ISO 28218:2010
(Main)Radiation protection — Performance criteria for radiobioassay
Radiation protection — Performance criteria for radiobioassay
This International Standard provides criteria for quality assurance and control, and evaluation of performance of radiobioassay service laboratories. Criteria and guidance for in vivo radiobioassay and in vitro radiobioassay are given in separate clauses. The following are within the scope of this International Standard: the accuracy of in vivo measurements of activity and quantities of selected important radionuclides in test phantoms, and in vitro measurements of activity and quantities of selected important radionuclides in test samples; minimal requirements for detection limit; minimum testing levels and testing ranges; requirements for reporting radiobioassay results by service laboratories; quality assurance in service laboratories; quality control in service laboratories; protocol for reporting test evaluations by service laboratories to the testing laboratory; default procedures when the service laboratory customer does not specify the performance criteria; applications of y# for different methods (see Annexes A and B). The following are not within the scope of this International Standard: detailed radiochemical methods for separating radionuclides from biological samples; detailed procedures for in vivo and in vitro radioactivity measurements; biokinetic data and mathematical models for converting radiobioassay results into dose (dose assessment); procedures for the preparation and distribution of test samples and phantoms by the testing laboratories.
Radioprotection — Critères de performance pour l'analyse radiotoxicologique
General Information
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Standards Content (Sample)
INTERNATIONAL ISO
STANDARD 28218
First edition
2010-10-01
Radiation protection — Performance
criteria for radiobioassay
Radioprotection — Critères de performance pour l'analyse
radiotoxicologique
Reference number
ISO 28218:2010(E)
©
ISO 2010
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ISO 28218:2010(E)
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ii © ISO 2010 – All rights reserved
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ISO 28218:2010(E)
Contents Page
Foreword .iv
Introduction.v
1 Scope.1
2 Normative references.2
3 Terms and definitions .2
4 Symbols.6
5 Performance measures.7
* #
5.1 Decision threshold (y ) and detection limit (y ).7
5.2 Relative bias and bias performance criteria.10
5.3 Repeatability performance criteria .12
6 Performance criteria for in vivo radiobioassay.12
6.1 General .12
6.2 Responsibilities of the customer that could impact the service laboratory's performance .12
6.3 Service laboratory criteria .12
6.4 Identification of radionuclides .13
6.5 Quantification .13
6.6 Reporting results.14
6.7 Records retention.15
7 Performance criteria for in vitro radiobioassay .15
7.1 General .15
7.2 Responsibilities of the customer that could impact the service laboratory's performance .15
7.3 Analytical methodology.16
7.4 Reporting results.17
7.5 Records retention.17
8 Quality assurance and quality control for radiobioassay laboratories .18
8.1 General .18
8.2 Quality assurance.18
8.3 Quality assurance plan .19
8.4 Quality control .20
9 Performance testing programme.21
9.1 General .21
9.2 In vivo radiobioassay.22
9.3 In vitro radiobioassay .25
Annex A (informative) Detection limit — Models for applications.29
Annex B (informative) Detection limit — Application examples .32
Bibliography.45
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ISO 28218:2010(E)
Foreword
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 out through ISO
technical committees. Each member body interested in a subject 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 Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. ISO shall not be held responsible for identifying any or all such patent rights.
ISO 28218 was prepared by Technical Committee ISO/TC 85, Nuclear energy, nuclear technologies, and
radiological protection, Subcommittee SC 2, Radiological protection.
This first edition of ISO 28218 cancels and replaces ISO 12790-1:2001, which has been technically revised.
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ISO 28218:2010(E)
Introduction
In the course of employment, individuals might work with radioactive materials that, under certain
circumstances, could be taken into the body. Radiation protection programmes for these individuals can
include means for in vivo or in vitro measurements of radioactive material that has entered the body. The
performance criteria required for such measurements usually depend upon the purpose for the radiobioassay
measurement, which can include determining the internal human burden of radioactive material, estimating
doses and dose commitments, radiation protection management, medical management when appropriate,
and providing the necessary data for legal and record-keeping requirements.
