--- title: "European Pharmacopoeia Chapter 2.4.35 on Extractable Elements in Plastics for Pharmaceutical Use" description: "Ph. Eur. Chapter 2.4.35 defines a harmonized approach to assess extractable elements in plastic pharmaceutical materials, strengthening risk-based control of elemental impurities." url: https://qbdgroup.com/en/blog/url-european-pharmacopoeia-2-4-35-extractable-elements type: "Blog post" language: en published: 2025-11-19 author: "Yves Peeraer, Division Head Lab Services at QbD Group" category: "Lab Services" publisher: "QbD Group" citation: "QbD Group, \"European Pharmacopoeia Chapter 2.4.35 on Extractable Elements in Plastics for Pharmaceutical Use\", https://qbdgroup.com/en/blog/url-european-pharmacopoeia-2-4-35-extractable-elements" --- # European Pharmacopoeia Chapter 2.4.35 on Extractable Elements in Plastics for Pharmaceutical Use > Ph. Eur. Chapter 2.4.35 defines a harmonized approach to assess extractable elements in plastic pharmaceutical materials, strengthening risk-based control of elemental impurities. Since 2024, the **European Pharmacopoeia (Ph. Eur.)** has included **General Chapter 2.4.35 – Extractable Elements in Plastic Materials for Pharmaceutical Use**, providing a harmonized compendial procedure to characterize the potential release of elemental species from plastics that come into contact with medicinal products. Its publication formalizes an expectation long implicit in the industry: **the elemental contribution of primary packaging must be characterized**, not assumed negligible. ## Rationale and Regulatory Context Traditionally, **elemental impurities** in drug products have been controlled via **ICH Q3D** and related pharmacopeial texts, with focus on the finished dosage form. This approach, however, left a gap: materials in direct contact with the product — **such as containers, closures, and device components — can also introduce metals through catalysts, colourants, or stabilisers**. Under certain conditions, these elements may migrate, becoming part of the patient’s exposure profile. Chapter 2.4.35 addresses this **upstream source** by defining a **compendial stress-extraction procedure** to quantify elemental release under worst-case conditions. Rather than introducing new limits, it provides a **standardized analytical framework** for generating traceable, interpretable evidence to support risk assessments aligned with **ICH Q3D** principles. ## From Extractables to Risk Assessment Data generated under Chapter 2.4.35 feed directly into the **ICH Q3D risk assessment**, where the potential contribution of packaging materials is compared against **permitted daily exposure (PDE)** values and **elemental classifications** by toxicity and route of administration. This harmonized approach supports cross-functional evaluations, enabling consistency between materials science, toxicology, and regulatory affairs teams. For a broader overview of this framework — including identification, assessment, control options (1/2a/2b/3), and lifecycle integration — explore [this **Practical Guide to ICH Q3D**](https://qbdgroup.com/en/blog/safeguarding-drugs-controlling-elemental-impurities-ich-q3d?utm_source=chatgpt.com). ## Scope and Analytical Approach The chapter applies to **plastic materials intended for primary pharmaceutical packaging**. It specifies an **acidic extraction under elevated temperature (autoclave conditions)** to simulate worst-case element release, followed by instrumental quantification using **ICP-MS** or another validated method consistent with **Ph. Eur. 2.2.58**. This design ensures **reproducibility and comparability** across laboratories and suppliers, essential for regulatory submissions, supplier qualification, or change-control justifications. The selection of analytical technique depends on **sensitivity requirements, sample matrix and throughput**. - **ICP-MS** offers ultra-trace detection and broad elemental coverage. - **ICP-OES** provides cost-effective, robust performance in the ppb–ppm range, ideal for high-volume testing. For a concise comparison of both methods and their applicability in elemental impurity projects, see [ICP-MS vs ICP-OES: choosing the right technique](https://qbdgroup.com/en/blog/elemental-impurity-testing-icp-ms-vs-icp-oes?utm_source=chatgpt.com). Notably, earlier drafts proposed explicit numerical limits for certain elements, but these were **removed** in the final version. Instead, non-binding recommendations will appear in **General Text 5.42**, reinforcing a **risk-based, scientifically driven** approach rather than specification-led control. ## Strategic Relevance for Industry While Chapter 2.4.35 does not impose pass/fail criteria, it establishes a **shared procedural baseline** with tangible benefits: - **Comparability:** Enables like-for-like extractables data across suppliers and labs. - **Credibility:** Anchors extractables testing in a pharmacopeial framework rather than internal protocols. - **Regulatory clarity:** Facilitates consistent dossier justifications and smoother authority review. In short, the chapter elevates extractables testing from a case-by-case practice to a **recognized regulatory expectation**—supporting both scientific integrity and inspection readiness. ## Relationship to the Control of Elemental Impurities Chapter 2.4.35 complements, rather than replaces, **ICH Q3D**. While Q3D evaluates patient exposure from the finished dosage form, 2.4.35 provides the **upstream evidence** needed to determine whether packaging contributes significantly to that exposure. In practice, the resulting data can inform **material qualification**, **design-space justification**, and **lifecycle change control**, embedding extractables science into a broader **pharmaceutical quality system**. ## Key Takeaway By formalizing a method without imposing limits, **Chapter 2.4.35** recognizes that packaging materials can influence elemental impurity profiles, while preserving the flexibility for **risk-based scientific judgement**. Its inclusion in the **European Pharmacopoeia** harmonizes expectations across jurisdictions and strengthens the technical foundation for the generation and interpretation of extractables data in pharmaceutical materials science. At **QbD Group**, we help organizations bridge regulatory expectations with practical implementation. Our experts in **analytical chemistry**, **materials science**, and **regulatory strategy** support clients in aligning extractables and leachables studies with ICH Q3D and Ph. Eur. 2.4.35 requirements, ensuring compliant, science-based decision-making throughout the product lifecycle. 👉 **Need guidance on integrating 2.4.35 into your ICH Q3D strategy?** [Contact QbD Group to speak with our elemental impurities specialists.](https://qbdgroup.com/en/services/lab-services/elemental-impurities/) **[](https://qbdgroup.com/hs/cta/wi/redirect?encryptedPayload=AVxigLJ%2BIAzMoBPeLt2rFA%2Fz6Xbg87lxZTgteXmmPU0J8TRtqu77LPh4ei4dwzTk%2BdCWdFYRWPe%2BoKQrd%2Brs9azVpCkV4vYK%2Bu0YxLBck9Hq4AAXufelRlz6FqV00N5Meu2n8paHzfoDClD47ZayQehRdQUztKQvzwjyGVvoYLqKwM1S7kRj29DC3uzcsQYzTmDuMA%2B8&webInteractiveContentId=182180411438&portalId=7030766)** ## Need reliable lab testing and validation? ## Ready for reliable results? --- Source: https://qbdgroup.com/en/blog/url-european-pharmacopoeia-2-4-35-extractable-elements — © QbD Group. Quote freely with attribution and a link back.