ASTM F619-2003 Standard Practice for Extraction of Medical Plastics《医学塑料制品萃取的标准实施规范》.pdf

1、Designation: F 619 03Standard Practice forExtraction of Medical Plastics1This standard is issued under the fixed designation F 619; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the year of last revision. A number in parentheses

2、indicates the year of last reapproval. Asuperscript epsilon (e) indicates an editorial change since the last revision or reapproval.1. Scope1.1 This practice covers methods of extraction of medicalplastics and may be applicable to other materials. This practiceidentifies a method for obtaining “extr

3、act liquid” for use indetermining the biological response in preclinical testing.Further testing of the “extract liquid” is specified in otherASTM standards. The extract may undergo chemical analysisas part of the preclinical evaluation of the biological response,and the material after extraction ma

4、y also be examined.1.2 This practice may be used for, but is not limited to thefollowing areas: partial evaluation of raw materials, auditingmaterials within the manufacturing process, and testing finalproducts. This practice may also be used as a referee methodfor the measurement of extractables in

5、 plastics used in medicaldevices.1.3 The values stated in SI units are to be regarded as thestandard.1.4 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 hea

6、lth practices and determine the applica-bility of regulatory limitations prior to use.2. Referenced Documents2.1 ASTM Standards:2D 543 Practices for Evaluating the Resistance of Plastics toChemical ReagentsD 570 Test Method for Water Absorption of PlasticsD 1193 Specification for Reagent WaterD 1239

7、 Test Method for Resistance of Plastic Films toExtraction by ChemicalsD 1898 Practice for Sampling of Plastics3F 748 Practice for Selecting Generic Biological Test Meth-ods for Materials and Devices2.2 Other Documents:USP NF 24 or current edition43. Terminology Definitions3.1 extraction vehiclea liq

8、uid specified for use in testingthe plastic. Specific extraction vehicles are to be designated bythe ASTM standard that references this practice (see Section 7for a list of standard extraction vehicles).3.2 extract liquidthat liquid which, after extraction of thespecimen, is used in tests.3.3 specim

9、en portionthe unit or units of plastic placedinto the extraction vehicle.3.4 blankthe extraction vehicle not containing the speci-men under test which is used for comparison with the extractliquid.4. Summary of Practice4.1 Standard-size specimens of the plastic, which mayclosely simulate the intende

10、d device depending upon the use,are immersed in defined volumes of selected liquids (extractionvehicles) for the time and temperature specified.4.2 A choice is made, based on the end use, of the extractionvehicles (see Section 7) and one of the combinations of timeand temperature for the test (see S

11、ection 12).4.3 The resultant test liquids (extract liquids) are kept inglass containers until used for testing. The test liquids shall bestored tightly stoppered at normal room temperature. Testliquids for biological testing are kept in sterile glass containers.Consideration should be given as to wh

12、ether the extractionshould be done under aseptic conditions. The test liquids forbiological testing should be used within 24 h.5. Significance and Use5.1 These extraction procedures are the initial part ofseveral test procedures used in the biocompatibility screeningof plastics used in medical devic

13、es.1This practice is under the jurisdiction of ASTM Committee F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.16 on Biocompatibility Test Methods.Current edition approved Nov. 1, 2003. Published December 2003. Originallyapproved in 1979. Last prev

14、ious edition approved in 2002 as F 619 02.2For 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.3Withdrawn.4Availab

15、le from U.S. Pharmacopeia (USP), 12601 Twinbrook Pkwy., Rockville,MD 20852.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.5.2 The limitations of the results obtained from this practiceshould be recognized. The choice of extraction v

16、ehicle, dura-tion of immersion, and temperature of the test is necessarilyarbitrary. The specification of these conditions provides a basisfor standardization and serves as a guide to investigatorswishing to compare the relative resistance of various plastics toextraction vehicles.5.3 Correlation of

17、 test results with the actual performance orserviceability of materials is necessarily dependent upon thesimilarity between the testing and end-use conditions (see12.1.2 and Note 4).5.4 Caution should be exercised in the understanding andintent of this practice as follows:5.4.1 No allowance or disti

18、nction is made for variables suchas end-use application and duration of use. Decisions onselection of tests to be done should be made based on PracticeF 748.5.4.2 This practice was originally designed for use withnonporous, solid materials. Its application for other materials,such as those that are

19、porous, or absorptive, or resorptive,should be considered with caution. Consideration should begiven to altering the specified material to liquid ratio to allowadditional liquid to fully hydrate the material and additionalliquid or other methods to fully submerge the test article.Additional procedur

