ASTM E2857-11(2016)

Standard Guide for Validating Analytical Methods

SIGNIFICANCE AND USE
4.1 Method validation is a process of demonstrating that the method meets the required performance capabilities. International standards such as ISO/IEC 17025, certifying bodies, and regulatory agencies require evidence that analytical methods are capable of producing valid results. This applies to laboratories using published standard test methods, modified standard test methods, and in-house test methods.  
4.2 Although a collaborative study is part of this guide, this guide may be used by a single laboratory for method validation when a formal collaboration study is not practical. This guide may also be applied before a full collaboration study to predict the reliability of the method.  
4.3 The use of multiple validation techniques described in this guide increases confidence in the validity or application of the method.  
4.4 It is beyond the scope of this guide to describe fully the fundamental considerations in Section 5. For a more descriptive definition of these concepts, refer to the International Union of Pure and Applied Chemistry (IUPAC) technical report, “Harmonized Guidelines for Single Laboratory Validation of Methods of Analysis,”5 the IUPAC Compendium of Analytical Nomenclature (Orange Book),6 and the Eurachem publication, The Fitness for Purpose of Analytical Methods, A Laboratory Guide to Method Validation and Related Topics.7
SCOPE
1.1 This guide describes procedures for the validation of chemical and spectrochemical analytical methods of analysis that are used by a metals, ores, and related materials analysis laboratory.  
1.2 This guide may be applied to the validation of laboratory developed (in-house) methods, addition of analytes to an existing standard test method, variation or scope expansion of an existing standard method, or the use of new or different laboratory equipment.  
1.3 This guide may also be used to validate the implementation of standard test methods used routinely by laboratories of the mining, ore processing, and metals industry.

General Information

• Status: Historical
• Publication Date: 30-Sep-2016
• ICS: 71.040.40 - Chemical analysis
• ICS: 71.040.50 - Physicochemical methods of analysis
• Technical Committee: E01 - Analytical Chemistry for Metals, Ores, and Related Materials
• Drafting Committee: E01.22 - Laboratory Quality

Standards Content (Sample)

NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
Contact ASTM International (www.astm.org) for the latest information
Designation: E2857 − 11 (Reapproved 2016)
Standard Guide for
Validating Analytical Methods
This standard is issued under the fixed designation E2857; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope 3.2 Definitions of Terms Specific to This Standard:
3.2.1 validation (of an analytical method), n—confirmation,
1.1 This guide describes procedures for the validation of
by the provision of objective evidence and examination, that a
chemical and spectrochemical analytical methods of analysis
method meets performance requirements and is suitable for its
that are used by a metals, ores, and related materials analysis
intended use.
laboratory.
4. Significance and Use
1.2 This guide may be applied to the validation of labora-
tory developed (in-house) methods, addition of analytes to an
4.1 Method validation is a process of demonstrating that the
existing standard test method, variation or scope expansion of
method meets the required performance capabilities. Interna-
an existing standard method, or the use of new or different
tional standards such as ISO/IEC 17025, certifying bodies, and
laboratory equipment.
regulatory agencies require evidence that analytical methods
are capable of producing valid results. This applies to labora-
1.3 This guide may also be used to validate the implemen-
toriesusingpublishedstandardtestmethods,modifiedstandard
tation of standard test methods used routinely by laboratories
test methods, and in-house test methods.
of the mining, ore processing, and metals industry.
4.2 Although a collaborative study is part of this guide, this
2. Referenced Documents
guidemaybeusedbyasinglelaboratoryformethodvalidation
2.1 ASTM Standards:
when a formal collaboration study is not practical. This guide
E135 Terminology Relating to Analytical Chemistry for
may also be applied before a full collaboration study to predict
Metals, Ores, and Related Materials
the reliability of the method.
E1601 Practice for Conducting an Interlaboratory Study to
4.3 The use of multiple validation techniques described in
Evaluate the Performance of an Analytical Method
this guide increases confidence in the validity or application of
E1763 Guide for Interpretation and Use of Results from
the method.
