1、Designation: F1635 16Standard Test Method forin vitro Degradation Testing of Hydrolytically DegradablePolymer Resins and Fabricated Forms for SurgicalImplants1This standard is issued under the fixed designation F1635; the number immediately following the designation indicates the year oforiginal ado
2、ption 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 test method covers in vitro degradation of hydro-lytically degrada
3、ble polymers (HDP) intended for use insurgical implants.1.2 The requirements of this test method apply to HDPs invarious forms:1.2.1 Virgin polymer resins, or1.2.2 Any form fabricated from virgin polymer such as asemi-finished component of a finished product, a finishedproduct, which may include pac
4、kaged and sterilized implants,or a specially fabricated test specimen.1.3 This test method provides guidance for mechanicalloading or fluid flow, or both, when relevant to the device beingevaluated. The specifics of loading type, magnitude, andfrequency for a given application are beyond the scope o
5、f thistest method.1.4 The values stated in SI units are to be regarded asstandard. No other units of measurement are included in thisstandard.1.5 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
6、 to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.2. Referenced Documents2.1 ASTM Standards:2D638 Test Method for Tensile Properties of PlasticsD671 Test Method for Flexural Fatigue of Plastics byConstant-Amplitude-of-Force
7、 (Withdrawn 2002)3D695 Test Method for Compressive Properties of RigidPlasticsD747 Test Method for Apparent Bending Modulus of Plas-tics by Means of a Cantilever BeamD790 Test Methods for Flexural Properties of Unreinforcedand Reinforced Plastics and Electrical Insulating Materi-alsD882 Test Method
8、for Tensile Properties of Thin PlasticSheetingD1708 Test Method for Tensile Properties of Plastics by Useof Microtensile SpecimensD1822 Test Method for Tensile-Impact Energy to BreakPlastics and Electrical Insulating MaterialsD2857 Practice for Dilute Solution Viscosity of PolymersF748 Practice for
9、Selecting Generic Biological Test Methodsfor Materials and Devices2.2 ISO Standards:4ISO 318 Physical Chemistry and Molecular Physics - Part8: Quantities and UnitsISO 109931 Biological Evaluation of Medical DevicesPart 1 Evaluation and TestingISO 109939 Biological Evaluation of Medical DevicesPart 9
10、 Framework for Identification and Quantification ofPotential Degradation ProductsISO 13781 Poly(L-lactide) resins and fabricated forms forsurgical implants In vitro degradation testing2.3 NIST Standard:5NIST Special Publication SP811 Guide for the Use of theInternational System of Units (SI)3. Termi
11、nology3.1 Definitions:1This test method is under the jurisdiction of ASTM Committee F04 on Medicaland Surgical Materials and Devices and is the direct responsibility of SubcommitteeF04.15 on Material Test Methods.Current edition approved Dec. 1, 2016. Published January 2017. Originallyapproved in 19
12、95. Last previous edition approved in 2011 as F1635 11. DOI:10.1520/F1635-16.2For 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 ont
13、he ASTM website.3The last approved version of this historical standard is referenced onwww.astm.org.4Available from American National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.5Available from National Institute of Standards and Technology (NIST), 10
14、0Bureau Dr., Stop 1070, Gaithersburg, MD 20899-1070, at http:/physics.nist.gov/cuu/Units/bibliography.html.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United StatesThis international standard was developed in accordance with internationally rec
15、ognized principles on standardization established in the Decision on Principles for theDevelopment of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.13.1.1 absorbable, adjin the bodyan initially distinctforeign m
16、aterial or substance that either directly or throughintended degradation can pass through or be assimilated bycells and/or tissue.NOTE 1See Appendix X2 for a discussion regarding the usage ofabsorbable and other related terms.3.1.2 hydrolytically degradable polymer (HDP)any poly-meric material in wh
17、ich the primary mechanism of chemicaldegradation in the body is by hydrolysis (water reacting withthe polymer resulting in cleavage of the chain).3.1.3 resinany polymer that is a basic material for plas-tics.64. Summary of Test Method4.1 Samples of polymer resins, semi-finished components,finished s
18、urgical implants, or specially designed test specimensfabricated from those resins are placed in buffered salinesolution at physiologic temperatures. Samples are periodicallyremoved and tested for various material or mechanical prop-erties at specified intervals. The required test intervals varygrea
