ISO 28218:2010

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 2010
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ii © ISO 2010 – All rights reserved

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

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.
iv © ISO 2010 – All rights reserved

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.

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.
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
2 © ISO 2010 – All rights reserved

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
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
()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)
4 © ISO 2010 – All rights reserved

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
()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.
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
6 © ISO 2010 – All rights reserved

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.
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
the input quantities X are independently measured and standard uncertainties u(x) associated with the
i i
estimates x are given, from the following relation:
i
m
⎛⎞
∂G
uy = u x (3)
() ⎜⎟ ()
∑ i
∂X
i
⎝⎠
i=1
5.1.2.1.4 Calculation of the standard uncertainty ũ (ỹ)
If u(x ) is known as a function h (x ), y is replaced by ỹ and Equation (2) is solved for x . This results in x as a
1 1 1 1 1
function of ỹ and x ,…x . The function replaces x in Equation (3) and in h (x ) yielding ũ (ỹ).
2 m 1 1 1
If u(x ) is known as a function h (x ), it is often sufficient to use the following approximation, especially if the
1 1 1
primary measurement result of the measurand is not much larger than the associated uncertainty u(y):
uy =uy (4)
() ( )
8 © ISO 2010 – All rights reserved

If only ũ(0) = u(y ) (measurement of background or blank) and y > 0 (measurement currently carried out) are
0 1
known, then the following linear interpolation often suffices:
⎛⎞
yy
22 2
 
uy=⋅u 01− +u y⋅ (5)
() ( )⎜⎟ ()
yy
⎝⎠
*
5.1.2.2 Calculation of the decision threshold y
The decision threshold is calculated as
*

yk= u 0 (6)
()
1−α
*
An effect of the measurand Y is recognized as present if y > y . If not, the calculation of the confidence limits
and of the best estimate ŷ of the measurand with the associated standard uncertainty u(ŷ) are omitted.
*
With the approximation ũ(ỹ) = u(y), the relation y = k u(y) applies.
1−α
#
5.1.2.3 Calculation of the detection limit y
#
The detection limit y is the smallest solution of Equation (7):
#* #
yy=+k uy (7)
1−β()
Equation (7) is an implicit equation. The detection limit can be calculated by solving it or, more simply, by
#
iteration. The approximation ỹ for y is repeatedly substituted in the right-hand side of Equation (7) to produce
i
#

with the starting approximation y . As starting approximation, ỹ = 2y can be chosen.
i+1
# *
The detection limit does not exist if y < y .
If the approximation in Equation (4) is used, Equation (7) simplifies to Equation (8):
#
yk=+k ⋅uy (8)
()
()
11−−αβ
If the linear interpolation in accordance with Equation (5) is used, Equation (7) becomes Equation (9):
k
1−β
#22 2 2 22
⎡ ⎤
ya=+a +k −k ⋅u 0 ; ak=⋅⎡⎤u00+⋅ u y−u (9)
() () ()
()11−−βα 11−α ()
⎣⎦
⎢ ⎥
⎣ ⎦
2 y
If α = β, then
#
ya=⋅2 (10)
5.1.2.4 Calculation of the confidence limits
The limits of a confidence interval are provided for a physical effect, recognized as present in accordance with
5.1.2.2, in such a way that the confidence interval contains the true value of the measurand with the specified
γ. The confidence limits take into account that the measurand is non-negative.
probability 1−
The confidence limits are calculated as follows:

