section_id,title_number,title_name,chapter,subchapter,part_number,part_name,subpart,subpart_name,section_number,section_heading,agency,authority,source_citation,amendment_citations,full_text 21:21:8.0.1.1.20.1.1.1,21,Food and Drugs,I,H,866,,A,Subpart A—General Provisions,,§ 866.1 Scope.,FDA,,,"[52 FR 17733, May 11, 1987, as amended at 68 FR 5827, Feb. 5, 2003; 79 FR 50552, Aug. 25, 2014]","(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." 21:21:8.0.1.1.20.1.1.2,21,Food and Drugs,I,H,866,,A,Subpart A—General Provisions,,§ 866.3 Effective dates of requirement for premarket approval.,FDA,,,"[52 FR 17733, May 11, 1987; 52 FR 22577, June 12, 1987]","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." 21:21:8.0.1.1.20.1.1.3,21,Food and Drugs,I,H,866,,A,Subpart A—General Provisions,,"§ 866.9 Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).",FDA,,,"[65 FR 2311, Jan. 14, 2000]","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)." 21:21:8.0.1.1.20.2.1.1,21,Food and Drugs,I,H,866,,B,Subpart B—Diagnostic Devices,,§ 866.1620 Antimicrobial susceptibility test disc.,FDA,,,,"(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)." 21:21:8.0.1.1.20.2.1.2,21,Food and Drugs,I,H,866,,B,Subpart B—Diagnostic Devices,,§ 866.1640 Antimicrobial susceptibility test powder.,FDA,,,,"(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)." 21:21:8.0.1.1.20.2.1.3,21,Food and Drugs,I,H,866,,B,Subpart B—Diagnostic Devices,,§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.,FDA,,,"[68 FR 5827, Feb. 5, 2003]","(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.”" 21:21:8.0.1.1.20.2.1.4,21,Food and Drugs,I,H,866,,B,Subpart B—Diagnostic Devices,,§ 866.1650 A cellular analysis system for multiplexed antimicrobial susceptibility testing.,FDA,,,"[90 FR 24963, June 13, 2025]","(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." 21:21:8.0.1.1.20.2.1.5,21,Food and Drugs,I,H,866,,B,Subpart B—Diagnostic Devices,,§ 866.1655 System for detection of microorganisms and antimicrobial resistance using reporter expression.,FDA,,,"[87 FR 6417, Feb. 4, 2022]","(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." 21:21:8.0.1.1.20.2.1.6,21,Food and Drugs,I,H,866,,B,Subpart B—Diagnostic Devices,,§ 866.1700 Culture medium for antimicrobial susceptibility tests.,FDA,,,,"(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)." 21:21:8.0.1.1.20.3.1.1,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2050 Staphylococcal typing bacteriophage.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25045, June 12, 1989; 66 FR 38790, July 25, 2001]","(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." 21:21:8.0.1.1.20.3.1.10,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2350 Microbiological assay culture medium.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(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." 21:21:8.0.1.1.20.3.1.11,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2360 Selective culture medium.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(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." 21:21:8.0.1.1.20.3.1.12,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2390 Transport culture medium.,FDA,,,,"(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)." 21:21:8.0.1.1.20.3.1.13,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2410 Culture medium for pathogenic,FDA,,,,"(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)." 21:21:8.0.1.1.20.3.1.14,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2420 Oxidase screening test for gonorrhea.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 52 FR 17734, May 11, 1987]","(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." 21:21:8.0.1.1.20.3.1.15,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2440 Automated medium dispensing and stacking device.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 66 FR 38791, July 25, 2001; 90 FR 55982, Dec. 4, 2025]","(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." 21:21:8.0.1.1.20.3.1.16,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2450 Supplement for culture media.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(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." 21:21:8.0.1.1.20.3.1.17,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2480 Quality control kit for culture media.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(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." 21:21:8.0.1.1.20.3.1.18,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2500 Microtiter diluting and dispensing device.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(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." 21:21:8.0.1.1.20.3.1.19,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2540 Microbiological incubator.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 66 FR 38791, July 25, 2001; 90 FR 55982, Dec. 4, 2025]","(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." 21:21:8.0.1.1.20.3.1.2,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2120 Anaerobic chamber.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 66 FR 38790, July 25, 2001; 90 FR 55981, Dec. 4, 2025]","(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." 21:21:8.0.1.1.20.3.1.20,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2560 Microbial growth monitor.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 60 FR 38482, July 27, 1995]","(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." 21:21:8.0.1.1.20.3.1.21,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2580 Gas-generating device.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(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." 21:21:8.0.1.1.20.3.1.22,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2600 Wood's fluorescent lamp.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 66 FR 38791, July 25, 2001; 90 FR 55982, Dec. 4, 2025]","(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." 21:21:8.0.1.1.20.3.1.23,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2660 Microorganism differentiation and identification device.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000]","(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." 21:21:8.0.1.1.20.3.1.24,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2680,FDA,,,"[82 FR 50074, Oct. 30, 2017]","(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." 21:21:8.0.1.1.20.3.1.25,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2850 Automated zone reader.,FDA,,,,"(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)." 21:21:8.0.1.1.20.3.1.26,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2900 Microbiological specimen collection and transport device.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 84 FR 71800, Dec. 30, 2019; 85 FR 18445, Apr. 2, 2020]","(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." 21:21:8.0.1.1.20.3.1.27,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2950 Microbial nucleic acid storage and stabilization device.,FDA,,,"[90 FR 19645, May 9, 2025]","(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." 21:21:8.0.1.1.20.3.1.3,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2160 Coagulase plasma.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 61 FR 1119, Jan. 16, 1996; 66 FR 38790, July 25, 2001]","(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." 21:21:8.0.1.1.20.3.1.4,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2170 Automated colony counter.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25045, June 12, 1989; 66 FR 38790, July 25, 2001]","(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." 21:21:8.0.1.1.20.3.1.5,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2180 Manual colony counter.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 66 FR 38790, July 25, 2001; 90 FR 55981, Dec. 4, 2025]","(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." 21:21:8.0.1.1.20.3.1.6,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2190 Automated image assessment system for microbial colonies on solid culture media.,FDA,,,"[82 FR 47969, Oct. 16, 2017, as amended at 90 FR 55982, Dec. 4, 2025]","(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." 21:21:8.0.1.1.20.3.1.7,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2300 Multipurpose culture medium.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38790, July 25, 2001]","(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." 21:21:8.0.1.1.20.3.1.8,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2320 Differential culture medium.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38790, July 25, 2001]","(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." 21:21:8.0.1.1.20.3.1.9,21,Food and Drugs,I,H,866,,C,Subpart C—Microbiology Devices,,§ 866.2330 Enriched culture medium.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(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." 21:21:8.0.1.1.20.4.1.1,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3010,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(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." 21:21:8.0.1.1.20.4.1.10,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3110,FDA,,,,"(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)." 21:21:8.0.1.1.20.4.1.100,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3940 West Nile virus serological reagents.,FDA,,,"[68 FR 61745, Oct. 30, 2003]","(a) Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum, from individuals who have signs and symptoms consistent with viral meningitis/encephalitis. The detection aids in the clinical laboratory diagnosis of viral meningitis/encephalitis caused by West Nile virus. (b) Classification. Class II (special controls). The special control is FDA's guidance entitled “Class II Special Controls Guidance Document: Serological Reagents for the Laboratory Diagnosis of West Nile Virus.” See § 866.1(e) for the availability of this guidance document." 21:21:8.0.1.1.20.4.1.101,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3945 Dengue virus serological reagents.,FDA,,,"[79 FR 31023, May 30, 2014]","(a) Identification. Dengue virus serological reagents are devices that consist of antigens and antibodies for the detection of dengue virus and dengue antibodies in individuals who have signs and symptoms of dengue fever or dengue hemorrhagic fever. The detection aids in the clinical laboratory diagnosis of dengue fever or dengue hemorrhagic fever caused by dengue virus. (b) Classification. Class II (special controls). The special control is FDA's guideline entitled “Class II Special Controls Guideline: Dengue Virus Serological Reagents.” For availability of the guideline document, see § 866.1(e)." 21:21:8.0.1.1.20.4.1.102,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3946 Dengue virus nucleic acid amplification test reagents.,FDA,,,"[79 FR 53609, Sept. 10, 2014]","(a) Identification. Dengue virus nucleic acid amplification test reagents are devices that consist of primers, probes, enzymes, and controls for the amplification and detection of dengue virus serotypes 1, 2, 3, or 4 from viral ribonucleic acid (RNA) in human serum and plasma from individuals who have signs and symptoms consistent with dengue (mild or severe). The identification of dengue virus serotypes 1, 2, 3, or 4 in human serum and plasma (sodium citrate) collected from human patients with dengue provides epidemiologic information for surveillance of circulating dengue viruses. (b) Classification. Class II (special controls). The special control is FDA's guideline entitled “Class II Special Controls Guideline: Dengue Virus Nucleic Acid Amplification Test Reagents.” For availability of the guideline document, see § 866.1(e)." 21:21:8.0.1.1.20.4.1.103,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.,FDA,,,"[72 FR 44382, Aug. 8, 2007]","(a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid reagent primers and probes together with software for predicting drug resistance/susceptibility based on results obtained with these primers and probes. It is intended for use in detecting HIV genomic mutations that confer resistance to specific antiretroviral drugs, as an aid in monitoring and treating HIV infection. (b) Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: In Vitro HIV Drug Resistance Genotype Assay.” See § 866.1(e) for the availability of this guidance document." 21:21:8.0.1.1.20.4.1.104,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3955 Human immunodeficiency virus (HIV) drug resistance genotyping assay using next generation sequencing technology.,FDA,,,"[85 FR 7217, Feb. 7, 2020]","(a) Identification. The HIV drug resistance genotyping assay using next generation sequencing (NGS) technology is a prescription in vitro diagnostic device intended for use in detecting HIV genomic mutations that confer resistance to specific antiretroviral drugs. The device is intended to be used as an aid in monitoring and treating HIV infection. (b) Classification. Class II (special controls). The special controls for this device are: (1) The intended use of the device must: (i) Specify the analyte (RNA or DNA), the genes in which mutations are detected, the clinical indications appropriate for test use, the sample type, and the specific population(s) for which the device in intended. (ii) State that the device in not intended for use as an aid in the diagnosis of infection with HIV or to confirm the presence of HIV infection, or for screening donors of blood, plasma, or human cells, tissues, and cellular and tissue-based products. (2) The labeling must include: (i) A detailed device description, including but not limited to, all procedures from collection of the patient sample to reporting the final result, all device components, the control elements incorporated into the test procedure, instrument requirements, and reagents required for use but not provided as part of the device. (ii) Performance characteristics from analytical studies and all intended specimen types. (iii) A list of specific mutations detected. (iv) The name and version of the standardized database used for sequence comparison and results derivation. (v) A detailed explanation of the interpretation of test results, including acceptance criteria for evaluating the validity of a test run. (vi) A limitation statement that the device is intended to be used in conjunction with clinical history and other laboratory findings. Results of this test are intended to be interpreted by a physician or equivalent. (vii) A limitation statement that lack of detection of drug resistance mutations does not preclude the possibility of genetic mutation. (viii) A limitation statement indicating the relevant genetic mutations that are included in the standardized database of HIV genomic sequences used for comparison and results derivation but that are not detected by the test. (ix) A limitation statement that detection of a genomic drug resistance mutation may not correlate with phenotypic gene expression. (x) A limitation statement that the test does not detect all genetic mutations associated with antiviral drugs. (xi) A limitation statement listing the HIV types for which the test is not intended, if any. (3) Device verification and validation must include: (i) Design of primer sequences and rationale for sequence selection. (ii) Computational path from collected raw data to reported result. (iii) Detailed documentation of analytical studies including, but not limited to, characterization of the cutoff, analytical sensitivity, inclusivity, reproducibility, interference, cross reactivity, instrument and method carryover/cross contamination, sample stability, and handling for all genomic mutations claimed in the intended use. (iv) Precision studies that include all genomic mutations claimed in the intended use. (v) Detailed documentation of a multisite clinical study evaluating the sensitivity and specificity of the device. Clinical study subjects must represent the intended use population and device results for all targets claimed in the intended use must be compared to Sanger sequencing or other methods found acceptable by FDA. Drug resistance-associated mutations at or above the 20 percent frequency level must detect the mutations in greater than 90 percent of at least 10 replicates, for each of drug class evaluated. (vi) Documentation that variant calling is performed at a level of coverage that supports positive detection of all genomic mutations claimed in the intended use. (vii) Detailed documentation of limit of detection (LoD) studies in which device performance is evaluated by testing a minimum of 100 HIV-positive clinical samples including samples with analyte concentrations near the clinical decision points and near the LoD. (A) The LoD for the device must be determined using a minimum of 10 HIV-1 group M genotypes if applicable. A detection rate at 1 × LoD greater than or equal to 95 percent must be demonstrated for mutations with a frequency greater than 20 percent. (B) The LoD of genetic mutations at frequency levels less than 20 percent must be established. (viii) A predefined HIV genotyping bioinformatics analysis pipeline (BAP). The BAP must adequately describe the bioinformatic analysis of the sequencing data, including but not limited to read alignment, variant calling, assembly, genotyping, quality control, and final result reporting. (ix) A clear description of the selection and use of the standardized database that is used for sequence comparison and results derivation. (4) Premarket notification submissions must include the information in paragraphs (b)(3)(i) through (ix) of this section." 21:21:8.0.1.1.20.4.1.105,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3956 Human immunodeficiency virus (HIV) serological diagnostic and/or supplemental test.,FDA,,,"[87 FR 29665, May 16, 2022]","(a) Identification. Human immunodeficiency virus (HIV) serological diagnostic and supplemental tests are prescription devices for the qualitative detection of HIV antigen(s) and/or detection of antibodies against HIV in human body fluids or tissues. The tests are intended for use as an aid in the diagnosis of infection with HIV and are for professional use only. The test results are intended to be interpreted in conjunction with other relevant clinical and laboratory findings. These tests are not intended to be used for monitoring patient status, or for screening donors of blood or blood products, or human cells, tissues, and cellular and tissue-based products (HCT/Ps). (b) Classification. Class II (special controls). The special controls for this device are: (1) For all HIV serological diagnostic and supplemental tests (i) The labeling must include: (A) An intended use that states that the device is not intended for use for screening donors of blood or blood products or HCT/Ps. (B) A detailed explanation of the principles of operation and procedures used for performing the assay. (C) A detailed explanation of the interpretation of results and recommended actions to take based on results. (D) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate: ( 1 ) The matrices with which the device has been cleared, and that use of this test kit with specimen types other than those specifically cleared for this device may result in inaccurate test results. ( 2 ) The test is not intended to be used to monitor individuals who are undergoing treatment for HIV infection. ( 3 ) A specimen with a reactive result should be investigated further following current guidelines. ( 4 ) All test results should be interpreted in conjunction with the individual's clinical presentation, history, and other laboratory results. ( 5 ) A test result that is nonreactive does not exclude the possibility of exposure to or infection with HIV. Nonreactive results in this assay may be due to analyte levels that are below the limit of detection of this assay. (ii) Device verification and validation must include: (A) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the methodology. Additional information appropriate to the technology must be included, such as the amino acid sequence of antigen(s) and design of capture antibodies. (B) For devices with assay calibrators, the design of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a reference material. In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance, or when there is a transition to a new calibration standard. (C) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including, but not limited to, limit of blank, limit of detection, cutoff determination, precision, endogenous and exogenous interferences, cross reactivity, carryover, quality control, matrix equivalency, and sample and reagent stability. Samples selected for use in analytical studies or used to prepare samples for use in analytical studies must be from subjects with clinically relevant circulating genotypes in the United States. (D) Multisite reproducibility study that includes the testing of three independent production lots. (E) Analytical sensitivity of the test must be the same as or better than that of other cleared or approved tests. Samples tested must include appropriate numbers