Journal of ASTM International, February 2006, Vol. 3, No. 2
Paper ID JAI13391
Available online at www.astm.org
Daniel Zurbrügg1
Cleanliness Testing and Identification of Residues on
Polymer Medical Devices
ABSTRACT: Machining and cleaning are key processes in the manufacturing of metal, ceramic, and
polymer medical devices. During these processes, the components and final devices are exposed to
processing aids, handling equipment, cleaning agents, and packaging materials. Methods for the cleanliness testing of such potential residues are discussed in this paper. To assess the effectiveness of the total
organic carbon 共TOC兲 analysis for cleanliness testing, the recovery of organic residues was studied. Spiking tests showed that nonpolar hydrocarbons are not well extracted, neither by 1 h ultrasonication nor by
24 h refluxing in boiling water. This results in a very poor TOC recovery for mineral oil-like residues. Good
recovery and a high sensitivity for such residues are obtained by solvent extraction following Fourier
transform infrared spectroscopy 共FTIR兲 analysis. Furthermore, extracted organic residues from machined
polymer devices were identified by gas chromatography mass spectrometry 共GC-MS兲. The results indicate
that nonpolar polymers like ultra-high molecular weight polyethylene 共UHMWPE兲 absorb hydrocarbons
from mineral oil-based processing aids during machining.
KEYWORDS: cleanliness, medical devices, polymers, TOC, FTIR, GC-MS
Introduction
Manufacturers of medical devices are continuously improving their products to increase the safety for
patients. Thereby not only the functionality is improved but also the production processes are optimized.
Key processes in the manufacturing of metal, ceramic, and polymer medical components and devices are
machining, cleaning, and packaging. During these processes, the devices are exposed to processing aids
such as lubricants, handling equipment, cleaning agents, and packaging materials.
According to legal regulations and guidelines of regulatory bodies 关1–3兴, the cleaning process of
medical devices has to be validated by the manufacturer. Furthermore, the cleaning of the final devices has
to be monitored. Additional cleanliness testing is suggested before critical production steps such as coating
of components. The presence of even small amounts of surface residues can physically impair and reduce
coating adhesion on a component. In general, quality control is important for any manufacturing company
to reduce failure costs. For the long-term success of medical companies cleanliness control and assurance
of selling clean devices are key factors.
Since the U.S. Food and Drug Administration 共FDA兲 does not intend to set residual limits on medical
devices 关2兴, it is the manufacturer’s responsibility to specify an acceptable level of cleanliness. Thus the
question of appropriate test methods and tolerable amounts of residues often remain unanswered. To help
answer these questions, the ASTM subcommittee 共F04.15.17兲 has been focusing on these issues. Its first
aim is the development of a standard for the testing of residues from metallic medical components 关4兴.
Since polymers are getting more and more important, the following paper will focus on the quantification
and identification of potential contaminants on polymer medical devices.
Evaluation of Methods for Cleanliness Testing of Polymer Medical Devices
There are many different techniques and methods for the cleanliness testing of medical devices. While the
testing of microbial contaminants is well established and standardized, testing of nonmicrobial residues
Manuscript received May 23, 2005; accepted for publication September 28, 2005; published online January 2006. Presented at
ASTM Symposium on Cleanliness of Implants on 18 May 2005 in Reno, NV; S. H. Spiegelberg, J. E. Lemons, and
R. A. Gsell, Guest Editors.
1
Chemist, Niutec Inc., PO Box 65, CH-8404 Winterthur, Switzerland, [email protected]
Copyright © 2006 by ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959.
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has not developed to this stage yet. Each manufacturer has its own strategy and methods to assure the
cleanliness of its products. These strategies are often based on their historical clinical results. Due to the
fast changing of manufacturing processes and the development of more complex geometries, surface
structures and coatings, the assurance should not rely only on historical experience. The advances of
analytical techniques allow detecting residues from the manufacturing at levels low enough to assure the
cleanliness. To evaluate appropriate cleanliness test methods for polymers the following factors have to be
considered:
• Detectability of potential residues
• Limit of detection must be below specified cleanliness limits
• Ability to capture a broad range of different residues
• Compatibility of test method and extraction media with the polymer
• Robustness of the test method
• Sample throughput
• Infrastructure and equipment
• Assistant skills and operating costs
The ability to detect potential contaminants at low enough levels is essential. Test results are useless if
the detection limit of a method is above acceptable limits or the recovery is not sufficient. Therefore the
application range of a method has to be assessed critically.
