IMMUNOLOGY AND MICROBIOLOGY DEVICES

• Citation: 21 CFR Part 866
• Sections: 252

§ 866.1 Scope.

(a) This part sets forth the classification of immunology and microbiology devices intended for human use that are in commercial distribution.

(b) The indentification of a device in a regulation in this part is not a precise description of every device that is, or will be, subject to the regulation. A manufacturer who submits a premarket notification submission for a device under part 807 may not show merely that the device is accurately described by the section title and identification provisions of a regulation in this part, but shall state why the device is substantially equivalent to other devices, as required by § 807.87.

(c) To avoid duplicative listings, an immunology and microbiology device that has two or more types of uses (e.g., used both as a diagnostic device and as a microbiology device) is listed only in one subpart.

(d) References in this part to regulatory sections of the Code of Federal Regulations are to chapter I of title 21, unless otherwise noted.

(e) Guidance documents referenced in this part are available on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm.

§ 866.3 Effective dates of requirement for premarket approval.

A device included in this part that is classified into class III (Premarket approval) shall not be commercially distributed after the date shown in the regulation classifying the device unless the manufacturer has an approval under section 515 of the act (unless an exemption has been granted under section 520(g)(2) of the act). An approval under section 515 of the act consists of FDA's issuance of an order approving an application for premarket approval (PMA) for the device or declaring completed a product development protocol (PDP) for the device.

(a) Before FDA requires that a device commercially distributed before the enactment date of the amendments, or a device that has been found substantially equivalent to such a device, has an approval under section 515 of the act FDA must promulgate a regulation under section 515(b) of the act requiring such approval, except as provided in paragraphs (b) and (c) of this section. Such a regulation under section 515(b) of the act shall not be effective during the grace period ending on the 90th day after its promulgation or on the last day of the 30th full calendar month after the regulation that classifies the device into class III is effective, whichever is later. See section 501(f)(2)(B) of the act. Accordingly, unless an effective date of the requirement for premarket approval is shown in the regulation for a device classified into class III in this part, the device may be commercially distributed without FDA's issuance of an order approving a PMA or declaring completed a PDP for the device. If FDA promulgates a regulation under section 515(b) of the act requiring premarket approval for a device, section 501(f)(1)(A) of the act applies to the device.

(b) Any new, not substantially equivalent, device introduced into commercial distribution on or after May 28, 1976, including a device formerly marketed that has been substantially altered, is classified by statute (section 513(f) of the act) into class III without any grace period and FDA must have issued an order approving a PMA or declaring completed a PDP for the device before the device is commercially distributed unless it is reclassified. If FDA knows that a device being commercially distributed may be a “new” device as defined in this section because of any new intended use or other reasons, FDA may codify the statutory classification of the device into class III for such new use. Accordingly, the regulation for such a class III device states that as of the enactment date of the amendments, May 28, 1976, the device must have an approval under section 515 of the act before commercial distribution.

(c) A device identified in a regulation in this part that is classified into class III and that is subject to the transitional provisions of section 520(l) of the act is automatically classified by statute into class III and must have an approval under section 515 of the act before being commercially distributed. Accordingly, the regulation for such a class III transitional device states that as of the enactment date of the amendments, May 28, 1976, the device must have an approval under section 515 of the act before commercial distribution.

§ 866.9 Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

The exemption from the requirement of premarket notification (section 510(k) of the act) for a generic type of class I or II device is only to the extent that the device has existing or reasonably foreseeable characteristics of commercially distributed devices within that generic type or, in the case of in vitro diagnostic devices, only to the extent that misdiagnosis as a result of using the device would not be associated with high morbidity or mortality. Accordingly, manufacturers of any commercially distributed class I or II device for which FDA has granted an exemption from the requirement of premarket notification must still submit a premarket notification to FDA before introducing or delivering for introduction into interstate commerce for commercial distribution the device when:

(a) The device is intended for a use different from the intended use of a legally marketed device in that generic type of device; e.g., the device is intended for a different medical purpose, or the device is intended for lay use where the former intended use was by health care professionals only;

(b) The modified device operates using a different fundamental scientific technology than a legally marketed device in that generic type of device; e.g., a surgical instrument cuts tissue with a laser beam rather than with a sharpened metal blade, or an in vitro diagnostic device detects or identifies infectious agents by using deoxyribonucleic acid (DNA) probe or nucleic acid hybridization technology rather than culture or immunoassay technology; or

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

(1) For use in the diagnosis, monitoring, or screening of neoplastic diseases with the exception of immunohistochemical devices;

(2) For use in screening or diagnosis of familial or acquired genetic disorders, including inborn errors of metabolism;

(3) For measuring an analyte that serves as a surrogate marker for screening, diagnosis, or monitoring life-threatening diseases such as acquired immune deficiency syndrome (AIDS), chronic or active hepatitis, tuberculosis, or myocardial infarction or to monitor therapy;

(4) For assessing the risk of cardiovascular diseases;

(5) For use in diabetes management;

(6) For identifying or inferring the identity of a microorganism directly from clinical material;

(7) For detection of antibodies to microorganisms other than immunoglobulin G (IgG) or IgG assays when the results are not qualitative, or are used to determine immunity, or the assay is intended for use in matrices other than serum or plasma;

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

(9) For near patient testing (point of care).

