1、Designation: F 2212 08Standard Guide forCharacterization of Type I Collagen as Starting Material forSurgical Implants and Substrates for Tissue EngineeredMedical Products (TEMPs)1This standard is issued under the fixed designation F 2212; the number immediately following the designation indicates th
2、e year oforiginal adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon (e) indicates an editorial change since the last revision or reapproval.INTRODUCTIONCollagen-based medical products are becoming more
3、 prevalent, especially in the area of soft tissueaugmentation. The use of collagen in surgery dates back to the late 1800s, with the use of catgutsutures, human cadaveric skin, and fascia. More recently, collagen has been used in hemostaticsponges, dermal equivalents, injectables for soft tissue aug
4、mentation, as a matrix for cell-basedproducts and as a vehicle for drug delivery. It is because of the versatility of collagen in medicalapplications that specific characterizations should be performed as a way to compare materials.1. Scope1.1 This guide for characterizing collagen-containing bio-ma
5、terials is intended to provide characteristics, properties, andtest methods for use by producers, manufacturers, and re-searchers to more clearly identify the specific collagen mate-rials used. With greater than 20 types of collagen and thedifferent properties of each, a single document would becumb
6、ersome. This guide will focus on the characterization ofType I collagen, which is the most abundant collagen inmammals, especially in skin and bone. Collagen isolated fromthese sources may contain other types of collagen, for example,Type III and Type V. This guide does not provide specificparameter
7、s for any collagen product or mix of products or theacceptability of those products for the intended use. Thecollagen may be from any source, including, but not limited toanimal or cadaveric sources, human cell culture, or recombi-nant sources. The biological, immunological, or toxicologicalproperti
8、es of the collagen may vary depending on the sourcematerial. The properties of the collagen prepared from each ofthe above sources must be thoroughly investigated, as thechanges in the collagen properties as a function of sourcematerials is not thoroughly understood. This guide is intendedto focus o
9、n purified Type I collagen as a starting material forsurgical implants and substrates for tissue engineered medicalproducts (TEMPs); some methods may not be applicable forgelatin nor for tissue implants. This guide may serve as atemplate for characterization of other types of collagen.1.2 The biolog
10、ical response to collagen in soft tissue hasbeen well documented by a history of clinical use (1, 2)2andlaboratory studies (3, 4, 5, 6). Biocompatibility and appropri-ateness of use for a specific application(s) is the responsibilityof the product manufacturer.1.3 The following precautionary caveat
11、pertains only to thetest method portion, Section 5, of this guide. This standarddoes not purport to address all of the safety concerns, if any,associated with its use. It is the responsibility of the user of thisstandard to establish appropriate safety and health practicesand determine the applicabi
12、lity of regulatory requirementsprior to use.2. Referenced Documents2.1 ASTM Standards:3E 1298 Guide for Determination of Purity, Impurities, andContaminants in Biological Drug ProductsF 619 Practice for Extraction of Medical PlasticsF 720 Practice for Testing Guinea Pigs for Contact Aller-gens: Guin
13、ea Pig Maximization TestF 748 Practice for Selecting Generic Biological Test Meth-ods for Materials and DevicesF 749 Practice for Evaluating Material Extracts by Intracu-taneous Injection in the RabbitF 756 Practice for Assessment of Hemolytic Properties ofMaterials1This guide is under the jurisdict