Analytical methods for radiobioassay are not currently standardized, but are available in the literature.
Guidance on the evaluation of data from the monitoring of workers occupationally exposed to the risk of
internal contamination by radioactive substances is provided in ISO 27048 as well as other publications of
national and international regulations and guides, the International Commission on Radiological Protection
(ICRP), the National Council on Radiation Protection and Measurement (NCRP), the International Atomic
Energy Agency (IAEA) and the International Commission on Radiological Units and Measurements (ICRU).
Recommendations of the ICRP, NCRP, IAEA and ICRU, as well as experience with the practical application of
these recommendations to the conduct of radiobioassay services and the interpretation and use of
radiobioassay results in radiation protection programmes, have been considered in the development of this
International Standard.
In addition to superseding ISO 12790-1:2001, this International Standard complements the requirements of
ISO 20553. This International Standard develops, expands and applies the principles defined in the
aforementioned standards for radiobioassay laboratories. It also provides a consensus on the statistical
definitions and formulations of the quantitative performance criteria of decision threshold, detection limit,
relative bias and repeatability. These concepts follow the requirements of ISO 11929. In particular, the
concept of minimum detectable amount (MDA) used in ISO 12790-1:2001 has been abandoned in favour of
#
detection limit (y ).
Clauses 5 to 8 primarily provide guidance for radiobioassay service laboratories, whereas Clause 9 relates to
testing laboratories and provides criteria for performance testing. The information in these clauses provides
beneficial insight for service laboratories, for users of the laboratory's services, and for testing laboratories, and
it provides a possible basis for an inter-laboratory quality assurance plan.
In this International Standard, the following verbal forms apply:
⎯ “shall” is used to denote a requirement;
⎯ “should” is used to denote a recommendation;
⎯ “may” is used to denote permission (neither a requirement nor a recommendation).
To conform with this International Standard, all radiobioassay needs to be performed in accordance with its
requirements, but not necessarily with its recommendations; however, justification needs to be documented for
deviations from recommendations.
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INTERNATIONAL STANDARD ISO 28218:2010(E)
Radiation protection — Performance criteria for radiobioassay
1 Scope
This International Standard provides criteria for quality assurance and control, and evaluation of performance
of radiobioassay service laboratories.
Criteria and guidance for in vivo radiobioassay and in vitro radiobioassay are given in separate clauses.
The following are within the scope of this International Standard:
⎯ the accuracy of
⎯ in vivo measurements of activity and quantities of selected important radionuclides in test phantoms,
and
⎯ in vitro measurements of activity and quantities of selected important radionuclides in test samples;
⎯ minimal requirements for detection limit;
⎯ minimum testing levels and testing ranges;
⎯ requirements for reporting radiobioassay results by service laboratories;
⎯ quality assurance in service laboratories;
⎯ quality control in service laboratories;
⎯ protocol for reporting test evaluations by service laboratories to the testing laboratory;
⎯ default procedures when the service laboratory customer does not specify the performance criteria;
#
⎯ applications of y for different methods (see Annexes A and B).
The following are not within the scope of this International Standard:
⎯ detailed radiochemical methods for separating radionuclides from biological samples;
⎯ detailed procedures for in vivo and in vitro radioactivity measurements;
⎯ biokinetic data and mathematical models for converting radiobioassay results into dose (dose
assessment);
⎯ procedures for the preparation and distribution of test samples and phantoms by the testing laboratories.
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ISO 28218:2010(E)
2 Normative references
The following referenced documents are indispensable for the application of this document. For dated
references, only the edition cited applies. For undated references, the latest edition of the referenced
document (including any amendments) applies.