19、tly depending on the specific polymeric composition. Forexample, poly(l-lactide) and poly(e-caprolactone) degrade veryslowly and can require two or more years for completedegradation. Polymers based substantially on glycolide cancompletely degrade in two to three months depending on theexact composi
20、tion and on the size of the specimen. Degrada-tion time is also strongly affected by specimen size, polymermolar mass, and crystallinity.NOTE 2The term molecular weight (abbreviated MW) is obsolete andshould be replaced by the SI (Systme Internationale) equivalent of eitherrelative molecular mass (M
21、r), which reflects the dimensionless ratio of themass of a single molecule to an atomic mass unit see ISO 318, or molarmass (M), which refers to the mass of a mole of a substance and istypically expressed as grams/mole. For polymers and othermacromolecules, use of the symbols Mw, Mn, and Mzcontinue,
22、 referringto mass-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. Significance and Use5.1 This test method is intended to help assess the degrada-tion rates (th
23、at is, the mass loss rate) and changes in material orstructural properties, or both, of HDP materials used in surgicalimplants. Polymers that are known to degrade primarily byhydrolysis include but are not limited to homopolymers andcopolymers of l-lactide, d-lactide, d,l-lactide glycolide,caprolact
24、one, and p-dioxanone.75.2 This test method may not be appropriate for all types ofimplant applications or for all known absorbable polymers.The user is cautioned to consider the appropriateness of the testmethod in view of the materials being tested and their potentialapplication (see X1.1.1).5.3 Si
25、nce it is well known that mechanical loading canincrease the degradation rate of absorbable polymers, thepresence and extent of such loading needs to be consideredwhen comparing in vitro behavior with that expected orobserved in vivo.5.3.1 Mechanically Unloaded Hydrolytic EvaluationConditioning of a
26、 hydrolysable device under mechanicallyunchallenged hydrolytic conditions at 37C in buffered salineis a common means to obtain a first approximation of thedegradation profile of an absorbable material or device. It doesnot necessarily represent actual in vivo service conditions,which can include mec
27、hanical loading in a variety of forms (forexample. static tensile, cyclic tensile, shear, bending, and soforth). If the performance of a device under its indicated useincludes loading, hydrolytic aging alone is NOT sufficient tofully characterize the device.5.3.2 Mechanically Loaded Hydrolytic Evalu
28、ationThe ob-jective of loading is to approximate (at 37C in buffered saline)the actual expected device service conditions so as to betterunderstand potential physicochemical changes that may occur.Such testing can be considered as necessary if loading can bereasonably expected under in vivo service
29、conditions. Whenfeasible, test specimens should be loaded in a manner thatsimulates in vivo conditions, both in magnitude and type ofloading. Clinically relevant cyclic load tests may includetesting to failure or for a specified number of cycles followedby testing to evaluate physicochemical propert
30、ies.5.3.2.1 Static LoadingIt is notable that for some poly-meric materials it has been shown that a constant load resultsin the same failure mechanism (for example, creep) and is theworst case when compared to a cyclic load (where themaximum amplitude of the cyclic load is equal to the constantload)
31、. Thus, in specific cases it may be acceptable to simplifythe test by using a constant load even when the anticipated invivo loading is cyclic. It is encumbent upon the user of this testmethod to demonstrate through experiment or specific refer-ence that this simplification is applicable to the poly
32、mer underinvestigation and does not alter the failure mode of the testspecimen. If such evidence is not available ,it is necessary torecognize that static loading and cyclic loading are measuringdifferent material properties and are not comparable. Using oneto replace the other could lead to misinte
33、rpretation of theresults.NOTE 3Caution must be taken to ensure that fixturing does notintroduce artifactual performace or degradation issues, or both. Anexample is the use of rigid foam block, which restricts swelling once per week is generally practicaland suggested. In cases where no prior knowled
34、ge of thedegradation rate is available, it is suggested that the pH betested at least daily until a baseline is established. Thisincreased sampling frequency may need to be repeated duringperiods of elevated mass loss (that is, pH change).8. Sample and Test Specimen8.1 All test samples shall be repr
