Extractables and leachables (E&L) testing is a core regulatory requirement for the qualification of pharmaceutical packaging, medical devices, and manufacturing equipment.
The new ICH Q3E standard unifies and strengthens the international framework for these studies. FILAB supports you in the design, execution, and documentation of your E&L studies, in accordance with ICH Q3E, USP <1663> (extractables), and USP <1664> (leachables).
ICH Q3E: the new international framework for E&L
Published on August 1, 2025 and endorsed by the ICH Assembly at Step 2b, ICH Q3E — Guideline for Extractables and Leachables is the first major international harmonization on this topic. It is currently open for public consultation until December 18, 2025. Its final adoption (Step 4) is expected in the coming months.
ICH Q3E builds on the ICH guidelines on impurities — Q3A (drug substances), Q3B (drug products), Q3C (residual solvents), Q3D (elemental impurities), M7 (mutagenic impurities) — and follows the ICH Q9 quality risk management principles. It covers new and approved drug products, including cell and gene therapy products, as well as drug-device combination products.
This framework provides a holistic, risk-based approach for identifying, assessing, and controlling leachable impurities throughout the product lifecycle — from development through post-approval management.
Extractables and leachables: what are they?
These two terms refer to families of chemical impurities associated with materials in contact with the medicinal product:
Term | Definition | Source | Study conditions |
Extractables | Chemical entities extracted from a material under controlled laboratory conditions | Packaging components, devices, manufacturing equipment | Exaggerated conditions (solvents, temperatures, prolonged contact times) — worst case |
Leachables | Chemical entities that actually migrate into the medicinal product under normal manufacturing and storage conditions | Same sources as extractables | Real manufacturing and storage conditions — product shelf life |
Extractables are potential leachables: they generally represent a superset of which leachables are a subgroup. The concentration of a leachable is typically lower than that of the corresponding extractable identified in a well-conducted study. Establishing an extractables/leachables (E&L) correlation is a key requirement of ICH Q3E.
Does your dossier require E&L studies compliant with ICH Q3E?
Our experts design your study plan and support you through to the final report.
FILAB services for your E&L studies
FILAB offers comprehensive support for your extractables and leachables studies, from defining the study strategy through to producing the COFRAC-accredited report that can be used in your regulatory dossier.
Our experts support you in defining your risk-based E&L approach, in line with the principles of ICH Q3E and ICH Q9. We analyze the risk matrix specific to your product — formulation type, route of administration, treatment duration, material nature — and propose a tailored, proportionate study plan that can be documented in your CTD.
FILAB carries out a complete extractables profile of your components (primary packaging, delivery devices, manufacturing equipment) using a combination of complementary analytical techniques: GC-MS and GC-MS/MS for volatile and semi-volatile compounds, LC-MS/MS (UHPLC coupled with high-resolution mass spectrometry) for non-volatile and high-molecular-weight compounds, and ICP-MS for elemental extractables. Extraction conditions are defined on a worst-case basis with respect to the formulation (polar and non-polar solvents, extreme pH, representative temperatures and durations).
For pharmaceutical dosage forms with significant risk (injectables, inhaled products, ophthalmic products, modified-release forms), FILAB performs leachables studies on the finished drug product in its commercial packaging. Targeted analytical procedures are developed and validated according to ICH requirements (LOD, LOQ, linearity, accuracy, repeatability). A non-targeted screening (GC-MS, LC-HRMS) is systematically included to detect any unexpected leachable or interaction product.
If it is technically impossible to perform a study on the finished product (matrix interferences, large-volume parenterals, challenging AET), FILAB can carry out a simulated study using a solvent representative of your formulation's leaching propensity, under accelerated conditions that are documented and scientifically justified.
FILAB can support you in the toxicological assessment of substances identified above the AET: classification (Classes 1, 2, 3 according to ICH Q3E), calculation of PDEs and exposure margins, assessment of mutagenic potential (ICH M7 principles), and consideration of route-specific requirements (ophthalmic, intrathecal, dermal) and special populations (pediatric, oncology ICH S9).
Our analytical reports are structured for direct integration into module 3.2.P.7 of your CTD. We can also support you in drafting the E&L section of your dossier and in preparing responses to agency questions (FDA, EMA, ANSM) regarding your extractables and leachables studies.
Technical methods used for ICH Q3E analysis
- the GC-MS, HPLC, or UHPLC/MS/MS for the detection, identification, and quantification of organic compounds present in solvents, UV stabilizers, antioxidants, colorants, inks, detergent residues, sterilization residues, polymer residues… that have been extracted and/or leached from the material by a standardized simulant
- the ICP-AES and ICP-MS particularly suitable for mineral or metallic contaminants or additives, such as heavy metals, mineral or metallic fillers, colorants…
- microscopy MEB-EDX, a true rapid and versatile diagnostic tool for assessing the surface condition of the material after aging, observing particles, deposits…
Why entrust your E&L studies to FILAB?
