1、Designation: F748 06 (Reapproved 2010)Standard Practice forSelecting Generic Biological Test Methods for Materials andDevices1This standard is issued under the fixed designation F748; the number immediately following the designation indicates the year of originaladoption or, in the case of revision,
2、 the year of last revision. A number in parentheses indicates the year of last reapproval. A superscriptepsilon () indicates an editorial change since the last revision or reapproval.1. Scope1.1 This practice recommends generic biological test meth-ods for materials and devices according to end-use
3、applica-tions. While chemical testing for extractable additives andresidual monomers or residues from processing aids is neces-sary for most implant materials, such testing is not included aspart of this practice. The reader is cautioned that the area ofmaterials biocompatibility testing is a rapidl
4、y evolving field,and improved methods are evolving rapidly, so this practice isby necessity only a guideline.Athorough knowledge of currenttechniques and research is critical to a complete evaluation ofnew materials.1.2 These test protocols are intended to apply to materialsand medical devices for h
5、uman application. Biological evalu-ation of materials and devices, and related subjects such aspyrogen testing, batch testing of production lots, and so on, arealso discussed. Tests include those performed on materials, endproducts, and extracts. Rationale and comments on currentstate of the art are
6、 included for all test procedures described.1.3 The biocompatibility of materials used in single ormulticomponent medical devices for human use depends to alarge degree on the particular nature of the end-use application.Biological reactions that are detrimental to the success of amaterial in one de
7、vice application may have little or no bearingon the successful use of the material for a different application.It is, therefore, not possible to specify a set of biocompatibilitytest methods which will be necessary and sufficient to establishbiocompatibility for all materials and applications.1.4 T
8、he evaluation of tissue engineered medical products(TEMPs) may, in some cases, involve different or additionaltesting beyond those suggested for non-tissue-based materialsand devices. Where appropriate, these differences are discussedin this practice and additional tests described.1.5 The ethical us
9、e of research animals places the obligationon the individual investigator to determine the most efficientmethods for performing the necessary testing without undueuse of animals. Where adequate prior data exists to substantiatecertain types of safety information, these guidelines should notbe interp
10、reted to mean that testing should be unnecessarilyrepeated.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-bi
11、lity of regulatory limitations prior to use.2. Referenced Documents2.1 ASTM Standards:2E1202 Guide for Development of Micronucleus AssayStandardsE1262 Guide for Performance of Chinese Hamster OvaryCell/Hypoxanthine Guanine Phosphoribosyl TransferaseGene Mutation AssayE1263 Guide for Conduct of Micro
12、nucleus Assays in Mam-malian Bone Marrow ErythrocytesE1280 Guide for Performing the Mouse Lymphoma Assayfor Mammalian Cell MutagenicityE1397 Practice for In Vitro Rat Hepatocyte DNA RepairAssayE1398 Practice for In Vivo Rat Hepatocyte DNA RepairAssayF619 Practice for Extraction of Medical PlasticsF7
13、19 Practice for Testing Biomaterials in Rabbits for Pri-mary Skin IrritationF720 Practice for Testing Guinea Pigs for Contact Aller-gens: Guinea Pig Maximization TestF749 Practice for Evaluating Material Extracts by Intracu-taneous Injection in the RabbitF750 Practice for Evaluating Material Extract
14、s by SystemicInjection in the MouseF756 Practice for Assessment of Hemolytic Properties ofMaterialsF763 Practice for Short-Term Screening of Implant Materi-als1This practice is under the jurisdiction ofASTM Committee F04 on Medical andSurgical Materials and Devices and is direct responsibility of Su
15、bcommittee F04.16on Biocompatibility Test Methods.Current edition approved June 1, 2010. Published September 2010. Originallyapproved in 1982. Last previous edition approved in 2006 as F748 06. DOI:10.1520/F0748-06R10.2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact AS
16、TM Customer Service at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.F813 Practice for Direct Con
17、tact Cell Culture Evaluation ofMaterials for Medical DevicesF895 Test Method for Agar Diffusion Cell Culture Screen-ing for CytotoxicityF981 Practice for Assessment of Compatibility of Biomate-rials for Surgical Implants with Respect to Effect ofMaterials on Muscle and BoneF1027 Practice for Assessm
