food and drug administration, hhs pt. 864 · 2018-03-19 · drugs test system. (a) identification....

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Food and Drug Administration, HHS Pt. 864

§ 862.3880 Theophylline test system.

(a) Identification. A theophylline testsystem is a device intended to measuretheophylline (a drug used for stimula-tion of the muscles in the cardio-vascular, respiratory, and central nerv-ous systems) in serum and plasma.Measurements obtained by this deviceare used in the diagnosis and treat-ment of theophylline overdose or inmonitoring levels of theophylline toensure appropriate therapy.

(b) Classification. Class II.

§ 862.3900 Tobramycin test system.

(a) Identification. A tobramycin testsystem is a device intended to measuretobramycin, an aminoglycoside anti-biotic drug, in plasma and serum.Measurements obtained by this deviceare used in the diagnosis and treat-ment of tobramycin overdose and inmonitoring levels of tobramycin to en-sure appropriate therapy.


§ 862.3910 Tricyclic antidepressantdrugs test system.

(a) Identification. A tricyclicantidepressant drugs test system is adevice intended to measure any of thetricyclic antidepressant drugs inserum. The tricyclic antidepressantdrugs include imipramine,desipramine, amitriptyline,nortriptyline, protriptyline, anddoxepin. Measurements obtained bythis device are used in the diagnosisand treatment of chronic depression toensure appropriate therapy.


§ 862.3950 Vancomycin test system.

(a) Identification. A vancomycin testsystem is a device intended to measurevancomycin, an antibiotic drug, inserum. Measurements obtained by thisdevice are used in the diagnosis andtreatment of vancomycin overdose andin monitoring the level of vancomycinto ensure appropriate therapy.


PART 864—HEMATOLOGY ANDPATHOLOGY DEVICES

Subpart A—General Provisions

Sec.864.1 Scope.864.3 Effective dates of requirement for pre-

market approval.864.9 Limitations of exemptions from sec-

tion 510(k) of the Federal Food, Drug,and Cosmetic Act (the act).

Subpart B—Biological Stains

864.1850 Dye and chemical solution stains.864.1860 Immunohistochemistry reagents

and kits.

Subpart C—Cell and Tissue CultureProducts

864.2220 Synthetic cell and tissue culturemedia and components.

864.2240 Cell and tissue culture supplies andequipment.

864.2260 Chromosome culture kit.864.2280 Cultured animal and human cells.864.2360 Mycoplasma detection media and

components.864.2800 Animal and human sera.864.2875 Balanced salt solutions or formula-

tions.

Subpart D—Pathology Instrumentation andAccessories

864.3010 Tissue processing equipment.864.3250 Specimen transport and storage

container.864.3300 Cytocentrifuge.864.3400 Device for sealing microsections.864.3600 Microscopes and accessories.864.3800 Automated slide stainer.864.3875 Automated tissue processor.

Subpart E—Specimen PreparationReagents

864.4010 General purpose reagent.864.4020 Analyte specific reagents.864.4400 Enzyme preparations.

Subpart F—Automated and Semi-Automated Hematology Devices

864.5200 Automated cell counter.864.5220 Automated differential cell

counter.864.5240 Automated blood cell diluting appa-

ratus.864.5260 Automated cell-locating device.864.5300 Red cell indices device.

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21 CFR Ch. I (4–1–00 Edition)Pt. 864

864.5350 Microsedimentation centrifuge.864.5400 Coagulation instrument.864.5425 Multipurpose system for in vitro

coagulation studies.864.5600 Automated hematocrit instrument.864.5620 Automated hemoglobin system.864.5680 Automated heparin analyzer.864.5700 Automated platelet aggregation

system.864.5800 Automated sedimentation rate de-

vice.864.5850 Automated slide spinner.864.5950 Blood volume measuring device.

Subpart G—Manual Hematology Devices

864.6100 Bleeding time device.864.6150 Capillary blood collection tube.864.6160 Manual blood cell counting device.864.6400 Hematocrit measuring device.864.6550 Occult blood test.864.6600 Osmotic fragility test.864.6650 Platelet adhesion test.864.6675 Platelet aggregometer.864.6700 Erythrocyte sedimentation rate

test.

Subpart H—Hematology Kits andPackages

864.7040 Adenosine triphosphate releaseassay.

864.7060 Antithrombin III assay.864.7100 Red blood cell enzyme assay.864.7140 Activated whole blood clotting time

tests.864.7250 Erythropoietin assay.864.7275 Euglobulin lysis time tests.864.7290 Factor deficiency test.864.7300 Fibrin monomer paracoagulation

test.864.7320 Fibrinogen/fibrin degradation prod-

ucts assay.864.7340 Fibrinogen determination system.864.7360 Erythrocytic glucose-6-phosphate

dehydrogenase assay.864.7375 Glutathione reductase assay.864.7400 Hemoglobin A2 assay.864.7415 Abnormal hemoglobin assay.864.7425 Carboxyhemoglobin assay.864.7440 Electrophoretic hemoglobin anal-

ysis system.864.7455 Fetal hemoglobin assay.864.7470 Glycosylated hemoglobin assay.864.7490 Sulfhemoglobin assay.864.7500 Whole blood hemoglobin assays.864.7525 Heparin assay.864.7660 Leukocyte alkaline phosphatase

test.864.7675 Leukocyte peroxidase test.864.7695 Platelet factor 4 radioimmuno-

assay.864.7720 Prothrombin consumption test.864.7735 Prothrombin-proconvertin test and

thrombotest.864.7750 Prothrombin time test.864.7825 Sickle cell test.

864.7875 Thrombin time test.864.7900 Thromboplastin generation test.864.7925 Partial thromboplastin time tests.

Subpart I—Hematology Reagents

864.8100 Bothrops atrox reagent.864.8150 Calibrator for cell indices.864.8165 Calibrator for hemoglobin or hem-

atocrit measurement.864.8175 Calibrator for platelet counting.864.8185 Calibrator for red cell and white

cell counting.864.8200 Blood cell diluent.864.8500 Lymphocyte separation medium.864.8540 Red cell lysing reagent.864.8625 Hematology quality control mix-

ture.864.8950 Russell viper venom reagent.

Subpart J—Products Used In EstablishmentsThat Manufacture Blood and BloodProducts

864.9050 Blood bank supplies.864.9100 Empty container for the collection

and processing of blood and blood compo-nents.

864.9125 Vacuum-assisted blood collectionsystem.

864.9145 Processing system for frozen blood.864.9160 Blood group substances of

nonhuman origin for in vitro diagnosticuse.

864.9175 Automated blood grouping andantibody test system.

864.9185 Blood grouping view box.864.9195 Blood mixing devices and blood

weighing devices.864.9205 Blood and plasma warming device.864.9225 Cell-freezing apparatus and re-

agents for in vitro diagnostic use.864.9245 Automated blood cell separator.864.9275 Blood bank centrifuge for in vitro

diagnostic use.864.9285 Automated cell-washing centrifuge

for immuno-hematology.864.9300 Automated Coombs test systems.864.9320 Copper sulfate solution for specific

gravity determinations.864.9400 Stabilized enzyme solution.864.9550 Lectins and protectins.864.9575 Environmental chamber for storage

of platelet concentrate.864.9600 Potentiating media for in vitro di-

agnostic use.864.9650 Quality control kit for blood bank-

ing reagents.864.9700 Blood storage refrigerator and

blood storage freezer.864.9750 Heat-sealing device.864.9875 Transfer set.

AUTHORITY: 21 U.S.C. 351, 360, 360c, 360e,360j, 371.


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Food and Drug Administration, HHS § 864.9


§ 864.1 Scope.(a) This part sets forth the classifica-

tion of hematology and pathology de-vices intended for human use that arein commercial distribution.

(b) The identification of a device in aregulation in this part is not a precisedescription of every device that is, orwill be, subject to the regulation. Amanufacturer who submits a pre-market notification submission for adevice under part 807 may not showmerely that the device is accuratelydescribed by the section title and iden-tification provisions of a regulation inthis part, but shall state why the de-vice is substantially equivalent toother devices, as required by § 807.87.

(c) References in this part to regu-latory sections of the Code of FederalRegulations are to chapter I of title 21,unless otherwise noted.

[52 FR 17732, May 11, 1987]

§ 864.3 Effective dates of requirementfor premarket approval.

A device included in this part that isclassified into class III (premarket ap-proval) shall not be commercially dis-tributed after the date shown in theregulation classifying the device unlessthe manufacturer has an approvalunder section 515 of the act (unless anexemption has been granted under sec-tion 520(g)(2) of the act). An approvalunder section 515 of the act consists ofFDA’s issuance of an order approvingan application for premarket approval(PMA) for the device or declaring com-pleted a product development protocol(PDP) for the device.