14、ion of ASTM Committee F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.42 on Biomaterials and Biomolecules for TEMPs.Current edition approved Feb. 1, 2008. Published March 2008. Originallyapproved in 2002. Last previous edition approved in 2007 as
15、F 2212 02 (2007)e1.2The boldface numbers in parentheses refer to the list of references at the end ofthis standard.3For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Customer Service at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to t
16、he standards Document Summary page onthe ASTM website.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.F 763 Practice for Short-Term Screening of Implant Mate-rialsF 813 Practice for Direct Contact Cell Culture Evaluation ofMaterials
17、for Medical DevicesF 895 Test Method for Agar Diffusion Cell Culture Screen-ing for CytotoxicityF 981 Practice for Assessment of Compatibility of Bioma-terials for Surgical Implants with Respect to Effect ofMaterials on Muscle and BoneF 1251 Terminology Relating to Polymeric Biomaterials inMedical a
18、nd Surgical DevicesF 1439 Guide for Performance of Lifetime Bioassay for theTumorigenic Potential of Implant MaterialsF 1903 Practice for Testing For Biological Responses toParticles in vitroF 1904 Practice for Testing the Biological Responses toParticles in vivoF 1905 Practice For Selecting Tests f
19、or Determining thePropensity of Materials to Cause ImmunotoxicityF 1906 Practice for Evaluation of Immune Responses InBiocompatibility Testing Using ELISA Tests, LymphocyteProliferation, and Cell MigrationF 1983 Practice for Assessment of Compatibility ofAbsorbable/Resorbable Biomaterials for Implan
20、t Applica-tionsF 2148 Practice for Evaluation of Delayed Contact Hyper-sensitivity Using the Murine Local Lymph Node Assay(LLNA)2.2 ISO Standards:4ISO 109931 Biological Evaluation of Medical DevicesPart 1: Evaluation and TestingISO 109933 Tests for Genotoxicity, Carcinogenicity andReproductive Toxic
21、ityISO 109939 Framework for Identification and Quantifica-tion of Potential Degradation ProductsISO 1099310 Biological Evaluation of Medical DevicesPart 10: Tests for Irritation and Delayed-Type Hypersen-sitivityISO 1099317 Methods for Establishment of AllowableLimits for Leachable Substances Using
22、Health-BasedRisk AssessmentISO 134081 Aseptic Processing of Health Care ProductsPart 1: General RequirementsISO 14971 Medical DevicesApplication of Risk Manage-ment to Medical Devices2.3 EN (European Norm) Documents:5EN 124421 Animal Tissues and their Derivatives Utilizedin the Manufacture of Medica
23、l DevicesPart 1: Analysisand Management of RiskEN 124422 Controls on Sourcing, Collection and Han-dlingEN 124423 Validation of the Elimination and/or Inactiva-tion of Virus and Transmissible Agents2.4 U. S. and European Pharmacopeia Documents:6United States Pharmacopeia (USP), Edition XXX (30)USP 30
24、/NF 19 Viral Safety Evaluation of BiotechnologyProducts Derived from Cell Lines of Human or AnimalOriginEuropean Pharmacopeia 5.02.5 Code of Federal Regulations:721 CFR 312 Investigational New Drug Application21 CFR Part 820 Quality System RegulationFederal Register Vol. 43, No. 141, Friday, July 21
25、, 197821 CFR Parts 207, 807, and 1271 Human Cells, Tissues andCellular and Tissue-Based Products, Establishment Reg-istration and ListingFederal Register, Vol. 66, No. 13, Jan 19, 2001/Rules andRegulations, p. 5447Federal Register, Vol. 72, No. 8, Jan. 12, 2007, pp.15811619, Proposed Rule: Use of Ma