and types of samples, including real clinical samples near the lower limit of detection. Analytical specificity of the test must be the same as or better than that of other cleared or approved tests. Samples must include appropriate numbers and types of samples from patients with different underlying illnesses or infections and from patients with potential endogenous interfering substances. (F) Detailed documentation of performance from a multisite clinical study. Performance must be analyzed relative to an FDA-cleared or approved comparator. This study must be conducted using patient samples, with an appropriate number of HIV positive and HIV negative samples in applicable risk categories. Additional subgroups or types must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. The study designs, including number of samples tested, must be sufficient to meet the following criteria: ( 1 ) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 99 percent. ( 2 ) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 99 percent. (G) Strategies for detection of new strains, types, subtypes, genotypes, and genetic mutations as they emerge. (H) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (I) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (J) All stability protocols, including acceptance criteria. (K) Appropriate and acceptable procedure(s) for evaluating customer complaints and other device information that determines when to submit a medical device report. (L) Premarket notification submissions must include the information contained in paragraph (b)(1)(ii)(A) through (K) of this section. (iii) Manufacturers must submit a log of all complaints. The log must include the following information regarding each complaint if available: The type of event ( e.g., false negative/false nonreactive or false positive/false reactive), lot, date, population, and whether or not the complaint was reported under part 803 of this chapter (Medical Device Reporting). The log must be submitted annually on the anniversary of clearance for 5 years following clearance of a traditional premarket notification. (2) If the test is intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraph (b)(1) of this section apply: (i) The PoC labeling must include a statement that the test is intended for PoC use. (ii) The PoC labeling must include the following information near the statement of the intended use: (A) That the test is for distribution to clinical laboratories that have an adequate quality assurance program, including planned systematic activities that provide adequate confidence that requirements for quality will be met and where there is assurance that operators will receive and use the instructional materials. (B) That the test is for use only by an agent of a clinical laboratory. (C) Instructions for individuals to receive the “Subject Information Notice” prior to specimen collection and appropriate information when test results are provided. (iii) PoC labeling must include instructions to follow current guidelines for informing the individual of the test result and its interpretation. (iv) The instructions in the labeling must state that reactive results are considered preliminary and should be confirmed following current guidelines. (v) Device verification and validation for PoC use must include: (A) Detailed documentation of performance from a multisite clinical study conducted at appropriate PoC sites. Performance must be analyzed relative to an FDA cleared or approved comparator. This study must be conducted using patient samples, with appropriate numbers of HIV positive and HIV negative samples in applicable risk categories. Additional subgroup or type claims must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. If the test is intended solely for PoC use, the test must meet only the performance criteria in paragraphs (b)(2)(v)(A)( 1 ) and ( 2 ) of this section and not the criteria in paragraph (b)(1)(ii)(F) of this section: ( 1 ) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 98 percent. ( 2 ) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 98 percent. (B) Premarket notification submissions must include the information contained in paragraph (b)(2)(v)(A) of this section. (3) If the test is intended for supplemental use in addition to use as an aid in initial diagnosis, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV antibodies or antigens in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) Device validation and verification for supplemental use must include a clinical study, including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a different confirmatory test. Premarket notification submissions must include this information. (4) If the test is intended solely as a supplemental test, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, except those in paragraphs (b)(1)(ii)(F) and (b)(2)(v)(A) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV antibodies or antigens in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) The labeling must clearly state that the test is not for use for initial diagnosis or is not intended as a first-line test. (iii) Device validation and verification must include a clinical study including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a confirmatory test. Premarket notification submissions must include this information. (5) If the test is intended to differentiate different HIV types, the following special controls, in addition to those listed in paragraphs (b)(1) through (4) of this section, as appropriate, apply: (i) The labeling must include the statement that the test is intended for the confirmation of initial results from a diagnostic test and differentiation of different HIV types. (ii) The results interpretation in the labeling must include instructions for the user on how to interpret the results, including un-typeable and co-infection results. (iii) Device validation and verification must include evaluation of analytical and clinical sensitivity and specificity for each of the HIV types, strains, and subtypes of HIV intended to be differentiated. Premarket notification submissions must include this information." 21:21:8.0.1.1.20.4.1.106,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3957 Human immunodeficiency virus (HIV) nucleic acid (NAT) diagnostic and/or supplemental test.,FDA,,,"[87 FR 29667, May 16, 2022]","(a) Identification. Human immunodeficiency virus (HIV) nucleic acid (NAT) diagnostic and supplemental tests are prescription devices for the qualitative detection of HIV nucleic acid in human body fluids or tissues. The tests are intended for use as an aid in the diagnosis of infection with HIV and are for professional use only. The test results are intended to be interpreted in conjunction with other relevant clinical and laboratory findings. These tests are not intended to be used for monitoring patient status, or for screening donors of blood or blood products, or human cells, tissues, or cellular or tissue-based products (HCT/Ps). (b) Classification. Class II (special controls). The special controls for this device are: (1) For all HIV NAT diagnostic and/or supplemental tests (i) The labeling must include: (A) An intended use that states that the device is not intended for use for screening donors of blood or blood products, or HCT/Ps. (B) A detailed explanation of the principles of operation and procedures used for performing the assay. (C) A detailed explanation of the interpretation of results and recommended actions to take based on results. (D) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate: ( 1 ) The matrices with which the device has been cleared, and that use of this test kit with specimen types other than those specifically cleared for this device may result in inaccurate test results. ( 2 ) The test is not intended to be used to monitor individuals who are undergoing treatment for HIV infection. ( 3 ) A specimen with a reactive result should be investigated further following current guidelines. ( 4 ) All test results should be interpreted in conjunction with the individual's clinical presentation, history, and other laboratory results. ( 5 ) A test result that is nonreactive does not exclude the possibility of exposure to or infection with HIV. Nonreactive results in this assay may be due to analyte levels that are below the limit of detection of this assay. (ii) Device verification and validation must include: (A) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the methodology. Additional information appropriate to the technology must be included, such as design of primers and probes. (B) For devices with assay calibrators, the design and nature of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a reference material. In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance, or when there is a transition to a new calibration standard. (C) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including, but not limited to, limit of blank, limit of detection, cutoff determination, precision, endogenous and exogenous interferences, cross reactivity, carryover, quality control, matrix equivalency, and sample and reagent stability. Samples selected for use in analytical studies or used to prepare samples for use in analytical studies must be from subjects with clinically relevant circulating genotypes in the United States. The effect of each claimed nucleic-acid isolation and purification procedure on detection must be evaluated. (D) Multisite reproducibility study that includes the testing of three independent production lots. (E) Analytical sensitivity of the test must be the same as or better than that of other cleared or approved tests. Samples tested must include appropriate numbers and types of samples, including real clinical samples near the lower limit of detection. Analytical specificity of the test must be as the same as or better than that of other cleared or approved tests. Samples must include appropriate numbers and types of samples from patients with different underlying illnesses or infections and from patients with potential endogenous interfering substances. (F) Detailed documentation of performance from a multisite clinical study. Performance must be analyzed relative to an FDA cleared or approved comparator. This study must be conducted using appropriate patient samples, with appropriate numbers of HIV positive and negative samples in applicable risk categories. Additional subtype, strain, or types must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. The study designs, including number of samples tested, must be sufficient to meet the following criteria: ( 1 ) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 99 percent. ( 2 ) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 99 percent. (G) Strategies for detection of new strains, types, subtypes, genotypes, and genetic mutations as they emerge. (H) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (I) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (J) All stability protocols, including acceptance criteria. (K) Appropriate and acceptable procedure(s) for evaluating customer complaints and other device information that determine when to submit a medical device report. (L) Premarket notification submissions must include the information contained in paragraph (b)(1)(ii)(A) through (K) of this section. (iii) Manufacturers must submit a log of all complaints. The log must include the following information regarding each complaint, if available: The type of event ( e.g., false negative/false nonreactive or false positive/false reactive), lot, date, population, and whether or not the complaint was reported under part 803 of this chapter (Medical Device Reporting). The log must be submitted annually on the anniversary of clearance for 5 years following clearance of a traditional premarket notification. (2) If the test is intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraph (b)(1) of this section, apply: (i) The PoC labeling must include a statement that the test is intended for PoC use. (ii) The PoC labeling must include the following information near the statement of the intended use: (A) That the test is for distribution to clinical laboratories that have an adequate quality assurance program, including planned systematic activities that provide adequate confidence that requirements for quality will be met and where there is assurance that operators will receive and use the instructional materials. (B) That the test is for use only by an agent of a clinical laboratory. (C) Instructions for individuals to receive the “Subject Information Notice” prior to specimen collection and appropriate information when test results are provided. (iii) PoC labeling must include instructions to follow current guidelines for informing the individual of the test result and its interpretation. (iv) The instructions in the labeling must state that reactive results are considered preliminary and should be confirmed following current guidelines. (v) Device verification and validation for PoC use must include: (A) Detailed documentation from a well-conducted multisite clinical study conducted at appropriate PoC sites. Performance must be analyzed relative to an FDA cleared or approved comparator. This study must be conducted using patient samples, with appropriate numbers of HIV positive and HIV negative samples in applicable risk categories. Additional subgroup or type claims must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. If the test is intended solely for PoC use, the test must meet only the performance criteria in paragraphs (b)(2)(v)(A)( 1 ) and ( 2 ) of this section and not the criteria in paragraph (b)(1)(ii)(F) of this section: ( 1 ) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 98 percent. ( 2 ) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 98 percent. (B) Premarket notification submissions must include the information contained in paragraph (b)(2)(v)(A) of this section. (3) If the test is intended for supplemental use in addition to use as an aid in initial diagnosis, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV viral nucleic acid in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) Device validation and verification for supplemental use must include a clinical study, including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a confirmatory test. Premarket notification submissions must include this information. (4) If the test is intended solely as a supplemental test, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, except those in paragraphs (b)(1)(ii)(F) and (b)(2)(v)(A) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV viral nucleic acid in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) The labeling must clearly state that the test is not for use for initial diagnosis or is not intended as a first-line test. (iii) Device validation and verification must include a clinical study including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a confirmatory test. Premarket notification submissions must include this information. (5) If the test is intended to differentiate different HIV types, the following special controls, in addition to those listed in paragraphs (b)(1) through (4) of this section, as appropriate, apply: (i) The labeling must include the statement that the test is intended for the confirmation of initial results and differentiation of different HIV types. (ii) The results interpretation in the labeling must include instructions for the user on how to interpret the results, including un-typeable and co-infection results. (iii) Device validation and verification must include evaluation of analytical and clinical sensitivity and specificity for each of the types, strains, and subtypes of HIV intended to be differentiated. Premarket notification submissions must include this information." 21:21:8.0.1.1.20.4.1.107,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3958 Human immunodeficiency virus (HIV) viral load monitoring test.,FDA,,,"[87 FR 66548, Nov. 4, 2022]","(a) Identification. A human immunodeficiency virus (HIV) viral load monitoring test is an in vitro diagnostic prescription device for the quantitation of the amount of HIV ribonucleic acid (RNA) in human body fluids. The test is intended for use in the clinical management of individuals living with HIV and is for professional use only. The test results are intended to be interpreted in conjunction with other relevant clinical and laboratory findings. The test is not intended to be used as an aid in diagnosis or for screening donors of blood or blood products or human cells, tissues, or cellular and tissue-based products (HCT/Ps). (b) Classification. Class II (special controls). The special controls for this device are: (1) The labeling must include: (i) An intended use that states that the device is not intended for use as an aid in diagnosis or for use in screening donors of blood or blood products, or HCT/Ps. (ii) A detailed explanation of the principles of operation and procedures used for assay performance. (iii) A detailed explanation of the interpretation of results and that recommended actions should be based on current clinical guidelines. (iv) Limitations, which must be updated to reflect current clinical practice and patient management. The limitations must include, but are not limited to, statements that indicate: (A) The matrices and sample types with which the device has been cleared and that use of this test with specimen types other than those specifically cleared for this device may cause inaccurate test results. (B) Mutations in highly conserved regions may affect binding of primers and/or probes resulting in the under-quantitation of virus or failure to detect the presence of virus. (C) All test results should be interpreted in conjunction with the individual's clinical presentation, history, and other laboratory results. (2) Device verification and validation must include: (i) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the device methodology. Additional information appropriate to the technology must be included, such as detailed information on the design of primers and probes. (ii) For devices with assay calibrators, the design and nature of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a reference material. In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance, or when there is a transition to a new calibration standard. (iii) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including but not limited to, limit of blank, limit of detection, limit of quantitation, cutoff determination, precision, linearity, endogenous and exogenous interferences, cross-reactivity, carry-over, quality control, matrix equivalency, sample and reagent stability. Samples selected for use in analytical studies or used to prepare samples for use in analytical studies must be from subjects with clinically relevant genotypes circulating in the United States. (iv) Multisite reproducibility study that includes the testing of three independent production lots. (v) Analytical sensitivity of the device must demonstrate acceptable performance at current clinically relevant medical decision points. Samples tested to demonstrate analytical sensitivity must include appropriate numbers and types of samples, including real clinical samples near the lower limit of quantitation and any clinically relevant medical decision points. Analytical specificity of the device must demonstrate acceptable performance. Samples tested to demonstrate analytical specificity must include appropriate numbers and types of samples from patients with different underlying illnesses and infection and from patients with potential interfering substances. (vi) Detailed documentation of performance from a multisite clinical study or a multisite analytical method comparison study. (A) For devices evaluated in a multisite clinical study, the study must use specimens from individuals living with HIV being monitored for changes in viral load, and the test results must be compared to the clinical status of the patients. (B) For tests evaluated in a multisite analytical method comparison study, the performance of the test must be compared to an FDA-cleared or approved comparator. The multisite method comparison study must include appropriate numbers and types of samples with analyte concentrations across the measuring range of the assay, representing clinically relevant genotypes. The multisite method comparison study design, including number of samples tested, must be sufficient to meet the following criteria: ( 1 ) Agreement between the two tests across the measuring range of the assays must have an r2 of greater than or equal to 0.95. ( 2 ) The bias between the test and comparator assay, as determined by difference plots, must be less than or equal to 0.5 log copies/mL. (vii) Detailed documentation of a single-site analytical method comparison study between the device and an FDA-cleared or approved comparator if a multisite clinical study is performed under paragraph(b)(2)(vi) of this section. The analytical method comparison study must use appropriate numbers and types of samples with analyte concentrations across the measuring range of the assay, representing clinically relevant genotypes. The results must meet the criteria in paragraphs (b)(2)(vi)(B)( 1 ) and ( 2 ) of this section. (viii) Strategies for detection of new strains, types, subtypes, genotypes, and genetic mutations as they emerge. (ix) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (x) Final release criteria to be used for manufactured device lots with an appropriate justification that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (xi) All stability protocols, including acceptance criteria. (xii) Appropriate and acceptable procedure(s) for addressing complaints and other device information that determines when to submit a medical device report. (xiii) Premarket notification submissions must include the information contained in paragraphs (b)(2)(i) through (xii) of this section." 