Interlaboratory Testing of Chemical Analysis Methods
4.4 It is beyond the scope of this guide to describe fully the
(Withdrawn 2015)
4 fundamental considerations in Section 5. For a more descrip-
2.2 ISO Standard:
tive definition of these concepts, refer to the International
ISO/IEC 17025 General requirements for the competence of
Union of Pure and Applied Chemistry (IUPAC) technical
testing and calibration laboratories
report, “Harmonized Guidelines for Single Laboratory Valida-
tion of Methods of Analysis,” the IUPAC Compendium of
3. Terminology
Analytical Nomenclature (Orange Book), and the Eurachem
3.1 Definitions—For definitions of terms used in this guide,
publication, The Fitness for Purpose of Analytical Methods, A
refer to Terminology E135.
Laboratory Guide to Method Validation and Related Topics.
5. Fundamental Considerations
This guide is under the jurisdiction of ASTM Committee E01 on Analytical
Chemistry for Metals, Ores, and Related Materials and is the direct responsibility of 5.1 During the process of method validation, the user of an
Subcommittee E01.22 on Laboratory Quality.
analyticalmethodshouldapplyanumberoffundamentaltenets
Current edition approved Oct. 1, 2016. Published October 2016. Originally
approved in 2011. Last previous edition approved in 2011 as E2857–11. DOI:
10.1520/E2857–11R16. M. Thompson, S. Ellison, and R. Wood, “Harmonized Guidelines for Single-
For referenced ASTM standards, visit the ASTM website, www.astm.org, or Laboratory Validation of Methods of Analysis,” Pure Appl. Chem., Vol 71, No. 2,
contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM 2002, pp. 835-855. http://iupac.org/publications/pac
Standards volume information, refer to the standard’s Document Summary page on International Union of Pure and Applied Chemistry Compendium of Analytical
the ASTM website. Nomenclature: Definitive Rules 1997, http://old.iupac.org/publications/analytical_
The last approved version of this historical standard is referenced on compendium/
www.astm.org. EURACHEM Guide, The Fitness for Purpose of Analytical Methods, A
Available fromAmerican National Standards Institute (ANSI), 25 W. 43rd St., Laboratory Guide to Method Validation and Related Topics, LGC, Teddington,
4th Floor, New York, NY 10036, http://www.ansi.org. Middlesex, United Kingdom, 1998. www.eurachem.org
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
E2857 − 11 (2016)
of analytical chemistry as they relate to the development and fraction) of the analyte than the laboratory must quantify. For
implementation of test methods. It is important to make the additional information, consult the IUPAC Orange Book and
distinction between the validation of a test method by a the Currie paper.
standards-developing organization and the implementation of 5.1.3 Limit of Quantification (L )—The limit of quantifica-
Q
that test method by a laboratory. Whether the test method was tion is defined as the amount of analyte above which the
developed by a committee of experts or by one chemist in a estimated relative standard deviation (RSD) is ≤10 %. It is
company laboratory, the laboratory shall implement the important to demonstrate and document that the measurement
methodinthelaboratoryandshalldemonstratethatthemethod process has the capability to quantify amounts less than or
is being performed sufficiently well and that the results meet equal to those found in materials to which the test method is
the goals for data quality.That is, they should ascertain that the applied.Foradditionalinformation,consulttheIUPACOrange
measurement process provides sufficient levels of performance Book and the Currie paper.
fit for the purpose of testing the materials at hand. It is 5.1.4 Bias—Bias is the difference between the obtained
advisable to determine and document performance character- result for a measurand and the true value of the measurand.An
istics of the method including repeatability precision, limit of analytical method may be subject to a known amount of bias
detection,limitofquantification,andperhapsotherparameters. that was estimated when the standard test method was devel-
The laboratory is advised to evaluate the method for bias and oped and validated by a committee. In an analogous manner, a
for susceptibility to introduction of bias (namely, ruggedness). laboratory developing a new test method or implementing a
A number of important considerations are discussed in published standard test method shall perform tests to estimate
5.1.1-5.1.7, but specific procedures for determination and biasanddemonstratethemethod’sresistancetointroductionof
calculation are beyond the scope of this guide. additional bias, that is, ruggedness. Documentation of this
performance enables the laboratory to elucidate the scope of
NOTE 1—In the following discussion, the term measurement process is
the method and defend the results obtained using the method.
taken to mean the entire process by which a laboratory performs a test
including sample preparation, measurements, and calculation of results.
