1、Designation: F641 09 (Reapproved 2014)Standard Specification forImplantable Epoxy Electronic Encapsulants1This standard is issued under the fixed designation F641; the number immediately following the designation indicates the year of originaladoption or, in the case of revision, the year of last re
2、vision.Anumber in parentheses indicates the year of last reapproval.Asuperscriptepsilon () indicates an editorial change since the last revision or reapproval.1. Scope1.1 This specification covers thermoset plastics based ondiglycidyl ethers of bisphenol A and amino functional curingagents or amine
3、catalysts.1.2 The epoxy encapsulants covered by this specificationare intended to provide a tissue-compatible protective coveringfor implantable medical devices such as pulse generators,telemetry devices and RF receivers. The biocompatibility ofepoxy plastics has not been established. Epoxy plastic
4、is ageneric term relating to the class of polymers formed fromepoxy resins, certain curing agents or catalysts and variousadditives. Since many compositions and formulations fallunder this category, it is essential that the fabricator assuresafety of implantability of the specific composition or for
5、mu-lation for the intended use by current state-of-the-art testmethods. This specification can be used as a basis for stan-dardized evaluation of biocompatibility for such implantableencapsulants.1.3 The encapsulants covered by this specification are foruse in devices intended as long-term implants.
6、1.4 LimitationsThis specification covers only the initialqualification of epoxy encapsulants for implantable electroniccircuitry. Some of the requirements are not applicable toroutine lot-to-lot quality control.1.5 The values stated in SI units are to be regarded asstandard. No other units of measur
7、ement are included in thisstandard.1.6 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 to establish appro-priate safety and health practices and determine the applica-bility of regulatory limit
8、ations prior to use.2. Referenced Documents2.1 ASTM Standards:2D149 Test Method for Dielectric Breakdown Voltage andDielectric Strength of Solid Electrical Insulating Materialsat Commercial Power FrequenciesD150 Test Methods forAC Loss Characteristics and Permit-tivity (Dielectric Constant) of Solid
9、 Electrical InsulationD257 Test Methods for DC Resistance or Conductance ofInsulating MaterialsD570 Test Method for Water Absorption of PlasticsD638 Test Method for Tensile Properties of PlasticsD790 Test Methods for Flexural Properties of Unreinforcedand Reinforced Plastics and Electrical Insulatin
10、g Materi-alsD1042 Test Method for Linear Dimensional Changes ofPlastics Caused by Exposure to Heat and MoistureD1239 Test Method for Resistance of Plastic Films toExtraction by ChemicalsD1434 Test Method for Determining Gas Permeability Char-acteristics of Plastic Film and SheetingD2240 Test Method
11、for Rubber PropertyDurometer Hard-nessD2471 Practice for GelTime and Peak ExothermicTempera-ture of Reacting Thermosetting Resins (Withdrawn 2008)3D2562 Practice for Classifying Visual Defects in PartsMolded from Reinforced Thermosetting PlasticsD2566 Test Method for Linear Shrinkage of Cured Thermo
12、-setting Casting Resins During Cure (Withdrawn 1993)3D2734 Test Methods for Void Content of Reinforced PlasticsD3137 Test Method for Rubber PropertyHydrolytic Sta-bility (Withdrawn 0)3F74 Practice for Determining Hydrolytic Stability of PlasticEncapsulants for Electronic Devices (Withdrawn 1994)31Th
13、is specification 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 Nov. 1, 2014. Published November 2014. Originallyapproved in 1979. Last previous editio
14、n approved in 2009 as F641 09. DOI:10.1520/F0641-09R14.2For 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.3The l
15、ast approved version of this historical standard is referenced onwww.astm.org.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States1F135 Test Method for Embedment Stress Caused by CastingCompounds on Glass-Encased Electronic (Withdrawn1997)
16、3F602 Criteria for Implantable Thermoset Epoxy PlasticsF748 Practice for Selecting Generic Biological Test Methodsfor Materials and DevicesF895 Test Method forAgar Diffusion Cell Culture Screeningfor CytotoxicityF981 Practice for Assessment of Compatibility of Biomate-rials for Surgical Implants wit
17、h Respect to Effect ofMaterials on Muscle and Bone2.2 AAMI Standard:EOS-D E-O Sterilization Standard42.3 ISO Standard:ISO 10993 Biological Evaluation of Medical Devices53. Classification3.1 Encapsulants shall be classified as follows:3.1.1 Type IThose encapsulants which contact the tissuedirectly or
18、 indirectly.3.1.2 Type IIThose encapsulants used only within her-metically sealed containers. The epoxy encapsulant has nocontact with tissues or physiological fluids.4. Chemical Composition4.1 Additives (Type I Encapsulants Only):4.1.1 Reactive DiluentsThe following compounds whenused as reactive d
