CFR - Code of Federal Regulations Title 21 (2023)

TITLE 21 – FOOD AND MEDICINES
CHAPTER I - FOOD AND MEDICATION ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER H - MEDICAL DEVICES

(a) This part specifies the classification of immunological and microbiological products intended for human use and commercially marketed.

(b) The identification of a device in a regulation in this part is not an accurate description of every device that is or will be subject to the regulation. A manufacturer submitting a pre-notification for a Part 807 device must demonstrate not only that the device is accurately described in the section heading and the provisions that identify a regulation in that part, but must also indicate why the device is essentially equivalent to other devices as required. per §807.87.

(c) To avoid double listing, an immunological and microbiological product that has two or more uses (eg, used as a diagnostic product and as a microbiological product) is only included in one subsection.

(d) References in this part to regulatory sections of the Code of Federal Regulations refer to Chapter I of Title 21 unless otherwise indicated.

(e) The guides referenced in this part are available on the Internet athttp://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm.

[52 FR 17733, May 11, 1987, amended 68 FR 5827, February 5, 2003; 79 FR 50552, August 25, 2014]

Equipment covered by this part that is classified as Class III (premarket approval) may not be commercially distributed after the date specified in the equipment classification regulation, unless the manufacturer has a License pursuant to Section 515 of the Act (unless a waiver has been granted). ). pursuant to Section 520(g)(2) of the Act). An approval under Section 515 of the Act consists of the issuance of an order by the FDA authorizing a Premarket Authorization Application (PMA) for the device or stating that a Product Development Protocol has been completed. (PDP) for the device.

(a) Before the FDA requires that a device sold commercially before the effective date of the amendments, or a device determined to be substantially equivalent to such a device, be approved under Section 515 of the Act, FDA must obtain an Order issued pursuant to Section 515(b) of the Act requires such approval, except as provided in paragraphs (b) and (c) of this section. Such provision under Section 515(b) of the Act shall not be effective during the grace period ending on the 90th day after its enactment or the last day of the 30th full calendar month after the provision classifying the device as Class III, as applicable after what comes after. See Section 501(f)(2)(B) of the Act. Therefore, unless the regulation provides a preauthorization effective date for a device classified as Class III in this part, the device may be distributed commercially without FDA issuing an order to approve a PMA or declare a PDP complete. If the FDA issues a rule under Section 515(b) of the Act that requires prior approval of a device, Section 501(f)(1)(A) of the Act applies to the device.

(b) Any new, non-substantially equivalent appliance introduced into commercial distribution on or after May 28, 1976, including previously marketed appliances that have been substantially modified, is made by law (Section 513(f) of the Act) to a Class III with no grace period, and the FDA must have issued an order approving a PMA or declaring a full PDP for the device before the device is commercially distributed, unless reclassified. If FDA knows that a commercially distributed device may be a "new" device for purposes of this section because of a new intended use or for other reasons, FDA may codify the device's regulatory classification as Class III for that new use. Accordingly, the regulation for such a Class III device provides that as of the effective date of the amendments, May 28, 1976, the device must have an approval under Section 515 of the Act prior to commercial distribution.

(c) Equipment identified in any regulation of this part that is classified as Class III and subject to the transitory provisions of Section 520(l) of the Act is automatically classified as Class III by Act and must be approved under Section 515 of the Act. Act before it is commercially distributed. Accordingly, the regulation for a Class III transitional device of this type provides that, effective May 28, 1976, the device must have an approval under Section 515 of the Act prior to commercial distribution.

[52 FR 17733, May 11, 1987; 52 FR 22577, June 12, 1987]

The exemption from the prior notification requirement (Section 510(k) of the Act) for a generic type of Class I or II device applies only to the extent that the device has existing or reasonably foreseeable characteristics of devices commercially distributed within a generic type or, in the case of in vitro diagnostic devices, only to the extent that misdiagnosis resulting from use of the device is not associated with high morbidity or mortality. Consequently, manufacturers of commercial Class I or II devices for which the FDA has granted a waiver of the premarket notification requirement are still required to file a premarket notification with FDA before placing the device in interstate commerce. for release for commercial distribution or supply for release if:

(a) the product is intended for a use other than its intended use for a legally marketed product in that generic device type; eg B. the product is intended for another medical purpose or the product is intended for non-professional use if the previous intended use was by healthcare professionals only;

(b) the modified product employs a different basic scientific technology than a legitimately marketed product of that generic device type; e.g. For example, a surgical instrument cuts tissue with a laser beam instead of a sharp metal blade, or an in vitro diagnostic device detects or identifies infectious agents using a deoxyribonucleic acid (DNA) probe or nucleic acid hybridization technology instead of culture or immunoassay technology. use; either

(c) The product is an in vitro device intended for:

(1) For use in the diagnosis, monitoring, or investigation of neoplastic diseases, excluding immunohistochemical devices;

(2) for use in the detection or diagnosis of familial or acquired genetic disorders, including inborn errors of metabolism;

(3) To measure an analyte that serves as a surrogate marker for the detection, diagnosis, or monitoring of life-threatening diseases, such as acquired immunodeficiency syndrome (AIDS), chronic or active hepatitis, tuberculosis, or myocardial infarction, or for surveillance therapy;

(4) for cardiovascular disease risk assessment;

(5) For use in the control of diabetes;

(6) To identify or derive the identity of a microorganism directly from clinical material;

(7) for the detection of antibodies against 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 non-invasive tests as defined in Section 812.3(k) of this chapter; Y

(9) For point-of-care testing.

[65 FR 2311, Jan. 14, 2000]

(a)ID.An antimicrobial susceptibility test disk is a device consisting of antimicrobial-impregnated paper disks used to measure the in vitro susceptibility of most clinically important bacterial pathogens to antimicrobial agents using an agar diffusion technique. in disk or a disk broth elution technique. In the agar disk diffusion technique, bacterial susceptibility is assessed by directly measuring the size of a zone of bacterial inhibition around the disk on an agar surface. The disk broth elution technique is coupled to an automated rapid susceptibility test system and uses a liquid medium in which susceptibility is determined by photometrically measuring changes in bacterial growth that occur when antimicrobial material is eluted from the disk. to the liquid medium. The test results are used to determine the antimicrobial of choice in the treatment of bacterial diseases.

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

(a)ID.An antimicrobial susceptibility test powder is a device consisting of antimicrobial drug powder packaged in vials in specified quantities and intended for use in clinical laboratories to determine the in vitro susceptibility of bacterial pathogens to these therapies. The test results are used to determine the antimicrobial of choice in the treatment of bacterial diseases.

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

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

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

[68 FR 5827, February 5, 2003]

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

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

(1) The purpose of use of the device in the labeling required by § 809.10 of this Chapter shall include a detailed description of the targets that the device detects, the nature of the results provided to the user, the appropriate clinical indications for the 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 (stand-alone or as part of a test system) for the collection of the types of specimens claimed by that device that maintains viability. of the target microorganisms; Alternatively, the sample collection device must be released in a pre-market presentation as part of this device.

(3) The identification required by section 809.10(b) of this chapter shall include the following:

(i) A detailed description of the product, including reagents, instruments, ancillary materials, appropriate sample collection and transport equipment, and control items, and a detailed explanation of the methodology, including preanalytical methods for handling and process samples and controls. to maintain the viability of the organism;

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

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

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

(v) A qualifying statement that a negative test result does not preclude colonization or infection with organisms lacking detectable levels of the reporter identified by the device.

