ASTM F2579-2010 Standard Specification for Amorphous Poly(lactide) and Poly(lactide-co-glycolide) Resins for Surgical Implants《外科植入物用非晶态聚乙烯(交酯)和聚乙烯(交酯-甘醇酸树脂)的标准规范》.pdf

1、Designation: F2579 10Standard Specification forAmorphous Poly(lactide) and Poly(lactide-co-glycolide)Resins for Surgical Implants1This standard is issued under the fixed designation F2579; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revi

2、sion, 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 virgin amorphous poly(lactide)homopolymer and poly(lactide-co-glycolide) c

3、opolymer resinsintended for use in surgical implants. The poly(DL-lactide)homopolymers covered by this specification are considered tobe amorphous (that is, void of crystallinity) and are polymer-ized either from meso-lactide or from equimolar (racemic)combinations of D-lactide and L-lactide. The po

4、ly(DL-lactide-co-glycolide) copolymers covered by this specification are alsoconsidered to be amorphous and are co-polymerized from acombination of glycolide and either meso-lactide or racemicquantities of D-lactide and L-lactide, and typically possessnominal mole fractions that equal or exceed 50 %

5、 lactide.1.2 Since poly(glycolide) is commonly abbreviated 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.

6、PLAis a term that carries no stereoisomeric specificity and 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. Therefore, specific reference to DL-

7、PLA isessential to appropriately differentiate the amorphous atactic/syndiotactic DL-lactide-based polymers and copolymers cov-ered by this specification. Thus, inclusion of stereoisomericspecificity within the lactic acid-based acronyms results in thefollowing: poly(L-lactide) as PLLA for poly(L-la

8、ctic acid),poly(D-lactide) as PDLA for poly(D-lactic acid), and poly(DL-lactide) as PDLLA for poly(DL-lactic acid).1.3 This specification covers virgin amorphouspoly(lactide)-based resins able to be fully solvated at 30C byeither methylene chloride (dichloromethane) or chloroform(trichloromethane).

9、This specification is not applicable tolactide-based polymers or copolymers that possess isotacticpolymeric segments sufficient in size to carry potential forlactide-based crystallization, which are covered by Specifica-tion F1925 and typically possess nominal mole fractions thatequal or exceed 50 %

10、 L-lactide. This specification is notapplicable to lactide-co-glycolide copolymers that possessglycolide segments sufficient in size to deliver potential forglycolide-based crystallization, thereby requiring fluorinatedsolvents for complete dissolution under room temperatureconditions. This specific

11、ation is specifically not applicable tolactide-co-glycolide copolymers with glycolide mole fractionsgreater than or equal to 70 % (65.3 % in mass fraction), whichare covered by Specification F2313. This specification is notapplicable to block copolymers or to polymers or copolymerssynthesized from c

12、ombinations of D-lactide and L-lactide thatdiffer by more than 1.5 total mole percent (1.5 % of totalmoles).1.4 This specification addresses material characteristics ofboth poly(DL-lactide) and poly(DL-lactide-co-glycolide) resinsintended for use in surgical implants and does not apply topackaged an

13、d sterilized finished implants fabricated from thesematerials.1.5 As with any material, some characteristics may bealtered by processing techniques (such as molding, extrusion,machining, assembly, sterilization, and so forth) required forthe production of a specific part or device. Therefore, proper

14、-ties of fabricated forms of this resin should be evaluatedindependently using appropriate test methods to assure safetyand efficacy.1.6 The values stated 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 addre

15、ss all of thesafety concerns, if any, associated with its use. It is theresponsibility of the user of this standard to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.1This specification is under the jurisdiction of ASTM Comm

16、ittee 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 2006. Last previous edition approved in 2008 as F2579 08. DOI:10.1520/F2579-10.1Co

17、pyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.2. Referenced Documents2.1 ASTM Standards:2D1505 Test Method for Density of Plastics by the Density-Gradient TechniqueD2857 Practice for Dilute Solution Viscosity of PolymersD4603 Test Met

18、hod for Determining Inherent Viscosity ofPoly(Ethylene Terephthalate) (PET) by Glass CapillaryViscometerD5296 Test Method for Molecular Weight Averages andMolecular Weight Distribution of Polystyrene by HighPerformance Size-Exclusion ChromatographyE386 Practice for Data Presentation Relating to High

