1、Designation: F2313 10Standard Specification forPoly(glycolide) and Poly(glycolide-co-lactide) Resins forSurgical Implants with Mole Fractions Greater Than orEqual to 70 % Glycolide1This standard is issued under the fixed designation F2313; the number immediately following the designation indicates t
2、he 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.1. Scope1.1 This specification covers both virgin poly(glycol
3、ide)homopolymer and poly(glycolide-co-lactide) copolymer resinsintended for use in surgical implants. The poly(glycolide-co-lactide) copolymers covered by this specification possessnominal mole fractions greater than or equal to 70 % glycolide(65.3 % in mass fraction). This specification is also app
4、licableto lactide-co-glycolide copolymers that possess glycolide seg-ments sufficient in size to deliver potential for glycolide basedcrystallization, thereby requiring fluorinated solvents for com-plete dissolution under room temperature conditions.1.2 Since poly(glycolide) is commonly abbreviated
5、as PGAfor poly(glycolic acid) and poly(lactide) is commonly abbre-viated as PLA for poly(lactic acid), these polymers are com-monly referred to as PGA, PLA, and PLA:PGA resins for thehydrolytic byproducts to which they respectively degrade. PLAis a term that carries no stereoisomeric specificity and
6、 thereforeencompasses both the amorphous atactic/syndiotactic DL-lactide-based polymers and copolymers as well as the isotacticD-PLA and L-PLA moieties, each of which carries potential forcrystallization.1.3 This specification is specifically not applicable to amor-phous poly(lactide-co-glycolide) o
7、r poly(lactide)-based resinsable to be fully solvated at 30C by either methylene chloride(dichloromethane) or chloroform (trichloromethane), whichare covered in Specification F2579 and typically possess molarglycolide levels of 50 % or less. This specification is notapplicable to lactide-based polym
8、ers or copolymers that pos-sess isotactic polymeric segments sufficient in size to carrypotential for lactide-based crystallization, which are coveredby Specification F1925 and typically possess nominal molefractions that equal or exceed 50 % L-lactide.1.4 This specification addresses material chara
9、cteristics ofboth virgin poly(glycolide) and poly(70 % glycolide-co-lactide) resins intended for use in surgical implants and doesnot apply to packaged and sterilized finished implants fabri-cated from these materials.1.5 As with any material, some characteristics may bealtered by processing techniq
10、ues (such as molding, extrusion,machining, assembly, sterilization, etc.) required for the pro-duction of a specific part or device. Therefore, properties offabricated forms of this resin should be evaluated indepen-dently using appropriate test methods to assure safety andefficacy.1.6 The values st
11、ated in SI units are to be regarded asstandard. No other units of measurement are included in thisstandard.1.7 This standard does not purport to address all of thesafety concerns, if any, associated with its use. It is theresponsibility of the user of this standard to establish appro-priate safety a
12、nd health practices and determine the applica-bility of regulatory limitations prior to use.2. Referenced Documents2.1 ASTM Standards:2D1505 Test Method for Density of Plastics by the Density-Gradient TechniqueD2857 Practice for Dilute Solution Viscosity of PolymersD3418 Test Method for Transition T
13、emperatures and En-thalpies of Fusion and Crystallization of Polymers byDifferential Scanning CalorimetryD5296 Test Method for Molecular Weight Averages andMolecular Weight Distribution of Polystyrene by HighPerformance Size-Exclusion ChromatographyD4603 Test Method for Determining Inherent Viscosit
14、y ofPoly(Ethylene Terephthalate) (PET) by Glass CapillaryViscometerE386 Practice for Data Presentation Relating to High-Resolution Nuclear Magnetic Resonance (NMR) Spectros-copyE473 Terminology Relating to Thermal Analysis and Rhe-ology1This specification is under the jurisdiction of ASTM Committee
15、F04 onMedical and Surgical Materials and Devices and is the direct responsibility ofSubcommittee F04.11 on Polymeric Materials.Current edition approved Dec. 1, 2010. Published January 2011. Originallyapproved in 2003. Last previous edition approved in 2008 as F2313 081. DOI:10.1520/F2313-10.2For ref
16、erenced 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 ASTM website.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, We
17、st Conshohocken, PA 19428-2959, United States.E793 Test Method for Enthalpies of Fusion and Crystalli-zation by Differential Scanning CalorimetryE794 Test Method for Melting And Crystallization Tem-peratures By Thermal AnalysisE967 Test Method for Temperature Calibration of Differen-tial Scanning Ca