y =−yk u y with p=⋅ωγ(1− / 2) (11)
()
p
and

y =+yku y with q=−1 ωγ / 2
()
q
where ω is the integral of the standardized normal distribution
yu/(y)
ων=−exp / 2dyν=Φ⎡⎤/u(y) (12)
()
⎣⎦
∫
2π
−∞
and Φ(k ) = p.
p
ω = 1 may be set if yu/ (y)W 4 and the value of the approximations symmetrical to y apply:
,
y =±yk u y (13)
()
1/−γ 2
5.1.2.5 Calculation of the best estimate of the measurand with the associated standard uncertainty
The determined primary measurement result y of the measurand shall be compared with the decision
* *
threshold y . If y > y , then the physical effect quantified by the measurand is recognized as present.
Otherwise, the hypothesis that the effect is absent cannot be rejected.
On the basis of the measured quantity y and its standard uncertainty u(y), the best estimate of the measurand
and its associated standard uncertainty are calculated as follows:
⎡⎤
uy()⋅−exp y / 2u (y)
{ }
⎣⎦
yyˆ=+ ; uy()ˆˆ=−u (y) (y−y)yˆ (14)
ωπ2
For /yu(y)W4 , the following approximations apply:
ˆ ˆ
yy= ; uy() =u()y (15)
5.2 Relative bias and bias performance criteria
The relative bias is a measure of how close the assessed activity is to the actual activity. Since the actual
activity is rarely known, this criterion applies to measurements on suitable mock-ups, phantoms, or test
samples. These may be used with appropriate reference to standards to determine and minimize fixed
(deterministic) errors, for determining the detection limit and for replications to determine repeatability. The
rationale for the selection of the particular statistics is given in this subclause and in 5.3:
⎯ a relative bias statistic is defined in this International Standard for the purposes of performance testing of
a finite number of measurements in each category of analysis;
⎯ the relative bias statistic (B ) for the ith measurement in a category with respect to the correct value of the
ri
measurand is defined as:
AA−
()
iia
B = (16)
ri
A
ai
where
A is the value of the ith measurement in a category being tested, not necessarily a replicate, but
i
possibly a different quantity of measurand for each measurement;
A is the actual quantity in the measurand for the ith measurement.
ai
10 © ISO 2010 – All rights reserved

The relative bias B for that category is calculated as the average of the individual relative biases B and is
r ri
defined as follows:
n
B
ri
B = (17)
r ∑
n
i=1
where n is the number of test measurements in a given test category.
The sample size n shall be at least five to ensure statistical reliability.
For testing purposes, as described in Clause 9 and in the service laboratory internal quality control, B shall be
r
between −0,25 and +0,50 (unless the customer or regulator specifies a narrower range) when A is greater
ai
than or equal to the customer's MTL (or the MTL given in Tables 1 and 2 when the customer does not specify
MTLs) for any specified radionuclide. The MTL should be greater than the detection limit, since uncertainties
#
will be large at this level: 5 to 10 times y is appropriate unless contractually specified. Test samples with
quantities below the MTL should be analysed for purposes of periodically checking performance near the
#
service laboratory's y of a given analytical procedure; however, performance on test samples below the MTL
is not required to meet the performance criteria for B . When B is outside the −0,25 to +0,50 range in internal
r r
service laboratory quality control checks, the service laboratory shall make appropriate corrections in phantom
calibrations or measurement protocols to reduce or eliminate bias.

Key
B relative bias
r
s repeatability
Br
Figure 1 — Acceptable limits for relative bias, B , and repeatability, s
r Br
5.3 Repeatability performance criteria
For testing purposes and for service laboratory quality control, the repeatability of the measurement process is
selected to be the relative dispersion of the values of B from their mean B and is defined as follows:
ri r
n
()BB−
∑ rri
i=1
s =
Br
(1n −)
The absolute value of the repeatability statistic, s , shall be less than or equal to 0,4 (unless the customer
Br
specifies a smaller value) when A is equal to or greater than the customer's MTL for any given radionuclide
ai
in a category (or the MTL given in Tables 1 and 2 when the customer does not specify MTLs). Performance
on test samples below the MTL is not required to meet the acceptable value of s . When s is greater than
Br Br
0,4 in internal service laboratory quality control checks, appropriate corrective action shall be taken to bring
the repeatability into the acceptable range.
It should be noted that the statistics B and s were selected to be unbiased estimators of the underlying true
r Br
bias and repeatability.
6 Performance criteria for in vivo radiobioassay
6.1 General
The provisions of this International Standard apply to any in vivo radiobioassay system used to measure
radionuclides that are distributed throughout the whole body or localized in individual tissues or organs such
as thyroid, lungs, liver, bone and so on. Procedures shall be validated, written, reviewed and approved in
accordance with the service laboratory's quality assurance plan.
6.2 Responsibilities of the customer that could impact the service laboratory's performance
This subclause includes items that could impact the quality of the work performed by the service laboratory.
The service laboratory should request that the customer take the following precautions prior to submitting
workers to the service laboratory:
a) specify the radionuclide(s) to be analysed;
b) provide accurate and unambiguous identification of the workers;
c) provide information about the material to which the worker may have been exposed [e.g. physical,
specially activity median aerodynamic diameter (AMAD), chemical form, isotopic composition];
d) provide information on the main suspected route of exposure and on the frequency of the monitoring;
e) specify the part of the body on which the measurement has to be made, whole body counting or organ
(lungs, thyroid, etc.);
f) specify the required reporting requirements.
6.3 Service laboratory criteria
6.3.1 General
The in vivo radiobioassay service laboratory shall be adequately equipped, shielded, provided with the
necessary services, and be appropriately located. The minimum requirements for the facility are described in
6.3.2 and 6.3.3.
12 © ISO 2010 – All rights reserved

