Biocompatibility Chemical Characterization

Chemical Characterization & ISO 10993-18

Analytical procedures provide the initial means for investigating the biocompatibility of medical device materials. Knowledge of device materials and their propensity for releasing leachable matter will help manufacturers assess the risks of in vivo reactivity and preclude subsequent toxicology problems with finished devices.

Increasingly, FDA has been asking for analytical characterization of device materials and potential leachables per ISO 10993-17 and ISO 10993-18 testing.  Many firms also use analytical procedures for routine QC of raw materials or finished products.

The degree of chemical characterization required should reflect the nature and duration of the clinical exposure and should be determined be based on the data necessary to evaluate the biological safety of the device. It will also depend on the nature of the materials used, e.g. liquids, gels, polymers, metals, ceramics, composites or biologically sourced material.

Chemical Characterization Strategy

The following strategy is suggested as a sound program for chemical characterization of a device material:

  • Determine the qualitative composition of each device component or material. This information should be available from the material vendor, or it can be determined through laboratory testing. The list of constituents should include
    • the identity of the matrix (i.e. the major component such as the specific polymer, alloy, or metal)
    • all plasticizers, colorants, anti-oxidants, fillers, etc. deliberately added during fabrication of the material
    • impurities such as unreacted monomers and oligomers
    • manufacturing materials such as solvent residues, slip agents, and lubricants.
  • Estimate the potential for patient exposure for each item on the material constituent list. Use literature searches of toxicological databases to assess the likelihood of tissue reactivity. For potentially toxic constituents, design and conduct laboratory studies to determine the extractable levels of those constituents. Use exaggerated conditions of time and temperature, and consider appropriate detection limits. Additional studies may be needed to assess levels of extractables released in actual use conditions.
  • Data generated from this characterization process can be used to create a material data file. The information can then be used as a reference for continued testing of device materials to ensure consistency of future production lots. This may in turn reduce the need for routine biological testing.

Additional uses of analytical characterization data might include:

  • Use in an assessment of the overall biological safety of a medical device.
  • Measurement of the level of any leachable substance in a medical device in order to allow the assessment of compliance with the allowable limit derived for that substance from health based risk assessment.
  • Judging equivalence of a proposed material to a clinically established material.
  • Judging equivalence of a final device to a prototype device to check the relevance of data on the latter to be used to support the assessment of the former.
  • Screening of potential new materials for suitability in a medical device for a proposed clinical application.

Traditional Extractable Material Characterization

  • USP Physicochemical Tests – Plastics
  • USP Physicochemical Test Panel for Elastomeric Closures for Injections
  • USP Polyethylene Containers Tests – Heavy Metals and Non-volatile Residues
  • Indirect Food Additives and Polymers Extractables (21CFR Part 177)
  • Sterilant Residues – Ethylene Oxide, Ethylene Chlorohydrin, Ethylene Glycol

Tests Procedures For Extractable Material

  • UV/Visible Spectroscopy
  • Gas Chromatography
  • Liquid Chromatography
  • Infrared Spectroscopy (IR)
  • Mass Spectrometry
  • Residual Solvents
  • Atomic Absorption Spectroscopy (AAS)
  • Inductively-coupled Plasma Spectroscopy (ICP)

Bulk Material Characterization

  • Infrared Spectroscopy Analysis for Identity and Estimation of Gross Composition
    • Reflectance Spectroscopy
    • Transmission Spectroscopy
  • Atomic Absorption Spectroscopy (AAS)
  • Inductively-coupled Plasma Spectroscopy (ICP)
  • Thermal Analysis

Surface Characterization

  • IR Reflectance Spectroscopy
  • Scanning Electron Microscopy (SEM)


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