Your needs: analyze extractables and leachables to assess the compliance of your healthcare products
What do we mean by “Extractables and Leachables”?
In materials science, “Extractables and Leachables,” or “Extractables and Leachables” in English, refer to the movement of chemical species, atoms, ions, or molecules within matter, whether it is solid (crystalline or amorphous), liquid, or gaseous.
This irreversible transport phenomenon, more commonly known as migration, is therefore a macroscopic concept that refers to the concentrations of chemical species in the different constituents of a medium and which may evolve during its use.
This natural phenomenon therefore refers to the diffusion of matter in order to make the concentrations of chemical species in a given medium more uniform.
Extractables are, by definition, compounds that can be extracted from a material when they are in contact with solvents of varying polarity under extreme conditions.
Our solutions: migration analysis of extractables and leachables
With a wide range of analytical equipment and dual expertise in chemistry and materials, the FILAB laboratory supports you at every stage of the assessment of extractable and leachable substances in healthcare products (medical devices, pharmaceutical products and cosmetic products), through the following services:
For medical devices (implantable MDs such as stents, catheters, or administered MDs such as syringes or bags), the FILAB laboratory follows the recommendations of the MDR (Europe) and the FDA (US)
- Sample preparation according to ISO 10993-12*
- Chemical characterization of materials according to ISO 10993-18* including AET calculation and justification
For the pharmaceutical sector, the FILAB laboratory follows the ICH Q3E guideline.
- Extractables identification according to USP <1663>
- Leachables identification according to USP <1664>
- Extractables & Leachables analysis according to BPOG (Good Operating Practices)
- Plastic packaging analysis according to USP <665> and USP <1665>
- Analysis of plastic material components according to USP <661.1>
- Packaging analysis and verification: interactions with the drug according to <USP 661.2>
The E&L standards mastered by FILAB
| Reference framework | Purpose | Sector |
| USP 1663 | Extractables from pharmaceutical packaging systems | Pharma / Packaging |
| USP 1664 | Leachables in medicines — focus on OINDPs | Inhalation, MDI, DPI |
| USP 665 | Polymers in contact with biologics — manufacturing | Biopharma / Single-use |
| USP 661-1 | Pharmaceutical glass containers | Glass packaging |
| USP 661-2 | Pharmaceutical plastic containers | Plastic packaging |
| ISO 10993 / MDR | Medical device biocompatibility — EU Regulation 2017/745 | EU medical devices |
| ISO 10993-18 / FDA | Medical device chemical characterization — FDA requirements | US-export medical devices |
| BPOG | Extractables for single-use bioprocess equipment | Biopharma / SUS |
Extractables and Leachables (E&L) Analysis
The study of extractables and leachables is an essential analysis to ensure the safety of materials that come into contact with sensitive products (medicines, medical devices, cosmetics, etc.).
Extractables are substances that can be extracted from a material when it is subjected to aggressive solvents under controlled conditions (temperature, pH, duration).
Leachables are compounds that actually migrate from a material into a finished product under normal conditions of use.
Our analytical techniques for extractables and leachables
- 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 released from the material by a standardized simulant
- the ICP-AES and ICP-MS particularly suited to mineral or metallic contaminants or additives, such as heavy metals, mineral or metallic fillers, colorants…
- microscopy SEM-EDX, a truly rapid and versatile diagnostic tool for assessing the material surface condition after aging, and for observing particles, deposits…
Why entrust your E&L studies to FILAB?
- COFRAC ISO 17025 accreditation and GMP environment
Guarantees technical expertise, the traceability of our measurements, and the enforceability of our analytical results with French and European regulatory authorities, as well as the U.S. FDA. - Comprehensive multi-technique analytical platform
- Mastery of regulatory thresholds (AET, SCT, etc.)
- Structured reports for your regulatory submissions
Each FILAB report is structured for direct integration into your submissions: CTD Module 3, 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.
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Do you need extractables & leachables studies?
The FILAB laboratory supports manufacturers in the study of extractables and leachables
The study of E&L applies to several sectors where the interaction between materials and finished products is critical:
- Pharmaceuticals: contact between containers (vials, syringes, blisters) and medicines.
- Medical devices: infusions, catheters, implants, tubing.
- Biotechnology: cell culture media, single-use systems.
- Cosmetics: packaging and applicators in contact with sensitive formulations.
- Agri-food: packaging and the potential migration of chemical substances.
In general, the material manufacturer knows the type of compounds that can be extracted and, ideally, provides the user with the list of extractable chemical species.
Since a specific formulation may affect the type and amount of leachables, it is the manufacturer's responsibility to demonstrate that the level of leachables does not contribute to adverse toxicological effects. Current guidelines (for example, the Food and Drug Administration (FDA) document "Container Closure Systems for Packaging Human Drugs and Biologics") and the European Medicines Agency (EMA) guideline "Guideline on Plastic Immediate Packaging Materials" clearly state that it is preferable to test leachables with the final formulation.
