abot the reference material prodcer>s compliance with its own policies and procedres#
the corrective action procedres in 0.54 shall be promptly followed to identify the cases of the problem and to
eliminate them.
4%'0 "orrecti&e actions
4%'0%' General
The reference material prodcer shall establish a policy and procedres and shall designate appropriate
athorities for implementing corrective actions when non$conforming reference materials# non$conforming
work on the prodction of reference materials or departres from the policies and procedres in the
management system have been identified.
7OT! . problem with the management system or with technical operations may be identified throgh a variety of
activities within the management system# sch as control of non$conforming reference materials# internal or e6ternal adits#
management reviews and feedback from cstomers or staff observations.
4%'0%2 "ause anal-sis
%orrective action procedres shall start with an investigation to identify the root cases of the problem. This is
sometimes the most difficlt# bt is the key part in the corrective action procedre.
Often the root case is not obvios and ths a carefl analysis of all potential cases of the problem is
re*ired. Potential cases cold inclde# inter alia# the natre of the reference material and its specifications#
methods and procedres sed for characterization# staff skills and training# and the materials and e*ipment
(and&or its calibration) sed in the prodction processes. This shall be reviewed for both in$hose prodction
and# where re*ired# any work performed by sbcontractors.
4%'0%3 Selection and implementation of correcti&e actions
Ihere corrective actions are needed# the reference material prodcer shall identify potential corrective actions.
It shall select and implement the action(s) most likely to eliminate the problem and to prevent recrrence.
.ny corrective action taken to eliminate the cases of non$conformities or other departres shall be
appropriate to the magnitde of the problem and commensrate with the risks encontered.
10
The reference material prodcer shall docment and implement any re*ired changes to the operational
procedres reslting from corrective action investigations.
4%'0%4 ,onitorin* of correcti&e actions
.fter having implemented the corrective actions# the reference material prodcer shall monitor the reslts to
ensre that the corrective actions taken have been effective in eliminating the root cases of the problems.
4%'0%3 9dditional audits
Ihere the identification of non$conformities or departres casts dobt on the prodcer>s compliance with its
own policies and procedres# or on its compliance with this )ide# the prodcer shall ensre that the
appropriate areas of activity are adited in accordance with 0.50 as soon as possible.
4%'' 5re&enti&e actions
4%''%' 1e*ired improvements and potential sorces of non$conformities# either technical or concerning the
management system# shall be identified. Ihen improvement opportnities are identified or if preventive action
is re*ired# action plans shall be developed# implemented and monitored to redce the likelihood of the
occrrence of sch non$conformities and to take advantage of the opportnities for improvement.
4%''%2 .fter the implementation of the preventive actions# the reference material prodcer shall monitor the
reslts to establish any redction in deficiencies or other improvements in this operational area# thereby
establishing the effectiveness of the preventive action.
4%'2 Impro&ement
The reference material prodcer shall continally improve the effectiveness of its management system
throgh the se of the *ality policy# *ality ob"ectives# adit reslts# analysis of data# corrective and
preventive actions and management review.
4%'3 0ecords
4%'3%' General
4%'3%'%' The reference material prodcer shall establish and maintain procedres for identification#
collection# inde6ing# access# storage# maintenance and disposal of *ality and technical records.
a) ?ality records
?ality records are records providing ob"ective evidence of the e6tent of the flfilment of the re*irements for
*ality or the effectiveness of the operation of the management system. They inclde reports from internal
adits and management reviews# and corrective and preventive action records.
b) Technical records
Technical records are accmlations of data and information which reslt from carrying ot testing and (if
applicable) calibration procedres and which indicate whether specified *ality or process parameters are
achieved. They inclde forms# contracts# work sheets# work books# check sheets# control charts&graphs#
calibration reports&certificates# reports# certificates and other statements to cstomers.
The reference material prodcer shall ensre that it has recorded sch information that might be needed in a
ftre dispte sitation.
11
4%'3%'%2 .ll records shall be legible and shall be stored and retained in sch a way that they are readily
retrievable and in facilities that provide a sitable environment to prevent damage# deterioration or loss.
1etention time of records shall be established in accordance with legal# accreditation body or cstomer
re*irements# where relevant# and shall be docmented.
1ecords may be in the form of any type of media# sch as hard copy or electronic media.
4%'3%'%3 Ihen mistakes occr in records# each mistake shall be crossed ot# not erased# made illegible or
deleted# and the correct information entered alongside. .ll sch alterations to records shall be signed or
initialled by the person making the correction. In the case of records stored electronically# e*ivalent
measres shall be taken to avoid the loss or change of original information.
4%'3%'%4 .ll records shall be held secrely and# where appropriate# in confidence.
4%'3%'%3 The reference material prodcer shall have procedres to protect electronically held data at all
times and to prevent nathorized access to# or amendment of# sch data.
4%'3%2 0ecords and reports
The reference material prodcer shall establish and maintain a record system to sit its particlar
circmstances and to comply with any applicable reglations. The reference material prodcer shall arrange
for all individal measrement observations# appropriate calclations and derived data (e.g. statistical
treatments and ncertainty bdgets)# calibration records and preparation reports to be retained for a defined
period beyond which it is no longer probable that they will be referred to# taking into accont the period for
which the reference material remains valid.
The reslts of each calibration or measrement (or series of either) carried ot by the reference material
prodcer shall be reported in accordance with ISO&I!% 5+4(,.
0.5/.( refers to internal reports of the reference material prodcer which shold not be confsed with a
certificate of analysis or certification report which is spplied with a reference material to the cstomer.
4%'4 Internal audits
4%'4%' The reference material prodcer shall# periodically and in accordance with a predetermined schedle
and procedre# condct internal adits of its activities to verify that its operations contine to comply with the
re*irements of the management system and the re*irements of this )ide. The internal adit programme
shall address all elements of the management system# inclding the technical and prodction activities leading
to the finished prodct (reference material). It is the responsibility of the *ality manager to plan and organize
adits as re*ired by the schedle and re*ested by management. Sch adits shall be carried ot by trained
and *alified personnel who are# wherever resorces permit# independent of the activity to be adited.
Personnel shall not adit their own activities.
7OT! The cycle for internal aditing shold normally be completed in one year.
4%'4%2 Ihen adit findings cast dobt on the effectiveness of the operations or on the integrity of the
reference materials or on the correctness of their docmentation# the reference material prodcer shall take
timely corrective actions and shall notify# in writing# its cstomers whose activities may have been adversely
affected.
4%'4%3 .ll adit findings and corrective actions that arise from them shall be recorded. The reference material
prodcer>s management shall ensre that these actions are discharged within an appropriate and agreed
timescale.
4%'4%4 <ollow$p activities shall verify and record the implementation and effectiveness of the corrective
actions taken.
12
4%'3 ,ana*ement re&ie$s
4%'3%' In accordance with a predetermined schedle and procedre# the reference material prodcer>s top
management shall periodically condct a review of its management system and prodction processes to
ensre their contining sitability and effectiveness and to introdce any necessary changes or improvements.
The review shall take accont of
the sitability of policies and procedresH
reports from managerial and spervisory personnelH
the otcome of recent internal aditsH
corrective and preventive actionsH
assessments by e6ternal bodiesH
changes in volme and type of workH
feedback from cstomersH
recommendations for improvement inclding complaintsH
other relevant factors sch as resorces# staff training and# where re*ired# technical isses relating to
the competence of the sbcontractor and distribtor of the reference materials.
