RT Journal Article SR Electronic T1 Correcting the Analytical Evaluation Threshold (AET) and Reported Extractable's Concentrations for Analytical Response Factor Uncertainty Associated with Chromatographic Screening for Extractables/Leachables JF PDA Journal of Pharmaceutical Science and Technology JO PDA J Pharm Sci Technol FD Parenteral Drug Association (PDA) SP 348 OP 358 DO 10.5731/pdajpst.2019.010520 VO 74 IS 3 A1 Jenke, Dennis YR 2020 UL http://journal.pda.org/content/74/3/348.abstract AB It is generally acknowledged that quantitation in extractables and leachables (E&L) can be variably reproducible and accurate, depending on the quantitation approach taken. This is especially true for “simple” quantitation, which is the practice of estimating an analyte's concentration based on its response relative to that of an internal standard that has been added to the sample in a known amount. Simple quantitation is prone to error and variation as it is based on the largely false premise that the response factors for all extractables, leachables, and internal standard candidates are the same. It has been proposed that this uncertainty (inaccuracy and variation) be accounted for by adjusting two key parameters in E&L assessment, the reported concentrations themselves and the analytical evaluation threshold (AET) via an uncertainty factor (UF). This paper examines quantitation variation and discusses the means of establishing and utilizing the UF to adjust the AET to lower values and to adjust reported concentrations to higher values, enabling an impact assessment performed with this data to be more protective of patient safety. Although adjustment of the AET lower with the UF is supported, flaws in the concept of using the UF to adjust reported concentrations upward are considered, and it is recommended that the UF not be used in this manner. Rather, E&L quantitation should be based on compound-specific relative response factors, collected and collated in an E&L database.