(4) The verification and validation of the design will 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 algorithms and methods of data processing from signal acquisition to result classification;

(ii) A detailed description of the effects of the software, including software applications and hardware-based devices containing software, on the functions of the device;

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

(iv) Detailed documentation of quality control procedures, including an explanation of the selection of quality control materials, recommended testing frequency, control preparation methods, performance acceptance criteria, and quality control test results. quality tests performed during analytical and clinical studies as required by paragraphs (b)(3)(iii) and (iv) of this section;

(v) Detailed documentation of studies performed to determine the stability of reagents on board and in use, including test methods, data analysis plans, acceptance criteria, final study reports, and test lists. data lines;

(vi) Detailed documentation of studies to determine the stability of reagents for the test kit and any applicable sample collection and transport devices, including study protocols with descriptions of test methods, data analysis plans, and criteria acceptance; Y

(vii) Documentation of an appropriate end-user instrument training program provided as part of an effort to ensure proper assay performance and mitigate the risk associated with false results, including improper use of the instrument or misinterpretation of the instruments. results.

[87 FR 6417, Feb 4, 2022]

(a)ID.An antimicrobial susceptibility testing culture medium is a medical grade device consisting of any medium that can support the growth of many bacterial pathogens that are subjected to antimicrobial susceptibility testing. The medium should be free of components known to be antagonistic to common agents for which susceptibility testing is performed in the treatment of diseases.

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

(a)ID.A staphylococcal typing bacteriophage is a device composed of a bacterial virus intended for medical use to identify pathogenic staphylococcal bacteria based on the susceptibility of the bacterium to destruction by the virus. Test results are mainly used to collect 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25045, Jun. 12, 1989; 66 FR 38790, July 25, 2001]

(a)ID.An anaerobic chamber is a device designed for medical use to maintain an anaerobic environment (without oxygen). 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 equipment is also exempt from the good manufacturing practice requirements of the Quality Systems Regulations in Part 820 of this chapter, except Section 820.180 relating to general record keeping requirements and Section 820.198 relating to record keeping. complaints.

[47 FR 50823, November 9, 1982, modified 66 FR 38790, July 25, 2001]

(a)ID.Coagulase plasma is a device consisting of lyophilized human or animal plasma intended for medical use for coagulase testing primarily on staphylococcal bacteria. After reconstitution, the liquid plasma is coagulated by the action of the coagulase enzyme produced by pathogenic staphylococci. Test results are used primarily as an aid in the diagnosis of diseases caused by pathogenic bacteria of the genusstaphand provide epidemiological information on the 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.

[47 FR 50823, Nov. 9, 1982, changed to 61 FR 1119, Jan. 16, 1996; 66 FR 38790, July 25, 2001]

(a)ID.An automatic colony counter is a mechanical device intended for medical use to determine the number of bacterial colonies present in a bacteriological culture medium in a Petri dish. The number of colonies counted is used in disease diagnosis 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25045, Jun. 12, 1989; 66 FR 38790, July 25, 2001]

(a)ID.A manual colony counter is a medical grade device consisting of a printed grid system superimposed on an illuminated display. Petri dishes with bacterial colonies to be counted are placed on the screen for better visualization and easier counting. The number of colonies counted is used in disease diagnosis 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 equipment is also exempt from the good manufacturing practice requirements of the Quality Systems Regulations in Part 820 of this chapter, except Section 820.180 relating to general record keeping requirements and Section 820.198 relating to record keeping. complaints.

[47 FR 50823, November 9, 1982, modified 66 FR 38790, July 25, 2001]

(a)ID.An Automated Imaging Assessment System for Microbial Colonies on Solid Culture Media is a system designed to assess the presence or absence of microbial colonies on solid microbiological culture media and to interpret their number, phenotypic and morphological characteristics by analyzing digital images. two-dimensional for help. the diagnosis of infectious diseases.

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

(1) The prior notification submission must contain a detailed description of the device, including the technology, components and software modules used, as well as a detailed explanation of the resulting algorithms and any expert rules used for feature evaluation from the colony. and enumeration of colony image acquisition to the final result.

(2) Premarket notification submissions must include detailed documentation of analytical studies performed to characterize product performance to support intended use, if applicable.

(3) Premarket notification submissions must include detailed documentation of clinical trials conducted in a population consistent with the intended use population.

(i) Clinical studies must determine the performance of the product based on a comparison with the results of an acceptable reference method, when applicable.

(ii) The documentation of the clinical study must include the study protocol with a predefined statistical analysis plan and the final report that documents the support of the indications and the results of the statistical analysis, as appropriate.

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

(5) Submission of premarket notifications shall include detailed documentation of the appropriate instructions for use related to the intended user device quality control procedures for the instrument system and components, where applicable.

(6) Labeling of equipment that complies with 21 CFR 809.10 must include:

(i) Detailed instructions for the user to reduce the risk of incorrect operation of the instrument.

(ii) A detailed explanation of the interpretation of the results and limitations on the need to review the culture plates by a qualified microbiologist, if applicable.

(iii) A summary of performance data derived from analytical studies used to support device performance, where applicable.

(iv) A summary of performance data obtained from clinical studies conducted in a population consistent with the population for the intended use, where applicable.

(7) Pursuant to design control compliant with 21 CFR 820.30, device manufacturers may be required to:

(i) Perform human factors/usability validation tests on the final version of the label and associated materials to adequately mitigate the risk of incorrect operation of the instrument.

(ii) Document a training program on the device offered to the end user to adequately mitigate the risk of misuse of the device.

[82 FR 47969, oct. 16, 2017]

(a)ID.A polyvalent culture medium is a device consisting mainly of liquid or solid biological materials intended for medical use in the cultivation and identification of various types of pathogenic microorganisms without the need for additional nutritional supplements. Test results help diagnose diseases and also provide epidemiological information about 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38790, July 25, 2001]

(a)ID.A differential culture medium is a device composed mainly of liquid biological materials intended for medical use to cultivate and identify different types of pathogenic microorganisms. These microorganisms are identified by adding one or more specific biochemical components to the medium. Microorganisms are identified by a visible change (eg, color change) in one or more specific biochemical components, indicating that specific metabolic reactions have occurred. Test results help diagnose diseases and also provide epidemiological information about 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38790, July 25, 2001]

(a)ID.An enriched culture medium is a device consisting primarily of liquid or solid biological materials intended for medical use in the cultivation and identification of fastidious microorganisms (with complex nutritional needs). The device consists of a relatively simple basal medium enriched by the addition of nutritive components such as blood, blood serum, vitamins, and extracts of plant or animal tissue. The device is designed to diagnose diseases caused by pathogenic microorganisms and also provides epidemiological information about 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID.A microbiological test culture medium is a device composed primarily of liquid or solid biological materials intended for medical use for culturing selected test microorganisms for the purpose of determining the concentration of certain substances such as amino acids or antimicrobial agents in a patient's serum by microbiological methods. and vitamins. The concentration of these substances is measured by their ability to promote or inhibit the growth of the test organism in the inoculated medium. Test results help diagnose diseases that result from deficient or excessive levels of these substances in a patient's serum. The test results can 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID.A selective culture medium is a device composed primarily of liquid or solid biological materials intended for medical use to cultivate and identify specific pathogenic microorganisms. The device contains one or more components that suppress the growth of certain microorganisms while promoting or not affecting the growth of other microorganisms. The device helps diagnose diseases caused by pathogenic microorganisms and also provides epidemiological information about 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID.A transport culture medium is a device consisting of a semi-solid medium, usually nutrient-free, that maintains the viability of suspected pathogens contained in patient specimens during transport from the specimen collection area to the laboratory. The device helps diagnose diseases caused by pathogenic microorganisms and also provides epidemiological information about these diseases.

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

(a)ID.A culture medium for pathogens.Neisseriasp. is a device composed primarily of liquid or solid biological materials that is used to culture and identify pathogensNeisseriasp. Identification helps diagnose diseases caused by bacteria of the genusNeisseria,B. epidemic cerebrospinal meningitis, other meningococcal diseases, and gonorrhea, and also provides epidemiologic information on these microorganisms.