1eslts shold feed into the corporate planning programme# shold inclde the goals# ob"ectives and action
plans for the coming year and shold be commnicated to the staff.
7OT! . typical period for condcting a management review is once every year.
4%'3%2 <indings from management reviews and the actions that arise from them shall be recorded. The
management shall ensre that these actions are discharged within an appropriate and agreed timescale.
3 )echnical and production requirements
3%' General
This )ide covers the prodction of certified and non$certified reference materials. <or non$certified reference
materials# the prodction re*irements are less stringent than for certified reference materials.
Comogeneity and stability assessments are always re*ired to establish that the degree of homogeneity and
stability is fit for prpose (see ,.5(# ,.5/# ,.50).
Ihere replacement batches of reference materials are prodced by applying the same procedres sed for
previos batches to similar starting materials which lead to final prodcts with e*ivalent properties#
appropriate verification assessments are re*ired to ensre that ncertainty estimations obtained on previos
batches remain applicable for the new batchH see ,.0./ n).
To flfil the minimm re*irements for a non$certified reference material# the following may not be necessary3
a) designing interlaboratory e6ercises# assessing commtability# assigning property vales and establishing
ncertainty bdgets D,.0./ ")# k)# l)# m)EH
b) providing detailed information to sers on the homogeneity stdyH however# information on the degree of
homogeneity shall be provided (,.5/.5)H
c) providing detailed information to sers on the stability stdyH however# information on the degree of
stability shall be provided (,.50.5)H
13
d) characterization of the material (,.5,)H
e) assignment of property vales and their ncertainties (,.5:)H
f) establishing metrological traceability of assigned vales (,.5(.0).
3%2 5ersonnel
3%2%' The prodcer of reference materials shall have# where possible# competence in the prodction of the
particlar type of reference material (or related material)# as well as having access to e6perience in the
measrement of the properties being determined.
It is recognized that# for the prodction of novel reference materials# persons or organizations with sitable
competence may not be available. In sch cases# the reference material prodcer shold be able to
demonstrate the accmlation of knowledge and e6perience throgh the prodction records of its reference
materials.
3%2%2 The reference material prodcer shall ensre the ade*ate competence of all personnel who
ndertake activities relating to the prodction of reference materials. There shall be sfficient personnel
having the necessary edcation# training# technical knowledge and e6perience for their assigned fnctions.
3%2%3 The reference material prodcer shall formlate goals with respect to edcation# training and skills of
its personnel. The reference material prodcer shall have a policy and procedres for identifying training
needs and providing training of personnel. The training programme shall be relevant to the present and
anticipated tasks of the prodcer. The effectiveness of training actions shall be evalated.
The need to retrain staff periodically shold be considered (e.g. the reference material prodcer shold have
in place a policy for retraining staff when a method or measrement techni*e is not in reglar se). Staff
training and retraining policies shold take into accont technological changes and aim at continos
pgrading of skills.
3%2%4 The reference material prodcer shall maintain an p$to$date record of "ob descriptions for the
managerial# technical and spport staff involved in reference material prodction activities.
3%2%3 The reference material prodcer shall se personnel who are employed by# or nder contract to# the
prodcer. Ihere contracted and additional technical and spport personnel are sed# the prodcer shall
ensre that sch personnel are spervised and competent and that they work in accordance with the
prodcer>s management system.
3%2%. The reference material prodcer shall athorize specific personnel to perform particlar activities
relating to reference material prodction. The reference material prodcer shall maintain an p$to$date record
of the athorizations# competence and edcational and professional *alifications of all staff members. These
records shall provide evidence that individal staff members have been ade*ately trained and that their
competence to complete particlar types of material processing and measrement has been assessed. This
information shall be readily available and shall inclde the date on which athorization and&or competence is
confirmed.
3%3 Su4contractors
3%3%' Ihere a reference material prodcer ses sbcontractors to ndertake part of the procedre for the
prodction# inclding processing# homogeneity and stability testing# characterization# handling# storage or
distribtion of a reference material# the prodcer shall be able to demonstrate that the sbcontractor is
competent to perform the concerned part of the procedre# and that the work carried ot and&or the reslts
prodced are of the re*ired *ality. Ihen assessing the competence of a sbcontractor# the reference
material prodcer shall ac*ire and evalate information on the sbcontractor>s knowledge of the sb"ect and
details of past e6perience in the field and make sre that e6perienced staff is available as well as appropriate
accommodation and environmental conditions# instrmentation and measring e*ipment as re*ired.
14
Processes that shall not be carried ot by sbcontractors are pro"ect planning# selection of sbcontractors and
the assignment of and decision on property vales. .lso# athorization of property vales and isse of
certificates&statements&analysis reports&information sheets (or however named) shall be done by the reference
material prodcer.
3%3%2 !vidence of the sbcontractor>s competence shall be established and records of its competence
maintained. This can be done by different means. .ccreditation to ISO&I!% 5+4(, when testing or calibration
is carried ot# or certification of the *ality management system to ISO ;445 for other (non$testing&calibration)
activities by a recognized body# is generally appropriate. In cases where accreditation is not practical#
evidence of sbcontractors sccessflly participating in a relevant proficiency testing scheme and prodcing
acceptable reslts on well$characterized materials of similar or e*ivalent natre to that of the candidate
reference material may also be considered appropriate. In cases where the competence of sbcontractors
cannot be ascertained via provision of docmentary evidence# the reference material prodcer may need to
assess the competence of the sbcontractor on$site or may need to spervise on$site the operations carried
ot by the sbcontractor.
The prodcer may consider distribting materials of a comparable matri6 whose property vales are well
established and at appropriate concentration levels# etc.# prior to or together with distribting any candidate
reference material samples to help in the evalation of the sbcontractor.
3%3%3 In certain cases# the reference material prodcer may have no laboratory facilities or processing
facilities# or may choose not to se its own facilities. It shall ensre that all work carried ot by sbcontractors
who may contribte to the assignment of the property vales of interest is fit for that prpose and in
compliance with this )ide and ISO&I!% 5+4(, for measrement# calibration and testing.
@nder these circmstances the reference material prodcer shall
employ personnel having knowledge to ensre that sbcontracted activities are e6ected in compliance
with this )ide and ISO&I!% 5+4(, for measrement and testing# and
evalate the reslts of all sbcontracted activities (e.g. analytical and statistical aspects).
3%3%4 The reference material prodcer shall ensre that all details of the methodology# reslts and the
descriptions of procedres of any sbcontractor are available. Sitable details of methodology shall be
maintained by the reference material prodcer to allow the technical evalation of data. If re*ired# it shall
ensre that a register&database of all sbcontractors and the accreditation for testing# calibration and
measrement activities# certification of the management system or other forms of competence stats are
maintained.
3%4 5roduction plannin*
3%4%' The reference material prodcer shall identify and plan those processes which directly affect the
*ality of reference material prodction and shall ensre that they are carried ot in accordance with specified
procedres. Ihere available# procedres given in technical standards for the prodction of specific reference
materials shall be sed.