§ 866.1620 Antimicrobial susceptibility test disc.

(a) Identification. An antimicrobial susceptibility test disc is a device that consists of antimicrobic-impregnated paper discs used to measure by a disc-agar diffusion technique or a disc-broth elution technique the in vitro susceptibility of most clinically important bacterial pathogens to antimicrobial agents. In the disc-agar diffusion technique, bacterial susceptibility is ascertained by directly measuring the magnitude of a zone of bacterial inhibition around the disc on an agar surface. The disc-broth elution technique is associated with an automated rapid susceptibility test system and employs a fluid medium in which susceptibility is ascertained by photometrically measuring changes in bacterial growth resulting when antimicrobial material is eluted from the disc into the fluid medium. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.

(b) Classification. Class II (performance standards).

§ 866.1640 Antimicrobial susceptibility test powder.

(a) Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.

(b) Classification. Class II (performance standards).

§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.

(a) Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.

(b) Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”

§ 866.1650 A cellular analysis system for multiplexed antimicrobial susceptibility testing.

(a) Identification. A cellular analysis system for multiplexed antimicrobial susceptibility testing is a multiplex qualitative and/or quantitative in vitro diagnostic device intended for the identification and determination of the antimicrobial susceptibility results of organisms detected in samples from patients with suspected microbial infections. This device is intended to aid in the determination of antimicrobial susceptibility or resistance when used in conjunction with other laboratory findings.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) Design verification and validation must include:

(i) Detailed device description documentation, including the device components, ancillary reagents required but not provided, a detailed explanation of the methodology, including primer/probe sequence, design, rationale for sequence selection, and details of the antimicrobial agents, as applicable.

(ii) Detailed documentation from the following analytical and clinical performance studies: limit of detection, inclusivity, precision, reproducibility, interference, cross-reactivity, carryover, and cross-contamination, quality control and additional studies, as applicable to specimen type and assay intended use.

(iii) Detailed documentation from an appropriate clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods.

(iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) Limitations and protocols regarding the need for correlation of results by standard laboratory procedures, as applicable.

(ii) A detailed explanation of the interpretation of results and acceptance criteria.

(iii) A detailed explanation of the principles of operation and procedures for assay performance and troubleshooting.

§ 866.1655 System for detection of microorganisms and antimicrobial resistance using reporter expression.

(a) Identification. A system for detection of microorganisms and antimicrobial resistance using reporter expression is an in vitro diagnostic device intended for the detection and identification of live microorganisms and the detection of associated antimicrobial drug susceptibility or resistance in specimens from patients at risk of colonization or suspected of infection.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) The intended use for the device in the labeling required under § 809.10 of this chapter must include a detailed description of the targets the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.

(2) Any device used for specimen collection and transport must be FDA-cleared, approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of the specimen types claimed by this device and for the maintenance of viability of the targeted microorganisms; alternatively, the specimen collection device must be cleared in a premarket submission as a part of this device.

(3) The labeling required under § 809.10(b) of this chapter must include:

(i) A detailed description of the device, including reagents, instruments, ancillary materials, applicable specimen collection and transport device(s) and control elements, and a detailed explanation of the methodology, including all pre-analytical methods for handling and processing of specimens and controls to maintain organism viability;

(ii) Detailed descriptions of the test procedure, including the preparation and maintenance of quality controls and the interpretation of test results;

(iii) Detailed discussion of the performance characteristics of the device for all claimed organisms and specimen types based on analytical studies, including evaluation of analytical sensitivity, inclusivity, cross-reactivity, potentially interfering substances and microorganisms, contamination, specimen stability, precision, and reproducibility;

(iv) Detailed discussion of the performance characteristics of the device observed in a clinical study performed on a population that is consistent with the intended use population in comparison to the results obtained by a reference or comparator method determined to be acceptable by FDA, for microbial detection, identification, and antimicrobial susceptibility testing; and

(v) A limiting statement indicating that a negative test result does not preclude colonization or infection with organisms that do not express detectable levels of the reporter that is identified by the device.

(4) Design verification and validation must include:

(i) A detailed description of the device, including an explanation of the technology, hardware, software, and consumables, as well as an explanation of the result algorithms and method(s) of data processing from signal acquisition to result assignment;

(ii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions;

(iii) Detailed documentation of the analytical and clinical studies required in paragraphs (b)(3)(iii) and (iv) of this section, including the study protocols containing descriptions of the test methods, prescribed methods of data analysis and acceptance criteria, final study reports, and data line listings;

(iv) Detailed documentation of quality control procedures, including an explanation of how quality control materials were selected, the recommended frequency of testing, methods of control preparation, acceptance criteria for performance and the results from quality control testing performed during the analytical and clinical studies required under paragraphs (b)(3)(iii) and (iv) of this section;

(v) Detailed documentation of studies performed to establish onboard and in-use reagent stability, including the test method(s), data analysis plans, acceptance criteria, final study reports, and data line listings;

(vi) Detailed documentation of studies to establish reagent shelf-life for the assay kit and each applicable specimen collection and transport device, including study protocols containing descriptions of the test method(s), data analysis plans, and acceptance criteria; and

(vii) Documentation of an appropriate end user device training program that will be offered as part of efforts to assure appropriate conduct of the assay and to mitigate the risk associated with false results, including failure to use the device correctly or correctly interpret results.