18、lorimeters and Differential Thermal Ana-lyzersE968 Practice for Heat Flow Calibration of DifferentialScanning CalorimetersE1142 Terminology Relating to Thermophysical PropertiesE1252 Practice for General Techniques for Obtaining Infra-red Spectra for Qualitative AnalysisE1356 Test Method for Assignm
19、ent of the Glass TransitionTemperatures by Differential Scanning CalorimetryE1994 Practice for Use of Process Oriented AOQL andLTPD Sampling PlansF748 Practice for Selecting Generic Biological Test Meth-ods for Materials and DevicesF1925 Specification for Semi-Crystalline Poly(lactide)Polymer and Co
20、polymer Resins for Surgical ImplantsF2579 Specification for Amorphous Poly(lactide) andPoly(lactide-co-glycolide) Resins for Surgical Implants2.2 ANSI Standards:3ANSI/ISO/ASQ Q9000 Quality Management Systems;Fundamentals and VocabularyANSI/ISO/ASQ Q9001 Quality Management Systems; Re-quirements2.3 I
21、SO Standards:3ISO 318 Physical Chemistry and Molecular PhysicsPart8: Quantities and UnitsISO 10993 Biological Evaluation of Medical DevicesISO 11357 PlasticsDifferential Scanning Calorimetry(DSC)2.4 U. S. Pharmacopeia (USP) Standard:4USP30/NF25 United States Pharmacopeia (USP), May 2,20072.5 Other D
22、ocuments/Websites:ICH Q3C(R3) International Conference on Harmonisationof Technical Requirements for Registration of Pharmaceu-ticals for Human Use, Quality Guideline: Impurities:Residual Solvents521 CFR 820 Code of Federal Regulations, Title 21, Part820, Quality System Regulation6NIST Special Publi
23、cation SP811 Guide for the Use of theInternational System of Units (SI)73. Terminology3.1 Definition:3.1.1 virgin polymer, nthe initially delivered form of apolymer as synthesized from its monomers and prior to anyprocessing or fabrication into a medical device.4. Materials and Manufacture4.1 All ra
24、w monomer components and other materialscontacting either the raw monomer(s) or resin product shall beof a quality suitable to allow for use of such resin in themanufacture of an implantable medical product. Such qualityincludes adequate control of particles and other potentialcontaminants that may
25、affect either the toxicity of or the cellresponse to the as-implanted or degrading final product.4.2 All polymer manufacturing (including monomer han-dling, synthesis, pelletization/grinding and all subsequentsteps) shall be undertaken under conditions suitable to allowfor use of such resin in the m
26、anufacture of an implantablemedical product.5. Chemical Composition5.1 The poly(glycolide) polymers covered by this specifica-tion shall be composed of glycolide or a combination ofglycolide or lactide where the lactide content does not exceed30 % mole fraction (34.7 % by mass fraction). To assure s
27、uchcomposition and the attainment of the desired properties, thefollowing tests are to be conducted.5.2 Chemical Identification:5.2.1 The identity of the virgin polymer shall be confirmedeither by infrared,1H-NMR, or13C-NMR spectroscopy.5.2.2 Infrared Identification:5.2.2.1 Identity of either poly(g
28、lycolide) homopolymer orpoly(glycolide-co-lactide) copolymer may be confirmedthrough an infrared spectrum exhibiting major absorptionbands only at the wavelengths that appear in a suitablereference spectrum. Analysis shall be conducted using infra-red spectroscopy practices similar to those describe
29、d in Prac-tice E1252. Typical infrared transmission and absorbancereference spectra are presented for PGA homopolymer in Fig.1 and 90 % PGA:10 % L-PLA copolymer in Fig. 2. Whilepoly(glycolide-co-lactide) copolymers will each have theirown respective spectrum that will vary in response to copoly-mer
30、ratio, this analytic method typically lacks sensitivitysufficient for quantification of copolymer ratio as specified in7.1.2.5.2.2.2 Additional or variable spectral bands may be indica-tive of sample crystallinity or either known or unknownimpurities, including residual monomer, solvents, and cataly
31、sts(refer to limits specified in Table 1).5.2.3 Proton Nuclear Magnetic Resonance (1H-NMR) Iden-tification:5.2.3.1 Identity of either poly(glycolide) homopolymer orpoly(glycolide-co-lactide) copolymer may be confirmedthrough sample dissolution,1H-NMR spectroscopy, and theuse of a suitable reference
32、spectrum. Sample dissolution is ineither deuterated hexafluoroisopropanol (D-HFIP) or othersubstantially proton-free solvent able to fully solvate the3Available from American National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.4Available from U.S. Ph
33、armacopeia (USP), 12601 Twinbrook Pkwy., Rockville,MD 20852-1790, http:/www.usp.org.5Available from ICH Secretariat, c/o IFPMA, 30 rue de St-Jean, P.O. Box 758,1211 Geneva 13, Switzerland. Available online at http:/www.ich.org/LOB/media/MEDIA423.pdf6Available from U.S. Government Printing Office Sup
34、erintendent of Documents,732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401, http:/www.access.gpo.gov.7Available from National Institute of Standards and Technology (NIST), 100Bureau Dr., Stop 1070, Gaithersburg, MD 20899-1070, at http:/physics.nist.gov/cuu/Units/bibliography.html.F2313 10
