Method Validation Challenges in Extractables and Leachables Analysis

Extractables and Leachables (E&L) studies are critical to ensure the quality of pharmaceutical products and medical devices. The design and execution of an E&L study dictate the value associated with the outcome of a study. Analytical methods employed in E&L investigations play an important role and shall be suitable for such studies. However, method validation of analytical methods employed in E&L studies could be quite challenging. Some of the challenges are associated with the fact that the identities of E&L compounds are not generally known at the time of analysis and the reference standards are not commercially available in many cases. Furthermore, significantly lower Analytical evaluation threshold (AET) associated with large volume parenteral products present another sophisticated challenge during method validation. Different strategies to address method validation concerns will be discussed including the use of surrogate standards and selected extractable compounds and employing preconcentration technique. Relevant information from compendial chapters and literature will also be discussed.