§ 866.1700 Culture medium for antimicrobial susceptibility tests.

(a) Identification. A culture medium for antimicrobial susceptibility tests is a device intended for medical purposes that consists of any medium capable of supporting the growth of many of the bacterial pathogens that are subject to antimicrobial susceptibility tests. The medium should be free of components known to be antagonistic to the common agents for which susceptibility tests are performed in the treatment of disease.

(b) Classification. Class II (performance standards).

§ 866.2050 Staphylococcal typing bacteriophage.

(a) Identification. A staphylococcal typing bacteriophage is a device consisting of a bacterial virus intended for medical purposes to identify pathogenic staphylococcal bacteria through use of the bacteria's susceptibility to destruction by the virus. Test results are used principally for the collection of epidemiological information.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2120 Anaerobic chamber.

(a) Identification. An anaerobic chamber is a device intended for medical purposes to maintain an anaerobic (oxygen free) environment. It is used to isolate and cultivate anaerobic microorganisms.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9. The device is also exempt from the good manufacturing practice requirements of the quality management system regulation in part 820 of this chapter, except for requirements concerning records and complaint files under § 820.35 of this chapter.

§ 866.2160 Coagulase plasma.

(a) Identification. Coagulase plasma is a device that consists of freeze-dried animal or human plasma that is intended for medical purposes to perform coagulase tests primarily on staphylococcal bacteria. When reconstituted, the fluid plasma is clotted by the action of the enzyme coagulase which is produced by pathogenic staphylococci. Test results are used primarily as an aid in the diagnosis of disease caused by pathogenic bacteria belonging to the genus Staphylococcus and provide epidemiological information on disease caused by these microorganisms.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2170 Automated colony counter.

(a) Identification. An automated colony counter is a mechanical device intended for medical purposes to determine the number of bacterial colonies present on a bacteriological culture medium contained in a petri plate. The number of colonies counted is used in the diagnosis of disease as a measure of the degree of bacterial infection.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2180 Manual colony counter.

(a) Identification. A manual colony counter is a device intended for medical purposes that consists of a printed grid system superimposed on an illuminated screen. Petri plates containing bacterial colonies to be counted are placed on the screen for better viewing and ease of counting. The number of colonies counted is used in the diagnosis of disease as a measure of the degree of bacterial infection.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9. The device is also exempt from the good manufacturing practice requirements of the quality management system regulation in part 820 of this chapter, except for requirements concerning records and complaint files under § 820.35 of this chapter.

§ 866.2190 Automated image assessment system for microbial colonies on solid culture media.

(a) Identification. An automated image assessment system for microbial colonies on solid culture media is a system that is intended to assess the presence or absence of microbial colonies on solid microbiological culture medium, and to interpret their number, and phenotypic and morphologic characteristics through analysis of two dimensional digital images as an aid in diagnosis of infectious disease.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) Premarket notification submissions must include a detailed description of the device, including the technology employed, components and software modules, as well as a detailed explanation of the result algorithms and any expert rules that are used to assess colony characteristics and enumerate colonies from image capture through end result.

(2) Premarket notification submissions must include detailed documentation of the analytical studies performed to characterize device performance to support the intended use, as appropriate.

(3) Premarket notification submissions must include detailed documentation from clinical studies performed on a population that is consistent with the intended use population.

(i) The clinical studies must establish the device performance based on comparison to results obtained by an acceptable reference method, as appropriate.

(ii) The clinical study documentation must include the study protocol with a predefined statistical analysis plan and the final report documenting support for the Indications for Use and the results of the statistical analysis, as appropriate.

(4) Premarket notification submissions must include detailed documentation for device software, including but not limited to software applications and hardware based components that incorporate software, and any decision-making thresholds used to generate results for the device. If a part of a Total Laboratory Automation System, the premarket notification submission must include detailed documentation addressing the instrument and software system integration.

(5) Premarket notification submissions must include detailed documentation of appropriate instructions for use regarding the intended user's device quality control procedures for the instrument system and components, as appropriate.

(6) The 21 CFR 809.10 compliant device labeling must include:

(i) Detailed user instructions to mitigate the risk of failure to operate the instrument correctly.

(ii) A detailed explanation of the interpretation of results and limitations regarding the need for review of culture plates by a qualified microbiologist, as appropriate.

(iii) A summary of performance data obtained from the analytical studies used to support device performance, as appropriate.

(iv) A summary of performance data obtained from clinical studies performed on a population that is consistent with the intended use population, as appropriate.

(7) Under 21 CFR 820.10(c) design and development, device manufacturers must, as appropriate:

(i) Conduct human factors/usability validation testing with the final version of the labeling and related materials to adequately mitigate the risk of failure to operate the instrument correctly.

(ii) Document a device training program that will be offered to the end user to adequately mitigate the risk of failure to operate the instrument correctly.

§ 866.2300 Multipurpose culture medium.