(a) Before FDA requires that a devicecommercially distributed before theenactment date of the amendments, ora device that has been found substan-tially equivalent to such a device, hasan approval under section 515 of the actFDA must promulgate a regulationunder section 515(b) of the act requir-ing such approval, except as providedin paragraph (b) of this section. Such aregulation under section 515(b) of theact shall not be effective during thegrace period ending on the 90th dayafter its promulgation or on the lastday of the 30th full calendar month

after the regulation that classifies thedevice into class III is effective, which-ever is later. See section 501(f)(2)(B) ofthe act. Accordingly, unless an effec-tive date of the requirement for pre-market approval is shown in the regu-lation for a device classified into classIII in this part, the device may be com-mercially distributed without FDA’sissuance of an order approving a PMAor declaring completed a PDP for thedevice. If FDA promulgates a regula-tion under section 515(b) of the act re-quiring premarket approval for a de-vice, section 501(f)(1)(A) of the act ap-plies to the device.

(b) Any new, not substantially equiv-alent, device introduced into commer-cial distribution on or after May 28,1976, including a device formerly mar-keted that has been substantially al-tered, is classified by statute (section513(f) of the act) into class III withoutany grace period and FDA must haveissued an order approving a PMA or de-claring completed a PDP for the devicebefore the device is commercially dis-tributed unless it is reclassified. IfFDA knows that a device being com-mercially distributed may be a ‘‘new’’device as defined in this section be-cause of any new intended use or otherreasons, FDA may codify the statutoryclassification of the device into classIII for such new use. Accordingly, theregulation for such a class III devicestates that as of the enactment date ofthe amendments, May 28, 1976, the de-vice must have an approval under sec-tion 515 of the act before commercialdistribution.

[52 FR 17732, May 11, 1987]

§ 864.9 Limitations of exemptions fromsection 510(k) of the Federal Food,Drug, and Cosmetic Act (the act).

The exemption from the requirementof premarket notification (section510(k) of the act) for a generic type ofclass I or II device is only to the extentthat the device has existing or reason-ably foreseeable characteristics ofcommercially distributed devices with-in that generic type or, in the case ofin vitro diagnostic devices, only to theextent that misdiagnosis as a result ofusing the device would not be associ-ated with high morbidity or mortality.Accordingly, manufacturers of any


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21 CFR Ch. I (4–1–00 Edition)§ 864.1850

commercially distributed class I or IIdevice for which FDA has granted anexemption from the requirement ofpremarket notification must still sub-mit a premarket notification to FDAbefore introducing or delivering for in-troduction into interstate commercefor commercial distribution the devicewhen:

(a) The device is intended for a usedifferent from the intended use of a le-gally marketed device in that generictype of device; e.g., the device is in-tended for a different medical purpose,or the device is intended for lay usewhere the former intended use was byhealth care professionals only;

(b) The modified device operatesusing a different fundamental sci-entific technology than a legally mar-keted device in that generic type of de-vice; e.g., a surgical instrument cutstissue with a laser beam rather thanwith a sharpened metal blade, or an invitro diagnostic device detects or iden-tifies infectious agents by usingdeoxyribonucleic acid (DNA) probe ornucleic acid hybridization technologyrather than culture or immunoassaytechnology; or

(c) The device is an in vitro devicethat is intended:

(1) For use in the diagnosis, moni-toring, or screening of neoplastic dis-eases with the exception ofimmunohistochemical devices;

(2) For use in screening or diagnosisof familial or acquired genetic dis-orders, including inborn errors of me-tabolism;

(3) For measuring an analyte thatserves as a surrogate marker forscreening, diagnosis, or monitoringlife-threatening diseases such as ac-quired immune deficiency syndrome(AIDS), chronic or active hepatitis, tu-berculosis, or myocardial infarction orto monitor therapy;

(4) For assessing the risk of cardio-vascular diseases;

(5) For use in diabetes management;(6) For identifying or inferring the

identity of a microorganism directlyfrom clinical material;

(7) For detection of antibodies tomicroorganisms other thanimmunoglobulin G (IgG) or IgG assayswhen the results are not qualitative, orare used to determine immunity, or the

assay is intended for use in matricesother than serum or plasma;

(8) For noninvasive testing as definedin § 812.3(k) of this chapter; and

(9) For near patient testing (point ofcare).

[65 FR 2310, Jan. 14, 2000]

Subpart B—Biological Stains

§ 864.1850 Dye and chemical solutionstains.

(a) Identification. Dye and chemicalsolution stains for medical purposesare mixtures of synthetic or naturaldyes or nondye chemicals in solutionsused in staining cells and tissues for di-agnostic histopathology,cytopathology, or hematology.

(b) Classification. Class I. These de-vices are exempt from the premarketnotification procedures in subpart E ofpart 807. The devices are also exemptfrom the current good manufacturingpractice regulations in part 820 of thischapter, with the exception of § 820.180,with respect to general requirementsconcerning records, and § 820.198, withrespect to complaint files.

[45 FR 60583, Sept. 12, 1980, as amended at 54FR 25044, June 12, 1989]

§ 864.1860 Immunohistochemistry re-agents and kits.

(a) Identification. Immunohistochem-istry test systems (IHC’s) are in vitrodiagnostic devices consisting ofpolyclonal or monoclonal antibodieslabeled with directions for use and per-formance claims, which may be pack-aged with ancillary reagents in kits.Their intended use is to identify, byimmunological techniques, antigens intissues or cytologic specimens. Similardevices intended for use with flowcytometry devices are not consideredIHC’s.

(b) Classification ofimmunohistochemistry devices. (1) Class I(general controls). Except as describedin paragraphs (b)(2) and (b)(3) of thissection, these devices are exempt fromthe premarket notification require-ments in part 807, subpart E of thischapter. This exemption applies toIHC’s that provide the pathologist withadjunctive diagnostic information that


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may be incorporated into the patholo-gist’s report, but that is not ordinarilyreported to the clinician as an inde-pendent finding. These IHC’s are usedafter the primary diagnosis of tumor(neoplasm) has been made by conven-tional histopathology usingnonimmunologic histochemical stains,such as hematoxylin and eosin. Exam-ples of class I IHC’s are differentiationmarkers that are used as adjunctivetests to subclassify tumors, such askeratin.

(2) Class II (special control, guidancedocument: ‘‘FDA Guidance for Submis-sion of Immunohistochemistry Appli-cations to the FDA,’’ Center for De-vices and Radiologic Health, 1998).These IHC’s are intended for the detec-tion and/or measurement of certaintarget analytes in order to provideprognostic or predictive data that arenot directly confirmed by routinehistopathologic internal and externalcontrol specimens. These IHC’s providethe pathologist with information thatis ordinarily reported as independentdiagnostic information to the orderingclinician, and the claims associatedwith these data are widely acceptedand supported by valid scientific evi-dence. Examples of class II IHC’s arethose intended for semiquantitativemeasurement of an analyte, such ashormone receptors in breast cancer.

(3) Class III (premarket approval).IHC’s intended for any use not de-scribed in paragraphs (b)(1) or (b)(2) ofthis section.

(c) Date of PMA or notice of completionof a PDP is required. As of May 28, 1976,an approval under section 515 of theFederal Food, Drug, and Cosmetic Actis required for any device described inparagraph (b)(3) of this section beforethis device may be commercially dis-tributed. See § 864.3.

[63 FR 30142, June 3, 1998]

Subpart C—Cell And TissueCulture Products

§ 864.2220 Synthetic cell and tissueculture media and components.

(a) Identification. Synthetic cell andtissue culture media and componentsare substances that are composed en-tirely of defined components (e.g.,

amino acids, vitamins, inorganic salts,etc.) that are essential for the survivaland development of cell lines of hu-mans and other animals.

(b) Classification. Class I. These de-vices are exempt from the premarketnotification procedures in subpart E ofpart 807 of this chapter.


§ 864.2240 Cell and tissue culture sup-plies and equipment.

(a) Identification. Cell and tissue cul-ture supplies and equipment are de-vices that are used to examine, propa-gate, nourish, or grow cells and tissuecultures. These include such articles asslide culture chambers, perfusion androller apparatus, cell culture suspen-sion systems, and tissue culture flasks,disks, tubes, and roller bottles.

(b) Classification. Class I. These de-vices are exempt from the premarketnotification procedures in subpart E ofpart 807 of this chapter. If the devicesare not labeled or otherwise rep-resented as sterile, they are exemptfrom the current good manufacturingpractice regulations in part 820 of thischapter, with the exception of § 820.180,with respect to general requirementsconcerning records, and § 820.198, withrespect to complaint files.


