1、Designation:F163504a Designation: F1635 11Standard 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 th
2、e 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 test method covers in vitro degradation of hy
3、drolytically degradable polymers (HDP) intended for use in surgicalimplants.1.2 The requirements of this test method apply to HDPs in various forms:1.2.1 Virgin polymer resins, or1.2.2 Any form fabricated from virgin polymer such as a semi-finished component of a finished product, a finished product
4、,which may include packaged and sterilized implants, or a specially fabricated test specimen.1.3This test method has no provisions for mechanical loading, fluid flow, or other dynamic challenges.1.41.3 This test method provides guidance for mechanical loading or fluid flow, or both, when relevant to
5、 the device beingevaluated. The specifics of loading type, magnitude, and frequency for a given application are beyond the scope of this test method.1.4 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.1.5 This standard does no
6、t purport to address all of the safety concerns, if any, associated with its use. It is the responsibilityof the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatorylimitations prior to use.2. Referenced Documents2.1 ASTM Standards:
7、2D638 Test Method for Tensile Properties of PlasticsD671 Test Method for Flexural Fatigue of Plastics by Constant-Amplitude-of-Force3D695 Test Method for Compressive Properties of Rigid PlasticsD747 Test Method for Apparent Bending Modulus of Plastics by Means of a Cantilever BeamD790 Test Methods f
8、or Flexural Properties of Unreinforced and Reinforced Plastics and Electrical Insulating MaterialsD882 Test Method for Tensile Properties of Thin Plastic SheetingD1708 Test Method for Tensile Properties of Plastics by Use of Microtensile SpecimensD1822 Test Method for Tensile-Impact Energy to Break
9、Plastics and Electrical Insulating MaterialsD2857 Practice for Dilute Solution Viscosity of PolymersF748 Practice for Selecting Generic Biological Test Methods for Materials and Devices2.2 Other Referenced Standard:ISO 318 Physical Chemistry and Molecular Physics - Part 8: Quantities and UnitsISO 10
10、9931 Biological Evaluation of Medical DevicesPart 1 Evaluation and Testing4ISO 10993-9:1999Biological Evaluation of Medical DevicesPart 9 Framework for Identification and Quantification ofPotential Degradation Products ISO 109939 Biological Evaluation of Medical DevicesPart 9 Framework for Identific
11、ationand Quantification of Potential Degradation Products41This test method is under the jurisdiction of ASTM Committee F04 on Medical and Surgical Materials and Devices and is the direct responsibility of SubcommitteeF04.15 on Material Test Methods.Current edition approved Oct.March 1, 2004.2011. P
12、ublished October 2004.March 2011. Originally approved in 1995. Last previous edition approved in 2004 asF1635 04a. DOI: 10.1520/F1635-04A.10.1520/F1635-11.2For referenced ASTM standards, visit the ASTM website, www.astm.org, or contact ASTM Customer Service at serviceastm.org. For Annual Book of AST
13、M Standardsvolume information, refer to the standards Document Summary page on the ASTM website.3Withdrawn.4Available from American National Standards Institute (ANSI), 25 W. 43rd St., 4th Floor, New York, NY 10036, http:/www.ansi.org.1This document is not an ASTM standard and is intended only to pr
14、ovide the user of an ASTM standard an indication of what changes have been made to the previous version. Becauseit may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current versionof th
15、e standard as published by ASTM is to be considered the official document.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.NIST Special Publication SP811 Guide for the Use of the International System of Units (SI)53. Terminology3.1 Def
16、initions:3.1.1 resinany polymer that is a basic material for plastics. absorbable, adj in the bodyan initially distinct foreignmaterial or substance that either directly or through intended degradation can pass through or be assimilated by cells and/or tissue.NOTE 1See Appendix X2 for a discussion r
17、egarding the usage of absorbable and other related terms.3.1.2 hydrolytically degradable polymer (HDP)any polymeric material in which the primary mechanism of chemicaldegradation in the body is by hydrolysis (water reacting with the polymer resulting in cleavage of the chain).3.1.3 resinany polymer
