ICH Q3E Draft Guideline on E&Ls Available

The ICH Q3E draft “Guideline for Extractables and Leachables” and supporting documentation has reached Step 2b of the ICH Process on 1 August 2025 and entered the public consultation period. The deadline for comments in Europe is 18 December 2025.

Background

Currently, there exists no harmonized Extractables & Leachables guideline on a global level. Thus, the ICH Q3E guideline on the assessment and control of extractables & leachables (E&Ls) is expected to assist both applicants and regulators by providing focus on the risk management process, and improving transparency in requirements for medicinal products including drug delivery device components.

The draft Q3E guideline presents a holistic framework and process for the assessment and control of leachables to expand the existing ICH Q3 guideline series on impurities. The framework follows the principles of risk management as described in ICH Q9 (Quality Risk Management). However, while the guideline includes materials characterization and process understanding, its primary purpose is to protect patient safety and product quality through assessment and control of leachables in the drug product.

The Risk Management Process

The quality risk management (QRM) process for E&Ls provides a holistic strategy, based on prior knowledge and a thorough understanding of the critical attributes for the manufacturing / packaging components, as well as the manufacturing and storage conditions of the drug product. Close collaboration between the analytical chemists and drug safety experts is therefore essential for knowledge sharing and development of the E&L QRM process. According to the proposed guideline, a QRM process should be initiated with every product, each with its own risk assessment, risk control and lifecycle management process. For the overall risk assessment and control of leachables, it is important to consider the multidimensional nature of risk. The overall risk of a drug product is then determined by taking all dimensions into consideration.

The Risk Matrix should therefore include the following:

• Potential interaction between manufacturing / packaging components and the formulation,
• Chemical and physical properties of the equipment / component that likely contribute to leachables,
• Pre-treatment of components prior to use,
• Manufacturing and storage conditions (e.g., temperature, duration of contact, proximity of the downstream removal steps),
• Leaching tendency of the formulation (e.g., pH, organic co-solvents and surfactant / chelating agents).

In addition, the draft guideline provides an Appendix 1 illustrating typical workflows for E&L risk assessment and risk control for manufacturing components and packaging and delivery device components / systems. Typically, for manufacturing components / systems and under most circumstances for packing systems, a safety assessment of leachable studies considering worst case conditions is expected. Under certain low risk circumstances, alternative approaches can be used. However, in all cases, the approach taken should be justified and the extent of data and subsequent quality and safety assessment is aligned with the overall risk level.

The Q3E draft Guideline and supporting document is available for download on the Q3E EWG page and on the EMA website.