21:21:8.0.1.1.20.4.1.108,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,"§ 866.3960 Nucleic acid-based device for the amplification, detection, and identification of microbial pathogens directly from whole blood specimens.",FDA,,,"[82 FR 47967, Oct. 16, 2017, as amended at 90 FR 55982, Dec. 4, 2025]","(a) Identification. A nucleic acid-based device for the amplification, detection, and identification of microbial pathogens directly from whole blood specimens is a qualitative in vitro device intended for the amplification, detection, and identification of microbial-associated nucleic acid sequences from patients with suspected bloodstream infections. This device is intended to aid in the diagnosis of bloodstream infection when used in conjunction with clinical signs and symptoms and other laboratory findings. (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, carryover, 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) The device labeling must include limitations regarding the need for culture confirmation of negative specimens, as appropriate. (6) 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. (7) Premarket notification submissions must include details on an end user device training program that will be offered while marketing the device, as appropriate. (8) As part of the risk management activities performed under 21 CFR 820.10(c) design and development, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument." 21:21:8.0.1.1.20.4.1.109,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3966 Device to detect and identify selected microbial agents that cause acute febrile illness.,FDA,,,"[89 FR 66558, Aug. 16, 2024]","(a) Identification. A device to detect and identify selected microbial agents that cause acute febrile illness is identified as an in vitro device intended for the detection and identification of microbial agents in human clinical specimens from patients with signs and symptoms of acute febrile illness who are at risk for exposure or who may have been exposed to these agents. It is intended to aid in the diagnosis of acute febrile illness in conjunction with other clinical, epidemiologic, and laboratory data, including patient travel, pathogen endemicity, or other risk factors. (b) Classification. Class II (special controls). The special controls for this device are: (1) 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 specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (2) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use that includes a detailed description of targets the device detects and measures, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended. (ii) Limiting statements indicating: (A) Not all pathogens that cause febrile illness are detected by this test and negative results do not rule out the presence of other infections; (B) Evaluation of more common causes of acute febrile illness should be considered prior to evaluation with this test; (C) Test results are to be interpreted in conjunction with other clinical, epidemiologic, and laboratory data available to the clinician; and (D) When using this test, consider patient travel history and exposure risk, as some pathogens are more common in certain geographical locations. (iii) 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 specimens. (iv) Detailed discussion of the performance characteristics of the device for all claimed specimen types as shown by the analytical and clinical studies required under paragraphs (b)(3)(ii) and (iii) of this section, except specimen stability performance characteristics. (v) A statement that nationally notifiable results are to be reported to public health authorities in accordance with local, state, and federal law. (3) Design verification and validation must include: (i) A detailed device description ( e.g., 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, including those demonstrating Limit of Detection (LoD), inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate. (iii) Detailed documentation and performance results from a clinical study that includes prospective (sequentially collected) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA-accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses. (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." 21:21:8.0.1.1.20.4.1.11,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3120 Chlamydia serological reagents.,FDA,,,,"(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)." 21:21:8.0.1.1.20.4.1.110,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3970 Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid.,FDA,,,"[82 FR 48763, Oct. 20, 2017, as amended at 90 FR 55982, Dec. 4, 2025]","(a) Identification. A device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid is a qualitative in vitro device intended for the detection and identification of microbial-associated nucleic acid sequences from patients suspected of meningitis or encephalitis. A device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid is intended to aid in the diagnosis of meningitis or encephalitis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings. (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 studies: Analytical sensitivity (limit of detection), inclusivity, reproducibility, interference, cross reactivity, and specimen stability. (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 comparator 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) The Intended Use statement in the device labeling must include a statement that the device is intended to be used in conjunction with standard of care culture. (6) 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. (7) The device labeling must include a limitation stating that the negative results do not preclude the possibility of central nervous system infection. (8) The device labeling must include a limitation stating that device results are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. (9) The device labeling must include a limitation stating that positive results do not mean that the organism detected is infectious or is the causative agent for clinical symptoms. (10) As part of the risk management activities performed under 21 CFR 820.10(c) design and development, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument." 21:21:8.0.1.1.20.4.1.111,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3975 Device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis.,FDA,,,"[90 FR 40728, Aug. 21, 2025]","(a) Identification. A device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis is a qualitative in vitro diagnostic device intended for the detection of microbial nucleic acid sequences in vaginal specimens collected from patients with signs and symptoms of vaginitis or bacterial vaginosis. This device is intended to aid in the diagnosis of vaginitis or bacterial vaginosis when used in conjunction with clinical signs and symptoms and other laboratory findings. (b) Classification. Class II (special controls). The special controls for this device are: (1) Design verification and validation must include: (i) Documentation with a detailed device description of device components; ancillary reagents required but not provided; and explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection. (ii) Documentation with information that demonstrates the performance characteristics of the device, including: (A) Limit of Detection; (B) Precision (reproductivity); (C) Analytical specificity; (D) Analytical reactivity (inclusivity); (E) Specimen stability; and (F) Effects of interfering substances. (iii) Detailed documentation from a prospective clinical study. As appropriate to the intended use, the prospective clinical study must be performed on an appropriate study population, including women of various ages and ethnicities. The prospective clinical study must compare the device performance to results obtained from well-accepted comparator 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) A detailed explanation of the interpretation of results and acceptance criteria; (ii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, clinical performance stratified by patient demographics such as race, ethnicity, age, and pregnancy status. (iii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, a summary of device results in an asymptomatic population with demographic characteristics appropriate to the intended use population. (iv) For devices with an intended use that includes detection of either Candida species or bacteria associated with bacterial vaginosis, a limitation that Candida species and bacterial compositions associated with bacterial vaginosis can be present as part of normal vaginal flora and results should be considered in conjunction with available clinical information." 21:21:8.0.1.1.20.4.1.112,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.,FDA,,,"[74 FR 52138, Oct. 9, 2009]","(a) Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses: (1) Influenza A and Influenza B; (2) Influenza A subtype H1 and Influenza A subtype H3; (3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B; (4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus; (5) Human Metapneumovirus; (6) Rhinovirus; and (7) Adenovirus. (b) Classification. Class II (special controls). The special controls are: (1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;” (2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and (3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents." 21:21:8.0.1.1.20.4.1.113,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3981 Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test.,FDA,,,"[89 FR 66554, Aug. 16, 2024]","(a) Identification. A device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test is an in vitro diagnostic device intended for the detection and identification of SARS-CoV-2 and other microbial agents when in a multi-target test in human clinical respiratory specimens from patients suspected of respiratory infection who are at risk for exposure or who may have been exposed to these agents. The device is intended to aid in the diagnosis of respiratory infection in conjunction with other clinical, epidemiologic, and laboratory data or other risk factors. (b) Classification. Class II (special controls). The special controls for this device are: (1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: Analytes and targets the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate. (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 specimen types claimed by this device; alternatively, the sample 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 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 specimens; (ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies including the following, as applicable: Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, precision, reproducibility, and clinical studies; (iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing; (iv) A warning statement that viral culture should not be attempted in cases of positive results for SARS-CoV-2 and/or any similar microbial agents unless a facility with an appropriate level of laboratory biosafety ( e.g., BSL 3 and BSL 3+, etc.) is available to receive and culture specimens; and (v) A prominent statement that device performance has not been established for specimens collected from individuals not identified in the intended use population ( e.g., when applicable, that device performance has not been established in individuals without signs or symptoms of respiratory infection). (vi) Limiting statements that indicate that: (A) A negative test result does not preclude the possibility of infection; (B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician; (C) There is a risk of incorrect results due to the presence of nucleic acid sequence variants in the targeted pathogens; (D) That positive and negative predictive values are highly dependent on prevalence; (E) Accurate results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and (F) When applicable ( e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer-reviewed literature), that the clinical performance may be affected by testing a specific clinical subpopulation or for a specific claimed specimen type. (4) Design verification and validation must include: (i) Detailed documentation, including performance results, from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, as appropriate, additional characterized clinical samples. The clinical study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained using a comparator that FDA has determined is appropriate. Detailed documentation must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses. (ii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel respiratory pathogen isolates or strains ( e.g., regular review of published literature and periodic in silico analysis of target sequences to detect possible mismatches). All results of this protocol, including any findings, must be documented and must include any additional data analysis that is requested by FDA in response to any performance concerns identified under this section or identified by FDA during routine evaluation. Additionally, if requested by FDA, these evaluations must be submitted to FDA for FDA review within 48 hours of the request. Results that are reasonably interpreted to support the conclusion that novel respiratory pathogen strains or isolates impact the stated expected performance of the device must be sent to FDA immediately. (iii) A detailed description of the identity, phylogenetic relationship, and other recognized characterization of the respiratory pathogen(s) that the device is designed to detect. In addition, detailed documentation describing how to interpret the device results and other measures that might be needed for a laboratory diagnosis of respiratory infection. (iv) A detailed device description, including device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device ( e.g., saturation level of hybridization and maximum amplification and detection cycle number, etc.), internal and external controls, and computational path from collected raw data to reported result ( e.g., how collected raw signals are converted into a reported signal and result), as applicable. (v) A detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review. (vi) For devices intended for the detection and identification of microbial agents for which an FDA recommended reference panel is available, design verification and validation must include the performance results of an analytical study testing the FDA recommended reference panel of characterized samples. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens, the design verification and validation must include a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. An evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (5) When applicable, performance results of the analytical study testing the FDA recommended reference panel described in paragraph (b)(4)(vi) of this section must be included in the device's labeling under § 809.10(b) of this chapter. (6) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens in addition to detection of SARS-CoV-2 and similar microbial agents, the required labeling under § 809.10(b) of this chapter must include the following: (i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation. (ii) Where applicable, a warning statement that reads if infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to State or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. (iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required followup actions or retesting in the case of an unusual or unexpected device result. (iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated ( i.e., H1-2009 and H3), this result requires notification of appropriate local, State, or Federal public health authorities to determine necessary measures for verification and to further determine whether the specimen represents a novel strain of Influenza A. (7) If one of the actions listed at section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain: (i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those influenza viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. (ii) Within 60 days from the date that FDA notifies manufacturers that characterized influenza viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by: (A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or (B) In a section of the device's label or in other labeling that accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's website, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the website containing this information and must allow unrestricted viewing access." 21:21:8.0.1.1.20.4.1.114,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3985 Device to detect and identify microorganisms and associated resistance marker nucleic acids directly in respiratory specimens.,FDA,,,"[84 FR 9228, Mar. 14, 2019]","(a) Identification. A device to detect and identify microorganisms and associated resistance marker nucleic acids directly from respiratory specimens is an in vitro diagnostic device intended for the detection and identification of microorganisms and associated resistance markers in respiratory specimens collected from patients with signs or symptoms of respiratory infection. The device is intended to aid in the diagnosis of respiratory infection in conjunction with clinical signs and symptoms and other laboratory findings. These devices do not provide confirmation of antibiotic susceptibility since mechanisms of resistance may exist other than those detected by the device. (b) Classification. Class II (special controls). The special controls for this device are: (1) The intended use for the 21 CFR 809.10 labeling must include a detailed description of what 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) The 21 CFR 809.10(b) labeling must include: (i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens. (ii) Performance characteristics from analytical studies, including, but not limited to, limit of detection, inclusivity, reproducibility, cross reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, and linearity, as applicable. (iii) A limiting statement that the device is intended to be used in conjunction with clinical history, signs and symptoms, and results of other diagnostic tests, including culture and antimicrobial susceptibility testing. (iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing. (v) A limiting statement that negative results for microorganisms do not preclude the possibility of infection, and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. (vi) If applicable, a limiting statement that detected microorganisms may not be the cause of lower respiratory tract infection and may be indicative of colonizing or normal respiratory flora. (vii) If applicable, a limiting statement that detection of resistance markers cannot be definitively linked to specific microorganisms and that the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora. (viii) If applicable, a limiting statement that detection of antibiotic resistance markers may not correlate with phenotypic gene expression. (3) The 21 CFR 809.10(b) labeling and any test report generated by the device must include a limiting statement that negative results for resistance markers do not indicate susceptibility of detected microorganisms. (4) Design verification and validation must include: (i) Performance characteristics from clinical studies that include prospective (sequential) samples and, if appropriate, additional characterized samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from an FDA accepted reference method and/or FDA accepted comparator method, as appropriate. Results from the clinical studies must include the clinical study protocol (including predefined statistical analysis plan, if applicable), clinical study report, and results of all statistical analyses. (ii) A detailed device description including the following: (A) Thorough description of the assay methodology including, but not limited to, primer/probe sequences, primer/probe design, and rationale for target sequence selection, as applicable. (B) Algorithm used to generate a final result from raw data (e.g., how raw signals are converted into a reported result). (iii) A detailed description of device software, including, but not limited to, validation activities and outcomes. (iv) As part of the risk management activities, an appropriate end user device training program must be offered as an effort to mitigate the risk of failure from user error." 