ISO/IEC Guide 99, International vocabulary of metrology — Basic and general concepts and associated terms
(VIM)
ISO 5725-1, Accuracy (trueness and precision) of measurement methods and results — Part 1: General
principles and definitions
ISO 5725-2, Accuracy (trueness and precision) of measurement methods and results — Part 2: Basic method
for the determination of repeatability and reproducibility of a standard measurement method
ISO 5725-3, Accuracy (trueness and precision) of measurement methods and results — Part 3: Intermediate
measures of the precision of a standard measurement method
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO/IEC Guide 99, ISO 5725-1,
ISO 5725-2, ISO 5725-3 and the following apply.
3.1
accuracy
characteristic of an analysis or determination that ensures that both the bias and repeatability of the resulting
quantity remain within specified limits
3.2
activity
number of spontaneous nuclear disintegrations per unit time
3.3
aliquot
〈in vitro radiobioassay〉 representative portion of a whole
3.4
appropriate blank
uncontaminated sample, unexposed person or phantom that is ideally identical in physiochemically and
radiologically significant ways with the sample, person or phantom to be analysed
3.5
background
ambient signal response recorded by measurement instruments that is independent of radioactivity
contributed by the radionuclides concerned
3.6
bias
systematic error of the indication of a measuring instrument
3.7
freedom from bias
ability of a measuring instrument to give indications free from systematic error
3.8
blind testing
testing of capabilities when the service laboratory is not aware that they are being tested for conformance
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ISO 28218:2010(E)
3.9
certified reference material
CRM
reference material, characterized by a metrologically valid procedure for one or more specified properties,
accompanied by a certificate that provides the value of the specified property, its associated uncertainty and a
statement of the metrological traceability
3.10
concentration
activity or mass per unit volume or per unit mass
3.11
confidence interval
interval about an estimate of a stated quantity, within which the expected value of the quantity is expected to
lie (with a specified probability)
3.12
decision threshold
fixed value of the measurand by which, when exceeded by the result of an actual measurement of a
measurand quantifying a physical effect, it is decided that the physical effect is present
NOTE The decision threshold is the critical value of a statistical test for the decision between the hypothesis that the
physical effect is not present and the alternative hypothesis that it is present. When the critical value is exceeded by the
result of an actual measurement, this is taken to indicate that the hypothesis should be rejected. The statistical test is
designed in such a way that the probability of wrongly rejecting the hypothesis (error of the first kind) is at most equal to a
given value, α.
3.13
detection limit
smallest true value of the measurand that is detectable by the measuring method
NOTE The detection limit is the smallest true value of the measurand that is associated with the statistical test and
hypothesis in accordance with the decision threshold (3.12) by the following characteristics: if in reality the true value is
equal or exceeds the detection limit, the probability of wrongly not rejecting the hypothesis (error of the second kind) is at
most equal to a given value, β.
3.14
in vitro radiobioassay
measurements to determine the presence of, or to estimate the amount of, radioactive material in the excreta
or in other biological materials removed from the body
3.15
in vivo radiobioassay
measurements of radioactive material in the human body utilizing instrumentation that detects radiation
emitted from the radioactive material in the body
3.16
measurand
particular quantity subject to measurement
3.17
monitoring
measurements made for the purpose of assessment or control of exposure to radioactive material and the
interpretation of the results
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ISO 28218:2010(E)
3.18
minimum testing level
MTL
amount of radioactive material that the service laboratory is intended to be able to measure for participation in
the performance testing programme, assuming the samples are free of interference from other radionuclides,
unless specifically addressed
NOTE The MTLs are not intended to be interpreted as the appropriate detection limit required for a specific internal
dosimetry programme, but rather as an acceptable minimum testing level for radiobioassay service laboratories based on
good measurement practice.
3.19
phantom
surrogate person, or part of a person, used for calibration of in vivo measurement systems
NOTE A phantom is constructed to allow placement of radionuclides in a geometry approximating internal
depositions. A phantom could be used as an appropriate blank (3.4).
