Addressing Medical Device Extractables and Leachables via Non-Target Analysis (NTA); The Analytical Evaluation Threshold (AET) and Quantitation.

Leachables 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 non-targeted 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.

Correlating GC/MS Relative Response Factors to Analyte's Physicochemical and Chromatographic Properties to Facilitate the Quantitation of Organic Extractables and Leachables in Non-Targeted Analysis (NTA). Concepts and Empirical Considerations.

Leachables in drug products and from medical devices can adversely affect patient health and thus must be identified and quantified. Accurate and protective quantitation in target analysis for leachables (and extractables as potential leachables) is accomplished via compound-specific calibration curves. Quantification in non-targeted analysis (NTA) is complicated by the variable relative response factors (RRFs) among and between individual leachables and the circumstance that the leachables are not known until the NTA is completed.

Assessment of Biomolecule Reactivity with Leachables.

Leachables in pharmaceutical products may react with biomolecule active pharmaceutical ingredients (APIs), for example, monoclonal antibodies (mAb), peptides, and ribonucleic acids (RNA), potentially compromising product safety and efficacy or impacting quality attributes. This investigation explored a series of models to screen extractables and leachables to assess their possible reactivity with biomolecules. These models were applied to collections of known leachables to identify functional and structural chemical classes likely to be flagged by these approaches.

Identification and quantification of medical device extractables and leachables via non-target analysis (NTA); Analytical uncertainty.

Leachables are substances that are leached from a medical device during its clinical use and 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) to assess their potential impact on patient health and safety. This profiling is accomplished by screening extracts or leachates of the medical device for released organic substances via non-targeted analysis (NTA) employing chromatographic methods coupled with mass spectrometric detection.