OPERATIONAL INTEGRITY

MANAGEMENT SYSTEM

TEST AND CALIBRATION METHOD VALIDATION

GLOBAL GROUP MINIMUM STANDARD OI-L2-906

Revision: 00
Issue Date: 06 January 2014
Review Date: 06 January 2017
Author: T. Lombard
Approver: B. Dunagan

REVISION RECORD

Revision: Date: Changes Since Last Issue:

00 01/2014 (Initial issue)

© SGS Group Management SA - 2014 - All rights reserved - SGS is a registered trademark of SGS Group Management SA

This is an uncontrolled copy when printed, unless signed by an authorised signatory.

The latest revision of this document and the official distribution list are those approved in the OIMS database.
 TEST AND CALIBRATION METHOD VALIDATION
OI-L2-906 REV. 00 01/2014
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PURPOSE
Group minimum standard is to specify the protocol to be followed to prove the suitability of measurement
processes in the SGS RZA analytical, calibration and microbiological laboratories. This protocol shall be followed
as a guideline for the validation of all analytical processes used to generate measurement, and where applicable,
calibration results.

Validation or re-validation shall be performed under the following conditions:

 Before a piece of instrument or a method is introduced for routine use.
 Whenever the conditions of a method change, e.g. when another instrument with different characteristics is
used to perform a test.
 Whenever the method is changed and the method’s scope is outside the original scope.
 When quality control indicates an established method is changing with time
 To demonstrate the equivalence between two methods, e.g. a new method and a standard

NOTE: Validation protocols shall be established for testing methodologies outside the scope of this document.
The requirements stated below fully meet Group minimum standards and expectations. All SGS Operations and
Functions shall comply with this Group Minimum Standard and ensure that it is fully implemented within the
corresponding local Level 3 Procedure. The requirements stated below fully meet Group minimum standards
and expectations. All SGS Operations and Functions shall comply with this Group Minimum Standard and
ensure that it is fully implemented within the corresponding local Level 3 Procedure.

WHO IS THIS FOR?

Managers/Supervisors, Operational Integrity personnel, or any employee conducting an OIMS gap analysis.

WHAT SITUATIONS ARE/ARE NOT COVERED?

These requirements apply to all personnel, including employees, clients, and contractors, on SGS locations or
locations operated by SGS.

These requirements do not apply to Client employees operating on their own sites.

NOTE: Mandatory elements are in orange sections.

GROUP MINIMUM REQUIREMENTS

1. ACCOUNTABILITIES
All applicable personnel shall be held accountable for complying with SGS Group and local legal
requirements.

Laboratory Manager shall:

 Be responsible to ensure that the measurement uncertainties for analytical processes are
determined and utilized where applicable

Laboratory Manager together with the supervisors shall:

 Be responsible for the drafting of validation plans. The comprehensiveness of the plan will depend
on the criticality of the test.

Laboratory Supervisor shall:

 Have the responsibility and authority to ensure that instrument qualification is performed
satisfactorily and that a validation package is kept. The validation package shall contain the
documented evidence of instrument qualification.
 Authorize the validity of an instrument before use.
 Authorize the validity of all experimental claims, before a method is formalized
 Ensure that a validation package is kept and for each test method used within the laboratory. The

© SGS Group Management SA - 2014 - All rights reserved - SGS is a registered trademark of SGS Group Management SA

This is an uncontrolled copy when printed, unless signed by an authorised signatory.

The latest revision of this document and the official distribution list are those approved in the OIMS database.
 TEST AND CALIBRATION METHOD VALIDATION
OI-L2-906 REV. 00 01/2014
PAGE 3 OF 7

validation package shall contain the validation plan plus documented evidence of the conclusions
reached.

Operational Integrity shall:

 Review and approve this standard.

2. DEFINITIONS
 Matrix – A substance in which something is enclosed.
 Method validation – The process of establishing the performance characteristics and limitations of
a method and the identification of the influences which may change these characteristics and to
what extent.
 Performance parameter / characteristic – Functional quality that can be attributed to an
analytical method
 Validation – Confirmation by examination and provision of objective evidence that the particular
requirements for a specific intended use are fulfilled
 Verification – Confirmation by examination and provision of objective evidence that specified
requirements have been fulfilled.

3. METHOD VALIDATION
Laboratories shall confirm that the analysis process followed is valid when applied in a specific location.

If an analysis process comprises of several stages, the possible error in each individual stage must be
considered and summarized to a total uncertainty at the end of the process.

The chosen method shall be proven to be scientifically sound (does what it is intended to do, reliably
and reproducibly) and systematically evaluated in accordance with a validation plan. Any instrument,
test standards, samples and analytical operations form a single analytical system.