3%4%2 Technical inpt of the different sbcontractors involved shall be identified and the necessary
information docmented and reglarly reviewed. . mechanism (e.g. a management&technical advisory grop)
may be established to make recommendations on how to plan the prodction processes.
7OT! These cold inclde recommendations for prodction# setting p a monitoring system (to ensre timeliness
and *ality for each prodction phase) and having an evalation procedre to assess the prodction processes
retrospectively.
3%4%3 In planning the prodction processes# the reference material prodcer shall have procedres and
service facilities# for
a) definition of storage conditionsH
b) material selection (inclding# where appropriate# sampling)H
15
c) maintaining sitable environments for all aspects of prodction (,.:)H
d) material processing (,.=)H
e) measring&testing (,.;# ,.54)H
f) validation of measrement methods (,.;)H
g) verification and calibration of e*ipment (,.54)H
h) assessing material homogeneity (,.5/)H
i) assessing material stability (,.50)H
") designing and organizing appropriate interlaboratory e6ercises for the prpose of assigning property
vales# if applicable (,.5,)H
k) assessing commtability (where appropriate) (.nne6 G)H
l) assigning property vales based on the reslts of measrements# if applicable (,.5:)H
m) establishing ncertainty bdgets and estimating ncertainties of the assigned property vales# if
applicable (,.5:)H
n) defining acceptance criteria for verifying that ncertainty estimates are applicable for replacement
batches of reference materials prodced nder conditions described in ,.5H
o) establishing metrological traceability of the measrement reslt(s) (,.5()H
p) issing certificates and&or other docmentation (,.5+)H
*) ensring ade*ate storage facilities and conditions (,.+)H
r) ensring appropriate labelling and packaging of the samples meeting safety reglations (,.+)H
s) ensring appropriate transport arrangements which comply with shipping reglations (,.5=)H
t) ensring post$certification stability monitoring# if applicable (,.50)H
) ensring an ade*ate post$distribtion service for reference material cstomers (,.5=).
3%3 5roduction control
The reference material prodcer shall identify the verification procedres necessary to ensre the *ality of
each stage of reference material prodction# and shall assign ade*ate resorces and personnel for sch
activities. These activities shall inclde inspection# testing and monitoring of all stages of prodction.
3%. 9ccommodation and en&ironmental conditions
3%.%' The reference material prodcer shall ensre that all laboratory accommodation# calibration and
measrement areas (if applicable)# material processing and packaging areas# energy sorces# lighting#
hmidity# temperatre# pressre and ventilation are sch as to facilitate proper material processing and
packaging# as well as proper performance of calibration and measrements (if applicable).
Precations shall be taken against possible contamination of the reference material dring its processing and
characterization. .ll reference material processing and testing areas# in addition to satisfying re*irements for
hmidity and temperatre# shall be protected from vibration# airborne dst and microbiological contamination#
magnetic fields and electromagnetic radiation (as appropriate). The technical re*irements for
16
accommodation and environmental conditions that can affect the reslts and processes of the prodction of
reference materials shall be docmented.
7OT! <or e6ample# the packaging of a cement material re*ires conditions of low hmidity# while the processing and
characterization of a material in which the content of traces of lead is to be measred re*ires clean room conditions to
prevent contamination from dst containing lead. %lean room conditions may also be re*ired for other types of trace
analysis. Proper choice of container material and ade*ate cleaning procedres are also important to avoid contamination.
Processing of reference materials of genetically modified organisms re*ires measres to prevent '7.&protein
cross$contamination.
3%.%2 Ihere appropriate# the environment in which the reference material prodction activities are
ndertaken shall be monitored with appropriately calibrated e*ipment# controlled and recorded# sch that
reslts and processes are not adversely affected.
3%.%3 .ppropriate health# safety and environmental protection precations shall also be implemented where
necessary (e.g. when handling pesticides or serm).
3%/ ,aterial handlin* and stora*e
3%/%' In order to avoid any contamination# the reference material prodcer shall identify# preserve and
separate (i.e. from other chemicals and samples) all candidate materials and reference materials# from the
time of processing throgh to their distribtion to sers.
3%/%2 The reference material prodcer shall ensre ade*ate packaging of all reference materials (e.g.
where appropriate# se light shielding# air$free# moistre$free or inert$gas packaging) and provide secre
storage areas&stock rooms which prevent damage or deterioration of any item or material between
characterization and distribtion. .ppropriate procedres for dispatch shall be stiplated.
3%/%3 The condition of all stored&stocked items and materials shall be assessed at appropriate intervals
throghot the storage period# in order to detect possible deterioration.
3%/%4 The reference material prodcer shall control packing and labelling processes to the e6tent necessary
to ensre conformity with safety and transport re*irements.
7OT! The proper distribtion of samples can present a severe problem for some types of material which re*ire
ninterrpted storage in a freezer# or which shold not be e6posed to J$rays# shocks or vibrations. 2ost types of chemical
material benefit from air$tight packaging to avoid o6idation by atmospheric o6ygen and&or contamination by atmospheric
contaminants (e.g. fel vapors or engine e6hast gases) which may be encontered dring transport.
The reference material prodcer shall ensre that the integrity of each individal reference material nit is
maintained ntil the seal has been broken or p to the point when presented for analysis. The prodcer
cannot be held responsible for the material once its seal has been broken. This may re*ire# in some cases#
that the reference material is packaged in nit *antities sfficient for a single se.
3%/%3 The reference material label shall be secrely attached to the prodct container of an individal
reference material nit# and shall be designed to remain legible and intact nder the defined storage and
handling conditions within the lifetime of the reference material# i.e. the period dring which the reference
material is available from the reference material prodcer e6tended by the period of validity of its certificate.
The label shall identify the material# the prodcer# its batch and cataloge nmbers# and any other information
necessary to enable the material to be ni*ely distingished and referenced (sch as the individal sample
nmber)# where appropriate# to its statement or certificate. The labels shall also# where appropriate# comply
with re*irements related to safety and risk reglations# e.g. show to6icity symbols# risk and safety phrases.
Ihere the physical size of the reference material nit limits the amont of information that can be contained
on the label# the information shall be inclded elsewhere (e.g. in a certificate) and the ser shall be directed to
this information from the label. .t a minimm# a ni*e identity nmber shold be given.
3%/%. The reference material prodcer shall make arrangements to ensre the integrity of each reference
material throghot the entire prodction process. Ihere contractally specified# this protection shall be
e6tended to inclde delivery to destination.
17
3%2 ,aterial processin*
The reference material prodcer shall establish procedres to ensre that the item or material has ndergone
ade*ate processing for its intended se. Procedres for material processing shall inclde# where appropriate#
a) *alitative analysis for verification of material type and&or identityH
b) synthesis# prification (e.g. distillation# e6traction)# transformation into the final form (e.g. machining#
grinding# blending# sieving and riffling# e6trsion# melting)H
c) homogenizationH
d) proper handling (e.g. protection from contamination and se of inert e*ipment)H
e) measrements for processing control (e.g. particle size distribtion# moistre content)H
f) cleaning of sample containersH
g) stabilization of material (e.g. drying# irradiation# sterilization)H
h) packaging (e.g. bottling# ampoling) of the batch.