21:21:8.0.1.1.20.4.1.115,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3990 Gastrointestinal microorganism multiplex nucleic acid-based assay.,FDA,,,"[80 FR 67314, Nov. 2, 2015]","(a) Identification. A gastrointestinal microorganism multiplex nucleic acid-based assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple gastrointestinal microbial nucleic acids extracted from human stool specimens. The device detects specific nucleic acid sequences for organism identification as well as for determining the presence of toxin genes. The detection and identification of a specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestinal infection when used in conjunction with clinical evaluation and other laboratory findings. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks. (b) Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Gastrointestinal Microorganism Multiplex Nucleic Acid-Based Assays for Detection and Identification of Microorganisms and Toxin Genes from Human Stool Specimens.” For availability of the guideline document, see § 866.1(e)." 21:21:8.0.1.1.20.4.1.116,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.4001 A multiplex respiratory panel to detect and identify emerging respiratory pathogen(s) and common respiratory pathogens in human clinical specimens.,FDA,,,"[90 FR 40711, Aug. 21, 2025]","(a) Identification. A multiplex respiratory panel to detect and identify emerging respiratory pathogen(s) and common respiratory pathogens in human clinical specimens is identified as an in vitro diagnostic device intended for the qualitative detection and identification of both emerging and common respiratory pathogens from individuals meeting specific emerging respiratory pathogen clinical and/or epidemiological criteria. For example, clinical signs and symptoms associated with infection of the emerging respiratory pathogen, contact with a probable or confirmed emerging respiratory pathogen case, history of travel to geographic locations where cases of the emerging respiratory pathogen were detected, or other epidemiological links for which testing of the emerging respiratory pathogen may be indicated. A device to detect and identify emerging respiratory pathogen(s) and common respiratory pathogens in human clinical specimens, and in turn to distinguish emerging respiratory pathogen(s) from common respiratory pathogens, is intended to aid in the differential diagnosis of the emerging respiratory pathogen infection, in conjunction with other clinical, epidemiologic, and laboratory data, in accordance with the guidelines provided by the appropriate public health authorities. (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 description of what the device detects and measures, the specimen types, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate. (2) The labeling required under § 809.10 of this chapter must include: (i) A device description, including the parts that make up the device, ancillary reagents required but not provided, and an explanation of the methodology. (ii) Performance characteristics from analytical studies, including cut-off (if applicable), analytical sensitivity ( i.e., limit of detection), inclusivity, reproducibility, interference, cross-reactivity, instrument carryover/cross-contamination (if applicable), and specimen stability. (iii) Detailed instructions for minimizing the risk of potential users' exposure to the emerging respiratory pathogen(s) that may be present in test specimens and those used as control materials. (iv) Detailed instructions for minimizing the risk of generating false positive test results due to carry-over contamination from positive test specimens and/or positive control materials. (v) A warning statement that the interpretation of test results requires experienced healthcare professionals who have training in principles and use of infectious disease diagnostics and reporting of results, in conjunction with the patient's medical history, clinical signs and symptoms, and the results of other diagnostic tests. (vi) A warning statement that culture should not be attempted in cases of positive results for an emerging respiratory pathogen unless a facility with an appropriate level of laboratory biosafety ( e.g., BSL 3 and BSL 3+) is available to receive and culture specimens. (vii) A warning statement that device positive results for one or more common respiratory pathogens do not rule out bacterial infection, or co-infection with other common respiratory pathogens. (viii) A warning statement that respiratory pathogen(s) detected may not be the definite cause of disease. (ix) A warning statement that the use of additional laboratory testing ( e.g. bacterial culture, immunofluorescence, x-ray findings) and clinical presentation must be taken into consideration in order to obtain the final diagnosis of a respiratory infection. (x) A limiting statement that device negative results for the common respiratory pathogens do not preclude infection of a respiratory pathogen and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. (xi) A limiting statement that analyte targets ( e.g., pathogen nucleic acid sequences or other molecular signatures) may persist in vivo, independent of organism viability. Detection of analyte target(s) does not imply that the corresponding pathogen(s) is infectious, nor is the causative agent(s) for clinical symptoms. (xii) A limiting statement that detection of pathogen nucleic acid sequences or other molecular signatures is dependent upon proper specimen collection, handling, transportation, storage and preparation. Failure to observe proper procedures in any one of these steps can lead to incorrect results. There is a risk of false negative values resulting from improperly collected, transported, or handled specimens. (xiii) A limiting statement that there is a risk of false positive values resulting from cross-contamination by target organisms, their nucleic acids or amplified product, or from non-specific signals in the assay. (xiv) A limiting statement that there is a risk of false negative results due to the presence of nucleic acid sequence variants in the pathogen targets of the device. (xv) A limiting statement that device performance was not established in immunocompromised patients. (xvi) A limiting statement that positive and negative predictive values are highly dependent on prevalence. The device performance was established during one or more specific respiratory seasons. The performance for some respiratory pathogens may vary depending on the prevalence and patient population tested. False positive test results are likely when prevalence of disease due to a particular respiratory pathogen is low or non-existent in a community. (xvii) In situations where the performance of the device was estimated based largely on testing pre-selected banked retrospective clinical specimens and/or contrived clinical specimen, a limiting statement that the estimated device performance of that specific pathogen or pathogen subtype may not reflect the performance or prevalence in the intended use population. (xviii) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that testing with the device should not be performed unless the patient meets clinical and/or epidemiologic criteria for testing suspected specimens of the emerging respiratory pathogen. (xix) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that positive results obtained with the device for the emerging respiratory pathogen are for the presumptive identification of that pathogen and that the definitive identification of the emerging respiratory pathogen requires additional testing and confirmation procedures in consultation with the appropriate public health authorities ( e.g., local or state public health departments) for whom reporting is necessary. (xx) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that negative results for the emerging respiratory pathogen, even in the context of device positive results for one or more of the common respiratory pathogens, do not preclude infection with the emerging respiratory pathogen and should not be used as the sole basis for patient management decisions. (xxi) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that negative results for the emerging respiratory pathogen may be due to infection of the emerging respiratory pathogen at a specific respiratory tract location that may not be detected by a particular clinical specimen type. A negative result for the emerging respiratory pathogen in an asymptomatic individual does not rule out the possibility of future illness and does not demonstrate that the individual is not infectious. (xxii) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that a nationally notifiable Rare Disease of Public Health Significance caused by an emerging respiratory pathogen must be reported, as appropriate, to public health authorities in accordance with local, state, and federal law. (3) Design verification and validation must include: (i) Performance results of an appropriate clinical study ( e.g., a prospective clinical study) for each specimen type, and, if appropriate, results from additional characterized samples. The clinical study must be performed on a study population consistent with the intended use population and must compare the device performance to results obtained using FDA-accepted comparator methods or to expected negative results if the infection is not generally expected in the intended use population. Clinical specimens evaluated in the study must contain relevant organism concentrations applicable to the specimen type(s) and the targeted analyte(s). Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (ii) For devices with an intended use that includes detection of emerging respiratory pathogen(s) for which an FDA recommended panel is available, design verification and validation must include the performance results of an analytical study testing an FDA recommended reference panel of characterized samples that contain the emerging respiratory pathogen. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (iii) An appropriate risk mitigation strategy, including a detailed description of all procedures and methods, for the post-market identification of genetic mutations and/or novel respiratory pathogen isolates or strains ( e.g., regular review of published literature and annual in silico analysis of target sequences to detect possible mismatches. The required documentation for this device must also include all of the results, including any findings, from the application of this post-market mitigation strategy. (iv) For devices with an intended use that includes detection of multiple common respiratory pathogens, in addition to detecting emerging respiratory pathogen(s) in human clinical specimens, a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the common respiratory pathogens that the device is designed to detect is addressed. Also, address in detail how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory diagnosis of respiratory tract infection. Perform an evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (v) A detailed device description, including the parts that make up the device, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device ( e.g., saturation level of hybridization and maximum amplification and detection cycle number), internal and external controls, and computational path from collected raw data to reported result ( e.g., how collected raw signals are converted into a reported signal and result), as applicable and appropriate. (vi) A detailed description of the device software, including software applications and hardware-based devices that incorporate software. (vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiate between the Influenza A virus subtypes in human clinical specimens, in addition to detecting emerging respiratory pathogen(s), a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. Perform an evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (4) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiate between the Influenza A virus subtypes in human clinical specimens, in addition to detecting emerging respiratory pathogen(s), the labeling required under § 809.10 of this chapter must include the following: (i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary. (ii) Where applicable, a warning statement that reads if infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. (iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling required under § 809.10(b)(9) of this chapter must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required follow up actions or retesting in the case of an unusual or unexpected device result. (iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated ( e.g., H1-2009 and H3), this result requires notification of appropriate local, state, or federal public health authorities to determine necessary measures for verification and to further determine whether the specimen represents a novel strain of Influenza A. (5) The manufacturer must perform annual analytical reactivity testing of the device with contemporary influenza strains. This annual analytical reactivity testing must meet the following criteria: (i) The appropriate strains to be tested will be identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and sourced from CDC or an FDA designated source. If the annual strains are not available from CDC, FDA will identify an alternative source for obtaining the requisite strains. (ii) The testing must be conducted according to a standardized protocol considered and determined by FDA to be acceptable and appropriate. (iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity testing must be included as part of the device's labeling. If a device has not been on the market long enough for 3 years of annual analytical reactivity testing to have been conducted since the device received marketing authorization from FDA, then the results of every annual analytical reactivity testing since the device received marketing authorization from FDA must be included. The results must be presented as part of the device's labeling in a tabular format, which includes the detailed information for each virus tested as described in the certificate of authentication, either by: (A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or (B) In the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the web page containing this information and must allow unrestricted viewing access. (6) If one of the actions listed at section 564(b)(1)(A)-(D) of the FD&C Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain: (i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. The procedure and location of testing may depend on the nature of the emerging virus. (ii) Within 60 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by: (A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that physically accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or (B) In a section of the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the web page containing this information and must allow unrestricted viewing access." 21:21:8.0.1.1.20.4.1.12,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3125,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(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." 21:21:8.0.1.1.20.4.1.13,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3130 Clostridium difficile toxin gene amplification assay.,FDA,,,"[80 FR 51939, Aug. 27, 2015]","(a) Identification. A Clostridium difficile toxin gene amplification assay is a device that consists of reagents for the amplification and detection of target sequences in Clostridium difficile toxin genes in fecal specimens from patients suspected of having Clostridium difficile infection (CDI). The detection of clostridial toxin genes, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of CDI caused by Clostridium difficile. (b) Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Toxin Gene Amplification Assays for the Detection of Clostridium difficile; Guideline for Industry and Food and Drug Administration Staff.” See § 866.1(e) for information on obtaining this document." 21:21:8.0.1.1.20.4.1.14,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3135,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59226, Nov. 3, 1998]","(a) Identification. Coccidioides immitis serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Coccidioides immitis in serum. The identification aids in the diagnosis of coccidioidomycosis caused by a fungus belonging to the genus Coccidioides and provides epidemiological information on diseases caused by this microorganism. An infection with Coccidioides immitis produces symptoms varying in severity from those accompanying the common cold to those of influenza. (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." 21:21:8.0.1.1.20.4.1.15,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3140,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000]","(a) Identification. Corynebacterium spp. serological reagents are devices that consist of antisera conjugated with a fluorescent dye used to identify Corynebacterium spp. from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Corynebacterium and provides epidemiological information on diseases caused by these microorganisms. The principal human pathogen of this genus, Corynebacterium diphtheriae, causes diphtheria. However, many other types of corynebacteria form part of the normal flora of the human respiratory tract, other mucus membranes, and skin, and are either nonpathogenic or have an uncertain role. (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." 21:21:8.0.1.1.20.4.1.16,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3145 Coxsackievirus serological reagents.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000]","(a) Identification. Coxsackievirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to coxsackievirus in serum. Additionally, some of these reagents consist of coxsackievirus antisera conjugated with a fluorescent dye that are used to identify coxsackievirus from clinical specimens or from tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of coxsackievirus infections and provides epidemiological information on diseases caused by these viruses. Coxsackieviruses produce a variety of infections, including common colds, meningitis (inflammation of brain and spinal cord membranes), herpangina (brief fever accompanied by ulcerated lesions of the throat), and myopericarditis (inflammation of heart tissue). (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." 21:21:8.0.1.1.20.4.1.17,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3165,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59226, Nov. 3, 1998]","(a) Identification. Cryptococcus neoformans serological reagents are devices that consist of antigens used in serological tests to identify antibodies to Cryptococcus neoformans in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) and are used to identify Cryptococcus neoformans directly from clinical specimens or from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of cryptococcosis and provides epidemiological information on this type of disease. Cryptococcosis infections are found most often as chronic meningitis (inflammation of brain membranes) and, if not treated, are usually fatal. (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." 