NOTE 2—Accuracy is a concept related to both bias and precision. It is
the combination of knowledge of both the precision obtainable under
5.1.1 Precision—The first step in development and imple-
various conditions and the amount of bias inherent in a given result. The
mentation of an analytical method is demonstration that
concept of accuracy is often used in discussions of the fitness for purpose
measurements can be made with sufficient repeatability for the
and the reliability of results from a test method. In a published standard
purpose of quantitative analysis. Precision is defined as the test method, the statements of precision and bias taken together provide
the basis for judgments of the accuracy of the test method.
degree of agreement among a set of values. Precision under
repeatability conditions is measured by having a single analyst
5.1.5 Selectivity—Theselectivityofamethodisitsabilityto
in a single laboratory use a single set of equipment to prepare
produce a result that is not subject to change in the presence of
and analyze portions of a homogeneous material. Precision
interfering constituents. The selectivity of a method can be
under reproducibility conditions is measured by having a
investigated by introducing or varying amounts of substances
number of different analysts at different laboratories prepare
and evaluating the results for changes. By understanding the
and analyze portions of a homogeneous material.Any number
principal of measurement, the analyst may be able to define a
of conditions intermediate between repeatability conditions
short list of suspected interferences and, thereby, limit the
and reproducibility conditions may be used if the data serves a
amount of effort needed to establish the significant interference
useful purpose.Agood example is having multiple analysts in
effects.
a single laboratory perform the analyses, perhaps on multiple
5.1.6 Calibration Model—Relative methods require calibra-
days. In the terminology of Committee E01, repeatability is
tion using measurements of suitable reference materials and
synonymous with within-laboratory standard deviation, S ,
mathematicalfittingofthemeasuredresponsestoanalgorithm,
r
which is defined as the standard deviation of results collected
that is, an equation thought to describe adequately the relation-
on the same material in the same laboratory on different days.
shipbetweentheamountofanalyteandthemeasuredresponse.
In contrast, reproducibility is synonymous with between-
Algorithms are almost always an approximation of the real
laboratory standard deviation, S , which is defined as the
world,andassuch,theirabilitytofitthedatahaslimitsthatcan
R
standard deviation of results obtained on the same material in
be tested by a variety of means including, but not limited to,
different laboratories.
analyses of certified or other reference materials and statistical
5.1.1.1 The most common estimators of precision are stan-
evaluation of confidence intervals bracketing the calibration
darddeviation,relativestandarddeviation,andvariance.Equa- curve and extrapolating performance predictions beyond the
tions and examples are available in many texts on statistics.
range of the calibrants.
5.1.6.1 Working Range—The term working range is a name
5.1.1.2 Theconceptofmaintenanceoftherepeatabilityover
given to the concept of a portion of a calibration curve that
a period of time is known as statistical control. The laboratory
provides valid results as opposed to portions that are not fit for
can implement tools such as control charts to demonstrate
statistical control. purpose. The range in which the method is considered to be
valid can be characterized using a number of approaches. The
5.1.2 Limit of Detection (L )—Thedetectionlimitisdefined
D
as the lowest amount of analyte that can be distinguished from
background by an analytical method. It is important to dem-
L. A. Currie, “Nomenclature in Evaluation of Analytical Methods Including
onstrate that the measurement process has the capability to
DetectionandQuantificationCapabilities,” PureAppl. Chem.,Vol67,No.10,1995,
detect a significantly lower amount (concentration or mass pp. 1699-1723. http://iupac.org/publications/pac
E2857 − 11 (2016)
preferred methods are those that use objective data for the Assess the acceptability of the test method for generating data
purpose of illustrating under which circumstances a calibration in accordance with the laboratory’s measurement quality ob-
model is fit for purpose. jectives.