3%9 ,easurement methods
3%9%' The reference material prodcer shall meet the re*irements of ISO&I!% 5+4(,/) with respect to tests#
calibrations and measrements nder their responsibility (inclding preparation of items# sampling# handling#
preservation# storage# packaging# transport to sbcontractors# estimation of measrement ncertainty and
analysis of measrement data). These activities shall be consistent with the re*ired accracy# where
appropriate# of the assigned vales of the reference material# and with any standard specifications relevant to
the measrement concerned.
3%9%2 2easrement methods developed in$hose by the reference material prodcer shall be validated and
athorized before se. Sch methods shall be thoroghly investigated# and shall clearly and e6actly describe
the necessary conditions and procedres for which the measrement of the property vales of interest is valid
at the level of accracy commensrate with the intended se of the reference material. 1ecords of the method
of validation shall be retained. Balidation shall meet the re*irements of ISO&I!% 5+4(,.
3%9%3 Ihere sampling is carried ot as part of the measrement method (e.g. sb$sampling a
representative *antity from a batch of material)# the reference material prodcer shall se docmented
procedres and appropriate statistical techni*es to take test portions.
3%'0 ,easurin* equipment
3%'0%' 2easring e*ipment sed in reference material prodction shall be sed in compliance with
ISO&I!% 5+4(,. It shall be properly calibrated# verified and maintained# with all procedres being docmented
and the reslts recorded. Ihere appropriate# periodic performance checks shall be carried ot and recorded
(e.g. to check the response# stability# linearity# resoltion# alignment# repeatability) to ensre that the
measrement e*ipment is performing ade*ately. The fre*ency of sch performance checks shall be
determined by e6perience and based on the type and previos performance of the e*ipment. Intervals
between checks shall be shorter than the defined time within which the e*ipment has been fond to drift
otside acceptable limits# in accordance with the re*irements of ISO 5445(.
3%'0%2 .ny item of e*ipment that has been sb"ected to overloading or mishandling# shown to provide
sspect reslts# or shown by verification or otherwise to be defective# shall be clearly identified# withdrawn
from service and# wherever possible# stored at a specified location ntil repaired and shown by calibration#
/) <or tests performed in the medical field# ISO 5,5=; may be sed as reference instead of ISO&I!% 5+4(,.
18
verification or testing to perform satisfactorily. The reference material prodcer shall review the implications for
reslts obtained sing sch e*ipment# with particlar regard to the e6tent of the calibration deviation# the
reslts involved and the allowable tolerance on the reslts. Ihere reslts have been significantly in error# the
reference material prodcer shall have the reslts checked and shall take appropriate remedial action.
1ecords of the review and any checks&remedial action shall be maintained.
3%'0%3 !ach item of e*ipment# inclding any measrement standard# that is sed in the
calibration&validation of e*ipment&measrement methods sed for reference material prodction shall# where
appropriate# be labelled# marked or otherwise identified to indicate its calibration stats and e6piry date. This
shall also inclde reference materials# standard soltions and chemical reagents sed in chemical analysis#
microbiological testing# etc.
3%'0%4 .ll measring and testing e*ipment having an effect on the traceability and accracy of the
measrement reslts shall be calibrated and&or verified before being commissioned into service. The
reference material prodcer shall have an established programme for the calibration and verification of
measring and testing e*ipment.
3%'0%3 The overall programme of calibration and&or verification of e*ipment shall be designed and operated
so as to ensre that# wherever applicable# measrement reslts obtained by the reference material prodcer
are traceable to a stated reference throgh an nbroken chain of calibrations with stated ncertainties.
%alibration certificates of measrement instrments shall# wherever appropriate# indicate the metrological
traceability to this stated reference.
3%'' Data e&aluation
3%''%' The reference material prodcer shall ensre that calclations and data transfers are sb"ect to
appropriate checks# inclding those from its own sorces.
3%''%2 Ihere compters or compter$controlled systems are sed for the captre# processing# evalation#
recording# reporting# storage or retrieval of calibration or testing data# the reference material prodcer shall
ensre that
a) compter software developed in$hose or off$the$shelf software frther developed for specific se# which
affects the characterization or the properties of the reference material# shall be validated and shown to be
ade*ate for seH
b) procedres are established and implemented for protecting the integrity of dataH sch procedres shall
inclde# bt are not limited to# integrity of data entry and captre# data storage# data transmission and
data processingH
c) e*ipment is maintained to ensre proper fnctioning and is provided with the environmental and
operating conditions necessary to maintain data integrityH
d) appropriate procedres are established and implemented for the maintenance of data secrity# inclding
prevention of nathorized access to# and amendment of# compter records.
3%''%3 .ll technical data relating to the prodction of reference materials shall be retained in accordance with
the re*irements of 0.5/.(.
3%'2 ,etrolo*ical tracea4ilit-
3%'2%' The reference material prodcer shall provide docmentary evidence on the metrological traceability#
of the measrement reslts to a stated reference (see also /.+).
7OT! The concept of 8metrological traceability9 incldes identification of the property of interest of the reference
material# the nmerical vale and the stated reference.
3%'2%2 The stated reference shall be a definition of a measrement nit throgh its practical realization# a
measrement procedre inclding the measrement nit# or a measrement standard. Iherever possible#
19
metrological traceability shall be achieved throgh an nbroken chain of calibrations# all having stated
ncertainties. Ihere this cannot be achieved# the reference material prodcer shall provide satisfactory
evidence of the correlation of reslts with other stated vales# either by e6hastive evalation of the
measrement process or by comparison with known and accepted certified reference materials# which have
certified vales preferably with comparatively small ncertainty and which are higher in the metrological
traceability hierarchy with few steps of comparison.
The concept of 8metrological traceability9 applies to the measrement reslts for the assessment of
homogeneity and stability as well as to the assignment of vales as the reslt of the characterization process.
The definition of reference material as 8sfficiently homogeneos and stable with respect to one or more
specified properties9 inherently re*ires a clear definition of these properties. 2etrological traceability of
measrement reslts to the chosen reference shall be ensred to make relevant statements on the degree of
homogeneity and stability.
3%'2%3 'ifferent re*irements apply for relative assessments and absolte assessments.
3%'2%3%' <or stdies in which reslts are compared relative to each other (e.g. homogeneity stdies#
stability stdies with measrements performed nder repeatability conditions in isochronos schemes)# it shall
be ensred that
a) the measrand in the stdy is the same as the one for which the vale is assigned (i.e. the chosen
method is selective)H
b) the calibration fnction for the measrement procedre is valid in the range of the measrement resltsH
c) the measrement procedre is sfficiently precise to make meaningfl statements abot the variation of
the measrement reslts of the measrand.
In this case# no traceability to a higher order reference system is re*ired.
ISO )ide /,3(44:# +.0# allows homogeneity testing only on a sbset of the assigned vales. In this case#
docmentary evidence shall be provided that the measrand *antified indeed correlates with the measrand
for which the vale is assigned in the material in *estion.
7OT! 5 In principle# no treness of measrement reslts has to be established for this kind of stdy.
7OT! ( These re*irements are met if appropriate selectivity# working range and precision of a method have been
established.