21:21:8.0.1.1.20.4.1.18,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3169 Hepatitis C virus antibody tests.,FDA,,,"[86 FR 66176, Nov. 22, 2021]","(a) Identification. A hepatitis C virus (HCV) antibody test is identified as an in vitro diagnostic device intended for use with human serum, plasma, or other matrices as a prescription device that aids in the diagnosis of HCV infection in persons with signs and symptoms of hepatitis and in persons at risk for hepatitis C infection. The test is not intended for screening blood, plasma, cell, or tissue donors. (b) Classification. Class II (special controls). The special controls for this device are: (1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the test is not intended for the screening of blood, plasma, and cell or tissue donors. (ii) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate: (A) When appropriate, the performance characteristics of the test have not been established in populations of immunocompromised or immunosuppressed patients or, other special populations where test performance may be affected. (B) The detection of HCV antibodies indicates a present or past infection with hepatitis C virus, but does not differentiate between acute, chronic, or resolved infection. (C) The specimen types for which the device has been cleared, and that use of the test with specimen types other than those specifically cleared for this device may result in inaccurate test results. (D) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with the individual's clinical presentation, history, and other laboratory results. (E) A non-reactive test result may occur early during acute infection, prior to development of a host antibody response to infection, or when analyte levels are below the limit of detection of the test. (iii) A detailed explanation of the principles of operation and procedures for performing the test. (2) Design verification and validation must include the following: (i) A detailed device description, including all parts that make up the device, ancillary reagents required but not provided, an explanation of the device methodology, and design of the antigen(s) and capture antibody(ies) sequences, rationale for the selected epitope(s), degree of amino acid sequence conservation of the target, and the design and nature of all primary, secondary, and subsequent standards used for calibration. (ii) Documentation and characterization ( e.g., supplier, determination of identity, and stability) of all critical reagents (including description of the antigen(s) and capture antibody(ies)), and protocols for maintaining product integrity throughout its labeled shelf life. (iii) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (iv) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (v) Stability studies for reagents must include documentation of an assessment of real-time stability for multiple reagent lots using the indicated specimen types and must use acceptance criteria that ensure that analytical and clinical performance characteristics are met when stability is assigned based on the extremes of the acceptance range. (vi) All stability protocols, including acceptance criteria. (vii) Final release test results for each lot used in clinical studies. (viii) Multisite reproducibility study that includes the testing of three independent production lots. (ix) Analytical performance studies and results for determining the limit of blank (LoB), limit of detection (LoD), cutoff, precision (reproducibility) including lot-to-lot and/or instrument-to-instrument precision, interference, cross reactivity, carryover, hook effect, seroconversion panel testing, matrix equivalency, specimen stability, reagent stability, and cross-genotype antibody detection sensitivity, when appropriate. (x) Analytical sensitivity of the test is the same or better than that of other cleared or approved tests. (xi) Detailed documentation of clinical performance testing from a multisite clinical study. Performance must be analyzed relative to an FDA cleared or approved HCV antibody test, or a comparator that FDA has determined is appropriate. This study must be conducted using appropriate patient samples, with an acceptable number of HCV positive and negative samples in applicable risk categories. Additional relevant patient groups must be validated as appropriate. The samples may be a combination of fresh and repository samples, sourced from geographically diverse areas. The study designs, including number of samples tested, must be sufficient to meet the following criteria: (A) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 95 percent. (B) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 96 percent. (3) For any HCV antibody test intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, apply: (i) Clinical studies must be conducted at PoC sites. (ii) Additional labeling must include a brief summary of the instructions for use that are appropriate for use in a PoC environment." 21:21:8.0.1.1.20.4.1.19,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3170 Nucleic acid-based hepatitis C virus ribonucleic acid tests.,FDA,,,"[86 FR 66172, Nov. 22, 2021]","(a) Identification. A nucleic acid-based hepatitis C virus (HCV) ribonucleic acid (RNA) test is identified as an in vitro diagnostic device intended for prescription use as an aid in the diagnosis of HCV infection in specified populations, and/or as an aid in the management of HCV-infected patients including guiding the selection of genotype-specific treatment in individuals with chronic HCV infection. The test is intended for use with human serum or plasma. The test is not intended for use as a donor screening test for the presence of HCV antibodies in blood, blood products, or tissue donors. (b) Classification. Class II (special controls). The special controls for this device are: (1) For all nucleic acid-based HCV RNA tests, the labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the test is not intended for use as a donor screening test for the presence of HCV RNA from human cells, tissues, and cellular and tissue-based products. (ii) A detailed explanation of the principles of operation and procedures for performing the assay. (iii) A detailed explanation of the interpretation of results. (iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. These limitations must include, but are not limited to, statements that indicate: (A) The specimen types for which the device has been cleared and that use of this test kit with specimen types other than those specifically cleared for this device may result in inaccurate test results. (B) When applicable, that assay performance characteristics have not been established in populations of immunocompromised or immunosuppressed patients or, other populations where test performance may be affected. (C) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with the individual's clinical presentation, history, and other laboratory results. (2) For all nucleic acid-based HCV RNA tests, the design verification and validation must include: (i) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the device methodology. Additional information appropriate to the technology must be included such as design of primers and probes, rationale for the selected gene targets, specifications for amplicon size, and degree of nucleic acid sequence conservation. (ii) For devices with assay calibrators, the design and nature of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a standardized reference material that FDA has determined is appropriate ( e.g., a recognized consensus standard). In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance or approval, or when there is a transition to a new calibration standard. (iii) Documentation and characterization ( e.g., determination of the identity, supplier, purity, and stability) of all critical reagents (including nucleic acid sequences for primers and probes) and protocols for maintaining product integrity. (iv) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including, but not limited to, limit of detection (LoD), upper and lower limits of quantitation (ULoQ and LLoQ, respectively), linearity, precision, endogenous and exogenous interferences, cross reactivity, carryover, matrix equivalency, and sample and reagent stability. Samples selected for use in analytical studies or used to prepare samples for use in analytical studies must be from subjects with clinically relevant circulating genotypes in the United States. Cross-reactivity studies must include samples from HCV RNA negative subjects with other causes of liver disease, including autoimmune hepatitis, alcoholic liver disease, chronic hepatitis B virus, primary biliary cirrhosis, and nonalcoholic steatohepatitis, when applicable. The effect of each claimed nucleic-acid isolation and purification procedure on detection must be evaluated. (v) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (vi) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (vii) Multisite reproducibility study that includes the testing of three independent production lots. (viii) All stability protocols, including acceptance criteria. (ix) Final release test results for each lot used in clinical studies. (x) Analytical sensitivity and specificity of the test must be the same or better than that of other cleared or approved tests. (xi) Lot-to-lot precision studies, as appropriate. (3) For devices intended for the qualitative detection of HCV RNA, in addition to the special controls listed in paragraphs (b)(1) and (2) of this section, the design verification and validation must include detailed documentation of performance from a multisite clinical study. Performance must be analyzed relative to an FDA cleared or approved qualitative HCV RNA test, or a comparator that FDA has determined is appropriate. This study must be conducted using appropriate patient samples, with appropriate numbers of HCV positive and negative samples in applicable risk categories. Additional genotypes must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. The study designs, including number of samples tested, must be sufficient to meet the following criteria: (i) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 95 percent. (ii) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 96 percent. (4) For devices intended for the quantitative detection of HCV RNA, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, apply: (i) Labeling required under § 809.10(b) of this chapter must include a prominent statement that the test is not intended as a diagnostic test to confirm the presence of active HCV infection, when applicable. (ii) Design verification and validation must include the following: (A) Detailed documentation of the following analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including but not limited to: LoD, ULoQ and LLoQ. LoD, LLoQ, and linearity studies must demonstrate acceptable device performance with all HCV genotypes detected by the device. (B) Detailed documentation of clinical performance testing from either: ( 1 ) A multisite clinical study with an appropriate number of clinical samples from chronically HCV infected patients in which the results are compared to an FDA-cleared or approved quantitative HCV RNA test, or a comparator that FDA has determined is appropriate. This study must include a sufficient number of HCV positive samples containing an analyte concentration near the LLoQ to describe performance at this level. Clinical samples must cover the full range of the device output and must be consistent with the distribution of these genotypes in the U.S. population. Clinical samples may be supplemented with diluted clinical samples for those viral load concentrations that are not sufficiently covered by natural clinical specimens, or ( 2 ) A clinical study with prospectively collected samples demonstrating clinical validity of the device. (C) Detailed documentation of a qualitative analysis near the lower end of the measuring range demonstrating acceptable performance when used as an aid in diagnosis. (5) For devices intended for HCV RNA genotyping, in addition to the special controls listed in paragraphs (b)(1) and (2) of this section, design verification and validation must include the following: (i) Detailed documentation of an analytical performance study demonstrating the LoD for all HCV genotypes detected by the device. (ii) Detailed documentation, including results, of a multisite clinical study that assesses genotyping accuracy ( i.e., the proportion of interpretable results that match with the reference method result) and the genotyping rate ( i.e., the proportion of results that were interpretable). (6) For any nucleic acid-based HCV RNA test intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, apply: (i) Clinical studies must be conducted at PoC sites. (ii) Additional labeling must include a brief summary of the instructions for use that are appropriate for use in a PoC environment." 21:21:8.0.1.1.20.4.1.2,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3020 Adenovirus serological reagents.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(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." 21:21:8.0.1.1.20.4.1.20,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3172 Qualitative hepatitis B virus antigen assays.,FDA,,,"[90 FR 44975, Sept. 18, 2025]","(a) Identification. A qualitative hepatitis B virus (HBV) antigen assay is identified as an in vitro diagnostic device intended for prescription use for qualitative use with human serum, plasma, or other matrices that aids in the diagnosis of chronic or acute HBV infection. HBV surface antigen (HbsAg) is also used for screening of HBV infection in pregnant women to identify neonates who are at risk of acquiring hepatitis B during perinatal period. The assay is not intended for screening of blood, plasma, cells, or tissue donors. (b) Classification. Class II (special controls). The special controls for this device are: (1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the assay is not intended for the screening of blood, plasma, cells, or tissue donors. (ii) A detailed explanation of the principles of operation and procedures for performing the assay. (iii) A detailed explanation of the interpretation of results. (iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include statements that indicate: (A) The specimen types for which the device has been cleared, and that use of this assay with specimen types other than those specifically cleared for this device may result in inaccurate assay results. (B) When appropriate, performance characteristics of the assay have not been established in populations of immunocompromised or immunosuppressed patients or other populations where assay performance may be affected. (C) Diagnosis of hepatitis B infection should not be established on the basis of a single assay result but should be determined by a licensed healthcare professional in conjunction with the clinical presentation, history, and other diagnostic procedures. (D) Detection of HBV antigens indicates a current infection with hepatitis B virus but does not differentiate between acute or chronic infection. False reactive HbsAg result may occur for up to 2 weeks after vaccination with HbsAg containing vaccine. (E) Current methods for the detection of hepatitis B antigens may not detect all potentially infected individuals. A non-reactive assay result does not exclude the possibility of exposure to or infection with hepatitis B virus. A non-reactive assay result in individuals with prior exposure to hepatitis B may be due to but not limited to antigen levels below the detection limit of this assay or lack of antigen reactivity to the antibodies in this assay. HBV mutants lacking the ability to produce antigens have been reported. These may occur as “escape” mutants in the presence of anti-HBV antibodies and such patients may be infectious. (F) Results obtained with this assay may not be used interchangeably with results obtained with a different manufacturer's assay. (2) Design verification and validation must include the following: (i) A detailed device description, including all parts that make up the device, ancillary reagents required but not provided, an explanation of the device methodology, design of the capture antibody(ies), external controls, and computational path from collected raw data to reported result ( e.g., how collected raw signals are converted into a reported signal and result), as applicable to the detection method and device design. (ii) For devices with assay calibrators, the design and composition of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a standardized reference material that FDA has determined is appropriate ( e.g., a recognized consensus standard). In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance or approval, or when there is a transition to a new calibration standard. (iii) Documentation and characterization ( e.g., supplier, determination of identity, purity, and stability) of all critical reagents (including description of the capture antibody(ies)), and protocols for maintaining product integrity throughout its labeled shelf life. (iv) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on assay performance. (v) Final release criteria to be used for manufactured assay lots with appropriate evidence that lots released at the extremes of the specifications will meet the identified analytical and clinical performance characteristics as well as stability. (vi) Stability studies for reagents must include documentation of an assessment of real-time stability for multiple reagent lots using the indicated specimen types and must use acceptance criteria that ensure that analytical and clinical performance characteristics are met when stability is assigned based on the extremes of the acceptance range. (vii) All stability protocols, including acceptance criteria. (viii) Final release assay results for each lot used in clinical studies. (ix) Reproducibility study data that includes the testing of three independent production lots. (x) Detailed documentation of analytical performance studies conducted, as appropriate to the technology, specimen types tested, and intended use of the device, including, the limit of blank (LoB), limit of detection (LoD), cutoff, precision (reproducibility) including lot-to-lot and/or instrument-to-instrument precision, interference, cross reactivity, carryover, hook effect, seroconversion panel testing, matrix equivalency, prominent mutants/variants detection ( e.g., for HbsAg), specimen stability, reagent stability, and cross-genotype antigen detection sensitivity, when appropriate. (xi) Analytical sensitivity of the assay that is the same or better than that of other cleared or approved assays. (xii) For devices with associated software or instrumentation, documentation must include a detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review. (xiii) Detailed documentation and results from a clinical study. Performance must be analyzed relative to an FDA cleared or approved HBV antigen assay or a comparator that FDA has determined is appropriate. This study must be conducted using appropriate patient samples, with an appropriate number of HBV reactive and non-reactive samples in applicable risk and disease categories, and any applicable confirmatory testing. Additional relevant patient groups must be validated as appropriate. The samples must include prospective (sequential) samples for each identified specimen type and, as appropriate, additional characterized clinical samples. Samples must be sourced from geographically diverse areas. This study must be conducted in the appropriate settings by the intended users to demonstrate clinical performance." 