1、Designation: F 641 09Standard Specification forImplantable Epoxy Electronic Encapsulants1This standard is issued under the fixed designation F 641; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the year of last revision. A number
2、 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 thermoset plastics based ondiglycidyl ethers of bisphenol A and amino functional curingagents or amine catalysts.1.
3、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 is ageneric
4、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 formu-lation fo
5、r 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.1.4 Limitati
6、onsThis 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 measurement are in
7、cluded 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 limitations prior
8、 to use.2. Referenced Documents2.1 ASTM Standards:2D 149 Test Method for Dielectric Breakdown Voltage andDielectric Strength of Solid Electrical Insulating Materialsat Commercial Power FrequenciesD 150 Test Methods for AC Loss Characteristics and Per-mittivity (Dielectric Constant) of Solid Electric
9、al Insula-tionD 257 Test Methods for DC Resistance or Conductance ofInsulating MaterialsD 570 Test Method for Water Absorption of PlasticsD 638 Test Method for Tensile Properties of PlasticsD 790 Test Methods for Flexural Properties of Unreinforcedand Reinforced Plastics and Electrical Insulating Ma
10、terialsD 1042 Test Method for Linear Dimensional Changes ofPlastics Under Accelerated Service ConditionsD 1239 Test Method for Resistance of Plastic Films toExtraction by ChemicalsD 1434 Test Method for Determining Gas PermeabilityCharacteristics of Plastic Film and SheetingD 2240 Test Method for Ru
11、bber PropertyDurometerHardnessD 2471 Practice for Gel Time and Peak Exothermic Tem-perature of Reacting Thermosetting Resins3D 2562 Practice for Classifying Visual Defects in PartsMolded from Reinforced Thermosetting PlasticsD 2566 Test Method for Linear Shrinkage of Cured Ther-mosetting Casting Res
12、ins During Cure3D 2734 Test Methods for Void Content of Reinforced Plas-ticsD 3137 Test Method for Rubber PropertyHydrolytic Sta-bilityF74 Practice for Determining Hydrolytic Stability of Plas-tic Encapsulants for Electronic Devices3F 135 Test Method for Embedment Stress Caused by Cast-ing Compounds
13、 on Glass-Encased Electronic Components3F 602 Criteria for Implantable Thermoset Epoxy PlasticsF 748 Practice for Selecting Generic Biological Test Meth-ods for Materials and DevicesF 895 Test Method for Agar Diffusion Cell Culture Screen-ing for CytotoxicityF 981 Practice for Assessment of Compatib
14、ility of Bioma-terials for Surgical Implants with Respect to Effect ofMaterials on Muscle and Bone1This 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 edi
15、tion approved Aug. 1, 2009. Published September 2009. Originallyapproved in 1979. Last previous edition approved in 2003 as F 641 98a(2003).2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Customer Service at serviceastm.org. For Annual Book of ASTMStandards volum
16、e information, refer to the standards Document Summary page onthe ASTM website.3Withdrawn.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.2.2 AAMI Standard:EOS-D E-O Sterilization Standard42.3 ISO Standard:ISO 10993 Biological Evalua
17、tion of Medical Devices53. Classification3.1 Encapsulants shall be classified as follows:3.1.1 Type IThose encapsulants which contact the tissuedirectly or indirectly.3.1.2 Type IIThose encapsulants used only within her-metically sealed containers. The epoxy encapsulant has nocontact with tissues or
18、 physiological fluids.4. Chemical Composition4.1 Additives (Type I Encapsulants Only):4.1.1 Reactive DiluentsThe following compounds whenused as reactive diluents 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 glycid
19、yl 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 in concentrations sufficient to significantlyaffect the properties of the encapsulant or to produce asignificant biological reaction.NOTE 1Other a
20、dditives, as indicated in Criteria F 602, include com-pounds such as nonreactive diluents, fillers, release agents, and the like.4.1.3 Phthalate EstersPhthalate 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 AminesTh
21、e mix ratio shall be maintained at 65equivalent % of stoichiometry.4.2.2 CatalystsThe mix ratio shall be maintained withinthe ranges recommended by the formulator.4.3 Carbonates (Type I and Type II Encapsulants)Theencapsulant shall be poured under conditions such that theformation of amine carbonate
22、s is minimized. The devicemanufacturer may specify maximum limits for carbon dioxideor water vapor, or both, in the atmosphere in which theencapsulant is being mixed or poured.5. Physical Properties5.1 Type I Encapsulants:5.1.1 Peak Exotherm Temperature (Test Method D 2471)The peak exotherm temperat
23、ure 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 propertiesmeasured on fully cured specimens conditioned as in 6.1 are asfollows:5.1.2.1 TransparencyIn cases where no fillers or rein-forc
24、ements are used, the encapsulant shall have sufficienttransparency so that the circuitry may be visually inspectedafter encapsulation.5.1.2.2 Foreign ParticlesNo foreign particles, particulatematter, or gross contamination shall be observed when checkedunder 23 wide field magnification.5.1.2.3 Bioco
25、mpatibility TestingWhile cell culture meth-ods as described in Test Method F 895 may be appropriate forthe lot-to-lot screening of fully cured specimens, the basicrecipe used should have been qualified for its overall tissueresponse by methods such as those suggested in Practice F 748or ISO 10993 fo
26、r the intended application, including testingaccording to Practice F 981.(1) Biocompatibility testing should be performed on speci-mens that have been processed and sterilized per the methodsintended for the final device.5.1.2.4 USP Bacterial Endotoxin Test6or other Pyrogenmethods which have been de
27、monstrated to be of equal orgreater sensitivityPass.5.1.2.5 Sterilant Residues (AAMI EOS-D)Where appli-cable, the concentration of ethylene oxide, ethylene chlorohy-drin, ethylene glycol, and dichlorodifluoromethane (or theequivalents) at the time of implantation shall be shown to bewithin safe limi
28、ts prescribed by the device manufacturer.5.1.2.6 The cure shrinkage (Test Method D 2566)orem-bedment stress (Test Method F 135) shall be #2%. The stressshall not exceed the limits of the most pressure-sensitivecomponents.5.1.2.7 Tissue Culture Test (Agar Overlay)7or Test MethodF 895Pass.5.1.3 Requir
29、ed 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 % relative 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.