3%'2%3%2 <or stdies in which the absolte vales are compared (e.g. characterization stdies# stability
stdies with measrements nder reprodcibility conditions)# it shall be ensred that
a) the measrand in the stdy is the same as the one for which the vale is assigned (i.e. the chosen
method is selective)H
b) the calibration fnction for the measrement procedre is valid in the working range of the measrement
resltsH
c) the measrement procedre has an appropriate limit of *antificationH
d) the measrement procedre is sfficiently precise to make meaningfl statements abot the variation of
the measrement resltsH
e) the measrement procedre is calibrated with standards traceable to the same reference as the assigned
vale (refer to .nne6 . for more information)H
f) all other relevant inpt *antities have been appropriately calibrated.
20
7OT! These re*irements are met if appropriate selectivity# limit of *antification# working range# precision and
treness of a method have been established.
3%'2%4 To ensre the metrological traceability of the assigned vales# the reference material prodcer shall
provide docmentary evidence that all measrement reslts sed for vale assignment are traceable to the
same reference as the assigned vale.
7OT! . combination of reslts obtained by different methods and&or laboratories K all being traceable to the same
reference K is also traceable to this reference.
.n additional discssion on the concept and re*irements of metrological traceability is given in .nne6 ..
3%'3 9ssessment of homo*eneit-
3%'3%' .ssessment of homogeneity is always re*ired to establish that the degree of homogeneity of the
reference material with respect to the property(ies) of interest is fit for prpose.
The definition of reference material as 8sufficiently homogeneos9 inherently re*ires *antification or limits
for heterogeneity to demonstrate fitness for prpose. Therefore# the provisions of ISO )ide /, for
homogeneity testing also apply for the prodction of non$certified reference materials.
3%'3%2 The reference material prodcer shall carry ot an assessment of the homogeneity of any candidate
reference material. In most cases# this involves analysing a representative nmber of randomly# systematically
or stratified randomly chosen nits. Testing# calibration# measrement# sampling or other activities performed
for the assessment of homogeneity shall be carried ot in compliance with ISO&I!% 5+4(,. 2easrement
procedres shall be selected so that the repeatability is fit for the prpose re*ired. The homogeneity stdies
shall be designed and performed in accordance with ISO )ide /,. .lthogh the measrement vales do not
have to be commnicated to cstomers# the degree of homogeneity (e.g. e6pressed as ma6imm betweenbottle
variation) shall be indicated in the docmentation accompanying the reference material.
If the material is prodced in several batches# it is necessary to test the e*ivalence of the batches (or to
assign property vales to each batch separately).
The assessment shall be performed after the material has been packaged in its final form nless stability
stdies indicate that storage shold be maintained in blk form. In some cases# intermediate homogeneity
checks may be necessary (e.g. prior to bottling&ampoling).
7OT! 5 <or reference materials that are e6pected to be homogeneos on physical gronds# the main prpose of
homogeneity testing is to detect nforeseen problems# for e6ample point contamination dring packaging into individal
nits# or incomplete dissoltion or e*ilibration of an analyte in a solvent (which cold lead to steadily changing
concentrations). <or these types of e6amples# systematic sampling (e.g. one from every ,4 samples prodced in a
continos processH sampling at reglar intervals for each sb$batch in those cases where the sb$batch can be defined)
may be a better way to detect inhomogeneity than random sampling. . statistical trend analysis may also be helpfl in
detecting inhomogeneity.
7OT! ( . relatively inhomogeneos material may be the best available# and may therefore still be sefl as a
reference material# provided the ncertainties of the assigned property vales take de accont of this.
3%'3%3 The amont of tested material on which the homogeneity of the reference material has been
established shall be specified in the docmentation spplied by the reference material prodcer. This
docmentation shall also state the minimm sample size for se (see ISO )ide /5).
7OT! .lthogh ISO )ide /5 is strictly speaking established for certified reference materials# the re*irement for
indicating the minimm sample size is also valid for non$certified reference materials.
3%'4 9ssessment of sta4ilit-
3%'4%' .ssessment of stability is always re*ired to establish that the degree of stability of the reference
material is fit for prpose.
21
The definition of reference material as 8sufficiently stable9 inherently re*ires *antification or limits for
degradation to demonstrate fitness for prpose. Therefore# the provisions of ISO )ide /, for stability testing
also apply for the prodction of non$certified reference materials.
3%'4%2 The stability of the reference material shall be assessed. Testing# calibration# measrement# sampling
and other activities performed for the assessment of stability shall be carried ot in compliance with
ISO&I!% 5+4(,. Stability testing can be performed only if sfficient homogeneity is demonstrated. The stability
stdies shall be designed and performed in accordance to ISO )ide /,.
The evalation of measrement data as described in ISO )ide /, covers only apparently stable materials. In
case of detectable degradation# both the degradation and its ncertainty shall be inclded in the assessment.
The properties of interest of the candidate reference material shall be evalated for the adopted storage
conditions. !ffects of# for e6ample# light# moistre and temperatre shall be evalated in fnction of time for
estimating a lifetime of the reference material and hence establishing a period of validity of the certificate.
.lthogh the measrement vales do not have to be commnicated to cstomers# the degree of stability shall
be indicated in the docmentation accompanying the reference material.
3%'4%3 The stability of the material nder transport conditions shall be assessed.
3%'4%4 Ihere appropriate# an assessment of the stability of the reference material shall be performed at
periodic intervals after characterization# to confirm that all vales are maintained from prodction ntil the
e6piry date. The reference material prodcer shall provide a period of validity of the certificate which is stated
in the docmentation accompanying the material. It shall be made clear on the docmentation on which
starting date the period of validity is based (e.g. the date of certification# the date of shipment of the reference
material or the date of opening the packaging).
3%'4%3 The reference material prodcer shall inform its cstomers abot shelf$life changes of the reference
material inclding possible conse*ences for its se.
3%'3 "haracteri+ation
<or certified reference materials# the prodcer shall se and docment technically valid procedres to
characterize its reference materials. The characterization shall comply with the re*irements of ISO )ide /,
and ISO&I!% 5+4(, for testing# calibration and related activities.
There are several technically valid approaches for characterizing a reference material. These inclde carrying
ot measrements sing
a) a single (primary) method in a single laboratoryH
b) two or more independent reference methods in one or several laboratoriesH
c) one or more methods of demonstrable accracy# performed by a network of competent laboratoriesH
d) an approach providing method$specific# operationally defined property vales# sing a network of
competent laboratories.
'epending on the type of reference material# its intended se# the competence of the laboratories involved
and the *ality of methods employed# one approach may be chosen as appropriate.
1eslts obtained from proficiency testing can be sed only if the competence of the laboratories involved has
been checked and it has been ensred that the measrements done comply with ISO&I!% 5+4(, (see
also ,./).
The single (primary) method approach a) shall be carried ot only when the procedre and e6pertise enable it
to ensre metrological traceability. 2ore sally# a property vale can be reliably assessed when its vale is
confirmed by several laboratories working independently and sing more than one method# for each of which
the accracy has been well established.
22
3%'. 9ssi*nment of propert- &alues and their uncertainties
3%'.%' The reference material prodcer shall se docmented procedres# as otlined in ISO )ide /,# for
the assignment of property vales.