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

(a)ID.A gonorrhea oxidase screening test is an in vitro device consisting of elements designed to identify, through a chemical reaction, cytochrome oxidase, an oxidizing enzyme associated with certain bacteria, includingNeisseria gonorrhoeae.A sample of a man's urethral discharge is obtained with a swab placed in a wetting agent that contains an ingredient that reacts with cytochrome oxidase. If cytochrome oxidase is present, the swab will turn dark purple in 3 minutes. Because it is unlikely that other cytochrome oxidase-positive organisms other thanNeisseria gonorrhoeaeare present in male urethral discharge, identification of cytochrome oxidase with this device suggests a suspected 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, a permit is required under Section 515 of the Act before this device can be sold commercially. See § 866.3.

[47 FR 50823, November 9, 1982, modified 52 FR 17734, May 11, 1987]

(a)ID.An automatic media stacking and dispensing device is a device designed for medical use for dispensing a microbiological culture medium into Petri dishes and then mechanically stacking 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 equipment is also exempt from the good manufacturing practice requirements of the Quality Systems Regulations in Part 820 of this chapter, except Section 820.180 relating to general record keeping requirements and Section 820.198 relating to record keeping. complaints.

[47 FR 50823, November 9, 1982, modified 66 FR 38791, July 25, 2001]

(a)ID.A culture medium supplement 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 is intended for medical use to support the growth of fastidious microorganisms (those with complex nutrients). requirements). This device helps diagnose 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID.A culture media quality control kit is a device consisting of paper disks (or other suitable material) each impregnated with a specific viable, lyophilized microorganism, intended for medical use to determine whether a specific culture medium is capable of of these to support the growth of this microorganism. The device helps diagnose diseases caused by pathogenic microorganisms and also provides epidemiological information about 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID.A microtiter dispenser and diluent is a mechanical device designed for medical use to dispense or serially dilute very small amounts 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID.A microbiological incubator is a device with different chambers or compartments filled with water in which controlled environmental conditions are maintained, especially temperature. It is intended for medical use, to grow microorganisms, and to help diagnose 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 equipment is also exempt from the good manufacturing practice requirements of the Quality Systems Regulations in Part 820 of this chapter, except Section 820.180 relating to general record keeping requirements and Section 820.198 relating to record keeping. complaints.

[47 FR 50823, November 9, 1982, modified 66 FR 38791, July 25, 2001]

(a)ID.A microbial growth monitor is a medical grade device that measures the concentration of bacteria suspended in a liquid medium by measuring changes in light scattering properties, optical density, electrical impedance, or by direct bacterial counts. The device helps diagnose diseases caused by pathogenic microorganisms.

(b)Classification.Class I. With the exception of automated blood culture system devices used to test for bacteria, fungi, and other microorganisms in blood and other normally sterile body fluids, this device is exempt from the premarket notification procedures set forth in Subpart E of Part 807 of this Chapter.

[47 FR 50823, November 9, 1982, modified 60 FR 38482, July 27, 1995]

(a)ID.A gas generating device is a device intended for medical use that produces predetermined amounts of selected gases that are used in a closed chamber to create suitable atmospheric conditions for the cultivation of microorganisms with particular atmospheric requirements. The device helps in the diagnosis of 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID.A Wood's fluorescent lamp is a device designed for medical use to detect fluorescent materials (such as fluorescein pigments produced by certain microorganisms) to aid in the identification of those microorganisms. The device helps in the diagnosis of 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. The equipment is also exempt from the good manufacturing practice requirements of the Quality Systems Regulations in Part 820 of this chapter, except Section 820.180 relating to general record keeping requirements and Section 820.198 relating to record keeping. complaints.

[47 FR 50823, November 9, 1982, modified 66 FR 38791, July 25, 2001]

(a)ID.A microorganism differentiation and identification device is a device intended for medical use, consisting of one or more components, such as to differentiate and identify selected microorganisms. The device helps in the diagnosis of 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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2311, January 14, 2000]

(a)ID.AStreptococcus spp.The nucleic acid-based assay is a qualitative in vitro diagnostic device for the simultaneous detection and identification of variousStreptococcus spp.nucleic acids extracted directly from clinical samples. The device detects specific nucleic acid sequences to identify organisms. Identification helps diagnose diseases caused by bacteria of the genusstreptococciand 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 specific controls for this device are:

(1) Submission of premarket notifications must include detailed product description documentation, including product 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) Submission of premarket notifications must include detailed documentation of the following analytical and clinical performance studies: analytical sensitivity (limit of detection), reactivity, inclusiveness, precision, reproducibility, interference, cross-reactivity, carryover, and cross-contamination .

(3) Detailed documents of a clinical study must be attached to the prior notice submission. The study, conducted in a study population consistent with the intended use population, shall compare the performance of the device with the results obtained from accepted reference methods.

(4) Submission of pre-market notifications must include detailed documentation for device software, including but not limited to software applications and hardware-based devices containing software.

(5) The submission of pre-market notifications must include the database implementation methodology, design parameters and quality assurance protocols, where applicable.

(6) The labeling of the device must contain limitations regarding the need for culture confirmation of negative samples, when applicable.

(7) A detailed explanation of the interpretation of the results and the acceptance criteria shall be included on the 21 CFR 809.10(b)(9) compliant label of the device.

(8) The pre-market notification submission must include details of an end-user device training program that may be offered during the device's commercialization.

[82 FR 50074, October. 30, 2017]

(a)ID.An automated zone reader is a mechanical device designed for medical use to measure zone diameters of inhibition (or display) of microbial growth, as observed on the surface of certain culture media used in agar diffusion tests on disk for antimicrobial sensitivity. The device helps in decision-making regarding the treatment of diseases.

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

(a)ID.A microbiological sample collection and transport device is a sample collection chamber intended for medical use to maintain the viability or integrity of microorganisms in samples during sample storage after sample collection and during transport from the sample area. collection to the laboratory. The device may be labeled or otherwise represented as sterile. The device helps diagnose diseases caused by pathogenic microorganisms.

(b)Classification.Class I (general controls). The device, when intended solely for 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 of section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 84 FR 71800, Dec. 30, 2019; 85 FR 18445, April 2, 2020]

(a)ID. Acinetobacter calcoaceticusSerological reagents are devices consisting ofAcinetobacter calcoaceticusAntigens and antisera to identify this bacterium from isolated cultures derived from clinical samples. Identification helps diagnose diseases caused by the bacteria.Acinetobacter calcoaceticusand provides epidemiological information on diseases caused by this microorganism. This organism becomes pathogenic in burn or immunocompromised patients, and infection can lead to 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID.Adenovirus serological reagents are devices consisting of antigens and antisera used in serological tests to identify antibodies to adenovirus in serum. In addition, some of these reagents consist of adenovirus antisera conjugated to a fluorescent dye and are used to identify adenovirus directly from clinical specimens. Identification helps diagnose diseases caused by adenoviruses and provides epidemiological information about these diseases. Adenovirus infections can cause pharyngitis (sore throat), acute respiratory illness, and certain external diseases of the eye (eg, 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID. Arizonasp. Serological reagents are devices consisting of antisera and antigens that are used for identificationArizonasp. in isolated cultures derived from clinical samples. Identification helps diagnose diseases caused by bacteria of the genusArizonaand provides epidemiological information on diseases caused by these microorganisms.Arizonasp. it 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID. Aspergillussp. Serological reagents are devices consisting of antigens and antisera used in various serological tests to detect antibodies.sprinklersp. in the serum. Identification helps diagnose aspergillosis caused by fungi of the genussprinklerAspergillosis is a disease characterized by inflammatory granulomatous (tumor-like) lesions on the skin, ear, orbit, paranasal sinuses, lungs, and occasionally bone.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2311, January 14, 2000]

(a)ID.An in vitro diagnostic forBacillusSpecies recognition (spp.) is a prescription device used to identify and distinguish speciesBacillussp. and presumably identifyB. anthraxand anotherBacillussp. from culture isolates or clinical specimens as an aid in the diagnosis of anthrax and other anthrax diseasesBacillussp. This device may consist ofBacillussp. antisera conjugated to a fluorescent dye (immunofluorescence reagents) for the presumptive identification of bacillus-like organisms in clinical specimens; Bacteriophage used for differentiation.B. anthraxof othersBacillussp. based on susceptibility to lysis by phage; or antigens used to identify antibodiesB. anthrax(anti-toxin and anti-capsule) in serum. Bacilli infections include anthrax (cutaneous, inhalation, or gastrointestinal) caused byB. anthrax,and gastrointestinal diseases and non-gastrointestinal infections caused byB. Cereo.