21:21:8.0.1.1.20.4.1.21,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3173 Hepatitis B virus antibody assays.,FDA,,,"[90 FR 44976, Sept. 18, 2025]","(a) Identification. A hepatitis B virus (HBV) antibody assay is identified as an in vitro diagnostic device intended for prescription use in the detection of antibodies to HBV in human serum, plasma, or other matrices, and as a device that aids in the diagnosis of HBV infection in persons with signs and symptoms of hepatitis and in persons at risk for hepatitis B infection. Results from assays may be qualitative or quantitative, such as quantitative anti-HBs. In addition, results from an anti-HBc IgM (IgM antibodies to core antigen) assay indicating the presence of anti-HBc IgM are indicative of recent HBV infection. Anti-HBs (antibodies to surface antigen) assay results may be used as an aid in the determination of susceptibility to HBV infection in individuals prior to or following HBV vaccination or when vaccination status is unknown. The assay is not intended for screening of blood, plasma, cells, or tissue donors. The assay is intended as an aid in diagnosis in conjunction with clinical findings and other diagnostic procedures. (b) Classification. Class II (special controls). The special controls for this device are: (1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the assay is not intended for the screening of blood, plasma, cells, or tissue donors. (ii) A detailed explanation of the principles of operation and procedures for performing the assay. (iii) A detailed explanation of the interpretation of results. (iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include statements that indicate: (A) When appropriate, performance characteristics of the assay have not been established in populations of immunocompromised or immunosuppressed patients or other special populations where assay performance may be affected. (B) Detection of HBV antibodies to a single viral antigen indicates a present or past infection with hepatitis B virus, but does not differentiate between acute, chronic, or resolved infection. (C) The specimen types for which the device has been cleared, and that use of the assay with specimen types other than those specifically cleared for this device may result in inaccurate assay results. (D) Diagnosis of hepatitis B infection should not be established on the basis of a single assay result but should be determined by a licensed healthcare professional in conjunction with the clinical presentation, history, and other diagnostic procedures. (E) A non-reactive assay result may occur early during acute infection, prior to development of a host antibody response to infection, or when analyte levels are below the limit of detection of the assay. (F) Results obtained with this assay may not be used interchangeably with results obtained with a different manufacturer's assay. (v) For devices intended for the quantitative detection of HBV antibodies (anti-HBs), in addition to the special controls listed in paragraphs (b)(1) and (2) of this section, labeling required under § 809.10(b) of this chapter must include: (A) The assay calibrators' traceability to a standardized reference material that FDA has determined is appropriate ( e.g., a recognized consensus standard) and the limit of blank (LoB), limit of detection (LoD), limit of quantitation (LoQ), linearity, and precision to define the analytical measuring interval. (B) Performance results of the analytical sensitivity study testing a standardized reference material that FDA has determined is appropriate ( e.g., a recognized consensus standard). (2) Design verification and validation must include the following: (i) Detailed device description, including all parts that make up the device, ancillary reagents required but not provided, an explanation of the device methodology, and design of the antigen(s) and capture antibody(ies) sequences, rationale for the selected epitope(s), degree of amino acid sequence conservation of the target, and the design and composition of all primary, secondary and subsequent standards used for calibration. (ii) Documentation and characterization ( e.g., supplier, determination of identity, and stability) of all critical reagents (including description of the antigen(s) and capture antibody(ies)), and protocols for maintaining product integrity throughout its labeled shelf life. (iii) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on assay performance. (iv) Final release criteria to be used for manufactured assay lots with appropriate evidence that lots released at the extremes of the specifications will meet the identified analytical and clinical performance characteristics as well as stability. (v) Stability studies for reagents must include documentation of an assessment of real-time stability for multiple reagent lots using the indicated specimen types and must use acceptance criteria that ensure that analytical and clinical performance characteristics are met when stability is assigned based on the extremes of the acceptance range. (vi) All stability protocols, including acceptance criteria. (vii) When applicable, analytical sensitivity of the assay that is the same or better than that of other cleared or approved assays. (viii) Analytical performance studies and results for determining the limit of blank (LoB), limit of detection (LoD), cutoff, precision (reproducibility), including lot-to-lot and/or instrument-to-instrument precision, interference, cross reactivity, carryover, hook effect, seroconversion panel testing, matrix equivalency, specimen stability, reagent stability, and cross-genotype antibody detection sensitivity, when appropriate. (ix) For devices intended for the detection of antibodies for which a standardized reference material (that FDA has determined is appropriate) is available, the analytical sensitivity study and results testing the standardized reference material. Detailed documentation of that study and its results must be provided, including the study protocol, study report, testing results, and all statistical analyses. (x) For devices with associated software or instrumentation, documentation must include a detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review. (xi) Detailed documentation of clinical performance testing from a clinical study with an appropriate number of HBV reactive and non-reactive samples in applicable risk categories and conducted in the appropriate settings by the intended users. Performance must be analyzed relative to an FDA cleared or approved HBV antibody assay or a comparator that FDA has determined is appropriate. Additional relevant patient groups must be validated as appropriate. The samples must include prospective (sequential) samples for each identified specimen type and, as appropriate, additional characterized clinical samples. Samples must be sourced from geographically diverse areas. (3) For any HBV antibody assay intended for quantitative detection of anti-HBV antibodies, the following special controls, in addition to those special controls listed in paragraphs (b)(1) and (2) of this section, also apply: (i) Detailed documentation of the metrological calibration traceability hierarchy to a standardized reference material that FDA has determined is appropriate. (ii) Detailed documentation of the following analytical performance studies conducted, as appropriate to the technology, specimen types tested, and intended use of the device, including upper and lower limits of quantitation (UloQ and LloQ, respectively), linearity using clinical samples, and an accuracy study using the recognized international standard material." 21:21:8.0.1.1.20.4.1.22,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3174 Hepatitis B virus nucleic acid-based assays.,FDA,,,"[90 FR 44977, Sept. 18, 2025]","(a) Identification. A nucleic acid-based hepatitis B virus (HBV) assay is identified as an in vitro diagnostic device intended for prescription use in the detection of HBV nucleic acid in specimens from individuals with antibody evidence of HBV infection. In these devices, the detection of HBV nucleic acid is used as an aid in the management of HBV-infected individuals. The assay is intended for use with human serum or plasma (and other matrices as applicable) from individuals with HBV. The assay is not intended for use as a donor screening assay for the presence of HBV nucleic acids in blood, blood products, plasma, cells, or tissue donors, or as a diagnostic assay to confirm the presence of HBV infection. (b) Classification. Class II (special controls). The special controls for this device are: (1) Labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the assay is not intended for use as a screening assay for the presence of HBV DNA in blood or blood products, plasma, cells, or tissue donors, or as a diagnostic assay to confirm the presence of HBV infection. (ii) A detailed explanation of the principles of operation and procedures for performing the assay. (iii) A detailed explanation of the interpretation of results. (iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and/or management. These limitations must include statements that indicate: (A) Management of patients undergoing HBV treatment should not be established on the basis of a single assay result but should be determined by a licensed healthcare professional in conjunction with the clinical presentation, history, and other diagnostic procedures, e.g., HBV serologic testing, liver function assays, liver elastography, etc. (B) The specimen types for which the device has been cleared, and that use of this assay with specimen types other than those specifically cleared for this device may result in inaccurate assay results. (C) The results obtained with this assay may not be used interchangeably with results obtained with a different manufacturer's assay. (2) Design verification and validation must include the following: (i) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the device methodology. Additional information appropriate to the technology must be included such as design of primers and probes, rationale for the selected gene targets, specifications for amplicon size, and degree of nucleic acid sequence conservation. (ii) For devices with assay calibrators, the design and composition of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a standardized reference material that FDA has determined is appropriate ( e.g., a recognized consensus standard). In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance or approval, or when there is a transition to a new calibration standard. (iii) Documentation and characterization ( e.g., determination of the identity, supplier, purity, and stability) of all critical reagents (including nucleic acid sequences for primers and probes) and protocols for maintaining product integrity. (iv) Risk analysis and management strategies demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on assay performance. (v) Final release criteria to be used for manufactured assay lots with appropriate evidence that lots released at the extremes of the specification will meet the identified analytical and clinical performance characteristics as well as stability. (vi) Stability studies for reagents must include documentation of an assessment of real-time stability for multiple reagent lots using the indicated specimen types and must use acceptance criteria that ensure that analytical and clinical performance characteristics are met when stability is assigned based on the extremes of the acceptance range. (vii) All stability protocols, including acceptance criteria. (viii) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including limit of detection (LoD), linearity, precision, endogenous and exogenous interferences, cross-reactivity, carryover, matrix equivalency, sample and reagents stability, and as applicable, upper and lower limits of quantitation (ULoQ and LLoQ, respectively). Samples selected for use must be from subjects with clinically relevant circulating genotypes in the United States. Cross-reactivity studies must include samples from HBV nucleic acid negative subjects with other viral or non-viral causes of liver disease, including autoimmune hepatitis, alcoholic liver disease, chronic hepatitis C virus, primary biliary cirrhosis, and nonalcoholic steatohepatitis, when applicable. The effect of each identified nucleic-acid isolation and purification procedure on detection must be evaluated. (ix) Analytical sensitivity of the assay that is the same or better than that of other cleared or approved assays. (x) For devices with associated software or instrumentation, documentation must include a detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review. (xi) Detailed documentation of performance from a clinical study with a design and number of clinical samples (appropriately statistically powered) that is appropriate for the intended use of the device as well as conducted in the appropriate settings by the intended users. The samples must include prospective (sequential) samples for each claimed specimen type and, as appropriate, additional characterized clinical samples. Samples must be sourced from geographically diverse areas." 21:21:8.0.1.1.20.4.1.23,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3175 Cytomegalovirus serological reagents.,FDA,,,,"(a) Identification. Cytomegalovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to cytomegalovirus in serum. The identification aids in the diagnosis of diseases caused by cytomegaloviruses (principally cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease may cause severe congenital abnormalities, such as microcephaly (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and an infectious mononucleosis-like syndrome. (b) Classification. Class II (performance standards)." 21:21:8.0.1.1.20.4.1.24,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3180 Quantitative cytomegalovirus nucleic acid tests for transplant patient management.,FDA,,,"[89 FR 77450, Sept. 23, 2024]","(a) Identification. A quantitative cytomegalovirus (CMV) nucleic acid test for transplant patient management is identified as a device intended for prescription use in the detection of CMV and as an aid in the management of transplant patients to measure CMV deoxyribonucleic acid (DNA) levels in human plasma and/or whole blood using specified specimen processing, amplification, and detection instrumentation. The test is intended for use as an aid in the management of transplant patients with active CMV infection or at risk for developing CMV infection. The test results are intended to be interpreted by qualified healthcare professionals in conjunction with other relevant clinical and laboratory findings. (b) Classification. Class II (special controls). The special controls for this device are: (1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the device is not intended for use as a donor screening test for the presence of CMV DNA in blood or blood products. (ii) Limitations, which must be updated to reflect current clinical practice. The limitations must include, but are not limited to, statements that indicate: (A) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with clinical signs and symptoms and other relevant laboratory results; (B) Negative test results do not preclude CMV infection or tissue invasive CMV disease, and that CMV test results must not be the sole basis for patient management decisions. (iii) A detailed explanation of the interpretation of results and acceptance criteria must be provided and include specific warnings regarding the potential for variability in CMV viral load measurement when samples are measured by different devices. Warnings must include the following statement, where applicable: “Due to the potential for variability in CMV viral load measurements across different CMV assays, it is recommended that the same device be used for the quantitation of CMV viral load when managing CMV infection in individual patients.” (iv) A detailed explanation of the principles of operation and procedures for assay performance. (2) Design verification and validation must include the following: (i) Detailed documentation of the device description, including all parts that make up the device, reagents required for use with the CMV assay but not provided, an explanation of the methodology, design of the primer/probe sequences, rationale for the selected gene target, and specifications for amplicon size, guanine-cytosine content, and degree of nucleic acid sequence conservation. The design and nature of all primary, secondary, and tertiary quantitation standards used for calibration must also be described. (ii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's function. (iii) Documentation and characterization of all critical reagents ( e.g., determination of the identity, supplier, purity, and stability) and protocols for maintaining product integrity throughout its labeled shelf life. (iv) Stability data for reagents provided with the device and indicated specimen types, in addition to the basis for the stability acceptance criteria at all time points chosen across the spectrum of the device's indicated life cycle, which must include a time point at the end of shelf life. (v) All stability protocols, including acceptance criteria. (vi) Final lot release criteria, along with documentation of an appropriate justification that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (vii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel CMV stains ( e.g., regular review of published literature and annual in silico analysis of target sequences to detect possible primer or probe mismatches). All results of this protocol, including any findings, must be documented. (viii) Analytical performance testing that includes: (A) Detailed documentation of the following analytical performance studies: Limit of detection, upper and lower limits of quantitation, inclusivity, precision, reproducibility, interference, cross reactivity, carryover, quality control, specimen stability studies, and additional studies as applicable to specimen type and intended use for the device. (B) Identification of the CMV strains selected for use in analytical studies, which must be representative of clinically relevant circulating strains. (C) Inclusivity study results obtained with a variety of CMV genotypes as applicable to the specific assay target and supplemented by in silico analysis. (D) Reproducibility studies that include the testing of three independent production lots. (E) Documentation of calibration to a standardized reference material that FDA has determined is appropriate for the quantification of CMV DNA ( e.g., a recognized consensus standard). (F) Documentation of traceability performed each time a new lot of the standardized reference material to which the device is traceable is released, or when the field transitions to a new standardized reference material. (ix) Clinical performance testing that includes: (A) Detailed documentation of device performance data from either a method comparison study with a comparator that FDA has determined is appropriate, or results from a prospective clinical study demonstrating clinical validity of the device. (B) Data from patient samples, with an acceptable number of the CMV positive samples containing an analyte concentration near the lower limit of quantitation and any clinically relevant decision points. (C) The method comparison study must include predefined maximum acceptable differences between the test and comparator method across all primary outcome measures in the clinical study protocol. (D) The final release test results for each lot used in the clinical study." 21:21:8.0.1.1.20.4.1.25,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3181 Cytomegalovirus nucleic acid detection device for congenital cytomegalovirus infection.,FDA,,,"[90 FR 19636, May 9, 2025]","(a) Identification. A cytomegalovirus nucleic acid detection device for congenital cytomegalovirus infection is an in vitro diagnostic device intended for the qualitative detection of cytomegalovirus DNA in clinical samples from newborn babies to aid in the diagnosis of congenital cytomegalovirus infection. Negative results do not preclude infection and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results should be interpreted with consideration of other clinical information and laboratory findings and should not be used as the sole basis for treatment or other patient management decisions. (b) Classification. Class II (special controls). The special controls for this device are: (1) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use with a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) to be tested. (ii) A detailed device description, including all device components, instrument requirements, ancillary reagents required but not provided, and an explanation of the methodology, including all pre-analytical methods for specimen processing. (iii) Performance characteristics from analytical and clinical studies required under paragraphs (b)(2)(ii) and (iii) of this section. (iv) A detailed explanation of the interpretation of results and criteria for validity of results. (v) A limiting statement that device results are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. (vi) As applicable, a limiting statement and specific sample collection recommendations to indicate that breast milk can result in false positive results for saliva samples if samples are collected less than 1 hour after breastfeeding. Sample collection a minimum of 1 hour from breastfeeding must be recommended. (vii) Detailed instructions for use that minimize the risk of generating a false result. (2) Design verification and validation must include: (i) Detailed device description documentation, including methodology from obtaining sample to result, design of primer/probe sequences, rationale for sequence selection, and 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 including characterization of the cutoff, analytical sensitivity (limit of detection), inclusivity, reproducibility, interference, cross reactivity, instrument and method carryover/cross contamination, and sample stability and handling. (iii) Detailed documentation from a clinical study documenting sensitivity and specificity of the device; if the number of positive samples in the clinical study is insufficient to properly estimate device sensitivity, additional pre-selected positive samples must be evaluated to supplement the study. Clinical study subjects must be consistent with the intended use population ( i.e., infants younger than 21 days of age), and device results must be compared to FDA-accepted comparator methods. Documentation from the clinical study must include the clinical study protocol, the clinical study report, testing results, and results of all statistical analyses. (iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software." 