ASTM F2529-13
(Guide)Standard Guide for in vivo Evaluation of Osteoinductive Potential for Materials Containing Demineralized Bone (DBM)
Standard Guide for <emph type="bdit">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 and health 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.
General Information
Standards Content (Sample)
NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
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Designation: F2529 − 13
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 D5056Test Method for Trace Metals in Petroleum Coke by
Atomic Absorption
1.1 This guide covers general guidelines to evaluate the
E508Test Method for Determination of Calcium and Mag-
effectiveness of DBM-containing products intended to cause
nesium in Iron Ores by Flame Atomic Absorption Spec-
and/or promote bone formation when implanted or injected in
trometry
vivo. This guide is applicable to products that may be com-
F565PracticeforCareandHandlingofOrthopedicImplants
posed of one or more of the following components: natural
and Instruments
biomaterials (such as demineralized bone), and synthetic bio-
F895TestMethodforAgarDiffusionCellCultureScreening
materials (such as calcium sulfate, glycerol, and reverse phase
for Cytotoxicity
polymeric compounds) that act as additives, fillers, and/or
F981Practice for Assessment of Compatibility of Biomate-
excipients (radioprotective agents, preservatives, and/or han-
rials for Surgical Implants with Respect to Effect of
dling agents) to make the demineralized bone easier to ma-
Materials on Muscle and Insertion into Bone
nipulate. It should not be assumed that products evaluated
F1854Test Method for Stereological Evaluation of Porous
favorably using this guidance will form bone when used in a
Coatings on Medical Implants
clinical setting. The primary purpose of this guide is to
F2131Test Method forIn Vitro Biological Activity of Re-
facilitate the equitable comparison of unique bone-forming
combinant Human Bone Morphogenetic Protein-2
products in in vivo heterotopic models of osteoinductivity.The
(rhBMP-2) Using the W-20 Mouse Stromal Cell Line
purpose of this guide is not to exclude other established
F2721Guide for Pre-clinical in vivo Evaluation in Critical
methods.
Size Segmental Bone Defects
1.2 The values stated in SI units are to be regarded as
3
2.2 Federal Documents:
standard. No other units of measurement are included in this
21 CFR 58Good Laboratory Practice for Nonclinical Labo-
standard.
ratory Studies
1.3 This standard does not purport to address all of the
21 CFR 820Quality System Regulation
safety concerns, if any, associated with the use of DBM-
21 CFR 1270Human Tissue Intended for Transplantation
containing bone-forming/promoting products. It is the respon-
21 CFR 1271Human Cells, Tissues, and Cellular and
sibility of the user of this standard to establish appropriate
Tissue-Based Products
safetyandhealthpracticesinvolvedinthedevelopmentofsaid
21 CFR 610.12General Biological Products Standards—
products in accordance with applicable regulatory guidance
General Provisions—Sterility
documents and in implementing this guide to evaluate the
Q1E Evaluation of Stability Data,FDAGuidance for Indus-
bone-forming/promoting capabilities of the product.
try
Container and Closure Integrity Testingin Lieu of Sterility
2. Referenced Documents
Testing as a Component of the Stability Protocol for
2
2.1 ASTM Standards: Sterile Products, FDA Guidance Document
D1193Specification for Reagent Water
Eligibility Determination for Donors of Human Cells,
Tissues, and Cellular and Tissue-Based Products,Guid-
ance for Industry
1
ThistestmethodisunderthejurisdictionofASTMCommitteeF04onMedical
Guidance for the Preparation of a Premarket Notification
andSurgicalMaterialsandDevicesandisthedirectresponsibilityofSubcommittee
F04.44 on Assessment for TEMPs. Application for a Surgical Mesh,Guidance for Industry
Current edition approved Feb. 1, 2013. Published August 2013. DOI: 10.1520/
and/or for FDA Reviewers/Staff and/or Compliance
F2529–13.
2
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
3
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F2529 − 13
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2.3 AAMI/ISO Documents: 3.1.4 bone forming product (containing DBM)—as used in
AAMI TIR 17Compatibility of Materials Subject to Steril- this guide, a DBM-containing bone forming product may be
ization comprisedofmultiplecomponentsincluding,butn
...
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