Material selection and risk analysis are integral components of the design process for medical devices. The international standards revision for the medical device biological evaluation within the risk assessment process (ISO 10993-1) states that the description of the chemical components of direct and indirect contact medical devices and the consideration of material characterization, including chemical characterization, must precede any biological test (ISO 10993-18).

Chemical characterization with an appropriate toxicological threshold may be used to determine whether further testing is required (ISO 10993-17 and ISO 10993-18). Based on the proposed revisions, chemical characterization of a medical device provides the necessary input into the device’s biological evaluation and toxicological risk assessment.

Chemical Characterization

• Determine the chemical composition of the Medical Devices
• Extractables and leachables studies ISO 10993-17 and ISO 10993-18
  The interaction between both primary and secondary containers and the drug may affect the composition of the latter, thus adversely impacting its ability to produce the expected clinical outcome, or its safeness. Extractables and Leachables studies (link alla pagina nuova) provide a full integrated testing strategy together with toxicological assessment and risk analysis:
  • profiling of extractables
  • characterization of extractables
  • research of organic compounds using TOC, HPLC-UV/DAD, HPLC-ELSD, LC-MS/MS, LC-Q/Orbitrap and GC-MS
  • research of elemental impurities using AA, ICP-OES or ICP-MS
  • development and validation of methods suitable for the quantification of specific leachables present in the drug matrix, based on the extractables studies
• Structural composition or configuration of the Medical Device material evaluation:
  • Synthetic polymer ISO 10993-13
  • Metals and alloys ISO 10993-15
  • Ceramics ISO 10993-14
  • Natural macromolecules

Analytical techniques

• FT-IR
• ICP-OES / ICP-MS
• GC-FID
• GC-MS/HRMS
• GPC/SEC
• LC-MS/HRMS
• LC-UV/ELSD/RID
• MALDI-TOF/TOF
• Microscopy
• SEM-EDS / TEM-EDS
• IC-PAD/EC
• XRF

EXTRACTABLES & LEACHABLES STUDIES FOR MEDICAL DEVICES

Chemical characterization is the process of “obtaining chemical information about a medical device, relevant to their biological evaluation and any toxicological risk assessment”. Extractables and leachables studies take then a central role in the technical dossier that eventually allows medical devices to be released on the market, by serving as the basis for a toxicological risk assessment, and also by sometimes reducing the need for further tests (including animal testing).

• Extractables: substances that are released from a medical device or material of construction when the medical device or material is extracted using laboratory extraction conditions and vehicles.
• Leachables: substances that are released from a medical device and to a potentially affected individual during its clinical use.

Extractables & Leachables guidelines

• ISO 10993 – Biological evaluation of medical devices. Part 1: Evaluation and testing within a risk management process (2018)
• ISO 10993 – Biological evaluation of medical devices. Part 17: Toxicological risk assessment of medical device constituents (2002, now under revision)
• ISO 10993 – Biological evaluation of medical devices. Part 18: Chemical characterization of materials (2018)

Extractables & Leachables analytical methods

Extractables and Leachables studies provide a full-integrated testing strategy together with toxicological assessment and risk analysis, in six main steps:

1. Profiling of extractables: generation of the extract.

2. Characterization of extractables:

a. Screening research of VOC, SVOC and NVOC using different techniques (e.g. TOC, HS-GC/MS, GC-MS, GC-HRMS, HPLC-UV/DAD, LC-MS/MS, LC-HRMS)

b. Targeted analysis of elemental impurities and anions using different techniques (e.g. AAS, ICP-MS, IC)

c. Targeted analysis for specific compounds of toxicological concern, using dedicated methods that focus on monomers, additives and extractables typical of the material considered (more than 150 targeted methods available)

d. Extractable nanoparticles (link a https://www.merieuxnutrisciences.com/all-news/nanomaterials-identification-characterization) and microplastics (link a https://www.merieuxnutrisciences.com/content/microplastics) identification

3. Primary and secondary leachables profile.

4. Unknown extractables/leachables tentative identification by HRMS techniques (if needed).

5. Toxicological evaluation and risk assessment.

6. Development and validation of targeted methods suitable for the quantification of critical leachables.

Our instruments

• • HPLC-UV/DAD, HPLC-ELSD, IC
• • LC-MS/MS, LC-HRMS Q/Orbitrap
• • HS-GC, HS-GC/MS, GC/FID, GC-MS, GC-HRMS Q/Orbitrap
• • ICP-OES, ICP-MS, AAS
• • MALDI-TOF
• • TOC
• • SEM/EDS, TEM/EDS