19、-Resolution Nuclear Magnetic Resonance (NMR) Spectros-copyE1252 Practice for General Techniques for Obtaining Infra-red Spectra for Qualitative AnalysisE1994 Practice for Use of Process Oriented AOQL andLTPD Sampling PlansF748 Practice for Selecting Generic Biological Test Meth-ods for Materials and

20、 DevicesF1925 Specification for Semi-Crystalline Poly(lactide)Polymer and Copolymer Resins for Surgical ImplantsF2313 Specification for Poly(glycolide) andPoly(glycolide-co-lactide) Resins for Surgical Implantswith Mole Fractions Greater Than or Equal to 70 %Glycolide2.2 ANSI Standards:3ANSI/ISO/ASQ

21、 Q9000 Quality Management Systems,Fundamentals and VocabularyANSI/ISO/ASQ Q9001 Requirements2.3 ISO Standards:4ISO 31-8 Physical Chemistry and Molecular Physics, Part8: Quantities and UnitsISO 10993 Biological Evaluation of Medical Devices2.4 U. S. Pharmacopeia (USP) Standards:USP30/NF25 United Stat

22、es Pharmacopeia (USP), May 2,200752.5 Other Documents/Websites:ICH Q3C(R3) International Conference on Harmonisationof Technical Requirements for Registration of Pharmaceu-ticals for Human Use, Quality Guideline: Impurities:Residual Solvents621 CFR 820 Code of Federal Regulations, Title 21, Part820,

23、 Quality System Regulation7NIST Special Publication SP811 Guide for the Use of theInternational System of Units (SI)83. Terminology3.1 Definition:3.1.1 virgin polymerthe initially delivered form of apolymer as synthesized from its monomers and prior to anyprocessing or fabrication into a medical dev

24、ice.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 adequate control of particles

25、 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 subsequentsteps) shall be undertaken under conditions suita

26、ble to allowfor use of such resin in the manufacture of an implantablemedical product.5. Chemical Composition5.1 The amorphous poly(DL-lactide) polymers covered bythis specification shall be composed either of meso-lactide or aracemic combination of D-lactide and L-lactide. The amorphouspoly(DL-lact

27、ide-co-glycolide) copolymers covered by thisspecification can be of variable copolymer ratios and shall becomposed of a combination of glycolide and either meso-lactide or a racemic combination of D-lactide and L-lactidewhere the glycolide mole fraction is less than 70 % (65.3 % inmass fraction). To

28、 assure such composition and the attainmentof the desired properties, the following tests are to be con-ducted.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 ei

29、ther poly(lactide) homopolymer orpoly(lactide-co-glycolide) 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

30、 described in Prac-tice E1252. A typical infrared transmission reference spectrumand a typical infrared absorption reference spectrum forDL-PLA homopolymer are shown in Fig. 1, with examplespectra for copolymers presented in Fig. 2. While poly(lactide-co-glycolide) copolymers will each have their ow

31、n respectivespectrum that will vary in response to copolymer ratio, thisanalytic method typically lacks sensitivity sufficient for quan-tification of copolymer ratio as specified in 7.1.2.2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Customer Service at service

32、astm.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.3Available from American National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.4Available from American National Standards In

33、stitute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.5Available from U.S. Pharmacopeia (USP), 12601 Twinbrook Pkwy., Rockville,MD 20852-1790, http:/www.usp.org.6Available from ICH Secretariat, c/o IFPMA, 30 rue de St-Jean, P.O. Box 758,1211 Geneva 13, Switzerland. Availab

34、le online at http:/www.ich.org/LOB/media/MEDIA423.pdf7Available 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.8Available from National Institute of Standards and Technology (NIST), 100Bureau Dr.