21:21:8.0.1.1.20.4.1.26,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3183 Quantitative viral nucleic acid test for transplant patient management.,FDA,,,"[89 FR 75954, Sept. 17, 2024]","(a) Identification. A quantitative viral nucleic acid test for transplant patient management is identified as a device intended for prescription use in the detection of viral pathogens by measurement of viral DNA or RNA using specified specimen processing, amplification, and detection instrumentation. The test is intended for use as an aid in the management of transplant patients with active viral infection or at risk for developing viral infections. The test results are intended to be interpreted by qualified healthcare professionals in conjunction with other relevant clinical and laboratory findings. (b) Classification. Class II (special controls). The special controls for this device are: (1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the device is not intended for use as a donor screening test for the presence of viral nucleic acid in blood or blood products. (ii) Limitations which must be updated to reflect current clinical practice. These limitations must include, but are not limited to, statements that indicate: (A) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with clinical signs and symptoms and other relevant laboratory results; and (B) Negative test results do not preclude viral infection or tissue invasive viral disease and that test results must not be the sole basis for patient management decisions. (iii) A detailed explanation of the interpretation of results and acceptance criteria must be provided and include specific warnings regarding the potential for variability in viral load measurement when samples are measured by different devices. Warnings must include the following statement, where applicable: “Due to the potential for variability in [analyte] measurements across different [analyte] assays, it is recommended that the same device be used for the quantitation of [analyte] when managing individual patients.” (iv) A detailed explanation of the principles of operation and procedures for assay performance. (2) Design verification and validation must include the following: (i) Detailed documentation of the device description, including all parts that make up the device, ancillary reagents required for use with the assay but not provided, an explanation of the methodology, design of the primer/probe sequences, rationale for the selected gene target, and specifications for amplicon size, guanine-cytosine content, and degree of nucleic acid sequence conservation. The design and nature of all primary, secondary and tertiary quantitation standards used for calibration must also be described. (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) Documentation and characterization ( e.g., determination of the identity, supplier, purity, and stability) of all critical reagents and protocols for maintaining product integrity throughout its labeled shelf-life. (iv) Stability data for reagents provided with the device and indicated specimen types, in addition to the basis for the stability acceptance criteria at all time points chosen across the spectrum of the device's indicated life cycle, which must include a time point at the end of shelf life. (v) All stability protocols, including acceptance criteria. (vi) Final lot release criteria along with documentation of an appropriate justification that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (vii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Mode Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel viral stains ( e.g., regular review of published literature and annual in silico analysis of target sequences to detect possible primer or probe mismatches). All results of this protocol, including any findings, must be documented. (viii) Analytical performance testing that includes: (A) Detailed documentation of the following analytical performance studies: limit of detection, upper and lower limits of quantitation, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, quality control, specimen stability studies, and additional studies as applicable to specimen type and intended use for the device; (B) Identification of the viral strains selected for use in analytical studies, which must be representative of clinically relevant circulating strains; (C) Inclusivity study results obtained with a variety of viral genotypes as applicable to the specific assay target and supplemented by in silico analysis; (D) Reproducibility studies that include the testing of three independent production lots; (E) Documentation of calibration to a reference standard that FDA has determined is appropriate for the quantification of viral DNA or RNA ( e.g., a recognized consensus standard); and (F) Documentation of traceability performed each time a new lot of the standardized reference material to which the device is traceable is released, or when the field transitions to a new standardized reference material. (ix) Clinical performance testing that includes: (A) Detailed documentation from either a method comparison study with a comparator that FDA has determined is appropriate, or results from a prospective clinical study demonstrating clinical validity of the device; (B) Data from patient samples, with an acceptable number of the virus-positive samples containing an analyte concentration near the lower limit of quantitation and any clinically relevant decision points. If an acceptable number of virus-positive samples containing an analyte concentration near the lower limit of quantitation and any clinically relevant decision cannot be obtained, contrived samples may be used to supplement sample numbers when appropriate, as determined by FDA; (C) The method comparison study must include predefined maximum acceptable differences between the test and comparator method across all primary outcome measures in the clinical study protocol; and (D) The final release test results for each lot used in the clinical study." 21:21:8.0.1.1.20.4.1.27,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3200,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000]","(a) Identification. Echinococcus spp. serological reagents are devices that consist of Echinococcus spp. antigens and antisera used in serological tests to identify antibodies to Echinococcus spp. in serum. The identification aids in the diagnosis of echinococcosis, caused by parasitic tapeworms belonging to the genus Echinococcus and provides epidemiological information on this disease. Echinococcosis is characterized by the development of cysts in the liver, lung, kidneys, and other organs formed by the larva of the infecting organisms. (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." 21:21:8.0.1.1.20.4.1.28,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3205 Echovirus serological reagents.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(a) Identification. Echovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to echovirus in serum. Additionally, some of these reagents consist of echovirus antisera conjugated with a fluorescent dye used to identify echoviruses from clinical specimens or from tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of echovirus infections and provides epidemiological information on diseases caused by these viruses. Echoviruses cause illnesses such as meningitis (inflammation of the brain and spinal cord membranes), febrile illnesses (accompanied by fever) with or without rash, and the common cold. (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." 21:21:8.0.1.1.20.4.1.29,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3210 Endotoxin assay.,FDA,,,"[68 FR 62008, Oct. 31, 2003. Redesignated at 70 FR 53069, Sept. 7, 2005]","(a) Identification. An endotoxin assay is a device that uses serological techniques in whole blood. The device is intended for use in conjunction with other laboratory findings and clinical assessment of the patient to aid in the risk assessment of critically ill patients for progression to severe sepsis. (b) Classification. Class II (special controls). The special control for this device is the FDA guidance entitled “Class II Special Controls Guidance Document: Endotoxin Assay.” See § 866.1(e) for the availability of this guidance document." 21:21:8.0.1.1.20.4.1.3,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3035,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(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." 21:21:8.0.1.1.20.4.1.30,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis.,FDA,,,"[82 FR 49099, Oct. 24, 2017, as amended at 90 FR 55982, Dec. 4, 2025]","(a) Identification. A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings. (b) Classification. Class II (special controls). The special controls for this device are: (1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended. (2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection. (3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability. (4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information: (i) Results must demonstrate adequate device performance relative to a well-accepted comparator. (ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population. (iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses. (5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics ( e.g., age, racial, ethnic, and gender distribution) similar to the Intended Use population. (6) As part of the risk management activities performed under 21 CFR 820.10(c) design and development, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument. (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, and a detailed explanation of the interpretation of the limitations of the samples ( e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling." 21:21:8.0.1.1.20.4.1.31,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3220,FDA,,,"[47 FR 50823, Nov. 9, 1982; 47 FR 56846, Dec. 21, 1982, as amended at 63 FR 59226, Nov. 3, 1998]","(a) Identification. Entamoeba histolytica serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Entamoeba histolytica in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identify Entamoeba histolytica directly from clinical specimens. The identification aids in the diagnosis of amebiasis caused by the microscopic protozoan parasite Entamoeba histolytica and provides epidemiological information on diseases caused by this parasite. The parasite may invade the skin, liver, intestines, lungs, and diaphragm, causing disease conditions such as indolent ulcers, an amebic hepatitis, amebic dysentery, and pulmonary lesions. (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." 21:21:8.0.1.1.20.4.1.32,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3225 Enterovirus nucleic acid assay.,FDA,,,"[74 FR 8, Jan. 2, 2009]","(a) Identification. An enterovirus nucleic acid assay is a device that consists of primers, probes, enzymes, and controls for the amplification and detection of enterovirus ribonucleic acid (RNA) in cerebrospinal fluid (CSF) from individuals who have signs and symptoms consistent with meningitis or meningoencephalitis. The detection of enterovirus RNA, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of viral meningitis caused by enterovirus. (b) Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Nucleic Acid Amplification Assay for the Detection of Enterovirus RNA.” See § 866.1(e) for the availability of this guidance document." 21:21:8.0.1.1.20.4.1.33,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3230 Device to detect and measure non-microbial analytes to aid in the detection and identification of localized human infections.,FDA,,,"[90 FR 19643, May 9, 2025]","(a) Identification. A device to detect and measure non-microbial analytes to aid in the detection and identification of localized human infections is identified as an in vitro diagnostic device intended for the detection and qualitative measurement, quantitative measurement, or both of one or more non-microbial analytes in human clinical specimens to aid in the assessment, identification, or both of a localized microbial infection when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings. (b) Classification. Class II (special controls). The special controls for this device are: (1) 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 human specimens; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (2) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use with a detailed description of what the device detects and measures, the type of results provided to the user, the sample type, whether the measure is qualitative and/or quantitative, the clinical indications for the test use, and the specific population(s) for which the device is intended. (ii) A detailed description of the performance characteristics of the device for all intended specimen types from the analytical and clinical studies (as applicable) required under paragraphs (b)(3)(ii) and (iii) of this section. (iii) A detailed explanation of the interpretation of results, including acceptance criteria for evaluating the validity of individual runs ( e.g., assessment of internal and/or external quality controls, as applicable). (iv) The following limiting statements: (A) A statement that a negative test result does not preclude the possibility of infection; (B) A statement that the test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician; (C) A statement that consistent device performance is dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and (D) A statement that details any limitations associated with the samples, as appropriate ( e.g., collected on the day of admission to the intensive care unit). (3) Design verification and validation must include the following: (i) A detailed device description, including as appropriate, all device parts; control elements incorporated into the test procedure; instrument requirements; reagents required but not provided; and the principle of device operation and test methodology, including all preanalytical methods for the processing of specimens and the methodology from obtaining a sample to the result; design of primer/probe sequences; rationale for target analyte selection; and 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 including analytical sensitivity (Limit of Detection, Limit of Quantitation, and Limit of Blank), inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross-contamination, specimen stability, within-lab precision, reproducibility, and linearity, as applicable. (iii) Detailed documentation and results either from a clinical study, that includes prospective (sequentially collected) samples for each intended specimen type that are representative of the intended use populations and, when determined to be acceptable by FDA, additional characterized clinical samples; or, when determined to be acceptable by FDA, an equivalent sample set. The clinical study must compare the device performance to results obtained from an FDA-accepted reference method and/or FDA-accepted comparator method, as appropriate. Documentation from the clinical studies must include the clinical study protocol ( e.g., the predefined statistical analysis plan), clinical study report, testing results, and results of all statistical analyses. (iv) An evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics ( e.g., age, racial, ethnic, and sex distribution) similar to the intended use population of the device. (v) Documentation of an appropriate end user device training program that will be offered as part of efforts to mitigate the risks of false results, failure to operate the device correctly, and failure to interpret test results correctly. (vi) An appropriate risk mitigation strategy to ensure that the device does not prevent any other device(s) with which it is indicated for use, including incorporated device(s), from achieving their intended use ( e.g., safety and effectiveness of the functions of the indicated device(s) remain unaffected). (vii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions." 21:21:8.0.1.1.20.4.1.34,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3231 Device to detect bacterial protease activity in chronic wound fluid.,FDA,,,"[90 FR 23282, June 2, 2025]","(a) Identification. A device to detect bacterial protease activity in chronic wound fluid is a lateral flow prescription in vitro diagnostic device that may include a sterile swab. The device is intended for use in patients as an aid in assessing the risk for non-healing of chronic venous, diabetic foot, and pressure ulcers associated with wounds where there are no signs of wound infection and where patients are asymptomatic for clinical signs of infection. (b) Classification. Class II (special controls). The special controls for this device are: (1) Any swab used to collect a patient specimen must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of wound fluid specimens; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (2) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use that includes the following statements: (A) A statement that the device detects and measures bacterial proteases from a swab saturated with wound fluid. (B) A statement that the device provides a qualitative output to aid the user in assessing the risk for non-healing of wounds ( e.g., chronic venous, diabetic foot and pressure ulcers). (C) A description of the clinical indications for test use. (D) The specific population(s) for which the device is intended. (E) A description of the recommended training ( e.g., knowledge and experience) for safe and effective use of the device and to minimize the risks of incorrect results and misinterpretation. (ii) A detailed description of the performance characteristics of the device from the analytical and clinical studies required under paragraphs (b)(3)(ii) and (iii) of this section. (iii) A detailed explanation of the interpretation of results. (iv) A warning statement describing situations where the device has not been validated or may not perform as identified in the labeling ( e.g., not for use with wounds which are ≥6 months of age and ≥1 cm 2 in size). (v) The following limiting statements: (A) That the device is not intended to provide a risk assessment of chronic wound infection status or aid in the diagnosis of infection in chronic wounds, nor is the device intended for monitoring the effectiveness of anti-infective therapy. (B) That a negative result does not exclude the presence of bacterial proteases. Therefore, the results should be used in conjunction with clinical findings to make an accurate assessment of risk of nonhealing. The test result should be interpreted in conjunction with other risk factors, along with clinical and laboratory data available to the clinician. (C) That the device has been validated using wound fluid samples only. Other sample types ( e.g., whole blood from venous or capillary draws, other body fluids) have not been evaluated. (D) That skin flora may secrete bacterial proteases therefore, swab contact with intact skin should be avoided as this may yield false positive results. (vi) Labeling must include a brief reference sheet for healthcare professionals that includes the intended use, summary of clinical performance, results from analytical testing on normal skin and human proteases, and warning and limiting statements. (3) Design verification and validation must include the following: (i) A detailed device description ( e.g., all device parts, control elements incorporated into the test procedure, reagents required but not provided, and the principle of device operation and test methodology). (ii) Detailed documentation and results from analytical studies, including the limit of detection, inclusivity, cross-reactivity, microbial interference, analytical sensitivity for normal skin flora and human proteases, interfering substances, specimen stability, within-lab precision, and reproducibility. (iii) Detailed documentation and results from a clinical study that includes prospective (sequentially collected) samples for the intended specimen type that are representative of the intended use population(s). The clinical study must compare the device performance to results obtained from a reference or comparator method that FDA has determined is appropriate." 21:21:8.0.1.1.20.4.1.35,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3235 Epstein-Barr virus serological reagents.,FDA,,,,"(a) Identification. Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer). (b) Classification. Class I (general controls)." 