1、Designation: F 2313 03Standard Specification forVirgin Poly(glycolide) and Poly(glycolide-co-lactide) Resinsfor Surgical 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 in
2、dicates 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 (e) indicates an editorial change since the last revision or reapproval.1. Scope1.1 This specification covers both virgin p
3、oly(glycolide)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
4、 acid) and poly(lactide) is commonly abbre-viated as PLA for poly(lactic acid), these polymers are com-monly referred to as PGA and PGA:PLA resins for thehydrolytic byproducts to which they respectively degrade.1.3 This specification addresses material characteristics ofboth virgin poly(glycolide) a
5、nd poly($70 % glycolide-co-lactide) resins intended for use in surgical implants and doesnot apply to packaged and sterilized finished implants fabri-cated from this material.1.4 As with any material, some characteristics may bealtered by processing techniques (such as molding, extrusion,machining,
6、assembly, 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 This standard may suggest use of hazardous materia
7、ls,operations, and equipment. This standard does not purport toaddress safety concerns associated with its use. It is theresponsibility of the user of this standard to establish appro-priate safety and health practices and to determine theapplicability of regulatory limitations prior to use.2. Refer
8、enced Documents2.1 ASTM Standards:2D 1505 Test Method for Density of Plastics by the Density-Gradient TechniqueD 1898 Practice for Sampling of PlasticsD 2857 Practice for Dilute Solution Viscosity of PolymersD 3536 Test Method for Molecular Weight Averages andMolecular Weight Distribution by Liquid
9、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 Universal Calibration3D 4603 Test Method for Determining I
10、nherent Viscosity ofPoly(Ethylene Terephthalate) (PET) by Glass CapillaryViscometerE 386 Practice for Data Presentation Relating to High-Resolution Nuclear Magnetic Resonance (NMR) Spectros-copyE 1252 Practice for General Techniques for Obtaining In-frared Spectra for Qualitative AnalysisF 748 Pract
11、ice for Selecting Generic Biological Test Meth-ods for Materials and Devices2.2 Other Standards:United States Pharmacopeia (USP) Edition 264ISO 10993-9 Biological Evaluation of Medical Devices,Part 9: Framework for Identification and Quantification ofPotential Degradation Products, Annex A521 CFR 82
12、0, United States Code of Federal Regulations,Title 21Food and Drugs Services, Part 820QualitySystem Regulation6ANSI/ISO/ASQ Q9000-2000, Quality Management Sys-tems; Fundamentals and Vocabulary5ANSI/ISO/ASQ Q9001-2000, Quality Management Sys-tems; Requirements53. Terminology3.1 Definitions:1This spec
13、ification is under the jurisdiction of ASTM Committee F04 onMedical Surgical Materials and Devices and is the direct responsibility of Subcom-mittee F04.11 on Polymeric Materials.Current edition approved Nov. 1, 2003. Published November 2003.2For referenced ASTM standards, visit the ASTM website, ww
14、w.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.3Withdrawn.4Available from U.S. Pharmacopeia (USP), 12601 Twinbrook Pkwy., Rockville,MD 20852.5Available from American
15、National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036.6Available from U.S. Government Printing Office Superintendent of Documents,732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohoc
16、ken, PA 19428-2959, United States.3.1.1 virgin polymer, nthe form of poly(glycolide) orpoly(glycolide-co-lactide) as synthesized from its monomersand prior to fabrication into a medical device.4. Materials and Manufacture4.1 All raw monomer components and other materialscontacting either the raw mon
17、omer(s) or resin product shall beof a quality suitable to allow for use of such resin in themanufacture of an implantable medical product.4.2 All polymer manufacturing (including monomer han-dling, synthesis, pelletization/grinding and all subsequent)shall be undertaken under conditions suitable to
18、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 % (34.7 %by weight). To en