20、es that fully remove the extract liquid fromthe test article, such as pressure or physically squeezing thematerial, should also be considered as appropriate. Although nodefinitions are given in this practice for the following terms,such items as extraction vehicle surface tension at the specifiedext

21、raction condition and plastic specimen physical structureshould be taken into account.5.5 Test Methods D 543, D 570, and D 1239 may be usefulin providing supplemental information.6. Apparatus6.1 Autoclave, capable of maintaining a temperature of 1216 2.0C (249.8 6 3.8F) for at least 1 h and equipped

22、 with adisplay of temperature and pressure. A slow exhaust cycle isnecessary. A rack to hold the extraction containers above thewater level is also necessary. Loss of fluid volume should berecorded.6.1.1 Sealed, unvented extraction vessels should not beremoved until internal temperature and pressure

23、 have reachedambient conditions and the door can be opened. It is recom-mended that the extraction vessels be left undisturbed until anyrisk of boil over has passed. When the extraction vessels arecool to the touch, the lids should be sealed.6.2 Heating Equipment:6.2.1 Ovens or incubators that will

24、maintain temperatures of37, 50, 70 6 2C (98, 122, 158 6 3F).6.2.2 Water baths capable of maintaining temperatures de-scribed in 6.2.1. Those with the ability to agitate the extractionvessels are preferred.6.3 Extraction ContainersSuitable containers that protectthe extract liquid from the biological

25、 and chemical contamina-tion. They should allow expansion of the liquid, but then besealed to prevent evaporation. One suggested container is thescrew-cap culture test tube of borosilicate glass, unless a largercontainer is required for the size and shape of the material to beextracted. Screw caps,

26、if used, shall have polytetrafluoroethyl-ene liners.6.4 Balance, accurate to 60.1 mg.6.4.1 Caution should be exercised when performing weigh-ings in glassware. Depending upon the required accuracy, therelative humidity should be the same for weighings at differenttimes.6.5 Micrometers, capable of me

27、asuring dimensions of testspecimens to 0.025 mm (0.001 in.).7. Reagents and Materials7.1 Purity of ReagentsReagent grade, or better, chemicalsshall be used in all tests.5Other grades may be used, providedit is first ascertained that the reagent is of sufficiently highpurity to permit its use without

28、 lessening the accuracy of thedetermination.7.2 Extraction VehiclesThe following list of standardextraction vehicles is intended to simulate the main constitu-ents of human body fluids. The extraction vehicles shall be:7.2.1 Sodium Chloride Injection, USP, containing by weightnot less than 0.85 % an

29、d not more than 0.95 % sodiumchloride.7.2.1.1 Other aqueous solutions shall be made with USPWFI (water for injection).7.2.2 Vegetable Oil:7.2.2.1 Sesame Oil, USP.7.2.2.2 Cottonseed Oil, USP.7.3 Other extraction vehicles as required, such as polyeth-ylene glycol, DMSO, as specified in other standards

30、. Vehiclesshould be chosen based on biotolerance, the test protocols to beused, and the ability to extract contaminants from the materialto be tested.NOTE 1Depending upon the material under test and the users needs,extraction vehicles other than those in 7.2 and 7.3 may be used if thereasons are jus

31、tified.8. Sampling8.1 The application of this practice may be in various areas.Therefore, although some well-known quality sampling meth-ods may be used, a statistician might be consulted to ensure astatistically valid sampling plan.8.2 Practice D 1898 may also be consulted.9. Test Specimen9.1 This

32、practice is designed primarily for application tomaterials in the condition in which they are used. The materialshould be exposed to all conditions and substances as during aproduction run, such as washing, packaging, and sterilization.The extraction may be done on the end-use item, specimenportions

33、 thereof, or representative molded or extruded test5Reagent Chemicals, American Chemical Society Specifications, AmericanChemical Society, Washington, D.C. For suggestions on the testing of reagents notlisted by the American Chemical Society, see Analar Standards for LaboratoryChemicals, BDH Ltd., P

34、oole, Dorset, U.K., and the United States Pharmacopeiaand National Formulary, U.S. Pharmacopeial Convention, Inc. (USPC), Rockville,MD.F619032specimens of the formulated compound that are preconditionedby the same processing.NOTE 2Changes to a plastic formulation, specifically additives, suchas plas