§ 864.2260 Chromosome culture kit.(a) Identification. A chromosome cul-

ture kit is a device containing the nec-essary ingredients (e.g., Minimum Es-sential Media (MEM) of McCoy’s 5Aculture media, phytohemagglutinin,fetal calf serum, antibiotics, and hep-arin) used to culture tissues for diag-nosis of congenital chromosome abnor-malities.

(b) Classification. Class I. The deviceis exempt from the premarket notifica-tion procedures in subpart E of part 807of this chapter.


§ 864.2280 Cultured animal and humancells.

(a) Identification. Cultured animaland human cells are in vitro cultivated


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21 CFR Ch. I (4–1–00 Edition)§ 864.2360

cell lines from the tissue of humans orother animals which are used in var-ious diagnostic procedures, particu-larly diagnostic virology and cyto-genetic studies.

(b) Classification. Class I (general con-trols). The device is exempt from thepremarket notification procedures insubpart E of part 807 of this chaptersubject to § 864.9.

[45 FR 60585, Sept. 12, 1980, as amended at 65FR 2310, Jan. 14, 2000]

§ 864.2360 Mycoplasma detectionmedia and components.

(a) Identification. Mycoplasma detec-tion media and components are used todetect and isolate mycoplasmapleuropneumonia-like organisms(PPLO), a common microbial contami-nant in cell cultures.



§ 864.2800 Animal and human sera.(a) Identification. Animal and human

sera are biological products, obtainedfrom the blood of humans or other ani-mals, that provide the necessarygrowth-promoting nutrients in a cellculture system.

(b) Classification. Class I. The devicesare exempt from the premarket notifi-cation procedures in subpart E of part807 of this chapter.


§ 864.2875 Balanced salt solutions orformulations.

(a) Identification. A balanced salt so-lution or formulation is a defined mix-ture of salts and glucose in a simplemedium. This device is included as anecessary component of most cell cul-ture systems. This media componentcontrols for pH, osmotic pressure, en-ergy source, and inorganic ions.



Subpart D—PathologyInstrumentation and Accessories

§ 864.3010 Tissue processing equip-ment.

(a) Identification. Tissue processingequipment consists of devices used toprepare human tissue specimens for di-agnostic histological examination byprocessing specimens through the var-ious stages of decalcifying, infiltrating,sectioning, and mounting on micro-scope slides.

(b) Classification. Class I. The deviceis exempt from the premarket notifica-tion procedures in subpart E of part 807of this chapter. The device is also ex-empt from the current good manufac-turing practice regulations in part 820of this chapter, with the exception of§ 820.180, with respect to general re-quirements concerning records, and§ 820.198, with respect to complaintfiles.


§ 864.3250 Specimen transport andstorage container.

(a) Identification. A specimen trans-port and storage container, which maybe empty or prefilled, is a device in-tended to contain biological specimens,body waste, or body exudate duringstorage and transport in order that thematter contained therein can be de-stroyed or used effectively for diag-nostic examination. If prefilled, the de-vice contains a fixative solution orother general purpose reagent to pre-serve the condition of a biological spec-imen added to the container.

(b) Classification. Class I (general con-trols). The device is exempt from thepremarket notification procedures insubpart E of part 807 of this chaptersubject to § 864.9. If the device is not la-beled or otherwise represented as ster-ile, it is exempt from the current goodmanufacturing practice regulations inpart 820 of this chapter, with the excep-tion of § 820.180 of this chapter, with re-spect to general requirements con-cerning records, and § 820.198 of thischapter, with respect to complaintfiles.

[54 FR 47206, Nov. 13, 1989, as amended at 65FR 2310, Jan. 14, 2000]


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§ 864.3300 Cytocentrifuge.(a) Identification. A cytocentrifuge is

a centrifuge used to concentrate cellsfrom biological cell suspensions (e.g.,cerebrospinal fluid) and to depositthese cells on a glass microscope slidefor cytological examination.



§ 864.3400 Device for sealing microsec-tions.

(a) Identification. A device for sealingmicrosections is an automated instru-ment used to seal stained cells andmicrosections for histological andcytological examination.



§ 864.3600 Microscopes and acces-sories.

(a) Identification. Microscopes and ac-cessories are optical instruments usedto enlarge images of specimens, prep-arations, and cultures for medical pur-poses. Variations of microscopes andaccessories (through a change in thelight source) used for medical purposesinclude the following:

(1) Phase contrast microscopes,which permit visualization ofunstained preparations by altering thephase relationship of light that passesaround the object and through the ob-ject.

(2) Fluorescense microscopes, whichpermit examination of specimensstained with fluorochromes that fluo-resce under ultraviolet light.

(3) Inverted stage microscopes, whichpermit examination of tissue culturesor other biological specimens con-tained in bottles or tubes with thelight source mounted above the speci-men.

(b) Classification. Class I. These de-vices are exempt from the premarketnotification procedures in subpart E ofpart 807 of this chapter. The devices are

also exempt from the current goodmanufacturing practice regulations inpart 820 of this chapter, with the excep-tion of § 820.180, with respect to generalrequirements concerning records, and§ 820.198, with respect to complaintfiles.


§ 864.3800 Automated slide stainer.(a) Identification. An automated slide

stainer is a device used to stain his-tology, cytology, and hematologyslides for diagnosis.



§ 864.3875 Automated tissue processor.(a) Identification. An automated tis-

sue processor is an automated systemused to process tissue specimens for ex-amination through fixation, dehydra-tion, and infiltration.



Subpart E—Specimen PreparationReagents

§ 864.4010 General purpose reagent.(a) A general purpose reagent is a

chemical reagent that has general lab-oratory application, that is used to col-lect, prepare, and examine specimensfrom the human body for diagnosticpurposes, and that is not labeled orotherwise intended for a specific diag-nostic application. It may be either anindividual substance, or multiple sub-stances reformulated, which, whencombined with or used in conjunctionwith an appropriate analyte specific re-agent (ASR) and other general purposereagents, is part of a diagnostic testprocedure or system constituting a fin-ished in vitro diagnostic (IVD) test.General purpose reagents are appro-priate for combining with one or more


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21 CFR Ch. I (4–1–00 Edition)§ 864.4020

than one ASR in producing such sys-tems and include labware or disposableconstituents of tests; but they do notinclude laboratory machinery, auto-mated or powered systems. Generalpurpose reagents include cytologicalpreservatives, decalcifying reagents,fixative and adhesives, tissue proc-essing reagents, isotonic solutions andpH buffers. Reagents used in tests formore than one individual chemical sub-stance or ligand are general purpose re-agents (e.g., Thermus aquaticus (TAQ)polymerase, substrates for enzymeimmunoassay (EIA)).

(b) Classification. Class I. The deviceis exempt from the premarket notifica-tion procedures in subpart E of part 807of this chapter. If the device is not la-beled or otherwise represented as ster-ile, it is exempt from the current goodmanufacturing practice regulations inpart 820 of this chapter, with the excep-tion of § 820.180, with respect to generalrequirements concerning records, and§ 820.198, with respect to complaintfiles.

[45 FR 60592, Sept. 12, 1980, as amended at 54FR 25045, June 12, 1989; 62 FR 62260, Nov. 21,1997]

§ 864.4020 Analyte specific reagents.(a) Identification. Analyte specific re-

agents (ASR’s) are antibodies, bothpolyclonal and monoclonal, specific re-ceptor proteins, ligands, nucleic acidsequences, and similar reagents which,through specific binding or chemicalreaction with substances in a speci-men, are intended for use in a diag-nostic application for identificationand quantification of an individualchemical substance or ligand in bio-logical specimens. ASR’s that other-wise fall within this definition are notwithin the scope of subpart E of thispart when they are sold to:

(1) In vitro diagnostic manufacturers;or

(2) Organizations that use the re-agents to make tests for purposes otherthan providing diagnostic informationto patients and practitioners, e.g., fo-rensic, academic, research, and othernonclinical laboratories.

(b) Classification. (1) Class I (generalcontrols). Except as described in para-graphs (b)(2) and (b)(3) of this section,these devices are exempt from the pre-

market notification requirements inpart 807, subpart E of this chapter.

(2) Class II (special controls/guidancedocuments), when the analyte is usedin blood banking tests that have beenclassified as class II devices (e.g., cer-tain cytomegalovirus serological andtreponema pallidum nontreponemaltest reagents). Guidance Documents:

1. ‘‘Specifications for Immunological Test-ing for Infectious Disease; Approved Guide-line,’’ NCCLS Document I/LA18–A, December1994.

2. ‘‘Assessment of the Clinical Accuracy ofLaboratory Tests Using Receiver OperatingCharacteristic (ROC) Plots; Tentative Guide-line,’’ NCCLS Document KGP10–T, December1993.