Sample preparation forms part of the analytical process and should also be validated.

The need and extent of method validation (i.e. verification of performance characteristics, full validation,
etc) is dependent on how established the method is (i.e. the method is a published standard,
developed in-house, etc).

4. PERFORMANCE PARAMETERS / CHARACTERISTICS

The parameters / characteristics to be used for validation shall be dependent on how the result will be
used. Where results are used to make critical decisions or for legal purposes, the validation should be
thorough in all ranges and matrices analyzed.

It is implicit in the method validation process that the studies to determine method performance
parameters / characteristics are carried out. For each performance parameter / characteristic chosen
the following steps need to be followed:
 Performance of test procedure;
 Comparison of results to an established acceptance criteria; and
 Assembly of documentation to support conclusion.

Accuracy (Recovery)
The accuracy of an analytical method is a quantity referring to the differences between the mean of a

© SGS Group Management SA - 2014 - All rights reserved - SGS is a registered trademark of SGS Group Management SA

This is an uncontrolled copy when printed, unless signed by an authorised signatory.

The latest revision of this document and the official distribution list are those approved in the OIMS database.
 TEST AND CALIBRATION METHOD VALIDATION
OI-L2-906 REV. 00 01/2014
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set of results or an individual result and the value which is accepted as the true or correct value for the
quantity measured. Accuracy of a measuring instrument is the ability of a measuring instrument to give
responses close to a true value

NOTE: The term accuracy, when applied to a set of observed values, describes a combination of
random components and common systematic error or bias components.

Bias
It is the tendency of a method towards delivering a result that is skewed from the true value. It is the
difference between the experimental mean and the true value and is generated from a total systematic
error as contrasted to random error. There may be one or more systematic error components
contributing to the bias.

Precision
The closeness of agreement between independent test results obtained under stipulated conditions
(how close the measured values are to each other);

NOTE 1: “Independent” means results obtained in a manner not influenced by any previous result on
the same or similar material.

NOTE 2: Quantitative measures of precision depend critically on the stipulated conditions.

Repeatability (intra-assay)
Replicate analysis performed using the same method on identical test items using the same operator,
the same instruments and within the same laboratory over a short interval of time.

Ruggedness
The ruggedness of an analytical method is the degree of reproducibility of test results obtained by the
analysis of the same samples under a variety of normal, expected environmental and/or operational
conditions.
 Intermediate precision - Replicate analysis performed using the same method on identical test
items using different operators but under operational and environmental conditions that may differ
but are still within the specified parameters / characteristics of the assay. For example: multiple
instruments, different sources of reagents, different chromatographic columns and multiple days in
one lab.
 Reproducibility - Replicate analysis performed in multiple laboratories on identical test items.

Instrument (if applicable)

The degree of reproducibility among several independent measurements of the same sample for the
same analyte.

Regression Precision (if applicable)

The regression error introduced when an unknown concentration is read off a regression line.

Linearity
The ability of the method to produce test results that are directly, or by a well-defined mathematical
transformation, proportional to the concentration of analyte in samples within given working range.

Working Range
The range of an analytical method is the interval between the upper and lower levels of analyte
(including these levels) that have been demonstrated to be determined with precision, accuracy, and
linearity using the method as written.

Limit of Detection (LOD)

The limit of detection is defined as the lowest concentration of analyte that is detected, but not

© SGS Group Management SA - 2014 - All rights reserved - SGS is a registered trademark of SGS Group Management SA

This is an uncontrolled copy when printed, unless signed by an authorised signatory.

The latest revision of this document and the official distribution list are those approved in the OIMS database.
 TEST AND CALIBRATION METHOD VALIDATION
OI-L2-906 REV. 00 01/2014
PAGE 5 OF 7

necessarily quantified, under the stated experimental conditions in a specific matrix. It is the point at
which a measured value is larger than the uncertainty associated with it.

Limit of Quantification (LOQ)

The limit of quantification refers to the lowest and highest concentration of analyte that can be
determined with acceptable precision (repeatability) and accuracy under the stated experimental
conditions.

Sensitivity
Responsiveness of a method to small changes in analyte concentration over the working range.

Specificity (selectivity)
The analytical method’s ability to determine accurately and specifically the analyte of interest in the
presence of other components in a sample matrix under the stated conditions of the test. Possible
interferences include impurities, degradents and matrix effects. Thus, the ability of a method to
measure only what it is intended to measure. (Note: Chromatography and spectroscopy techniques
refer to resolution: the ability to effectively resolve two neighbouring analyte peaks.)

NOTE 1: Specificity refers to method which produces a response for only a single analyte.

NOTE 2: Selectivity implies that method separates potential process impurities, degradation products
and structural analogues.