18、that is a basic material for plastics.64. Summary of Test Method4.1 Samples of polymer resins, semi-finished components, finished surgical implants, or specially designed test specimensfabricated from those resins are placed in buffered saline solution at physiologic temperatures. Samples are period
19、ically removedand tested for various material or mechanical properties at specified intervals. The required test intervals vary greatly dependingon the specific polymeric composition. For example, poly(l-lactide) and poly(e-caprolactone) degrade very slowly and can requiretwo or more years for compl
20、ete degradation. Polymers based substantially on glycolide can completely degrade in two to threemonths depending on the exact composition and on the size of the specimen. Degradation time is also strongly affected byspecimen size, polymer molecular weight, and crystallinity. -caprolactone) degrade
21、very slowly and can require two or more yearsfor complete degradation. Polymers based substantially on glycolide can completely degrade in two to three months depending onthe exact composition and on the size of the specimen. Degradation time is also strongly affected by specimen size, polymer molar
22、mass, and crystallinity.NOTE 2The term molecular weight (abbreviated MW) is obsolete and should be replaced by the SI (Systme Internationale) equivalent of eitherrelative molecular mass (Mr), which reflects the dimensionless ratio of the mass of a single molecule to an atomic mass unit see ISO 318,
23、or molarmass (M), which refers to the mass of a mole of a substance and is typically expressed as grams/mole. For polymers and other macromolecules, use ofthe symbols Mw, Mn, and Mzcontinue, referring to mass-average molar mass, number-average molar mass, and z-average molar mass, respectively. Form
24、ore information regarding proper utilization of SI units, see NIST Special Publication SP811.5. Significance and Use5.1 This test method is intended to help assess the biodegradationdegradation rates (that is, the mass loss rate) and changes inmaterial or structural properties, or both, of HDP mater
25、ials used in surgical implants. Polymers that are known to degrade primarilyby hydrolysis include but are not limited to homopolymers and copolymers of l-lactide, d-lactide, d,l-lactide glycolide,caprolactone, and p-dioxanone.75.2 This test method may not be appropriate for all types of implant appl
26、ications or for all known absorbable polymers. Theuser is cautioned to consider the appropriateness of the test method in view of the materials being tested and their potentialapplication (see X1.1.1).5.3 Since it is well known that mechanical loading can increase the degradation rate of absorbable
27、polymers, the presence andextent of such loading needs to be considered when comparing in vitro behavior with that expected or observed in vivo. Wherefeasible, it is recommended during degradation testing to simulate the .5.3.1 Mechanically Unloaded Hydrolytic EvaluationConditioning of a hydrolysabl
28、e device under mechanically unchallengedhydrolytic conditions at 37C in buffered saline is a common means to obtain a first approximation of the degradation profile ofan absorbable material or device. It does not necessarily represent actual in vivo service conditions, which can include mechanicallo
29、ading in a variety of forms (for example. static tensile, cyclic tensile, shear, bending, and so forth). If the performance of a deviceunder its indicated use includes loading, hydrolytic aging alone is NOT sufficient to fully characterize the device.5.3.2 Mechanically Loaded Hydrolytic EvaluationTh
30、e objective of loading is to approximate (at 37C in buffered saline) theactual expected device service conditions so as to better understand potential physicochemical changes that may occur. Such testingcan be considered as necessary if loading can be reasonably expected under in vivo service condit
31、ions. When feasible, testspecimens should be loaded in a manner that simulates in vivo conditions, both in magnitude and type of loading. Clinicallyrelevant cyclic load tests may include testing to failure or for a specified number of cycles followed by testing to evaluatephysicochemical properties.
