【国外标准】 Standard Guide for Pre-clinical in vivo Evaluation of Spinal Fusion

4.1 This guide is aimed at providing a range of in vivo models to aid in pre-clinical research and development of tissue-engineered medical products (TEMPs) intended for the clinical repair or regeneration of bone in the spine.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 utilize 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.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.1.1 This guide covers general guidelines for the pre-clinical in vivo assessment of tissue-engineered medical products (TEMPs) intended to repair or regenerate bone in an interbody and/or posterolateral spinal environment. TEMPs included in this guide may be composed of, but are not limited to, natural or synthetic biomaterials 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 document represent a stringent test of a material’s ability to induce and/or augment bone growth in the spinal environment.1.2 While clinically TEMPs may be combined with hardware for initial stabilization or other purposes, the focus of this guide is on the appropriateness of the animal model chosen and evaluation of the TEMP-induced repair and as such does not focus on issues of components or constructs.1.3 Guidelines include a description and rationale of various animal models for the in vivo assessment of the TEMP. The animal models utilize a range of species including rat (murine), rabbit (lapine), dog (canine), goat (caprine), pig (porcine), sheep (ovine), and non-human primate (primates). Outcome measures include in vivo assessments based on radiographic, histologic, and CT imaging as well as subsequent in vitro assessments of the repair, including histologic analyses and mechanical testing. All methods are described briefly and referenced. The user should refer to specific test methods for additional detail.1.4 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 Referenced Documents (Section 2).1.5 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.1.6 Other pre-clinical 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.1.7 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.1.8 The values stated in inch-pound units are to be regarded as standard. The values given in parentheses are mathematical conversions to SI units that are provided for information only and are not considered standard.1.9 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.