Extractables and Leachables Examples
24 Mar 2025
Strategies for Overcoming Challenges in Pharmaceutical Packaging Evaluation
At each step of an E&L pharmaceutical study, understanding extractables and leachables examples is crucial as there are multiple potential challenges. It is, however, possible to anticipate these potential issues and overcome them by adopting a strategic approach.
The purpose of an extractables and leachables investigation is to guarantee that a pharmaceutical packaging container closure system (CCS) is safe, and does not negatively influence the drug product. In this context, combination products / devices such as inhalers or pre-filled syringes are regarded as primary packaging or container closure systems. However, this depends on the primary and secondary mode of action; they could also be considered as medical devices if marketed without the drug product. Understanding extractables and leachables examples is crucial.
The evaluation and design of the E&L study and method set-up must include a comprehensive analysis of the extractables and leachables, including volatiles, semi-volatiles & non-volatiles.
The extractables study would typically involve multiple techniques, and the Analytical Evaluation Threshold (AET) analysis values / design would follow recommendations from industry guideline documents such as those from the PQRI for PODPs (2013), CDER from FDA (2008), EMA, USP or ISO 10993-18 series as appropriate to the application and region of interest.
Common Challenges and Examples in Extractables and Leachables Studies
Extractions with both organic and aqueous solvents and formulation / placebo are required to establish the ‘complete picture’ under the worst-case conditions. At each step of the workflow, there are some typical challenges commonly experienced; however, examples can provide valuable insights. It is possible to overcome these challenges by adopting a strategic approach and the ability to anticipate any potential issues based on experience. Some of the common challenges include a lack of supplier data or incomplete supplier data for construction materials, choice of the right solvents or extraction conditions, interference of leachables with the matrix-related substance, and others.
Optimizing Your Extractables and Leachables Study and Strategy for Success
All steps of the extractables / leachables study should be considered with careful design established in order to avoid the risks of multiple unknown peaks, sensitivity issues and the complexity this brings to the study. It is a good strategy and approach to avoid generic studies, which might introduce the risk of overestimation of extractables due to harsh extraction conditions compared to the real application scenario – a more realistic extractables study gives you a more realistic insight into the potential leachables. Extractables and leachables examples and additional experiments related to pharmaceutical packaging and its components will help to identify or justify unknowns and to estimate the real risk for the patient. If required, there are additional analytical techniques, such as NMR, which could be used for identification, assuming it is possible to enrich the concentration of the unknown to levels suitable for analysis. Finally, extractables and leachables workflows that are flexible and scientifically justified are key for success.
Our experts, with over 25 years of experience in specialized analytical and toxicology assessment for extractables and leachables across various pharmaceutical packaging and product types, are here to assist you. Whether you need guidance, evaluation or examples to illustrate our expertise, we're ready to help. Find out more, and feel free to get in touch!
Dive deeper and download our comprehensive white paper – to learn how to anticipate potential extractables and leachables issues and put the most effective solutions into play: Extractables & Leachables: Problem Solving for Complicated Formulations.