5.1.6.2 Calibration Performance—There are statistical 6.2.4 The following protocol is one approach that has been
methods for measuring how well the chosen calibration found to be an acceptable means of assessing the acceptability
algorithm, often a line, fits the data consisting of known of data obtained using this validation methodology.
amountsofanalyteandmeasuredresponsesfromtheanalytical 6.2.4.1 Analyze each of the reference materials, for a
instrument for the calibrants. For every calibrant, one may
minimum of triplicate determinations, in random order of
calculate the difference between known and calculated analyte amount. Record all results.
amounts. This information can be used to describe the perfor-
6.2.4.2 It is recommended that this determination be re-
mance of all or part of the calibration. One can do any of a
peated over a specified number of days, under different
number of things with the information, including calculating
calibration/setup conditions, unless thorough ruggedness test-
the standard deviation of the differences described above,
ing was performed during method development.
constructingconfidenceintervalsaroundallofpartoftherange
6.2.4.3 For each reference material used, calculate the mean
of amounts, plotting the difference as a function of the amount
of analyzed results, the standard deviation of the set of
to look for trends, and spotting any individual calibrant that
measured results, and an interval around the mean for a given
clearly performs more poorly than the rest. Documenting
confidence level.The confidence level should be chosen by the
behaviors like these, seeking the causes, and taking corrective
laboratory and based on the definition of the uncertainty of the
actions are suggested means to validate a test method.
assigned value for the reference material. For each reference
material, the mean and its confidence interval may overlap the
NOTE 3—The applications of statistical tools, for example, confidence
assigned value and its confidence interval for the certified
intervalsaroundacalibration,neednotberestrictedtotheregionbounded
by the lowest and highest calibrants or the lowest and highest validation referencematerial.Ifnot,abiasmayexistandactionshouldbe
reference materials measured using the method and a particular calibra-
considered to identify source(s) of bias. If changes are made,
tion. These tools can be extrapolated and still provide valid estimates of
perform the validation analyses again.
method performance.
(1) Reference materials (typically older ones) may be
5.1.7 Ruggedness—Consid
...

This document is not an ASTM standard and is intended only to provide the user of an ASTM standard an indication of what changes have been made to the previous version. Because
it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version
of the standard as published by ASTM is to be considered the official document.
Designation: E2857 − 11 E2857 − 11 (Reapproved 2016)
Standard Guide for
Validating Analytical Methods
This standard is issued under the fixed designation E2857; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope
1.1 This guide describes procedures for the validation of chemical and spectrochemical analytical methods of analysis that are
used by a metals, ores, and related materials analysis laboratory.
1.2 This guide may be applied to the validation of laboratory developed (in-house) methods, addition of analytes to an existing
standard test method, variation or scope expansion of an existing standard method, or the use of new or different laboratory
equipment.
1.3 This guide may also be used to validate the implementation of standard test methods used routinely by laboratories of the
mining, ore processing, and metals industry.
2. Referenced Documents
2.1 ASTM Standards:
E135 Terminology Relating to Analytical Chemistry for Metals, Ores, and Related Materials
E1601 Practice for Conducting an Interlaboratory Study to Evaluate the Performance of an Analytical Method
E1763 Guide for Interpretation and Use of Results from Interlaboratory Testing of Chemical Analysis Methods (Withdrawn
2015)
2.2 ISO Standard:
ISO/IEC 17025 General requirements for the competence of testing and calibration laboratories
3. Terminology
3.1 Definitions—For definitions of terms used in this guide, refer to Terminology E135.
3.2 Definitions of Terms Specific to This Standard:
3.2.1 validation (of an analytical method), n—confirmation, by the provision of objective evidence and examination, that a
method meets performance requirements and is suitable for its intended use.
4. Significance and Use
4.1 Method validation is a process of demonstrating that the method meets the required performance capabilities. International
standards such as ISO/IEC 17025, certifying bodies, and regulatory agencies require evidence that analytical methods are capable
of producing valid results. This applies to laboratories using published standard test methods, modified standard test methods, and
in-house test methods.
4.2 Although a collaborative study is part of this guide, this guide may be used by a single laboratory for method validation
when a formal collaboration study is not practical. This guide may also be applied before a full collaboration study to predict the
reliability of the method.
4.3 The use of multiple validation techniques described in this guide increases confidence in the validity or application of the
method.
This guide is under the jurisdiction of ASTM Committee E01 on Analytical Chemistry for Metals, Ores, and Related Materials and is the direct responsibility of
Subcommittee E01.22 on Laboratory Quality.
Current edition approved Nov. 1, 2011Oct. 1, 2016. Published January 2012October 2016. Originally approved in 2011. Last previous edition approved in 2011 as
E2857–11. DOI: 10.1520/E2857–11.10.1520/E2857–11R16.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
The last approved version of this historical standard is referenced on www.astm.org.
