PEPFAR Quality Control and Method Validation Activity 14 Handout 2: Quant Validation Overview

166 Handout 2: Quant Validation Overview 1404 Quantitative Validation Overview Validation of a quantitative system (for example Chemistry analyzer or Hematology analyzer) consists of an established set of required experiments. Each laboratory should first design a validation plan describing how they will satisfy each of these requirements. The validation plan must also detail the acceptability criteria for each element. After completing all of the validation experiments, results should be compiled and filed in an organized manner. All validation records should be retained for the life of the instrument. A validation summary should be prepared that contains a place for the Laboratory Director to sign, indicating the validation has been reviewed and approved. The following are the required components of validation: 1. Precision is reproducibility - the agreement of the measurements of replicate runs of the same sample. Replication experiments are performed to estimate the imprecision or random error of the analytical method. See Precision Guidelines.) - 2. Accuracy is the true value of a substance being measured. Verification of accuracy is the process of determining that the test system is producing true, valid results. (See Accuracy Guidelines.) 3. Linearity - A quantitative analytical method is said to be linear when measured results from a series of sample solutions are directly proportional to the concentration or activity in the test specimens. This means that a straight line can be used to characterize the relationship between measured results and the concentrations or activity levels of an analyte for a determined range of analyte values. (See Linearity Guidelines.) a. The Analytical Measurement Range (AMR) is the range of analyte values that a method can directly measure on the specimen without any dilution, concentration, or other pretreatment not part of the usual assay process. AMR validation is the process of confirming that the assay system will correctly recover the concentration or activity of the analyte over the AMR. The manufacturer defines the AMR but it is the laboratory's responsibility to verify it. b. The Clinical Reportable Range (CRR) is the range of analyte values that a method can report as a quantitative result, allowing for specimen dilution, concentration or other pretreatment used to extend the AMR. The laboratory must specify the maximum concentration or dilution that may be performed to obtain a reportable numeric result. 4. Sensitivity is the lowest concentration of an analyte that can be measured (Lower Limit of Detection). For an FDA approved, unmodified method, the manufacturer's stated sensitivity will be used. The LoD will be verified for immunoassays, therapeutic drugs, drugs of abuse, cardiac markers, and tumor markers. 5. Specificity is the determination of the affect of interfering substances. For an FDA approved, unmodified method, the manufacturer's stated specificity will be used. 6. Reference Interval is the range of test values expected for a designated population where 95% of the individuals are presumed to be healthy (or normal). (See Reference Range Guidelines.) 7. Summary and Approval. See Validation Summary Report template. Modified from pSMILE.org website. Equ35-01_Quan_Val_Overview.doc. Last accessed May 3, 2013 HILS1746 Effective Date: 12/6/2016