3.20
quality assurance
planned and systematic actions necessary to provide adequate confidence that an analysis, measurement or
monitoring programme will perform satisfactorily in service
3.21
quality control
actions that control the attributes of the analytical process, standards, reagents, measurement equipment,
components, system or facility in accordance with predetermined quality requirements
3.22
radiobioassay
measurement of amount or concentration of radionuclide material in the body, or in biological material
excreted or removed from the body (measurand), and analysed for purposes of estimating the quantity of
radioactive material in the body
3.23
reagent blank
contribution of the reagents to the measurement process determined by carrying the reagents through all the
operations that are used for the sample
3.24
relative bias
quotient of the bias divided by the expected value
3.25
relative standard deviation
σ
r
quotient of the estimated standard deviation of a series of determinations, y , y , .yx , y , of a quantity divided
1 2 i n
by the arithmetic mean value, , of y , i.e.
y
i
n
2
()yy−
∑ i
i=1
(1n −)
σ =
r
y
or, for a single measurement, the quotient of the estimate of the standard deviation divided by the value of the
single measurement (synonymous with the relative standard deviation, multiplied by 100 when expressed as
percent)
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ISO 28218:2010(E)
3.26
repeatability
closeness of the agreement between the results of successive measurements of the same measurand carried
out under the same conditions of measurement
3.27
reproducibility
closeness of the agreement between the results of measurements of the same measurand carried out under
changed conditions of measurement
3.28
service laboratory
laboratory performing in vivo or in vitro radiobioassay measurements
3.29
standard deviation
s
quantity characterizing the dispersion of the results for a series of n measurements of the same measurand,
given by the equation
n
2
()yy−
∑ i
i=1
s =
(1n −)
where
y is the result of the ith measurement;
i
y is the arithmetic mean of the n results considered
3.30
systematic error
mean that would result from an infinite number of measurements of the same measurand carried out under
repeatability conditions minus a true value of the measurand
3.31
testing laboratory
laboratory responsible for evaluating the performance of service laboratories in meeting the performance
specifications of ISO 28218
3.32
traceability
property of the result of a measurement or the value of a standard, whereby it can be related to stated
references through an unbroken chain of comparisons all having stated uncertainties
NOTE 1 Stated references are usually national or International Standards.
NOTE 2 The unbroken chain of comparisons is called a traceability chain.
3.33
transfer reference standard
TRS
material that contains radionuclide components of interest in chemical and physical forms similar to
radiobioassay specimens and that is used to quantify the amount of activity present in a person or sample
measured
NOTE The radionuclides used for the preparation of the TRS are, when possible, related to CRMs. The preparation
procedures are verified and documented.
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ISO 28218:2010(E)
3.34
unbiased
in a state wherein a measurement of a random variable has zero bias
NOTE In other words, the measured value of the quantity is equal to the expected value of the quantity being
determined.
3.35
uncertainty of measurement
parameter, associated with the result of a measurement, that characterizes the dispersion of the values that
could reasonably be attributed to the measurement
3.36
validation
act of defining the method capability and determining whether it can be properly applied as intended, or a test
to determine whether the overall implemented analysis fulfils specified requirements
3.37
verification
act of confirming, substantiating or assuring that an action, condition or goal has been implemented,
completed or accomplished in accordance with the specified requirements or a test, in order to prove that a
particular step of the analysis fulfils specified requirements
4 Symbols
A actual quantity in the test phantom or in vitro sample for the ith measurement
ai
A value of the ith measurement in a category being tested
i
B relative bias
r
B relative bias statistic for the ith measurement
ri
n number of measurements of the same measurand
s standard deviation
s standard deviation of a total blank count
B
s standard deviation of the relative bias applied for performance testing
Br
t counting time interval used in the procedure (seconds)
m number of the input quantities
X input quantity (i = 1,., m)
i
x estimate of the input quantity X
i i
u(x ) standard uncertainty of the input quantity X associated with the estimate x
i i i
h (x) standard uncertainty u(x ) as a function of the estimate x
1 1 1 1
u (w) relative standard uncertainty of a quantity W associated with the estimate w
rel
G model function
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ISO 28218:2010(E)
Y random variable as an estimator of the measurand; also used as the symbol for the non-negative
measurand itself, which quantifies the physical effect of interest
ỹ true value of the measurand; if the physical effect of interest is not present, then ỹ = 0, otherwise,
ỹ > 0
y determined value of the estimator Y, estimate of the measurand, primary measurement result of
the measurand
y values y from different measurements (j = 0,1, 2,.)
