1、Designation: F2212 11Standard 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 F2212; the number immediately following the designation indicates the
2、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 () indicates an editorial change since the last revision or reapproval.INTRODUCTIONCollagen-based medical products are becoming more pr
3、evalent, 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 augmen
4、tation, 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-mater
5、ials 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 becumbers
6、ome. 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 specificparameters f
7、or 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 to,animal or cadaveric sources, human cell culture, or recombi-nant sources. The biological, immunological, or toxicologicalproperties
8、 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 on
9、 purified Type I collagen as a starting material forsurgical implants and substrates for tissue engineered medicalproducts (TEMPs); some methods may not be applicable forgelatin or tissue implants. This guide may serve as a templatefor characterization of other types of collagen.1.2 The biological r
10、esponse 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 values stated in SI units are to be r
11、egarded asstandard. No other units of measurement are included in thisstandard.1.4 WarningMercury has been designated by EPA andmany state agencies as a hazardous material that can causecentral nervous system, kidney, and liver damage. Mercury, orits vapor, may be hazardous to health and corrosive t
12、omaterials. Caution should be taken when handling mercury andmercury-containing products. See the applicable product Ma-terial Safety Data Sheet (MSDS) for details and EPAs website(http:/www.epa.gov/mercury/faq.htm) for additional informa-tion. Users should be aware that selling mercury or mercury-c
13、ontaining products, or both, in your state may be prohibited bystate law.1.5 The following precautionary caveat pertains only to thetest method portion, Section 5, of this guide. This standarddoes not purport to address all of the safety concerns, if any,1This guide is under the jurisdiction of ASTM
14、 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 April 1, 2011. Published May 2011. Originallyapproved in 2002. Last previous edition approved in 2009 as F2212 09 . D
15、OI:10.1520/F2212-11.2The boldface numbers in parentheses refer to the list of references at the end ofthis standard.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.associated with its use. It is the responsibility of the user of this
16、standard to establish appropriate safety and health practicesand determine the applicability of regulatory requirementsprior to use.2. Referenced Documents2.1 ASTM Standards:3E1298 Guide for Determination of Purity, Impurities, andContaminants in Biological Drug ProductsF619 Practice for Extraction
17、of Medical PlasticsF720 Practice for Testing Guinea Pigs for Contact Aller-gens: Guinea Pig Maximization TestF748 Practice for Selecting Generic Biological Test Meth-ods for Materials and DevicesF749 Practice for Evaluating Material Extracts by Intracu-taneous Injection in the RabbitF756 Practice fo
18、r Assessment of Hemolytic Properties ofMaterialsF763 Practice for Short-Term Screening of Implant Materi-alsF813 Practice for Direct Contact Cell Culture Evaluation ofMaterials for Medical DevicesF895 Test Method for Agar Diffusion Cell Culture Screen-ing for CytotoxicityF981 Practice for Assessment
19、 of Compatibility of Biomate-rials for Surgical Implants with Respect to Effect ofMaterials on Muscle and BoneF1251 Terminology Relating to Polymeric Biomaterials inMedical and Surgical DevicesF1439 Guide for Performance of Lifetime Bioassay for theTumorigenic Potential of Implant MaterialsF1903 Pra
20、ctice for Testing For Biological Responses toParticles In VitroF1904 Practice for Testing the Biological Responses toParticles in vivoF1905 Practice For Selecting Tests for Determining thePropensity of Materials to Cause Immunotoxicity4F1906 Practice for Evaluation of Immune Responses InBiocompatibi
21、lity Testing Using ELISA Tests, LymphocyteProliferation, and Cell Migration4F1983 Practice for Assessment of Compatibility ofAbsorbable/Resorbable Biomaterials for Implant Applica-tionsF2148 Practice for Evaluation of Delayed Contact Hyper-sensitivity Using the Murine Local Lymph Node Assay(LLNA)2.2
22、 ISO Standards:5ISO 109931 Biological Evaluation of Medical DevicesPart 1: Evaluation and TestingISO 109933 Tests for Genotoxicity, Carcinogenicity andReproductive ToxicityISO 109939 Framework for Identification and Quantifica-tion of Potential Degradation ProductsISO 1099310 Biological Evaluation o
