Extractables and leachables (E&L) testing is essential to ensure the safety and compatibility of pharmaceutical packaging and delivery systems. According to USP <1663>, extractables studies are performed under exaggerated conditions to identify compounds that could potentially migrate into drug products. Below, we explore the different types of materials tested and the conditions applied to simulate worst-case scenarios.
The materials tested are categorized based on their proximity to the drug product and their functional role in the packaging system.
These come into direct contact with the drug and are the highest priority in testing.
These materials do not touch the drug product directly but may pose a risk through indirect interaction (e.g., vapor migration).
Includes materials from inhalers, injectors, and ophthalmic applicators, where frequent or direct patient exposure is possible.
Materials that contact the drug during manufacturing are tested when there’s potential carryover into the final product.
Packaging for sensitive dosage forms like injectables or inhalables undergo additional scrutiny.
USP <1663> recommends using aggressive conditions that simulate or exaggerate the real-world scenarios to release as many potential extractables as possible.
A range of solvents is used to target compounds of various chemical properties:
| Solvent Type | Example | Purpose |
|---|---|---|
| Polar | Water, saline | Extracts hydrophilic compounds |
| Semi-polar | 50% ethanol-water, isopropanol | Extracts alcohol-soluble organics |
| Non-polar | Hexane, heptane | Extracts hydrophobic and oily residues |
| Acidic | 0.1 N HCl | Releases acid-sensitive compounds |
| Basic | 0.1 N NaOH | Targets base-sensitive leachables |
| Surfactant-based | Polysorbate 80, SDS | Extracts silicone oils, surfactants |
This ratio determines the amount of packaging material exposed to the solvent:
To enhance solvent-material interaction:
Applied as needed based on product type:
Understanding the types of materials and testing conditions outlined in USP <1663> is critical for designing an effective extractables study. By applying exaggerated solvent conditions, temperatures, and durations, scientists can identify potential leachables early and prevent safety risks in the final drug product.
In a future blog, we’ll discuss how the results of extractables testing under USP <1663> are used to design leachables studies according to USP <1664>, including the application of the Analytical Evaluation Threshold (AET).
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