1、Designation: F2064 00 (Reapproved 2006)1F2064 14Standard Guide forCharacterization and Testing of Alginates as StartingMaterials Intended for Use in Biomedical and Tissue-Engineered Medical Products ApplicationTissue EngineeredMedical Product Applications1This standard is issued under the fixed desi
2、gnation F2064; the number immediately following the designation indicates the 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
3、or reapproval.1 NOTEMercury warning was editorially added in April 2008.INTRODUCTIONAlginate has found uses in a variety of products ranging from simple technical applications such asviscosifiers to advanced biomedical matrices providing controlled drug delivery from immobilizedliving cells. As for
4、most hydrocolloids, the functionality of alginate is related to its chemical andstructural composition. The aim of this guide is to identify key parameters relevant for thefunctionality and characterization of alginates for the development of new commercial applications ofalginates for the biomedica
5、l and pharmaceutical industries.1. Scope1.1 This guide covers the evaluation of alginates suitable for use in biomedical or pharmaceutical applications, or both,including, but not limited to, tissue-engineered medical products (TEMPS).Tissue Engineered Medical Products (TEMPs).1.2 This guide address
6、es key parameters relevant for the functionality, characterization, and purity of alginates.1.3 As with any material, some characteristics of alginates may be altered by processing techniques (such as molding, extrusion,machining, assembly, sterilization, and so forth) required for the production of
7、 a specific part or device. Therefore, properties offabricated forms of this polymer should be evaluated using test methods that are appropriate to ensure safety and efficacy and arenot addressed in this guide.1.4 WarningMercury has been designated by EPA and many state agencies as a hazardous mater
8、ial that can cause centralnervous system, kidney, and liver damage. Mercury, or its vapor, may be hazardous to health and corrosive to materials. Cautionshould be taken when handling mercury and mercury-containing products. See the applicable product Material Safety Data Sheet(MSDS) for details and
9、EPAs website (http:/www.epa.gov/mercury/faq.htm) for additional information. Users should be awarethat selling mercury or mercury-containing products, or both, in your state may be prohibited by state law.1.5 This standard does not purport to address all of the safety concerns, if any, associated wi
10、th its use. It is the responsibilityof the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatorylimitations prior to use.2. Referenced Documents2.1 ASTM Standards:2D2196 Test Methods for Rheological Properties of Non-Newtonian Materi
11、als by Rotational (Brookfield type) ViscometerF619 Practice for Extraction of Medical PlasticsF748 Practice for Selecting Generic Biological Test Methods for Materials and Devices1 This guide is under the jurisdiction of ASTM Committee F04 on Medical and Surgical Materials and Devices and is the dir
12、ect responsibility of Subcommittee F04.42on Biomaterials and Biomolecules for TEMPs.Current edition approved March 1, 2006Oct. 1, 2014. Published April 2006February 2015. Originally approved in 2000. Last previous edition approved in 2000 asF2064 00.F2064 00 (2006)1. DOI: 10.1520/F2064-00R06E01.10.1
13、520/F2064-14.2 For referencedASTM standards, visit theASTM website, www.astm.org, or contactASTM Customer Service at serviceastm.org. For Annual Book of ASTM Standardsvolume information, refer to the standards Document Summary page on the ASTM website.This document is not an ASTM standard and is int
14、ended only to provide the user of an ASTM standard an indication of what changes have been made to the previous version. Becauseit may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the curr
15、ent versionof the standard as published by ASTM is to be considered the official document.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States1F749 Practice for Evaluating Material Extracts by Intracutaneous Injection in the RabbitF756 Pra
16、ctice for Assessment of Hemolytic Properties of MaterialsF763 Practice for Short-Term Screening of Implant MaterialsF813 Practice for Direct Contact Cell Culture Evaluation of Materials for Medical DevicesF895 Test Method for Agar Diffusion Cell Culture Screening for CytotoxicityF981 Practice for As
17、sessment of Compatibility of Biomaterials for Surgical Implants with Respect to Effect of Materials onMuscle and BoneF1251 Terminology Relating to Polymeric Biomaterials in Medical and Surgical Devices (Withdrawn 2012)3F1439 Guide for Performance of Lifetime Bioassay for the Tumorigenic Potential of
18、 Implant MaterialsF1903 Practice for Testing For Biological Responses to Particles In VitroF1904 Practice for Testing the Biological Responses to Particles in vivoF1905 Practice For Selecting Tests for Determining the Propensity of Materials to Cause Immunotoxicity (Withdrawn 2011)3F1906 Practice fo