19、iluents shall not be used in concentrationsgreater than 12 parts per hundred resin (phr).4.1.1.1 Butyl glycidyl ether (BGE).4.1.1.2 Phenyl glycidyl ether (PGE).4.1.2 Other Additives (see Note 1)Other additives shall beshown to be nonextractable in 37C physiological saline for thedevice design life i
20、n concentrations sufficient to significantlyaffect the properties of the encapsulant or to produce asignificant biological reaction.NOTE 1Other additives, as indicated in Criteria F602, includecompounds such as nonreactive diluents, fillers, release agents, and thelike.4.1.3 Phthalate EstersPhthalat
21、e esters such as dibutylphthalate shall not be used in concentrations 10 phr.4.2 Mix Ratios (Type I and Type II Encapsulants):4.2.1 AminesThe mix ratio shall be maintained at 65equivalent % of stoichiometry.4.2.2 CatalystsThe mix ratio shall be maintained withinthe ranges recommended by the formulat
22、or.4.3 Carbonates (Type I and Type II Encapsulants)Theencapsulant shall be poured under conditions such that theformation of amine carbonates is minimized. The devicemanufacturer may specify maximum limits for carbon dioxideor water vapor, or both, in the atmosphere in which theencapsulant is being
23、mixed or poured.5. Physical Properties5.1 Type I Encapsulants:5.1.1 Peak Exotherm Temperature (Test Method D2471)The peak exotherm temperature during cure shall be keptbelow the maximum acceptable value for the lowest tempera-ture rated component of the device.5.1.2 Fully Cured SpecimensThe required
24、 properties mea-sured on fully cured specimens conditioned as in 6.1 are asfollows:5.1.2.1 TransparencyIn cases where no fillers or rein-forcements are used, the encapsulant shall have sufficienttransparency so that the circuitry may be visually inspectedafter encapsulation.5.1.2.2 Foreign Particles
25、No foreign particles, particulatematter, or gross contamination shall be observed when checkedunder 2 wide field magnification.5.1.2.3 Biocompatibility TestingWhile cell culture meth-ods as described in Test Method F895 may be appropriate forthe lot-to-lot screening of fully cured specimens, the bas
26、icrecipe used should have been qualified for its overall tissueresponse by methods such as those suggested in Practice F748or ISO 10993 for the intended application, including testingaccording to Practice F981.(1) Biocompatibility testing should be performed on speci-mens that have been processed an
27、d sterilized per the methodsintended for the final device.5.1.2.4 USP Bacterial Endotoxin Test6or other Pyrogenmethods which have been demonstrated to be of equal orgreater sensitivityPass.5.1.2.5 Sterilant Residues (AAMI EOS-D)Whereapplicable, the concentration of ethylene oxide, ethylenechlorohydr
28、in, ethylene glycol, and dichlorodifluoromethane (orthe equivalents) at the time of implantation shall be shown tobe within safe limits prescribed by the device manufacturer.5.1.2.6 The cure shrinkage (Test Method D2566) or embed-ment stress (Test Method F135) shall be 2%. The stress shallnot exceed
29、 the limits of the most pressure-sensitive compo-nents.5.1.2.7 Tissue Culture Test (Agar Overlay)7or Test MethodF895Pass.5.1.3 Required Cured Properties Measured in Long-TermImmersion Tests for Type I EncapsulantsThe property valuesprescribed in Table 1 shall be obtained at 22 6 3C and 50 610 % rela
30、tive humidity on specimens conditioned as in 6.3.Samples shall be wiped dry prior to test with a lint-free tissue,as appropriate.5.1.4 Optional cured properties measured after acceleratedimmersion for Type I encapsulants may be determined forscreening purposes after conditioning as in 6.2.5.2 Type I
31、I Encapsulants:5.2.1 Peak Exotherm Temperature (Test Method D2471)The peak exotherm temperature during cure shall be kept4Available fromAssociation forAdvancement of Medical Instrumentation, 1500Wilson Blvd., Suite 417, Arlington, VA 22209.5Available from American National Standards Institute (ANSI)
32、, 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.6U.S. Pharmacopeia, USP-NF, , available from U.S. Pharmacopeia (USP),12601 Twinbrook Pkwy., Rockville, MD 20852-1790, http:/www.usp.org.7Guess, W. L., et al., Journal of Pharmaceutical Sciences , Vol 54, 1965, pp.15451547.F641 09 (20
33、14)2below the maximum acceptable value for the lowest tempera-ture rated component of the device.5.2.2 The property values prescribed in Table 2 shall bedetermined at 22 6 3C and 50 6 10 % relative humidity onfully cured samples conditioned as in 6.1.6. Specimen Preparation6.1 PreparationPrepare spe
34、cimens used for evaluation ofproperties of the cured material in the same manner as theintended product. Such conditioning shall include all specifiedrelevant variables for the product prior to implantation, includ-ing specimen size or shape, cure time, cure temperature,post-cure, cleaning, packagin
