Extractable and Leachable Compounds: The Importance of Having Unique Identifications and its Impact on Toxicological Risk Evaluation

The importance of extractable/leachable testing for container closure systems (CCS) in the pharmaceutical industry has grown considerably in the last few years, driven by well-documented incidents where impurities in the contained drug product – introduced by the container closure system via leaching – were found to be harmful to the patients, as well as an increase in global regulatory requirements associated with such concerns.

As a first step in the qualification of a container or closure from an E/L-perspective, a controlled extraction study must be performed to understand the associated extraction profile of that material. Apart from the technical issues in designing these extractable studies, it is of utmost importance to identify as many compounds as possible during a “First Pass” experiment. This is why Toxikon developed the TOX-RAY Screener Database, which allows to uniquely identify compounds, based upon the analysis of over 3500 actual standards. In addition, Toxikon has invested heavily in the high-end, state-of-the-art analytical techniques to further unravel the structure of some compounds that are not readily identified. These techniques can significantly contribute to further determine the chemical structure of a molecule.

Knowing the structure of a chemical compound is of high importance, even at the level of an extraction study, because it’s the chemical structure (a.o.) that will determine its toxicity. Toxikon developed a unique tool, called TOX-RITE (Rapid Initial Toxicological Evaluation) to allow a quick toxicological screening of the analytical results of an extraction study. This allows to rapidly identify which compounds should be monitored during the subsequent “formal” leachable study.

Key Topics:

• Introduction – Regulatory Aspects
• Designing an Extractable & Leachable Study
• Tools to assist in Unique Identifications: Toxikon’s TOX-RAY Screener Database
• High-End Analytical Techniques, used by Toxikon, which can contribute to further unravel the Structure of a Molecule
• The Importance of having a Chemical Structure for subsequent toxicological evaluations
• Toxikon’s TOX-RITE approach to Rapid Initial Toxicological Evaluations for Extractable Studies

Speakers

John Iannone, Program Manager – Extractables/Leachables & Special Studies, Toxikon Corporation

Since joining Toxikon in 2004, John has assisted several drug and medical device developers with the development of product safety testing strategies. His areas of expertise include biocompatibility testing of combination devices, material characterization, and study design for custom microbiological and extractable and leachable studies. His responsibilities focus on providing technical support in client interface regarding unique testing requirements and facilitating the attainment of sound technical risk assessments of medical devices.

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Karen Pieters, Project Manager – Extractables/Leachables, Toxikon Corporation

Karen Pieters graduated as a bio-engineer in chemistry in 2006. After graduation, she worked for three years as a Quality Document Expert at Merck and Sharp & Dohme (MSD), gaining experience in the regulatory and analytical challenges of the Pharmaceutical industry.

In 2010 Karen joined Toxikon Europe as Study Director of extractables and leachables with focus on disposable materials for bioproduction, large volume parenterals as well as ophthalmic and topical applications.

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Anja Cerstiaens, Study Director Coordinator, Toxikon Corporation

Anja Cerstiaens received her Ph.D. from the Faculty of Bioscience Engineering at the Catholic University of Leuven (Belgium) in 2000. She worked as a postdoctoral fellow at the University of Leuven (Biology Department) conducting research in the field of Peptidomics and Proteomics until 2004. During this period she gained expert knowledge in Mass Spectrometry (LC/MS/MS). From 2005 to 2006 she was employed by Unilever, performing contract research at the laboratory for Pharmacotechnology and Biopharmacy of the Leuven University.

Dr. Cerstiaens joined Toxikon Europe in 2006 as a Study Director, focusing on extractables and leachables studies for Orally Inhaled and Nasal Drug Products. Currently, she is heading the group of study directors (E&L) at Toxikon Europe.

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