These procedres shall inclde# as appropriate3
a) details of the e6perimental designs and statistical techni*es sedH
b) policies on treatment and investigation of statistical otliers and&or the se of robst statisticsH
c) whether weighting techni*es are sed for contribtions to assigned property vales derived from
different methods with different measrement ncertaintiesH
d) the approach sed to assign ncertainties to the property valesH
e) any other significant factors which may affect the assignment of property vales.
The reference material prodcer shall never rely entirely on only a statistical analysis of the characterization
data when assessing the property vales of interest. Otliers shall not be e6clded on statistical evidence ntil
they have been thoroghly investigated and# where possible# the reasons for the discrepancies identified.
.lternatively# the se of robst statistics may be appropriate in some cases.
Ihen several methods have been sed to characterize a reference material# difficlty may arise when the
reslts show significant differences# in which case a property vale based on the mean is inappropriate. It is
essential in sch cases that the reference material prodcer and its sbcontractors have considerable
e6perience of the different methods and are able to give more or less weight to the reslts from the se of a
particlar measrement method. In some cases# the reslts may be weighted according to the inverse of the
variance of each method. In some cases# measrement methods will prodce irreconcilable reslts and it may
be necessary to assign separate property vales according to the methods sed (i.e. a method$specific
approach).
In assigning the property vales of interest# the reference material prodcer shall consider establishing a
grop of independent e6perts whose responsibility is to check that all work# data and docments are fit for
their prpose.
3%'.%2 .n important aspect of establishing the property vales of the reference material being prodced is an
assessment of their ncertainties. The reference material prodcer shall carry ot an assessment of the
measrement ncertainties to be inclded in the assignment of the property vales in accordance with the
re*irements of the )@2 (ISO&I!% )ide ;=$/). In the process of estimating ncertainties of the property
vales of interest# any ncertainties reslting from between$nit variations and&or from possible dobts on
stability (both dring storage and dring transportation) shall be assessed in accordance with ISO )ide /,
and shall be inclded in the assigned ncertainty.
. statement of the measrement ncertainty is mandatory for certified vales. In case vales are assigned to
non$certified reference materials (e.g. 8indicative vales9 or 8information vales9)# a statement of ncertainties
is highly recommended to improve the se of the material.
3%'/ "ertificates or documentation for users
The reference material prodcer shall isse a certificate for certified reference materials and provide
appropriate docmentation for non$certified reference materials in the form of a statement# analysis report# or
information sheet howsoever named.
The contents of certificates for certified reference materials shall comply with the re*irements of
ISO )ide /5. If the certificate also contains non$certified vales# a clear distinction shall be made between
certified and non$certified vales.
23
The docmentation for non$certified reference materials shall inclde information on homogeneity and stability
and on the period of validity of the stated information. It shall also contain information for the ser on the
proper application and storage conditions of the reference material.
7OT! In some cases which are covered by specific legislation (e.g. most pharmacopoeia assay standards)# the
ncertainties of the assigned vales are not stated since they are considered to be negligible in relation to the defined
limits of the method$specific assays for which they are sed.
3%'2 Distri4ution ser&ice
3%'2%' The distribtion process shall be careflly stdied to avoid deterioration of the reference material
(see ,.50./). The prodcer shall determine the conditions of shipment# the ma6imal time the shipment may
endre nder the conditions chosen and what docmentation is re*ired to allow cstoms clearance.
7OT! <or some reference materials# additional docmentation related to# for e6ample# origin# conformity of the
material to safety re*irements# might be re*ired for cstoms clearance.
3%'2%2 The reference material prodcer shall maintain an p$to$date record of all reference material sales or
distribtion.
3%'2%3 The reference material prodcer shall offer to cstomers reasonable gidance and technical spport
related to the reference materials it prodces.
3%'2%4 The reference material prodcer shall employ best efforts to notify cstomers of any change to the
assigned vale or ncertainty for any prodcts not e6pired.
3%'2%3 Ihere goods are sb"ect to resale throgh an athorized distribtor# with whom the prodcer has a
contractal relationship# the reference material prodcer shall pass on to its athorized distribtor all
necessary information to ensre that an effective post$distribtion service is maintained and make
arrangements with the distribtor to ensre that its activities are e6ected in accordance to the relevant parts
of this )ide.
3%'2%. Ihere goods are sb"ect to resale by other organisations# the prodcer has no control over these
organisations> activities after they have prchased. Therefore# the re*irements regarding distribtion service
to sch resellers are limited to the first reseller as with any direct cstomer.
24
9nne: 9
(informative)
,etrolo*ical tracea4ilit- of certified propert-
&alues of reference materials
9%' "oncept of metrolo*ical tracea4ilit-
2etrological traceability is defined in the BI2 (ISO&I!% )ide ;;3(44+# (.05) as the 8property of a
measrement reslt whereby the reslt can be related to a reference throgh a docmented nbroken chain
of calibrations# each contribting to the measrement ncertainty9. In other words# when the reslt of a
measrement is described as traceable# it is essential to specify to which reference metrological traceability
has been established. It can be to a base *antity of the International System of @nits (SI) (sch as the
ampere)# to a derived *antity (sch as mass fraction)# to a defined scale (sch as pC or hardness)# to a vale
represented by a reference material or to a vale reslting from the se of a method described in a national or
international standard.
In the case of reference materials for physical properties# it is sally possible to establish metrological
traceability via a series of instrment calibrations to the appropriate base *antities of the SI. <or e6ample# the
certification of a reference material for specific heat capacity is based on measrements of electrical energy#
temperatre and mass. .ll those vales are readily traceable to the SI nits by means of instrments
calibrated by or traceable to measrement standards maintained at national metrology laboratories.
In the case of reference materials for chemical composition# establishing metrological traceability of the
assigned vales often involves more steps. <or e6ample# the amont of the analyte of interest is sally
determined by the physical response of an analytical instrment only after carrying ot a nmber of processes
sch as sampling# dissoltion or e6traction# separation by chromatography or more traditional wet$chemical
methods. .ny or all of these processes may constitte links in the metrological traceability chain of the final
reslt# each contribting to the ncertainty of the final reslt. The analytical chemist shall therefore assess the
inflence of the entire measrement process on the *antity vale. This incldes e.g. how efficient each
process has been in completely retaining the analyte# either nchanged or stoichiometrically converted to
another chemical species and how it separated the analyte from sbstances which interfere in the final
instrmental measrement and which contribtion each step has made to the ncertainty of the final reslt.
%are shall be taken that the measred *antity is sfficiently defined. <or e6ample# the measrand may be
defined as the mass of lead in a given volme of blood and e6pressed in nits of grams per litre# or as
amont$of$sbstance of ''T per mass of animal tisse# e6pressed in nits of moles per kilogram.
9%2 9ssi*nment of propert- &alues to reference materials
.s noted in the main te6t in ,.5,# this )ide recognizes for main procedres for the characterization leading
to the assignment of property vales of reference materials.
. single (primary) method is considered to be one where the property 8is either directly measred in terms of
the base nits of measrement or indirectly related to the base nits throgh physical or chemical theory
e6pressed in e6act mathematical e*ations9. !ven where sch a so$called primary method is available# it is
desirable that two or more analysts make independent determinations# preferably with different e6perimental
facilities.
Bale assignment by interlaboratory comparison prespposes the e6istence of a nmber of e*ally capable
laboratories employing methods which have been independently validated# and implies that differences
between individal reslts are statistical in natre and can therefore be treated by prely statistical procedres.
