1、Designation: F 2224 09Standard Specification forHigh Purity Calcium Sulfate Hemihydrate or Dihydrate forSurgical Implants1This standard is issued under the fixed designation F 2224; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, t
2、he year of last revision. A number 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 material requirements for un-fabricated and fabricated forms of hydrated calcium
3、sulfateintended for surgical implants. Fabricated forms may includepressed and cast surgical implants in various geometric shapes.The calcium sulfate hemihydrate in the unfabricated form canbe converted with the addition of water or other water-containing solutions to a fabricated calcium sulfate di
4、hydrateform.1.2 The requirements of this specification apply to calciumsulfate combined with two molecules of water or two calciumsulfate molecules sharing one water molecule.Approximate chemical formulae:Calcium Sulfate DihydrateCaSO42H2OCalcium Sulfate HemihydrateCaSO41/2H2O or CaSO4H2OCaSO41.3 Th
5、is specification specifically excludes calcium sulfateanhydrite and calcium sulfate forms that contain additives suchas reinforcing phases, medicaments, biological agents, and soforth.1.4 The presence of processing aids does not exclude aproduct from the physical and mechanical requirements of thiss
6、pecification.1.5 Some provisions of Specification C 59/C 59M and TestMethods C 472 apply. Special requirements that are detailed inthis specification are included to characterize the materialwhich will be used in surgical implants.1.6 The biological response to calcium sulfate in bone tissuehas been
7、 well characterized by a history of clinical use (1-14)2and by laboratory studies (15-18).1.7 The following precautionary caveat pertains only to thetest method portion, Sections 4, 5, and 6, of this specification.This standard does not purport to address all of the safetyconcerns, if any, associate
8、d with its use. It is the responsibilityof the user of this standard to establish appropriate safety andhealth practices and determine the applicability of regulatoryrequirements prior to use.2. Referenced Documents2.1 ASTM Standards:3C 59/C 59M Specification for Gypsum Casting Plaster andGypsum Mol
9、ding PlasterC 472 Test Methods for Physical Testing of Gypsum, Gyp-sum Plasters and Gypsum ConcreteF 648 Specification for Ultra-High-Molecular-Weight Poly-ethylene Powder and Fabricated Form for Surgical Im-plantsF 756 Practice for Assessment of Hemolytic Properties ofMaterialsF 763 Practice for Sh
10、ort-Term Screening of Implant Mate-rialsF 813 Practice for Direct Contact Cell Culture Evaluation ofMaterials for Medical DevicesF 895 Test Method for Agar Diffusion Cell Culture Screen-ing for CytotoxicityF 981 Practice for Assessment of Compatibility of Bioma-terials for Surgical Implants with Res
11、pect to Effect ofMaterials on Muscle and BoneF 1088 Specification for Beta-Tricalcium Phosphate forSurgical ImplantationF 1635 Test Method for in vitro Degradation Testing ofHydrolytically Degradable Polymer Resins and FabricatedForms for Surgical Implants2.2 Other Documents:BS 6463-102: 2001 Quickl
12、ime, Hydrated Lime and NaturalCalcium CarbonatePart 102: Methods for ChemicalAnalysis41This specification is under the jurisdiction of ASTM Committee F04 onMedical and Surgical Materials and Devices and is the direct responsibility ofSubcommittee F04.13 on Ceramic Materials.Current edition approved
13、Sept. 1, 2009. Published September 2009. Originallyapproved in 2003. Last previous edition approved in 2003 as F 2224 03.2The boldface numbers in parentheses refer to the list of references at the end ofthis standard.3For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact AST
14、M Customer Service at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.4Available from the British Standards Institution, c/o IHS Engineering/IHSInternational, 15 Inverness Way East, Englewood, CO 80112.1Copyright A
15、STM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.US Pharmacopeia XXIV (USP 24) NF-195CFR Title 21, Part 820 Quality System Requirements6Food Chemical Codex (FCC)7European Pharmacopeia8ISO 10993-1 Biological Evaluation of Medical Devices93. Termin
16、ology3.1 Definitions:3.1.1 calcium sulfate anhydritea chemical substance hav-ing approximate molecular formula of CaSO4.3.1.2 calcium sulfate dihydratea chemical having theapproximate molecular formula of CaSO42H2O. This sub-stance is also known as gypsum.3.1.3 calcium sulfate hemihydratea chemical