19、sure such composition and the attainment ofthe desired properties, the following 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
20、 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 similar to those described in Practice E
21、 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. 2.5.2.2.2 Additional spectral bands may be indicative ofknown or unknown impurities, including resid
22、ual solvents 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 the useo
23、f a suitable 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 indicati
24、ve ofknown 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 asoli
25、d state through13C-NMR spectroscopy and the use of asuitable reference spectrum. Analysis shall be conducted usingpractices similar to those described in Practice E 386.5.2.4.2 Additional spectral bands may be indicative ofknown or unknown impurities, including residual solvents andcatalysts (refer
26、to limits specified in Table 1).5.3 Molecular Weight:5.3.1 The molecular mass of the virgin polymer shall beindicated by inherent viscosity in dilute solution (IV). Inaddition to inherent viscosity (but not in place of), weightaverage molecular mass and molecular mass distributions maybe determined
27、by gel permeation chromatography (GPC)according to Test Methods D 3536 or D 3593, but usinghexafluoroisopropanol (HFIP) solvent and poly methyl-methacrylate (PMMA) calibration standards.5.3.1.1 Determine the inherent viscosity of the polymereither in hexafluoroisopropanol (HFIP) or hexafluoroacetone
28、sesquihydrate (HFAS) at 30C using procedures similar tothose described in Practice D 2857 and Test Method D 4603.Inherent viscosity is determined utilizing the following equa-tion:IV 5lnttov!w(1)where:IV = inherent viscosity (at 30C in dl/gram),t = efflux time in seconds for diluted solution,to= eff
29、lux time in seconds for source solvent,w = weight of polymer being diluted (in grams), andv = dilution volume in deciliters (Note: 1 dl = 100 mL).Resin concentration for IV analysis must be 0.5 % w/v orless, with resin analyte concentrations of 0.1 % w/v (that is,0.001 g/ml or 1 mg/ml) recommended.
30、When reporting results,identify the solvent utilized, analyte concentration, and analy-sis temperature.5.4 Residual Monomer:5.4.1 The virgin polymer shall have a combined totalresidual monomer content less than or equal to 2 % by weight.5.4.1.1 Determine weight percent residual monomer by gaschromat
31、ography,1H-NMR 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, determi
32、ne residual levels of any utilizedsolvent(s) by gas chromatography or other suitable method asagreed upon by supplier and purchaser. Acceptable residuallevels of a solvent shall be reflective of toxicity, with amaximum acceptable level (regardless of toxicity) presented inTable 1.5.6 Heavy Metals:5.
33、6.1 Determine residual Heavy Metals per Method II,Chapter 231 of U.S. Pharmacopeia.5.6.2 Heavy Metals generally refers to divalent cations ofthe elements antimony (Sb), arsenic (As), cadmium (Cd),copper (Cu), mercury (Hg), and lead (Pb). Since stannous tin(Sn2+) carries potential to influence test r
34、esults, the amountascertained by alternative analytic means (see below) to bedirectly attributable to tin in may be ignored, provided that theF2313032NOTESupplied example infra-red spectrum is of “Dexon Medical Suture (beige)” as acquired from the Hummel Polymer Library, available from:Thermo Nicole
35、t Corporation, 5225 Verona Road, Madison, WI 53711-4495, USA.FIG. 1 Poly(glycolide) Resin Infrared SpectrumF2313033NOTESupplied example infra-red spectrum is of “Vicryl Medical Suture (violet)” as acquired from the Hummel Polymer Library, available from:Thermo Nicolet Corporation, 5225 Verona Road,
36、Madison, WI 53711-4495, USA.FIG. 2 Poly(90 % glycolide-co-10 % lactide) Resin Infrared SpectrumF2313034cumulative total amount of the listed Heavy Metals elementsremains below the USP 10 ppm as lead limit.5.7 Residual Catalyst (Optional):5.7.1 Determine the amount of residual tin (Sn) by atomicabsor