Uncertainty of Measurement
The result of an evaluation aimed at characterizing the dispersion of values within which the true value
of a measurement is estimated to lie, generally with a given likelihood.

NOTE: Uncertainty of measurement comprises, in general, many components. Some of these

components may be estimated on the basis of the statistical distribution of the results of series of
measurements and can be characterized by experimental standard deviations. Estimates of other
components can only be based on experience or other information.

5. METHOD VALIDATION PLAN

How test method performance parameters / characteristics are determined, along with the criteria
against which they will be assessed, shall be described in a detailed validation plan.

The validation plan shall be produced before the start of any experiments.

The following shall be defined and recorded in the validation plan:

 Purpose of measurement (for what purpose will end results be used by customer);
 Sample matrices
 Measurement scope
 Equipment and accommodation and environmental conditions
 Principle of the method to be used for the analyte determination (including instruments to be used)
 Identification of appropriate validation parameters / characteristics
 Discipline-specific or customer required performance criteria shall be set for each parameter /
characteristic so as to demonstrate fitness for purpose.
 Design experiments for parameter /characteristic evaluation (detail on what type of samples to be
used, how experiment should be conducted and statistics to be used).

6. REVIEW
Use should be made of the appropriate statistical tools when analyzing data, e.g. validated calculation

© SGS Group Management SA - 2014 - All rights reserved - SGS is a registered trademark of SGS Group Management SA

This is an uncontrolled copy when printed, unless signed by an authorised signatory.

The latest revision of this document and the official distribution list are those approved in the OIMS database.
 TEST AND CALIBRATION METHOD VALIDATION
OI-L2-906 REV. 00 01/2014
PAGE 6 OF 7

templates, Dixon and Grubb outliers tests, Analysis of Variance (ANOVA) tool (on Excel), t-test, f-test,
etc.

Conventions regarding the use of significant figures and rounding off shall be applied before analyzing
data.

NOTE: When rounding data from chemical computations it may be necessary to carry one extra digit
through all the computations to avoid rounding error. In rounding a number ending in 5, always round
so that the result ends with an even number.

If the method does not meet performance criteria and further method development is required, the
validation shall be repeated on the revised method.

The approaches that can be used for the determination of the performance of the method could be one
of or a combination of:
 Calibration using reference standards or materials
 Comparison of results achieved with other validated methods
 Inter laboratory comparisons
 Systematic assessment of the factors influencing the results
 Assessment of the uncertainty of the results based on scientific understanding of the theoretical
principles of the method and practical experience

7. VALIDATION REPORT
The final validation report shall contain:
 The test method as validated including information about equipment used, reagents, calibrations
etc.
 Reference to or a copy of the validation plan used to generate the test method performance
characteristics.
 A summary of the test method performance characteristics and how these were calculated or
defined.
 The test method performance criteria against which the characteristics were evaluated and whether
or not the method is fit for purpose.
 The intended use of the method, and
 Estimates of uncertainty.

8. STABILITY
The stability of stock, standard, reagent sample solutions, and mobile phases should be determined.

Although this test is often considered as part of the ruggedness of the procedure, it shall be carried out
at the beginning of the validation procedure because it pre-qualifies the validity of the data of the other
tests.

9. RECORD RETENTION
Records shall be managed and retained as required by the Group Minimum Standard, OI-L2-715
Records Management. The following documents are required for a method validation process and
shall be cross-referenced to each other:
 Test Method;
 Validation package, including:

© SGS Group Management SA - 2014 - All rights reserved - SGS is a registered trademark of SGS Group Management SA

This is an uncontrolled copy when printed, unless signed by an authorised signatory.

The latest revision of this document and the official distribution list are those approved in the OIMS database.
 TEST AND CALIBRATION METHOD VALIDATION
OI-L2-906 REV. 00 01/2014
PAGE 7 OF 7

o Validation plan;
o Documented evidence of instrument qualification
o Validation report, including
 Reference to attachments
 Documented evidence of conclusions reached
 Measurement Uncertainty for each process (if applicable)
 Calibration (if applicable); and
 Reagents (if applicable).

10. TRAINING REQUIREMENTS

Training shall be managed and conducted as required by the Group Minimum Standard, OI-L2-112
Employee Training, Competency, and Certification.

__________________________________________________________________________________________

** End of Document **

Controlled printed copies carry authorised signature here.........................................................

__________________________________________________________________________________________

© SGS Group Management SA - 2014 - All rights reserved - SGS is a registered trademark of SGS Group Management SA

This is an uncontrolled copy when printed, unless signed by an authorised signatory.

The latest revision of this document and the official distribution list are those approved in the OIMS database.