Table 1 gives an overview of some important techniques which will be discussed in terms of their
advantages and disadvantages for polymer testing. Methods follow either a direct or an indirect approach.
Direct methods detect the residue directly on the surface while indirect methods require the residues to be
extracted before the analysis.
Direct Test Methods
In general, direct surface analysis methods can be used for testing metal as well as polymer components.
These methods have the advantage that residues need not be removed from the surface before analysis.
Particles, spots of residues, or very thin films can be examined and identified directly on the surface.
Surface methods like, e.g., scanning electron microscopy with energy dispersive X-ray 共SEM/EDX兲,
measuring the elemental composition of residues, are very powerful to throw light on the source of
contamination. Time-of-flight secondary ion mass spectrometry 共TOF-SIMS兲 is another highly sophisticated technique which provides high spatial resolution and molecular information to characterize ultratraces. But direct methods have limitations in terms of quantifying total residues on complex surfaces.
Residues are usually not homogeneously distributed on the surface. Consequently, the examination of a
small surface area won’t be representative for the whole device. Micromethods like, e.g., SEM or TOFSIMS, which only capture a low percentage of the device surface are less suitable for the cleanliness
control of the whole medical device. Porous surfaces and deep holes are further limiting factors for surface
analysis. After all, residues mostly remain in those pores and holes of a devices, which often can’t be
reached by direct methods. Nevertheless, visual examination of devices as a basic cleanliness control is
very helpful since a large surface can be controlled and larger contamination can be rapidly detected.
Indirect Test Methods
Indirect testing and analysis are mostly done after extracting the residues from the devices. The residues
are either dissolved or suspended in water, aqueous solution, or an organic solvent. Exceptions are volatile
organics or absorbed gases like ethylene oxide 共EO兲, which can be measured after thermal evaporation by
a headspace sampling technique.
The advantage of indirect methods compared to the direct methods is that the detection is not limited
by complex geometries or porous surfaces. With indirect methods, the sample is completely immersed or
rinsed. This also allows one to capture the critical residues in deep pores. Furthermore, it has to be
considered that the physiochemical properties of polymers allow certain residues to diffuse into the material. This is different from metals or ceramics where residues only remain on the surface. In particular,
organic solvents and nonpolar residues may diffuse into the polymers. Indirect testing methods also allow
the testing of absorbed and diffused residues.
A disadvantage of indirect methods is the need for the potential residues to be extractable and detectCopyright by ASTM Int'l (all rights reserved);
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ZURBRÜGG ON POLYMERS 3
TABLE 1—Analysis techniques for cleanliness control of metal and polymer medical devices.
Techniques
Surface Analysis
Visual examination
Extraction
Media
none
Detected Residues
Visible organic and inorganic
particles, spots ⬎20 ␮m
Visible organic and inorganic
particles, spots ⬎1 ␮m
Organics and inorganics,
particles ⬎10 ␮m
共e.g., debris from package兲
SEM: spots ⬎5 nm
EDX: particles, spots ⬎1 ␮m
Light microscopy
共1000:1兲
FTIR
none
SEM/EDX
none
TOF-SIMS
none
Inorganic and organic
molecular spots ⬎0.01 ␮m
e.g., water,
acids, bases
e.g., water,
acids, bases
water
Extractable inorganics
共e.g., Na, K, Ca, Mg, Si兲
Extractable elements
共e.g., Cr, Co, Ni, Mo兲
Extractable anions and cations
2+
2+
共e.g., F−, Cl−, SO2−
4 , Ca , Mg 兲
Extractable organics
共e.g., detergents, fatty acids兲
Extractable organics
共e.g., lubricants, fats兲
Volatile organics
共e.g., solvents, ethylene oxide兲
Indirect Specific Analysis
ICP-AES
ICP-MS
HPIC
LC-MS
GC-MS
Headspace-GC-MS
Universal Analysis
Total extractable
residues
共gravimetry兲
Total extractable
particles
共gravimetry after
filtration兲
Total extractable
particles 共counting兲
none
Water, org.
