TY - JOUR 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 DO - 10.5731/pdajpst.2019.010520 SP - pdajpst.2019.010520 AU - Dennis Jenke Y1 - 2020/01/01 UR - http://journal.pda.org/content/early/2020/04/15/pdajpst.2019.010520.abstract N2 - 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 which 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 Correspondence examines quantitation variation, and discusses the means of establishing and utilizing the UF to adjust the AET to lower values and 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 concentration 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. ER -