Available from American National Standards Institute (ANSI), 25 W. 43rd St., 4th Floor, New York, NY 10036, http://www.ansi.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
E2857 − 11 (2016)
4.4 It is beyond the scope of this guide to describe fully the fundamental considerations in Section 5. For a more descriptive
definition of these concepts, refer to the International Union of Pure and Applied Chemistry (IUPAC) technical report,
“Harmonized Guidelines for Single Laboratory Validation of Methods of Analysis,” the IUPAC Compendium of Analytical
Nomenclature (Orange Book), and the Eurachem publication, The Fitness for Purpose of Analytical Methods, A Laboratory Guide
to Method Validation and Related Topics.
5. Fundamental Considerations
5.1 During the process of method validation, the user of an analytical method should apply a number of fundamental tenets of
analytical chemistry as they relate to the development and implementation of test methods. It is important to make the distinction
between the validation of a test method by a standards-developing organization and the implementation of that test method by a
laboratory. Whether the test method was developed by a committee of experts or by one chemist in a company laboratory, the
laboratory shall implement the method in the laboratory and shall demonstrate that the method is being performed sufficiently well
and that the results meet the goals for data quality. That is, they should ascertain that the measurement process provides sufficient
levels of performance fit for the purpose of testing the materials at hand. It is advisable to determine and document performance
characteristics of the method including repeatability precision, limit of detection, limit of quantification, and perhaps other
parameters. The laboratory is advised to evaluate the method for bias and for susceptibility to introduction of bias (namely,
ruggedness). A number of important considerations are discussed in 5.1.1-5.1.7, but specific procedures for determination and
calculation are beyond the scope of this guide.
NOTE 1—In the following discussion, the term measurement process is taken to mean the entire process by which a laboratory performs a test including
sample preparation, measurements, and calculation of results.
5.1.1 Precision—The first step in development and implementation of an analytical method is demonstration that measurements
can be made with sufficient repeatability for the purpose of quantitative analysis. Precision is defined as the degree of agreement
among a set of values. Precision under repeatability conditions is measured by having a single analyst in a single laboratory use
a single set of equipment to prepare and analyze portions of a homogeneous material. Precision under reproducibility conditions
is measured by having a number of different analysts at different laboratories prepare and analyze portions of a homogeneous
material. Any number of conditions intermediate between repeatability conditions and reproducibility conditions may be used if
the data serves a useful purpose. A good example is having multiple analysts in a single laboratory perform the analyses, perhaps
on multiple days. In the terminology of Committee E01, repeatability is synonymous with within-laboratory standard deviation,
S , which is defined as the standard deviation of results collected on the same material in the same laboratory on different days.
r
In contrast, reproducibility is synonymous with between-laboratory standard deviation, S , which is defined as the standard
R
deviation of results obtained on the same material in different laboratories.
5.1.1.1 The most common estimators of precision are standard deviation, relative standard deviation, and variance. Equations
and examples are available in many texts on statistics.
5.1.1.2 The concept of maintenance of the repeatability over a period of time is known as statistical control. The laboratory can
implement tools such as control charts to demonstrate statistical control.
5.1.2 Limit of Detection (L )—The detection limit is defined as the lowest amount of analyte that can be distinguished from
D
background by an analytical method. It is important to demonstrate that the measurement process has the capability to detect a
significantly lower amount (concentration or mass fraction) of the analyte than the laboratory must quantify. For additional
information, consult the IUPAC Orange Book and the Currie paper.
5.1.3 Limit of Quantification (L )—The limit of quantification is defined as the amount of analyte above which the estimated
Q
relative standard deviation (RSD) is ≤10 %. It is important to demonstrate and document that the measurement process has the
capability to quantify amounts less than or equal to those found in materials to which the test method is applied. For additional
information, consult the IUPAC Orange Book and the Currie paper.
5.1.4 Bias—Bias is the difference between the obtained result for a measurand and the true value of the measurand. An analytical
method may be subject to a known amount of bias that was estimated when the standard test method was developed and validated
by a committee. In an analogous manner, a laboratory developing a new test method or implementing a published standard test
method shall perform tests to estimate bias and demonstrate the method’s resistance to introduction of additional bias, that is,
ruggedness. Documentation of this performance enables the laboratory to elucidate the scope of the method and defend the results
obtained using the method.
