ASTM F1904-23
(Guide)Standard Guide for Testing the Biological Responses to Medical Device Particulate Debris and Degradation Products in vivo
Standard Guide for Testing the Biological Responses to Medical Device Particulate Debris and Degradation Products <emph type="ital">in vivo</emph>
SIGNIFICANCE AND USE
5.1 This standard guide is to be used to help assess the biocompatibility of materials used in medical devices (for example, externally communicating, implants, and other body contact medical devices). It is designed to test the effect of particles and other wear debris and/or degradation products on the generation of FBR and other (local and systemic) host responses of immune/inflammatory origin.
5.2 The appropriateness of the selected testing methods should be carefully considered by the user since not all materials or applications need to be tested by this guide. Existing biocompatibility screening methods may not be fully predictive of the human response, and testing approaches such as those described here are needed for continuous improvement of the predictability of biocompatibility testing. The effectiveness of animal testing in terms of its predictability of human outcomes is dependent on the study design. If possible, study endpoints should be chosen to minimize interspecies variability and to investigate clinically relevant biological responses. While testing approaches should remain at the user’s discretion, the following should be taken into consideration when selecting most appropriate tests and study endpoints.
5.2.1 Device-induced responses usually involve both innate and adaptive immunities, which raises possible need for specific testing for each of these immune response types.
5.2.1.1 Device-related adaptive immune responses are mostly due to lymphocyte-mediated delayed-type hypersensitivity. In vivo allergenicity to a test material (which can be introduced via different routes) should be assessed by monitoring for any signs of allergic and acute toxicity reactions, for example, scratch, tremor, and dyspnea. In addition, ex vivo analysis on immunophenotyping of the isolated splenocytes/lymphocytes from the same studies should be considered.
5.2.1.2 Device-related innate immune responses are mostly mediated by macrophages and can be assess...
SCOPE
1.1 The purpose of this standard guide is to describe the principles and approaches to testing of medical device debris and degradation products from device materials (for example, particles from wear) for their potential to activate a cascade of biological responses at local and systemic levels in the body. In order to ascertain the role of device debris and degradation products in stimulating such responses, the nature of the responses and the consequences of the responses should be evaluated. This is an emerging area. The continuously updated information gained from the testing results and related published literature is necessary to improve the study designs, as well as predictive value and interpretation of the test results regarding debris/degradation product related responses. Some of the procedures listed here may, on further testing, not prove to be predictive of clinical responses to device-related debris and degradation products. However, only the continuing use of standard protocols will establish the most useful testing approaches with reliable study endpoints and measurement techniques. Since there are many possible and established ways of determining the debris/degradation product related responses in vivo, a single standard protocol is not stated. However, this recommended guide indicates which testing approaches are most applicable per expected biological responses and which necessary information should be supplied with the test results. To address the general role of chronic inflammation in exaggerating device-related foreign body response (FBR), the recommendations in this standard include the assessment of device-related pro-inflammatory responses and subsequent tissue remodeling potential.
1.2 This document is to provide the users with updated scientific knowledge that may help better characterize medical device debris related responses. It is to help the users to optimize their plans for particle...
General Information
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Standards Content (Sample)
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: F1904 − 23
Standard Guide for
Testing the Biological Responses to Medical Device
1
Particulate Debris and Degradation Products in vivo
This standard is issued under the fixed designation F1904; 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 patibility assessment by considering the testing principles and
methods available in published literature that are appropriate to
1.1 The purpose of this standard guide is to describe the
their products.
principles and approaches to testing of medical device debris
1.3 This standard is not sufficient to address device-related
and degradation products from device materials (for example,
degradation products that result in gas formation or that are
particles from wear) for their potential to activate a cascade of
exclusively represented by nanoparticles, or soluble species
biological responses at local and systemic levels in the body. In
such as dissolved metal ions.
order to ascertain the role of device debris and degradation
products in stimulating such responses, the nature of the 1.4 While devices should be designed and manufactured in
responses and the consequences of the responses should be such a way as to reduce as far as possible the risks posed by
evaluated. This is an emerging area. The continuously updated substances or particles (including wear debris, degradation
information gained from the testing results and related pub- products, and processing residues) that may be released from
the device, this standard guide may help users to identify the
lished literature is necessary to improve the study designs, as
well as predictive value and interpretation of the test results presence of wear debris and degradation products and subse-
quent adverse reactions that may occur.
regarding debris/degradation product related responses. Some
of the procedures listed here may, on further testing, not prove
1.5 Although this guide is based on the available device
to be predictive of clinical responses to device-related debris
debris-related knowledge that is largely based on orthopedic
and degradation products. However, only the continuing use of
devices, most of the recommendations are also applicable to
standard protocols will establish the most useful testing ap-
other (non-orthopedic) device areas.
