Document - FAVV

Table of Contents1. Foreword & scope & background ............................................................................... 1-11.1 Foreword ................................................................................................................................................................................ 1-11.2 Scope ....................................................................................................................................................................................... 1-21.2.1 Objective and strategy of the inventory task .............................................................................................................................................. 1-21.2.2 Objective and strategy of the administrative evaluation ............................................................................................................................ 1-21.2.3 Objective and strategy of the experimental evaluation .............................................................................................................................. 1-31.3 Background ............................................................................................................................................................................ 1-32. Inventory ...................................................................................................................... 2-92.1 Inventory results of providers of OTA kits ................................................................................................................... 2-113. Administrative evaluation .......................................................................................... 3-133.1 Quantitative kits .................................................................................................................................................................. 3-153.1.1 Overview of the kits .................................................................................................................................................................................... 3-153.1.2 Quality assurance ......................................................................................................................................................................................... 3-153.1.3 International approval frames .................................................................................................................................................................... 3-163.1.4 Characterisation by appropriate analytical performance criteria ............................................................................................................ 3-163.1.4.1 Calibration requirements .......................................................................................................................................................................... 3-173.1.4.2 Matrix applicability ................................................................................................................................................................................ 3-173.1.4.3 Limit of detection & quantification .......................................................................................................................................................... 3-183.1.4.4 Recovery .................................................................................................................................................................................................. 3-193.1.4.5 Accuracy ................................................................................................................................................................................................. 3-203.1.4.5.1 Accuracy and measurement uncertainties ............................................................................................................................................. 3-213.1.4.5.2 Confirmation (ELISA/LFD versus reference values) ......................................................................................................................... 3-213.1.4.5.2.1 Charm Science .......................................................................................................................................................................... 3-223.1.4.5.2.1.1 Descriptive comparison........................................................................................................................................................................... 3-223.1.4.5.2.1.2 Ordinary linear regression ....................................................................................................................................................................... 3-223.1.4.5.2.1.3 Conclusion ................................................................................................................................................................................................ 3-233.1.4.5.2.2 R-Biopharm ............................................................................................................................................................................. 3-233.1.4.5.2.2.1 Descriptive comparison........................................................................................................................................................................... 3-233.1.4.5.2.2.2 Ordinary linear regression ....................................................................................................................................................................... 3-243.1.4.5.2.2.3 Conclusion ................................................................................................................................................................................................ 3-253.1.4.6 Intra-run repeatability, inter-run repeatability and reproducibility ............................................................................................................... 3-253.1.4.6.1 Intra-run repeatability (same batch/operator) ...................................................................................................................................... 3-253.1.4.6.2 Inter-run repeatability (same batch/different operator).......................................................................................................................... 3-263.1.4.6.3 Reproducibility (different batch/different operator) ............................................................................................................................... 3-273.1.4.7 Cross-reactivity ........................................................................................................................................................................................ 3-293.1.5 Materials, time requirements and estimated costs .................................................................................................................................... 3-293.2 Qualitative kits .................................................................................................................................................................... 3-303.2.1 Overview of the kits .................................................................................................................................................................................... 3-303.2.2 Quality assurance ......................................................................................................................................................................................... 3-303.2.3 International approval frames .................................................................................................................................................................... 3-313.2.4 Characterisation by appropriate analytical performance criteria ............................................................................................................ 3-313.2.4.1 Calibration requirements .......................................................................................................................................................................... 3-323.2.4.2 Determination of unreliability region ......................................................................................................................................................... 3-323.2.4.3 Precision, sensitivity and specificity ............................................................................................................................................................ 3-323.2.4.4 Relative accuracy after confirmation of screening materials against reference method ....................................................................................... 3-333.2.4.5 Cross-reactivity ........................................................................................................................................................................................ 3-343.2.5 Materials, time requirements and estimated costs .................................................................................................................................... 3-343.3 Conclusions of the administrative evaluation ................................................................................................................ 3-354. Experimental evaluation ........................................................................................... 4-374.1 Materials and methods ....................................................................................................................................................... 4-394.1.1 Kits used ....................................................................................................................................................................................................... 4-394.1.2 Standards and reagents ................................................................................................................................................................................ 4-394.1.3 Equipment and materials ............................................................................................................................................................................ 4-404.1.3.1 Read-out ................................................................................................................................................................................................. 4-404.1.3.2 Matrix effect ........................................................................................................................................................................................... 4-404.1.3.3 Accuracy ................................................................................................................................................................................................. 4-404.1.3.4 Recovery .................................................................................................................................................................................................. 4-404.1.3.5 Standard solutions ................................................................................................................................................................................... 4-404.1.4 Work packages ............................................................................................................................................................................................. 4-404.1.4.1 Work package I: Concentration accuracy of standards ............................................................................................................................... 4-404.1.4.1.1 Study design ...................................................................................................................................................................................... 4-404.1.4.1.2 Data handling and statistical analyses ................................................................................................................................................ 4-41