ASTM F2695-2012 Standard Specification for Ultra-High Molecular Weight Polyethylene Powder Blended With Alpha-Tocopherol (Vitamin E) and Fabricated Forms for Surgical Implant Appli.pdf

1、Designation: F2695 12Standard Specification forUltra-High Molecular Weight Polyethylene Powder BlendedWith Alpha-Tocopherol (Vitamin E) and Fabricated Forms forSurgical Implant Applications1This standard is issued under the fixed designation F2695; 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 () indicates an editorial change since the last revision or reapproval.1. Scope1.1 This specification covers ultra-high mol

3、ecular weightpolyethylene (UHMWPE) powder blended with alpha-tocopherol (vitamin E) intended for use in surgical implants.1.2 The requirements of this specification apply to alpha-tocopherol-containing UHMWPE in two forms. One is virginpolymer powder blended with alpha-tocopherol prior to con-solida

4、tion (Section 4). The second is any form fabricated fromthis blended, alpha-tocopherol-containing powder from whicha finished product is subsequently produced (Section 5). Thisspecification does not apply to finished or semi-finishedproducts that are doped with vitamin E after consolidation.1.3 Asid

5、e from blending with alpha-tocopherol, the provi-sions of Specifications F648 and D4020 apply. Special require-ments detailed in this specification are added to describepowders containing alpha-tocopherol that will be used insurgical implants. This specification addresses material char-acteristics a

6、nd does not apply to the packaged and sterilizedfinished implant. This specification also does not apply toUHMWPE materials extensively crosslinked by gamma andelectron beam sources of ionizing radiation.1.4 The following precautionary caveat pertains only to thefabricated forms portion, Section 5,

7、of this specification. Thisstandard does not purport to address all of the safety concerns,if any, associated with its use. It is the responsibility of the userof this standard to establish appropriate safety and healthpractices and determine the applicability of regulatory limita-tions prior to use

8、.2. Referenced Documents2.1 ASTM Standards:2D648 Test Method for Deflection Temperature of PlasticsUnder Flexural Load in the Edgewise PositionD790 Test Methods for Flexural Properties of Unreinforcedand Reinforced Plastics and Electrical Insulating MaterialsD1898 Practice for Sampling of Plastics3D

9、4020 Specification for Ultra-High-Molecular-WeightPolyethylene Molding and Extrusion MaterialsF619 Practice for Extraction of Medical PlasticsF648 Specification for Ultra-High-Molecular-Weight Poly-ethylene Powder and Fabricated Form for Surgical Im-plantsF748 Practice for Selecting Generic Biologic

10、al Test Meth-ods for Materials and DevicesF749 Practice for Evaluating Material Extracts by Intracu-taneous Injection in the RabbitF756 Practice for Assessment of Hemolytic Properties ofMaterialsF763 Practice for Short-Term Screening of Implant Materi-alsF813 Practice for Direct Contact Cell Culture

11、 Evaluation ofMaterials for Medical DevicesF895 Test Method for Agar Diffusion Cell Culture Screen-ing for CytotoxicityF981 Practice for Assessment of Compatibility of Biomate-rials for Surgical Implants with Respect to Effect ofMaterials on Muscle and Bone2.2 ISO Standards:ISO 34511 PlasticsDetermi

12、nation of Ash, Part 1: Gen-eral Methods4ISO 10993 Biological Evaluation of Medical Devices, Parts11243. Terminology3.1 Definitions of Terms Specific to This Standard:3.1.1 crosslinkingthe process by which ionizing irradia-tion produces chemical bonds between two UHMWPE mol-ecules.1This specification

13、 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.Current edition approved May 15, 2012. Published June 2012. Originallyapproved in 2007. Last previous edition approved in 2007 a

14、s F2695 07. DOI:10.1520/F2695-12.2For referenced 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.3Withdrawn. The last approve

15、d version of this historical standard is referencedon www.astm.org.4Available from American National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, Unite

16、d States.3.1.2 extensively crosslinked UHMWPEUHMWPE mate-rial that has been subjected to total doses of gamma and/orelectron beam ionizing irradiation greater than 40 kGy.3.1.3 fabricated formany bulk shape of UHMWPE, fab-ricated from the virgin polymer powder, used during theprocess of fabricating

17、surgical implants prior to crosslinking,packaging, and sterilization. A fabricated form includes asemi-finished rod or sheet as well as a direct compressionmolded component.3.1.4 generic propertythat property which is determinedsolely by the chemical composition and structure of the virginpolymer.3.