21:21:8.0.1.1.20.4.1.36,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3236 Device to detect or measure nucleic acid from viruses associated with head and neck cancers.,FDA,,,"[89 FR 75493, Sept. 16, 2024]","(a) Identification. A device to detect or measure nucleic acid from viruses associated with head and neck cancers is an in vitro diagnostic test for prescription use in the detection of viral nucleic acid in nasopharyngeal or oropharyngeal cellular specimens from patients with signs and symptoms of head and neck cancer. The test result is intended to be used in conjunction with other clinical information to aid in assessing the clinical status of virus-associated head and neck cancers and/or the likelihood that head and neck cancer is present. (b) Classification. Class II (special controls). The special controls for this device are: (1) 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 human specimens; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (2) The labeling required under § 809.10(b) of this chapter must include, as determined to be appropriate by FDA: (i) An intended use statement that includes the following: (A) The analyte(s) detected by the device; (B) Data output of the device (qualitative, semiquantitative, or quantitative); (C) The specimen types with which the device is intended for use; (D) The clinical indications appropriate for test use ( e.g., in conjunction with endoscopy); (E) The intended use populations ( e.g., signs and symptoms, ethnicity); and (F) The intended use location(s) ( e.g., specific name and location of testing facility or facilities). (ii) A detailed device description, including reagents, instruments, ancillary materials, specimen collection and transport devices, controls, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens. (iii) A detailed explanation of the interpretation of results. (iv) Limiting statements indicating: (A) The device is not intended for use in screening for head and neck cancer in asymptomatic populations. (B) Results of the device are not predictive of a patient's future risk of head and neck cancer. (C) Patients who test negative for the virus should be managed in accordance with the standard of care, based on the assessment of endoscopy and/or other clinical information by a licensed healthcare professional. (D) Results of the device are not intended to be used as the sole basis for determining the need for biopsy or for any other patient management decision. (3) Design verification and validation must include the following: (i) A detailed device description including pre-analytical specimen processing, assay technology, target region, primer/probe sequences, reagents, controls, instrument requirements, and the computational path from collected raw data to reported result. (ii) Detailed documentation and results from analytical performance studies, including characterization of the cutoff(s), limit of detection, limit of quantitation, precision (including multisite reproducibility, if applicable), inclusivity, cross-reactivity, interference, carryover/cross-contamination, reagent stability, and specimen/sample stability, as determined to be appropriate by FDA. (iii) Detailed documentation of a clinical performance study that includes patients from the intended use population, including the clinical study protocol, with a predefined statistical analysis plan, and a clinical study report with testing results and results of all statistical analyses. (iv) A detailed description of the impact of any software, including software applications and software incorporated in hardware-based devices, on the device's functions." 21:21:8.0.1.1.20.4.1.37,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3240 Equine encephalomyelitis virus serological reagents.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000]","(a) Identification. Equine encephalomyelitis virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antobodies to equine encephalomyelitis virus in serum. The identification aids in the diagnosis of diseases caused by equine encephalomyelitis viruses and provides epidemiological information on these viruses. Equine encephalomyelitis viruses are transmitted to humans by the bite of insects, such as mosquitos and ticks, and may cause encephalitis (inflammation of the brain), rash, acute arthritis, or hepatitis. (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." 21:21:8.0.1.1.20.4.1.38,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3250,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(a) Identification. Erysipelothrix rhusiopathiae serological reagents are devices that consist of antigens and antisera used in serological tests to identify Erysipelothrix rhusiopathiae from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by this bacterium belonging to the genus Erysipelothrix. This organism is responsible for a variety of inflammations of the skin following skin abrasions from contact with fish, shellfish, or poultry. (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." 21:21:8.0.1.1.20.4.1.39,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3255,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]","(a) Identification. Escherichia coli serological reagents are devices that consist of antigens and antisera used in serological tests to identify Escherichia coli from cultured isolates derived from clinical specimens. Additionally, some of these reagents consist of Escherichia coli antisera conjugated with a fluorescent dye used to identify Escherichia coli directly from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by this bacterium belonging to the genus Escherichia, and provides epidemiological information on diseases caused by this microorganism. Although Escherichia coli constitutes the greater part of the microorganisms found in the intestinal tract in humans and is usually nonpathogenic, those strains which are pathogenic may cause urinary tract infections or epidemic diarrheal disease, especially in children. (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." 21:21:8.0.1.1.20.4.1.4,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3040,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000]","(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." 21:21:8.0.1.1.20.4.1.40,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3270,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38792, July 25, 2001]","(a) Identification. Flavobacterium spp. serological reagents are devices that consist of antigens and antisera used in serological tests to identify Flavobacteriuim spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Flavobacterium and provides epidemiological information on diseases caused by these microorganisms. Most members of this genus are found in soil and water and, under certain conditions, may become pathogenic to humans. Flavobacterium meningosepticum is highly virulent for the newborn, in whom it may cause epidemics of septicemia (blood poisoning) and meningitis (inflammation of the membranes of the brain) and is usually attributable to contaminated hospital equipment. (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." 21:21:8.0.1.1.20.4.1.41,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3280,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59226, Nov. 3, 1998]","(a) Identification. Francisella tularensis serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Francisella tularensis in serum or to identify Francisella tularensis in cultured isolates derived from clinical specimens. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identify Francisella tularensis directly from clinical specimens. The identification aids in the diagnosis of tularemia caused by Francisella tularensis and provides epidemiological information on this disease. Tularemia is a desease principally of rodents, but may be transmitted to humans through handling of infected animals, animal products, or by the bites of fleas and ticks. The disease takes on several forms depending upon the site of infection, such as skin lesions, lymph node enlargements, or pulmonary infection. (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." 21:21:8.0.1.1.20.4.1.42,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3290 Gonococcal antibody test (GAT).,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 52 FR 17734, May 11, 1987]","(a) Identification. A gonococcal antibody test (GAT) is an in vitro device that consists of the reagents intended to identify by immunochemical techniques, such as latex agglutination, indirect fluorescent antibody, or radioimmunoassay, antibodies to Neisseria gonorrhoeae in sera of asymptomatic females at low risk of infection. Identification of antibodies with this device may indicate past or present infection of the patient with Neisseria gonorrhoeae. (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." 21:21:8.0.1.1.20.4.1.43,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3300,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59226, Nov. 3, 1998]","(a) Identification. Haemophilus spp. serological reagents are devices that consist of antigens and antisera, including antisera conjugated with a fluorescent dye, that are used in serological tests to identify Haemophilus spp. directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genus Haemophilus and provides epidemiological information on diseases cause by these microorganisms. Diseases most often caused by Haemophilus spp. include pneumonia, pharyngitis, sinusitis, vaginitis, chancroid venereal disease, and a contagious form of conjunctivitis (inflammation of eyelid membranes). (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." 21:21:8.0.1.1.20.4.1.44,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3305 Herpes simplex virus serological assays.,FDA,,,"[72 FR 15830, Apr. 3, 2007, as amended at 74 FR 42775, Aug. 25, 2009; 76 FR 48717, Aug. 9, 2011]","(a) Identification. Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome. (b) Classification. Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e)." 21:21:8.0.1.1.20.4.1.45,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3307 Herpes simplex virus nucleic acid-based assay for central nervous system infections.,FDA,,,"[90 FR 27235, June 26, 2025]","(a) Identification. A herpes simplex virus nucleic acid-based assay for central nervous system infections is a qualitative in vitro diagnostic device intended for the detection and differentiation of HSV-1 and HSV-2 in cerebrospinal fluid (CSF) samples from patients suspected of Herpes Simplex Virus (HSV) infections of the central nervous system (CNS). This test is intended as an aid in the diagnosis of HSV-1 and HSV-2 infections of the CNS. Negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions. (b) Classification. Class II (special controls). The special controls for this device are: (1) Design verification and validation must include: (i) Detailed documentation for the device description, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including primer design and selection. (ii) Detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (limit of detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carryover, and cross contamination. Documentation must include reagent and sample stability recommendations. (iii) 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 the results of two polymerase chain reaction methods followed by bidirectional sequencing. (iv) Documentation of an appropriate end user device training program that will be offered as part of efforts to mitigate the risk of failure to correctly operate the instrument. (v) Quality assurance protocols and detailed documentation for device software, including standalone software applications and hardware-based devices that incorporate software. (2) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed explanation of the interpretation of results and acceptance criteria. (ii) A limiting statement indicating that negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions." 21:21:8.0.1.1.20.4.1.46,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3309 Herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel.,FDA,,,"[83 FR 52314, Oct. 17, 2018, as amended at 90 FR 55982, Dec. 4, 2025]","(a) Identification. A herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel is a qualitative in vitro diagnostic device intended for the simultaneous detection and differentiation of different herpes viruses in cutaneous and mucocutaneous lesion samples from symptomatic patients suspected of Herpetic infections. Negative results do not preclude infection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use in cerebrospinal fluid samples. (b) Classification. Class II (special controls). The special controls for this device are: (1) Premarket notification submissions must include detailed documentation for the device description, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology including primer design and 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 of a clinical study using lesion samples in which Herpes Simplex Virus 1, Herpes Simplex Virus 2, or Varicella Zoster Virus DNA detection was requested. The study must compare the device performance to an appropriate well established reference method. (4) 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. (5) The device labeling must include a limitation statement that reads: “The device is not intended for use with cerebrospinal fluid or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS).” (6) Premarket notification submissions must include quality assurance protocols and a detailed documentation for device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software. (7) The risk management activities performed as part of the manufacturer's 21 CFR 820.10(c) design and development activities must document an appropriate end user device training program that will be offered as part of efforts to mitigate the risk of failure to correctly operate the instrument." 21:21:8.0.1.1.20.4.1.47,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3310 Hepatitis A virus (HAV) serological assays.,FDA,,,"[71 FR 6679, Feb. 9, 2006]","(a) Identification. HAV serological assays are devices that consist of antigens and antisera for the detection of hepatitis A virus-specific IgM, IgG, or total antibodies (IgM and IgG), in human serum or plasma. These devices are used for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis to determine if an individual has been previously infected with HAV, or as an aid to identify HAV-susceptible individuals. The detection of these antibodies aids in the clinical laboratory diagnosis of an acute or past infection by HAV in conjunction with other clinical laboratory findings. These devices are not intended for screening blood or solid or soft tissue donors. (b) Classification. Class II (special controls). The special control is “Guidance for Industry and FDA Staff: Class II Special Controls Guidance Document: Hepatitis A Virus Serological Assays.” See § 866.1(e) for the availability of this guidance document." 21:21:8.0.1.1.20.4.1.48,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3320,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998]","(a) Identification. Histoplasma capsulatum serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Histoplasma capsulatum in serum. Additionally, some of these reagents consist of Histoplasma capsulatum antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identify Histoplasma capsulatum from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of histoplasmosis caused by this fungus belonging to the genus Histoplasma and provides epidemiological information on the diseases caused by this fungus. Histoplasmosis usually is a mild and often asymptomatic respiratory infection, but in a small number of infected individuals the lesions may spread to practically all tissues and organs. (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." 21:21:8.0.1.1.20.4.1.49,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3328 Influenza virus antigen detection test system.,FDA,,,"[82 FR 3618, Jan. 12, 2017]","(a) Identification. An influenza virus antigen detection test system is a device intended for the qualitative detection of influenza viral antigens directly from clinical specimens in patients with signs and symptoms of respiratory infection. The test aids in the diagnosis of influenza infection and provides epidemiological information on influenza. Due to the propensity of the virus to mutate, new strains emerge over time which may potentially affect the performance of these devices. Because influenza is highly contagious and may lead to an acute respiratory tract infection causing severe illness and even death, the accuracy of these devices has serious public health implications. (b) Classification. Class II (special controls). The special controls for this device are: (1) The device's sensitivity and specificity performance characteristics or positive percent agreement and negative percent agreement, for each specimen type claimed in the intended use of the device, must meet one of the following two minimum clinical performance criteria: (i) For devices evaluated as compared to an FDA-cleared nucleic acid based-test or other currently appropriate and FDA accepted comparator method other than correctly performed viral culture method: (A) The positive percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent. (B) The negative percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent. (ii) For devices evaluated as compared to correctly performed viral culture method as the comparator method: (A) The sensitivity estimate for the device when testing for influenza A must be at the point estimate of at least 90 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 80 percent. The sensitivity estimate for the device when testing for influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent. (B) The specificity estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent. (2) When performing testing to demonstrate the device meets the requirements in paragraph (b)(1) of this section, a currently appropriate and FDA accepted comparator method must be used to establish assay performance in clinical studies. (3) Annual analytical reactivity testing of the device must be performed with contemporary influenza strains. This annual analytical reactivity testing must meet the following criteria: (i) The appropriate strains to be tested will be identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and sourced from CDC or an FDA-designated source. If the annual strains are not available from CDC, FDA will identify an alternative source for obtaining the requisite strains. (ii) The testing must be conducted according to a standardized protocol considered and determined by FDA to be acceptable and appropriate. (iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity testing must be included as part of the device's labeling. If a device has not been on the market long enough for 3 years of annual analytical reactivity testing to have been conducted since the device received marketing authorization from FDA, then the results of every annual analytical reactivity testing since the device received marketing authorization from FDA must be included. The results must be presented as part of the device's labeling in a tabular format, which includes the detailed information for each virus tested as described in the certificate of authentication, either by: (A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or (B) In the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access. (4) If one of the actions listed at section 564(b)(1)(A)-(D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain: (i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. The procedure and location of testing may depend on the nature of the emerging virus. (ii) Within 60 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by: (A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or (B) In a section of the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access." 21:21:8.0.1.1.20.4.1.5,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3045 In vitro diagnostic device for,FDA,,,"[84 FR 12088, Apr. 1, 2019]","(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." 21:21:8.0.1.1.20.4.1.50,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3330 Influenza virus serological reagents.,FDA,,,"[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001]","(a) Identification. Influenza virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to influenza in serum. The identification aids in the diagnosis of influenza (flu) and provides epidemiological information on influenza. Influenza is an acute respiratory tract disease, which is often epidemic. (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." 21:21:8.0.1.1.20.4.1.51,21,Food and Drugs,I,H,866,,D,Subpart D—Serological Reagents,,§ 866.3332 Reagents for detection of specific novel influenza A viruses.,FDA,,,"[71 FR 14379, Mar. 22, 2006]","(a) Identification. Reagents for detection of specific novel influenza A viruses are devices that are intended for use in a nucleic acid amplification test to directly detect specific virus RNA in human respiratory specimens or viral cultures. Detection of specific virus RNA aids in the diagnosis of influenza caused by specific novel influenza A viruses in patients with clinical risk of infection with these viruses, and also aids in the presumptive laboratory identification of specific novel influenza A viruses to provide epidemiological information on influenza. These reagents include primers, probes, and specific influenza A virus controls. (b) Classification. Class II (special controls). The special controls are: (1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Reagents for Detection of Specific Novel Influenza A Viruses.” See § 866.1(e) for information on obtaining this document. (2) The distribution of these devices is limited to laboratories with experienced personnel who have training in standardized molecular testing procedures and expertise in viral diagnosis, and appropriate biosafety equipment and containment."