Plan For Your Extractables And Leachables Studies To Meet Submission Timelines

By Matthew Woods

Demonstrating the compatibility of any material in contact with drug product throughout its lifecycle (manufacture, containment, and delivery) is a necessity for a regulatory submission. Defined as extractables and leachables, these assessments continue to evolve and expand due to consistently increasing agency expectations. Agency expectations require you to act sooner rather than later. Waiting until Phase III in drug development can lead to delays and additional costs due to poor assessments that are questioned by the reviewer, or incomplete submissions that require you to redo or execute additional work.

E&L assessments are multi-step processes where you must use knowledge of your drug product and manufacturing process, along with data from vendors, analytical labs, and toxicologists to demonstrate compatibility between the drug product and any material in contact with the drug product.

Guidance documents from the United States Pharmacopeia (<1663>, <1664>) and the Product Quality Research Institute (Safety Thresholds and Best Demonstrated Practices for Extractables and Leachables in Parenteral Drug Products [Intravenous, Subcutaneous, and Intramuscular]), and ISO standard 10993-18 provide a framework of how to execute this assessment. In this article, review the four steps of the framework.