1、Designation: F 2313 08Standard 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 F 2313; the number immediately following the designation indicates
2、 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 or reapproval.1. Scope1.1 This specification covers both virgin poly(glyc
3、olide)resin and poly(glycolide-co-lactide) resin with mole fractionsgreater than or equal to 70 % glycolide. This specification isnot applicable to glycolide:lactide copolymers with molefractions exceeding 30 % lactide.1.2 Since poly(glycolide) is commonly abbreviated as PGAfor poly(glycolic acid) a
4、nd poly(lactide) is commonly abbre-viated as PLA for poly(lactic acid), these polymers are com-monly referred to as PGA and PLA:PGA resins for thehydrolytic byproducts to which they respectively degrade.1.3 This specification addresses material characteristics ofboth virgin poly(glycolide) and poly(
5、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.1.4 As with any material, some characteristics may bealtered by processing techniques (such as molding, extrusion,machining, assembl
6、y, sterilization, and so forth) required forthe production of a specific part or device. Therefore, proper-ties of fabricated forms of this resin should be evaluatedindependently using appropriate test methods to ensure safetyand efficacy.1.5 The values stated in SI units are to be regarded asstanda
7、rd. No other units of measurement are included in thisstandard.1.6 This standard may suggest use of hazardous materials,operations, and equipment. This standard does not purport toaddress all of the safety concerns, if any, associated with itsuse. It is the responsibility of the user of this standar
8、d toestablish appropriate safety and health practices and deter-mine the applicability of regulatory limitations prior to use.2. Referenced Documents2.1 ASTM Standards:2D 1505 Test Method for Density of Plastics by the Density-Gradient TechniqueD 2857 Practice for Dilute Solution Viscosity of Polyme
9、rsD 3417 Test Method for Enthalpies of Fusion and Crystal-lization of Polymers by Differential Scanning Calorimetry(DSC)3D 3418 Test Method for Transition Temperatures and En-thalpies of Fusion and Crystallization of Polymers byDifferential Scanning CalorimetryD 3536 Test Method for Molecular Weight
10、 Averages andMolecular Weight Distribution by Liquid Exclusion Chro-matography (Gel Permeation ChromatographyGPC)3D 3593 Test Method for Molecular Weight Averages andMolecular Weight Distribution of Certain Polymers byLiquid Size-Exclusion Chromatography (Gel PermeationChromatographyGPC) Using Unive
11、rsal Calibration3D 4603 Test Method for Determining Inherent Viscosity ofPoly(Ethylene Terephthalate) (PET) by Glass CapillaryViscometerE 386 Practice for Data Presentation Relating to High-Resolution Nuclear Magnetic Resonance (NMR) Spectros-copyE 473 Terminology Relating to Thermal Analysis and Rh
12、e-ologyE 793 Test Method for Enthalpies of Fusion and Crystalli-zation by Differential Scanning Calorimetry1This specification is under the jurisdiction of ASTM Committee F04 onMedical and Surgical Materials and Devices and is the direct responsibility ofSubcommittee F04.11 on Polymeric Materials.Cu
13、rrent edition approved Aug. 1, 2008. Published September 2008. Originallyapproved in 2003. Last previous edition approved in 2003 as F 2313 03.2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Customer Service at serviceastm.org. For Annual Book of ASTMStandards vo
14、lume information, refer to the standards Document Summary page onthe ASTM website.3Withdrawn.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.E 794 Test Method for Melting And Crystallization Tem-peratures By Thermal AnalysisE 967 Tes
15、t Method for Temperature Calibration of Differ-ential Scanning Calorimeters and Differential ThermalAnalyzersE 968 Practice for Heat Flow Calibration of DifferentialScanning CalorimetersE 1142 Terminology Relating to Thermophysical PropertiesE 1252 Practice for General Techniques for Obtaining In-fr
16、ared Spectra for Qualitative AnalysisE 1356 Test Method for Assignment of the Glass TransitionTemperatures by Differential Scanning CalorimetryE 1994 Practice for Use of Process Oriented AOQL andLTPD Sampling PlansF 748 Practice for Selecting Generic Biological Test Meth-ods for Materials and Device
17、s2.2 Other Standards:United States Pharmacopeia (USP) Edition 264ISO 31-8 Physical Chemistry and Molecular Physics, Part8: Quantities and Units5ISO 11357 PlasticsDifferential Scanning Calorimetry(DSC)5ICH Q3C(R3) International Conference on Harmonisationof Technical Requirements for Registration of
18、Pharmaceu-ticals for Human Use, Quality Guideline: Impurities:Residual Solvents621 CFR 820, United States Code of Federal Regulations,Title 21Food and Drugs Services, Part 820QualitySystem Regulation7ANSI/ISO/ASQ Q9000-2000, Quality Management Sys-tems; Fundamentals and Vocabulary5ANSI/ISO/ASQ Q9001
19、-2000, Quality Management Sys-tems; Requirements5NIST Special Publication SP811 Guide for the Use of theInternational System of Units (SI)83. Terminology3.1 Definition:3.1.1 virgin polymer, nthe initially delivered form of apolymer as synthesized from its monomers and prior to anyprocessing or fabri
20、cation into a medical device.4. Materials and Manufacture4.1 All raw 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 adeq
21、uate control of particles and other potentialcontaminants that may 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 subsequent)shall be undertaken und
22、er conditions suitable to allow for useof such resin in the manufacture of an implantable medicalproduct.5. Chemical Composition5.1 Polymers covered by this specification shall be com-posed either of glycolide, or of a combination of glycolide andlactide where the lactide content does not exceed 30
23、% molefraction (34.7 % by mass). To ensure such composition and theattainment of the desired properties, the following tests are tobe 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 Iden
24、tification:5.2.2.1 Identity of either poly(glycolide) 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 prac-tices sim
