ASTM F3306-19

This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
Designation: F3306 − 19
Standard Test Method for
Ion Release Evaluation of Medical Implants
This standard is issued under the fixed designation F3306; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope 1.8 Units—The values stated in SI units are to be regarded
as standard. No other units of measurement are included in this
1.1 This test method assesses metal or other ions released
standard.
from single-use, metallic, implantable medical devices, or
1.9 This standard does not purport to address all of the
components thereof, by exposing the device to solutions
safety concerns, if any, associated with its use. It is the
simulating the in-vivo environment and temperature in a
responsibility of the user of this standard to establish appro-
container for a predetermined time frame with regular sam-
priate safety, health, and environmental practices and deter-
pling at adequate intervals. Examples of device types that may
mine the applicability of regulatory limitations prior to use.
be evaluated by this test method include, but are not limited to:
1.10 This international standard was developed in accor-
cardiovascular devices, endovascular devices, and orthopedic
dance with internationally recognized principles on standard-
implants. Devices which are to be partially implanted, but in
ization established in the Decision on Principles for the
long-term contact within the body (such as external fixation
Development of International Standards, Guides and Recom-
devices) may also be evaluated using this method.
mendations issued by the World Trade Organization Technical
1.2 This test method is used to assess devices or device
Barriers to Trade (TBT) Committee.
components, or both, in their final form and finish, as they
would be implanted. For modular implants, consideration
2. Referenced Documents
should be given to individual testing of every part.
2.1 ASTM Standards:
1.3 This test method covers the selection of specimens,
D1193 Specification for Reagent Water
specimen preparation, test environment, method of exposure,
F2129 Test Method for Conducting Cyclic Potentiodynamic
and method for evaluating the results to characterize ion
Polarization Measurements to Determine the Corrosion
release. Because of the variety of configurations and sizes of
Susceptibility of Small Implant Devices
implants, a variety of specimen container configurations may
F3044 TestMethodforEvaluatingthePotentialforGalvanic
be used.
Corrosion for Medical Implants
2.2 ISO Standards:
1.4 This test method is not intended for ions only adsorbed
ISO 3696 Water for analytical laboratory use – Specification
onto the surface of the samples.
and test methods
1.5 This test method does not apply to absorbable metallic
ISO 10993-15 Biological evaluation of medical devices –
implants (for example, magnesium-based stents, bone screws,
Part 15: Identification and quantification of degradation
etc.) that are intentionally designed to degrade in-vivo.
products from metals and alloys
1.6 This test method does not cover the required subsequent
ISO 10993-17 Biological evaluation of medical devices –
chemical analysis, for example, by inductively coupled plasma
Part 17: Establishment of allowable limits for leachable
mass spectrometry (ICP-MS), or the validation of the analyti-
substances
cal instrumentation.
3. Terminology
1.7 This test method does not cover the influence of
3.1 Definitions:
dynamicloadingandassociatedsurfacedamageorwearonion
3.1.1 blank, n—a sample of the test solution prepared
release. Ion release may change under dynamic loading con-
without the specimen for baseline determination in the subse-
ditions and wear. Additional testing may be required, depend-
quent analysis.
ing on the application and outcome of this test method.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
This test method is under the jurisdiction ofASTM Committee F04 on Medical contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
and Surgical Materials and Devices and is the direct responsibility of Subcommittee Standards volume information, refer to the standard’s Document Summary page on
F04.15 on Material Test Methods. the ASTM website.
Current edition approved Feb. 1, 2019. Published March 2019. DOI: 10.1520/ Available fromAmerican National Standards Institute (ANSI), 25 W. 43rd St.,
F3306-19. 4th Floor, New York, NY 10036, http://www.ansi.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F3306 − 19
3.1.2 method detection limit (MDL), n—the minimum con- in-vivo environment); however, the results of this testing
centration of an analyte that can be identified, measured, and conducted in simulated physiological solutions can provide
reported with 99 % confidence that the analyte concentration is useful data to estimate exposure as part of a risk assessment
greater than zero. This confidence level is determined from (for example, as per ISO 10993-17) or to compare different
analysis of a sample in a given matrix containing the analyte(s) device materials, designs, or manufacturing processes.
(1).
