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VALIDATIONS GCLP TRAINING COURSE KEMRI-Wellcome Trust Research Programme

What is validation? Validation is the confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled Validation is the confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled. It is a process of determining how well one system replicates properties of some other system. In other words, any comparison between a representation of a system and specified criteria. those tests/methods and instruments must be validated before diagnostic use to ensure reliable results for patients, clinicians or referring laboratories and their quality must be maintained throughout use. In other words, the laboratory must demonstrate that their tests/methods are fit for the intended use before application to patient samples.

Purposes of Validation : To quantifiably characterize system performance To assess potential for error To identify method-to-method differences To meet regulatory guidelines Increase confidence that the output conform to reality in the required range. Validation provides confidence that the outputs of the model conform to the reality in the required range. It is also a regulatory requirements for the Laboratory to demonstrate that prior to reporting patient test results, it can obtain the performance specifications for accuracy, precision, and reportable range of patient test results, comparable to those established by the manufacturer.

Validation requirements Qualified and calibrated instruments Documented methods e.g. protocol manuals Reliable reference standards Qualified analysts Sample integrity Manufacturer’s package inserts Diagnostic validation is a formal requirement of accreditation standards, those tests/methods and instruments must be validated before diagnostic use to ensure reliable results for patients, clinicians or referring laboratories and their quality must be maintained throughout use. In other words, the laboratory must demonstrate that their tests/methods are fit for the intended use before application to patient samples

Validation Plan Statement of purpose and scope Responsibilities Documented test method List of materials and equipment Procedure for the experiments for each parameter Statistical analysis Acceptance criteria for each performance parameter As part of the planning the Laboratory shall assign the responsibility who shall be responsible for carrying out the validation process and deciding the outcome. The planning shall also involve the documented detailed description of the validation procedure to ensure its proper performance and repeatability. This ensures that all laboratory personnel that are qualified can do just as the method with comparable results.

When to Do Method Validation Studies: When considering purchasing a new system When placing a new system into service At regular intervals to assess on-going system performance When troubleshooting questionable system performance When examination procedures have been validated by the method developer (i.e., the manufacturer or author of a published procedure), the laboratory shall obtain information from the method developer to confirm that the performance characteristics of the method are appropriate for its intended use. When changes are made to a validated examination procedure, the influence of such changes shall be documented and, if appropriate, a new validation shall be carried out.

Basic Components of Method Validation Accuracy Precision Repeatability Reproducibility The approach in method validation is to perform a series of experiments designed to estimate certain types of analytical errors, e.g., a linearity experiment to determine reportable range, a replication experiment to estimate imprecision or random error, a comparison of methods experiment to estimate inaccuracy or systematic error, or interference and recovery experiments to specifically estimate constant and proportional systematic errors (analytical specificity), and a detection limit experiment to characterize analytical sensitivity

Basic Components of Method Validation Range Validation and Verification Linearity and range Specificity Sensitivity Limit of detection Limit of quantification The approach in method validation is to perform a series of experiments designed to estimate certain types of analytical errors, e.g., a linearity experiment to determine reportable range, a replication experiment to estimate imprecision or random error, a comparison of methods experiment to estimate inaccuracy or systematic error, or interference and recovery experiments to specifically estimate constant and proportional systematic errors (analytical specificity), and a detection limit experiment to characterize analytical sensitivity

Basic Components of Method Validation Range Validation and Verification Reportable Range Critical Limits Analytical Measurement Range Clinically Reportable Range Calibration Verification / Linearity Reference Range Studies

Validation Good Practices To select analytical procedures suitable for answering the analytical questions. To perform the selected test in Traceable manner According to clear and transparent procedures under proper conditions.