17、substancehaving approximate molecular formula of CaSO41/2H2OorCaSO4H2OCaSO4. The mineral name of this substance isbassanite and the substance is also known as Plaster of Paris inthe clinical literature.3.1.4 processing aidsany constituent intentionally used inthe processing of the raw material to fu
18、lfill a certain techno-logical purpose during treatment or processing. Some ex-amples would be: binders, lubricants, compaction aids, disin-tegrants, plasticizers, deflocculants, wetting agents, waterretention agents, antistatic agents, antifoam agents, foam sta-bilizers, chelating or sequestering a
19、gents, phase stabilizers, andso forth.3.1.4.1 DiscussionUse of a processing aid may result inthe unintentional but technically unavoidable presence ofresidues of the substance or its derivatives in the final product.3.1.5 set timefor a mixture of calcium sulfate hemihy-drate and an aqueous solution,
20、 set time is defined as the elapsedtime between the onset of mixing and the development ofsufficient mechanical properties to meet a specific criteria (forexample, hardness or resistance to indentation).4. Chemical Requirements4.1 Calcium sulfate for surgical implants (raw material)shall have a puri
21、ty of not less than 98 % for calcium sulfate(absent of water) when measured by USP 24 NF 19. (Thispurity measurement method may not be applicable to thefabricated forms containing substantial quantities of additives.)4.2 The total concentration of heavy metals (for example,lead, arsenic, cadmium, an
22、timony, bismuth, and mercury) inthe calcium sulfate raw material shall be limited to less than 10ppm. Other trace elements, such as iron, may also affectimplant performance and should be kept to a minimum. Forexample, for calcium sulfate to meet USP grade, the ironconcentration should not be higher
23、than 100 ppm. Methods formeasuring these trace elements are described in SpecificationF 1088 (Coupled PlasmaAtomic Absorption Spectrometry),the United States Pharmacopeia (USP), European Pharma-copeia, or Food Chemical Codex (FCC). A second method thatmay be used to analyze acid insoluble impurities
24、 is describedin BS 6463-102.4.2.1 When calcium sulfate dihydrate is converted intocalcium sulfate hemihydrate, the mass of the material isreduced by approximately 15 % due to dehydration. Dependingon the conversion process, the quantities (total mass) of mostor all of the trace elements present in t
25、he dihydrate are notaffected. Therefore, the concentration of those trace elementsin the resulting hemihydrate material can be expected toincrease by approximately 15 %. This should be taken intoaccount when setting acceptance criteria for a calcium sulfatedihydrate raw material that will be used to
26、 produce a hemihy-drate final product that is expected to conform to this specifi-cation.5. Physical and Mechanical Characterization5.1 The following physical and mechanical characterizationmay be applicable to calcium sulfate for surgical implantapplications in either the fabricated form or intra-o
27、perativefabricated form. When characterization test results are reportedin labeling, the test methods associated with these results shallbe referenced. Labeling can be defined as but is not limited tothe product label, brochures, technical monographs, and otherrelated documentation.5.2 Set TimeIf se
28、t time is an applicable property, it shouldbe reported along with the method by which it was determinedin order to inform the final user. Test Methods C 472 asdescribed in Specification C 59/C 59M can be used to define atypical set time. The actual method used for set time determi-nation shall be de
29、scribed or referenced in labeling.5.3 Compressive StrengthCalcium sulfate dihydrate in afabricated final form is intended to be used in non-load bearingapplications. If applicable to implant performance, documen-tation of typical compressive strength and the methods used todetermine it should be rep
30、orted in order to inform the final user.Test Methods C 472 as described in Specification C 59/C 59Mcan be used for the typical compression strength determination.The actual method used shall be described or referenced inlabeling.5.4 In vitro DegradationFor calcium sulfate dihydrate ina fabricated fi
31、nal form, weight loss from dissolution may bereported. If reported, the method used should be described orreferenced. Additional information is given in Appendix X1.4.6. Test Specimen Fabrication6.1 Prepare test specimens from material(s) produced ac-cording to the same manufacturing procedures and
