A Commentary on Several Study Design Considerations Pertaining to the Screening of Substances Extracted and/or...

The assessment of substances that can be extracted (extractables) or leached (leachables) from the materials that come in contact with pharmaceutical products often starts with a general screening of these substances in relevant samples. Although such screening studies may be of a qualitative and semi-quantitative nature, the data they generate are critical in ensuring the suitability of the system(s) used to manufacture, store, and/or administer the product. As such, it is important they are designed using appropriate analytical techniques and methodologies so that representative and reproducible data are obtained. The goal of this commentary is to provide insight into several, but by no means all, good practices for the preparation and analysis of samples in extractable and/or leachable screening studies in order to help ensure representative and reproducible results are ultimately obtained. The specific topics covered are extraction stoichiometry, the importance of verifying method performance, assessing the need for incorporating derivatization in gas chromatography-based analyses, and properly accounting for analytical uncertainty when calculating the analytical evaluation threshold.