35、, Stop 1070, Gaithersburg, MD 20899-1070, at http:/physics.nist.gov/cuu/Units/bibliography.html.F2579 1025.2.2.2 Additional or variable spectral bands may be indica-tive of sample crystallinity or either known or unknownimpurities, including residual monomer, solvents, and catalysts(refer to limits

36、specified in Table 1).5.2.2.3 Since an infrared spectrum cannot distinguish be-tween the different lactide stereoisomers, it is utilized here onlyas a means of identifying the non-stereospecific poly(lactide)component of a poly(lactide)-based polymer or copolymer.5.2.3 Proton Nuclear Magnetic Resona

37、nce (1H-NMR) Iden-tification:5.2.3.1 Identity of either poly(lactide) homopolymer orpoly(lactide-co-glycolide) copolymer may be confirmedthrough sample dissolution,1H-NMR spectroscopy, and theuse of a suitable reference spectrum. Sample dissolution is ineither deuterated chloroform, deuterated dichl

38、oromethane (me-thylene chloride) or other substantially proton-free solvent ableExample infrared spectra are alternative presentations of an amorphous 100 % DL-PLA homopolymer. (Spectra are courtesy of W. L. Gore available online at http:/pubs.acs.org/reagents/comminfo/minutes.htmlSupplied example N

39、MR spectra of amorphous 85 % DL-PLA:15% PGA and 50 % DL-PLA:50 % PGA (mole ratio) copolymers are courtesy of W. L. Gore with solvent, tempera-ture, and analyte concentration in solution); if requested by theTABLE 1 Physical/Chemical Property Requirements for Virgin Amorphous Poly(lactide) and Poly(l

40、actide-co-glycolide) ResinsAnalyteTotalResidualMonomer,(%)Total SolventCombinationResidual(s)(in ppm)Individual SolventResidual(s) andApplicable ICHLimit(s) (in ppm)(Optional)ResidualWater(%)Heavy Metals,(ppm as Pb)(Optional)ResidualCatalyst(in ppm)CopolymerRatioSpecificRotationRequirement Particula

41、te Matter in Injections. Unfortunately, at this time,there are no studies dealing with typical foreign particle levelsin this resin material or their effect upon resin properties. Sucha specification may be established in the future as informationregarding this parameter is developed by methods such

42、 asround-robin use of this standard for selected samples ofPLA-based resin from various commercial sources.X2.4 Chemical identification with comparison to a knownstandard (per 5.2 and 7.1.2) requires either an infrared or aNMR analysis, both of which provide broad chemical charac-terization of the a

43、nalytes organic composition. Utilization ofsuch broad characterization methods provides the analyticability to readily identify either a differing polymer (includingincorrect copolymer ratios) or the correct polymer containingsubstantial levels of non-specific organic contamination. Alter-native ana

44、lytical methods may be utilized specifically toquantify the copolymer ratio, providing sensitivity is adequateto assure compliance with specification requirements and bothresolution and specificity are adequate to exclude residualmonomer.X2.5 USP30/NF25 Heavy Metals is a limit test thatcomplexes num

45、erous cationic metals with the sulfide (S2-)anion, which imparts a coloration that is visually comparedwith an appropriate known concentration of lead standardsolution. While divalent lead is the specific cation utilized forsulfide complex quantification, coloration resulting from com-plexes with ot

46、her metallic cations is intentional and is directlycompared with the same lead standard solution. Since thespecified test conditions of this USP method define cationicsensitivity to sulfide coloration, no adjustment of non-leadcations for the their sulfide sensitivity is needed. However,correction t

47、o a lead equivalent concentration is necessary ifindividual non-lead metal concentrations are determined inde-pendently, as is typically the case when employing AA or ICPtechniques.X2.5.1 Assuming that all listed cations are ionically equiva-lent to divalent lead in their ability to create a sulfide

48、 colorcomplex, adjustments of resin sample concentrations to com-pensate for differences in atomic mass and oxidation state maybe made using the following formula:mg/kgof metalin sample3Atomic mass of PbAtomic mass of metal31charge metal21charge Pb5 ppm as Pb(X2.1)F2579 1010X2.5.2 Table X2.1 utilize

49、s the above calculation to providethe calculated Pb equivalent for each of the cations listed in5.7.2 as being responsive to Heavy Metals complexation.ASTM International takes no position respecting the validity of any patent rights asserted in connection with any item mentionedin this standard. Users of this standard are expressly advised that determination of the validity of any such patent rights, and the riskof infringement of such rights, are entirely their own responsibility.This standard is subject to revision at any time by the responsible technical committee and