Ask the Expert: Studies for Extractables and Leachables

In this episode of the Ask the Expert video series, Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, talks to Piet Christiaens, PhD, scientific director, E&L expert at Nelson Labs, and Dennis Jenke, PhD, principal consultant for Nelson Labs and chief executive scientist, Triad Scientific Solutions, about extractables and leachables (E&L). Specifically, Christiaens and Jenke highlight the differences between the E and the L in E&L and how these two compounds play off each other. Jenke goes into detail about the requirements for leachable studies, while Christiaens provides clarification on what is necessary for extractables.

“The design requirements for leachable studies are pretty clearly outlined in the global regulations,” says Jenke. “That's things like, use three batches of drug product. You use multiple time points over nominal shelf life and accelerated shelf life in order to establish trends. You use drug product units that represent commercial product. In other words, the formulation is the commercial formulation, the packaging is the commercial packaging, and the product has been manufactured using the commercial manufacturing process. There's the expectation that an eligible study has two components, targeted components, where you know it's exactly what it sounds. You know what the compounds are that you need to measure, and you validate [them]. You validate methods to do those measurements. The second component is a screening or non-target component, where you don't necessarily know what the compounds are that you're looking for, and you use qualified methods to look for these compounds above a reporting threshold. The analytical methods themselves, at least in terms of high-level, are relatively well established.”

“During a stability study, you have your different time points, and gradually you see those compounds coming out of the container closure system,” Christiaens says. “If you would not do that, then you would do some kind of impurities profiling of your drug product. That means that you would see everything that is present in the drug product without any differentiation between, is it eligible or not? And that is very important in terms of conclusions. You only want to report in this phase what is coming out of the container closure system and nothing else, because the other things will normally have been addressed in other studies. So, you don't need to repeat that over again.”

Click the video above to watch Piet and Dennis answer the following questions:

“What are the critical points in an E&L study that really need to be addressed before even considering a submission to the health authorities?”

“My company recently performed E&L studies on a product using different approaches and got different results each time. How can we be sure which results are ‘correct’?”

About the experts

Piet Christiaens, PhD, is scientific director, E&L expert at Nelson Labs. Dr. Christiaens develops analytical methods and protocols for both extractables and leachables studies for the pharmaceutical and medical industries.

Dennis Jenke, PhD, is principal consultant for Nelson Labs and chief executive scientist, Triad Scientific Solutions. Dr. Jenke supports the customers of Nelson Labs Europe in the discussion of general principles, concepts, tactics, and/or strategy related to chemical characterization and qualification of materials, components, and systems used in these industries.

About the moderator

Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates and a member of Pharmaceutical Technology®'s Editorial Advisory Board.

Ask the Expert Video Series

Welcome to the Ask the Expert video series. This series is an extension of the PharmTech Group’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. This new video series will expand on topic areas to include development and manufacturing concerns to help those working in the industry better understand bio/pharmaceutical requirements. Have a question you would like answered? Send it to PTProjects@mmhgroup.com, and it may appear in a future episode or print column.

We hope you enjoy the discussion!