25、ilar to those described in Practice E 1252. A typicalinfrared transmission reference spectrum for PGA homopoly-mer is shown in Fig. 1. A typical infrared transmissionreference spectrum for a 90 % PGA:10 % l-PLA copolymer isshown in Fig. 2. While poly(glycolide-co-lactide) copolymerswill each have th
26、eir own respective spectrum that will vary inresponse to copolymer ratio, this analytic method typicallylacks sensitivity sufficient for quantification of copolymer ratioas specified in 7.1.2.5.2.2.2 Additional spectral bands may be indicative ofknown or unknown impurities, including residual solven
27、ts andcatalysts (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 suitab
28、le reference spectrum. Sample dissolution is indeuterated hexafluoroisopropanol (D-HFIP) or other proton-free solvent able to fully solvate the specimen. Analysis shallbe conducted using practices similar to those described inPractice E 386.5.2.3.2 Additional spectral bands may be indicative ofknown
29、 or unknown impurities, including residual solvents andcatalysts (refer to limits specified in Table 1).5.2.4 Carbon-13 Nuclear Magnetic 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 th
30、rough13C-NMR spectroscopy and the use of asuitable reference spectrum. Analysis shall be conducted usingpractices similar to those described in Practice E 386.4Available from U.S. Pharmacopeia (USP), 12601 Twinbrook Pkwy., Rockville,MD 20852-1790, http:/www.usp.org.5Available from American National
31、Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.6Available 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.pdf7Available from U.S. Government Printing O
32、ffice Superintendent of Documents,732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401, http:/www.access.gpo.gov.8Available 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
33、.F2313082NOTESupplied 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 SpectrumF2313083NOTESupplied example infra
34、-red spectrum 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 SpectrumF23130845.2.4.2 Additional spectral bands may
35、be indicative ofknown or unknown impurities, including residual solvents andcatalysts (refer to limits specified in Table 1).5.3 Molar Mass:NOTE 1The term molecular weight (abbreviated MW) is obsolete andshould be replaced by the SI (Systme Internationale) equivalent of eitherrelative molecular mass
36、 (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 and other macromol-ecules, use of the symbols Mw, Mn, and Mzcon
37、tinue, 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 virgin polymer shall beindicated by inherent viscosity in dilut
38、e 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 Test Methods D 3536 or D 3593, but using hexafluor-oisopropanol (HFIP) solvent and poly methylmethacrylat
39、e(PMMA) calibration standards.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 D 2857 and Test Method D 4603.Determination at a lower temperature of 25C
40、 is allowable,provided the utilized equipment delivers the required thermalcontrol and an experimentally supported 30C equivalentconcentration-appropriate extrapolated result is also reportedwithin the supplied certification. Note that incomplete sampledissolution or precipitation from solution can
41、result in forma-tion of gels and will produce inconsistency and variation inobserved drop times. Inherent viscosity is determined utilizingthe following equation:IV 5lnttov!w(1)where:IV = inherent viscosity (at 30C in dl/gram),t = efflux time in seconds for diluted solution,to= efflux time in second
42、s for source solvent,w = mass of polymer being diluted (in grams), andv = dilution volume in deciliters (Note: 1 dl = 100 mL).5.3.1.2 Resin concentration for IV analysis must be 0.5 %w/v or less, with resin analyte concentrations of 0.1 % w/v(that is, 0.001 g/mL or 1 mg/mL) recommended. Whenreportin
43、g results, identify the solvent utilized, analyte concen-tration, and analysis temperature.5.4 Residual Monomer:5.4.1 The virgin polymer shall have a combined totalresidual monomer content less than or equal to 2.0 % by mass.5.4.1.1 Determine mass percent residual monomer by gaschromatography,1H-NMR
44、 spectroscopy (using D-HFIP orother proton-free solvent able to fully solvate the specimen), orother suitably sensitive analytic method as agreed upon bysupplier and purchaser.5.5 Residual Solvents:5.5.1 If any solvent is utilized in any resin manufacturing orpurification step, determine residual le
45、vels of any utilizedsolvent(s) by gas chromatography or other suitable method asagreed upon by supplier and purchaser. Acceptable residuallevels of a particular solvent shall be reflective of toxicity, witha maximum acceptable limit consistent with ICH Q3C(R3).The detection limit for the chosen anal
46、ytic method must beadequate to assure compliance with the applicable ICH guide-line and the determined residual(s) and applied concentrationlimit(s) shall be reported. If no ICH concentration guidelinehas been established for a utilized solvent, an entry of “no ICHguidance available” will be reporte
47、d in lieu of a limit.5.5.2 To minimize potential for toxic interaction of solventcombinations, cumulative Total Solvent Combination Residu-als will be limited to 1000 ppm (refer to limit specified in Table1). This limit carries the effect of allowing ICH QC3 QualityGuidelines when a single solvent s
48、ystem is utilized and lessthan 1000 ppm when combinations of more than one solventare utilized (regardless of individual solvent toxicity).5.6 Heavy Metals:5.6.1 Determine residual heavy metals per Method II, Chap-ter 231 of United States Pharmacopeia (USP).5.6.2 Heavy metals generally refers to div
49、alent cations ofthe elements cadmium (Cd), copper (Cu), mercury (Hg), andlead (Pb), to the trivalent cations of antimony (Sb), arsenic(As), and bismuth (Bi), and to tetravalent (stannic) tin (Sn4+)that form complexes with sulfide under slightly acidic condi-tions.9Since stannous tin (Sn2+) can also form tin (II) sulfideand thereby carries potential to influence test results, the excessamount ascertained by alternative analytic means to be directlyattributable to both stannic and stannous tin may be ignored,provided that the cumulative lead (Pb) equivalent tota