(b)Classification.Class II (special controls). Specific controls are described in the FDA Special Controls Guidance document titled "In Vitro Diagnostic Devices forBacillussp. Recognition; Class II Special Controls Guidelines for Industry and Food and Drug Administration Personnel.” See §866.1(e) for guidance document availability.

(C)Distribution Restriction.Distribution of these devices is restricted to laboratories that follow public health guidelines that address appropriate biosafety practices, interpretation of test results, and coordination of results with health authorities.

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

(1) The device must be owned by:

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

(B) A professional such as B. a physician who is legally authorized to use or direct the use of such device; Y

(ii) The Product may only be sold to or on the prescription or other indication of said physician for use in the practice of his profession.

(2) The device label must bear the statement "Caution: Federal law restricts this device to sale by or on behalf of ____" spaced-filled with the word "physician" or with the descriptive term of another licensed physician under the laws of the state in which you practice the use or direct the use of the device.

(3) Any labeling as defined in Section 201(m) of the Federal Food, Drug, and Cosmetic Act, whether on or within the packaging from which the product is dispensed, distributed by, or on behalf of the manufacturer, packer or distributor of the product. product that provides or purports to provide information on the use of the product contains information suitable for such use, including indications, effects, routes of administration, methods and frequency and duration of administration and any relevant dangers, contraindications, side effects and precautions under which physicians who are legally licensed to use the device may use it safely and for the purposes for which it is designed, including the purposes for which it is advertised or represented. This information is not required for so-called notepads, which refer to the name of the device but do not contain instructions or other instructions for use.

(4) All markings, other than labels and boxes, that provide information on the use of the equipment shall also bear the date of issue or the date of last revision of that marking.

[84 FR 12088, April 1, 2019]

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

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

[69 FR 56936, Sept. 23, 2004]

(a)ID. Blastomyces dermatitidisSerological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.Blastomyces determatidisin the serum. Identification helps diagnose blastomycosis caused by the fungusBlastomyces dermatitidis.Blastomycosis is a chronic granulomatous (tumor-like) disease that can be limited to the skin or lungs or spread widely throughout the body, causing damage to the bones, liver, spleen, and kidneys.

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

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59226, Nov. 3, 1998]

(a)ID. Brothelsp. Serological reagents are devices consisting of antigens and antisera, including antisera conjugated to a fluorescent dye, used in serological tests for identification.Brothelsp. from cultured isolates or directly from clinical samples. Identification helps diagnose diseases caused by bacteria of the genusBrotheland provides epidemiological information on these diseases.Brothelsp. cause a sore cough (Bordetella pertussis) and other similar contagious acute respiratory infections characterized by pneumonitis (inflammation of the lungs).

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

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID. brucellasp. Serological reagents are devices consisting of antigens and antisera used for serological identification.brucelasp. of isolate cultures derived from clinical samples or to identify antibodiesbrucelasp. in the serum. In addition, some of these reagents consist of antisera conjugated to a fluorescent dye (immunofluorescent reagents) that are used for identification.brucelasp. directly from clinical samples or culture isolates derived from clinical samples. Identification helps diagnose brucellosis (eg, undulant fever, Maltese fever) caused by bacteria of the genusbrucelaand provides epidemiological information on diseases caused by these microorganisms.

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

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59226, Nov. 3, 1998]

(a)ID. Campylobacter fetusSerological reagents are devices consisting of antisera conjugated to a fluorescent dye used for identification.Campylobacter fetofrom clinical samples or culture isolates derived from clinical samples. Identification helps diagnose diseases caused by this bacterium and provides epidemiological information about these diseases.Campylobacter fetoit is a common cause of abortion in sheep and cattle and 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).

(a)ID.Chlamydia serology reagents are devices consisting of antigens and antisera used in serology tests to detect antibodies to Chlamydia in serum. In addition, some of these reagents consist of Chlamydia antisera conjugated to a fluorescent dye, which is used to identify Chlamydia directly from clinical samples or culture isolates derived from clinical samples. Identification helps diagnose diseases caused by bacteria of the genusclamidiaand provides epidemiological information on these diseases. Chlamydia is the causative agent of psittacosis (a form of pneumonia), lymphogranuloma venereum (a sexually transmitted disease), and trachoma (a chronic disease of the eye and eyelid).

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

(a)ID. citrobactersp. Serological reagents are devices consisting of antigens and antisera used in serological tests for the identificationcitrobactersp. of cultured isolates derived from clinical samples. Identification helps diagnose diseases caused by bacteria of the genuscitrobacterand provides epidemiological information on diseases caused by these microorganisms.citrobactersp. they 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID.AClostridium difficileThe Toxin Gene Amplification Assay is a device consisting of reagents for the amplification and detection of target sequences.Clostridium difficileToxin genes in stool samples from patients suspected of having toxin genesClostridium difficileinfection (ICD). Screening for clostridial toxin genes in conjunction with other laboratory tests aids in the clinical laboratory diagnosis of CDI caused byClostridium difficile.

(b)Classification.Class II (special controls). Special controls are described in the FDA guidance document titled Class II Special Controls Guideline: Toxin Gene Amplification Assays for the Detection ofClostridium difficile;Guidelines for Food and Drug Administration and Industry Personnel.” See § 866.1(e) for information on how to obtain this document.

[80 FR 51939, August 27, 2015]

(a)Ruthless Coccidia IdentificationSerological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.merciless coccidiain the serum. Identification helps diagnose coccidioidomycosis, which is caused by a fungus belonging to the genusof coccidiaand provides epidemiological information on diseases caused by this microorganism. An infection withmerciless coccidiait causes symptoms of varying severity, from those that accompany a common cold to those of the flu.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59226, Nov. 3, 1998]

(a)ID. Corynebacteriumsp. Serological reagents are devices consisting of antisera conjugated to a fluorescent dye used for identification.Corynebacteriumsp. of clinical samples. Identification helps diagnose diseases caused by bacteria of the genusCorynebacteriumand provides epidemiological information on diseases caused by these microorganisms. The most important human pathogen of this genus,Corynebacterium diphtheriae,causes diphtheria. However, many other Corynebacteria species are part of the normal flora of the human respiratory tract, other mucous 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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2311, January 14, 2000]

(a)ID.Coxsackievirus serology reagents are devices consisting of antigens and antisera that are used in serology tests to detect antibodies to coxsackievirus in serum. In addition, some of these reagents consist of coxsackievirus antisera conjugated with a fluorescent dye, which are used to identify coxsackievirus from clinical specimens or from tissue culture isolates derived from clinical specimens. Identification helps diagnose coxsackie virus infections and provides epidemiologic information about diseases caused by these viruses. Coxsackie viruses cause a variety of infections, including the common cold, meningitis (inflammation of the membranes of the brain and spinal cord), herpangina (brief fever accompanied by ulcerative lesions in 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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2311, January 14, 2000]

(a)ID. Cryptococcus neoformansSerological reagents are devices composed of antigens used in serological tests to detect antibodies.Cryptococcus neoformansin the serum. In addition, some of these reagents consist of antisera conjugated to a fluorescent dye (immunofluorescence reagents) and are used for identification.Cryptococcus neoformansdirectly from clinical samples or from culture isolates derived from clinical samples. Identification helps diagnose cryptococcosis and provides epidemiological information about this type of disease. Cryptococcal infections most often present as chronic meningitis (inflammation of the lining of the brain) and are usually fatal if left untreated.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59226, Nov. 3, 1998]

(a)ID.A hepatitis C virus (HCV) antibody test is identified as an in vitro diagnostic medical device intended for use with human serum, plasma, or other matrices as a prescription device that can diagnose HCV infection in persons with signs and symptoms of hepatitis in people at risk. for hepatitis C infection. The test is not designed to screen donor blood, plasma, cells, or tissue.

