1、Designation: F 641 98a (Reapproved 2003)Standard 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
2、 revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon (e) 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 o
3、r amine 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
4、plastic 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 compositio
5、n or formu-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 i
6、mplants.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 This standard does not purport to address all of thesafety concerns, if any,
7、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 to use.2. Referenced Documents2.1 ASTM Standards:D 149 Test Method for Dielectric Breakdown Voltage and
8、Dielectric Strength of Solid Electrical Insulating Materialsat Commercial Power Frequencies2D 150 Test Methods for ac Loss Characteristics and Permit-tivity (Dielectric Constant) of Solid Electrical InsulatingMaterials2D 257 Test Methods for dc Resistance or Conductance ofInsulating Materials2D 570
9、Test Method for Water Absorption of Plastics3D 638 Test Method for Tensile Properties of Plastics3D 790 Test Methods for Flexural Properties of Unreinforcedand Reinforced Plastics and Electrical Insulating Materi-als3D 883 Terminology Relating to Plastics3D 1042 Test Method for Linear Dimensional Ch
10、anges ofPlastics Under Accelerated Service Conditions3D 1239 Test Method for Resistance of Plastic Films toExtraction by Chemicals3D 1434 Test Method for Determining Gas PermeabilityCharacteristics of Plastic Film and Sheeting4D 1763 Specification for Epoxy Resins3D 1898 Practice for Sampling of Pla
11、stics5D 2240 Test Method for Rubber PropertyDurometerHardness6D 2471 Test Method for Gel Time and Peak ExothermicTemperature of Reacting Thermosetting Resins7D 2562 Practice for Classifying Visual Defects in PartsMolded from Reinforced Thermosetting Plastics7D 2566 Test Method for Linear Shrinkage o
12、f Cured Ther-mosetting Casting Resins During Cure8D 2734 Test Method for Void Content of Reinforced Plas-tics7D 3137 Test Method for Rubber PropertyHydrolytic Sta-bility6F 74 Practice for Determining Hydrolytic Stability of Plas-tic Encapsulants for Electronic Devices9F 135 Test Method for Embedment
13、 Stress Caused by Cast-ing Compounds on Glass-Encased Electronic Compo-nents10F 602 Criteria for Implantable Thermoset Epoxy Plastics11F 748 Practice For Selecting Generic Biological Test Meth-ods for Materials and Devices111This specification is under the jurisdiction of ASTM Committee F04 onMedica
14、l and Surgical Materials and Devices and is the direct responsibility ofSubcommittee F04.11 on Polymeric Materials.Current edition approved Apr. 10, 2003. Published May 2003. Originallyapproved in 1979. Last previous edition approved in 1998 as F 641 98a.2Annual Book of ASTM Standards, Vol 10.01.3An
15、nual Book of ASTM Standards, Vol 08.01.4Annual Book of ASTM Standards, Vol 15.09.5Discontinued; See 1997 Annual Book of ASTM Standards, Vol 08.01.6Annual Book of ASTM Standards, Vol 09.01.7Annual Book of ASTM Standards, Vol 08.02.8Discontinued; See 1992 Annual Book of ASTM Standards, Vol 08.02.9Disc
16、ontinued; See 1994 Annual Book of ASTM Standards, Vol 10.04.10Discontinued; See 1996 Annual Book of ASTM Standards, Vol 10.02.11Annual Book of ASTM Standards, Vol 13.01.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.F 895 Test Metho
17、d for Agar Diffusion Cell Culture Screen-ing for Cytotoxicity11F 981 Practice for Assessment of Compatibility of Bioma-terials for Surgical Implants with Respect to Effect ofMaterials on Muscle and Bone112.2 AAMI Standard:EOS-D E-O Sterilization Standard123. Classification3.1 Encapsulants shall be c
18、lassified 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 physiological fluids.4. Chemical Composition4.1 Additives (Type I E
19、ncapsulants 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 glycidyl ether (PGE).4.1.2 Other Additives (see Note 1)Other additives sha
20、ll 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 additives, as indicated in Criteria F 602, includecompounds such as n
21、onreactive diluents, fillers, release agents, and thelike.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 AminesThe mix ratio shall be maintained at 65equivalent % of stoichiometry.4.2.