FAQ
Correlating extractables data with potential leachables must be done with caution, as not all leachables are found in extractables studies. Since a drug formulation can chemically alter known extractable compounds, it is possible to detect leachables that were not identified by the extractables study.
In addition, sample matrix effects, differences in the analytical system, changes in the test method, etc., limit the possibility of direct correlations.
Assessing a material, its proper aging over time, and the compatibility between materials and objects (polymer, metal or glass containers) that come into contact with its contents (cosmetic, pharmaceutical, food products, medical devices, etc.) is a major concern for companies in the agri-food, cosmetics, pharmaceutical, and medical device sectors. The impact of chemical migration from the material (container, packaging, tableware, utensils, implant, equipment, etc.) in contact with the product (medical devices, bulk, powder, tablet, liquid, the human body, etc.) can be critical: contamination, non-compliance, complaints, harm to consumers/users, etc.
For example, the FDA published as early as 1999 a Guidance for Industry: Container Closure Systems for Packaging Human Drugs and Biologics in which it is specified that:
"packaging components must be made of materials that do not leach undesirable or hazardous substances to the patient treated with the product.
Accordingly, dossiers must include extraction tests on the packaging to determine which chemical components or materials are likely to migrate into the product. A toxicity study of these components must be carried out".
In 2005, this text was supplemented by a European guideline from the EMA: Guideline on plastic immediate packaging material which specifies that the purpose of extraction tests is to identify and quantify additives (antioxidants, plasticizers, catalysts, etc.) that can be extracted by the contents in contact with the packaging, whether the product is liquid or solid.
Following this, in 2006, the Product Quality Research Institute (PQRI) carried out extensive research on inhaled or nasally administered products.
These studies led to recommendations: Safety Thresholds and Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Product.
These recommendations now serve as a reference for the FDA and for the rest of the pharmaceutical world.
These studies mainly concern packaging components (blisters, bottles, prefilled syringes, metering valves, inhalers, etc.), but also those in contact with the product during the manufacturing process (filtration systems, transfer tubing, single-use equipment, big bags...).
Leached substances may have an effect either on the patient, for example through demonstrated carcinogenicity (N-nitrosamines, polycyclic aromatic hydrocarbons, etc.) or on the physicochemical stability of the drug itself.
The main challenges concern regulatory compliance, material variability, and result interpretation. Pharmaceutical and medical industries must comply with strict standards (USP, ISO 10993, ICH Q3D), which requires in-depth analyses and rigorous validation. The complexity of modern materials (multilayer structures, coatings, technical polymers) can lead to unpredictable migration behavior. Finally, interpreting the data requires advanced expertise to distinguish critical impurities from harmless compounds while ensuring the safety of the final product.
Extractables are substances that can be extracted from a material when it is exposed to specific solvents under controlled conditions. Leachables, on the other hand, are substances that actually migrate from the material into the finished product under normal conditions of use.
The leachables study is more representative of the real risk for the end user.
Medical devices come into direct contact with biological fluids, medicines, or injectable solutions. An E&L study helps identify substances that may migrate and verify their safety. This analysis is essential to meet biocompatibility requirements, particularly those defined by ISO 10993-18.
The materials concerned are those in direct contact with a sensitive product: plastics, polymers, rubber, metals, inks and adhesives. These materials are found in pharmaceutical packaging, syringes, tubing, infusion bags, and even medical implants.
La FDA ne possède pas de guideline spécifique dédiée aux E&L, mais elle aborde ces aspects dans plusieurs documents réglementaires, notamment pour les dispositifs médicaux (ISO 10993-18), les emballages pharmaceutiques et les systèmes d’administration de médicaments. L’agence recommande des études approfondies pour identifier les impuretés potentielles pouvant migrer dans les médicaments et évalue leur impact toxicologique en fonction des seuils de sécurité acceptables. Les attentes de la FDA s’alignent sur celles des pharmacopées américaines (USP <1663>, <1664>) et des recommandations internationales comme celles de l’ICH.
L’USP définit les exigences des extractibles et relargables (E&L) dans les matériaux en contact avec les produits pharmaceutiques à travers les chapitres USP <1663> et USP <1664>.
L’USP <1663> décrit les principes et méthodologies pour identifier les extractibles, c’est-à-dire les substances pouvant être extraites d’un matériau sous des conditions agressives. L’USP <1664> concerne les relargables, qui sont les composés effectivement migrés dans le produit fini dans des conditions normales d’utilisation.
Ces directives aident à garantir la sécurité des patients et la conformité réglementaire en caractérisant les impuretés potentielles pouvant affecter la stabilité et l’innocuité des médicaments.
An Extractables and Leachables E&L study is required when selecting or changing a primary packaging material, when developing a new medical device, when changing a component supplier, for any regulatory submission (CTD, IMPD, 510(k), PMA, STED), and when investigating a quality anomaly or an out-of-specification result.
Yes. FILAB offers a turnkey service covering study design, extractions, multi-technique analyses, identification and quantification of compounds, toxicological assessment, and final report writing. Our experts work with qualified toxicologists for assessments requiring a PDE/TI/MoS calculation.