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

(1) The identification required by section 809.10(b) of this chapter shall include the following:

(i) A clear indication that the test is not intended for the screening of blood, plasma, and cell or tissue donors.

(ii) Constraints that need to be updated to reflect current clinical practice and disease presentation and treatment. Limitations must include, among other things, statements that state:

(A) Where applicable, the performance characteristics of the test have not been established in immunocompromised or immunocompromised patient populations or other special populations in which test performance may be affected.

(B) Detection of HCV antibodies indicates current or past infection with hepatitis C virus, but does not distinguish between acute, chronic, or resolved infection.

(C) The sample types for which the device is approved and that use of the test with sample types other than those specifically approved for this device may result in inaccurate test results.

(D) Test results must be interpreted by a licensed and qualified healthcare professional in conjunction with the individual's clinical presentation, history, and other laboratory results.

(E) A non-reactive test result may occur early during an acute infection, before the development of a host antibody response to the infection, or when analyte levels are below the detection limit of the test.

(iii) A detailed explanation of the principles of operation and procedures for performing the test.

(2) The verification and validation of the design will include:

(i) A detailed description of the device, including all component parts of the device, ancillary reagents required but not provided, an explanation of the device methodology and design of the antigen and capture antibody sequences, justification of the epitope( s) selected, degree of conservation of the target amino acid sequence, and the design and nature of any primary, secondary, and subsequent standards used for calibration.

(ii) Documentation and characterization (z.B.,suppliers, identity and stability determination) of all critical reagents (including description of antigen(s) and capture antibody(s)) and protocols to maintain product integrity throughout the label shelf life.

(iii) Risk analysis and management strategies, such as B. Failure mode impact analysis and/or hazard analysis and critical control point summaries and their impact on test performance.

(iv) Final release criteria to be used for test batches manufactured, with adequate evidence that batches released at the extremes of the specifications meet the declared clinical and analytical performance and stability claims.

(v) Reagent stability studies shall include documentation of a real-time stability evaluation for multiple lots of reagents using the specified sample types and use acceptance criteria that ensure analytical and performance characteristics are met. clinical when stability is assigned based on the extremes of acceptance. range.

(vi) All stability protocols, including acceptance criteria.

(vii) Final results of the release tests for each lot used in the clinical studies.

(viii) Multi-site reproducibility study, including testing of three independent production lots.

(ix) Analytical studies of performance and results to determine limit of blank (LoB), limit of detection (LoD), cut-off, precision (reproducibility), including lot-to-lot and/or instrument-to-instrument precision , interference and cross-reactivity. , carryover, hook effect, seroconversion panel tests, matrix equivalence, sample stability, reagent stability, and genotype antibody detection sensitivity where applicable.

(x) The analytical sensitivity of the test is equal to or better than that of other approved or approved tests.

(xi) Detailed documentation of clinical performance testing from a multi-site clinical study. Performance must be tested against an FDA approved or approved HCV antibody test or comparator assay deemed appropriate by the FDA. This study should be performed using appropriate patient samples with an acceptable number of HCV positive and negative samples in the appropriate risk categories. Other relevant patient groups may need to be validated. Samples may be a combination of fresh samples and stored samples obtained from geographically distinct areas. The study design, including the number of samples tested, must be sufficient to meet the following criteria:

(A) The clinical sensitivity of the test should have a lower limit of the 95 percent confidence interval greater than or equal to 95 percent.

(B) The clinical specificity of the test must have a lower limit of the 95 percent confidence interval greater than or equal to 96 percent.

(3) For each HCV antibody test intended for point-of-care (PoC) use, the following specific controls shall apply in addition to the specific controls listed in paragraphs (b)(1) and (2) of this Section:

(i) Clinical trials must be conducted at PoC sites.

(ii) The additional marking shall include a brief summary of the Instructions for Use suitable for use in a PoC environment.

[86 FR 66176, Nov. 22, 2021]

(a)ID.A nucleic acid-based hepatitis C virus (HCV) ribonucleic acid (RNA) test is identified as an in vitro diagnostic medical device available for prescription use as an aid in the diagnosis of HCV infection in certain populations and / or as an aid in management. of HCV-infected patients, including guidance on the selection of genotype-specific treatment in people with chronic HCV infection. The test is designed for use with human serum or plasma. The test is not intended for use as a donor screening test to detect the presence of HCV antibodies in blood, blood products, or tissue donors.

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

(1) For all nucleic acid-based HCV RNA tests, the labeling required by Section 809.10(b) of this Chapter shall include the following:

(i) A clear indication that the test is not intended to be a donor screening test for the presence of HCV RNA from human cells, tissues, and cell- and tissue-based products.

(ii) A detailed explanation of the principles of operation and procedures for conducting the test.

(iii) A detailed explanation of the interpretation of the results.

(iv) Restrictions that must be updated to reflect current clinical practice and disease presentation and treatment. These limitations must include, among other things, statements that establish:

(A) The sample types for which the device is approved and that use of this test kit with sample types other than those specifically approved for this device may result in inaccurate test results.

(B) Where applicable, assay performance characteristics have not been established in immunocompromised or immunocompromised patient populations or other populations in which assay performance may be compromised.

(C) Test results must be interpreted by a licensed and qualified healthcare professional in conjunction with the individual's clinical presentation, history, and other laboratory results.

(2) For all nucleic acid-based HCV RNA tests, design verification and validation must include:

(i) Detailed description of the device, including device components, ancillary reagents required but not provided, and an explanation of device methodology. Additional information appropriate to the technology should be included, such as: B. primer and probe design, rationale for selected genes, specifications for amplicon size, and degree of conservation of the nucleic acid sequence.

(ii) For devices with assay calibrators, the design and nature of all primary, secondary, and subsequent quantitation standards used for calibration, and their traceability to a standardized reference material established by the FDA, are appropriate (z.B.,a recognized consensus standard). Additionally, analytical testing should be performed after the release of a new batch of the standard material used for device release or approval, or when transitioning to a new calibration standard occurs.

(iii) Documentation and Characterization (z.B.,Determination of identity, suppliers, purity and stability) of all critical reagents (including nucleic acid sequences for primers and probes) and protocols to maintain product integrity.

(iv) Detailed documentation of analytical performance studies performed in accordance with the technology, sample types tested, and intended use of the device, including, but not limited to, limit of detection (LoD), upper and lower limit of quantification (ULoQ and LLoQ). ), linearity, precision, endogenous and exogenous interferences, cross-reactivity, carryover, matrix equivalence, and stability of samples and reagents. Specimens selected for use in analytical studies or used in preparation of samples for use in analytical studies must be derived from subjects with clinically relevant circulating genotypes in the United States. Cross-reactivity studies should 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. as appropriate. The effect of each claimed nucleic acid isolation and purification method on detection should be evaluated.

(v) risk analysis and management strategies, such as B. Failure modes and effects analysis and/or hazard analysis and critical control point summaries and their impact on test performance.

(vi) Final release criteria to be used for test batches manufactured, with appropriate evidence that batches released at the extremes of the specifications meet the stated analytical and clinical performance and stability requirements.

(vii) Multi-site reproducibility study comprising testing of three independent production lots.

(viii) All stability protocols, including acceptance criteria.

(ix) Final results of the release tests for each lot used in the clinical studies.

