1.1本含胶原蛋白生物材料特性指南旨在提供特性、特性和测试方法，供生产商、制造商和研究人员使用，以更清楚地识别所用的特定胶原蛋白材料。由于胶原蛋白的种类超过20种，并且每种胶原蛋白的性质不同，单个文档将很麻烦。本指南将重点介绍I型胶原蛋白的特性，I型胶原蛋白是哺乳动物中最丰富的胶原蛋白，尤其是在皮肤和骨骼中。从这些来源分离的胶原蛋白可能包含其他类型的胶原蛋白，例如III型和V型。本指南不提供任何胶原蛋白产品或产品混合物的具体参数，也不提供这些产品的预期用途的可接受性。胶原蛋白可以来自任何来源，包括但不限于动物或尸体来源、人类细胞培养或重组来源。 胶原蛋白的生物学、免疫学或毒理学特性可能因原料而异。必须彻底研究从上述每种来源制备的胶原蛋白的性质，因为尚未完全了解胶原蛋白性质随来源材料的变化。本指南旨在重点介绍纯化的I型胶原作为外科植入物和组织工程医疗产品基质的起始材料；有些方法可能不适用于明胶或组织植入物。本指南可作为其他类型胶原蛋白表征的模板。 1.2临床使用历史充分证明了软组织中胶原蛋白的生物反应 (1, 2) 和实验室研究 (3, 4, 5, 6) . 产品制造商负责特定应用的生物相容性和适用性。 1.3以国际单位制表示的数值应视为标准值。本标准不包括其他计量单位。 1.4 警告 — 环保局和许多国家机构已将汞指定为一种有害物质，可导致中枢神经系统、肾脏和肝脏损害。汞或其蒸汽可能对健康有害，并对材料具有腐蚀性。处理汞和含汞产品时应小心。有关详细信息和EPA，请参阅适用的产品材料安全数据表（MSDS） ’ s网站(http://www.epa.gov/mercury/faq.htm)了解更多信息。用户应意识到，州法律可能禁止在您所在州销售汞或含汞产品，或同时销售两者。 1.5 以下预防性警告仅适用于本指南第5节的试验方法部分。 本标准并非旨在解决与其使用相关的所有安全问题（如有）。本标准的用户有责任在使用前制定适当的安全和健康实践，并确定监管要求的适用性。 ====意义和用途====== 本指南的目的是为I型胶原作为外科植入物和组织工程医疗产品基质的起始材料的特性提供指导。本指南列出了与胶原蛋白功能直接相关的物理和化学参数。本指南可用于帮助选择和表征特定用途的适当胶原蛋白起始材料。并非所有测试或参数都适用于胶原蛋白的所有用途。 本指南涵盖的胶原蛋白可用于广泛的应用、形式或医疗产品，例如（但不限于）医疗设备、组织工程医疗产品（TEMP）或用于植入的细胞、药物或DNA传递设备。除其他因素外，胶原蛋白在实际应用中的使用应基于生物相容性和物理测试数据。本指南中的建议不应被解释为任何组织工程医疗产品或药物递送应用中临床成功的保证。 在确定所提供的胶原蛋白是否满足TEMP的使用要求时，应考虑以下一般方面。这些都是胶原蛋白的来源，化学和物理特性和测试，以及杂质概况。 在确定所提供的胶原蛋白是否满足在TEMPs中使用的要求时，应考虑与TEMPs产品的生产、监管和监管批准相关的适当监管机构的以下文件或其他适当指南: FDA CFR: 21 CFR 3:产品管辖权: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFR研究。cfm？CFRPart=3 21 CFR 58:非临床实验室研究的良好实验室规范: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFR研究。cfm？CFRPart=58 FDA/CDRH CFR和指南: 21 CFR第803部分:医疗器械报告: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFR研究。cfm？CFRPart=803 21 CFR 812:试验装置豁免: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFR研究。cfm？CFRPart=812 21 CFR 814:医疗器械上市前批准: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFR研究。cfm？CFRPart=814 21 CFR 820:质量体系法规: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFR研究。cfm？CFRPart=820 医疗器械制造商的设计控制指南: http://www.fda.gov/cdrh/comp/designgd.pdf 生产前质量保证规划建议 医疗器械制造商（FDA 90-4236）: http://www.fda.gov/cdrh/manual/appende.html 根据 生物研究监测计划 — 行业和FDA员工指南草案: http://www.fda.gov/cdrh/comp/guidance/1602.pdf FDA/CDRH搜索引擎: CDRH引导搜索引擎: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfggp/search.cfm CDRH上市前审批（PMA）搜索引擎: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm CDRH 510（k）搜索引擎: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm CDRH认可的标准搜索引擎: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm FDA/CBER CFR和指南: 21 CFR 312:研究性新药申请: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFR研究。cfm？CFRPart=312 21 CFR 314:FDA批准新药上市的申请: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFR研究。cfm？CFRPart=31 21 CFR 610:通用生物制品标准: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFR研究。cfm？CFRPart=610 21 CFR 1271:人体细胞、组织以及细胞和组织制品: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFR研究。cfm？CFRPart=1271 细胞的 & 基因治疗指南和其他出版物: http://www.fda.gov/cber/genetherapy/gtpubs.htm 人体组织指南和其他出版物: http://www.fda.gov/cber/tissue/docs.htm CBER产品批准信息: http://www.fda.gov/cber/efoi/approve. htm 21 CFR 600，601 BLA法规: http://www.access.gpo.gov/nara/cfr/waisidx_07/21cfrv7_07.html 21 CFR 210、211 GMP法规: http://www.access.gpo.gov/nara/cfr/waisidx_07/21cfr210_07.html

1.1 This guide for characterizing collagen-containing biomaterials is intended to provide characteristics, properties, and test methods for use by producers, manufacturers, and researchers to more clearly identify the specific collagen materials used. With greater than 20 types of collagen and the different properties of each, a single document would be cumbersome. This guide will focus on the characterization of Type I collagen, which is the most abundant collagen in mammals, especially in skin and bone. Collagen isolated from these sources may contain other types of collagen, for example, Type III and Type V. This guide does not provide specific parameters for any collagen product or mix of products or the acceptability of those products for the intended use. The collagen may be from any source, including, but not limited to, animal or cadaveric sources, human cell culture, or recombinant sources. The biological, immunological, or toxicological properties of the collagen may vary, depending on the source material. The properties of the collagen prepared from each of the above sources must be thoroughly investigated, as the changes in the collagen properties as a function of source materials is not thoroughly understood. This guide is intended to focus on purified Type I collagen as a starting material for surgical implants and substrates for tissue engineered medical products (TEMPs); some methods may not be applicable for gelatin or tissue implants. This guide may serve as a template for characterization of other types of collagen. 1.2 The biological response to collagen in soft tissue has been well documented by a history of clinical use (1, 2) and laboratory studies (3, 4, 5, 6) . Biocompatibility and appropriateness of use for a specific application(s) is the responsibility of the product manufacturer. 