Structural Alert Screening Assays and Target Methods to Assess Genotoxicity of Pharma Packaging Leachables

Elly Spies Faber 

TNO Quality of Life
Utrechtsweg 48, P.O. Box 360, NL-3700 AJ Zeist, The Netherlands
Tel: +31 30 694 4113   Fax: +31 30 694 4894
Email: elly.spies@tno.nl

Biography

Elly Spies-Faber, studied Molecular Science at the University of Wageningen in the Netherlands. She received her PhD from the Bio-Organic chemistry department of the University of Utrecht in the Netherlands where she conducted research on the structure of polysaccharides.

From 2000 onwards, Mrs. Spies-Faber worked as a Project Manager in the Analytical Research department of the Netherlands Organization for applied scientific research (TNO Quality of Life).

She is leading projects concerning the analysis of packaging material for food and pharmaceutical industry. Furthermore, she is involved in developing advanced analytical strategies to asses the safety of extractables and leachables of pharmaceutical packaging.

Abstract

For safety evaluation of new packaging materials information should be collected regarding its physico-chemical characteristics, material composition, content of residues of starting materials, extractables, leachables and migration of substances. Also, interaction products of packaging migrants and the pharmaceutical ingredients must be taken in account. When a new packaging material is not described in either the (European) Pharmacopoiea or is not in accordance with foodstuff legislation, information regarding these interaction products and − when biologically relevant − their toxicities have to be collected.

Therefore a pragmatic protocol for safety assessment of of extractables and leachables migrants is currently under development which is based on an integrated assessment of exposure, toxicology and chemical analysis
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Currently, TNO is developing new (bio-) analytical tools which are capable to exclude or determine and quantify the presence of high risk components (e.g. substances with structural alerts for genotoxicity) in complex matrices using mass spectrometric data and/or after selective derivatisation. Using these tools we aim to be able to assign specific functional groups in complex mixtures present at toxicological relevant concentrations, rather than  performing time consuming peak-by-peak identification and quantification. This approach requires generally applicable toxicological reference values for specific chemical classes or groups. For this the thresholds as defined by Kroes et al. (TTC principle) are used.

The feasibility of this novel analytical assessment strategy will be demonstrated for aromatic amines and epoxides.