18、1.5 ionizing irradiationgamma ray or high energy elec-tron irradiation sources.3.1.6 virgin polymer powderthe initially delivered formof the polymer as synthesized from its monomers prior to anyprocessing or fabrication into a medical device. The providedresin is typically in the form of pellets, gr

19、anules, or powder andis the material from which fibers, tubes, rods, slabs, sheets,films, or specific parts and devices are fabricated. Specifically,it is the form of UHMWPE as obtained from the powdermanufacturer and prior to blending and fabrication into a bulkshape.4. Alpha-Tocopherol-Blended UHM

20、WPE PowderRequirements4.1 Generic Properties:4.1.1 The virgin polymer shall be a homopolymer of ethyl-ene in accordance with Specification D4020.4.1.2 The resin type and solution viscosity number require-ments are listed in Table 1 of Specification F648.4.1.3 To promote uniformity between different

21、lots of thevirgin polymer powder, concentration limits for trace elementshave been established and are listed in Table 1 of SpecificationF648.4.1.4 When determined as described in ISO 34511, themean ash of duplicate samples shall not exceed the limitsestablished in Table 1 of Specification F648.4.2

22、Nongeneric Properties:4.2.1 When a 300 g sample is prepared and viewed inaccordance with section 7.1.2 of Specification F648, there shallbe no more particles of extraneous matter than that specified inTable 1 of Specification F648.4.3 Compositional Requirements:4.3.1 Only alpha-tocopherol (certified

23、 pharmaceuticalgrade) is to be blended with the virgin polymer powder.4.3.1.1 The alpha-tocopherol content in the blended powdermay be based on agreement between the vendor and purchaser.4.3.1.2 When measured based on agreement between thevendor and purchaser, the alpha-tocopherol content added toth

24、e powder shall be reported in units of ppm and percent mass.4.3.1.3 Uniformity of the alpha-tocopherol in the blendedpowder will be measured based on agreement between thevendor and the purchaser.4.3.1.4 No other stabilizers or processing aids are to beadded to the virgin polymer powder.5. Alpha-Toc

25、opherol-Blended UHMWPE FabricatedForm Requirements5.1 Compositional Requirements:5.1.1 Only alpha-tocopherol-blended powder, specified inSection 4, is to be used to produce the fabricated form.5.1.1.1 The alpha-tocopherol content in the fabricated formmay be based on agreement between the vendor and

26、 purchaser.5.1.1.2 When measured based on agreement between thevendor and purchaser, the alpha-tocopherol content used toproduce the fabricated form shall be reported in units of ppmand percent mass.5.1.2 Uniformity of the alpha-tocopherol in the fabricatedform shall be measured based on agreement b

27、etween thevendor and the purchaser.5.1.3 No other stabilizers or processing aids are to be addedto the alpha-tocopherol-blended polymer powder during manu-facture of the fabricated form.5.2 Physical Requirements:5.2.1 Foreign Matter Requirements:5.2.1.1 When 3200 cm2is evaluated according to section

28、7.2.2 of Specification F648, there shall be no more than 10particles of extraneous matter visible on the surface whenvisually inspected by normal or corrected vision.5.2.2 Morphology Requirements:5.2.2.1 When evaluated according to Annex 2 of Specifica-tion F648, the calculated Morphology Index (MI)

29、 shall bereported.5.3 Mechanical Requirements:5.3.1 UHMWPE in fabricated form from which implantsshall be made shall meet the requirements listed in Table 2 ofSpecification F648.5.3.2 The following mechanical tests may be conductedbased on agreement between the vendor and purchaser: (1)Deflection te

30、mperature; Test Method D648 (1.8 MPa); (2)Flexural modulus; Test Methods D790 (secant, 2 % offset).6. Sampling6.1 Where applicable, the requirements of this specificationshall be determined for each lot of powder and fabricated formby sampling sizes and procedures according to Practice D1898,or as a

31、greed upon between the purchaser and seller.7. Biocompatibility7.1 No known surgical implant material has ever beenshown to be completely free of adverse reactions in the humanbody. However, published studies (1-5)5of specific formula-tions of alpha-tocopherol doped UHMWPE have shown that anacceptab

32、le level of biological response can be expected, asfurther discussed in Appendix X1.5. Virgin (undoped) UHM-WPE has been shown to produce a well-characterized level ofbiological response following long term clinical use. Theclinical history for virgin UHMWPE indicates an acceptablelevel of biologica

33、l response in the applications in which theundoped material has been utilized. When new applications ofthe material, or modification to the material or physical forms5The boldface numbers in parentheses refer to the list of references at the end ofthis standard.F2695 122of the materials are being co

34、ntemplated (such as, blending withalpha-tocopherol), the recommendations of ISO 10993, Parts112 and Practice F748 should be considered and testingconsidered as described in Practices F619, F749, F756, F763,F813, and F981 as well as Test Method F895.8. Keywords8.1 alpha-tocopherol; fabricated forms;