3. ‘‘Review Criteria for Assessment of InVitro Diagnostic Devices for Direct Detec-tion of Mycobacterium spp,’’ FDA, July 6,1993, and its ‘‘Attachment 1,’’ February 28,1994.

4. ‘‘Draft Review Criteria for Nucleic AcidAmplification-Based In Vitro Diagnostic De-vices for Direct Detection of InfectiousMicroorganisms,’’ FDA, July 6, 1993.

5. The Center for Biologics Evaluation andResearch, FDA, ‘‘Points to Consider in theManufacture and Clinical Evaluation of InVitro Tests to Detect Antibodies to theHuman Immunodeficiency Virus, Type I’’ (54FR 48943, November 28, 1989).

(3) Class III (premarket approval),when:

(i) The analyte is intended as a com-ponent in a test intended for use in thediagnosis of a contagious conditionthat is highly likely to result in a fataloutcome and prompt, accurate diag-nosis offers the opportunity to miti-gate the public health impact of thecondition (e.g., human immuno-deficiency virus (HIV/AIDS)or tuber-culosis (TB)); or

(ii) The analyte is intended as a com-ponent in a test intended for use indonor screening for conditions forwhich FDA has recommended or re-quired testing in order to safeguard theblood supply or establish the safe useof blood and blood products (e.g., testsfor hepatitis or tests for identifyingblood groups).

(c) Date of 510(k), or date of PMA ornotice of completion of a product develop-ment protocol is required. (1)Preamendments ASR’s; No effectivedate has been established for the re-quirement for premarket approval for


217


the device described in paragraph (b)(3)of this section. See § 864.3.

(2) For postamendments ASR’s; No-vember 23, 1998.

(d) Restrictions. Restrictions on thesale, distribution and use of ASR’s areset forth in § 809.30 of this chapter.

[62 FR 62260, Nov. 21, 1997]

§ 864.4400 Enzyme preparations.

(a) Identification. Enzyme prepara-tions are products that are used in thehistopathology laboratory for the fol-lowing purposes:

(1) To disaggregate tissues and cellsalready in established cultures forpreparation into subsequent cultures(e.g., trypsin);

(2) To disaggregate fluid specimensfor cytological examination (e.g.,papain for gastric lavage or trypsin forsputum liquefaction);

(3) To aid in the selective staining oftissue specimens (e.g., diastase for gly-cogen determination).



Subpart F—Automated and Semi-Automated Hematology Devices

§ 864.5200 Automated cell counter.

(a) Identification. An automated cellcounter is a fully-automated or semi-automated device used to count redblood cells, white blood cells, or bloodplatelets using a sample of the pa-tient’s peripheral blood (blood circu-lating in one of the body’s extremities,such as the arm). These devices mayalso measure hemoglobin or hemato-crit and may also calculate or measureone or more of the red cell indices (theerythrocyte mean corpuscular volume,the mean corpuscular hemoglobin, orthe mean corpuscular hemoglobin con-centration). These devices may use ei-ther an electronic particle countingmethod or an optical counting method.

(b) Classification. Class II (perform-ance standards).

[45 FR 60593, Sept. 12, 1980]

§ 864.5220 Automated differential cellcounter.

(a) Identification. An automated dif-ferential cell counter is a device usedto identify and classify one or more ofthe formed elements of the blood.

(b) Classification. (1) Class II (per-formance standards) when the device isintended to flag or identify specimenscontaining abnormal blood cells.

(2) Class III (premarket approval)when the device is intended for otheruses, including to count or classify ab-normal cells of the blood.

(c) Date PMA or notice of completion ofa PDP is required. No effective date hasbeen established of the requirement forpremarket approval for the deviceidentified in paragraph (b)(2) of thissection. See § 864.3.


§ 864.5240 Automated blood cell dilut-ing apparatus.

(a) Identification. An automated bloodcell diluting apparatus is a fully auto-mated or semi-automated device usedto make appropriate dilutions of ablood sample for further testing.



§ 864.5260 Automated cell-locating de-vice.

(a) Identification. An automated cell-locating device is a device used to lo-cate blood cells on a peripheral bloodsmear, allowing the operator to iden-tify and classify each cell according totype. (Peripheral blood is blood circu-lating in one of the body’s extremities,such as the arm.)


[45 FR 60597, Sept. 12, 1980]

§ 864.5300 Red cell indices device.(a) Identification. A red cell indices

device, usually part of a larger system,calculates or directly measures theerythrocyte mean corpuscular volume


218

21 CFR Ch. I (4–1–00 Edition)§ 864.5350

(MCV), the mean corpuscular hemo-globin (MCH), and the mean corpus-cular hemoglobin concentration(MCHC). The red cell indices are usedfor the differential diagnosis ofanemias.


[45 FR 60597, Sept. 12, 1980]

§ 864.5350 Microsedimentation cen-trifuge.

(a) Identification. A microsedimenta-tion centrifuge is a device used to sedi-ment red cells for the microsedimenta-tion rate test.


[45 FR 60598, Sept. 12, 1980, as amended at 59FR 63007, Dec. 7, 1994]

§ 864.5400 Coagulation instrument.(a) Identification. A coagulation in-

strument is an automated or semiauto-mated device used to determine theonset of clot formation for in vitro co-agulation studies.


[45 FR 60598, Sept. 12, 1980]

§ 864.5425 Multipurpose system for invitro coagulation studies.

(a) Identification. A multipurpose sys-tem for in vitro coagulation studies isa device consisting of one automated orsemiautomated instrument and its as-sociated reagents and controls. Thesystem is used to perform a series ofcoagulation studies and coagulationfactor assays.


[45 FR 60599, Sept. 12, 1980]

§ 864.5600 Automated hematocrit in-strument.

(a) Identification. An automated hem-atocrit instrument is a fully auto-mated or semi-automated device whichmay or may not be part of a larger sys-tem. This device measures the packedred cell volume of a blood sample todistinguish normal from abnormalstates, such as anemia and

erythrocytosis (an increase in the num-ber of red cells).


[45 FR 60600, Sept. 12, 1980]

§ 864.5620 Automated hemoglobin sys-tem.

(a) Identification. An automated he-moglobin system is a fully automatedor semi-automated device which mayor may not be part of a larger system.The generic type of device consists ofthe reagents, calibrators, controls, andinstrumentation used to determine thehemoglobin content of human blood.


[45 FR 60601, Sept. 12, 1980]

§ 864.5680 Automated heparin ana-lyzer.

(a) Identification. An automated hep-arin analyzer is a device used to deter-mine the heparin level in a blood sam-ple by mixing the sample with prot-amine (a heparin-neutralizing sub-stance) and determiningphotometrically the onset of air-acti-vated clotting. The analyzer also deter-mines the amount of protamine nec-essary to neutralize the heparin in thepatient’s circulation.

(b) Classification. Class II (specialcontrols).

[45 FR 60601, Sept. 12, 1980, as amended at 52FR 17733, May 11, 1987; 58 FR 51571, Oct. 4,1993]

§ 864.5700 Automated platelet aggrega-tion system.

(a) Identification. An automatedplatelet aggregation system is a deviceused to determine changes in plateletshape and platelet aggregation fol-lowing the addition of an aggregatingreagent to a platelet-rich plasma.


[45 FR 60602, Sept. 12, 1980]

§ 864.5800 Automated sedimentationrate device.

(a) Identification. An automated sedi-mentation rate device is an instrumentthat measures automatically theerythrocyte sedimentation rate in


219


whole blood. Because an increased sedi-mentation rate indicates tissue dam-age or inflammation, the erythrocytesedimentation rate device is useful inmonitoring treatment of a disease.



§ 864.5850 Automated slide spinner.

(a) Identification. An automated slidespinner is a device that prepares auto-matically a blood film on a microscopeslide using a small amount of periph-eral blood (blood circulating in one ofthe body’s extremities, such as thearm).



§ 864.5950 Blood volume measuring de-vice.

(a) Identification. A blood volumemeasuring device is a manual, semi-automated, or automated system thatis used to calculate the red cell mass,plasma volume, and total blood vol-ume.


[45 FR 60603, Sept. 12, 1980]

Subpart G—Manual HematologyDevices

§ 864.6100 Bleeding time device.

(a) Identification. A bleeding time de-vice is a device, usually employing twospring-loaded blades, that produces twosmall incisions in the patient’s skin.The length of time required for thebleeding to stop is a measure of the ef-fectiveness of the coagulation system,primarily the platelets.

(b) Classification. Class II (specialcontrols). The device is exempt fromthe premarket notification procedures

in subpart E of part 807 of this chaptersubject to § 864.9.