19、r Evaluation of Immune Responses In Biocompatibility Testing Using ELISATests, Lymphocyte Proliferation,and Cell Migration (Withdrawn 2011)3F2259 Test Method for Determining the Chemical Composition and Sequence in Alginate by Proton Nuclear MagneticResonance (1H NMR) SpectroscopyF2315 Guide for Imm
20、obilization or Encapsulation of Living Cells or Tissue in Alginate GelsF2605 Test Method for Determining the Molar Mass of Sodium Alginate by Size Exclusion Chromatography with Multi-angleLight Scattering Detection (SEC-MALS)2.2 USP Document:4USP Monograph USP 24/NF 1935/NF 30 Sodium Alginate2.3 ISO
21、 Documents:5ISO 31-8 Quantities and units Part 8: Physical chemistry and molecular physicsISO 10993 Biological Evaluation of Medical Devices:ISO 10993-1 Biological Evaluation of Medical DevicesPart 1: Evaluation and TestingISO 10993-3 Part 3: Tests for Genotoxicity, Carcinogenicity and Reproductive
22、ToxicityISO 10993-9Part 9: Framework for Identification and Quantification of Potential Degradation ProductsISO 10993-17Part 17: Methods for Establishment of Allowable Limits for Leachable Substances Using Health-Based RiskAssessmentISO 13408-1: 1998: Aseptic Processing of Health Care ProductsPart 1
23、: General Requirements.2.4 ICH Documents:6International Conference on Harmonization (ICH) S2B Genotoxicity:S2 A Standard Battery for Genotoxicity Testing ofPharmaceuticals (July 1997)Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended forHuman UseInternational Confe
24、rence on Harmonization (ICH) Q1AICH Harmonized Tripartite Guidance for Stability Testing of New DrugSubstances and Products (September 23, 1994)(2003)2.5 FDA Documents:7FDA Guideline on Validation of the Limulus Amebocyte Test as an End-Product Endotoxin Test for Human and AnimalParenteral Drugs, Bi
25、ological Products and Healthcare Products. DHHS, December 1987FDA.FDA Interim Guidance for Interim Guidance for Human and Veterinary Drug Products and Biologicals. Kinetic LALtechniques. DHHS, July 15, 19912.6 ANSI Documents:5ANSI/AAMI/ISO 11737-1: 1995:2006 Sterilization of Medical DevicesMicrobiol
26、ogical MethodsPart 1: Estimation ofBioburden on Product.ANSI/AAMI/ISO 11737-2: 1998:1998 Sterilization of Medical DevicesMicrobiological MethodsPart 2: Tests of SterilityPerformed in the Validation of a Sterilization Process2.7 AAMI Documents:8AAMI/ISO 141601998:141601998 Sterilization of Single-Use
27、 Medical Devices Incorporating Materials of AnimalOriginValidation and Routine Control of Sterilization by Liquid Chemical SterilantsAAMI ST67/CDV-2: 1999:ST67: 2011 Sterilization of Medical DevicesRequirements for Health Care ProductsRequirements and Guidance for Selecting a Sterility Assurance Lev
28、el (SAL) for Products Labeled “Sterile”3 The last approved version of this historical standard is referenced on www.astm.org.4 Available from U.S. Pharmacopeia (USP), 12601 Twinbrook Pkwy., Rockville, MD 20852.5 Available from American National Standards Institute (ANSI), 25 W. 43rd St., 4th Floor,
29、New York, NY 10036.6 Available from ICH Secretariat, c/o IFPMA, 30 rue de St-Jean, P.O. Box 758, 1211 Geneva 13, Switzerland.7 Available from U. S. Food and Drug Administration, 5600 Fishers Lane, Rockville MD 20857-0001.8 Association for the Advancement of Medical Instrumentation 1110 North Glebe R
30、d., Suite 220, Arlington, VA 222014795.F2064 142AAMI TIR No. 191998:191998 Guidance for ANSI/AAMI/ISO 10993-7: 1995, Biological Evaluation of MedicalDevicesPart 7: Ethylene Oxide Sterilization Residuals2.8 prEN Documents:National Institute of Standards and Technology:9prEN 12442-1NIST SP811 Animal T
31、issues and their Derivative Utilized in the Manufacture of Medical DevicesPart 1:Analysis and Management of RiskSpecial Publication: Guide for the Use of the International System of UnitsprEN 12442 Part 3:Validation of the Elimination and/or Inactivation of Virus and Transmissible Agents2.9 Other Do
32、cuments:21CFR184.1724 Listing of Specific Substances Affirmed as GRASSodium Alginate103. Terminology3.1 Definitions of Terms Specific to This Standard: (see also Terminology F1251):3.1.1 alginate, na polysaccharide substance containing calcium, magnesium, sodium, and potassium salts obtained from so
33、meof the more common species of marine algae. Alginate exists in brown algae as the most abundant polysaccharide, mainlyoccurring in the cell walls and intercellular spaces of brown seaweed and kelp. Its main function is to contribute to the strengthand flexibility of the seaweed plant.Alginate is c
34、lassified as a hydrocolloid. The most commonly used alginate is sodium alginate.3.1.2 decomposition, nstructural changes of alginates due to exposure to environmental, chemical or thermal factors, such astemperatures greater than 180C. Decomposition can result in deleterious changes to the alginate.