(x) The analytical sensitivity and specificity of the test must be equal to or better than other approved 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 paragraph (b)(1) and (2) of this section, design verification and validation shall include detailed documentation of performance of a clinical study. in various places. Performance must be tested against an FDA-cleared or approved HCV RNA qualitative test or a comparative test that the FDA deems appropriate. This study should be performed using appropriate patient samples with an adequate number of HCV positive and negative samples in the applicable risk categories. Additional genotypes should be validated using an appropriate number and type of samples. Samples may be a combination of fresh and stored samples, obtained from within and outside of the United States, as needed. The study design, including the number of samples tested, must be sufficient to meet the following criteria:

(i) The clinical sensitivity of the test must have a lower limit of the 95 percent confidence interval greater than or equal to 95 percent.

(ii) The clinical specificity of the test must have a lower limit of the 95 percent confidence interval greater than or equal to 96 percent.

(4) For devices intended for the quantitative detection of HCV RNA, the following specific controls shall apply in addition to the specific controls listed in paragraphs (b)(1) and (2) of this Section:

(i) The labeling required by Section 809.10(b) of this Chapter, when applicable, shall include a clear statement that the Test is not intended to be a diagnostic test to confirm the presence of active HCV infection.

(ii) The verification and validation of the design must include:

(A) Detailed documentation of the following analytical performance studies performed in accordance with the technology, sample types tested, and intended use of the device, including, but not limited to, LoD, ULoQ, and LLoQ. LoD, LLoQ, and linearity studies should demonstrate acceptable device performance across all HCV genotypes recognized by the device.

(B) Detailed documentation of clinical performance testing of:

(1) A multi-center clinical study using an adequate number of clinical specimens from patients with chronic HCV infection, in which results will be compared with an FDA-approved or approved quantitative HCV-RNA assay or with a comparator assay that the FDA deems appropriate. This study should include a sufficient number of HCV positive samples containing an analyte concentration close to the LLoQ to describe performance at that level. Clinical samples should cover the full range of device performance and reflect the distribution of these genotypes in the US population. Clinical samples may be supplemented with diluted clinical samples for those viral load concentrations not adequately covered by clinical samples natural.

(2) A clinical study with prospectively collected samples demonstrating the clinical validity of the device.

(C) Detailed documentation of a qualitative analysis near the lower end of the measurement range showing acceptable performance when used as an aid in diagnosis.

(5) For devices intended for HCV RNA genotyping, design verification and validation shall include the following, in addition to the specific controls listed in paragraph (b)(1) and (2) of this Section:

(i) Detailed documentation of an analytical performance study demonstrating LoD for all HCV genotypes recognized by the device.

(ii) Detailed documentation, including results, of a multicenter clinical study evaluating genotyping accuracy (dhthe proportion of interpretable results that agree with the reference method result) and the genotyping rate (dhPercentage of interpretable results).

(6) For each nucleic acid-based HCV-RNA test intended for point-of-care (PoC) use, the following specific controls apply in addition to those set forth in paragraphs (b)(1) and (2) listed in this section:

(i) Clinical trials must be conducted at PoC sites.

(ii) The additional marking shall include a brief summary of the Instructions for Use suitable for use in a PoC environment.

[86 FR 66172, Nov. 22, 2021]

(a)ID.Cytomegalovirus serological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies to cytomegalovirus in serum. Identification helps diagnose diseases caused by cytomegalovirus (mainly cytomegalovirus inclusion disease) and provides epidemiological information about these diseases. Cytomegalovirus inclusion disease is a systemic infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease can cause severe birth defects, such as microcephaly (abnormally small head), motor disability, and intellectual disability. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and infectious mononucleosis-like syndrome.

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

(a)ID. echinococcussp. Serological reagents are devices consisting ofEquinococosp. Antigens and antisera used in serological tests to detect antibodiesEquinococosp. in the serum. Identification helps diagnose hydatidosis, which is caused by parasitic tapeworms of the genusEquinococoand provides epidemiological information on this disease. Echinococcosis is characterized by the development of cysts in the liver, lungs, kidneys, and other organs, formed by the larvae 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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2311, January 14, 2000]

(a)ID.Echovirus serological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies to echovirus in serum. In addition, some of these reagents consist of echovirus antisera conjugated to a fluorescent dye that is used to identify echoviruses from clinical samples or from tissue cultures isolated from clinical samples. Identification helps diagnose echovirus infections and provides epidemiological information about diseases caused by these viruses. Echoviruses cause illnesses such as meningitis (inflammation of the lining of the brain and spinal cord), febrile illness (accompanied by fever) with or without a 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID.An endotoxin assay is a device that uses serological techniques on whole blood. The device is intended to be used in conjunction with other laboratory findings and clinical evaluation of the patient to aid in the assessment of risk of progression to severe sepsis in critically ill patients.

(b)Classification.Class II (special controls). The specific control for this device is the FDA guideline titled Class II Special Controls Guidance Document: Endotoxin Assay. See §866.1(e) for the availability of this guidance document.

[68 FR 62008, October 31, 2003. Renamed 70 FR 53069, September 7, 2005]

(a)ID.A device for the detection and measurement of nonmicrobial analyte(s) in human clinical specimens to aid in the evaluation of patients with suspected sepsis is identified as an in vitro device used for qualitative and/or quantitative detection and measurement of one or more nonmicrobial microbial analytes in human clinical specimens to aid in the evaluation 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 specific controls for this device are:

(1) Submission of premarket notifications must include the detailed indication statement of the device, describing what the device detects and measures, the results provided to the user, whether the measurement is qualitative and/or quantitative, the clinical indications, for whom the test is intended to be used and the specific population(s) for which the device is intended to be used.

(2) Premarket notification submissions must include detailed product description documentation, including (if applicable) all device components, software, ancillary reagents required but not provided, an explanation of principle and methodology of the product, and for molecular devices, detailed documentation. of the sequence Primer/probe, design and justification for the selection of the sequence.

(3) Submission of premarket notifications must include detailed documentation of applicable analytical studies, such as sample stability.

(4) The pre-market notification submission must contain detailed documentation of a prospective clinical study or, where appropriate, the results of an equivalent set of samples. This detailed documentation must contain the following information:

(i) Results must show reasonable device performance compared to a well-accepted comparison device.

(ii) Results from clinical samples shall demonstrate consistency of device output across the entire measurement range of the device likely to be found in the population of intended use.

(iii) Clinical study documentation must include the original study protocol (including the predefined statistical analysis plan), the study report documenting support for the indications, and the results of all statistical analyses.

(5) The submission of the prior notification shall include an assessment of the concentration of the nonmicrobial analyte in asymptomatic patients with demographic characteristics (z.B.,Age, race, ethnicity and gender distribution) similar to the intended use population.

(6) As part of risk management activities conducted in accordance with 21 CFR 820.30 Design Controls, you must document an appropriate instrument training program for end users that is provided as part of your efforts to mitigate the risk of misuse. instrument operation.

(7) A detailed explanation of the interpretation of the results and the acceptance criteria must be included in the labeling of the device that complies with 21 CFR 809.10(b)(9), as well as a detailed explanation of the interpretation of the limitations of the sample (z.B.,collected on the day of diagnosis) must be included on the 21 CFR 809.10(b)(10) label of the device.

[82 FR 49099, oct. 24, 2017]

(a)ID. entamoeba histolyticaSerological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.Entamoeba histolyticain the serum. In addition, some of these reagents consist of antisera conjugated to a fluorescent dye (immunofluorescent reagents) that are used for identification.Entamoeba histolyticadirectly from clinical samples. Identification helps diagnose amoebiasis caused by the microscopic single-celled parasiteEntamoeba histolyticaand provides epidemiological information on the diseases caused by this parasite. The parasite can invade the skin, liver, intestines, lungs, and diaphragm and cause diseases such as indolent ulcers, amebic hepatitis, amebic dysentery, and lung 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 section 866.9.