37、ption/emission (AA) spectroscopy or inductively coupledplasma (ICP) spectroscopy. If a catalyst other than tin isutilized, suitable methods to both determine and report residueshall be utilized.6. Physical Properties6.1 Determine the density in accordance with Test MethodD 1505.7. Performance Requir
38、ements7.1 Identification Requirements:7.1.1 Identity of poly(glycolide) homopolymer orpoly(glycolide-co-lactide) copolymer must be confirmedthrough either an infrared, a1H-NMR spectrum (using D-HFIPor other proton-free solvent able to fully solvate the specimen),or a13C-NMR spectrum which exhibits m
39、ajor absorption bandsonly at the wavelengths/chemical shifts that appear in asuitable reference spectrum.7.1.2 Copolymer ratio of poly(glycolide-co-lactide) poly-mer must be determined through a1H-NMR spectrum (usingD-HFIP or other proton-free solvent able to fully solvate thespecimen). Ratio of gly
40、colide to lactide should be 63 % molepercentage of target. This same1H-NMR spectrum may also beutilized to provide the identification requirements of 7.1.1.7.2 Molecular Weight Requirements:7.2.1 The finished resin product must meet the specifiedmolecular weight requirements agreed upon between the
41、sup-plier and purchaser as measured by inherent viscosity. Optionalmolecular weight distribution criteria may also be specified andagreed upon as measured by the GPC methods describedabove.7.3 Physical/Chemical Property Requirements:7.3.1 The virgin polymer shall have the chemical andphysical proper
42、ties as listed in Table 1 as determined by themethods described above.8. Dimensions, Mass, and Permissible Variations8.1 Finished product resin may be supplied in either pellet-ized or granular form, with requirements as agreed uponbetween the supplier and purchaser.9. Sampling9.1 Where applicable,
43、the requirements of this specificationshall be determined for each lot of the virgin polymer bysampling sizes and procedures according to Practice D 1898.10. Certification10.1 A certificate of compliance that contains, at minimum,the following information shall be supplied for each shipment:10.1.1 S
44、upplier identification (including address and phonecontact numbers),10.1.2 Resin lot number,10.1.3 Date of certification,10.1.4 Chemical description of polymer (including, if ap-propriate, the targeted copolymer ratio designated specificallyby weight or by mole),10.1.5 Applicable CAS registry number
45、,10.1.6 Experimentally determined copolymer ratio (if acopolymer, with results designated by weight or by mole),10.1.7 Inherent viscosity (in dl/g; with solvent, temperature,and analyte concentration in solution),10.1.8 Residual monomer content (combined total inweight %), and10.1.9 Heavy metals (pa
46、ss or fail, with applicable limitspecified).11. Packaging and Package Marking11.1 Packaging material shall be of such composition that itprovides an effective barrier to the entry of moisture.11.2 Each of the individually supplied product packagingshall possess a label that contains, at minimum, the
47、 followinginformation:11.2.1 Supplier identification,11.2.2 A chemical description of the polymer (including, ifappropriate, the targeted copolymer ratio designated specifi-cally by weight or by mole),11.2.3 Resin lot number,11.2.4 Net weight of contents,11.2.5 Inherent viscosity (in dl/g), and11.2.
48、6 Final packaging date.12. Supplementary Requirements12.1 Biocompatibility:12.1.1 Due to potential for an increase in local acidity as aresult of the normal hydrolytic degradation process, suitabilityof these materials for human implantation will be dependent onthe specific application. The biologic
49、al tests appropriate for thespecific site, such as those recommended in Practice F 748 maybe used as a guideline.12.1.2 No known surgical implant material has ever beenshown to be completely free of adverse reactions in the humanbody. However, long term clinical experience with specificcompositions and formulations of the material class referred toin this specification has shown that an acceptable level ofbiological response can be expected, if the material is used inappropriate applications.13. Guidance for Manufacturing Control and QualityAssurance13.1 Acceptable levels of