j
u(y) standard uncertainty of the measurand associated with the primary measurement result y
ũ(ỹ) standard uncertainty of the estimator Y as a function of the true value ỹ of the measurand
ŷ best estimate of the measurand
u(ŷ) standard uncertainty of the measurand associated with the best estimate ŷ
*
y decision threshold of the measurand
#
y detection limit of the measurand
#
ỹ approximations of the detection limit y
i
y lower confidence limit of the measurand
y upper confidence limit of the measurand
α probability of the error of the first kind
β probability of the error of the second kind
1−γ probability for the confidence interval of the measurand
k quantile of the standardized normal distribution for the probability p (e.g. p = 1−α, 1−β, or 1−γ/2)
p
k quantile of the standardized normal distribution for the probability q
q
Φ(t) distribution function of the standardized normal distribution; Φ(k ) = p applies.
p
5 Performance measures
* #
5.1 Decision threshold (y ) and detection limit (y )
5.1.1 Preamble
The value of the detection limit indicates the ability of the service laboratory to detect a radionuclide in a
sample or person. The decision threshold provides a way of distinguishing the difference between the count
rate from the measurand under analysis and the count rate from the appropriate blank. For in vivo
measurements, the sample matrix (i.e. the person) of the measurand is a variable, therefore the detection limit
is person dependent. For consistency, the detection limit calculated for a given sample represented by a
uniform source distribution, either in a person or in a phantom, shall therefore be used to characterize the
detection capability of the service laboratory. The service laboratory shall determine and document typical
values of the detection limit for documented measurement conditions for each measurand for which a service
is provided.
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ISO 28218:2010(E)
5.1.2 General procedure for the determination of the characteristic limits
5.1.2.1 Introduction
5.1.2.1.1 Preamble
The general procedures for the calculation of the characteristic limits are given in ISO 11929. The main
features are summarized here to facilitate the presentation of the examples given in Annexes A and B. Further
details are provided in ISO 11929. A short presentation of the meaning of the symbols taken from ISO 11929,
and the logical connection between them, is given below.
A non-negative measurand shall be assigned to the physical effect to be investigated in any given
measurement task. This measurand quantifies the effect and assumes the true value ỹ = 0 if the effect is not
present in a particular case. A random variable Y, an estimator, shall be assigned to the measurand. In the
following discussion, the symbol Y is used for the measurand itself. A value y of the estimator Y, determined
from measurements, is an estimate of the measurand. This value shall be calculated as the primary
measurement result, together with the primary standard uncertainty u(y) associated with y. These two values
form the primary complete measurement result for the measurand and are obtained in accordance with
ISO/IEC Guide 98-1 by evaluation of the measurement data and other information by means of a model (of
the evaluation), which mathematically connects all the quantities involved. In general, the fact that the
measurand is non-negative is not explicitly taken into account in the evaluation. Therefore, y may be negative,
especially when the measurand approaches a true value ỹ = 0. The best estimate ỹ of the measurand is
calculated in 5.1.2.5 from the primary measurement result y and its standard uncertainty u(y). In deriving the
value of ỹ, the knowledge that the measurand is non-negative is taken into account. The standard uncertainty
u(ỹ) associated with ỹ is smaller than u(y).
5.1.2.1.2 General model
In general, the non-negative measurand Y is a function of several input quantities X in the following form:
i
YG= X ,.,X (1)
()
1 m
5.1.2.1.3 Calculation of the primary measurement result y and the associated standard uncertainty
Equation (1) is the model of the evaluation. Substituting given estimates x of the input quantities x in the
i
model function G of Equation (1) yields the primary measurement result y of the measurand as
y =Gx ,.,x (2)
()
1 m
The standard uncertainty u(y) of the measurand associated with the primary measurement result y follows, if
...
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