[47 FR 50823, Nov. 9, 1982; 47 FR 56846, December 21, 1982, modified 63 FR 59226, November 3, 1998]

(a)ID.An enterovirus nucleic acid assay is a device consisting of primers, probes, enzymes, and controls for the amplification and detection of enterovirus ribonucleic acid (RNA) in the cerebrospinal fluid (CSF) of individuals presenting with signs and symptoms associated with meningitis. or coincidental meningoencephalitis. Detection of enterovirus RNA, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of enterovirus-induced viral meningitis.

(b)Classification.Class II (special controls). The special control is the FDA guidance document titled Class II Special Controls Guidance Document: Nucleic Acid Amplification Assay for Enterovirus RNA Detection. See §866.1(e) for the availability of this guidance document.

[74 FR 8, January 2, 2009]

(a)ID.Epstein-Barr virus serological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies to Epstein-Barr virus in serum. Identification helps diagnose Epstein-Barr virus infections and provides epidemiologic information about diseases caused by these viruses. The Epstein-Barr virus is believed to cause infectious mononucleosis and has been linked to Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).

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

(a)ID.Equine Encephalomyelitis Virus Serological Reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies to Equine Encephalomyelitis Virus in serum. Identification helps diagnose diseases caused by equine encephalomyelitis viruses and provides epidemiological information about these viruses. Equine encephalomyelitis viruses are transmitted to humans by biting insects such as mosquitoes and ticks and can 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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2311, January 14, 2000]

(a)ID. Erysipelothrix rhusiopathiaeSerological reagents are devices consisting of antigens and antisera used in serological tests for the identificationErysipelothrix rhusiopathiaeof cultured isolates derived from clinical samples. Identification aids in the diagnosis of diseases caused by this genus of bacteria.Erysipelothrix.This organism is responsible for a variety of dermatitis 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID. Escherichia coliSerological reagents are devices consisting of antigens and antisera used in serological tests for the identificationEscherichia coliof cultured isolates derived from clinical samples. Furthermore, some of these reagents consist ofEscherichia coliantisera conjugated to a fluorescent dye for identificationEscherichia colidirectly from clinical samples or culture isolates derived from clinical samples. Identification aids in the diagnosis of diseases caused by this genus of bacteria.Escherichia,and provides epidemiological information on diseases caused by this microorganism. AlthoughEscherichia colimakes up the majority of microorganisms found in the human intestinal tract and is generally non-pathogenic, pathogenic strains can cause urinary tract infections or epidemic diarrheal diseases, 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]

(a)ID. Flavobacteriasp. Serological reagents are devices consisting of antigens and antisera used in serological tests for the identificationFlavobakteriumsp. of cultured isolates derived from clinical samples. Identification helps diagnose diseases caused by bacteria of the genusFlavobakteriumand provides epidemiological information on diseases caused by these microorganisms. Most of the representatives of this genus are found in soil and water and can become pathogenic to humans under certain conditions.Flavobacterium meningosepticumit is highly contagious to newborns, where it can cause epidemics of septicemia (blood poisoning) and meningitis (inflammation of the lining of the brain), and is usually due 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25046, June 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID. Francisella tularensisSerological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.Francisella tularensisin serum or for identificationFrancisella tularensisin isolated cultures derived from clinical samples. In addition, some of these reagents consist of antisera conjugated to a fluorescent dye (immunofluorescent reagents) that are used for identification.Francisella tularensisdirectly from clinical samples. Identification helps diagnose tularemia caused byFrancisella tularensisand provides epidemiological information on this disease. Tularemia is primarily a rodent disease, but it can be transmitted to humans through handling of infected animals, animal products, or through flea and tick bites. The disease takes different forms depending on the site of the infection, such as skin lesions, enlarged lymph nodes, or lung infections.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59226, Nov. 3, 1998]

(a)ID.A gonococcal antibody test (GAT) is an in vitro device consisting of reagents designed to identify antibodies by immunochemical techniques such as latex agglutination, indirect fluorescent antibody, or radioimmunoassay.Neisseria gonorrhoeaein sera from asymptomatic females with low risk of infection. Identification of antibodies with this device may indicate a past or current infection in the patientNeisseria 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, a permit is required under Section 515 of the Act before this device can be sold commercially. See § 866.3.

[47 FR 50823, November 9, 1982, modified 52 FR 17734, May 11, 1987]

(a)ID. hemophilussp. Serological reagents are devices consisting of antigens and antisera, including antisera conjugated to a fluorescent dye, used in serological tests for identification.hemophilussp. Tissue culture isolates obtained directly from clinical samples or from clinical samples. Identification helps diagnose diseases caused by bacteria of the genushemophilusand provides epidemiological information on diseases caused by these microorganisms. Diseases most frequently caused byhemophilussp. they include pneumonia, pharyngitis, sinusitis, vaginitis, venereal ulcers, and a contagious form of conjunctivitis (inflammation of the membranes of the eyelids).

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59226, Nov. 3, 1998]

(a)ID.Herpes simplex virus serological assays are devices consisting of antigens and antisera that are used in various serological tests to identify antibodies to the herpes simplex virus in serum. In addition, some of the assays consist of herpes simplex virus antisera conjugated to a fluorescent dye (immunofluorescence assays) that are used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates obtained from clinical specimens. Identification helps diagnose diseases caused by the herpes simplex virus and provides epidemiological information about these diseases. Herpes simplex virus infections range from common, mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpesvirus infections range from mild infection to severe systemic disease with fatal outcome.

(b)Classification.Class II (special controls). The device is classified as class II (special controls). The specific control for the device is the revised FDA guidance document titled Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays. See §866.1(e) for document availability. revised guidance.

[72 FR 15830, 3 Apr 2007, modified to 74 FR 42775, 25 Aug 2009; 76 FR 48717, August 9, 2011]

(a)ID.Herpesvirus Nucleic Acid-Based Panel for Skin and Mucocutaneous Lesions is a qualitative in vitro diagnostic device intended for the simultaneous detection and differentiation of various herpesviruses in skin and mucocutaneous lesion specimens from symptomatic patients with suspected herpetic infections. Negative results do not exclude infection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use on CSF samples.

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

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

(2) Submission of premarket notifications must include detailed documentation of the following analytical and clinical performance studies: analytical sensitivity (limit of detection), reactivity, inclusiveness, precision, reproducibility, interference, cross-reactivity, carryover, and cross-contamination .

(3) The submission of the prior notification must contain detailed documentation of a clinical study with samples of lesions in which the detection of DNA of the herpes simplex virus 1, herpes simplex virus 2 or varicella zoster virus was requested. The study should compare the performance of the device with an appropriate and well-established reference method.

(4) A detailed explanation of the interpretation of the results and the acceptance criteria shall be included on the 21 CFR 809.10(b)(9) compliant label of the device.

(5) The product label must include a disclaimer stating: "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) Submission of pre-market notifications must include quality assurance records and detailed documentation for device software, including but not limited to stand-alone software applications and hardware-based devices containing software.

(7) Risk management activities performed as part of the manufacturer's 21 CFR 820.30 design controls shall document an appropriate end-user instrument training program that is provided as part of efforts to mitigate the risk of malfunction of the instrument.

[83 FR 52314, October. 17, 2018]

(a)ID.HAV serological assays are devices consisting of antigens and antisera for the detection of IgM, IgG, or total antibodies (IgM and IgG) specific to the hepatitis A virus in human serum or plasma. These devices are used to test samples from people who have signs and symptoms consistent with acute hepatitis to determine if a person has been previously infected with HAV or to identify people who are susceptible to HAV. Detection of these antibodies aids in the clinical laboratory diagnosis of current or past HAV infection in conjunction with other clinical laboratory findings. These devices are not intended for the screening of soft or hard tissue or blood donors.

(b)Classification.Class II (special controls). The specific control is FDA Industry and Personnel Guidance: Class II Special Controls Guidance Document: Hepatitis A Virus Serological Assays. See §866.1(e) for the availability of this guidance document.