[45 FR 60604, Sept. 12, 1980, as amended at 63FR 59225, Nov. 3, 1998]

§ 864.6150 Capillary blood collectiontube.

(a) Identification. A capillary bloodcollection tube is a plain orheparinized glass tube of very small di-ameter used to collect blood by cap-illary action.


[45 FR 60604, Sept. 12, 1980, as amended at 54FR 25045, June 12, 1989; 65 FR 2310, Jan. 14,2000]

§ 864.6160 Manual blood cell countingdevice.

(a) Identification. A manual blood cellcounting device is a device used tocount red blood cells, white blood cells,or blood platelets.



§ 864.6400 Hematocrit measuring de-vice.

(a) Identification. A hematocrit meas-uring device is a system consisting ofinstruments, tubes, racks, and a sealerand a holder. The device is used tomeasure the packed red cell volume inblood to determine whether the pa-tient’s total red cell volume is normalor abnormal. Abnormal states includeanemia (an abnormally low total redcell volume) and erythrocytosis (an ab-normally high total red cell mass). Thepacked red cell volume is produced bycentrifuging a given volume of blood.

(b) Classification. Class II (specialcontrols). The device is exempt fromthe premarket notification proceduresin subpart E of part 807 of this chaptersubject to § 864.9.



220

21 CFR Ch. I (4–1–00 Edition)§ 864.6550

§ 864.6550 Occult blood test.(a) Identification. An occult blood test

is a device used to detect occult bloodin urine or feces. (Occult blood is bloodpresent in such small quantities that itcan be detected only by chemical testsof suspected material, or by micro-scopic or spectroscopic examination.)


[45 FR 60606, Sept. 12, 1980]

§ 864.6600 Osmotic fragility test.(a) Identification. An osmotic fragility

test is a device used to determine theresistance of red blood cells to hemol-ysis (destruction) in varying con-centrations of hypotonic saline solu-tions.



§ 864.6650 Platelet adhesion test.(a) Identification. A platelet adhesion

test is a device used to determine invitro platelet function.


[45 FR 60608, Sept. 12, 1980]

§ 864.6675 Platelet aggregometer.(a) Identification. A platelet

aggregometer is a device, used to de-termine changes in platelet shape andplatelet aggregation following the ad-dition of an aggregating reagent to aplatelet rich plasma.


[45 FR 60608, Sept. 12, 1980]

§ 864.6700 Erythrocyte sedimentationrate test.

(a) Identification. An erythrocytesedimentation rate test is a device thatmeasures the length of time requiredfor the red cells in a blood sample tofall a specified distance or a devicethat measures the degree of sedimenta-tion taking place in a given length oftime. An increased rate indicates tis-sue damage or inflammation.



Subpart H—Hematology Kits andPackages

§ 864.7040 Adenosine triphosphate re-lease assay.

(a) Identification. An adenosinetriphosphate release assay is a devicethat measures the release of adenosinetriphosphate (ATP) from platelets fol-lowing aggregation. This measurementis made on platelet-rich plasma using aphotometer and a luminescent fireflyextract. Simultaneous measurementsof platelet aggregation and ATP re-lease are used to evaluate plateletfunction disorders.

(b) Classification. Class I (generalcontrols).

[45 FR 60609, Sept. 12, 1980]

§ 864.7060 Antithrombin III assay.

(a) Identification. An antithrombin IIIassay is a device that is used to deter-mine the plasma level of antithrombinIII (a substance which acts with theanticoagulant heparin to prevent co-agulation). This determination is usedto monitor the administration of hep-arin in the treatment of thrombosis.The determination may also be used inthe diagnosis of thrombophilia (a con-genital deficiency of antithrombin III).


[45 FR 60609, Sept. 12, 1980]

§ 864.7100 Red blood cell enzymeassay.

(a) Identification. Red blood cell en-zyme assay is a device used to measurethe activity in red blood cells of clini-cally important enzymatic reactionsand their products, such as pyruvatekinase or 2,3-diphosphoglycerate. A redblood cell enzyme assay is used to de-termine the enzyme defects responsiblefor a patient’s hereditary hemolyticanemia.


221



[45 FR 60610, Sept. 12, 1980]

§ 864.7140 Activated whole blood clot-ting time tests.

(a) Identification. An activated wholeblood clotting time tests is a device,used to monitor heparin therapy forthe treatment of venous thrombosis orpulmonary embolism by measuring thecoagulation time of whole blood.


[45 FR 60611, Sept. 12, 1980]

§ 864.7250 Erythropoietin assay.(a) Identification. A erythropoietin

assay is a device that measures theconcentration of erythropoietin (an en-zyme that regulates the production ofred blood cells) in serum or urine. Thisassay provides diagnostic informationfor the evaluation of erythrocytosis(increased total red cell mass) and ane-mia.

(b) Classification. Class II. The specialcontrol for this device is FDA’s ‘‘Docu-ment for Special Controls for Erythro-poietin Assay Premarket Notification(510(k)s).’’

[45 FR 60612, Sept. 12, 1980, as amended at 52FR 17733, May 11, 1987; 65 FR 17144, Mar. 31,2000]

EFFECTIVE DATE NOTE: At 65 FR 17144, Mar.31, 2000, § 864.7250 was amended by revisingparagraph (b) and by removing paragraph (c),effective May 1, 2000. For the convenience ofthe user, the superseded text follows.

§ 864.7250 Erythropoietin assay.

* * * * *

(b) Classification. Class III (premarket ap-proval).

(c) Date PMA or notice of completion of aPDP is required. No effective date has beenestablished of the requirement for premarketapproval. See § 864.3.

§ 864.7275 Euglobulin lysis time tests.(a) Identification. A euglobulin lysis

time test is a device that measures thelength of time required for the lysis(dissolution) of a clot formed fromfibrinogen in the euglobulin fraction(that fraction of the plasma responsiblefor the formation of plasmin, a clot

lysing enzyme). This test evaluatesnatural fibrinolysis (destruction of ablood clot after bleeding has been ar-rested). The test also will detect accel-erated fibrinolysis.


[45 FR 60612, Sept. 12, 1980]

§ 864.7290 Factor deficiency test.

(a) Identification. A factor deficiencytest is a device used to diagnose spe-cific coagulation defects, to monitorcertain types of therapy, to detect co-agulation inhibitors, and to detect acarrier state (a person carrying both arecessive gene for a coagulation factordeficiency such as hemophilia and thecorresponding normal gene).


[45 FR 60613, Sept. 12, 1980]

§ 864.7300 Fibrin monomerparacoagulation test.

(a) Identification. A fibrin monomerparacoagulation test is a device used todetect fibrin monomer in the diagnosisof disseminated intravascular coagula-tion (nonlocalized clotting within ablood vessel) or in the differential diag-nosis between disseminatedintravascular coagulation and primaryfibrinolysis (dissolution of the fibrin ina blood clot).

(b) Classification. Class II. The specialcontrol for this device is FDA’s ‘‘InVitro Diagnostic Fibrin MonomerParacoagulation Test.’’

[45 FR 60614, Sept. 12, 1980, as amended at 52FR 17733, May 11, 1987; 65 FR 17144, Mar. 31,2000]

EFFECTIVE DATE NOTE: At 65 FR 17144, Mar.31, 2000, § 864.7300 was amended by revisingparagraph (b) and by removing paragraph (c),effective May 1, 2000. For the convenience ofthe user, the superseded text follows.

§ 864.7300 Fibrin monomer paracoagulationtest.

* * * * *

(b) Classification. Class III (premarket ap-proval).

(c) Date PMA or notice of completion of aPDP is required. No effective date has beenestablished of the requirement for premarketapproval. See § 864.3.


222

21 CFR Ch. I (4–1–00 Edition)§ 864.7320

§ 864.7320 Fibrinogen/fibrin degrada-tion products assay.

(a) Identification. A fibrinogen/fibrindegradation products assay is a deviceused to detect and measure fibrinogendegradation products and fibrin deg-radation products (protein fragmentsproduced by the enzymatic action ofplasmin on fibrinogen and fibrin) as anaid in detecting the presence and de-gree of intravascular coagulation andfibrinolysis (the dissolution of thefibrin in a blood clot) and in moni-toring therapy for disseminatedintravascular coagulation (nonlocal-ized clotting in the blood vessels).


[45 FR 60615, Sept. 12, 1980]

§ 864.7340 Fibrinogen determinationsystem.

(a) Identification. A fibrinogen deter-mination system is a device that con-sists of the instruments, reagents,standards, and controls used to deter-mine the fibrinogen levels in dissemi-nated intravascular coagulation (non-localized clotting within the blood ves-sels) and primary fibrinolysis (the dis-solution of fibrin in a blood clot).