6.3.2 Equipment
The minimum requirement for the equipment comprising the in vivo measurement system, which includes the
detectors, electronic support, shielding and software, shall be such that the performance of the system meets
the bias and repeatability requirements of Clause 5 and the customer's requirements for the detection limit.
The laboratory should also consider installing a background radiation counter and recording or alarming
systems or other appropriate devices to alert the operator when background changes occur that are sufficient
in magnitude to affect the required detection capabilities.
6.3.3 Services
Personnel decontamination facilities shall be provided at the in vivo radiobioassay service laboratory, should
be in proximity to the counting facility and should be kept away from contaminated areas.
Anti-claustrophobial features in the measurement area, such as a failsafe, door-opening device that can be
operated by the individual being counted, a two-way intercom, music, and restful lighting, may be helpful.
Appropriate means (either procedural or instrumental) shall be used to confirm any activity detected as
internal deposition rather than external contamination. Decontamination measures, such as showering,
followed by recounting may be used as a means for removing and distinguishing external contamination.
Adequate ventilation and, in services where liquid nitrogen is used, oxygen analysers and alarms shall be
provided in the measurement area. Contamination-free clothing shall be available to personnel for in vivo
measurements.
6.3.4 Location
In order to minimize background radiation levels and the possibility of contamination, the service laboratory
should be located at an appropriate distance from areas where radioactive materials are processed, stored or
transported or where radiation is generated. The location shall be subsequently reviewed at intervals in order
to determine whether the interference from sources such as accelerators, reactors and other radiation sources
has increased. The in vivo radiobioassay laboratory shall be designed with sufficient ventilation, filtration and
shielding in order to avoid interfering background fluctuations, such as those due to radon.
6.4 Identification of radionuclides
Except for circumstances where there is only one radionuclide of interest or for systems used for screening,
measurement systems shall provide identification of the radionuclides they are designed to measure. The
method of identification, either automated or manually performed, shall be capable of identifying the significant
components in mixtures of radionuclides of interest to the customer.
6.5 Quantification
Quantification shall be accomplished by calibration with known sources of the radionuclide incorporated in a
suitable mock-up or phantom of the body or the body part of interest (or suitably validated mathematical
phantom). Whenever the phantom does not sufficiently match the subject's physical characteristics, as in
chest wall thickness for low-energy photons, physical measurements of the subject may be used to establish
an appropriate calibration. If not, a correction factor shall be used so that performance criteria can be met.
The in vivo programme (both the counter design and the operational protocol) shall be designed to minimize
measurement uncertainties when used to measure actual depositions of measurand in individuals. A major
source of uncertainty can occur because individuals and the distribution of radionuclides within those
individuals will be different from those represented by phantoms used for counter calibration and performance
testing.
An estimate shall be generated and documented to assess the magnitudes of the uncertainties associated
with the procedure for the radionuclides of importance to the customer. At least an estimate of the uncertainty
associated with each of the following items should be quantified:
a) subject size;
b) chest wall thickness for lung measurements;
c) counting geometries of the organ with respect to the detector;
d) distribution of the activity within the organ;
e) interference from the activity in portions of the body not being measured;
f) interference from other radionuclides;
g) counting statistics during calibration;
h) counting statistics during the in vivo count of the subject; and
i) calibration source uncertainties.
Steps in an in vivo radiobioassay programme that can be taken to reduce uncertainty include calibration for
varying subject size or chest wall thickness, multiple measurements over the retention period, and use of
geometries that minimize source location dependence.
For some types of in vivo measurements, the radionuclide measured might be only an intermediate step to
determine the measurand of interest (e.g. bismuth-214 for radium-226; americium-241 for plutonium-239;
thorium-234 for uranium-238; uranium-235 for uranium-234). The ratio of the radionuclide of interest to the
radionuclide being counted shall be determined or estimated. Steps shall be taken to quantify the
uncertainties involv
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