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The Necessity of Extractable and Leachable Qualifications for Lyophilized Drug Products: Some Fallacies Addressed

Published Date: October 26, 2020

When selecting and qualifying the primary packaging for lyophilized drug products, an obvious question is: How deep should one go into the extractables and leachables qualifaction process of a lyophilization container?

As the drug product is in a solid state, it is expected that the interaction between the lyophilized drug product and the components of a lyo-container will be low. This is also reflected in the USP <1664> Monograph on Leachables and the EMA Guideline on “Plastic Immediate Packaging Materials” (2005).

However, the mechanism of interaction between the lyo-cake and the rubber stopper of a lyo vial is not always fully understood. The interaction mechanism is based upon outgassingof the rubber stopper, where the lyo cake acts as an adsorbent. Not only can this lead to substantial accumulation of the volatile and semi-volatile leachable compounds onto the lyophilized drug product, it may also induce chemical reactions between the leachables and the drug product, (i.e. when the adsorbed leachables show electrophilic properties).

The webcast will explain the outgassingmechanism of the lyo-stoppers, which may lead to further accumulation of leachables adsorbed onto the lyo-cake. In addition, an experimental testing strategy will be explained that covers both the discovery, identification, and quantification of those leachables, as well as the formation of secondary leachables through chemical reactions between these reactive leachables and the drug product and its ingredients.

Watch our 30 second animated video to get an idea of ​​what to expect from this webinar:



Key Learning Objectives:

  • Understand the need to perform extractable and leachable evaluations for lyophilized drug products from a scientific perspective.
  • Understand the interaction mechanism between lyo-vial system components and the drug product (outgassing)
  • Understand a combined testing protocol can determine the presence and concentration of both the leachables, accumulated onto the lyo-cake, as well as the secondary leachables that were formed after a chemical reaction with the drug product (ingredients)
Piet Christiaens, PhD

Piet Christiaens, PhD

Scientific Director, E&L Expert

Piet Christiaens received his Ph.D. from the Analytical Chemistry Department of the University of Leuven (Belgium) in 1991. From 1992 to 1997, he was Lab Manager in two CROs. From 1997 to 2000, he worked as an independent consultant with Shell Chemical Company in Houston, Texas (US), working on hydrogenated triblock co-polymers. Since 2001, Piet...

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