35、g, sterilization, and aeration.6.2 Accelerated Immersion:6.2.1 For screening purposes, immerse specimens preparedas in 6.1 in refluxing physiological saline of pH 7.4 6 0.2 for7 days.6.2.2 Prior to evaluation, allow the specimens to equilibrateto the test temperature of 22 6 3C in physiological sali
36、ne ofpH 7.4 6 0.2.6.2.3 Condition one set of controls at 100 6 3C andanother set at 22 6 3C for 7 days at 50 6 10 % relativehumidity.6.2.4 Since two variables, heat and moisture, are inherent inthis test, data from specimens refluxed 7 days in saline may becompared to controls conditioned dry at 100
37、C and at 22C.Thus, one may estimate the long-term effects of moisture asopposed to the effects of moisture and heat or heat alone.6.3 Long-Term Immersion (Test Method D3137 or PracticeF74):6.3.1 Prepare the specimens in accordance with 6.1.6.3.2 During initial qualification of the formulation, im-me
38、rse specimens in 37 6 3C aerated physiological saline ofpH 7.4 6 0.2 with periodic sampling for evaluation as isappropriate for a period of time consistent with projectedservice life. Immersion shall continue for the projected servicelife of the device. For devices intended for long-term implant,how
39、ever, it may not be practical to complete tank tests over thedevices projected service life before one can claim compliancewith the specification. One shall be considered in complianceTABLE 1 Cure Requirements for Long-Term Immersion Tests for Type I EncapsulantsProperty Requirement ASTM MethodExtra
40、ction 11.8 kV/mm D149Dielectric constant 2.0 D150Dissipation factor 1.5 % D638Flexural strength $1380 MPa D790Gas permeationAD1434Hardness $60 Shore D D2240Dimensional stability 2.0 D150Dielectric strength 11.8 kV/mm D149Dissipation factor 0.05 D150Dimensional stability 0.5 % change D1042Visual defe
41、cts none that adversely affect the safety, efficacy, or reliability ofthe deviceD2562Voids none that adversely affect the safety, efficacy, or reliability ofthe deviceD2734Volume resistivity 1010cm D257F641 09 (2014)3with this section of the specification, therefore, if specimensmeet the requirement
42、s of 5.4 after 1 years immersion.6.3.3 Store controls at 22 6 3C and 50 6 10 % relativehumidity.7. Inspection7.1 As a minimum, the following methods shall be used tocharacterize the formulation prior to mixing:7.1.1 Infrared spectroscopy on each component.7.1.2 Amine number on curing agent.7.1.3 Epo
43、xide equivalent weight on resin.7.2 As a minimum, the following methods shall be used tocharacterize the “mixed” or “hardened” polymer:7.2.1 Infrared spectroscopy.7.2.2 Spectrographic analysis.7.2.3 Total nitrogen.8. Packaging and Package Marking8.1 Packaging shall bear appropriate lot numbers that
44、di-rectly relate to the identification of the homogeneous batcheswhich are the source of the encapsulant.8.2 Packaging shall provide appropriate protection for theepoxy components of the device.9. Keywords9.1 encapsulants; evaluation of biocompatibility; implant-able medical devicesAPPENDIXES(Nonman
45、datory Information)X1. RATIONALEX1.1 Epoxies as a general class of thermoset polymers mayexhibit a wide range of properties, depending upon the formu-lation. This specification is intended to describe minimumrequirements for materials for use as encapsulants in implant-able electronic components. It
46、 remains the responsibility of thedevice manufacturer to determine whether the particular for-mulation utilized meets other specific requirements of theparticular end-use application.X1.2 Epoxy encapsulants have been used in the manufac-ture of implantable electronic components for many years andhav
47、e been found to exhibit acceptable tissue response. When-ever changes are made in the formulation of an encapsulant,the possibility exists that there may be changes in the tissueresponse. This specification therefore calls for requalificationof different formulations to assure no adverse effects on
48、thetissue response while allowing for cell culture screeningbatch-to-batch. This specification does not attempt to addressthe amount of change in formulation which would necessitatere-testing. The material and device manufacturers will need tomake that determination based upon their own experience,p
49、ublished data, and consultations with experts experienced inthis area.X2. BIOCOMPATIBILITYX2.1 The suitability of these materials from a humanimplant perspective is dependent on the specific application.The biologic tests appropriate for the specific site, such asrecommended in Practice F748 or ISO 10993 should be used asa guideline.X2.2 No known surgical implant material has ever beenshown to be completely free of adverse reactions in the humanbody. However, long-term clinical experience of use of specificcompositions and formulations of
