Metrology and Calibration in GLP

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Metrology and Calibration in GLPTechnical and Practical Aspects for Contract Research OrganisationsXIX SEGCIB Congress Barcelona, 18 november 2010

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Topics

GLP Guidelines and Equipment Calibrations Basic Concepts in Metrology Calibrations and Uncertainty of Measurement Certificates of Calibration Practical Aspects when using values from certificates of calibration within CROs

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GLP Guidelines and Equipment Calibrations

OECD Series No. 1 Principles of Good Laboratory PracticePoint 4.2 Apparatus used in a study should be periodically inspected, cleaned, maintained, and calibrated according to Standard Operating Procedures. Records of these activities should be maintained. Calibration should, where appropriate, be traceable to national or international standards of measurement.

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GLP Guidelines and Equipment Calibrations International Vocabulary of Metrology (VIM)Calibration 2.39 (6.11) operation that, under specified conditions, in a first step, establishes a relation between the quantity values with measurement uncertainties provided by measurement standards and corresponding indications with associated measurement uncertainties and, in a second step, uses this information to establish a relation for obtaining a measurement result from an indication

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GLP Guidelines and Equipment CalibrationsNOTES: 1- A calibration may be expressed by a statement, calibration function, calibration diagram, calibration curve, or calibration table. In some cases, it may consist of an additive or multiplicative correction of the indication with associated measurement uncertainty. 2 - Calibration should not be confused with adjustment of a measuring system, often mistakenly called self-calibration, nor with verification of calibration. 3 - Often, the first step alone in the above definition is perceived as being calibration.

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GLP Guidelines and Equipment CalibrationsVerification (2.44) provision of objective evidence that a given item fulfils specified requirements NOTES: 1 The item may be, e.g. a process, measurement procedure, material, compound, or measuring system. 2 The specified requirements may be, e.g. that a manufacturer's specifications are met..

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GLP Guidelines and Equipment CalibrationsNOTES (Continued) 3 Verification in legal metrology, as defined in VIML[53], and in conformity assessment in general, pertains to the examination and marking and/or issuing of a verification certificate for a measuring system. 4 Verification should not be confused with calibration. Not every verification is a validation. 5 In chemistry, verification of the identity of the entity involved, or of activity, requires a description of the structure or properties of that entity or activity. 6 - When applicable, measurement uncertainty should be taken into consideration.

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Basic Concepts in Metrology and Calibration Tolerancetolerance is a condition imposed on a measurement and is defined as the total permissible variation of a quantity from a designated value. We could express it as: 20+/- 2, 75-80, >= 100, etc.

True Quantity Value vs Conventional Quantity ValueValue that characterises a magnitude perfectly defined in the conditions when the magnitude is considered. Its always an uthopy and cannot be never known. The second one is an approximation of the first. (In a CRO, the value assigned to a reference pattern may be considered as the True Quantity Value)

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Basic Concepts in Metrology and Calibration Influence Quantityquantity that, in a direct measurement, does not affect the quantity that is actually measured, but affects the relation between the indication and the measurement result

Resolution of an instrumentsmallest change in a quantity being measured that causes a perceptible change in the corresponding indication. It is in fact a quantitative expression of the ability of a gauge to distinguish significantly between two values that are very close of the indicated quantity

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Basic Concepts in Metrology and Calibration Instrumental Driftcontinuous or incremental change over time in indication, due to changes in metrological properties of a measuring instrument NOTE: Instrumental drift is related neither to a change in a quantity being measured nor to a change of any recognized influence quantity. It depends, mainly on the time and proper use of equipment. It can be determined by the manufacturer but if this is not the case we can estimate it bigger and correct it with time until its real value

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Basic Concepts in Metrology and Calibration Correcctioncompensation for an estimated systematic effect. Its a value that added to the result of a measurement compensates the systematic measurement error NOTE: The compensation can take different forms, such as an addend or a factor, or can be deduced from a table.Measurement Standard 100 Instrument 95 Correction -5

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Basic Concepts in Metrology and Calibration Measurement Accuracy and PrecisionAccuracy is the closeness of agreement between a measured quantity value and a true quantity value of a measurand NOTE 1 The concept measurement accuracy is not a quantity and is not given a numerical quantity value. A measurement is said to be more accurate when it offers a smaller measurement error. Precision is the closeness of agreement between indications or measured quantity values obtained by replicate measurements on the same or similar objects under specified conditions. It refers to the dispersion of values obtained after measuring repeatitively a quantity. As the dispersion is lower the accuracy is higher. Consequently the standard deviation is a good estimator of the accuracy and can be estimate in function of that

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Basic Concepts in Metrology and Calibration Repeatability and y ReproducibilityRepeatability is the condition of measurement, out of a set of conditions that includes the same measurement procedure, same operators, same measuring system, same operating conditions and same location, and replicate measurements on the same or similar objects over a short period of time Reproducibility is the condition of measurement, out of a set of conditions that includes different locations, operators, measuring systems, and replicate measurements on the same or similar objects

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Calibrations and Uncertainty of Measurements MEASUREMENT UNCERTAINTYIts a non-negative parameter characterizing the dispersion of the quantity values being attributed to a measurand, based on the information used NOTE 1 - Measurement uncertainty includes components arising from systematic effects, such as components associated with corrections and the assigned quantity values of measurement standards, as well as the definitional uncertainty. Sometimes estimated systematic effects are not corrected for but, instead, associated measurement uncertainty components are incorporated.

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Calibrations and Uncertainty of MeasurementsNOTE 2 - The parameter may be, for example, a standard deviation called standard measurement uncertainty (or a specified multiple of it) NOTE 3 - Measurement uncertainty comprises, in general, many components. Some of these may be evaluated by Type A evaluation of measurement uncertainty from the statistical distribution of the quantity values from series of measurements and can be characterized by standard deviations. The other components, which may be evaluated by Type B evaluation of measurement uncertainty, can also be characterized by standard deviations, evaluated from probability density functions based on experience or other information.

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Calibrations and Uncertainty of MeasurementsType A evaluation Its the evaluation of a component of measurement uncertainty by a statistical analysis of measured quantity values obtained under defined measurement conditions NOTE 1 - For various types of measurement conditions, see repeatability condition of measurement, intermediate precision condition of measurement, and reproducibility condition of measurement. NOTE 2 - For information about statistical analysis, see e.g. ISO/IEC Guide 98-3, ISO/IEC Guide 98-3:2008, 2.3.2, ISO 5725, ISO 13528, ISO/TS 21748, ISO/TS 21749.

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Calibrations and Uncertainty of MeasurementsType B evaluation Its the evaluation of a component of measurement uncertainty determined by means other than a Type A evaluation of measurement uncertainty EXAMPLES Evaluation based on information associated with authoritative published quantity values, associated with the quantity value of a certified reference material, obtained from a calibration certificate, about drift, obtained from the accuracy class of a verified measuring instrument, obtained from limits deduced through personal experience. NOTE: See also ISO/IEC Guide 98-3:2008, 2.3.3.

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Calibration and Metrolog