solvents
org. solvents
none,
thermal
extraction
Practicable
Detection Limitsa
Morphology,
color
Morphology,
color
Molecular
structure
Difficult 共counting
particles/area兲
Difficult 共counting
particles/area兲
⬎1%
Morphology,
elements with
atomic no. ⬎5
Element and
molecular mass
EDX: 0.1–0.5%
1 nm residual film
Elements
1 ␮g/device
Elements
0.05 ␮g/device
Elements
10 ␮g/device
Retention time,
molecular mass
Retention time,
molecular mass
Retention time,
molecular mass
ng-␮g/device
ng-␮g/device
ng-␮g/device
Water or
org. solvent
All nonvolatile extractable
residues 共e.g., polymer debris,
salts, lubricants兲
All extractable particles
共e.g., sand blasting particles兲
Water or
org. solvent
All extractable particles
共e.g., dust, metal debris兲
none
TOC
Water
none
FTIR
e.g., CCl4,
C2Cl3F3
Water or
alcohols/
water
Water extractable organic
compounds
共e.g., detergents, surfactants兲
Extractable hydrocarbons
共e.g., lubricants, coolants, fats兲
Organic and inorganic ions
共e.g., salts, ionic detergents,
acids, bases兲
Particle size and
technique
dependent
0.02 mg/device
none
0.04 mg/device
none
0.1 mg/device
共calculated as
cloride兲
Conductivity
Water or
org. solvent
Identification
by
none
0.3 mg/device
none
0.1 mg/device
a
Detection limits strongly depend on equipment, method and sample.
able by the analytical technique chosen. Therefore the recovery of the extraction methods has to be
critically assessed. If there are no residues measured in the extract, this does not necessarily mean that no
residual contaminants are present.
Identification of Residues by Specific Analysis Techniques
While direct methods like SEM/EDX and TOF-SIMS are effective for the identification of localized
residues, inductively coupled plasma atomic emission spectrometry 共ICP-AES兲 and inductively coupled
plasma-mass spectrometry 共ICP-MS兲 are advantageous to identify and quantify the elemental composition
of extractable residues. High-performance ion chromatography 共HPIC兲 is best suitable for the identification of extractable anions such as fluoride, chloride, sulfate, and nitrate. This technique can also be applied
to detect organic acids, ionic surfactants, and cations like lithium, sodium, and potassium.
For the identification and quantification of a complex mixture of extracted organic residues, the most
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4 JOURNAL OF ASTM INTERNATIONAL
powerful techniques are liquid chromatography mass spectrometry 共LC-MS兲 and gas chromatography
mass spectrometry 共GC-MS兲. Due to the chromatographic step the mixture of residues is separated and
then identified by mass spectra. This allows distinguishing between leachables from the polymers and
residues from processing aids. These methods are usually too specific for routine cleanliness control of
medical devices and therefore only applied if identification of residues is required.
Universal Test Methods
Universal test methods are capable of detecting a broad range of residues. Gravimetry is one of the most
universal methods, since weighting is a unspecific analysis techniques. This makes gravimetry a very
suitable method for nonmicrobial cleanliness control.
The method in development by the ASTM subcommittee allows one to measure total nonvolatile
extractable residues 关4兴. This includes almost all potential residues except absorbed gases or volatile
compounds. The detection limits listed in Table 1 depend on the equipment and the infrastructure. A
detection limit of, e.g., 0.3 mg for gravimetry allows the assessment of an overall cleanliness. Much lower
detection limits can be obtained for particles using particle counting techniques. Total organic carbon
共TOC兲 and Fourier transform infrared spectrometry 共FTIR兲 analysis are further important universal techniques, which also allow detection of extractable organic residues at much lower levels than gravimetry.
TOC analysis is an established technique for water purity control, e.g., in the pharmacy, microelectronic, and medical device industry where ultrapure water is required. The method is best suited to detect
water extractable organic residues on medical devices. Since this technique can only be applied as an
indirect method, extraction of the medical device is required. The extraction can be done thermally, where
carbon containing residues are released in a combustion chamber. This is not applicable for polymer
medical devices, since a high temperature would combust the device itself. Thus, polymer devices have to
be extracted with water. Water extraction and TOC analysis is suitable for cleanliness control of polar
organic residues, e.g., from cleaning agents.
FTIR analysis is done after extraction with nonpolar solvents like carbon tetrachloride 共CCl4兲 or
1,1,2-trichlorotrifluoroethane 共C2Cl3F3兲. These solvents are best suited for the extraction of nonpolar
organic residues. This makes FTIR analysis, which measures the hydrocarbons, a very powerful method
for the cleanliness testing of processing aids like lubricants, coolants, greases, and even for residues from
fingerprints. The disadvantage of this method is the use of chlorinated or chlorofluorinated ozone depleting
solvents, which require special safety precautions to prevent their release into the atmosphere.