[45 FR 60615, Sept. 12, 1980]

§ 864.7360 Erythrocytic glucose-6-phos-phate dehydrogenase assay.

(a) Identification. An erythrocyticglucose-6-phosphate dehydrogenaseassay is a device used to measure theactivity of the enzyme glucose-6-phos-phate dehydrogenase or of glucose-6-phosphate dehydrogenase isoenzymes.The results of this assay are used inthe diagnosis and treatment ofnonspherocytic congenital hemolyticanemia or drug-induced hemolytic ane-mia associated with a glucose-6-phos-phate dehydrogenase deficiency. Thisgeneric device includes assays based onfluorescence, electrophoresis,methemoglobin reduction, catalase in-hibition, and ultraviolet kinetics.


[45 FR 60616, Sept. 12, 1980]

§ 864.7375 Glutathione reductaseassay.

(a) Identification. A glutathione re-ductase assay is a device used to deter-mine the activity of the enzyme gluta-thione reductase in serum, plasma, orerythrocytes by such techniques as flu-orescence and photometry. The resultsof this assay are used in the diagnosisof liver disease, glutathione reductasedeficiency, or riboflavin deficiency.


[45 FR 60616, Sept. 12, 1980]

§ 864.7400 Hemoglobin A2 assay.

(a) Identification. A hemoglobin A2

assay is a device used to determine thehemoglobin A2 content of human blood.The measurement of hemoglobin A2 isused in the diagnosis of thethalassemias (hereditary hemolyticanemias characterized by decreasedsynthesis of one or more types of he-moglobin polypeptide chains).


[45 FR 60617, Sept. 12, 1980]

§ 864.7415 Abnormal hemoglobin assay.

(a) Identification. An abnormal hemo-globin assay is a device consisting ofthe reagents, apparatus, instrumenta-tion, and controls necessary to isolateand identify abnormal genetically de-termined hemoglobin types.


[45 FR 60618, Sept. 12, 1980]

§ 864.7425 Carboxyhemoglobin assay.

(a) Identification. A carboxy-hemoglobin assay is a device used todetermine the carboxyhemoglobin (thecompound formed when hemoglobin isexposed to carbon monoxide) content ofhuman blood as an aid in the diagnosisof carbon monoxide poisoning. Thismeasurement may be made usingmethods such as spectroscopy, colorim-etry, spectrophotometry, andgasometry.


[45 FR 60619, Sept. 12, 1980]


223


§ 864.7440 Electrophoretic hemoglobinanalysis system.

(a) Identification. An electrophoretichemoglobin analysis system is a devicethat electrophoretically separates andidentifies normal and abnormal hemo-globin types as an aid in the diagnosisof anemia or erythrocytosis (increasedtotal red cell mass) due to a hemo-globin abnormality.


[45 FR 60620, Sept. 12, 1980]

§ 864.7455 Fetal hemoglobin assay.

(a) Identification. A fetal hemoglobinassay is a device that is used to deter-mine the presence and distribution offetal hemoglobin (hemoglobin F) in redcells or to measure the amount of fetalhemoglobin present. The assay may beused to detect fetal red cells in the ma-ternal circulation or to detect the ele-vated levels of fetal hemoglobin exhib-ited in cases of hemoglobin abnormali-ties such as thalassemia (a hereditaryhemolytic anemia characterized by adecreased synthesis of one or moretypes of hemoglobin polypeptidechains). The hemoglobin determinationmay be made by methods such as elec-trophoresis, alkali denaturation, col-umn chromatography, or radialimmunodiffusion.


[45 FR 60620, Sept. 12, 1980]

§ 864.7470 Glycosylated hemoglobinassay.

(a) Identification. A glycosylated he-moglobin assay is a device used tomeasure the glycosylated hemoglobins(A1a, A1b, and A1c) in a patient’s bloodby a column chromatographic proce-dure. Measurement of glycosylated he-moglobin is used to assess the level ofcontrol of a patient’s diabetes and todetermine the proper insulin dosage fora patient. Elevated levels ofglycosylated hemoglobin indicate un-controlled diabetes in a patient.


[45 FR 60621, Sept. 12, 1980]

§ 864.7490 Sulfhemoglobin assay.(a) Identification. A sulfhemoglobin

assay is a device consisting of the re-agents, calibrators, controls, and in-strumentation used to determine thesulfhemoglobin (a compound of sulfurand hemoglobin) content of humanblood as an aid in the diagnosis ofsulfhemoglobinemia (presence ofsulfhemoglobin in the blood due todrug administration or exposure to apoison). This measurement may bemade using methods such as spectros-copy, colorimetry, spectrophotometry,or gasometry.


[45 FR 60621, Sept. 12, 1980]

§ 864.7500 Whole blood hemoglobin as-says.

(a) Identification. A whole blood he-moglobin assay is a device consistingor reagents, calibrators, controls, orphotometric or spectrophotometric in-strumentation used to measure the he-moglobin content of whole blood forthe detection of anemia. This genericdevice category does not include auto-mated hemoglobin systems.


[45 FR 60622, Sept. 12, 1980]

§ 864.7525 Heparin assay.(a) Identification. A heparin assay is a

device used to determine the level ofthe anticoagulant heparin in the pa-tient’s circulation. These assays arequantitative clotting time proceduresusing the effect of heparin on activatedcoagulation factor X (Stuart factor) orprocedures based on the neutralizationof heparin by protamine sulfate (a pro-tein that neutralizes heparin).


[45 FR 60623, Sept. 12, 1980]

§ 864.7660 Leukocyte alkaline phos-phatase test.

(a) Identification. A leukocyte alka-line phosphatase test is a device usedto identify the enzyme leukocyte alka-line phosphatase in neutrophilicgranulocytes (granular leukocytesstainable by neutral dyes). The


224

21 CFR Ch. I (4–1–00 Edition)§ 864.7675

cytochemical identification of alkalinephosphatase depends on the formationof blue granules in cells containing al-kaline phosphatase. The results of thistest are used to differentiate chronicgranulocytic leukemia (a malignantdisease characterized by excessiveovergrowth of granulocytes in the bonemarrow) and reactions that resembletrue leukemia, such as those occuringin severe infections and polycythemia(increased total red cell mass).



§ 864.7675 Leukocyte peroxidase test.(a) Identification. A leukocyte peroxi-

dase test is a device used to distinguishcertain myeloid cells derived from thebone marrow, i.e., neutrophils,eosinophils, and monocytes, fromlymphoid cells of the lymphatic systemand erythroid cells of the red blood cellseries on the basis of their peroxidaseactivity as evidenced by staining. Theresults of this test are used in the dif-ferential diagnosis of the leukemias.



§ 864.7695 Platelet factor 4radioimmunoassay.

(a) Identification. A platelet factor 4radioimmunoassay is a device used tomeasure the level of platelet factor 4, aprotein released during platelet activa-tion by radioimmunoassay. This devicemeasures platelet activiation, whichmay indicate a coagulation disorder,such as myocardial infarction or coro-nary artery disease.


[45 FR 60625, Sept. 12, 1980; 46 FR 14890, Mar.3, 1981]

§ 864.7720 Prothrombin consumptiontest.

(a) Identification. A prothrombin con-sumption tests is a device that meas-

ures the patient’s capacity to generatethromboplastin in the coagulationprocess. The test also is an indirect in-dicator of qualitative or quantitativeplatelet abnormalities. It is a screen-ing test for thrombocytopenia (de-creased number of blood platelets) andhemophilia A and B.


[45 FR 60625, Sept. 12, 1980]

§ 864.7735 Prothrombin-proconvertintest and thrombotest.

(a) Identification. The prothrombin-proconvertin test and thrombotest aredevices used in the regulation of cou-marin therapy (administration of acoumarin anticoagulant such as so-dium warfarin in the treatment of ve-nous thrombosis and pulmonary embo-lism) and as a diagnostic test in con-junction with, or in place of, the Quickprothrombin time test to detect coagu-lation disorders.


[45 FR 60626, Sept. 12, 1980]

§ 864.7750 Prothrombin time test.

(a) Identification. A prothrombin timetest is a device used as a generalscreening procedure for the detectionof possible clotting factor deficienciesin the extrinsic coagulation pathway,which involves the reaction betweencoagulation factors III and VII, and tomonitor patients receiving coumarintherapy (the administration of one ofthe coumarin anticoagulants in thetreatment of venous thrombosis or pul-monary embolism).


[45 FR 60626, Sept. 12, 1980]

§ 864.7825 Sickle cell test.

(a) Identification. A sickle cell test isa device used to determine the sicklecell hemoglobin content of humanblood to detect sickle cell trait or sick-le cell diseases.


[45 FR 60627, Sept. 12, 1980]


225


§ 864.7875 Thrombin time test.