26、terials Derivedfrom Cattle in Medical Products Intended for Use inHumans and Drugs Intended for Use in Ruminants21 CFR Part 1271, Part C Suitability Determination forDonors of Human Cell and Tissue-based Products, Pro-posed RuleCurrent Good Tissue Practice for Manufacturers of HumanCellular and Tiss
27、ue-Based Products, Inspection and En-forcement. Proposed Rule. Federal Register/Vol. 66, No.5/January 8, 2001/Proposed Rules, pp. 1552-1559Guidance for Screening and Testing of Donors of HumanTissue Intended for Transplantation, Availability. FederalRegister/Vol. 62, No. 145/July 29, 1997/NoticesDra
28、ftGuidance for Preclinical and Clinical Investigations ofUrethral Bulking Agents used in the Treatment of UrinaryIncontinence. November 29, 1995. (ODE/DRARD/ULDB), Document No. 850Guidance for Industry and for FDA Reviewers, MedicalDevices Containing Materials Derived from AnimalSources (Except for
29、In Vitro Diagnostic Devices), Novem-ber 6, 1998, U.S. Department of Health and HumanServices, Food and Drug Administration, Center for De-vices and Radiological HealthCFR 610.13(b) Rabbit Pyrogen Assay2.6 ICH Documents:8ICH M3 Guidance for Industry M3 Nonclinical SafetyStudies for the Conduct of Hum
30、an Clinical Trials forPharmaceuticals 62 FR 62922 (1997)ICH S2A Guideline for Industry S2A Specific Aspects ofRegulatory Genotoxicity Tests for Pharmaceuticals. 61 FR18199 (1996)ICH S2B Guidance for Industry S2B Genotoxicity: A Stan-dard Battery for Genotoxicity Testing of Pharmaceuticals4Available
31、from International Organization for Standardization (ISO), 1 rue deVaremb, Case postale 56, CH-1211, Geneva 20, Switzerland, http:/www.iso.ch.5Available from European Committee for Standardization (CEN), 36 rue deStassart, B-1050, Brussels, Belgium, http:/www.cenorm.be.6Available from U.S. Pharmacop
32、eia (USP), 12601 Twinbrook Pkwy., Rockville,MD 20852-1790, http:/www.usp.org.7Available from U.S. Government Printing Office Superintendent of Documents,732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401, http:/www.access.gpo.gov.8Available from International Conference on Harmonisation of
33、 TechnicalRequirements for Registration of Pharmaceuticals for Human Use (ICH), ICHSecretariat, c/o IFPMA, 15 ch. Louis-Dunant, P.O. Box 195, 1211 Geneva 20,Switzerland, http:/www.ich.org.F221208262 FR 62472 (1997)ICH S5A Guideline for Industry S5A Detection of Toxicityto Reproduction for Medicinal
34、Products. 59 FR 48746(1994)ICH S5B Guidance for Industry S5B Detection of Toxicityto Reproduction for Medicinal Products: Addendum onToxicity to Male Fertility. 61 FR 15360 (1996)ICH S1A Guideline for Industry S1A The Need for Long-term Rodent Carcinogenicity Studies of Pharmaceuticals.61 FR 8153 (1
35、996)ICH S1B Guidance for Industry S1B Testing for Carcino-genicity of Pharmaceuticals. 63 FR 8983 (1998)ICH S1C Guideline for Industry S1C Dose Selection forCarcinogenicity Studies of Pharmaceuticals. 60 FR 11278(1995)ICH S1C(R) Guidance for Industry Addendum to DoseSelection for Carcinogenicity Stu
36、dies of Pharmaceuticals:Addition of a Limit Dose and Related Notes. 62 FR 64259(1997)ICH Q1AICH Harmonized Tripartite Guidance for StabilityTesting of New Drug Substances and Products (September23, 1994)U.S. Food and Drug Administration (FDA and Committeefor Proprietary Medicinal Products (CPMP), 19
37、98 Inter-national Conference on Harmonization (ICH), Quality ofBiotechnological Products: Viral Safety Evaluation ofBiotechnology Products Derived from Cell Lines of Hu-man or Animal Origin, Consensus Guideline ICH ViralSafety Document: Step 52.7 FDA Documents:9FDA Guideline on Validation of the Lim
38、ulus AmebocyteTest as an End-Product Endotoxin Test for Human andAnimal Parenteral Drugs, Biological Products and Health-care Products, DHHS, December 1987U.S. Food and Drug Administration (FDA) Center forBiologics Evaluation and Research (CBER), 1993 Pointsto Consider in the Characterization of Cel