30、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 II Encapsulants:5.2.1 Peak Exotherm Temperature (Test Method D 2471)The peak exotherm temperature during cure shall be keptbelow the m
31、aximum 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 specimens used for
32、 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, packaging, sterilizatio
33、n, and aeration.6.2 Accelerated Immersion:4Available fromAssociation forAdvancement of Medical Instrumentation, 1500Wilson Blvd., Suite 417, Arlington, VA 22209.5Available from American National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.6U.S. Pharma
34、copeia, 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.F6410926.2.1 For screening purposes, immerse specimens preparedas in 6.1 in refluxing phys
35、iological 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 saline 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 S
36、ince two variables, heat and moisture, are inherent inthis test, data from specimens refluxed 7 days in saline may becompared to controls conditioned dry at 100C 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-T
37、erm Immersion (Test Method D 3137 or PracticeF74):6.3.1 Prepare the specimens in accordance with 6.1.6.3.2 During initial qualification of the formulation, im-merse 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
38、 time consistent with projectedservice life. Immersion shall continue for the projected servicelife of the device. For devices intended for long-term implant,however, it may not be practical to complete tank tests over thedevices projected service life before one can claim compliancewith the specifi
39、cation. One shall be considered in compliancewith this section of the specification, therefore, if specimensmeet the requirements 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 tocharact
40、erize the formulation prior to mixing:7.1.1 Infrared spectroscopy on each component.7.1.2 Amine number on curing agent.7.1.3 Epoxide 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 Spe
41、ctrographic analysis.7.2.3 Total nitrogen.8. Packaging and Package Marking8.1 Packaging shall bear appropriate lot numbers that di-rectly relate to the identification of the homogeneous batcheswhich are the source of the encapsulant.TABLE 1 Cure Requirements for Long-Term Immersion Tests for Type I
42、EncapsulantsProperty Requirement ASTM MethodExtraction 11.8 kV/mm D 149Dielectric constant 2.0 D 150Dissipation factor 1.5 % D 638Flexural strength $1380 MPa D 790Gas permeationAD 1434Hardness $60 Shore D D 2240Dimensional stability 2.0 D 150Dielectric strength 11.8 kV/mm D 149Dissipation factor 0.0
43、5 D 150Dimensional stability 0.5 % change D 1042Visual defects none that adversely affect the safety, efficacy, or reliability ofthe deviceD 2562Voids none that adversely affect the safety, efficacy, or reliability ofthe deviceD 2734Volume resistivity 1010Vcm D 257F6410938.2 Packaging shall provide
44、appropriate protection for theepoxy components of the device.9. Keywords9.1 encapsulants; evaluation of biocompatibility; implant-able medical devicesAPPENDIXES(Nonmandatory Information)X1. RATIONALEX1.1 Epoxies as a general class of thermoset polymers mayexhibit a wide range of properties, dependin
45、g upon the formu-lation. This specification is intended to describe minimumrequirements for materials for use as encapsulants in implant-able electronic components. It remains the responsibility of thedevice manufacturer to determine whether the particular for-mulation utilized meets other specific
46、requirements of theparticular end-use application.X1.2 Epoxy encapsulants have been used in the manufac-ture of implantable electronic components for many years andhave been found to exhibit acceptable tissue response. When-ever changes are made in the formulation of an encapsulant,the possibility e
47、xists that there may be changes in the tissueresponse. This specification therefore calls for requalificationof different formulations to assure no adverse effects on thetissue response while allowing for cell culture screeningbatch-to-batch. This specification does not attempt to addressthe amount
48、of change in formulation which would necessitatere-testing. The material and device manufacturers will need tomake that determination based upon their own experience,published data, and consultations with experts experienced inthis area.X2. BIOCOMPATIBILITYX2.1 The suitability of these materials fro
49、m a humanimplant perspective is dependent on the specific application.The biologic tests appropriate for the specific site, such asrecommended in Practice F 748 or ISO 10993 should be usedas a 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 this material class referred toin this standard has shown that an acceptable level of biologicalresponse can be expected, if the material
