Extractables & Leachables
The selection and qualification of a container for a pharmaceutical product includes extractables & leachables testing as per international regulations.
Volatile, semi-volatile, and non-volatile compounds are analyzed to ensure the safety of the drug. Especially when using packaging systems like syringes, that are built of different components and materials, a detailed E&L data-set is mandatory. We offer to organize and conduct your extractables & leachables studies tailored to your needs.
System Performance
In order to meet clients’ needs and the requirements of regulatory agencies, we have developed specialized tests for thorough characterization of pharmaceutical packaging. We can can provide pharmacopeia (US/EP/JP) and industry standard (ISO, DIN, ASTM) methods. Container closure integrity, functionality testing, analysis of tungsten levels, and free and total silicone oil quantification are among the most popular tests we carry out. Herewith we support our customers to better understand the performance of their pharmaceutical container systems.
Extractables Study
Customer oriented extractables studies for determination of inorganic (including cations and anions) and organic substances extracted out of primary packaging materials. These substances are potentially hazardous directly or after interaction with the drug formulation.
Typical stoppers used as primary packaging material Extraction of container closures
Leachables Study
Determination of leachables and cross reaction products after storage in different containers under standard conditions. All analyses are performed with state-of-the-art equipment.
Chromatogram of leachables testing with an antioxidant in different oxidation states
Accelerated Leachables Study
Determination of leachables after storage under accelerated conditions. First information about leachables after a few weeks compared to stability storage times of up to 36 months.
Storage under accelerating conditions (e.g. higher temperature)
Inspection of stored containers
Secondary Packaging Material
Long-term storage or accelerated storage of containers in combination with secondary packaging material. Determination of volatile organic contamination.
Vials with different meniscus, but same filling volume causing problems in inspection sytem
Chromatogram of an extract from a vial with bad wetting behaviour
Functionality Testing
To meet regulatory requirements and customer needs, we have specific testing methods in place. Container closure integrity, permeability, leakage, dye ingress, axial compression, and functionality tests including breakaway and gliding forces, tip cap removal, tip cap leakage, needle penetration, or pull force tests are performed on a routine basis.
Fluorescent dye is used to verify container closure integrity during dye ingress testing
The functionality of the syringe system is tested with respect to breakaway and gliding forces, for example.
Tungsten Analysis
Tungsten residues in syringes are a major concern for biotech products. In order to assess potential risks we offer both comprehensive characterization of tungsten contamination and provide spiking solutions to test the actual effect on the drug product.
The tungsten concentration, composition, solubility in water or buffer, and exact location of particles in the syringe are types of analysis performed prior and after storage. For spiking studies, tungsten extracts are tailor-made with the actual formulation. The extracts can either be made of the tungsten pin or the actual tungsten contamination in the syringe.
Tungsten particles in needle channel by stereo microscopy.
Tungsten particles in needle channel by SEM (scanning electron microscopy).
Siliconization Testing
For the functionality and safety of the drug delivery system over the whole shelf life, it is critical to control the silicone oil distribution and the amount of silicone, especially free silicone.
For mapping the thickness distribution of the silicone oil layer in syringes and other pharmaceutical glass or plastic containers, we use a reflectrometry system. Free silicone (i.e. small silicone oil droplets detachable from the silicone layer) is seen as a potential trigger for protein aggregation. Wet chemical methods to quantify the amount of free silicone have been established. The total amount of silicone is determined by soxhlet extraction and spectroscopy.
During drug development, our analytical expertise in the determination of silicone distribution and free silicone helps you to ensure the drug stability and the functionality of the drug delivery system.
Adequately distributed silicone oil
Inadequately distributed silicone oil
