WuXi AppTec’s Chemical Characterization Capabilities: ISO 10993-1 & 10993-18
In accordance with ISO 10993-1:2018, every medical device must be evaluated and tested as part of a risk management strategy; and Chemical Characterization is the starting point. Chemical Characterization along with Toxicological Risk Assessment (ISO 10993-17) inform the biological test plan. All data is then combined into an expert-written weight of evidence argument known as the Biological Evaluation.
- In order to assess the risk of chemicals to patients for many products, Chemical Characterization will require analytical chemistry programs to identify and quantify the chemical constituents of the device. Typically, an extractables or exhaustive extractables study will include a range of analytical methods to uncover compounds that are organic, semi-volatile, non-volatile and volatile in nature. The most common analytical equipment used to gather this information includes:
Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) to identify elements and metals;
- Gas Chromatography-Mass Spectrometry (GC-MS) and Headspace Gas Chromatography-Mass Spectrometry (HS-GC-MS) to identify volatile and semi- volatile compounds;
- Liquid Chromatography- High Resolution Mass Spectrometry (LC-MS) to identify semi-volatile compounds to non-volatile compounds.
Identification of compounds is extremely important for a toxicologist to accurately assess risk. While identification using some analytical methods is relatively straight-forward, identification of compounds from LC-MS can be challenging, as no commercial databases exist. With today’s devices that include polymers and plastics, LC-MS is an analytical method that tends to yield more chemicals – what means the laboratories must tap into their experts to make the identification; a significant resource commitment. WuXi AppTec’s Chemical Characterization lab is the only lab committed to complete characterization as part of our standard service—a commitment we refer to as “Unknowns are Unacceptable.”
ISO 10993 Part 18
Designing an extractables/leachables study for your device requires an understanding of the materials and manufacturing process. Even commonly used materials can have different extractables/leachables results based on impurities and processing. Our team of chemists and toxicologists will meet with customers to develop an appropriate test plan that aligns with current regulatory expectations.
Analytical Equipment Commonly Used for Extractables/Leachables Studies Include:
- Inductively Coupled Plasma-Mass Spectrometry to identify elements and metals [ICPMS]
- Gas Chromatography-Mass Spectrometry and Headspace Gas Chromatography-Mass Spectrometry to identify volatile and semi-volatile compounds [GCMS & HS-GC-MS]
- Liquid Chromatography-High Resolution Mass Spectrometry, such as LCMS QToF, to identify semi-volatile compounds to non-volatile compounds [LCMS]
- Ion Chromatography (IC) is sometimes required for the evaluation of ionic contaminants
- Multiple analytical techniques aid in uncovering the full range of extracted chemicals associated with your product. Regulatory bodies are looking for this as part of the assessment of risk associated with your product.
- Full identification of the chemicals is required, and unknowns must be treated as worst-case scenarios. WuXi AppTec Medical Device Testing is the industry leader in identification, and our chemistry program was built knowing that chemistry data alone—without a toxicological risk assessment—is not enough to support product safety.
Full characterization of all chemicals is required for an accurate assessment of risk, and it is our goal to identify all of the potential chemicals that could come out of your product. Utilizing multiple analytical methods, our team of chemistry experts works tirelessly to understand your materials, process and product to detect a full range of organic, semi-volatile and volatile chemicals, providing you with the data you need to make informed decisions and meet current regulatory requirements.
Fourier Transform Infrared (FTIR) Scan
This test is a type of infrared spectroscopy in which the sample is subjected to all the wavelengths in the region of interest at all times, instead of only a small portion at a time.
Trace Metals – Elemental Analysis
This method is used to determine the presence of trace metals by atomic absorption spectroscopy.
This refers to absorption spectroscopy or reflectance spectroscopy in the ultraviolet-visible spectral region or light in the visible and adjacent ranges. The absorption or reflectance in the visible range directly affects the perceived color of the chemicals involved.
Particulate Matter Light Obscuration Method – Medical Device Extraction
This involves extraction of the medical device in water followed by analysis of subvisible particulates using a light obscuration particle counting method.
One of the major inorganic anions found in the environment, the chloride ion, in the form of a salt, is an integral component of many isotonic and physiological solutions.
Conductivity is a physical test that measures the ability of an aqueous solution to carry an electric current.
Glutaraldehyde is used as a liquid chemical sterilant in the medical device industry and in hospital environments.
This USP semi-quantitative test determines whether the total level of metallic impurities that react with the sulfide ion, under test conditions, exceeds the heavy metals limit specified in the individual USP monograph. Results are reported as weight percent (wt%) lead, based on color-comparison.
Moisture Determination – Karl Fischer
The Karl Fischer reaction uses a coulometric titration to determine the amount of water in a sample.
Osmotic pressure is fundamentally related to all biological processes that involve diffusion of solutes or transfer of fluids through membranes.
The pH value represents the acidity or alkalinity of an aqueous solution or suspension.
Physiochemical Tests – Plastics
These tests, designed to determine the physical and chemical properties of plastics and their extracts, are based on the aqueous extraction of the polymer.
Physicochemical Tests, USP Test Panel – Elastomeric Closures for Injections <381>
This series of tests is designed to provide information about the physical and chemical characteristics of elastomeric (rubber) closures.
The modified version of the classic Lowry protein assay is used to determine the amount of saline-extractable protein associated with products made from natural rubber (e.g., latex gloves).
Purified Water, USP
USP requirements for purified water include water conductivity and total organic carbon.
Total Organic Carbon
Total Organic Carbon (TOC) is a measure of the organic compounds (reported as carbon) present in water.
Total Dissolved Solids
Total Dissolved Solids (TDS) is a measure of the combined content of all inorganic and organic substances contained in a liquid, typically minerals and salts.
Total solids is the term applied to the material residue left in a vessel after evaporation of the sample and its subsequent drying in an oven at a specified temperature, usually between 103°C and 105°C.
This method is designed to measure the turbidity by comparing the intensity of light scattered by an aqueous sample with the intensity of light scattered by a standard reference suspension under the same conditions.
USP Chemistry Tests
Testing is based on each individual USP monograph.
Water for Injection, USP
USP requirements for water for injection include water conductivity and total organic carbon.
Absorbent Gauze, USP
According to current USP specifications, “absorbent gauze” is cotton or a mixture of cotton and rayon (not more than 53% by weight) that is in the form of a plain woven cloth conforming to the standards set forth in the monograph.
Flashpoint is used to determine the temperature at which a liquid or volatile solid gives off vapor sufficient to form an ignitable mixture with the air just above the surface of the sample within the test vessel.
The melting point of a chemical is the temperature at which a substance changes physical state from a solid to a liquid at normal atmospheric pressure.
Moisture – Residual
This is a gravimetric method for determination of water.
Calcium – Residual
This method is used to determine the residual calcium of demineralized bone and other tissue-based products.
The refractive index of various liquids is measured using a Reichert AR200 digital refractometer.
Residue on Ignition
This test determines the total mineral content of a sample or extract when ignited to 800°C in a muffle furnace.
Specific gravity is the ratio of the density of a substance to the density of a referenced substance.
Viscosity is the internal resistance to flow exhibited by a liquid.
- HPLC-DAD and RI, size exclusion
- HS-GC-FID/MS and DI-GC-FID/MS
- Direct Inject GCMS
- Microscope FTIR
- Dynamic Light Scattering
- Particle Count