ASTM F2721-09(2023)

Standard Guide for Preclinical <emph type="ital">in vivo</emph> Evaluation in Critical-Size Segmental Bone Defects

SIGNIFICANCE AND USE
4.1 This guide is aimed at providing a range of  in vivo models to aid in preclinical research and development of tissue-engineered medical products (TEMPs) intended for the clinical repair or regeneration of bone.  
4.2 This guide includes a description of the animal models, surgical considerations, and tissue processing as well as the qualitative and quantitative analysis of tissue specimens.  
4.3 The user is encouraged to use appropriate ASTM and other guidelines to conduct cytotoxicity and biocompatibility tests on materials, TEMPs, or both, prior to assessment of the in vivo models described herein.  
4.4 It is recommended that safety testing be in accordance with the provisions of the FDA Good Laboratory Practices Regulations 21 CFR 58.  
4.5 Safety and effectiveness studies to support regulatory submissions (for example, Investigational Device Exemption (IDE), Premarket Approval (PMA), 510K, Investigational New Drug (IND), or Biologics License Application (BLA) submissions in the U.S.) should conform to appropriate guidelines of the regulatory bodies for development of medical devices, biologics, or drugs, respectively.  
4.6 Animal model outcomes are not necessarily predictive of human results and should, therefore, be interpreted cautiously with respect to potential applicability to human conditions.
SCOPE
1.1 This guide covers general guidelines for the in vivo assessment of tissue-engineered medical products (TEMPs) intended to repair or regenerate bone. TEMPs included in this guide may be composed of natural or synthetic biomaterials (biocompatible and biodegradable) or composites thereof, and may contain cells or biologically active agents such as growth factors, synthetic peptides, plasmids, or cDNA. The models described in this guide are segmental critical size defects which, by definition, will not fill with viable tissue without treatment. Thus, these models represent a stringent test of a material’s ability to induce or augment bone growth.  
1.2 Guidelines include a description and rationale of various animal models including rat (murine), rabbit (leporine), dog (canine), goat (caprine), and sheep (ovine). Outcome measures based on radiographic, histologic, and mechanical analyses are described briefly and referenced. The user should refer to specific test methods for additional detail.  
1.3 This guide is not intended to include the testing of raw materials, preparation of biomaterials, sterilization, or packaging of the product. ASTM standards for these steps are available in the Referenced Documents (Section 2).  
1.4 The use of any of the methods included in this guide may not produce a result that is consistent with clinical performance in one or more specific applications.  
1.5 Other preclinical methods may also be appropriate and this guide is not meant to exclude such methods. The material must be suitable for its intended purpose. Additional biological testing in this regard would be required.  
1.6 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.  
1.7 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.  
1.8 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.

General Information

• Status: Published
• Publication Date: 28-Feb-2023
• ICS: 11.100.10 - In vitro diagnostic test systems
• Technical Committee: F04 - Medical and Surgical Materials and Devices
• Drafting Committee: F04.44 - Assessment for TEMPs

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: F2721 − 09 (Reapproved 2023)
Standard Guide for
Preclinical in vivo Evaluation in Critical-Size Segmental Bone
1
Defects
This standard is issued under the fixed designation F2721; 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 responsibility of the user of this standard to establish appro-
priate safety, health, and environmental practices and deter-
1.1 This guide covers general guidelines for the in vivo
mine the applicability of regulatory limitations prior to use.
assessment of tissue-engineered medical products (TEMPs)
1.8 This international standard was developed in accor-
intended to repair or regenerate bone. TEMPs included in this
dance with internationally recognized principles on standard-
guide may be composed of natural or synthetic biomaterials
ization established in the Decision on Principles for the
(biocompatible and biodegradable) or composites thereof, and
Development of International Standards, Guides and Recom-
may contain cells or biologically active agents such as growth
mendations issued by the World Trade Organization Technical
factors, synthetic peptides, plasmids, or cDNA. The models
Barriers to Trade (TBT) Committee.
described in this guide are segmental critical size defects
which, by definition, will not fill with viable tissue without
2. Referenced Documents
treatment. Thus, these models represent a stringent test of a
2
material’s ability to induce or augment bone growth. 2.1 ASTM Standards:
F561 Practice for Retrieval and Analysis of Medical
1.2 Guidelines include a description and rationale of various
Devices, and Associated Tissues and Fluids
animal models including rat (murine), rabbit (leporine), dog
F565 Practice for Care and Handling of Orthopedic Implants
(canine), goat (caprine), and sheep (ovine). Outcome measures
and Instruments
based on radiographic, histologic, and mechanical analyses are
F895 Test Method for Agar Diffusion Cell Culture Screening
described briefly and referenced. The user should refer to
for Cytotoxicity
specific test methods for additional detail.
F981 Practice for Assessment of Compatibility of Biomate-
1.3 This guide is not intended to include the testing of raw
rials for Surgical Implants with Respect to Effect of
materials, preparation of biomaterials, sterilization, or packag-
Materials on Muscle and Insertion into Bone
ing of the product. ASTM standards for these steps are
F1983 Practice for Assessment of Selected Tissue Effects of
available in the Referenced Documents (Section 2).
Absorbable Biomaterials for Implant Applications
1.4 The use of any of the methods included in this guide F2150 Guide for Characterization and Testing of Biomate-
rial Scaffolds Used in Regenerative Medicine and Tissue-
may not produce a result that is consistent with clinical
performance in one or more specific applications. Engineered Medical Products
2.2 Other Documents:
1.5 Other preclinical methods may also be appropriate and
21 CFR Part 58 Good Laboratory Practice for Nonclinical
this guide is not meant to exclude such methods. The material
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Laboratory Studies
must be suitable for its intended purpose. Additional biological
21 CFR 610.12 General Biological Products Standards—
testing in this regard would be required.
3
Sterility
1.6 The values stated in SI units are to be regarded as
standard. No other units of measurement are included in this
3. Terminology
standard.
3.1 Definitions:
1.7 This standard does not purport to address all of the
safety concerns, if any, associated with its use. It is the
2
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
1
This guide is under the jurisdiction of ASTM Committee F04 on Medical and contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM
Surgical Materials and Devices and is the direct responsibility of Subcommittee Standards volume information, refer to the standard’s Document Summary page on
F04.44 on Assessment for TEMPs. the ASTM website.
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Current edition approved March 1, 2023. Published March 2023. Originally Available from U.S. Government Printing Office Superintendent of Documents,
approved in 2008. Last previous edition approved in 2014 as F2721 – 09 (2014). 732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401, http://
DOI: 10.1520/F2721-09R23. www.access.gpo.gov.
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