Chapter USP <1663> ” Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems ” is the United States Pharmacopeia’s informative reference framework for evaluating extractable substances. It defines the scientific principles and best practices validated by the FDA and the EMA to ensure the safety of packaging systems.
As a pharmaceutical manufacturer, you want to carry out an extractables analysis according to USP 1663
What does USP 1663 say?
USP 1663 is a guideline from the United States Pharmacopeia (USP) focused on assessing the leaching risks of packaging materials in contact with pharmaceutical products.
This section focuses on the identification and quantification of extractable compounds that may be released from packaging materials into the drug product. This includes establishing protocols for the extraction and analysis of chemical compounds that could migrate from packaging or delivery systems into the pharmaceutical product. The goal is to understand the extractables profile in order to assess potential risks to drug stability and patient safety.
Why conduct a study according to USP 1663?
USP 1663 does not set out a rigid procedure, but answers a central question: which scientific principles should be applied for a rigorous assessment of extractables? FILAB supports you with two types of approaches defined by the chapter:
The logic behind selecting extraction solvents
Solvent selection is the most critical parameter. According to USP 1663, the choice follows this order of preference:
The formulation itself or its vehicle (placebo).
"Surrogate" solvents with similar polarity, pH, and ionic strength.
Several solvents with different polarities for high-risk dosage forms (injectables, inhaled products).
Examples of recommended solvents by component type:
Closure/Bag (injectable): Water pH 5.2 / Water pH 9.5 / Isopropanol:water 50:50.
Elastomeric seal (MDI): Dichloromethane, Isopropanol, Hexane.
Extraction techniques and validity criterion
FILAB implements the six extraction techniques described by the USP : maceration (reference for simulation), reflux, Soxhlet (for characterization), closed vessel/autoclave, instrumental extraction (ASE) and sonication.
A key point: reaching equilibrium.
In accordance with USP <1663>, we monitor the extractables profile until an asymptotic plateau is reached. An extraction stopped too early could underestimate the patient’s actual exposure.
The FILAB laboratory supports pharmaceutical manufacturers in leachables analysis according to USP 1663
For the pharmaceutical sector, the FILAB laboratory follows the ICH Q3E guideline.
- Leachables assessment according to USP <1664>
- Extractables & Leachables analysis according to BPOG (Best Practice Operating Guidelines)
- Analysis of components in plastic materials according to USP <661.1>
- Packaging analysis and verification: interactions with the drug according to USP <661.2>
- Leachables analysis of process materials according to USP <665>
- Identification of extractables according to USP <1665>
Analytical strategy and identification levels
FILAB deploys a wide range of analytical techniques to cover all compound families:
| Technique | USP <1663> application | Target compounds |
| GC-MS | Discovery, Identification, Quantitation | VOCs and SVOCs (semi-volatile organic compounds) |
| LC-HR/MS | Discovery, Identification, Quantitation | Polar and non-volatile compounds |
| ICP-MS | Discovery, Identification, Quantitation | Trace elements and metals |
| HS-GC-MS | Discovery | Very volatile compounds |
| TOC / NVR | Scouting | Total organic load / Non-volatile residue |
Why choose FILAB for your analyses according to USP 1663?
- 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.
Our related services
Analyses des métaux lourds et des impuretés élémentaires ICH Q3D
Validation analytique selon l’USP 233 pour l’analyse des impuretés élémentaires
Did you know?
FILAB is COFRAC ISO 17025 accredited for the following scope, since 2015: Analysis and quantification of elemental and mineral impurities, including heavy metals, by ICP-AES and ICP-MS in cosmetic and pharmaceutical products according to European Pharmacopoeia 2.4.20 and USP 233
Our FAQ
Le risque de lixiviation, dans le contexte de l'industrie pharmaceutique et des matériaux d'emballage, fait référence au potentiel de transfert de substances chimiques depuis le matériau d'emballage vers le produit pharmaceutique.
Ce phénomène peut survenir lorsque des composés chimiques présents dans les matériaux d'emballage, comme les plastiques, les caoutchoucs, les encres, les adhésifs, et les revêtements, migrent dans le médicament qu'ils contiennent. Ce processus de migration est souvent appelé "lixiviation".
Les risques associés à la lixiviation comprennent:
- Contamination du produit pharmaceutique: les substances chimiques lixiviées peuvent contaminer le médicament, affectant sa pureté, sa stabilité et sa sécurité.
- Altération des propriétés du médicament: les composés lixiviés peuvent interagir avec les ingrédients actifs ou d'autres composants du médicament, potentiellement altérant son efficacité, sa stabilité ou son profil de dissolution.
- Risques pour la santé des patients: si les substances lixiviées sont toxiques ou irritantes, elles peuvent présenter un risque direct pour la santé des patients qui utilisent le médicament.
- Non-conformité réglementaire: la présence de lixiviats non approuvés ou en quantités supérieures aux limites autorisées peut conduire à des problèmes de conformité avec les réglementations pharmaceutiques, comme celles établies par l'USP, la FDA, et d'autres organismes de réglementation.
Pour obtenir un devis, vous pouvez contacter nos équipes via notre formulaire de contact, par téléphone ou par e-mail.
Il vous suffit de nous transmettre votre besoin (type de matériau, analyse souhaitée, norme éventuelle, urgence, quantité d’échantillons…). Nous vous envoyons ensuite une proposition technique et tarifaire personnalisée en 24-48H.
Les délais varient selon la nature de l’analyse et la complexité du projet d’expertise.
FILAB s’engage toutefois à fournir des délais rapides et adaptés à vos contraintes et urgences industrielles.
