Characterizing Extractables and Leachables Chemical Space to Support In Silico Toxicological Hazard Assessments.

This article describes the development of a representative dataset of extractables and leachables (E&L) from the combined Extractables and Leachables Safety Information Exchange (ELSIE) Consortium and the Product Quality Research Institute (PQRI) published datasets, representing a total of 783 chemicals. A chemical structure-based clustering of the combined dataset identified 142 distinct chemical classes with two or more chemicals across the combined dataset. The majority of these classes (105 chemical classes out of 142) contained chemicals from both datasets, whereas 8 classes contained only chemicals from the ELSIE dataset and 29 classes contain only chemicals from the PQRI dataset.

Hemoadsorption Therapy for Calcium Channel Blocker Overdose: A Case Report.

Background: Modern resin hemoadsorption/hemoperfusion for calcium channel blocker overdose is yet to be reported. The characteristics of calcium channel blockers make them unamenable to removal by hemodiafiltration or charcoal hemoperfusion; however, elimination, using styrene bead adsorption in an ex vivo model, has been demonstrated. Its clinical use is described.

Cell and Gene Therapies: Challenges in Designing Extractables and Leachables Studies and Conducting Safety Assessments.

Over the past decade, Cell and Gene Therapies (C>) have been an emerging therapeutic area with more than twenty C> drug products approved and over 1000 registered trials. The remarkable progress in these modalities brings new challenges for scientists who evaluate manufacturing and storage materials, including risk assessments for extractables and leachables (E&L). Establishing a business process to qualify materials for these applications is an important risk mitigation strategy in support of these assessments.

Harmonisation of read-across methodology for drug substance extractables and leachables (E&Ls).

Health-based exposure limits (HBELs) are derived for leachables from polymeric components that interact with the drug substance which exceed a safety concern threshold (SCT). However, given the nature of leachables, there is not always chemical-specific toxicology data. Read-across methodology specific to extractables and leachables (E&Ls) was developed based on survey data collected from 11 pharmaceutical companies and methodology used in other industries.