Standard Guide for Performance of Lifetime Bioassay for the Tumorigenic Potential of Implant Materials

SIGNIFICANCE AND USE
4.1 This guide is not intended to specify the exact method of conducting a test for any particular material but only to present some of the criteria that should be considered in method design and possible problems that could lead to misleading results. In the development of the actual test protocol, it is recommended that recognized tumorigenesis bioassay procedures be consulted.  
4.2 The recommendations given in this guide may not be appropriate for all applications or types of implant materials. These recommendations should be utilized by experienced testing personnel in conjunction with other pertinent information and the requirements of the specific material application.
SCOPE
1.1 This guide is intended to assist the biomaterials testing laboratory in the conduct and evaluation of tumorigenicity tests to evaluate the potential for new materials to evoke a neoplastic response. The procedure is generally reserved only for those materials which have not previously been used for human implantation for a significant period of time.  
1.2 Assessment of tumorigenicity is one of several procedures employed in determining the biological response to a material as recommended in Practice F748. It is assumed that the investigator has already determined that this type of testing is necessary for a particular material before consulting this guide. The recommendations of Practice F748 should be considered before a study is commenced.  
1.3 Whenever possible, it is recommended that a battery of genotoxicity procedures be initiated and proposed as an alternative to an in-vivo tumorigenicity bioassay. Genotoxicity assays may also be considered as initial screening procedures due to the sensitivity of the assays, the significant reduction in time to gain valuable data, and the desire to reduce the use of animals for testing. Genotoxicity assays that may be considered are outlined in Guides E1262, E1263, E1280, and E2186, and Practices E1397 and E1398. Additionally, other genotoxicity testing which might be considered (but which do not yet have ASTM test methods) include Salmonella/Mammalian-Microsomal Plate Incorporation Mutagenicity Assay, In Vivo Cytogenetics Bone Marrow Chromosomal Damage Assay, BALB/3T3 Morphological Transformation of Mouse Embryo Cells, and the Mouse Micronucleus Assay. The investigator is advised to consider carefully the appropriateness of a particular method for his application after a review of the published literature.  
1.4 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, health, and environmental practices and determine the applicability of regulatory limitations prior to use.  
1.5 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.

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Publication Date
31-Jan-2018
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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: F1439 − 03 (Reapproved 2018)
Standard Guide for
Performance of Lifetime Bioassay for the Tumorigenic
1
Potential of Implant Materials
This standard is issued under the fixed designation F1439; 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 priate safety, health, and environmental practices and deter-
mine the applicability of regulatory limitations prior to use.
1.1 This guide is intended to assist the biomaterials testing
1.5 This international standard was developed in accor-
laboratoryintheconductandevaluationoftumorigenicitytests
dance with internationally recognized principles on standard-
toevaluatethepotentialfornewmaterialstoevokeaneoplastic
ization established in the Decision on Principles for the
response. The procedure is generally reserved only for those
Development of International Standards, Guides and Recom-
materials which have not previously been used for human
mendations issued by the World Trade Organization Technical
implantation for a significant period of time.
Barriers to Trade (TBT) Committee.
1.2 Assessment of tumorigenicity is one of several proce-
dures employed in determining the biological response to a
2. Referenced Documents
material as recommended in Practice F748. It is assumed that
2
2.1 ASTM Standards:
the investigator has already determined that this type of testing
E1262 Guide for Performance of Chinese Hamster Ovary
is necessary for a particular material before consulting this
Cell/Hypoxanthine Guanine Phosphoribosyl Transferase
guide. The recommendations of Practice F748 should be
Gene Mutation Assay
considered before a study is commenced.
E1263 Guide for Conduct of Micronucleus Assays in Mam-
3
1.3 Whenever possible, it is recommended that a battery of
malian Bone Marrow Erythrocytes (Withdrawn 2014)
genotoxicity procedures be initiated and proposed as an alter-
E1280 Guide for Performing the Mouse Lymphoma Assay
3
native to an in-vivo tumorigenicity bioassay. Genotoxicity
for Mammalian Cell Mutagenicity (Withdrawn 2014)
assays may also be considered as initial screening procedures
E1397 Practice for In Vitro Rat Hepatocyte DNA Repair
3
due to the sensitivity of the assays, the significant reduction in
Assay (Withdrawn 2013)
time to gain valuable data, and the desire to reduce the use of
E1398 Practice for In Vivo Rat Hepatocyte DNA Repair
3
animals for testing. Genotoxicity assays that may be consid-
Assay (Withdrawn 2013)
ered are outlined in Guides E1262, E1263, E1280, and E2186,
E2186 Guide for Determining DNA Single-Strand Damage
and Practices E1397 and E1398. Additionally, other genotox-
in Eukaryotic Cells Using the Comet Assay
icity testing which might be considered (but which do not yet
F748 PracticeforSelectingGenericBiologicalTestMethods
have ASTM test methods) include Salmonella/Mammalian-
for Materials and Devices
Microsomal Plate Incorporation Mutagenicity Assay, In Vivo
2.2 Other Documents:
Cytogenetics Bone Marrow Chromosomal Damage Assay,
National Toxicology Program General Statement of Work
BALB/3T3 Morphological Transformation of Mouse Embryo
fortheConductofToxicityandCarcinogenicityStudiesin
Cells, and the Mouse Micronucleus Assay. The investigator is 4
Laboratory Animals
advisedtoconsidercarefullytheappropriatenessofaparticular
OECD Guidelines for Testing of Chemicals: Guideline 451,
method for his application after a review of the published
literature.
1.4 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 appro-
2
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
contact ASTM Customer Service at service@astm.org. For Annual Book ofASTM
Standards volume information, refer to the standard’s Document Summary page on
1
This guide is under the jurisdiction of ASTM Committee F04 on Medical and the ASTM website.
3
Surgical Materials and Devices and is the direct responsibility of Subcommittee The last approved version of this historical standard is referenced on
F04.16 on Biocompatibility Test Methods. www.astm.org.
4
Current edition approved Feb. 1, 2018. Published April 2018. Originally Available from National Institute of Environmental Health Sciences, 111 T. W.
approved in 1992. Last previous edition approved in 2013 as F1439 – 03 (2013). Alexander Drive, Research Triangle Park, NC, August 1988. http://
DOI: 10.1520/F1439-03R1
...

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