(a) Identification. A thrombin timetest is a device used to measurefibrinogen concentration and detectfibrin or fibrinogen split products forthe evaluation of bleeding disorders.


[45 FR 60628, Sept. 12, 1980]

§ 864.7900 Thromboplastin generationtest.

(a) Identification. A thromboplastingeneration test is a device used to de-tect and identify coagulation factor de-ficiencies and coagulation inhibitors.



§ 864.7925 Partial thromboplastin timetests.

(a) Identification. A partial thrombo-plastin time test is a device used forprimary screening for coagulation ab-normalities, for evaluation of the ef-fect of therapy on procoagulant dis-orders, and as an assay for coagulationfactor deficiencies of the intrinsic co-agulation pathway.


[45 FR 60629, Sept. 12, 1980]

Subpart I—Hematology Reagents

§ 864.8100 Bothrops atrox reagent.(a) Identification. A Bothrops atrox

reagent is a device made from snakevenom and used to determine bloodfibrinogen levels to aid in the evalua-tion of disseminated intravascular co-agulation (nonlocalized clotting in theblood vessels) in patients receivingheparin therapy (the administration ofthe anticoagulant heparin in the treat-ment of thrombosis) or as an aid in theclassification of dysfibrinogenemia(presence in the plasma of functionallydefective fibrinogen).


[45 FR 60629, Sept. 12, 1980]

§ 864.8150 Calibrator for cell indices.(a) Identification. A calibrator for cell

indices is a device that approximateswhole blood or certain blood cells andthat is used to set an instrument in-tended to measure mean cell volume(MCV), mean corpuscular hemoglobin(MCH), and mean corpuscular hemo-globin concentration (MCHC), or othercell indices. It is a suspension of par-ticles or cells whose size, shape, con-centration, and other characteristicshave been precisely and accurately de-termined.


[45 FR 60631, Sept. 12, 1980]

§ 864.8165 Calibrator for hemoglobinor hematocrit measurement.

(a) Identification. A calibrator for he-moglobin or hematocrit measurementis a device that approximates wholeblood, red blood cells, or a hemoglobinderivative and that is used to set in-struments intended to measure hemo-globin, the hematocrit, or both. It is amaterial whose characteristics havebeen precisely and accurately deter-mined.


[45 FR 60632, Sept. 12, 1980]

§ 864.8175 Calibrator for plateletcounting.

(a) Identification. A calibrator forplatelet counting is a device that re-sembles platelets in plasma or wholeblood and that is used to set a plateletcounting instrument. It is a suspensionof particles or cells whose size, shapeconcentration, and other characteris-tics have been precisely and accuratelydetermined.


[45 FR 60633, Sept. 12, 1980]

§ 864.8185 Calibrator for red cell andwhite cell counting.

(a) Identification. A calibrator for redcell and white cell counting is a devicethat resembles red or white blood cellsand that is used to set instruments in-tended to count red cells, white cells,or both. It is a suspension of particles


226

21 CFR Ch. I (4–1–00 Edition)§ 864.8200

or cells whose size, shape, concentra-tion, and other characteristics havebeen precisely and accurately deter-mined.


[45 FR 60634, Sept. 12, 1980]

§ 864.8200 Blood cell diluent.(a) Identification. A blood cell diluent

is a device used to dilute blood for fur-ther testing, such as blood cell count-ing.



§ 864.8500 Lymphocyte separation me-dium.

(a) Identification. A lymphocyte sepa-ration medium is a device used to iso-late lymphocytes from whole blood.



§ 864.8540 Red cell lysing reagent.(a) Identification. A red cell lysing re-

agent is a device used to lyse (destroy)red blood cells for hemoglobin deter-minations or aid in the counting ofwhite blood cells.



§ 864.8625 Hematology quality controlmixture.

(a) Identification. A hematology qual-ity control mixture is a device used toascertain the accuracy and precision ofmanual, semiautomated, and auto-mated determinations of cell param-eters such as white cell count (WBC),red cell count (RBC), platelet count(PLT), hemoglobin, hematocrit (HCT),mean corpuscular volume (MCV), meancorpuscular hemoglobin (MCH), and

mean corpuscular hemoglobin con-centration (MCHC).


[45 FR 60637, Sept. 12, 1980]

§ 864.8950 Russell viper venom rea-gent.

(a) Identification. Russell viper venomreagent is a device used to determinethe cause of an increase in the pro-thrombin time.

(b) Classification. Class I (general con-trols).

[45 FR 60637, Sept. 12, 1980]

Subpart J—Products Used In Es-tablishments That Manufac-ture Blood and Blood Products

§ 864.9050 Blood bank supplies.

(a) Identification. Blood bank suppliesare general purpose devices intendedfor in vitro use in blood banking. Thisgeneric type of device includes prod-ucts such as blood bank pipettes, bloodgrouping slides, blood typing tubes,blood typing racks, and cold packs forantisera reagents. The device does notinclude articles that are licensed bythe Center for Biologics Evaluationand Research of the Food and Drug Ad-ministration.

(b) Classification. Class I (general con-trols).

[45 FR 60638, Sept. 12, 1980, as amended at 53FR 11253, Apr. 6, 1988]

§ 864.9100 Empty container for the col-lection and processing of blood andblood components.

(a) Identification. An empty containerfor the collection and processing ofblood and blood components is a deviceintended for medical purposes that isan empty plastic bag or plastic or glassbottle used to collect, store, or transferblood and blood components for furtherprocessing.


[45 FR 60638, Sept. 12, 1980]


227


§ 864.9125 Vacuum-assisted blood col-lection system.

(a) Identification. A vacuum-assistedblood collection system is a device in-tended for medical purposes that uses avacuum to draw blood for subsequentreinfusion.

(b) Classification. Class I (general con-trols). The manual device is exemptfrom the premarket notification proce-dures in subpart E of part 807 of thischapter subject to § 864.9.


§ 864.9145 Processing system for fro-zen blood.

(a) Identification. A processing systemfor frozen blood is a device used toglycerolize red blood cells prior tofreezing to minimize hemolysis (disrup-tion of the red cell membrane accom-panied by the release of hemoglobin)due to freezing and thawing of redblood cells and to deglycerolize andwash thawed cells for subsequent re-infusion.


[45 FR 60639, Sept. 12, 1980]

§ 864.9160 Blood group substances ofnonhuman origin for in vitro diag-nostic use.

(a) Identification. Blood group sub-stances of nonhuman origin for in vitrodiagnostic use are materials, such asblood group specific substances pre-pared from nonhuman sources (e.g.,pigs, cows, and horses) used to detect,identify, or neutralize antibodies tovarious human blood group antigens.This generic type of device does not in-clude materials that are licensed bythe Center for Biologics Evaluationand Research of the Food and Drug Ad-ministration.


[45 FR 60640, Sept. 12, 1980, as amended at 53FR 11253, Apr. 6, 1988; 63 FR 59225, Nov. 3,1998]

§ 864.9175 Automated blood groupingand antibody test system.

(a) Identification. An automated bloodgrouping and antibody test system is adevice used to group erythrocytes (redblood cells) and to detect antibodies toblood group antigens.


[45 FR 60641, Sept. 12, 1980]

§ 864.9185 Blood grouping view box.(a) Identification. A blood grouping

view box is a device with a glass orplastic viewing surface, which may beilluminated and heated, that is used toview cell reactions in antigen-antibodytesting.



§ 864.9195 Blood mixing devices andblood weighing devices.

(a) Identification. A blood mixing de-vice is a device intended for medicalpurposes that is used to mix blood orblood components by agitation. Ablood weighing device is a device in-tended for medical purposes that isused to weigh blood or blood compo-nents as they are collected.

(b) Classification. Class I (general con-trols). The manual device is exemptfrom the premarket notification proce-dures in subpart E of part 807 of thischapter subject to § 864.9.


§ 864.9205 Blood and plasma warmingdevice.

(a) Nonelectromagnetic blood or plasmawarming device—(1) Identification. Anonelectromagnetic blood and plasmawarming device is a device that warmsblood or plasma, by means other thanelectromagnetic radiation, prior to ad-ministration.

(2) Classification. Class II (perform-ance standards).

(b) Electromagnetic blood and plasmawarming device—(1) Identification. Anelectromagnetic blood and plasma


228

21 CFR Ch. I (4–1–00 Edition)§ 864.9225

warming device is a device that em-ploys electromagnetic radiation(radiowaves or microwaves) to warm abag or bottle of blood or plasma priorto administration.

(2) Classfication. Class III (premarketapproval).

(c) Date PMA or notice of completion ofa PDP is required. No effective date hasbeen established of the requirement forpremarket approval for the device de-scribed in paragraph (b)(1). See § 864.3.