39、l Lines Used toProduce BiologicalsU.S. Food and Drug Administration (FDA) Center forBiologics Evaluation and Research (CBER), 1997 Pointsto Consider in the Manufacture and Testing of MonoclonalAntibody Products for Human Use, 94D-0259FDA Interim Guidance for Human and Veterinary DrugProducts and Bio
40、logicals, Kinetic LAL techniques,DHHS, July 15, 19912.8 AAMI Documents:10ANSI/AAMI/ISO 11737-1: 2006 Sterilization of MedicalDevicesMicrobiological MethodsPart 1: Estimationof Bioburden on ProductANSI/AAMI/ISO 11737-2: 1998 Sterilization of MedicalDevicesMicrobiological MethodsPart 2: Tests of Ste-r
41、ility Performed in the Validation of a Sterilization ProcessAAMI TIR No. 19-1998 Guidance for ANSI/AAMI/ISO10993-7: 1995, Biological Evaluation of MedicalDevicesPart 7: Ethylene Oxide Sterilization ResidualsAAMI/ISO 14160-1998 Sterilization of Single-Use MedicalDevices Incorporating Materials of Ani
42、mal OriginValidation and Routine Control of Sterilization by LiquidChemical SterilantsAAMI ST67/CDV-2: 1999 Sterilization of MedicalDevicesRequirements for Products Labeled “Sterile”2.9 Other References:Draft Guidance for Preclinical and Clinical Investigations ofUrethral BulkingAgents Used in the T
43、reatment of UrinaryIncontinence, November 29, 1995. (ODE/DRARD/ULDB), Document No. 85011Council Directive 93/42/EEC, with Respect to MedicalDevices Using Tissues of Animal Origin12Commission Directive 2003/32/EC, with Respect to Medi-cal Devices Manufactured Using Tissues of Animal Ori-gin12EMEA/410
44、/01-rev.2, Committee for Proprietary MedicalProducts, Note for Guidance on Minimizing the Risk ofTransmitting Animal Spongiform Encephalopathy Agentsvia Human and Veterinary Medical Products13The European Agency for the Evaluation of MedicinalProducts, (EMEA), Committee for Proprietary MedicinalProd
45、ucts (CPMP) Guidance Document for Decision Treesfor the Selection of Sterilisation Methods (CPMP/QWP/054/98 corr 2000) and Annex to Note for Guidance onDevelopment Pharmaceutics (CPMP/QWP/155/96)143. Terminology3.1 Definitions:3.1.1 adventitious agents, nan unintentionally introducedmicrobiological
46、or other infectious contaminant. In the produc-tion of TEMPs, these agents may be unintentionally introducedinto the process stream or the final product, or both.3.1.2 biocompatibility, na material may be consideredbiocompatible if the material performs with an appropriate hostresponse in a specific
47、 application (7).3.1.3 collagen, nCollagens form a family of secretedproteins with predominantly structural function. At leasttwenty genetically different family members have been iden-tified so far. Several groups of collagen molecules have beenclassified based upon protein domain structures, macro
48、molecu-lar assemblies, and exon structures of the corresponding genes.All collagens have a unique triple helical structure configura-tion of three polypeptide units known as alpha-chains. Properalignment of the alpha chains of the collagen molecule requiresa highly complex enzymatic and chemical int
49、eraction in vivo.9Available from Food and Drug Administration (FDA), 5600 Fishers Ln.,Rockville, MD 20857, http:/www.fda.gov.10Association for the Advancement of Medical Instrumentation, 1110 N. GlebeRd., Suite 220, Arlington, VA 222014795.11Available from the FDA, 5600 Fishers Ln., Rockville, MD 20857. http:/www.fda.gov/cdrh/ode/oderp850.html.12Available from Office for Official Publications of the EuropeanCommunitiesEuropean Law, 2, rue Mercier, L-2985, Luxembourg, http:/eur-lex.europa.eu/en/index.htm.13Available from European Medicines Agency (E