(a) Identification. A multipurpose culture medium is a device that consists primarily of liquid or solid biological materials intended for medical purposes for the cultivation and identification of several types of pathogenic microorganisms without the need of additional nutritional supplements. Test results aid in the diagnosis of disease and also provide epidemiological information on diseases caused by these microorganisms.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2320 Differential culture medium.

(a) Identification. A differential culture medium is a device that consists primarily of liquid biological materials intended for medical purposes to cultivate and identify different types of pathogenic microorganisms. The identification of these microorganisms is accomplished by the addition of a specific biochemical component(s) to the medium. Microorganisms are identified by a visible change (e.g., a color change) in a specific biochemical component(s) which indicates that specific metabolic reactions have occurred. Test results aid in the diagnosis of disease and also provide epidemiological information on diseases caused by these microorganisms.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2330 Enriched culture medium.

(a) Identification. An enriched culture medium is a device that consists primarily of liquid or solid biological materials intended for medical purposes to cultivate and identify fastidious microorganisms (those having complex nutritional requirements). The device consists of a relatively simple basal medium enriched by the addition of such nutritional components as blood, blood serum, vitamins, and extracts of plant or animal tissues. The device is used in the diagnosis of disease caused by pathogenic microorganisms and also provides epidemiological information on these diseases.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2350 Microbiological assay culture medium.

(a) Identification. A microbiological assay culture medium is a device that consists primarily of liquid or solid biological materials intended for medical purposes to cultivate selected test microorganisms in order to measure by microbiological procedures the concentration in a patient's serum of certain substances, such as amino acids, antimicrobial agents, and vitamins. The concentration of these substances is measured by their ability to promote or inhibit the growth of the test organism in the innoculated medium. Test results aid in the diagnosis of disease resulting from either deficient or excessive amounts of these substances in a patient's serum. Tests results may also be used to monitor the effects of the administration of certain antimicrobial drugs.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2360 Selective culture medium.

(a) Identification. A selective culture medium is a device that consists primarily of liquid or solid biological materials intended for medical purposes to cultivate and identify certain pathogenic microorganisms. The device contains one or more components that suppress the growth of certain microorganisms while either promoting or not affecting the growth of other microorganisms. The device aids in the diagnosis of disease caused by pathogenic microorganisms and also provides epidemiological information on these diseases.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2390 Transport culture medium.

(a) Identification. A transport culture medium is a device that consists of a semisolid, usually non-nutrient, medium that maintains the viability of suspected pathogens contained in patient specimens while in transit from the specimen collection area to the laboratory. The device aids in the diagnosis of disease caused by pathogenic microorganisms and also provides epidemiological information on these diseases.

(b) Classification. Class I (general controls).

§ 866.2410 Culture medium for pathogenic Neisseria spp.

(a) Identification. A culture medium for pathogenic Neisseria spp. is a device that consists primarily of liquid or solid biological materials used to cultivate and identify pathogenic Neisseria spp. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Neisseria, such as epidemic cerebrospinal meningitis, other meningococcal disease, and gonorrhea, and also provides epidemiological information on these microorganisms.

(b) Classification. Class II (performance standards).

§ 866.2420 Oxidase screening test for gonorrhea.

(a) Identification. An oxidase screening test for gonorrhea is an in vitro device that consists of the articles intended to identify by chemical reaction, cytochrome oxidase, an oxidizing enzyme that is associated with certain bacteria including Neisseria gonorrhoeae. A sample of a male's urethral discharge is obtained on a swab which is placed into a wetting agent containing an ingredient that will react with cytochrome oxidase. When cytochrome oxidase is present, the swab turns a dark purple color within 3 minutes. Because it is unlikely that cytochrome oxidase-positive organisms other than Neisseria gonorrhoeae are present in the urethral discharge of males, the identification of cytochrome oxidase with this device indicates presumptive infection of the patient with the causative agent of gonorrhea.

(b) Classification. Class III (premarket approval) (transitional device).

(c) Date PMA or notice of completion of a PDP is required. As of May 28, 1976, an approval under section 515 of the act is required before this device may be commercially distributed. See § 866.3.

§ 866.2440 Automated medium dispensing and stacking device.

(a) Identification. An automated medium dispensing and stacking device is a device intended for medical purposes to dispense a microbiological culture medium into petri dishes and then mechanically stack the petri dishes.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9. The device is also exempt from the good manufacturing practice requirements of the quality management system regulation in part 820 of this chapter, except for requirements concerning records and complaint files under § 820.35 of this chapter.

§ 866.2450 Supplement for culture media.

(a) Identification. A supplement for culture media is a device, such as a vitamin or sugar mixture, that is added to a solid or liquid basal culture medium to produce a desired formulation and that is intended for medical purposes to enhance the growth of fastidious microorganisms (those having complex nutritional requirements). This device aids in the diagnosis of diseases caused by pathogenic microorganisms.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2480 Quality control kit for culture media.

(a) Identification. A quality control kit for culture media is a device that consists of paper discs (or other suitable materials), each impregnated with a specified, freeze-dried, viable microorganism, intended for medical purposes to determine if a given culture medium is able to support the growth of that microorganism. The device aids in the diagnosis of disease caused by pathogenic microorganisms and also provides epidemiological information on these diseases.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2500 Microtiter diluting and dispensing device.