35、powdered form;ultra-high molecular weight polyethylene; vitamin EAPPENDIX(Nonmandatory Information)X1. RATIONALEX1.1 This specification is intended to describe the proper-ties required and the procedures to be followed in testingunirradiated raw materials of UHMWPE blended with alpha-tocopherol for

36、medical implant applications. This specificationdoes not purport to address the testing that is needed forimplants that are fabricated from the raw materials specifiedherein.X1.2 Alpha-tocopherol is a biocompatible stabilizer ofpolyolefins (1-6) and is intended to reduce oxidative degrada-tion durin

37、g processing, radiation processing, shelf life storage,and in vivo exposure of UHMWPE. Several laboratory studieshave demonstrated that alpha-tocopherol will stabilize irradi-ated UHMWPE from accelerated aging conditions intended tosimulate a variety of severe oxidative challenges (7-12).Human clini

38、cal use of implants fabricated from alpha-tocopherol blended UHMWPE is reported to have begun in2004. At present, the extent to which alpha-tocopherol willhelp stabilize UHMWPE implants from in vivo oxidation hasnot yet been determined.X1.3 While beneficial for oxidative stability, levels ofalpha-to

39、copherol $1000 ppm may later interfere with subse-quent radiation crosslinking steps (7, 10) during subsequentstages of the implant manufacturing process. With 1000 ppm ofalpha-tocopherol, Oral et al. have reported an average reduc-tion of 17 % in crosslink density following a dose of 100 kGy(7). On

40、 the other hand, levels of alpha tocopherol in the range125 to 500 ppm appear to be effective for stabilization ofUHMWPE, although the level of stabilization depends uponthe dose of radiation and the type of oxidative challenge (7, 11,12). Thus, crosslinking will be a function of both the alpha-toco

41、pherol content and the radiation dose, both of which maydepend upon the choice of the manufacturer. Consequently, thisstandard is not intended to specify a minimum alpha-tocopherol content for unirradiated raw materials that willsubsequently be used to fabricate orthopedic implants. Devicetesting is

42、 recognized to be crucial for UHMWPE implants, butis beyond the scope of this standard specification.X1.4 The current standard specifies alpha-tocopherol con-tent to be reported based on the mass percentage of antioxidantblended with the virgin resin powder prior to consolidation.Experimental techni

43、ques, including Fourier transform infraredspectroscopy and HPLC (4, 7), have been proposed in theliterature for characterizing the content of alpha-tocopherol,and its by-products, in consolidated UHMWPE. At presentthese research techniques have not been standardized. In thefuture, when quantificatio

44、n techniques for UHMWPE contain-ing alpha-tocopherol have been standardized, it is expected thatthe current specification will be updated to include morespecific details regarding appropriate test methodologies.X1.5 There is some limited biocompatibility regardingcytotoxicity, genotoxicity, and anim

45、al studies designed toevaluate the potential transformation products of Vitamin Efollowing consolidation and radiation of blended UHMWPEbiomaterials (1, 2. 4). These studies were performed using8000 ppm blended UHMWPE (GUR 1020), which was irradi-ated with 25 kGy (1, 2. 4), which results in the equi

46、valent, andmore voluminous, transformation products as 1,000 blendedUHMWPE irradiated with 200 kGy. However, additionalbiocompatibility testing in accordance with ISO 10993 may benecessary in order to fully address the biocompatibility ofdegradation products of alpha-tocopherol: (1) genotoxicitytest

47、ing in a mammalian test system capable of detecting genelevel and chromosome level mutations; (2) irritation sensitiza-tion testing; and (3) chronic toxicity and carcinogenicitytesting. Additional testing to address the effect degradationproducts of alpha-tocopherol on particulate mediated inflam-ma

48、tory response may also be required.F2695 123REFERENCES(1) Wolf, C., Lederer, K., Pfragner, R., Schauenstein, K., Ingolic, E., andSiegl, V., “Biocompatibility of Ultra-High Molecular Weight Polyeth-ylene (UHMW-PE) Stabilized with Alpha-Tocopherol Used for JointEndoprostheses Assessed In Vitro,” Journ

49、al of Materials Science,Feb 3, 2007.(2) Wolf, C., Lederer, K., Bergmeister, H., Losert, U., and Bock, P.,“Animal Experiments with Ultra-High Molecular Weight Polyethylene(UHMW-PE) Stabilized with Alpha-Tocopherol Used for ArticulatingSurfaces in Joint Endoprostheses,” Journal of Materials Science,17(12), Dec 2006, pp. 13411347.(3) Reno, F., Cannas, M., “UHMWPE and Vitamin E Bioactivity: AnEmerging Perspective,” Biomaterials, 27(16), Jun 2006, pp.30393043.(4) Wolf, C., Lederer, K., and Muller, U., “Tests of Biocompatibility ofAlpha-Tocopherol with Respect to the Use a