Chemical Characterization - Agina

INTRODUCTION
Chemical characterization is a crucial part of medical device biocompatibility assessment,

identifying and quantifying constituent chemicals to identify potentially unsafe levels. It
doesn't involve animal testing, making it cost-effective and ethically sound. It's also used
during product development to evaluate alternative material compositions, making the
process more efficient and reducing regulatory approval delays.
Individual standards in the ISO 10993 series that specifically apply to the
chemical characterization process include:
 ISO 10993-12: “Biological evaluation of medical devices – Part 12: Sample

preparation and reference materials,” specifies requirements for the selection of
reference materials and the preparation of samples for biological and chemical
characterization testing.
 ISO 10993-17: “Biological evaluation of medical devices – Part 17: Establishment of
allowable limits for leachable substances,” details the process for determining
allowing limits for substances leachable from medical devices in cases where such
limits do not exist.
 ISO 10993-18: “Biological evaluation of medical devices – Part 18: Chemical
characterization of medical device materials within a risk management process,”
provides a framework for identifying and quantifying material composition of a
medical device, including chemicals and other ingredients.
ISO 10993-18
ISO 10993-18 is a standard that outlines the process for conducting chemical
characterization of a medical device to ensure its overall biological safety. The goal is to
provide detailed information on the materials used, chemical constituents, and potential
chemical release. The characterization procedure includes establishing the device's
configuration and material composition, assessing material equivalence to a clinically
established material or medical device, assessing the hypothetical worst-case chemical
release based on total exposure, establishing an analytical evaluation threshold, estimating
the chemical release, performing an extraction study, assessing the estimated chemical
release, determining the actual chemical release, and performing a leachables study. The
standard also outlines the analytical evaluation threshold (AET) for the device, which is
calculated and verified in Annex.
New version- 10993-18:2020
The chemical characterization process can be approached through three methods:

compositional evaluation, extractables evaluation, and leachables evaluation, with
compositional evaluation being most efficient for indirect contact devices.
The chemical characterization process includes several steps:
o Identifying the materials of construction (medical device configuration).

o Characterizing the materials by identifying and quantifying their chemical
constituents (material composition).
o Assessing chemical substances introduced during manufacturing (e.g., mold
release agents, process contaminants, sterilization residues).
o Estimating the potential of the medical device or its materials to release
chemical substances under clinical use conditions (extractables).
o Measuring chemical substances released from the medical device during
clinical use (leachables).
o Additionally, it can be used for the chemical characterization of degradation
products.
The ISO 10993 series applies when the material or medical device has direct or indirect
body contact.
Compositional approach
The document describes device configuration, material composition, and other factors,
including patient exposure and material use history. It assesses risk through a tox
assessment and a broad biological evaluation.
Considerations
Composition information always needed, and may be sufficient • Materials with extensive
clinical use history • Well understood materials (e.g., ASTM Nitinol vascular stents) •
Devices/materials with short or non-invasive contact (e.g., ureteral dilator, bandages
Chemical analysis is necessary in certain situations, such as identifying a constituent of

concern, insufficient formulation and processing information, detecting safety signals from
biological testing, or as a substitute for biological testing.
Extractables and Leachables
Leachable – a chemical substance that is released from a device during its clinical use
Extractable – substance that is released from a medical device or material of construction
when the medical device or material is extracted using laboratory extraction conditions and
vehicles.
• These align with long established definitions in E&L community

• Leachables are most relevant, but often pose challenges
• Difficult to acquire sample (e.g., leachables in patient tissue/fluid)
• Difficult to analyze sample (e.g., interference of biological matrix) + May be most
practical for indirect contact devices (like drug container)
• NB: Simulated use extractions often incorrectly called leachables studies
Extraction Considerations
• Consider ISO 10993-12, but don’t be constrained by it
• For example, samples may need to be diluted or concentrated
• Regulators generally expect both polar and non-polar extraction vehicles, where possible
• In addition to polar and non-polar extraction vehicles, use of a 3rd, semi-polar vehicle
expected for long term contact (e.g., implants)
• If a non-polar solvent degrades material(s), use a less non-polar solvent.

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INTRODUCTION

Chemical characterization is a crucial part of medical device biocompatibility assessment,

 ISO 10993-12: “Biological evaluation of medical devices – Part 12: Sample

New version- 10993-18:2020

The chemical characterization process can be approached through three methods:

The chemical characterization process includes several steps:

o Identifying the materials of construction (medical device configuration).

Chemical analysis is necessary in certain situations, such as identifying a constituent of

Extractables and Leachables

• These align with long established definitions in E&L community

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