Extractable & leachable testing

During the development process of drug products or medical devices, it is important to evaluate the potential for various chemicals to migrate from container closure systems, manufacturing components or delivery devices into pharmaceuticals or biologics, from the components of a medical device into the solutions under administration, or to the blood stream or tissue at the point of contact.

Regulatory agencies require extractables and leachables (E&L) testing for medical devices and pharmaceutical drug products:

• To identify the safety risk posed to the patients from exposure to the leachables
• To identify any risk of product adulteration
• To identify toxic or harmful materials in the medical devices

We at Eurofins BioPharma Product Testing offer a broad range of services to support extractables and leachables testing for pharmaceutical drug products, single-use manufacturing components, container closure systems, delivery devices, chemical characterisation studies for medical devices and label migration studies.

Our approach

Our extractable and leachable studies can be designed per guidance’s such as USP <1663> and <1664>, as well as ISO 10993, PQRI, BPSA and BPOG documents. We design studies to meet the expectations of FDA’s CDER/ CBER/CDRH, EMEA, and other regulatory bodies.

Extraction test techniques

• Reflux
• Soxhlet
• Sonication
• Microwave
• Incubation in controlled temperature conditions (with agitation or recirculation if needed)

Analysis techniques

We have established the following semi-quantitative screening methodology to analyse extraction solutions by LC/MS/MS, GC/MS/MS and ICP/MS. If needed, quantitative methods can be developed for specific compounds.

Semi-quantitative screening for both volatile and semi-volatile organic compounds

• Use of GC/MS instrumentation with direct injection sample introduction and electron impact ionisation.
• Use of GC/MS instrumentation with headspace sample introduction and electron impact ionisation.
• For extractables compounds detected by GC/MS analysis, we utilise up-to-date Wiley/NIST databases to assist in identification.

Semi-quantitative screening for non-volatile organic compounds

• Analysis using LC/MS/MS (in positive and negative mode using electrospray and atmospheric pressure chemical ionisation), and LC/UV.

Semi-quantitative analysis for metals

• Evaluation of samples for elemental extractables, including all those listed in USP <232> and ICH Q3D using ICP/MS.
• Gravimetric determination of extractables
• Ion Chromatography for Ionic leachables.

Instrumentation

• Shimadzu LC/MS/MS 8060 & 8045
• Shimadzu GC/MS/MS – with headspace, direct injection
• Shimadzu GC/FID – both headspace and direct injection sample introduction
• Perkin elmer ICP/MS
• Thermo Scientific IC – 6000
• Waters HPLC- including UV/Vis, RI, PDA

Why choose Eurofins BioPharma Product Testing?

• We work with our clients to design a study that provides them with meaningful extractables data.
• We can assist you with conducting a risk assessment of your product configuration or manufacturing chain.
• We have the expertise to recommend testing options that are up to current industry standards and will meet regulatory expectations.
• We have the ability to write GMP-compliant protocols to direct extractables and leachables testing and to define conditions for stability studies for leachable studies.
• Our extractables studies include a customisable report detailing the results of the study, including system suitability results, sample chromatograms, and result tables.
• We offer toxicological evaluations on extractables and leachables data.
• Our E&L methods have been qualified in order to ensure accurate results and meet regulatory expectations.