- COFRAC ISO 17025 accreditation and GMP environment
Guarantees our technical expertise, the traceability of our measurements, and the admissibility of our analytical results before French and European regulatory authorities, as well as the U.S. FDA. - Comprehensive multi-technique analytical platform
- Mastery of regulatory thresholds (AET, SCT…).
- Structured reports for your regulatory submissions
Each FILAB report is structured for direct integration into your submissions: Module 3 CTD, IMPD, STED, BER, 510(k) or PMA dossier. Our deliverables include detailed operating conditions, annotated chromatograms, identification/quantification tables, and toxicological assessment of the detected compounds.
For the pharmaceutical sector, FILAB laboratory follows the ICH Q3E guidelines.
- Identification of extractables according to USP 1663
- Identification of leachables according to USP 1664
- Analysis of extractables and leachables according to BPOG (Good Operating Practices)
- Analysis of plastic packaging according to USP 665 and USP 1665
- Analysis of plastic material components according to USP 661.1
- Analysis and verification of packaging: interactions with the drug according to USP 661.2
Our other ICH services
ICH Q3D and ICH Q3E: two complementary frameworks mastered by FILAB
ICH Q3E: Extractables and Leachables
This guideline was created to manage substances that may migrate from direct contact materials (such as vials, stoppers, syringes) into the medicine itself. These substances are generally organic compounds that degrade or are released from the packaging material.
ICH Q3D: Elemental impurities
This ICH Q3D guideline aims to control and limit the presence of elements such as lead (Pb), mercury (Hg), arsenic (As), or cadmium (Cd) in pharmaceutical products. These elements may be present as traces in raw materials, excipients, catalysts, or may even migrate from production equipment.
FAQ
Extractables and leachables analysis is a process for evaluating and controlling the migration of chemical substances from packaging or manufacturing materials into a pharmaceutical product. The goal is to ensure that these substances, even in trace amounts, do not compromise the safety, quality, or efficacy of the drug.
Extractables are compounds that can be extracted from a material under extreme laboratory conditions, such as using aggressive solvents and high temperatures. Extractives analysis aims to identify as many of the chemical substances that make up a material as possible.
Leachables are compounds that actually migrate from the material into the finished product under normal use and storage conditions. Leachables are generally a subset of extractives.
The ICH Q3E is a guideline that harmonizes regulatory requirements globally (Europe, United States, Japan, etc.) for E&L studies. Its importance is paramount for the pharmaceutical industry because it:
- Ensures patient safety by limiting exposure to contaminants.
- Simplifies the new drug submission process by providing a single framework for safety studies.
- Eliminates the need to repeat analyses for each region of the world.
All finished medicinal products whose primary packaging or manufacturing equipment may release chemical substances are subject to these requirements. The level of requirements is proportional to the risk: very high for IV injectables, intrathecal, ophthalmic, and inhaled products; moderate for topical and liquid oral dosage forms; and lower for solid oral dosage forms and aqueous topicals compliant with food-contact regulations. Cell and gene therapy products and drug-device combination products are explicitly included within the scope of ICH Q3E.
The ICH Q3E specifies the documentation requirements to be included in registration dossiers (CTD, module 3.2.P.7). The E&L dossier must include:
- Justification of the conditions and methods of extractables studies (solvents, temperatures, durations, surface area/volume ratio, analytical methods and their qualification)
- All study reports, with all peaks above the AET identified and quantified (chemical name, structure, CAS number if available, observed level)
- Safety assessment of substances above the AET
- Establishment and documenting of the E&L correlation
- Implementation of the control strategy (supplier controls, component acceptance criteria, sampling plan)
- Demonstration of the effectiveness of any mitigation measures implemented
Lifecycle management is also covered by ICH Q3E: any change likely to impact the leachables profile—formulation modification, change of component supplier, evolution of the manufacturing process, new dosage regimen, change in patient population—must trigger a documented reassessment.
The Analytical Evaluation Threshold (AET) is the concentration threshold above which extractables and leachables must be identified, quantified, and subjected to toxicological evaluation. It is calculated by dividing the Safety Concern Threshold (SCT, generally 1.5 µg/day for organic compounds) by the analytical uncertainty factor (UF), which is itself determined by the qualification of the analytical method. The AET is therefore specific to each study, each product, and each analytical technique.
Not necessarily. ICH Q3E adopts a risk-based approach: for low-risk products (oral solids, aqueous topicals compliant with food-contact regulations), a simplified approach based on prior knowledge and extractables data may suffice. However, for injectables, inhalants, and high-risk formulations, a leachables study of the finished product is generally expected. Alternatives (simulated study, abridged dossier) are possible with justification and, where applicable, prior consultation with the regulatory authority.