(a) Identification. A microtiter diluting and dispensing device is a mechanical device intended for medical purposes to dispense or serially dilute very small quantities of biological or chemical reagents for use in various diagnostic procedures.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2540 Microbiological incubator.

(a) Identification. A microbiological incubator is a device with various chambers or water-filled compartments in which controlled environmental conditions, particularly temperature, are maintained. It is intended for medical purposes to cultivate microorganisms and aid in the diagnosis of disease.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9. The device is also exempt from the good manufacturing practice requirements of the quality management system regulation in part 820 of this chapter, except for requirements concerning records and complaint files under § 820.35 of this chapter.

§ 866.2560 Microbial growth monitor.

(a) Identification. A microbial growth monitor is a device intended for medical purposes that measures the concentration of bacteria suspended in a liquid medium by measuring changes in light scattering properties, optical density, electrical impedance, or by making direct bacterial counts. The device aids in the diagnosis of disease caused by pathogenic microorganisms.

(b) Classification. Class I. With the exception of automated blood culturing system devices that are used in testing for bacteria, fungi, and other microorganisms in blood and other normally sterile body fluids, this device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter.

§ 866.2580 Gas-generating device.

(a) Identification. A gas-generating device is a device intended for medical purposes that produces predetermined amounts of selected gases to be used in a closed chamber in order to establish suitable atmospheric conditions for cultivation of microorganisms with special atmospheric requirements. The device aids in the diagnosis of disease.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2600 Wood's fluorescent lamp.

(a) Identification. A Wood's fluorescent lamp is a device intended for medical purposes to detect fluorescent materials (e.g., fluorescein pigment produced by certain microorganisms) as an aid in the identification of these microorganisms. The device aids in the diagnosis of disease.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9. The device is also exempt from the good manufacturing practice requirements of the quality management system regulation in part 820 of this chapter, except for requirements concerning records and complaint files under § 820.35 of this chapter.

§ 866.2660 Microorganism differentiation and identification device.

(a) Identification. A microorganism differentiation and identification device is a device intended for medical purposes that consists of one or more components, such as differential culture media, biochemical reagents, and paper discs or paper strips impregnated with test reagents, that are usually contained in individual compartments and used to differentiate and identify selected microorganisms. The device aids in the diagnosis of disease.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.

§ 866.2680 Streptococcus spp. nucleic acid-based assay.

(a) Identification. A Streptococcus spp. nucleic acid-based assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify various Streptococcus spp. nucleic acids extracted directly from clinical specimens. The device detects specific nucleic acid sequences for organism identification. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genus Streptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) Premarket notification submissions must include detailed device description documentation, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection.

(2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (Limit of Detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, and cross contamination.

(3) Premarket notification submissions must include detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods.

(4) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, software applications and hardware-based devices that incorporate software.

(5) Premarket notification submissions must include database implementation methodology, construction parameters, and quality assurance protocols, as appropriate.

(6) The device labeling must include limitations regarding the need for culture confirmation of negative specimens, as appropriate.

(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.

(8) Premarket notification submissions must include details on an end user device training program that will be offered while marketing the device, as appropriate.

§ 866.2850 Automated zone reader.

(a) Identification. An automated zone reader is a mechanical device intended for medical purposes to measure zone diameters of microbial growth inhibition (or exhibition), such as those observed on the surface of certain culture media used in disc-agar diffusion antimicrobial susceptibility tests. The device aids in decisionmaking respecting the treatment of disease.

(b) Classification. Class I (general controls).

§ 866.2900 Microbiological specimen collection and transport device.

(a) Identification. A microbiological specimen collection and transport device is a specimen collecting chamber intended for medical purposes to preserve the viability or integrity of microorganisms in specimens during storage of specimens after their collection and during their transport from the collecting area to the laboratory. The device may be labeled or otherwise represented as sterile. The device aids in the diagnosis of disease caused by pathogenic microorganisms.

(b) Classification. Class I (general controls). The device, when solely intended for use in the collection of concentrated parasites from specimens and transport, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.2950 Microbial nucleic acid storage and stabilization device.

(a) Identification. A microbial nucleic acid storage and stabilization device is a device that consists of a container and reagents intended to stabilize microbial nucleic acids in human specimens for subsequent isolation and purification of nucleic acids for further molecular testing. The device is not intended for preserving morphology or viability of microorganisms.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of microorganisms and types of human specimens intended to be preserved.

(2) The labeling required under § 809.10(b) of this chapter must include the following:

(i) A detailed device description, including all device components;

(ii) Performance characteristics from applicable analytical studies, including nucleic acid stability and microorganism inactivation;

(iii) A limiting statement that erroneous results may occur when the transport device is not compatible with molecular testing; and

(iv) A limiting statement that the device has only been validated to preserve the representative microorganisms used in the analytical studies.

(3) Design verification and validation must include the following:

(i) Overall device design, including all device components and all control elements incorporated into the analytical validation procedures;

(ii) Thorough description of the microorganisms and methodology used in the validation of the device including, extraction platforms and assays used for the detection of preserved nucleic acids; and

(iii) The limit of detection (LoD) of the molecular test used to establish microorganism nucleic acid stability.