35、3.1.3 degradation, nchange in the chemical structure, physical properties, or appearance of a material. Degradation ofpolysaccharides occurs by means of cleavage of the glycosidic bonds, usually by acid catalyzed hydrolysis. Degradation can alsooccur thermally. It is important to note that degradati
36、on is not synonymous with decomposition. Degradation is often used as asynonym for depolymerization when referring to polymers.3.1.4 depolymerization, nreduction in length of a polymer chain to form shorter polymeric units. Depolymerization mayreduce the polymer chain to oligomeric or monomeric unit
37、s, or both. In alginates, hydrolysis of the glycosidic bonds is the primarymechanism.3.1.5 Endotoxin, na high-molecular weight lipopolysaccharide (LPS) complex associated with the cell wall of gram-negativebacteria that is pyrogenic in humans. Though endotoxins are pyrogens, not all pyrogens are end
38、otoxins.3.1.6 Gabbreviation for -L-guluronic acid, one of the two monomers making up the alginate polysaccharide molecule. G-richalginate has a greater than 50 % content of guluronate residues in the polymer chain. G-block refers to a homopolymeric blockof G residues.3.1.7 hydrocolloid, na water-sol
39、uble polymer of colloidal nature when hydrated.3.1.8 Mabbreviation for -D-mannuronic acid, one of the two monomers making up the alginate polysaccharide chain. M-richalginate has a greater than 50% content of mannuronate residues in the polymer chain.3.1.9 molecular mass average (molecular weight av
40、erage), molar mass average, nthe given molecular weight mass-averagemolar mass (Mw) of an alginate will always represent an average of all of the molecules in the population. The most common waysto express the Mw are as the number average M n! and the weight average M w!. The two averages are define
41、d by the followingequations:Mn 5(iNiMi(iNiand Mw 5(iwiMi(iwi5(iNiMi2(iNiMi(1)where:Ni = number of molecules having a specific molecular weight, Mi, andwi = weight of molecules having a specific molecular weight MiNi = number of molecules having a specific molar mass, Mi, andwi = mass of molecules ha
42、ving a specific molar mass, Mi.In a polydisperse molecular population the relation Mw Mn is always valid. The coefficient Mw/Mn is referred to as thepolydispersity index, and will typically be in the range from 1.5 to 3.0 for commercial alginates.3.1.9.1 DiscussionThe term molecular weight (abbrevia
43、ted MS) is obsolete and should be replaced by the SI (Systme Internationale) equivalent of9 Available from European Committee for Standardization CEN, Management Centre 36, rue de Stassart B-1050 Brussels, Belgium.National Institute of Standards andTechnology (NIST), 100 Bureau Dr., Stop 1070, Gaith
44、ersburg, MD 20899-1070, http:/physics.nist.gov/cuu/ Units/bibliography.html.10 Available from Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402.F2064 143either relative molecular mass (Mr), which reflects the dimensionless ratio of the mass of a single molecule to an
45、 atomic mass unit(see ISO 31-8), or molar mass (M), which refers to the mass of a mole of a substance and is typically expressed as grams/mole.For polymers and other macromolecules, use of the symbols Mw, Mn, and Mz continue, referring to mass-average molar mass,number-average molar mass, and z-aver
46、age molar mass, respectively. For more information regarding proper utilization of SI units,see NIST SP811.3.1.10 pyrogen, nany substance that produces fever when administered parenterally.4. Significance and Use4.1 This guide contains a listing of those characterization parameters that are directly
47、 related to the functionality of alginate.This guide can be used as an aid in the selection and characterization of the appropriate alginate for a particular application. Thisguide is intended to give guidance in the methods and types of testing necessary to properly characterize, assess, and ensure
48、consistency in the performance of a particular alginate. It may have use in the regulation of these devices by appropriate authorities.4.2 The alginate covered by this guide may be gelled, extruded, or otherwise formulated into biomedical devices for use intissue-engineered medical products or drug
49、delivery devices for implantation as determined to be appropriate, based on supportingbiocompatibility and physical test data. Recommendations in this guide should not be interpreted as a guarantee of clinical successin any tissue engineered medical product or drug delivery application. Further guidance for immobilizing or encapsulating livingcells or tissue in alginate gels can be found in Guide F2315.4.3 To ensure that the material supplied satisfies requirements for use in TEMPS, several general areas of characterizatio