[45 FR 60642, Sept. 12, 1980, as amended at 52FR 17733, May 11, 1987]

§ 864.9225 Cell-freezing apparatus andreagents for in vitro diagnostic use.

(a) Identification. Cell-freezing appa-ratus and reagents for in vitro diag-nostic use are devices used to freezehuman red blood cells for in vitro diag-nostic use.



§ 864.9245 Automated blood cell sepa-rator.

(a) Identification. An automated bloodcell separator is a device that auto-matically removes whole blood from adonor, separates the blood into compo-nents (red blood cells, white bloodcells, plasma, and platelets), retainsone or more of the components, and re-turns the remainder of the blood to thedonor. The components obtained aretransfused or used to prepare bloodproducts for administration. These de-vices operate on either a centrifugalseparation principle or a filtrationprinciple. The separation bowls of cen-trifugal blood cell separators may bereusable or disposable.

(b) Classification. Class III (premarketapproval).

(c) Date PMA or notice of completion ofa PDP is required. No effective date hasbeen established of the requirement forpremarket approval. See § 864.3.

[45 FR 60645, Sept. 12, 1980, as amended at 52FR 17733, May 11, 1987]

§ 864.9275 Blood bank centrifuge for invitro diagnostic use.

(a) Identification. A blood bank cen-trifuge for in vitro diagnostic use is adevice used only to separate blood cellsfor further diagnostic testing.



§ 864.9285 Automated cell-washingcentrifuge for immuno-hematology.

(a) Identification. An automated cell-washing centrifuge for immuno-hema-tology is a device used to separate andprepare cells and sera for further invitro diagnostic testing.


[45 FR 60646, Sept. 12, 1980]

§ 864.9300 Automated Coombs test sys-tems.

(a) Identification. An automatedCoombs test system is a device used todetect and identify antibodies in pa-tient sera or antibodies bound to redcells. The Coombs test is used for thediagnosis of hemolytic disease of thenewborn, and autoimmune hemolyticanemia. The test is also used incrossmatching and in investigatingtransfusion reactions and drug-inducedred cell sensitization.


[45 FR 60646, Sept. 12, 1980]

§ 864.9320 Copper sulfate solution forspecific gravity determinations.

(a) Identification. A copper sulfate so-lution for specific gravity determina-tions is a device used to determinewhether the hemoglobin content of apotential donor’s blood meets the re-quired level (12.5 grams per 100 milli-liters of blood for women and 13.5grams per 100 milliliters of blood formen).

(b) Classification. Class I (general con-trols). The device is exempt from thepremarket notification procedures in


229


subpart E of part 807 of this chaptersubject to § 864.9.


§ 864.9400 Stabilized enzyme solution.(a) Identification. A stabilized enzyme

solution is a reagent intended for med-ical purposes that is used to enhancethe reactivity of red blood cells withcertain antibodies, including anti-bodies that are not detectable by othertechniques. These enzyme solutions in-clude papain, bromelin, ficin, andtrypsin.


[45 FR 60647, Sept. 12, 1980]

§ 864.9550 Lectins and protectins.(a) Identification. Lectins and

protectins are proteins derived fromplants and lower animals that causecell agglutination in the presence ofcertain antigens. These substances areused to detect blood group antigens forin vitro diagnostic purposes.



§ 864.9575 Environmental chamber forstorage of platelet concentrate.

(a) Identification. An environmentalchamber for storage of platelet con-centrate is a device used to hold plate-let-rich plasma within a preselectedtemperature range.



§ 864.9600 Potentiating media for invitro diagnostic use.

(a) Identification. Potentiating mediafor in vitro diagnostic use are media,such as bovine albumin, that are usedto suspend red cells and to enhance cellreactions for antigen-antibody testing.



§ 864.9650 Quality control kit for bloodbanking reagents.

(a) Identification. A quality controlkit for blood banking reagents is a de-vice that consists of sera, cells, buffers,and antibodies used to determine thespecificity, potency, and reactivity ofthe cells and reagents used for bloodbanking.


[45 FR 60649, Sept. 12, 1980]

§ 864.9700 Blood storage refrigeratorand blood storage freezer.

(a) Identification. A blood storage re-frigerator and a blood storage freezerare devices intended for medical pur-poses that are used to preserve bloodand blood products by storing them atcold or freezing temperatures.



§ 864.9750 Heat-sealing device.(a) Identification. A heat-sealing de-

vice is a device intended for medicalpurposes that uses heat to seal plasticbags containing blood or blood compo-nents.



§ 864.9875 Transfer set.(a) Identification. A transfer set is a

device intended for medical purposesthat consists of a piece of tubing withsuitable adaptors used to transferblood or plasma from one container toanother.


230

21 CFR Ch. I (4–1–00 Edition)Pt. 866


[45 FR 60651, Sept. 12, 1980]

PART 866—IMMUNOLOGY ANDMICROBIOLOGY DEVICES


Sec.866.1 Scope.866.3 Effective dates of requirement for pre-

market approval.866.9 Limitations of exemptions from sec-

tion 510(k) of the Federal Food, Drug,and Cosmetic Act (the act).

Subpart B—Diagnostic Devices

866.1620 Antimicrobial susceptibility testdisc.

866.1640 Antimicrobial susceptibility testpowder.

866.1700 Culture medium for antimicrobialsusceptibility tests.

Subpart C—Microbiology Devices

866.2050 Staphylococcal typingbacteriophage.

866.2120 Anaerobic chamber.866.2160 Coagulase plasma.866.2170 Automated colony counter.866.2180 Manual colony counter.866.2300 Multipurpose culture medium.866.2320 Differential culture medium.866.2330 Enriched culture medium.866.2350 Microbiological assay culture me-

dium.866.2360 Selective culture medium.866.2390 Transport culture medium.866.2410 Culture medium for pathogenic

Neisseria spp.866.2420 Oxidase screening test for gonor-

rhea.866.2440 Automated medium dispensing and

stacking device.866.2450 Supplement for culture media.866.2480 Quality control kit for culture

media.866.2500 Microtiter diluting and dispensing

device.866.2540 Microbiological incubator.866.2560 Microbial growth monitor.866.2580 Gas-generating device.866.2600 Wood’s fluorescent lamp.866.2660 Microorganism differentiation and

identification device.866.2850 Automated zone reader.866.2900 Microbiological specimen collection

and transport device.

Subpart D—Serological Reagents

866.3010 Acinetobacter calcoaceticus sero-logical reagents.

866.3020 Adenovirus serological reagents.866.3035 Arizona spp. serological reagents.866.3040 Aspergillus spp. serological reagents.866.3060 Blastomyces dermatitidis serological

reagents.866.3065 Bordetella spp. serological reagents.866.3085 Brucella spp. serological reagents.866.3110 Campylobacter fetus serological re-

agents.866.3120 Chlamydia serological reagents.866.3125 Citrobacter spp. serological reagents.866.3135 Coccidioides immitis serological re-

agents.866.3140 Corynebacterium spp. serological re-

agents.866.3145 Coxsackievirus serological re-

agents.866.3165 Cryptococcus neoformans serological

reagents.866.3175 Cytomegalovirus serological re-

agents.866.3200 Echinococcus spp. serological re-

agents.866.3205 Echovirus serological reagents.866.3220 Entamoeba histolytica serological re-

agents.866.3235 Epstein-Barr virus serological re-

agents.866.3240 Equine encephalomyelitis virus se-

rological reagents.866.3250 Erysipelothrix rhusiopathiae sero-

logical reagents.866.3255 Escherichia coli serological reagents.866.3270 Flavobacterium spp. serological re-

agents.866.3280 Francisella tularensis serological re-

agents.866.3290 Gonococcal antibody test (GAT).866.3300 Haemophilus spp. serological re-

agents.866.3305 Herpes simplex virus serological re-

agents.866.3320 Histoplasma capsulatum serological

reagents.866.3330 Influenza virus serological re-

agents.866.3340 Klebsiella spp. serological reagents.866.3350 Leptospira spp. serological reagents.866.3355 Listeria spp. serological reagents.866.3360 Lymphocytic choriomeningitis

virus serological reagents.866.3370 Mycobacterium tuberculosis

immunofluorescent reagents.866.3375 Mycoplasma spp. serological re-

agents.866.3380 Mumps virus serological reagents.866.3390 Neisseria spp. direct serological test

reagents.866.3400 Parainfluenza virus serological re-

agents.866.3405 Poliovirus serological reagents.866.3410 Proteus spp. (Weil-Felix) serological

reagents.866.3415 Pseudomonas spp. serological re-

agents.866.3460 Rabiesvirus immunofluorescent re-

agents.