§ 866.2952 Device to preserve and stabilize relative abundances of microbial nucleic acids in clinical samples.

(a) Identification. A device to preserve and stabilize relative abundances of microbial nucleic acids in clinical samples is a device that consists of a container and reagents intended to stabilize microbial nucleic acids for the subsequent assessment of the relative abundance of microbial nucleic acids ( i.e., microbiome) in human specimens by an assay validated for use with the device. The device may also be indicated for sample collection. The device is not intended for preserving morphology or viability of microorganisms.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) The intended use on the device's label and labeling required under § 809.10 of this chapter must include a detailed description of the type(s) of human specimens intended for collection and preservation, and the characteristics of the microbial population intended for subsequent analysis.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) A detailed device description, including reagents, ancillary reagents required but not provided, and all other parts that make up the device.

(ii) A warning statement that the device is not for the detection of specific microbial pathogens.

(iii) A warning statement that the device should only be used with legally marketed assays that are indicated for use with the device, including, as appropriate, indicated for the relevant storage and transport conditions.

(iv) Description of the microorganisms used for studies, including the results and performance summaries, required under paragraph (b)(3)(i) of this section.

(3) Design verification and validation must include:

(i) Detailed documentation and results from studies used for device validation. This detailed documentation must include a detailed identification of each of the following (which must be representative of the spectrum of situations in which the device might be used that are within the scope of the device's intended use): the panel of microorganisms, the extraction platforms, the assay protocols used to measure the stabilization of relative ratios (relative abundance) of the microorganisms in the sample, and the bioinformatic pipelines used in the validation studies for the determination of relative abundances of preserved nucleic acids.

(ii) For devices intended for the collection of samples, detailed documentation and results from studies that demonstrate the device's usability, including user collection studies that demonstrate that the user instructions are appropriate for the intended collection methods ( e.g., self-collection or clinician/laboratory collection) and users.

§ 866.3010 Acinetobacter calcoaceticus serological reagents.

(a) Identification. Acinetobacter calcoaceticus serological reagents are devices that consist of Acinetobacter calcoaceticus antigens and antisera used to identify this bacterium from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by the bacterium Acinetobacter calcoaceticus and provides epidemiological information on disease caused by this microorganism. This organism becomes pathogenic in patients with burns or with immunologic deficiency, and infection can result in sepsis (blood poisoning).

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.3020 Adenovirus serological reagents.

(a) Identification. Adenovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to adenovirus in serum. Additionally, some of these reagents consist of adenovirus antisera conjugated with a fluorescent dye and are used to identify adenoviruses directly from clinical specimens. The identification aids in the diagnosis of disease caused by adenoviruses and provides epidemiological information on these diseases. Adenovirus infections may cause pharyngitis (inflammation of the throat), acute respiratory diseases, and certain external diseases of the eye (e.g., conjunctivitis).

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.3035 Arizona spp. serological reagents.

(a) Identification. Arizona spp. serological reagents are devices that consist of antisera and antigens used to identify Arizona spp. in cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Arizona and provides epidemiological information on diseases caused by these microorganisms. Arizona spp. can cause gastroenteritis (food poisoning) and sepsis (blood poisoning).

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.3040 Aspergillus spp. serological reagents.

(a) Identification. Aspergillus spp. serological reagents are devices that consist of antigens and antisera used in various serological tests to identify antibodies to Aspergillus spp. in serum. The identification aids in the diagnosis of aspergillosis caused by fungi belonging to the genus Aspergillus. Aspergillosis is a disease marked by inflammatory granulomatous (tumor-like) lessions in the skin, ear, eyeball cavity, nasal sinuses, lungs, and occasionally the bones.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.

§ 866.3045 In vitro diagnostic device for Bacillus spp. detection.

(a) Identification. An in vitro diagnostic device for Bacillus species (spp.) detection is a prescription device used to detect and differentiate among Bacillus spp. and presumptively identify B. anthracis and other Bacillus spp. from cultured isolates or clinical specimens as an aid in the diagnosis of anthrax and other diseases caused by Bacillus spp. This device may consist of Bacillus spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to presumptively identify bacillus-like organisms in clinical specimens; bacteriophage used for differentiating B. anthracis from other Bacillus spp. based on susceptibility to lysis by the phage; or antigens used to identify antibodies to B. anthracis (anti-toxin and anti-capsular) in serum. Bacillus infections include anthrax (cutaneous, inhalational, or gastrointestinal) caused by B. anthracis, and gastrointestinal disease and non-gastrointestinal infections caused by B. cereus.

(b) Classification. Class II (special controls). The special controls are set forth in FDA's special controls guideline document entitled “In Vitro Diagnostic Devices for Bacillus spp. Detection; Class II Special Controls Guideline for Industry and Food and Drug Administration Staff.” For availability of the guideline document, see § 866.1(e).

(c) Restriction on Distribution. The distribution of these devices is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities.