Electrical conductivity measurement is a further valuable testing technique for controlling the effectiveness of a cleaning process. Conductivity is usually measured on-line to control the salt content of
deionized water used for rinsing after washing. Residual ions on medical devices are measured after
extraction with water or with a mixture of water and organic solvent 共e.g., water/ethanol兲. This allows to
detect all forms of extractable ions on devices without distinguishing between different cations and anions.
Methods for Quantification and Identification of Organic Residues
The ability to detect potential residues is one of the most important factors for the evaluation of an
appropriate method. The recovery of low amounts of organic residues detected by TOC and FTIR and
identified by GC-MS was examined as follows.
Water Extraction and TOC Analysis
The recovery of oil-like residues was determined through spiking tests. Thus, a low amount 共0.3 mg兲 of
cooling agent Honilo 981 共Castrol Inc., Switzerland兲, which is representative for nonpolar processing aids,
was spiked on titanium test samples. To completely eliminate TOC traces the samples were previously
heated to 500° C.
The recovery of two extraction methods has been tested. For this, the spiked test samples were
completely immersed in 300 mL water and extracted as follows:
• 1 h ultrasonic extraction in water starting at 23° C
• 24 h refluxing in boiling water 共100° C兲
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ZURBRÜGG ON POLYMERS 5
The extracts were analyzed with a TOC 5000 analyzer 共Shimatzu Inc.兲. The recovery was calculated
considering the carbon content of the spiked Honilo 981.
Extraction with Nonpolar Solvents and FTIR Analysis
The recovery of oil-like residues, extracted with nonpolar solvents, was determined through spiking tests.
Small amounts 共0.2– 0.3 mg兲 of cooling agents Honilo 981 共Castrol Inc.兲, Mobile DTE 24 共Mobile Inc.兲
and n-Hexadecane 共Fluka Inc.兲, were spiked on ultra-high molecular weight polyethylene 共UHMWPE兲
tribal knee inserts, on woven polyethylene terephthalate 共PET兲 ligaments and on porous coated titanium
test cups. Previous to spiking, the test samples were cleaned in carbon tetrachloride 共15 min ultrasonication and 1 h shaking兲. The spiked samples were extracted with CCl4 or C2Cl3F3. Less than 300 mL
extraction media was required to completely immerse the samples. The UHMWPE samples were extracted
for 10 min in an ultrasonic bath starting at 23° C. The PET and metal samples were extracted for 15 min
in an ultrasonic bath starting at 23° C and then slightly shaken for 60 min at room temperature.
The extracts were analyzed by transmission FTIR BioRad FTS-45 共BioRad Inc.兲 using a 1 cm cuvette.
The peak area associated to the hydrocarbon vibrations of organic compounds was integrated from
3000– 2800 cm−1. The recovery was quantified against a calibration of Honilo 981, Mobile DTE 24, or
n-Hexadecane, respectively.
Identification of Organic Residues
To distinguish between organic residues from the manufacturing process and leachables released from the
polymer itself, GC-MS analysis was performed.
UHMWPE tibial knee inserts were machined with a mineral oil-based coolant. During the wet machining the whole surface was in contact with the coolant. All test samples were washed using a conventional industrial washing machine with water and detergents. The samples were finally rinsed with deionized water and then dried in an oven. To eliminate cross contamination, the test samples were washed and
rinsed separately from other devices.
The UHMWPE tibial knee inserts were completely immersed in CCl4 and sequentially extracted by
the following three extraction steps:
• 10 min ultrasonication starting at 23° C
• 30 min ultrasonication starting at 23° C followed by 120 min slightly shaking at room temperature
• 60 min ultrasonication starting at 23° C followed by three days slightly shaking at room temperature
The sum of extracted hydrocarbons was determined by FTIR as described in the previous section. For
the identification of organic residues, the extracts were concentrated by evaporation at 40° C under vacuum
and then analyzed by GC-MS 共Saturn 4D, Varian Inc.兲 on a Rtx-5MS 共Restek兲 column with a GC oven
program from 70 to 300° C. The mass range between 120 and 500 Dalton 共m/z兲 was recorded. The peaks
were identified using an NIST mass spectral database. Further identification was done by matching the
chromatograms and mass spectra of the residues with those of reference processing aids. To quantify the
amount of extracted residues, the characteristic peaks were integrated and evaluated against a calibration
of reference processing aids. This made the allowance to quantitatively distinguish between organic processing residues and leachables from the UHMWPE.
