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Quantification of Extractable Residue by Gravimetric Analysis

Quantification of Extractable Residue by Gravimetric Analysis

The Quantification of Extractable Residue by Gravimetric Analysis test evaluates manufacturing and cleaning residues, such as oils, lubricants and detergents, found on newly manufactured medical devices and/or single use implants. It’s important to assess these surface residues in order to minimize potential adverse biological responses to surface contamination and extractable residue. 

This test complies with the ASTM F2459 Standard Test Method for Extracting Residue from Metallic Medical Components and Quantifying via Gravimetric Analysis. Nelson Laboratories participated on the ASTM committee that developed the standard for this test method.

For more information on the gravimetric test options please see our supplemental test guide

Please see the Study Outline for Test Option guidance. A recommended gravimetric package could include RMM301, RMM304, RMM306, and RMM309.

Applicable Standards

  • ASTM F2459

Test Options

Standard turn around times (TAT) are listed below. Ask an expert for a specific consultation on your product. If you are ready to submit your samples for testing, click here to fill out the Sample Submission Form.

For more information on the gravimetric test options please see our supplemental test guide.

Code Test TAT (days) Request Quote
RMM300 Gravimetric Quantitation no FTIR (polar extraction standard test) ASTM F2459 14 Add
RMM301 Gravimetric Quantitation w/ Microscope FTIR (polar extraction standard test) ASTM F2459 18 Add
RMM302 Gravimetric Quantitation w/ ATR FTIR (polar extraction standard test) ASTM F2459 18 Add
RMM303 Gravimetric Quantitation w/soluble/insoluble determination (polar extraction standard) ASTM F2459 19 Add
RMM304 Gravimetric Quantitation Extraction Efficiency (polar extraction) ASTM F2459 14 Add
RMM305 Gravimetric Quantitation no FTIR (nonpolar extraction (not hexane) standard test) ASTM F2459 14 Add
RMM306 Gravimetric Quantitation w/ Microscope FTIR (nonpolar extraction (not hexane) standard) ASTM F2459 18 Add
RMM307 Gravimetric Quantitation w/ATR FTIR (nonpolar extraction (not hexane) standard test) ASTM F2459 18 Add
RMM308 Gravimetric Quant. w/soluble/insoluble determination (nonpolar extraction (not hexane) standard) 19 Add
RMM309 Gravimetric Quantitation Extraction Efficiency (nonpolar extraction, not hexane) ASTM F2459 14 Add
RMM310 Gravimetric Quantitation no FTIR (hexane extraction standard test) ASTM F2459 21 Add
RMM311 Gravimetric Quantitation w/ Microscope FTIR (hexane extraction standard test) ASTM F2459 25 Add
RMM312 Gravimetric Quantitation w/ATR FTIR (hexane extraction standard test) ASTM F2459 25 Add
RMM313 Gravimetric Quantitation w/soluble/insoluble determination (hexane extraction standard) ASTM F2459 26 Add
RMM314 Gravimetric Quantitation Extraction Efficiency (hexane extraction) ASTM F2459 21 Add
RMM300 - Gravimetric Quantitation no FTIR (polar extraction standard test) ASTM F2459
TAT: 14 days
RMM301 - Gravimetric Quantitation w/ Microscope FTIR (polar extraction standard test) ASTM F2459
TAT: 18 days
RMM302 - Gravimetric Quantitation w/ ATR FTIR (polar extraction standard test) ASTM F2459
TAT: 18 days
RMM303 - Gravimetric Quantitation w/soluble/insoluble determination (polar extraction standard) ASTM F2459
TAT: 19 days
RMM304 - Gravimetric Quantitation Extraction Efficiency (polar extraction) ASTM F2459
TAT: 14 days
RMM305 - Gravimetric Quantitation no FTIR (nonpolar extraction (not hexane) standard test) ASTM F2459
TAT: 14 days
RMM306 - Gravimetric Quantitation w/ Microscope FTIR (nonpolar extraction (not hexane) standard) ASTM F2459
TAT: 18 days
RMM307 - Gravimetric Quantitation w/ATR FTIR (nonpolar extraction (not hexane) standard test) ASTM F2459
TAT: 18 days
RMM308 - Gravimetric Quant. w/soluble/insoluble determination (nonpolar extraction (not hexane) standard)
TAT: 19 days
RMM309 - Gravimetric Quantitation Extraction Efficiency (nonpolar extraction, not hexane) ASTM F2459
TAT: 14 days
RMM310 - Gravimetric Quantitation no FTIR (hexane extraction standard test) ASTM F2459
TAT: 21 days
RMM311 - Gravimetric Quantitation w/ Microscope FTIR (hexane extraction standard test) ASTM F2459
TAT: 25 days
RMM312 - Gravimetric Quantitation w/ATR FTIR (hexane extraction standard test) ASTM F2459
TAT: 25 days
RMM313 - Gravimetric Quantitation w/soluble/insoluble determination (hexane extraction standard) ASTM F2459
TAT: 26 days
RMM314 - Gravimetric Quantitation Extraction Efficiency (hexane extraction) ASTM F2459
TAT: 21 days