35、2NOTESupplied example infra-red spectrum is of “Dexon Medical Suture (beige)” as acquired from the Hummel Polymer Library, available from:Thermo Nicolet Corporation, 5225 Verona Road, Madison, WI 53711-4495, USA.FIG. 1 Poly(glycolide) Resin Infrared SpectrumF2313 103NOTESupplied example infra-red sp
36、ectrum is of “Vicryl Medical Suture (violet)” as acquired from the Hummel Polymer Library, available from:Thermo Nicolet Corporation, 5225 Verona Road, Madison, WI 53711-4495, USA.FIG. 2 Poly(90 % glycolide-co-10 % lactide) Resin Infrared SpectrumF2313 104specimen without inducing competing spectral
37、 bands. Analysisshall be conducted using practices similar to those described inPractice E386.5.2.3.2 Additional spectral bands may be indicative ofknown or unknown impurities, including residual monomer,solvents, and catalysts (refer to limits specified in Table 1).5.2.4 Carbon-13 Nuclear Magnetic
38、Resonance (13C-NMR)Identification:5.2.4.1 Identity of either poly(glycolide) homopolymer orpoly(glycolide-co-lactide) copolymer may be confirmed in asolid state through13C-NMR spectroscopy and the use of asuitable reference spectrum. Analysis shall be conducted usingpractices similar to those descri
39、bed in Practice E386.5.2.4.2 Additional spectral bands may be indicative ofknown or unknown impurities, including residual solvents andcatalysts (refer to the limits specified in Table 1).5.3 Molar Mass:NOTE 1The term molecular weight (abbreviated MW) is obsolete andshould be replaced by the SI (Sys
40、tme Internationale) equivalent of eitherrelative molecular mass (Mr), which reflects the dimensionless ratio of themass of a single molecule to an atomic mass unit see ISO 31-8, or molarmass (M), which refers to the mass of a mole of a substance and istypically expressed as grams/mole. For polymers
41、and other macromol-ecules, use of the symbols Mw, Mn, and Mzcontinue, referring tomass-average molar mass, number-average molar mass, and z-averagemolar mass, respectively. For more information regarding proper utiliza-tion of SI units, see NIST Special Publication SP811.5.3.1 The molar mass of the
42、virgin polymer shall beindicated by inherent viscosity in dilute solution (IV). Inaddition to inherent viscosity (but not in place of), massaverage molar mass and molar mass distributions may bedetermined by gel permeation chromatography (GPC) accord-ing to the general procedure described in Test Me
43、thod D5296,but using hexafluoroisopropanol (HFIP) solvent and polymethylmethacrylate (PMMA) calibration standards.NOTE 2Molar mass calibration standards (for example, polystyrene orpolymethylmethacrylate) provide relative values only, and are not to beconfused with an absolute determination of a lac
44、tide-based polymersmolar mass.5.3.1.1 Determine the inherent viscosity of the polymereither in hexafluoroisopropanol (HFIP) or hexafluoroacetonesesquihydrate (HFAS) at 30C using procedures similar tothose described in Practice D2857 and Test Method D4603.Determination at a lower temperature of 25C i
45、s allowable,provided the utilized equipment delivers the required thermalcontrol and, if requested by the purchaser, an experimentallysupported 30C equivalent concentration-appropriate extrapo-lated result is also reported within the supplied certification.Note that any incomplete sample dissolution
46、, precipitationfrom solution, or the formation of gels will produce inconsis-tency and variation in observed drop times.NOTE 3The IV test duration for each sample should be minimized toreduce risk of resin concentration changes due to evaporative loss ofsolvent.5.3.1.2 Inherent viscosity is determin
47、ed utilizing the follow-ing:IV 5ln t/to! vw(1)orIV 5ln t/to!C(2)where:IV = inherent viscosity (at 30C in dL/g),t = efflux time in seconds for diluted solution,to= efflux time in seconds for source solvent,w = mass of polymer being diluted (in grams),v = dilution volume in deciliters (Note: 1 dL = 10
48、0 mL),andC = concentration of dilute solution (w/v).5.3.1.3 Resin concentration shall be 0.5 % w/v or less, withresin analyte concentrations of 0.1 % w/v (that is, 0.001 g/mLor 1 mg/mL) recommended. When reporting results, identifythe solvent utilized, analyte concentration, and analysis tem-peratur
49、e.5.4 Residual Monomer:5.4.1 The virgin polymer shall have a combined totalresidual monomer content less than or equal to 2.0 % in massfraction.5.4.1.1 Determine the mass fraction of residual monomer bygas chromatography, HPLC,1H-NMR spectroscopy (usingD-HFIP or other substantially proton-free solvent able to fullysolvate the specimen), or other suitably sensitive analyticmethod as agreed upon by the supplier and purchaser.5.5 Residual Solvents:5.5.1 If any solvent is utilized in any resin manufacturing orpurification step, determine residual levels of