This approach to certification has to inclde sfficient assessment based on technical knowledge and
25
"dgement. Statistical treatment of data shold not predominate. . sbset of this procedre is when the
analysis is method$specific.
The metrological traceability of the property vales assigned to reference materials can therefore range from a
rigoros chain of instrmental calibrations back to the base nits of the SI to the se of a well$defined
reference method. In each case# the reference material prodcer needs to consider how to apply the relevant
principle. Ihat is essential is that the certificate contains a statement of metrological traceability indicating the
principles and procedres on which the property vales (together with their ncertainties) are based. .
certified vale withot this additional information is generally considered nacceptable for a certified reference
material.
26
9nne: ;
(informative)
"ommuta4ilit- of reference materials
;%' "oncept of commuta4ilit-
. material is said to be commtable when e*ivalent mathematical ratios are observed for the reslts for a
stated measrand obtained from the application of different measrement procedres both to the material and
to a set of rotine test samples containing the measrand.
In the particlar case of a reference material# the assessment of commtability re*ires a comparison of the
relationship between the property vales assigned to a reference material and to standard test samples sing
both a 8higher$order9 reference measrement procedre and one or more 8lower$order9 rotine measrement
procedres. If the ratio between the reslts obtained for the reference material by the reference procedre and
each of the rotine measrement procedres is the same as the ratio of the reslts for representative test
samples analysed by the same set of measrement procedres# the reference material is said to be
commtable and can be sed for establishment of metrological traceability.
If a 8higher order9 reference measrement procedre is not available# at least harmonization can be achieved
if commtability has been established throgh comparison of the relationship between the property vale
assigned to a reference material and to representative rotine test samples sing the two measrement
procedres to be harmonized.
In other words# a reference material is commtable if the behavior of the target analyte towards a given
measrement procedre is e*ivalent in the reference material and in rotine test samples. This implies that
the application of the procedre to the reference material wold prodce the same *antitative response as a
normal test sample containing the same amont&activity&concentration of the analyte. It is important to note
that there is no a priori re*irement that the application of different procedres nominally for determination of
the same measrand to a commtable reference material will necessarily prodce *antitative reslts for the
measrand that are in close absolte agreement. The only constraint for the establishment of commtability is
that the ratio of the reslts obtained with the different procedres be e*ivalent both for the reference material
and for the rotine samples.
Statements abot the commtability of a reference material always re*ire specification of the measrement
procedres for which it is fond to be commtable. Fikewise# commtability of the reference material may be
demonstrated relative to some rotine procedres bt not towards others. In cases where the reference
material is commtable with all methods investigated# it does not imply that it is commtable with any method.
There are a nmber of definitions of commtability given in varios standard or gidance docments. They all
agree on the basic principles of the concept and the process for the establishment of commtability# bt differ
in wording and details of the natre of the materials sed in the assessment of commtability and the
description of how the relationship between measrement procedres is to be established.
In this )ide# the BI2 (ISO&I!% )ide ;;3(44+# ,.5,) definition of commtability is sed (see /.:).
The desirability of determining the commtability of reference materials was first established in clinical
chemistry# where a range of measrement procedres are sed for the rotine clinical testing of particlar
measrands in patient samples. These procedres rely on a nmber of different physicochemical or
biochemical principles or are based on the detection and measrement of varios sb$components of a
comple6 biomoleclar species that are assmed to relate directly to the level of the clinically significant forms
of the molecle present in the sample. The procedres are sensitive to varying degrees to interferences
arising from differences between the matri6 of a reference material and that of clinical samples# or to
differences in response de to alterations of the analyte (sch as denatration# changes in aggregation#
27
oligomeric state# metal binding) and the matri6 in the corse of the prodction of the reference material.
%onse*ently# it is not possible to attribte discrepancies observed among measrement procedres that
have been calibrated or validated by reference materials of nknown commtability to genine problems with
the measrement procedre(s) or to a bias introdced by differences in response of the reference materials
towards the varios procedres nder test.
%alibration or treness control sing reference materials of demonstrated commtability prodces test reslts
that are in principle comparable# traceable to the reference measrement system sed to assign the reference
material property vales and withot a calibration bias among the assessed procedres.
The need for the establishment of the commtability of reference materials is not limited to clinical chemistry.
It is desirable in any field where the measrement procedres in rotine se are based on different physical or
chemical principles in comparison to the reference method sed to assign the property vales of a reference
material. It is particlarly important to assess commtability where differences between the matri6 of the
reference material or changes to the secondary&tertiary strctre of the analyte in the reference material
relative to normal test samples cold potentially introdce a bias between reslts obtained with one
measrement procedre relative to the reslts obtained with (an)other procedre(s) when sed on
representative test samples. In the particlar case of clinical chemistry# it is desirable that the commtability of
reference materials be assessed relative to representative clinical samples from healthy individals and if
necessary also from diseased individals.
;%2 9ssessment of the commuta4ilit- of reference materials
There are varios approaches reported for assessing commtability of reference materials and leading
references are provided in the accompanying bibliography. In particlar# the %linical and Faboratory Standards
Institte (%FSI) prodces gidelines relevant to the establishment of commtability for reference materials for
se in clinical chemistry.
The simplest case is the establishment of the commtability of a reference material relative to two
measrement procedres# one of them preferably being a measrement procedre of higher metrological
order. The mathematical relationship between the reslts obtained sing rotine test samples is determined
sing both measrement procedres. 1egression analysis can be sed to establish the relation between the
reslts obtained with the two procedres and typically a ;, - prediction interval is calclated to describe the
distribtion of the reslt ratio e6pected for rotine samples. If the reslt ratio obtained for the reference
material sing the two methods is consistent with the confidence interval calclated for representative test
samples# the reference material is commtable with respect to the rotine measrement procedre. The ;, -
prediction interval shold be consistent with the precision level allowable for given applications of the
measrement procedres. Therefore# a large scatter in the correlation plot shold trigger either a refinement
of the measrement procedres to make them detect the same analyte or different analytes in a constant
concentration ratio in typical rotine samples or shold lead to a redefinition of the analyte and eventally
e6isting reference measrement procedres. Only then can comparability between reslts of different
measrements procedres on typical rotine samples be achieved.
!6amples of references to more comple6 approaches sing mltivariate statistical assessments that can be
sed to establish the commtability of a reference material to mltiple test procedres are given in the
Gibliography (see 1eferences D(E# D/E# D0E# D5:E).
28
9nne: "
(informative)
ISO8IE" '/0238ISO Guide 34 cross6reference ta4le
Only closely corresponding sbclases are listed in the same row. %ells are left empty if the respective
docment has no closely corresponding sbclase.