(d) Restriction on Use. The use of this device is restricted to prescription use and must comply with the following:

(1) The device must be in the possession of:

(i)(A) A person, or his agents or employees, regularly and lawfully engaged in the manufacture, transportation, storage, or wholesale or retail distribution of such device; or

(B) A practitioner, such as a physician, licensed by law to use or order the use of such device; and

(ii) The device must be sold only to or on the prescription or other order of such practitioner for use in the course of his professional practice.

(2) The label of the device shall bear the statement “Caution: Federal law restricts this device to sale by or on the order of a ____”, the blank to be filled with the word “physician” or with the descriptive designation of any other practitioner licensed by the law of the State in which he practices to use or order the use of the device.

(3) Any labeling, as defined in section 201(m) of the Federal Food, Drug, and Cosmetic Act, whether or not it is on or within a package from which the device is to be dispensed, distributed by, or on behalf of the manufacturer, packer, or distributor of the device, that furnishes or purports to furnish information for use of the device contains adequate information for such use, including indications, effects, routes, methods, and frequency and duration of administration and any relevant hazards, contraindications, side effects, and precautions, under which practitioners licensed by law to employ the device can use the device safely and for the purposes for which it is intended, including all purposes for which it is advertised or represented. This information will not be required on so-called reminder-piece labeling which calls attention to the name of the device but does not include indications or other use information.

(4) All labeling, except labels and cartons, bearing information for use of the device also bears the date of the issuance or the date of the latest revision of such labeling.

§ 866.3046 Simple in vitro diagnostic device for the detection of secreted proteins from Bacillus species (spp.) in human clinical samples.

(a) Identification. A simple in vitro diagnostic device for the detection of secreted proteins from Bacillus species (spp.) is a prescription in vitro diagnostic device used to detect and presumptively identify B. anthracis and other Bacillus spp. in human clinical samples as an aid in the diagnosis of anthrax and other diseases caused by Bacillus spp. This device is simple to use and does not involve sample manipulation or measurement of an analyte that could be affected by conditions such as sample turbidity or cell lysis. This device may be used to aid in the presumptive diagnosis of anthrax in individuals who have signs and symptoms consistent with anthrax and a likelihood of exposure. Bacillus infections include anthrax (cutaneous, inhalational, or gastrointestinal) caused by B. anthracis, gastrointestinal disease, non-gastrointestinal infections, and an anthrax-like illness caused by B. cereus.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) The distribution of these devices is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities.

(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of the sample types with which this device is intended to be used; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.

(3) The labeling required under 21 CFR 809.10(b) of this chapter must include:

(i) An intended use statement that includes the following:

(A) A detailed description of targets the device detects and measures;

(B) The results provided to the user ( i.e., whether the measurement is qualitative, semi-quantitative, or quantitative);

(C) The clinical indications appropriate for test use ( e.g., in conjunction with patient history, epidemiological information, clinical observations, and other laboratory evidence to make patient management decisions);

(D) Sample types with which it is intended for use;

(E) The specific population(s) with which the device is intended to be used;

(F) The testing location(s) where the device is to be used (if not intended for all locations);

(G) A statement that the device results are for the presumptive identification of Bacillus spp., and definitive identification requires additional testing and confirmation procedures in consultation with the appropriate public health authorities;

(H) A statement that negative results do not preclude infection with Bacillus spp. and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions; and

(I) A statement that testing is to be performed and reported in accordance with current guidelines provided by the appropriate public health authorities.

(ii) Detailed instructions for minimizing the risk of user exposure to Bacillus spp. that may be present in test samples and those used as control materials.

(iii) Detailed instructions for minimizing the risk of generating false positive test results due to contamination from positive test samples and/or positive control materials.

(iv) A prominent and conspicuous precaution that interpretation of test results is intended to be performed by experienced healthcare professionals who have training in principles and use of infectious disease diagnostics and the expertise to report results.

(v) A prominent and conspicuous warning statement that the test results alone do not conclusively establish infection and that additional testing and confirmation procedures may be necessary in consultation with the appropriate public health or other authorities to whom reporting is required.

(vi) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of samples.

(vii) Detailed descriptions of the performance characteristics of the device for all claimed sample types as shown by the analytical and clinical studies required under paragraphs (b)(4)(ii) and (b)(4)(iii) of this section, except sample stability performance characteristics.

(viii) For any devices intended for use in a near-patient setting, a brief reference sheet for healthcare professionals that accompanies the device and that includes the name and intended use of the test, step-by-step instructions of all control and sample testing procedures for the claimed sample types, the result(s) interpretation, warning and limitation statements, and information for troubleshooting or technical assistance with the device.

(ix) A statement that a nationally notifiable disease caused by a biothreat microbial agent must be reported to public health authorities in accordance with local, state, and federal law.

(x) Limiting statements indicating, as applicable:

(A) Situations where the device has been demonstrated to fail or may not perform at its expected performance level ( e.g., any disease specific circumstances or circumstances identified by human factors or robustness studies);

(B) Any specific circumstances that pose significant risk to public health, and for which the device has not been validated. For example:

( 1 ) Testing of matrices and patient populations that are not identified in the intended use; or

( 2 ) Testing individuals without signs and symptoms of infection, including mass infection screening (such as airport or border screening) that is not limited to individuals who have signs and symptoms and a risk of exposure to biothreat microbial agents.