6. Apparatus
4. Summary of Test Method
6.1 Waterbath,oven,orheatingchamber/cabinet,calibrated
4.1 To quantify ion release from the device over time, in the relevant temperature range to maintain the test solution
successive immersion testing is conducted on the same device. temperature at 37 °C 6 2 °C.
Initially, the device is placed in an appropriate container, filled
6.2 Clean, non-metallic apparatus (for example, tweezers,
with an appropriate simulated physiological solution, and
string, or similar means) that can be used to transfer a sample
stored at a physiological temperature for a predetermined time
from one container to the next.
frame. At subsequent predetermined intervals, the immersion
6.3 Plastic ware or glassware for making solution.
procedure is repeated by removing the test sample from the
NOTE 1—In general, whatever apparatus that will come into contact
container, sampling the media for chemical analysis, and
with the samples (that is, glassware, tweezers, etc.) must be appropriately
placing the test sample into a container with fresh media.
clean (see 10.1.1).
5. Significance and Use
7. Specimen Containers and Pouches
5.1 Components of implanted medical devices can release
7.1 There are a variety of containers, pouches, and caps that
ions,whichmayleadtoadversebiologicaleffectsifreleasedin
may be used in this test method. The size and design of the
sufficient quantities. Therefore, it may be necessary to charac-
containersandcapsshouldbechosenaccordinglyandjustified.
terize the ion release behavior over time to verify that a
NOTE2—Containersandpoucheswillbothbegeneralizedascontainers
medical device or device components, or both, will not pose an
for this test method.
unacceptable risk to patients. Some examples of when time-
7.1.1 To allow complete immersion of the sample being
dependent ion release testing should be considered include:
tested.
5.1.1 New materials,
7.1.2 To contain enough fluid volume to allow analysis.
5.1.2 New applications (for example, different in-vivo en-
7.1.3 To contain sufficient volume to accommodate disso-
vironments or new designs) that may degrade corrosion
lution limits of the analyzed ions.
resistance,
5.1.3 Manufacturing processes that may lead to increased 7.2 The determined volume should be used consistently
ion release susceptibility, throughout the test.
5.1.4 Results of other corrosion testing (for example, Test
7.3 The container material should be selected such that the
Methods F2129 and F3044) indicate high susceptibility to
likelihood of ions adhering to or diffusing into the container
corrosion.
wall can be neglected.Therefore, the container walls should be
5.2 Forming and finishing steps used to create an implant- smooth and manufactured of a suitable material. This can be
able device may have significant effects on the ion release evaluated by performing a spike and recovery test as described
behavior of the material from which the device is fabricated.
in Appendix X2. Such validation testing should be performed
Preconditioning can impact the ion release behavior of im- and included in the test report.Ajustification shall be provided
plants; therefore, prior to testing, devices should be subjected
if validation testing is not conducted.
to preconditioning that is appropriate to their application. A
7.4 Pre-cleaned containers may be used in the as-received
justification shall be provided if preconditioning is omitted.
conditions. Pre-cleaned vials shall meet or exceed require-
Additional information on preconditioning is found in Appen-
ments of a Level 3 container per the U.S. EPA“Specifications
dix X1. Substitute test articles (tubes, plates, wires, device
and Guidance for Contaminant-Free Sample Containers” (that
subcomponents, etc.) may be used for testing with adequate
is, pre-cleaned with a certificate of analysis) (2). Certified
justification, if all processing steps, including sterilization and
metal-free containers are acceptable for use without pre-
preconditioning, are comparable to the finished device.
cleaning for analysis of metal ion release. For cleaning
5.3 To accommodate the wide variety of device shapes and non-pre-cleaned containers, please refer to Section 10.
sizes likely to be encountered, various sizes and shapes of
7.5 Borosilicateglass,sodalimeglass,orothernon-metallic
containers manufactured from various materials can be used.
containers(Polypropylene(PP),Perfluoroalkoxyalkane(PFA),
The container material choice should be justified.
etc.) can be used.
NOTE 3—Container materials can release ions themselves. Containers
5.4 Note that the test conditions described in this test
should be chosen according to the intended ions to be measured. For an
methodmaynotcompletelysimulatethoseencounteredinvivo
example of how containers can be tested for suitability, see Appendix X2.
(cells, proteins, mechanical loading, and other specifics of the
NOTE 4—Some media might need sterilized containers to prevent
growth of microorganisms.