35、esentative of the materialunder evaluation.8.1.1 For most HDP resins, inter-lot variations in the molarmass and residual monomer content can be significant. Sincethese factors can strongly affect degradation rates, molar mass(or inherent viscosity) and residual monomer content of thesource resin and
36、 fabricated test parts need to be understood.8.1.2 Where evaluation aims allow, it is recommended thatsamples comparing variations in design be produced from thesame material lot (or batch) and under the same fabricationconditions.8.1.3 When testing for inter-lot variability in degradationrate (for
37、example, for process validation purposes), a minimumof three resin lots should be used.8.2 If a test is intended to be representative of actualperformance in vivo, specimens shall be packaged and steril-ized in a manner consistent with that of the final device.Unsterilized control specimens may be i
38、ncluded for compara-tive purposes showing the effects of sterilization.F1635 1639. Procedure9.1 Test A, Mass Loss:9.1.1 Test samples, in either resin or fabricated form, shallbe weighed to a precision of 0.1 % of the total sample massprior to placement in the physiological solution. Samples shallbe
39、dried to a constant mass before initial weighing (see Note 6and X1.8). Drying conditions, including final relative humidity(if applicable), shall be reported and may include the use of adesiccator, partial vacuum, or elevated temperatures (see Note7).9.1.2 Test samples shall be fully immersed in the
40、 physi-ological solution for a specified period of time as discussed in4.1 (for example, 1 week, 2 weeks, and so forth).9.1.3 Upon completion of the specified time period, eachsample shall be removed, gently rinsed with sufficient distilledwater to remove saline, placed in a tared container, and dri
41、ed toa constant mass (see Note 6 and X1.8). The weight shall berecorded to a precision of 0.1 % of the original total samplemass.NOTE 6Drying to a constant mass may be quantified as less than0.1 % mass change over a period of 48 h, or less than 0.05 % change in24 h if the balance used is capable of
42、such precision. Section X1.8provides additional information.NOTE 7Elevated temperatures may be used to assist drying of thesample provided that the temperature used does not induce material orchemical changes in the sample. Vacuum drying with a dry gas purge canalternately be used without concern fo
43、r material degradation. The dryingconditions used for the samples prior to aging and for the samplesretrieved at each test interval shall be identical. The actual dryingconditions used are to be reported.NOTE 8Sample debris/fragments may be produced during the degra-dation study. It may not be appro
44、priate or relevant to consider separateddebris/fragments as part of the test sample mass. In such cases, collectionand measurement of sample fragments are optional. In the event thatrecovery and quantification are needed, refer to ISO 13781, Clause“Separation of samples and debris.”9.1.4 After weigh
45、ing, the samples shall not be returned tothe physiological solution and shall be retired from thedegradation study. Dried samples from the measurement ofmass loss shall not be used for mechanical testing, but can bereused for evaluation of changes in molar mass (9.2) or othernon-mechanical testing (
46、e.g., differential scanning calorimetry,etc.).9.2 Test B, Molar Mass:9.2.1 Prior to placement of samples in the physiologicalsolution, determine the molar mass of representative samplesusing either inherent viscosity (logarithmic viscosity number)testing following the recommendations of Test Method
47、D2857or size exclusion chromatography. Testing shall be done in asolvent appropriate for the test polymer and at a temperaturesufficient to allow solubility and temperature control. Forexample, the molar mass of poly(l-lactide) should be deter-mined in chloroform at 30C. The sample dilution ratio(mg
48、/cm3) and test temperature shall be reported. Alternativemeans of molar mass determination may be used whenfeasible.9.2.2 Test samples shall be fully immersed in the physi-ological solution for the specified period of time (for example,1 week, 3 weeks, 52 weeks, and so forth).9.2.3 Samples shall be
49、removed at each specified timeperiod throughout the duration of the test, dried as in 9.1.1, andtested for inherent viscosity or size exclusion chromatographyfor degradation monitoring as above. For polymers that un-dergo very rapid degradation, the molar mass may changesignificantly during the drying procedure, causing an overesti-mate of the degradation rate. Therefore the user should exercisecaution in interpretation of this data. This caution does notgenerally apply to mass loss measurements, since continueddegradation after the samples are placed in
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