22、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 carbonates is minimized. The devicemanufacturer may specify maximum limits of ca
23、rbon 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 temperature during cure shall be keptbelow the maximum acceptable value for the
24、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-forcements are used, the encapsulant shall have sufficienttransparency so th
25、at the circuitry may be visually inspectedafter encapsulation.5.1.2.2 Foreign ParticlesNo foreign particles, particulatematter and gross contamination shall be observed whenchecked under 23 wide field magnification.5.1.2.3 USP Biological Tests Plastic Containers, ClassIV13Pass.5.1.2.4 USP Pyrogen Te
26、st14or other Pyrogen methodswhich have been demonstrated to be of equal or greatersensitivityPass.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 imp
27、lant shall be shown to be withinsafe limits prescribed by the device manufacturer.5.1.2.6 The cure shrinkage (Test Method D 2566) or em-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 Ov
28、erlay)15or Test MethodF 895Pass.5.1.2.8 While cell culture methods as described in TestMethod F 895 may be appropriated for the batch-to-batchscreening of fully cured specimens, the basic recipe usedshould have been qualified for its overall tissue response bymethods such as those suggested in Pract
29、ice F 748 for “Im-planted Devices Principally Contacting Tissue and TissueFluid” including testing according to Practice F 981.5.1.3 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
30、% relative humidity on specimens conditioned as in 6.3.Samples shall be wiped dry prior to test with a lint-free tissue,as appropriate.5.1.4 Optional cured properties measured after acceleratedimmersion for Type I encapsulants may be determined forscreening purposes after conditioning as in 6.2.5.2
31、Type II Encapsulants:5.2.1 Peak Exotherm Temperature (Test Method D 2471)The peak exotherm temperature during cure shall be keptbelow 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 (
32、71.6 6 5.7F) and 506 10 % relativehumidity on fully cured samples conditioned as in 6.1.6. Specimen Preparation6.1 PreparationPrepare specimens used for evaluation ofproperties of the cured material in the same manner as theintended product. Such conditioning shall include all specifiedrelevant vari
33、ables for the product prior to implant including12Available from Association for Advancement of Medical Instrumentation,1500 Wilson Blvd., Suite 417, Arlington, VA 22209.13U.S. Pharmacopeia, XXIII, 1995, pp. 1783-1787.14Ibid., pp. 1696-1697.15Guess, W. L., et al., Journal of Pharmaceutical Sciences,
34、 Vol 54, 1965, pp.15451547.F 641 98a (2003)2specimen size or shape, cure time, cure temperature, post-cure,cleaning, packaging, 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 fo
35、r7 days.6.2.2 Prior to evaluation, allow the specimens to equilibrateto the test temperature of 22 6 3C (71 6 5F) in physiologicalsaline of pH 7.4 6 0.2.6.2.3 Condition one set of controls at 100 6 3C (212 65F) and another set at 22 6 3C (71.6 6 5F) for 7 days at 506 10 % relative humidity.6.2.4 Sin
36、ce 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-Ter
37、m Immersion (Test Method D 3137 or PracticeF 74):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 (73 6 5F) aerated physiologicalsaline of pH 7.4 6 0.2 with periodic sampling for evaluation asis appropriate for a
38、period of time consistent with projectedservice life. It is required that immersion continue for theprojected service life of the device. For devices intended forlong-term implant, however, it may not be practical to com-plete tank tests over the devices projected service life beforeone can claim co
39、mpliance with the specification. One shall beconsidered in compliance with this section of the specification,therefore, if specimens meet the requirements of 5.4 after 1years immersion.6.3.3 Store controls at 22 6 3C (71 6 5F) and 50 6 10 %relative humidity.7. Inspection7.1 As a minimum, the followi
40、ng 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 Epoxide equivalent weight on resin.7.2 As a minimum, the following methods shall be used tocharacterize the “mixed” or “hardened” polymer:7.2
41、.1 Infrared spectroscopy.7.2.2 Spectrographic analysis.7.2.3 Total nitrogen.TABLE 1 Cure Requirements for Long-Term Immersion Tests for Type I EncapsulantsProperty Requirement ASTM MethodExtraction 11.8 kV/mm D 149Dielectric constant 2.0 D 150Dissipation factor 1.5 % D 638Flexural strength $1380 MPa
42、 D 790Gas permeationAD 1434Hardness $60 Shore D D 2240Dimensional stability 2.0 D 150Dielectric strength 11.8 kV/mm D 149Dissipation factor 0.05 D 150Dimensional stability 0.5 % change D 1042Visual defects none that adversely affect the safety, efficacy, or reliability ofthe deviceD 2562Voids none t
43、hat adversely affect the safety, efficacy, or reliability ofthe deviceD 2734Volume resistivity 1010Vcm D 257F 641 98a (2003)38. 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
44、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(Nonmandatory Information)X1. RATIONALEX1.1 Epoxies as a general class of thermoset polymers may
45、exhibit 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 remains the responsibility of thedevice manufacturer to determine whether the particular
46、for-mulation utilizes 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 andhave been found to exhibit acceptable tissue response. When-ever changes are made in the form
47、ulation 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 thetissue response while allowing for cell culture screeningbatch-to-batch. This specifica
48、tion does not attempt to addressthe amount of change in formulation which would necessitatere-testing. The material and device manufactures will need tomake that determination based upon their own experience,published data, and consultations with experts experienced inthis area.X2. BIOCOMPATIBILITYX
49、2.1 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 F 748 should be used as 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