7.6 The container should be adequately closed and sealed to
The boldface numbers in parentheses refer to the list of references at the end of
this standard. prevent leakage or evaporation, or both, of the test solution.
F3306 − 19
8. Reagents these actions can potentially affect the overall ion release
behavior of the material (a study concerning the impact of
8.1 Reagent-grade chemicals shall be used for this test
device loading on nickel ion release can be found in Ref 4).A
method when they are commercially available (for example,
justification should be provided if preconditioning is omitted.
some components in bile solutions are not available in reagent-
See also Appendix X1 for rationale for preconditioning.
grade). Such reagents shall conform to the specifications of the
NOTE 8—As an example, for endovascular devices, testing should be
Committee on Analytical Reagents of the American Chemical
performed after subjecting the device to preconditioning, which includes
Society. A justification shall be provided if reagent-grade
tracking and deployment of the device through an in-vitro fixture that
chemicals are not used.
mimics in-vivo anatomic conditions and deployment in deionized water at
37 °C 62°C (5). Non-endovascular medical devices may require other
8.2 Water shall be distilled or deionized conforming to the
types of preconditioning.
purity requirements of Specification D1193, Type IV reagent
water, or better.
10. Procedure for Test Preparation and Start of the Test
NOTE 5—ISO 10993-15 requires Grade 2 water (ISO 3696) or better as
the basis for its test media. If tests need to comply with the immersion test
10.1 Before the test starts, various activities should be
described in ISO 10993-15, the water needs to be at least Type III
carried out, including cleaning of test containers (if not
according to Specification D1193, if the total silica content of the used
pre-cleaned), preparing the test and spike and recovery solu-
water is below 20 µg/L.
tions (see Appendix X2), and sample preparation (including
8.3 If possible, buffered solutions should be used to avoid
loading, tracking, or deployment, or combinations thereof, if
excursions in pH. An example of a phosphate-buffered saline
warranted).
(PBS) formulation is given in Appendix X2 of Test Method
F2129. Other simulated physiological solutions are permitted, NOTE 9—A visual inspection step, outside of any normal Quality
Assurance Inspection, can be done before testing, but poses the risk of
depending on the ultimate use of the device in the body. For
additional contamination of samples.
reference, other test solution formulations are also provided in
Appendix X2 of Test Method F2129. 10.1.1 The cleaning procedure should be designed to mini-
NOTE 6—Some media might need sterilization and a specialized work
mize contamination of the test solution from the container and
environment to prevent growth of microorganisms.
all lab equipment coming into direct contact with it. An
NOTE 7—These test fluids were chosen not because they are the most
example of a cleaning procedure for containers made of
realistic, but because they are the most likely to reflect the worst possible
borosilicate glass and other materials that can withstand direct
outcome and because they make quantitative analysis simpler.
exposure to nitric acid, is to fill the container with a nitric acid
9. Test Specimens solution(50 mLconcentrated(68 %to70 %)nitricacidand50
mL of deionized (DI) water in a 100 mL solution), store it for
9.1 Unless otherwise justified, all samples selected for
10 min, empty it, and then rinse the container three times with
testing should be taken from as-manufactured, clinical-quality
DI water.
product. Cosmetic rejects or other nonclinical samples may be
used if the cause for rejection does not affect the ion release
NOTE 10—Measure the pH of the final rinse to ensure that the pH is
behavior of the device. Sterilization may be omitted if it can be
60.1 pH of the stock DI water. This will ensure minimal residual
contamination by the nitric acid cleaning.
demonstrated that prior sterilization has no effect on the ion
release behavior of the device (3) and is not tested in media
10.1.2 Prepare the specimen such that the portion exposed
prone to microorganism growth.
to the test solution is in the same metallurgical and surface
9.1.1 Test specimens used for design parameter studies can
condition as the implantable form of the medical device being
beused,withtherequirementthatthemetallurgicalandsurface
studied, including simulated deployment if warranted.
conditions of the specimens are the same as the intended
10.1.3 Estimate the total surface area of interest exposed to
implantable medical device.
the solution in order to determine the surface/volume ratio of
9.1.2 The number of samples tested should be justified. The
the specimen during the test.
devices should be selected such that they represent the worst
10.
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