18、ent of Tissue and Cell Compat-ibility of Orofacial Prosthetic Materials and DevicesF1408 Practice for Subcutaneous Screening Test for Im-plant MaterialsF1439 Guide for Performance of Lifetime Bioassay for theTumorigenic Potential of Implant MaterialsF1877 Practice for Characterization of ParticlesF1
19、903 Practice for Testing For Biological Responses toParticles In VitroF1904 Practice for Testing the Biological Responses toParticles in vivoF1905 Practice For Selecting Tests for Determining thePropensity of Materials to Cause ImmunotoxicityF1906 Practice for Evaluation of Immune Responses InBiocom
20、patibility Testing Using ELISA Tests, LymphocyteProliferation, and Cell MigrationF1983 Practice for Assessment of Compatibility ofAbsorbable/Resorbable Biomaterials for Implant Applica-tionsF1984 Practice for Testing for Whole Complement Activa-tion in Serum by Solid MaterialsF2065 Practice for Test
21、ing for Alternative PathwayComplement Activation in Serum by Solid MaterialsF2147 Practice for Guinea Pig: Split Adjuvant and ClosedPatch Testing for Contact AllergensF2148 Practice for Evaluation of Delayed Contact Hyper-sensitivity Using the Murine Local Lymph Node Assay(LLNA)F2151 Practice for As
22、sessment of White Blood Cell Mor-phology After Contact with Materials3F2382 Test Method for Assessment of Intravascular Medi-cal Device Materials on Partial Thromboplastin Time(PTT)2.2 Other Referenced Documents:ISO/AAMI/ANSI 10993-1 Biological Testing of Medicaland Dental Materials and Devices - Pa
23、rt 1: Guidance onSelection of Tests4EN 309931 Biological Testing of Medical and DentalMaterials and Devices - Part 1: Guidance on Selection ofTests4General Program Memorandum #G95-1 FDA5Immunotoxicity Testing Guidance-FDA53. Summary of Practice3.1 A matrix listing biological test methods versus mate
24、rials(devices) and their applications is included in Table 1. Theexpected duration of use of the device is also considered.Intraoperative is less than 24 h, short-term is up to andincluding 30 days, chronic is greater than 30 days. The positionof row and column intersection is marked to indicate whe
25、therthe test is recommended for a material or device for the specificapplication indicated. The terms relating to device or materialtype and application are addressed in Section 5. Discussion ofapplicability, current state of the art, and rationale for indi-vidual test methods also appears in that s
26、ection.4. Significance and Use4.1 The objective of this practice is to recommend sufficientbiological testing to establish a reasonable level of confidenceconcerning the biological response to a material or device,while at the same time avoiding unnecessary testing.4.2 This practice is intended to p
27、rovide guidance to thematerials investigator in selecting the proper procedures to becarried out for the screening of new or modified materials.Because each material and each implant situation involves itsown unique circumstances, these recommendations should bemodified as necessary and do not const
28、itute the only testingthat will be required for a material nor should these guidelinesbe interpreted as minimum requirements for any particularsituation. While an attempt has been made to provide recom-mendation for different implant circumstances, some of therecommended testing may not be necessary
29、 or reasonable for aspecific material or application.5. Classification of Materials and Devices by End-UseApplications5.1 General:5.1.1 When new materials are sought for a medical appli-cation for use on humans, the material(s) may comprise thewhole final device product, or may be one of many compon
30、entmaterials in the device. The first step is a thorough literaturesearch for previous use of the material or biocompatibilitytesting studies to ensure that it has not been known to producean adverse biological response that exceeds the expectedbenefit in the use of the device. Note that the final f
31、abricatedproduct may differ chemically, physically, or biologically fromthe raw materials used to fabricate the product due to process-ing and this has to be considered when designing test protocols.For some devices, it may be necessary or desirable to takematerial test samples directly from the fin
32、al device product.Samples should be fully representative of the finished productin terms of processing, cleaning, packaging, sterilization, andany other procedures that are performed on the materials beforethe device is used.5.1.2 At this point, preliminary material screening may beemployed, dependi
33、ng on the expertise of the organizationsevaluating the materials. Since preliminary screening is nor-mally an option to minimize the economic impact of acandidate material failing final biological tests after extensivetime and effort, it is not a required procedure. The investigatorshould be aware t
34、hat, should an adverse tissue response beobserved with a final product, it may be impossible todetermine which component or process is responsible withoutthese initial screening tests.3Withdrawn. The last approved version of this historical standard is referencedon www.astm.org.4Available from Ameri