35、ticizers, stabilizers, antioxidants, pigments, and lubricants areperhaps more prone to produce differences in the extract liquid than thepolymer itself.9.2 Specimen SizeUse a specimen size as described in thefollowing sections. Suitable-size containers will allow a 20-mLextraction vehicle volume for

36、 each of the following specimensizes:9.2.1 The total surface area of a specimen (both sides) isequivalent to 120 cm2(18.6 in.2) when the specimen thicknessis 0.50 mm (0.020 in.) or less, or equivalent to 60 cm2(9.3 in.2)when the thickness is greater than 0.50 mm (0.020 in.).9.2.2 An alternative for

37、specimens of intricate geometry orthose specimens with a thickness greater than 1.0 mm (0.039in.) is a specimen whose weight is 0.2 g/ml.9.2.3 Specimens shall be of such dimensions as to conve-niently fit within the extraction container and their total surfacearea shall be completely covered by the

38、extraction vehicle.9.2.3.1 To ensure full submersion of a large or bulkyspecimen, it may be necessary to cut the specimen to providefor full immersion of its component pieces in the extractionvehicle. Under no circumstances shall such cutting be allowedto reduce the appropriate sample extraction rat

39、io as determinedin 9.2.1 or 9.2.2. If the specimen cannot be cut, coupons knownto possess the same surface characteristics and sized to deliverthe same overall surface area as the original test specimen canalternately be utilized.9.2.4 It may be necessary to subdivide the specimen, utilizeinert and

40、noncontaminating spacers or weights or both, orinitially agitate the extraction vehicle to ensure the entirespecimen surface is contacted.9.3 Number of Specimen PortionsIn both procedures setforth in Section 12, test at least three specimen portions witheach extraction vehicle to account for variabi

41、lity.10. Preparation of Apparatus10.1 Clean all reusable glassware thoroughly with a chro-mic acid cleansing mixture, or if necessary, with hot nitric acid,followed by prolonged rinsing with tap water and then at leasttwo rinses with distilled water.10.2 Clean cutting devices by an appropriate metho

42、d, forexample, successive cleaning with suitable solvents prior touse in subdividing the sample.10.3 Clean all other equipment by thorough scrubbing witha suitable detergent and prolonged rinsing with tap water andthen at least two rinses with distilled water.10.4 Render containers and devices used

43、for extraction andin transfer and administration of the extract liquids, sterile anddry by a suitable process.NOTE 3If ethylene oxide is used as the sterilizing agent, allowadequate conditioning for complete degassing. Ethylene oxide residualsmay vary among different material formulations.11. Specim

44、en Portion and Conditioning11.1 Biological Response ExtractionSelect and cut tosize, as in 9.2 and 9.3, at least three specimen portions for eachextraction vehicle to be used. Aseptic precautions should beused if the extract liquid is to be used in a test requiring aseptictechnique or if the extract

45、 is to be stored for more than a fewhours before use.12. Procedure12.1 Biological Response Extraction:12.1.1 Prepare a set of four 20-mL portions of each extrac-tion vehicle. Place one appropriate specimen portion in each ofthree containers; the extraction vehicle in the fourth containerwill serve a

46、s a blank. Secure the cap on each container.12.1.2 Extraction ConditionsEmploy one of the follow-ing conditions in accordance with the specified requirements.Sufficient time, in addition to that specified, should be allowedfor the liquid to reach the extraction temperature. It is recom-mended that t

47、he extraction be done at the highest temperaturethe material will withstand. If the material dissolves at 37C,then the solution should be used in the tests. Mixing duringextraction is preferable. This should be done such that theextractant is mixed with the extraction vehicle, but the fluid/specimen

48、 interface is not disturbed and air bubbles should notbe formed. Mixing or agitation in the autoclave should not beattempted.12.1.2.1 37 6 1C (95 6 1.8F) for 120 h. (For some testprotocols, extraction at 37C for 24 6 2hor726 2hisspecified.)12.1.2.2 50 6 2C (122 6 3.6F) for 72 h.12.1.2.3 70 6 2C (158

49、 6 3.6F) for 24 h.12.1.2.4 121 6 2C (250 6 3.6F) for 1h.NOTE 4There may be the assumption that these conditions areequivalent to one another. The same combination of plastic and extractionvehicle, when subjected to different extraction conditions, is generallyknown to have significantly different responses when tested. The idealevaluation of a material should employ times and temperatures thatsimulate the intended use of a plastic. Exaggerated conditions of extrac-tion attempt to provide a margin of safety with a reasonable increase intemperature. The pre