The chapter USP <1664> “Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems” is an informational chapter of the United States Pharmacopeia (USP). It applies to the evaluation of leachables in the finished pharmaceutical product
As a pharmaceutical manufacturer, you want to carry out an extractables analysis according to USP 1664
What does USP 1664 say?
USP 1664 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 leachable compounds (leachables), which are the chemical entities that actually migrate from packaging or delivery systems into the finished pharmaceutical product under its real storage conditions. Unlike extractables obtained under forced conditions, the study according to USP <1664> establishes rigorous protocols for analyzing substances in direct contact with the formulation, as well as migrants crossing the physical barriers of secondary packaging.
Why carry out a study according to USP 1664?
The main objective is to characterize the leachables profile in order to assess risks to patient safety, based on strict toxicity thresholds such as the SCT (Safety Concern Threshold) and the QT (Qualification Threshold). This approach not only helps ensure the drug’s stability, but also establishes a qualitative and quantitative correlation with the extractables studies (USP <1663>) previously carried out.
The FILAB laboratory supports pharmaceutical manufacturers in leachables analysis according to USP 1664
Study strategies: real study or simulation?
Depending on the complexity of your formulation matrix, FILAB supports you with two approaches defined by USP 1664:
- The formal leachables study: carried out on the actual product, in its final commercial packaging, including real-time testing (stability).
- The simulation study: a core concept of USP 1664, it makes it possible to replace the complex matrix of the finished product with a simulating solvent (surrogate) with the same extraction power. This approach is recommended when direct analysis is not feasible due to very low thresholds or major interferences.
Our analytical techniques for extractables according to USP 1664
- the GC-MS, HPLC or UHPLC/MS/MS for the search, 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 suited to mineral or metallic contaminants or additives, such as heavy metals, mineral or metallic fillers, colorants…
- microscopy SEM-EDX, a true rapid and versatile diagnostic tool for assessing the material surface condition after aging, observing particles, deposits…
For the pharmaceutical sector, the FILAB laboratory follows the ICH Q3E guideline.
- Extractables & Leachables Analysis according to BPOG (Best Practices Operational Group)
- Identification of extractables according to USP <1663>
- Analysis of plastic material components according to USP <661.1>
- Analysis and verification of packaging: interactions with the drug according to USP <661.2>
- Analysis of process material leachables according to USP <665>
- Identification of extractables according to USP <1665>
Why choose FILAB for your USP 1664 analyses?
- COFRAC ISO 17025 accreditation and GMP environment
Guarantees technical competence, the traceability of our measurements, and the enforceability of our analytical results with French, European, and U.S. FDA regulatory authorities. - 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 files: 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.
Let's discuss your project
Do you need extractables & leachables studies?
Our related services
Heavy Metal Analysis and ICH Q3D Elemental Impurities
Analytical Validation according to USP 233 for the analysis of elemental impurities
Did you know?
The FILAB laboratory has been COFRAC ISO 17025 accredited for the following scope since 2015: Analysis and quantification of elemental impurities and minerals, 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
Ideally, no. USP 1663 provides the list of target compounds. Without this profile, it is difficult to demonstrate the completeness of leachable monitoring.
USP <1664> introduces an important distinction: leachables result from direct contact between the formulation and the primary or secondary packaging components. Migrants, on the other hand, are substances that pass through a physical barrier from secondary or tertiary packaging (for example, label ink migrating through a plastic bottle). Both must nevertheless be assessed with the same level of safety rigor.
Although it has been officially in force since December 2020 , USP <1664> is a chapter with a number above 1000, which means it provides recommendations and methodological frameworks. However, for regulatory authorities (such as the FDA), its application is often essential to demonstrate the safety of high-risk dosage forms such as inhalers (OINDP) or injectables.
To be considered valid, the study must demonstrate that the concentration of each potential leachable in the actual product will be less than or equal to the concentration found in the simulated extract. The chosen solvent must accurately simulate the extractive power of the actual formulation.
To obtain a quote, you can contact our teams via our contact form, by phone, or by email.
All you need to do is send us your requirements (material type, analysis requested, applicable standard, urgency, sample quantity, etc.). We will then send you a tailored technical and pricing proposal within 24-48 hours.
Lead times vary depending on the nature of the analysis and the complexity of the expert assessment project.
However, FILAB is committed to providing fast turnaround times adapted to your constraints and industrial urgencies.