35、can National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.5Available from CDRH, 5600 Fishers Ln., Rockville, MD 20857.F748 06 (2010)2TABLE 1 Applicable TestsClassification ofMaterial or Deviceand ApplicationCellCultureCytotoxicitySensi-tizationSkinIrri
36、tationor Intra-cutaneousMucousMembraneIrritationSystemicToxicity, Acuteor SubchronicBloodCompatibilityHemolysisPyrogenTestShort-termImplantationLong-termImplantationImmuneResponseGenotoxicity CarcinogenicityExternal devicesIntact surfaces (all timeperiods)xxxBreached surfacesIntraoperative x x xShor
37、t-Term x x x xChronic x x x x xExternal Devices Communicating with:Intact Natural ChannelsIntraoperative x x x xShort-term x x x x x xChronic x x x x x x x x xBody Tissues and FluidsIntraoperative x x x x iAShort-term x x x x iAxxChronic x x x x iAxxBlood Path, indirectIntraoperative x x x x x x xSh
38、ort-term x x x x x x xChronic x x x x x x x x xBlood Path, directIntraoperative x x x x x x xShort-term x x x x x x x x xChronic x x x x x x x x x x xImplanted Devices principally contactingBone/Tissue/tissue fluidIntraoperative x x x xShort-term x x x x x xChronic x x x x x x x x x xBloodIntraopera
39、tive x x x x x x xShort-term x x x x x x x x x xChronic x x x x x x x x x x x xA(i) Pyrogenicity testing may be considered for all devices contacting the central nervous system.F74806(2010)35.1.3 This practice addresses two dimensions of tissue-material interactions: duration and tissue type. A thir
40、d dimen-sion, which should be considered, is the relative size differencebetween the host and the material, that is, to how muchmaterial surface area is the host exposed. The material surfacearea to body weight ratio may become a significant factor forporous materials, and devices of repeated short-
41、term applica-tions (for example, dialysis products). While this practice doesnot address the issue of “intensity factor” of increased surfacearea, the biocompatibility testing facility personnel shouldconsider it in their material screening and testing protocoldesign.5.1.4 For the purposes of this p
42、ractice, devices and thematerials that comprise them are classified as to end-use humanapplication as outlined in 5.2-5.4.5.1.5 In general, the testing for tissue engineered medicalproducts (TEMPs) should address the same issues specific tothe type, location, and duration of use as other medical dev
43、icesand products. The selection of additional testing for compat-ibility criteria unique to these type of products should beconducted with these recommendations in mind.5.1.6 When testing materials that are intended to degradeand/or be metabolized while implanted in the body (bothsynthetic and TEMPs
44、), consideration should be given to thedegradation or metabolic products and appropriate modifica-tions made in test and sample selection so that the compatibil-ity of degradation products is tested as well as the undegradedproduct.5.2 External Devices:5.2.1 Devices That Contact Intact Body Surfaces
45、 Onlyexamples include electrodes, splints, external prostheses, cer-tain dressings, monitors of various types, or ostomy appliances.5.2.2 Devices That Contact Breached Body Surfacesexamples include ulcer, burn, and granulation tissue dressings,or healing devices.5.3 Externally Communicating Devices:
46、5.3.1 Devices Communicating with Intact Natural Chan-nels:5.3.1.1 Intraoperative (30 days)examples include urinarycatheters for chronic use and intrauterine devices.5.3.2 Devices Communicating with Body Tissues and Flu-ids:5.3.2.1 Intraoperative (30 days)examples include percutane-ous electrodes, ac
47、tive penetrating electrodes, stapedectomyprostheses, partial and total ossicular replacement prostheses,or tympanoplasty ventilation tubes.5.3.3 Blood Path, IndirectProducts contacting blood pathat one point for usually less than 24 hours, and serves as aconduit for fluid entry into the vascular sys
48、tem. Examplesinclude solution administration sets, extension sets, transfersets, or blood administration sets.5.3.3.1 Products that are used for 24 hours or that are usedrepeatedly in the same patient will be considered as chronicusage and should undergo extended testing.5.3.4 Blood, Path, DirectSin
49、gle recirculating blood expo-sure or product is in blood path generally less than 24 hours.Examples include intravenous catheters, oxygenators, extracor-poreal oxygenator tubing and accessories.5.3.5 Blood Path, Direct, Short Term, or Chronic, or re-peated exposureExamples include dialyzers or dialysis tub-ing and accessories, shunts.5.4 Implanted Long-Term Devices:5.4.1 Devices Principally Contacting Bonesexamples in-cludd orthopedic pins, screws, replacement joints, bone pros-theses, cements, or dental implants.5.4.2 Devices Principally Residing in the SubcutaneousSpace