23、f Medical DevicesPart 10: Tests for Irritation and Delayed-Type Hypersen-sitivityISO 1099317 Methods for Establishment of AllowableLimits for Leachable Substances Using Health-BasedRisk AssessmentISO 134081 Aseptic Processing of Health Care ProductsPart 1: General RequirementsISO 14971 Medical Devic
24、esApplication of Risk Manage-ment to Medical DevicesISO 224421 Animal Tissues and their Derivatives Utilizedin the Manufacture of Medical DevicesPart 1: Analysisand Management of RiskISO 224422 Animal Tissues and their Derivatives Utilizedin the Manufacture of Medical DevicesPart 2: Controlson Sourc
25、ing, Collection, and HandlingISO 224423 Animal Tissues and their Derivatives Utilizedin the Manufacture of Medical DevicesPart 3: Valida-tion and the Elimination and/or Inactivation of Virus andTransmissable Agents2.3 U. S. and European Pharmacopeia Documents:6United States Pharmacopeia (USP), Editi
26、on XXX (30)USP 30/NF 19 Viral Safety Evaluation of BiotechnologyProducts Derived from Cell Lines of Human or AnimalOriginEuropean Pharmacopeia 5.02.4 Code of Federal Regulations:721 CFR 312 Investigational New Drug Application21 CFR Part 820 Quality System RegulationFederal Register Vol. 43, No. 141
27、, Friday, July 21, 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, Propose
28、d Rule: Use of Materials 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 Human
29、Cellular and Tissue-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
30、, 1997/NoticesDraftGuidance for Preclinical and Clinical Investigations of3For 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 the standards Document Summary page onthe
31、ASTM website.4Withdrawn. The last approved version of this historical standard is referencedon www.astm.org.5Available from International Organization for Standardization (ISO), 1 rue deVaremb, Case postale 56, CH-1211, Geneva 20, Switzerland, http:/www.iso.ch.6Available from U.S. Pharmacopeia (USP)
32、, 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.F2212 112Urethral Bulking Agents used in the Treatment of UrinaryInco
33、ntinence. November 29, 1995. (ODE/DRARD/ULDB), Document No. 850Guidance for Industry and for FDA Reviewers, MedicalDevices Containing Materials Derived from AnimalSources (Except for In Vitro Diagnostic Devices), Novem-ber 6, 1998, U.S. Department of Health and HumanServices, Food and Drug Administr
34、ation, Center for De-vices and Radiological HealthCFR 610.13(b) Rabbit Pyrogen Assay2.5 ICH Documents:8ICH M3 Guidance for Industry M3 Nonclinical SafetyStudies for the Conduct of Human Clinical Trials forPharmaceuticals 62 FR 62922 (1997)ICH S2A Guideline for Industry S2A Specific Aspects ofRegulat
35、ory Genotoxicity Tests for Pharmaceuticals. 61 FR18199 (1996)ICH S2B Guidance for Industry S2B Genotoxicity: A Stan-dard Battery for Genotoxicity Testing of Pharmaceuticals62 FR 62472 (1997)ICH S5A Guideline for Industry S5A Detection of Toxicityto Reproduction for Medicinal Products. 59 FR 48746(19
36、94)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 (1996)ICH S1B Guidance for
37、 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 Studies of Pharmaceuticals:
38、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), 1998 Inter-national Confer
39、ence 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 52.6 FDA Documents:9FDA Guideline on Validation of the Limulus AmebocyteTest as an
40、 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 Cell Lines Used toProduce B
41、iologicalsU.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 Biologicals, Kinetic LAL te
42、chniques,DHHS, July 15, 19912.7 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-rility Performed in the V
43、alidation 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 Animal OriginValidation and
44、 Routine Control of Sterilization by LiquidChemical SterilantsAAMI ST67/CDV-2: 1999 Sterilization of MedicalDevicesRequirements for Products Labeled “Sterile”2.8 Other References:Draft Guidance for Preclinical and Clinical Investigations ofUrethral BulkingAgents Used in the Treatment of UrinaryIncon
45、tinence, 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/410/01-rev.2, Committee for
46、 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 MedicinalProducts (CPMP) Guidance Doc
47、ument for Decision Treesfor the Selection of Sterilisation Methods (CPMP/QWP/8Available from International Conference on Harmonisation of TechnicalRequirements for Registration of Pharmaceuticals for Human Use (ICH), ICHSecretariat, c/o IFPMA, 15 ch. Louis-Dunant, P.O. Box 195, 1211 Geneva 20,Switze
48、rland, http:/www.ich.org.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., Rockvill
49、e, 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 (EMEA), 7 Westferry Circus,Canary Wharf, London E14 4HB, U.K., http:/www.eudora.org/emea.html, andhttp:/www.emea.europa.eu/pdfs/human/bwp/TSE%20NFG%20410-rev2.pdf.F2212 113054/98 corr 2000) and Annex to Note for Guidance onDevelopment Pharmaceutics (CPMP/QWP/155/96)143. Terminology3.1 D