NOTE 2—Accuracy is a concept related to both bias and precision. It is the combination of knowledge of both the precision obtainable under various
M. Thompson, S. Ellison, and R. Wood, “Harmonized Guidelines for Single-Laboratory Validation of Methods of Analysis,” Pure Appl. Chem., Vol 71, No. 2, 2002, pp.
835-855. http://iupac.org/publications/pac
International Union of Pure and Applied Chemistry Compendium of Analytical Nomenclature: Definitive Rules 1997, http://old.iupac.org/publications/analytical_
compendium/
EURACHEM Guide, The Fitness for Purpose of Analytical Methods, A Laboratory Guide to Method Validation and Related Topics, LGC, Teddington, Middlesex, United
Kingdom, 1998. www.eurachem.org
L. A. Currie, “Nomenclature in Evaluation of Analytical Methods Including Detection and Quantification Capabilities,” Pure Appl. Chem., Vol 67, No. 10, 1995, pp.
1699-1723. http://iupac.org/publications/pac
E2857 − 11 (2016)
conditions and the amount of bias inherent in a given result. The concept of accuracy is often used in discussions of the fitness for purpose and the
reliability of results from a test method. In a published standard test method, the statements of precision and bias taken together provide the basis for
judgments of the accuracy of the test method.
5.1.5 Selectivity—The selectivity of a method is its ability to produce a result that is not subject to change in the presence of
interfering constituents. The selectivity of a method can be investigated by introducing or varying amounts of substances and
evaluating the results for changes. By understanding the principal of measurement, the analyst may be able to define a short list
of suspected interferences and, thereby, limit the amount of effort needed to establish the significant interference effects.
5.1.6 Calibration Model—Relative methods require calibration using measurements of suitable reference materials and
mathematical fitting of the measured responses to an algorithm, that is, an equation thought to describe adequately the relationship
between the amount of analyte and the measured response. Algorithms are almost always an approximation of the real world, and
as such, their ability to fit the data has limits that can be tested by a variety of means including, but not limited to, analyses of
certified or other reference materials and statistical evaluation of confidence intervals bracketing the calibration curve and
extrapolating performance predictions beyond the range of the calibrants.
5.1.6.1 Working Range—The term working range is a name given to the concept of a portion of a calibration curve that provides
valid results as opposed to portions that are not fit for purpose. The range in which the method is considered to be valid can be
characterized using a number of approaches. The preferred methods are those that use objective data for the purpose of illustrating
under which circumstances a calibration model is fit for purpose.
5.1.6.2 Calibration Performance—There are statistical methods for measuring how well the chosen calibration algorithm, often
a line, fits the data consisting of known amounts of analyte and measured responses from the analytical instrument for the
calibrants. For every calibrant, one may calculate the difference between known and calculated amounts. This information can be
used to describe the performance of all or part of the calibration. One can do any of a number of things with the information,
including calculating the standard deviation of the differences described above, constructing confidence intervals around all of part
of the range of amounts, plotting the difference as a function of the amount to look for trends, and spotting any individual calibrant
that clearly performs more poorly than the rest. Documenting behaviors like these, seeking the causes, and taking corrective actions
are suggested means to validate a test method.
NOTE 3—The applications of statistical tools, for example, confidence intervals around a calibration, need not be restricted to the region bounded by
the lowest and highest calibrants or the lowest and highest validation reference materials measured using the method and a particular calibration. These
tools can be extrapolated and still provide valid estimates of method performance.
5.1.7 Ruggedness—Considered in its classical sense, ruggedness of an analytical method is the resistance of the results to change
caused by variations in the operational aspects of a test method. Operations characteristics may include substitution of machines
used to prepare a specimen, substitution of sources of reagents and ingredients, changes to environmental conditions, and even
changes of personnel. A task group of a standard development committee will perform ruggedness testing at an early stage in the
validation process and at a small number of laboratories before a larger set of laboratories are asked to invest in an interlaboratory
study. The laboratory implementing a test method is advised to perform their own ruggedness tests at any time during
implementation and regular use of the method to identify and document effects of changes of these types.
6. Means of Method Validation
6.1 Once method development following the cons
...