Sample Specifications

At least one sample set per solvent type (samples may be pooled or tested individually). It is recommended that 20 cm2 or more be provided per sample. Testing multiple lots or cleaning batches to include repeatability in a cleanliness validation is also encouraged.

Study Outline

This test method is used to detect and quantify extractable residual manufacturing materials on medical devices. The residues are extracted from the devices in an appropriate solvent using sonication. The extract is evaporated to determine the extractable residue.

Extraction Solvent: The extraction solvent is chosen based on the solubility of the target residue(s) and the characteristics of the device material(s). Several solvents may be required if more than one type of residue may be present on the device(s). Expected contaminants should be categorized by solubility. A polar or purified water extraction should be chosen to quantify polar or water-soluble contaminants, such as detergents. Nonpolar or non-water-soluble contaminants require nonpolar extraction solvent options. Examples of possible solvents include chloroform, methylene chloride, hexane and 2-propanol.
After the gravimetric analysis the residue can then be qualified by infrared spectroscopy (FTIR) or the residue amount can be separated into soluble and insoluble residue.

FTIR Qualification of Residue:  Nelson Labs offers two FTIR options: ATR and Microscope. If enough residue is obtained from the gravimetric analysis (approximately 1 mg or more) then the ATR FTIR can be used. However, it is recommended the Microscope FTIR be planned for in case smaller residue amounts are obtained. Both FTIR options provide qualitative information on the residue. As noted on the gravimetric test guide this may be omitted; however, we recommend FTIR analysis to aide in the identification of organic compounds present in the extracted residue. It is particularly helpful as an investigative tool for unexpectedly high residue results.

Soluble/Insoluble Determination: The residue obtained from the gravimetric test can be filtered to separate the portion of residue that is soluble in the extraction solvent used.  If this filtration is included two residue mass results would be produced and reported.  For example, after extraction in USP purified water the residue obtained from a device with both detergent and metallic particulates could be filtered to separate the mass of the particles from the mass of the detergent (soluble in water) residue.
  
Extraction Efficiency: In order to meet the criteria specified in ASTM F2459, the extraction parameters must be adjusted in order to achieve an extraction efficiency of greater than 75%. There are two techniques which can be used to determine extraction efficiency: exhaustive extraction and spike recovery.

Exhaustive Extraction: The exhaustive extraction technique uses positive controls which contain an unknown level of contamination. The positive controls are normally created by exposing devices to the regular manufacturing processes but then not subjecting them to the cleaning process being validated. These are “real-life” positive controls. Exhaustive extraction positive controls should be extracted until no significant increase in the cumulative residue level is detected upon re-extraction, or until the amount extracted is less than 10% of what was detected in the first extraction.

Spike Recovery Extraction: The spike recovery technique uses positive controls which contain a known level of contamination. The positive controls are created at Nelson Laboratories using clean devices which are spiked with a known amount of the target residue(s). The sponsor must provide samples of the target residue(s). Spike recovery positive controls only need to be extracted once.

For more information on the gravimetric test options please see our supplemental test guide.

Limits for the target residue(s) may be established based on the recovery level or reduction comparison when comparing clean devices and positive controls. The sponsor is responsible for preparing specific risk assessment and justifications to ensure that regulatory reviewers can determine the rationale for a test plan and any established limits for residue levels.
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