32、5Polymer Technology Dictionary, Tony Whelan ed., Chapman once per week is generally practical and suggested. In cases where no prior knowledge of the degradation rateis available, it is suggested that the pH be tested at least daily until a baseline is established. This increased sampling frequencym
33、ay need to be repeated during periods of elevated mass loss (that is, pH change).8. Sample and Test Specimen8.1 All test samples shall be representative of the material under evaluation.8.1.1 For most HDP resins, inter-lot variations in the molecular weightmolar mass and residual monomer content can
34、 besignificant. Since these factors can strongly affect degradation rates, molecular weightmolar mass (or inherent viscosity) andresidual monomer content of the source resin and fabricated test parts need to be understood.8.1.2 Where evaluation aims allow, it is recommended that samples comparing va
35、riations in design be produced from the samematerial lot (or batch) and under the same fabrication conditions.8.1.3 When testing for inter-lot variability in degradation rate (for example, for process validation purposes), a minimum ofthree resin lots should be used.8.2 If a test is intended to be r
36、epresentative of actual performance in vivo, specimens shall be packaged and sterilized in amanner consistent with that of the final device. Unsterilized control specimens may be included for comparative purposes showingthe effects of sterilization.9. Procedure9.1 Test A, Weight Loss:9.1.1 Test samp
37、les, in either resin or fabricated form, shall be weighed to a precision of 0.1 % of the total sample weight priorto placement in the physiological solution. Samples shall be dried to a constant weight before initial weighing (see Note 2 Note6 and X1.8). Drying conditions, including final relative h
38、umidity (if applicable), shall be reported and may include the use of adesiccator, partial vacuum, or elevated temperatures (see Note 3Note 7).9.1.2 Test samples shall be fully immersed in the physiological solution for a specified period of time as discussed in 4.1 (forexample, 1 week, 2 weeks, and
39、 so forth).9.1.3 Upon completion of the specified time period, each sample shall be removed, gently rinsed with sufficient distilled waterto remove saline, placed in a tared container, and dried to a constant weight (see Note 2 Note 6 and X1.8). The weight shall berecorded to a precision of 0.1 % of
40、 the original total sample weight.NOTE2Drying 6Drying to a constant weight may be quantified as less than 0.1 % weight change over a period of 48 h, or less than 0.05 % changein 24 h if the balance used is capable of such precision. Section X1.8 provides additional information.NOTE 37Elevated temper
41、atures may be used to assist drying of the sample provided that the temperature used does not induce material or chemicalchanges in the sample. Vacuum drying with a dry gas purge can alternately be used without concern for material degradation. The drying conditions usedfor the samples prior to agin
42、g and for the samples retrieved at each test interval shall be identical. The actual drying conditions used are to be reported.9.1.4 After weighing, the samples shall not be returned to the physiological solution and shall be retired from the study.9.2 Test B, Molecular WeightTest B, Molar Mass:9.2.
43、1Prior to placement of samples in the physiological solution, determine the inherent viscosity (logarithmic viscosity number)of representative samples using Test Method9.2.1 Prior to placement of samples in the physiological solution, determine the molar mass of representative samples usingeither in
44、herent viscosity (logarithmic viscosity number) testing following the recommendations of Test Method D2857 in a solventappropriate for the test polymer and at a temperature sufficient to allow adequate solubility and temperature control. For example,poly(or size exclusion chromatography. Testing sha
45、ll be done in a solvent appropriate for the test polymer and at a temperaturesuffcient to allow solubility and temperature control. For example, the molar mass of poly(l-lactide) IV should be determined inchloroform at 25C.30C. The sample dilution ratio (mg/cm3) and test temperature shall be reporte
46、d. Alternative means ofmolecular weightmolar mass determination such as size exclusion chromatography may be used when feasible.9.2.2 Test samples shall be fully immersed in the physiological solution for the specified period of time (for example, 1 week,3 weeks, 52 weeks, and so forth).9.2.3 Sample
47、s shall be removed at each specified time period throughout the duration of the test, dried as in 9.1.1, and testedfor inherent viscosity as above. For polymers that undergo very rapid degradation, the molecular weightmolar mass may changesignificantly during the drying procedure, causing an overest
48、imate of the degradation rate. Therefore the user should exercisecaution in interpretation of this data. This caution does not generally apply to mass loss measurements, since continued degradationafter the samples are placed in tared containers will not affect the sample mass unless the degradation
49、 products are volatile. ForF1635 114rapidly degrading HDP materials, alternative procedures such as vacuum drying should be considered.9.3 Test C, Mechanical Testing:9.3.1 Determine the appropriate mechanical properties of representative samples of resin or fabricated forms using tensile,compressive, torque, bending or other appropriate mechanical tests prior to placement of the samples in the physiological solution(time zero). Relevant ASTM test methods may include one or more of the following:Test Method D638Test Method D671Test Method D695Test Method
