ASTM F2529-13(2021)
(Guide)Standard Guide for in vivo Evaluation of Osteoinductive Potential for Materials Containing Demineralized Bone (DBM)
Standard Guide for <emph type="ital"> in vivo</emph> Evaluation of Osteoinductive Potential for Materials Containing Demineralized Bone (DBM)
SIGNIFICANCE AND USE
4.1 This guide covers animal implantation methods and analysis of the explanted DBM-containing material to determine whether a material or substance possesses osteoinductive potential, as defined by its ability to cause bone to form in vivo at a site that would otherwise not support bone formation, that is, heterotopically in a skeletal muscle implant site. For in vitro evaluation see Test Method F2131 for in vitro assessment of rhBMP 2.
4.2 The test methods described here may be suitable for defining product specifications, cGMP lot release testing, research evaluation, regulatory submission, and so forth, but a positive outcome should not be presumed to indicate that the product will be osteoinductive in a human clinical application. At present, the only direct assays to assess new bone formation are in vivo, since the property of bone conduction or induction can only be assessed in a heterotopic or orthotopic site in a living animal. When these products are implanted in an orthotopic site, osteogenic factors already present at the implantation site may contribute to and enhance bone formation in conjunction with the osteoconductive nature of the product. Thus, orthotopic implantation of products may result in bone formation by acting on existing bone-forming cells and not by causing mesenchymal stem cells to become osteochondroprogenitor cells. In contrast, when these products are implanted in a heterotopic site, no native osteogenic factors are present to contribute to or enhance bone formation. Thus, heterotopic implantation of products will only result in new bone formation by causing mesenchymal stem cells to become osteochondroprogenitor cells. In vitro assays have been described and some believe they may correlate to the results obtained from in vivo assays. However such in vitro assays measure only some of the biochemical marker(s) associated with in vivo bone formation and are therefore only indirect assays for osteoinductive activity or the capacity t...
SCOPE
1.1 This guide covers general guidelines to evaluate the effectiveness of DBM-containing products intended to cause and/or promote bone formation when implanted or injected in vivo. This guide is applicable to products that may be composed of one or more of the following components: natural biomaterials (such as demineralized bone), and synthetic biomaterials (such as calcium sulfate, glycerol, and reverse phase polymeric compounds) that act as additives, fillers, and/or excipients (radioprotective agents, preservatives, and/or handling agents) to make the demineralized bone easier to manipulate. It should not be assumed that products evaluated favorably using this guidance will form bone when used in a clinical setting. The primary purpose of this guide is to facilitate the equitable comparison of unique bone-forming products in in vivo heterotopic models of osteoinductivity. The purpose of this guide is not to exclude other established methods.
1.2 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.
1.3 This standard does not purport to address all of the safety concerns, if any, associated with the use of DBM-containing bone-forming/promoting products. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices involved in the development of said products in accordance with applicable regulatory guidance documents and in implementing this guide to evaluate the bone-forming/promoting capabilities of the product.
1.4 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
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: F2529 − 13 (Reapproved 2021)
Standard Guide for
in vivo Evaluation of Osteoinductive Potential for Materials
1
Containing Demineralized Bone (DBM)
This standard is issued under the fixed designation F2529; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision.Anumber in parentheses indicates the year of last reapproval.A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope mendations issued by the World Trade Organization Technical
Barriers to Trade (TBT) Committee.
1.1 This guide covers general guidelines to evaluate the
effectiveness of DBM-containing products intended to cause
2. Referenced Documents
and/or promote bone formation when implanted or injected in
2
2.1 ASTM Standards:
vivo. This guide is applicable to products that may be com-
D1193Specification for Reagent Water
posed of one or more of the following components: natural
D5056Test Method for Trace Metals in Petroleum Coke by
biomaterials (such as demineralized bone), and synthetic bio-
Atomic Absorption
materials (such as calcium sulfate, glycerol, and reverse phase
E508Test Method for Determination of Calcium and Mag-
polymeric compounds) that act as additives, fillers, and/or
nesium in Iron Ores by Flame Atomic Absorption Spec-
excipients (radioprotective agents, preservatives, and/or han-
trometry
dling agents) to make the demineralized bone easier to ma-
F565PracticeforCareandHandlingofOrthopedicImplants
nipulate. It should not be assumed that products evaluated
and Instruments
favorably using this guidance will form bone when used in a
F895TestMethodforAgarDiffusionCellCultureScreening
clinical setting. The primary purpose of this guide is to
for Cytotoxicity
facilitate the equitable comparison of unique bone-forming
F981Practice for Assessment of Compatibility of Biomate-
products in in vivo heterotopic models of osteoinductivity.The
rials for Surgical Implants with Respect to Effect of
purpose of this guide is not to exclude other established
Materials on Muscle and Insertion into Bone
methods.
F1854Test Method for Stereological Evaluation of Porous
1.2 The values stated in SI units are to be regarded as
Coatings on Medical Implants
standard. No other units of measurement are included in this
F2131Test Method forIn Vitro Biological Activity of Re-
standard.
combinant Human Bone Morphogenetic Protein-2
(rhBMP-2) Using the W-20 Mouse Stromal Cell Line
1.3 This standard does not purport to address all of the
F2721Guide for Pre-clinical in vivo Evaluation in Critical
safety concerns, if any, associated with the use of DBM-
Size Segmental Bone Defects
containing bone-forming/promoting products. It is the respon-
3
sibility of the user of this standard to establish appropriate 2.2 Federal Documents:
safety, health, and environmental practices involved in the 21 CFR 58Good Laboratory Practice for Nonclinical Labo-
development of said products in accordance with applicable ratory Studies
regulatory guidance documents and in implementing this guide 21 CFR 820Quality System Regulation
to evaluate the bone-forming/promoting capabilities of the 21 CFR 1270Human Tissue Intended for Transplantation
product. 21 CFR 1271Human Cells, Tissues, and Cellular and
Tissue-Based Products
1.4 This international standard was developed in accor-
21 CFR 610.12General Biological Products Standards—
dance with internationally recognized principles on standard-
General Provisions—Sterility
ization established in the Decision on Principles for the
Q1E Evaluation of Stability DataFDAGuidance for Indus-
Development of International Standards, Guides and Recom-
try
1 2
This guide is under the jurisdiction ofASTM Committee F04 on Medical and For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Surgical Materials and Devices and is the direct responsibility of Subcommittee contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
F04.44 on Assessment for TEMPs. Standardsvolumeinformation,refertothestandard’sDocumentSummarypageon
Current edition approved Aug. 1, 2021. Published August 2021. Originally the ASTM website.
3
approved in 2013. Last previous edition approved in 2013 as F2529–13. DOI: Available from Food and DrugAdministration (FDA), 10903 New Hampshire
10.1520/F2529-13R21. Ave., Silver Spring, MD 20993-0002, http://www.fda.gov.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
1
---------------------- Page: 1 ----------------------
F2529 − 13 (2021)
Container and Closure Integrity Testing in Lieu o
...
Questions, Comments and Discussion
Ask us and Technical Secretary will try to provide an answer. You can facilitate discussion about the standard in here.