32、processesemployed in fabricating the implant device.7. Quality Program Requirements7.1 The manufacturer shall conform to Quality SystemsRegulations (see Title 21, part 820, of the U.S. Code of FederalRegulations) or its equivalent.8. Keywords8.1 bone; calcium sulfate; gypsum; implant; plaster5Availa
33、ble from U.S. Pharmacopeia (USP), 12601 Twinbrook Pkwy., Rockville,MD 20852.6Available from U.S. Government Printing Office Superintendent of Documents,732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401.7Available from National Academy Press, 500 Fifth St., NW, Lockbox 285,Washington, DC 2
34、0055.8Available from EDQM, European Pharmacopeia, Council of Europe, B.P. 907,F-67029, Strasbourg, France.9Available from American National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036.F2224092APPENDIX(Nonmandatory Information)X1. RATIONALEX1.1 The biocompatibility of cal
35、cium sulfate may dependupon processing conditions and source material, both whichmay not be identified by the compositional requirements of thisspecification. The biocompatibility of these products should beensured by a combination of preclinical testing and processcontrols. Material derived under t
36、he desired process conditionsshould be tested in accordance with the recommendations ofPractices F 756, F 763, F 813, and F 981; Test Methods F 895and F 1635; Specification F 648; and ISO 10993-1, and manu-facturing controls put in place to ensure that process variationsoutside of acceptable toleran
37、ces do not occur. Substantialchanges in process conditions or source material parameterswill necessitate additional biocompatibility or preclinical func-tional testing to ensure maintenance of an acceptable tissueresponse.X1.2 X-ray powder diffraction (XRD) analysis of thematerial provides different
38、iation between calcium sulfate dihy-drate and calcium sulfate hemihydrate. The International Cen-tre for Diffraction Data (ICDD) designation of calcium sulfatehemihydrate for surgical implants is ICDD # 41-0224 (Bas-sanite, syn). A typical calcium sulfate dihydrate XRD patternwill show the peaks fro
39、m ICDD #s 33-0311 (Gypsum, syn),37-1496 (Anhydrite syn), and 41-0224 (Bassanite, syn).X1.3 The setting time measurement in Section 5 is usefulfor the calcium sulfate hemihydrate since the hemihydrate mustbe hydrated to a calcium sulfate dihydrate before surgical use.Likewise, the calcium sulfate hem
40、ihydrate and dihydrate rawmaterial powders do not have the compressive strength ordegradation attributes that are needed for surgical applicationswithout being converted by hydration to calcium sulfatedihydrate or with the dihydrate form pressed into a geometricshape.X1.4 The mechanism of resorption
41、 of calcium sulfate invivo is complex and involves both physical dissolution and cellmediated resorption. As a result, in vitro dissolution experi-ments should not be expected to accurately predict in vivoresorption rates. In addition, it has been shown that the choiceof simulated body fluid can rad
42、ically alter in vitro resorptionrates. For example, calcium sulfate dihydrate pellets immersedin a phosphate buffered saline solution (PBS) can develop ashell of recrystallized hydroxyapatite on their surface whichsignificantly slows the process of dissolution (19). This behav-ior has not been obser
43、ved in vivo. Similarly, the use of distilledor deionized water for in vitro testing has been shown toaccelerate the rate of degradation relative to rates observedclinically and in pre-clinical animal studies (19).REFERENCES(1) Alexander, D. I., et al, “Efficacy of Calcium Sulfate Plus Decompres-sion
44、 Bone in Lumbar and Lumbosacral Spinal Fusion: PreliminaryResults in 40 Patients,” Can. J. Surg., 44(4), 2001, pp. 262-266.(2) Kelly, C. M., et al, “The Use of a Surgical Grade Calcium Sulfate asa Bone Graft Substitute,” Clin. Orthop. Rel. Res., 382, 2001, pp.42-50.(3) Mirzayan, R., et al, “The Use
45、of Calcium Sulfate in the Treatment ofBenign Bone Lesions,” J. Bone Joint Surg., 83A (3), 2001, pp.355-358.(4) Peltier, L. F., “The Use of Plaster of Paris to Fill Defects in Bone,”Clin. Orthop. Rel. Res., 21, 1961, pp. 1-31.(5) Peltier, L. F. and Speer, D. P., “Calcium Sulfate,” Bone Grafts andBone
46、 Substitutes, Habal, M. B. and Reddi, A. H., eds., W. B. SaundersCompany, 1993, pp. 243-246.(6) Damien, et al, “Bone Grafts and Bone Graft Substitutes,” J. AppliedBiomat., 2, 1991, pp. 187-208.(7) Bahn, S., “Plaster: A Bone Substitute,” Oral Surg. Oral Med. or through the ASTM website(www.astm.org).F2224094