Results and Discussion
Cleanliness Testing of Organic Residues on Medical Devices by TOC and FTIR Analysis
The ability to detect potential residues with sufficient recovery is one of the most important evaluation
criteria for cleanliness test methods.
Recoveries of nonpolar processing aids analyzed by TOC and FTIR are listed in Table 2. Neither 1 h
ultrasonication with water nor 24 h refluxing resulted in a good recovery. For both extraction procedures
TOC was mostly below 0.05 mg carbon/sample, which equates to a recovery below 20%.
The poor recovery can be explained by the low water solubility of mineral oils. The longer the carbon
chain of aliphatic hydrocarbons, the lower their solubility in water. n-Hexadecane 共C16H34兲, which is a
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TABLE 2—Recovery of spiked organic residues determined by TOC- and FTIR-analysis.
Extraction
Media
Extraction
TOC-ANALYSIS
Water
1 h US,a 23° C
Water
24 h refluxing, 100° C
FTIR-ANALYSIS
CCl4
10 min US,a 23° C
CCl4
15 min USa and 60 min
slightly shaking, 23° C
CCl4d
15 min USaand 60 min
slightly shaking, 23° C
15 min USa and 60 min
CCl4d
slightly shaking, 23° C
15 min USa and 60 min
C2Cl3F3e
slightly shaking, 23° C
Spike
Spiked
Amount
mg/device
Recovery of
Spike
%
Titanium
Titanium
Honilo 981b
Honilo 981b
0.3
0.3
⬍20
⬍20
UHMWPE
PET
Honilo 981b
Mobil DTE 24b
0.3
0.2
70c
93c
Titanium
Honilo 981b
0.3
97
Titanium
n-Hexadecane
0.3
93
Titanium
n-Hexadecane
0.3
94
Material
Surface
a
Ultrasonic extracation.
Honilo 981 and Mobil DTE 24 are mineral oil-based processing aids.
c
After subtraction of the leachables from the cleaned polymers.
d
Carbon tetrachloride.
e
1,1,2-trichlorotrifluoroethane.
b
relative short-chain hydrocarbon compared to those in lubricants and coolants, has a solubility of only
0.004 mg/ L water 关5兴. Thus, mineral oil containing processing aids are almost insoluble and therefore
difficult to extract with water. Ultrasonication and increased temperature during refluxing allows for better
removal of mineral oils. Due to the low solubility small droplets of oil are formed which occasionally are
injected in the TOC analyzer. This may result in irregularly higher but not reproducible TOC recoveries.
As summarized in Table 2 indirect FTIR analysis showed good recoveries since this technique permits
the quantification of hydrocarbon residues after extraction with nonpolar solvents 共CCl4 or C2Cl3F3兲. The
recovery of mineral oil-based processing aids on PET and metal devices are very good. Due to the stronger
adhesion of nonpolar hydrocarbons on UHMWPE and the shorter extraction time 共10 min ultrasonication兲
recovery on UHMWPE was lower, but still sufficient to detect organic contaminations.
Recovery may be increased by a higher extraction temperature or a longer extraction time, which both
would also increase the leachables from the polymer. Since universal methods such as TOC, FTIR, and
gravimetry do not differentiate between residues and leachables, the extraction has to be optimized for a
good recovery of residues while keeping the amount of extracted leachables from the polymer to a
minimum.
Identification of Extractable Organic Residues
Extracted residues from UHMWPE were identified by GC-MS. Chromatograms of characteristic mass
fragments from the organic residues are shown in Fig. 4. Each peak in the chromatogram represents a
specific compound. The main amount of compounds which are co-eluted and overlapping in the region
between 1900–2900 scans, are identified as hydrocarbons with a broad distribution in carbon chain length.
These chromatograms are characteristic for residues from mineral oil-based processing aids. For further
identification, the chromatograms from the samples are matched with chromatograms of reference processing aids. Two example chromatograms of mineral oil-based reference processing aids are shown in
Figs. 1 and 2. Comparing the chromatograms of the extracted UHMWPE sample 共Fig. 3兲 with those of the
references, the main amount detected by GC-MS is identified as residues from processing aid A 共Fig. 1兲.
