Extractables and Leachables (E&L) studies require a carefully planned design for extraction and data interpretation due to the complex nature of the materials, manufacturing processes, storage of medical devices along with their intended use. However, E&L studies are often treated as routine tasks assigned to laboratory technicians trained in routine sample preparation with limited knowledge investigating complex extractables and leachables issues, data interpretation and correlation. Preparation of sample extracts is a very important process for trace level analysis of unknown components in complex matrices. Preparation and analysis of extracts require profound knowledge of sample handling, chemistry, chromatography, spectroscopy, technical skills, laboratory equipment along with, extensive training in data acquisition, molecular structure identification and confirmation and data interpretation. Identification relying solely on search libraries or databases as is generally followed and practiced in most laboratories, may lead to misidentification and mischaracterization of analytes. Furthermore, quantification using relative response factors of representative standard compounds can swing the results by many fold either way.
This presentation will highlight critical issues facing not only analytical chemists but toxicologists, consultants, manufacturers and suppliers. We hope to provide scientific guidance and principles for harmonization of E&L investigations. Specifically, we will focus on the following points:
1. Optimization of data acquisition using selective instrumentation based on the rule of solubility that “like dissolves like”
2. Contradictions, vagueness, confusion and controversy of regulatory guidance documents, FDA feedback and reviews
3. Pros and cons of use of the non-polar solvent (hexane) relative to its effect on device integrity prompting calls for its elimination during recent E&L conference
4. Presentation of data highlighting shortfalls of Artificial Intelligence/Library Search for compound identification
5. Emphasis on training and qualification of analytical investigators and technical reviewers