(4) Design verification and validation must include:

(i) A detailed device description, including all device parts, control elements incorporated into the test procedure, reagents required but not provided, the principle of device operation and test methodology, and the computational path from collected raw data to reported result ( e.g., how collected raw signals are converted into a reported result).

(ii) Detailed documentation of analytical studies, as applicable, including those demonstrating limit of detection, inclusivity, cross-reactivity, microbial interference, interfering substances, carryover/cross contamination, sample stability, within lab precision, hook effect, reproducibility, and other studies relevant to the technology ( e.g., linearity), as determined to be appropriate by FDA.

(iii) Detailed documentation and results from either a clinical study or, when determined to be acceptable by FDA, a study with an equivalent data set. Documentation from this study must include study reports, testing results, and results of all statistical analyses, including line data of all test samples, and an appropriate justification describing how the sample set is representative of the intended use population. This study must compare the device performance to results obtained from a reference or comparator method that FDA has determined to be appropriate. This study must include prospective (sequentially collected) samples for each intended sample type that are representative of the intended use populations and may, when determined to be acceptable by FDA, include additional characterized clinical samples; or, as an alternative, when determined to be acceptable by FDA, an equivalent sample set. This study must include samples spanning all relevant analyte concentrations for all of the indicated sample type(s) and the targeted analyte(s).

(iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions, as applicable.

(v) For any devices that detect the presence of an analyte directly from sample, detailed documentation and results from a shelf-life assessment that includes samples formulated in the most complex clinical matrix identified in the device's intended use.

(vi) As part of the risk management activities, if the labeling includes hyperlinks to documents from public health authorities regarding sampling, sample shipment, sample testing, or clinical management of patients suspected of being infected; or if the labeling includes direct contact information for any such public health authority, then the hyperlinks and contact information must be reviewed at least annually and updated to reflect any changes to those hyperlinks or contact information.

§ 866.3050 Beta-glucan serological assays.

(a) Identification. Beta-glucan serological assays are devices that consist of antigens or proteases used in serological assays. The device is intended for use for the presumptive diagnosis of fungal infection. The assay is indicated for use in patients with symptoms of, or medical conditions predisposing the patient to invasive fungal infection. The device can be used as an aid in the diagnosis of deep seated mycoses and fungemias.

(b) Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Serological Assays for the Detection of Beta-Glucan.” See § 866.1(e) for the availability of this guidance document.

§ 866.3060 Blastomyces dermatitidis serological reagents.

(a) Identification. Blastomyces dermatitidis serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Blastomyces determatitidis in serum. The identification aids in the diagnosis of blastomycosis caused by the fungus Blastomyces dermatitidis. Blastomycosis is a chronic granulomatous (tumor-like) disease, which may be limited to the skin or lung or may be widely disseminated in the body resulting in lesions of the bones, liver, spleen, and kidneys.

(b) Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.

§ 866.3065 Bordetella spp. serological reagents.

(a) Identification. Bordetella spp. serological reagents are devices that consist of antigens and antisera, including antisera conjugated with a fluorescent dye, used in serological tests to identify Bordetella spp. from cultured isolates or directly from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genus Bordetella and provides epidemiological information on these diseases. Bordetella spp. cause whooping cough ( Bordetella pertussis ) and other similiarly contagious and acute respiratory infections characterized by pneumonitis (inflammation of the lungs).

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

§ 866.3085 Brucella spp. serological reagents.

(a) Identification. Brucella spp. serological reagents are devices that consist of antigens and antisera used for serological identification of Brucella spp. from cultured isolates derived from clinical specimens or to identify antibodies to Brucella spp. in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identify Brucella spp. directly from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of brucellosis (e.g., undulant fever, Malta fever) caused by bacteria belonging to the genus Brucella and provides epidemiological information on diseases caused by these microorganisms.

(b) Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.

§ 866.3110 Campylobacter fetus serological reagents.

(a) Identification. Campylobacter fetus serological reagents are devices that consist of antisera conjugated with a fluorescent dye used to identify Campylobacter fetus from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by this bacterium and provides epidemiological information on these diseases. Campylobacter fetus is a frequent cause of abortion in sheep and cattle and is sometimes responsible for endocarditis (inflammation of certain membranes of the heart) and enteritis (inflammation of the intestines) in humans.

(b) Classification. Class I (general controls).

§ 866.3120 Chlamydia serological reagents.

(a) Identification. Chlamydia serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to chlamydia in serum. Additionally, some of these reagents consist of chlamydia antisera conjugated with a fluorescent dye used to identify chlamydia directly from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Chlamydia and provides epidemiological information on these diseases. Chlamydia are the causative agents of psittacosis (a form of pneumonia), lymphogranuloma venereum (a venereal disease), and trachoma (a chronic disease of the eye and eyelid).

(b) Classification. Class I (general controls).

§ 866.3125 Citrobacter spp. serological reagents.

(a) Identification. Citrobacter spp. serological reagents are devices that consist of antigens and antisera used in serological tests to identify Citrobacter spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Citrobacter and provides epidemiological information on diseases caused by these microorganisms. Citrobacter spp. have occasionally been associated with urinary tract infections.

(b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.