In contrast to the chromatogram of reference A, the sample extract shows some additional peaks indicating
further residues, but those were present at a much lower concentration compared to the residues from
processing aid A.
The amount of extracted organic residues quantified via GC-MS and the total of organic residues
including UHMWPE leachables, measured by FTIR, are shown in Fig. 4. The differences between the
FTIR and GC-MS results were assumed to be leachables from the UHMWPE. It is shown that residues and
leachables are extracted at each of the three sequential extraction steps. The relatively short first extraction
共10 min ultrasonication兲 mainly removes the residues from the surface while the second and third step also
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ZURBRÜGG ON POLYMERS 7
FIG. 1—GC-MS chromatograms of the reference processing aid A containing mineral oils.
FIG. 2—GC-MS chromatograms of the reference processing aid B containing mineral oils.
FIG. 3—GC-MS chromatograms of a UHMWPE test device after the first extraction (10 min ultrasonication with CCl4).
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FIG. 4—The organic residues on UHMWPE samples, identified as processing aid A, were quantified via
GC-MS. The total of extractable organic residues including UHMWPE leachables were quantified as
hydrocarbons via FTIR. The differences between the FTIR and GC-MS results were assumed to be leachables from the UHMWPE.
extract absorbed and diffused residues from the subsurface. The results in Fig. 4 indicate that although the
majority of organic residue was removed by conventional washing, residues of processing aids could still
be detected on UHMWPE samples.
Conclusion
In general, cleanliness testing methods used for metallic medical devices can also be applied for the testing
of polymer components and devices. Both surface analysis techniques as well as indirect analysis after
extraction have their advantages and disadvantages. Surface analysis is limited to assess overall contamination, especially of devices with porous surfaces and complex geometries. For indirect methods it has to
be proven that potential residues can be removed from the device with a sufficient recovery, without
extracting interfering leachables from the polymer.
Water extraction following TOC analysis is powerful for cleanliness control of polar organic residues
as cleaning agents. Due to the low solubility of nonpolar hydrocarbons, the water extraction shows a poor
recovery for mineral oil-based processing aids such as lubricants and coolants. Therefore, TOC analysis
alone is not representative enough for cleanliness testing of organic residues on polymer or metal components. An additional extraction with nonpolar solvents is proposed, followed by, e.g., gravimetry or
FTIR analysis.
While gravimetry captures the total nonvolatile residues, CCl4-extraction followed by FTIR analysis is
specific to organic residues and allows a detection of organic residues at much lower levels. FTIR analysis
showed a good recovery of mineral oil-based processing aids on PET and metal. For UHMWPE, the
relatively short extraction time 共10 min ultrasonication兲, resulted in a sufficient recovery at relatively low
amounts of interfering UHMWPE leachables. For examination of absorbed residues in the subsurface of
UHMWPE longer extraction is proposed 共60 min ultrasonication and 120 min slightly shaking兲.
While universal methods, detecting a broad rage of residues, are most suitable for nonmicrobial overall
cleanliness control, more sophisticated techniques are required for residue identification. Organic residues
on UHMWPE test devices were identified by GC-MS. The results indicate that although the majority of
organic residue was removed by conventional aqueous washing, residues of mineral oil-based processing
aids could still be detected on machined UHMWPE. Therefore, cleanliness testing of polymer medical
devices should be focused on components and devices which came into contact with nonpolar organic
processing aids.
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ZURBRÜGG ON POLYMERS 9
References
关1兴
关2兴
关3兴
关4兴
关5兴
Official Publications of the European Communities, Council Directive 93/42/EEC concerning medical devices, June 1993.
U. S. Food and Drug Administration, Validation of Cleaning Processes, July 1993.
U. S. Food and Drug Administration, Guideline on General Principles of Process Validation, May
1987.
ASTM, Draft, Standard Test Method for Extracting Residue from Metallic Medical Components and
Quantifying via Gravimetric Analysis, WK5031—ITEM 12, 2005.
Huibers, P. D. T. and Katritzky, A. R., “Correlation of the Aqueous Solubility of Hydrocarbons and
Halogenated Hydrocarbons with Molecular Structure,” J. Chem. Inf. Comput. Sci., Vol. 38, 1998, pp.
283–292.
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