RT Journal Article
SR Electronic
T1 Addressing Medical Device Extractables and Leachables via Non-Target Analysis (NTA); The Analytical Evaluation Threshold (AET) and Quantitation
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 98
OP 113
DO 10.5731/pdajpst.2024.012945
VO 79
IS 1
A1 Jenke, Dennis
A1 Christiaens, Piet
A1 Heise, Ted
YR 2025
UL http://journal.pda.org/content/79/1/98.abstract
AB Substances leached from a medical device during its clinical use are important due to the patient health-related effects they may have. Thus, medical devices are profiled for leachables (and/or extractables as probable leachables) by screening extracts or leachates of the medical device for released organic substances via a non-target analysis (NTA) employing chromatographic methods coupled with mass spectrometric detection. Chromatographic mass spectral response factors for extractables and leachables vary significantly from compound to compound, complicating the application of assessment strategies such as the analytical evaluation threshold (AET), which is the concentration threshold at or above which an extractable or leachable must be reported for quantitative toxicological risk assessment. The analytical uncertainty resulting from response variation can make interpretation of the AET difficult, potentially leading to both false positive and false negative outcomes. Furthermore, response factor variation complicates the estimation of leachables' and extractables’ concentrations (quantification). This Correspondence discusses practices for the calculation and application of the AET and for performing quantification, including a discussion of accuracy versus protectiveness.