1.3 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard. 1.4 Warning — Mercury has been designated by EPA and many state agencies as a hazardous material that can cause central nervous system, kidney, and liver damage. Mercury, or its vapor, may be hazardous to health and corrosive to materials. Caution should be taken when handling mercury and mercury-containing products. See the applicable product Material Safety Data Sheet (MSDS) for details and EPA ’ s website (http://www.epa.gov/mercury/faq.htm) for additional information. Users should be aware that selling mercury or mercury-containing products, or both, in your state may be prohibited by state law. 1.5 The following precautionary caveat pertains only to the test method portion, Section 5, of this guide. 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 and health practices and determine the applicability of regulatory requirements prior to use. ====== Significance And Use ====== The objective of this guide is to provide guidance in the characterization of Type I collagen as a starting material for surgical implants and substrates for tissue engineered medical products (TEMPs). This guide contains a listing of physical and chemical parameters that are directly related to the function of collagen. This guide can be used as an aid in the selection and characterization of the appropriate collagen starting material for the specific use. Not all tests or parameters are applicable to all uses of collagen. The collagen covered by this guide may be used in a broad range of applications, forms, or medical products, for example (but not limited to) medical devices, tissue engineered medical products (TEMPs) or cell, drug, or DNA delivery devices for implantation. The use of collagen in a practical application should be based, among other factors, on biocompatibility and physical test data. Recommendations in this guide should not be interpreted as a guarantee of clinical success in any tissue engineered medical product or drug delivery application. The following general areas should be considered when determining if the collagen supplied satisfies requirements for use in TEMPs. These are source of collagen, chemical and physical characterization and testing, and impurities profile. The following documents or other appropriate guidances from appropriate regulatory bodies relating to the production, regulation and regulatory approval of TEMPs products should be considered when determining if the collagen supplied satisfies requirements for use in TEMPs: FDA CFR: 21 CFR 3: Product Jurisdiction: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?CFRPart=3 21 CFR 58: Good Laboratory Practice for Nonclinical Laboratory Studies: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?CFRPart=58 FDA/CDRH CFR and Guidances: 21 CFR Part 803: Medical Device Reporting: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?CFRPart=803 21 CFR 812: Investigational Device Exemptions: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?CFRPart=812 21 CFR 814: Premarket Approval of Medical Devices : http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?CFRPart=814 21 CFR 820: Quality System Regulation: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?CFRPart=820 Design Control Guidance for Medical Device Manufacturers: http://www.fda.gov/cdrh/comp/designgd.pdf Preproduction Quality Assurance Planning Recommendations for Medical Device Manufacturers (FDA 90-4236): http://www.fda.gov/cdrh/manual/appende.html The Review and Inspection of Premarket Approval Applications under the Bioresearch Monitoring Program — Draft Guidance for Industry and FDA Staff: http://www.fda.gov/cdrh/comp/guidance/1602.pdf FDA/CDRH Search Engines: CDRH Guidance Search Engine: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfggp/search.cfm CDRH Premarket Approval (PMA) Search Engine: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm CDRH 510(k) Search Engine: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm CDRH Recognized STANDARDS Search Engine : http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm FDA/CBER CFR and Guidances: 21 CFR 312: Investigational New Drug Application : http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?CFRPart=312 21 CFR 314: Applications for FDA Approval to Market a New Drug: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?CFRPart=31 21 CFR 610: General Biological Products Standards: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?CFRPart=610 21 CFR 1271: Human Cells, Tissues and Cellular and Tissue-Based Products: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?CFRPart=1271 Cellular & Gene Therapy Guidances and Other Publications: http://www.fda.gov/cber/genetherapy/gtpubs.htm Human Tissue Guidances and Other Publications: http://www.fda.gov/cber/tissue/docs.htm CBER Product Approval Information: http://www.fda.gov/cber/efoi/approve.htm 21 CFR 600, 601 BLA Regulations: http://www.access.gpo.gov/nara/cfr/waisidx_07/21cfrv7_07.html 21 CFR 210, 211 GMP Regulations: http://www.access.gpo.gov/nara/cfr/waisidx_07/21cfr210_07.html