ISO8IE"'/023:2003 ISO Guide 34:2009
' = Scope ' = Scope
2 = (ormati&e reference 2 = (ormati&e references
3 = )erms and definitions 3 = )erms and definitions
4 = ,ana*ement requirements 4 = Or*ani+ation and mana*ement requirements
4%' Or*ani+ation 4%2 Or*ani+ation and mana*ement
0.5.5 0.(.5
0.5.( 0.(.(
0.5./ 0.(.(
0.5.0 0.(./b)# d)
0.5., 0.(./
0.5.:
4%2 ,ana*ement s-stem 4%' ,ana*ement s-stem requirements
0.(.5 0.5.5
0.(.( 0.5.(
0.(./ 0.5.(e)
0.(.0
0.(.,
0.(.: 0.5./
0.(.+
4%3 Document control 4 %3 Document and information control
0./.5 0./.5
0./.( 0./.(
0././ 0././
4%4 0e&ie$ of requests1 tenders and contracts 4%4 0equest1 tender and contract re&ie$s
0.0.5 0.0.5
0.0.( 0.0.(
0.0./ 0.0./
0.0.0
0.0.,
4%3 Su4contractin* of tests and cali4rations 4%3 Use of su4contractors
0.,.5 0.,.5
0.,.(
0.,./
29
ISO8IE"'/023:2003 ISO Guide 34:2009
0.,.0 0.,.0
0.,.(
0.,./
4%. 5urchasin* ser&ices and supplies 4%. 5rocurement of ser&ices and supplies
0.:.5 0.:.5
0.:.( 0.:.0
0.:./
0.:.0 0.:.,
0.:.(
0.:./
4%/ Ser&ice to the customer 4%/ "ustomer ser&ice
0.+.5 0.+.5
0.+.( 0.+.(
4%2 "omplaints 4%2 "omplaints
4%9 "ontrol of nonconformin* testin* and8or
cali4ration $or7
4%9 "ontrol of non6conformin* $or7 and8or
reference materials
0.;.5 0.;.5
0.;.( 0.;.(
4%'0 Impro&ement 4%'2 Impro&ement
4%'' "orrecti&e action 4%'0 "orrecti&e actions
0.55.5 0.54.5
0.55.( 0.54.(
0.55./ 0.54./
0.55.0 0.54.0
0.55., 0.54.,
4%'2 5re&enti&e action 4%'' 5re&enti&e actions
0.5(.5 0.55.5
0.5(.( 0.55.(
4%'3 "ontrol of records 4%'3 0ecords
0.5/.5. 0.5/.5
0.5/.( 0.5/.(
4%'4 Internal audits 4%'4 Internal audits
0.50.5 0.50.5
0.50.( 0.50.(
0.50./ 0.50./
0.50.0 0.50.0
4%'3 ,ana*ement re&ie$s 4%'3 ,ana*ement re&ie$s
0.5,.5 0.5,.5
0.5,.( 0.5,.(
3 = )echnical requirements 3 = )echnical and production requirements
30
ISO8IE"'/023:2003 ISO Guide 34:2009
3%' General 3%' General
,.5.5
,.5.(
3%2 5ersonnel 3%2 5ersonnel
,.(.5 ,.(.(
,.(.( ,.(./
,.(./ ,.(.,
,.(.0 ,.(.0
,.(., ,.(.:
,.(.5
3%3 9ccommodation and en&ironmental
conditions
3%. 9ccommodation and en&ironmental
conditions
,./.5 ,.:.5
,./.( ,.:.5# ,.:./
,././ ,.:.5
,./.0
,./.,
,.:.(
3%4 )est and cali4ration methods and method
&alidation
3%9 ,easurement methods
,.0.5 ,.;.5
,.0.(
,.0./
,.0.0 ,.;.(
,.0.,
,.0.:
,.0.+ ,.55.5# ,.55.(
,.;./
3%3 Equipment 3%'0 ,easurin* equipment
,.,.5
,.,.( ,.54.5# ,.54.0
,.,./
,.,.0
,.,.,
,.,.:
,.,.+ ,.54.(
,.,.= ,.54./
,.,.;
,.,.54
,.,.55
,.,.5(
,.54.,
31
ISO8IE"'/023:2003 ISO Guide 34:2009
3%. ,easurement tracea4ilit- 3%'2 ,etrolo*ical tracea4ilit-
,.:.5
,.:.(
,.:./
,.5(.5
,.5(.(
,.5(./
,.5(.0
3%/ Samplin*
,.+.5
,.+.( ,.;./
,.+./
3%2 >andlin* of test and cali4ration items
,.=.5
,.=.(
,.=./
,.=.0
3%9 9ssurin* the qualit- of test and cali4ration
results
,.;.5
,.;.(
3%'0 0eportin* of results
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,.54.0
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,.54.:
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3%3 Su4contractors
,./.5
,./.(
,././
,./.0
3%4 5roduction plannin*
,.0.5
,.0.(
,.0./
32
ISO8IE"'/023:2003 ISO Guide 34:2009
3%3 5roduction control
3%/ ,aterial handlin* and stora*e
,.+.5
,.+.(
,.+./
,.+.0
,.+.,
,.+.:
3%2 ,aterial processin*
3%'' Data e&aluation
,.0.+.5 ,.55.5
,.0.+.( ,.55.(
,.55./
3%'3 9ssessment of homo*eneit-
,.5/.5
,.5/.(
,.5/./
3%'4 9ssessment of sta4ilit-
,.50.5
,.50.(
,.50./
,.50.0
,.50.,
3%'3 "haracteri+ation
3%'. 9ssi*nment of propert- &alues and their
uncertainties
,.5:.5
,.5:.(
3%'/ "ertificates or documentation for users
3%'2 Distri4ution ser&ice
,.5=.5
,.5=.(
,.5=./
,.5=.0
,.5=.,
,.5=.:
33
;i4lio*raph-
D5E %IT.%&!@1.%C!2 )ide3(44(# Guide to 'uality in *nalytical Chemistry: an *id to *ccreditation
D(E %FSI&7%%FS %,/$P# Characteri+ation and 'ualification of Commutable Reference Materials for
,aboratory Medicine- Proposed Guideline. /anuary 0112
D/E %FSI )ide !P50$.( ((44,)# 3#aluation of Matrix 3ffects: *ppro#ed Guideline
D0E %FSI 1eport J,$1 ((44:)# Metrolo$ical Traceability and "ts "mplementation- * Report
D,E !7 0,444 series35;=;# General criteria for the operation of testin$ laboratories
D:E !@1.%C!2&%IT.% )ide3(44/# Traceability in Chemical Measurement
D+E IF.%$)5(3(444# Guidelines for the Re)uirements for the Competence of Reference Material
Producers
D=E IF.%$)(0&OI2F ' 543(44+# Guidelines for the determination of calibration inter#als of measurin$
instruments
D;E IF.%$P543(44(# ",*C Policy on Traceability of Measurement Results
D54E ISO )ide /(35;;+# Calibration in analytical chemistry and use of certified reference materials
D55E ISO )ide //3(444# Uses of certified reference materials
D5(E ISO /,/0$53(44:# 4tatistics &ocabulary and symbols Part 5: General statistical terms and terms
used in probability
D5/E ISO /,/0$(3(44:# 4tatistics &ocabulary and symbols Part 0: *pplied statistics
D50E ISO ;4453(44=# 'uality mana$ement systems Re)uirements
D5,E ISO 5+,553(44/# In vitro dia$nostic medical de#ices Measurement of )uantities in biolo$ical
samples Metrolo$ical traceability of #alues assi$ned to calibrators and control materials
D5:E B!SP!1# C.I.# 2IFF!1# I.). and 2L!1S# ).F.# %lin. Giochem. 1ev.# 22# (44+# p. 50# Reference
Materials and Commutability
34