proaches with reliable study endpoints and measurement tech-
1.6 This standard does not purport to address all of the
niques. Since there are many possible and established ways of
safety concerns, if any, associated with its use. It is the
determining the debris/degradation product related responses
responsibility of the user of this standard to establish appro-
in vivo, a single standard protocol is not stated. However, this
priate safety, health, and environmental practices and deter-
recommended guide indicates which testing approaches are
mine the applicability of regulatory limitations prior to use.
most applicable per expected biological responses and which
1.7 This international standard was developed in accor-
necessary information should be supplied with the test results.
dance with internationally recognized principles on standard-
To address the general role of chronic inflammation in exag-
ization established in the Decision on Principles for the
gerating device-related foreign body response (FBR), the
Development of International Standards, Guides and Recom-
recommendations in this standard include the assessment of
mendations issued by the World Trade Organization Technical
device-related pro-inflammatory responses and subsequent tis-
Barriers to Trade (TBT) Committee.
sue remodeling potential.
2. Referenced Documents
1.2 This document is to provide the users with updated
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scientific knowledge that may help better characterize medical 2.1 ASTM Standards:
F561 Practice for Retrieval and Analysis of Medical
device debris related responses. It is to help the users to
optimize their plans for particle characterization and biocom- Devices, and Associated Tissues and Fluids
F619 Practice for Extraction of Materials Used in Medical
Devices
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This guide is under the jurisdiction of ASTM Committee F04 on Medical and
Surgical Materials and Devices and is the direct responsibility of Subcommittee
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F04.16 on Biocompatibility Test Methods. For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Current edition approved April 1, 2023. Published April 2023. Originally contact A
...
This document is not an ASTM standard and is intended only to provide the user of an ASTM standard an indication of what changes have been made to the previous version. Because
it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version
of the standard as published by ASTM is to be considered the official document.
Designation: F1904 − 14 F1904 − 23
Standard PracticeGuide for
Testing the Biological Responses to Particles Medical
1
Device Particulate Debris and Degradation Products in vivo
This standard is issued under the fixed designation F1904; 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
1.1 This practice covers the production of wear particles and degradation products from implanted materials that may lead to a
cascade of biological responses resulting in damage to adjacent and remote tissues. In order to ascertain the role of particles in
stimulating such responses, the nature of the responses, and the consequences of the responses, established protocols are needed.
This is an emerging, rapidly developing area and the information gained from standard protocols is necessary to interpret
responses. Some of the procedures listed here may, on further testing, not prove to be predictive of clinical responses to particulate
debris. However, only the use of standard protocols will establish which are useful techniques. Since there are many possible and
established ways of determining responses, a single standard protocol is not stated. However, this recommended practice indicates
which necessary information should be supplied with test results. For laboratories without established protocols, recommendations
are given and indicated with an asterisk (*).
1.2 This standard is not designed to provide a comprehensive assessment of the systemic toxicity, carcinogenicity, teratogenicity,
or mutagenicity of the material.
1.3 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility
of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory
limitations prior to use.
2. Referenced Documents
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2.1 ASTM Standards:
F561 Practice for Retrieval and Analysis of Medical Devices, and Associated Tissues and Fluids
F619 Practice for Extraction of Materials Used in Medical Devices
F748 Practice for Selecting Generic Biological Test Methods for Materials and Devices
F1877 Practice for Characterization of Particles
3. Summary of Practice
3.1 Biological responses to particles testing may be done using specimens from animals being tested in accordance with the
Practice F748 matrix for irritation and sensitivity, or for implantation. If particles were implanted during the testing procedures or
generated during the experimental time period, the response to those particles may form a part of the overall investigation of
response to particles. Blood, organs, or tissues from the animals may be used.
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This practiceguide is under the jurisdiction of ASTM Committee F04 on Medical and Surgical Materials and Devices and is the direct responsibility of Subcommittee
F04.16 on Biocompatibility Test Methods.
Current edition approved March 1, 2014April 1, 2023. Published May 2014April 2023. Originally approved in 1998. Last previous edition approved in 20082014 as
F1904 – 98 (2008).F1904 – 14. DOI: 10.1520/F1904-14.10.1520/F1904-23.
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For referenced ASTM standards, visit the ASTM website, www.astm.org, or contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
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F1904 − 23
3.2 Biological responses to particles may be tested using the actual particulate materials or extracts in accordance with Practice
F619. The increased surface area of small particles may enhance the amount of extracted substances but, since the response to
particles may be related to the physical size, shape and composition, the use of only extracts will not completely address the
question of the impact of particle formation on the tissue response and actual implantation or other testing of particles should be
included as a part of the characterization of tissue response when particle generation is likely during actual usage. These materials
or extracts may be used in in vivo tests or for the in vitro tests. Particles generated by other methods may also be used. The method
o
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