[71 FR 6679, February 9, 2006]

(a)ID. Histoplasma capsulatumSerological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.Histoplasma capsulatumin the serum. Furthermore, some of these reagents consist ofHistoplasma capsulatumAntisera conjugated to a fluorescent dye (immunofluorescent reagents) used for identificationHistoplasma capsulatumfrom clinical samples or culture isolates derived from clinical samples. Identification helps diagnose histoplasmosis caused by this fungus belonging to the genusHistoplasmaand provides epidemiological information on the diseases caused by this fungus. Histoplasmosis is usually a mild and often asymptomatic respiratory infection, but in a small number of infected people, the lesions can spread to virtually any tissue and organ.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59227, Nov. 3, 1998]

(a)ID.An influenza virus antigen detection test system is a device designed for the qualitative detection of influenza virus antigens directly from clinical specimens in patients with signs and symptoms of respiratory infection. The test helps diagnose influenza infection and provides epidemiological information about influenza. Due to the propensity of the virus to mutate, new strains emerge over time that can potentially affect the performance of these devices. Because influenza is highly contagious and can cause an acute respiratory infection that can lead to severe illness and even death, the accuracy of these devices has serious public health implications.

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

(1) The sensitivity and specificity performance characteristics or percent positive agreement and percent negative agreement of the device shall meet one of the following two minimum clinical performance criteria for each specimen type declared for the intended use of the device :

(i) For devices being evaluated with an FDA-approved nucleic acid-based test or other currently appropriate and FDA-accepted comparative method that is not a properly 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 limit of the 95 percent confidence interval higher 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 limit of the 95 percent confidence interval greater or equal to 90 percent.

(ii) For products evaluated as a comparison method against a correctly performed viral culture method:

(A) The estimated sensitivity for the device when testing for influenza A must be at the point estimate of at least 90 percent, with a lower limit of the 95 percent confidence interval that is greater than or equal to 80 percent. The sensitivity estimate of the device when testing for influenza B should be at the point estimate of at least 80 percent, with a lower limit 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 limit of the 95 percent confidence interval greater than or equal to the 90 percent.

(2) When testing to demonstrate that the device meets the requirements of paragraph (b)(1) of this section, a currently appropriate and FDA-accepted comparison method must be used to determine test performance in clinical trials. clinical.

(3) Annual analytical reactivity testing of the device should be performed with current strains of influenza. This annual analytical reactivity test must meet the following criteria:

(i) Strains eligible for testing are identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and obtained from CDC or an FDA-designated source. If annual strains are not available from CDC, FDA will identify an alternate source to obtain the required strains.

(ii) Testing must be performed in accordance with a standardized protocol deemed acceptable and appropriate by the FDA.

(iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity tests must be included as part of the product labeling. If a device has not been on the market long enough for an annual analytical reactivity test to have been performed for 3 years since the device received FDA marketing approval, all reactivity test results must be submitted. annual analytical reactivity since the device received FDA marketing approval. It will be included. The results must be presented as part of the labeling of the device in tabular form, containing the detailed information of each virus tested, as described in the Certificate of Authentication, either by:

(A) place the results directly on the §809.10(b) compliant device label that physically accompanies the device in a separate section of the label where analytical reactivity test data can be found; either

(B) On the device label or other label that physically accompanies the device, with a prominent hyperlink to the manufacturer's public website where analytical reactivity test data can be found. The manufacturer's home page, as well as the main part of the manufacturer's website dealing with the device, must contain a conspicuously placed hyperlink to the web page containing this information and allow unrestricted viewing access.

(4) If any of the actions listed in Section 564(b)(1)(A)-(D) of the Federal Food, Drug, and Cosmetic Act occurs in connection with a strain of influenza virus, or if the Secretary of Health and Human Services (HHS) determines under Section 319(a) of the Public Health Services Act that a disease or disorder constitutes a public health emergency or that a public health emergency exists in connection with a strain of influenza virus:

(i) Within 30 days of the date FDA notifies manufacturers that characterized virus samples are available for assay interpretation, the manufacturer must have the device tested with those virus samples in accordance with a standardized protocol approved by the FDA as considered acceptable, determined and reasonable. The test procedure and location may depend on the type of emerging virus.

(ii) Within 60 days from the date FDA notifies manufacturers that characterized virus specimens are available for assay interpretation and up to 3 years after that date, reactivity test results Emergency influenza testing, including detailed virus information tested, as described in the Certificate of Authenticity, be included as part of the device identification in tabular form, either by:

(A) Place the results directly on the §809.10(b) compliant device label that physically accompanies the device, in a separate section of the label where the analytical reactivity test data can be found but separate from the results. results of the annual analytical reactivity test; either

(B) On a section of the device label, or on another label that physically accompanies the device, with a prominent hyperlink to the manufacturer's public website where analytical reactivity test data can be found. The manufacturer's home page, as well as the main part of the manufacturer's website dealing with the device, must contain a conspicuously placed hyperlink to the web page containing this information and allow unrestricted viewing access.

[82 FR 3618, Jan 12, 2017]

(a)ID.Influenza virus serologic reagents are devices consisting of antigens and antisera that are used in serologic tests to detect antibodies to influenza in serum. Identification helps diagnose influenza (flu) and provides epidemiological information about influenza. Influenza is an acute respiratory disease that 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID.Specific Novel Influenza A Virus Detection Reagents are products intended for use in a nucleic acid amplification assay for the direct detection of specific viral RNA in human respiratory specimens or viral cultures. Detection of specific viral RNA aids in the diagnosis of influenza caused by specific novel influenza A viruses in patients clinically at risk for infection with these viruses, and also aids in the presumptive laboratory identification of specific novel influenza A viruses to provide information epidemiology of influenza. These reagents include primers, probes, and controls specific for influenza A virus.

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

(1) FDA guidance titled Class II Special Controls Guidance Document: Reagents for the Detection of Novel Influenza A-Specific Viruses. See § 866.1(e) for information on how to obtain this document.

(2) Distribution of this kit is restricted to laboratories with experienced staff trained in standardized molecular testing procedures and expertise in virus diagnosis and appropriate biosafety and containment equipment.

[71 FR 14379, March 22, 2006]

(a)ID.John Cunningham virus serological reagents are devices consisting of antigens and antisera used in serological assays to detect antibodies to John Cunningham virus in serum and plasma. Identification aids in risk stratification of developing progressive multifocal leukoencephalopathy in patients with multiple sclerosis and Crohn's disease receiving natalizumab treatment. These devices are intended for adjunctive use in the context of other clinical risk factors for the development of PML.

(b)Classification.Class II (special controls). The specific control for this device is the FDA guidance document titled Class II Special Controls Guideline: John Cunningham Virus Serology Reagents. See § 866.1(e) for policy document availability.

[79 FR 3740, Jan. 23, 2014]

(a)ID. Klebsiellasp. Serological reagents are devices consisting of antigens and antisera, including antisera conjugated with a fluorescent dye (immunofluorescent reagents), used in serological tests for the identificationKlebsiellasp. of cultured isolates derived from clinical samples. Identification helps diagnose diseases caused by bacteria of the genusKlebsiellaand provides epidemiological information on these diseases. These pathogens can cause serious urinary and pulmonary infections, especially in hospitalized patients.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID. leptospirasp. Serological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.leptospirasp. in serum or identifyleptospirasp. of cultured isolates derived from clinical samples. In addition, some of these antisera are conjugated to a fluorescent dye (immunofluorescent reagents) and used for identification.leptospirasp. directly from clinical samples. Identification helps diagnose leptospirosis, which is caused by a bacterium of the genusleptospiraand provides epidemiological information on this disease.leptospiraInfections range from mild illnesses causing fever to severe involvement of the liver and kidneys causing bleeding and kidney dysfunction.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59227, Nov. 3, 1998]

(a)ID. listeriasp. Serological reagents are devices consisting of antigens and antisera used in serological tests for the identificationListeriasp. of cultured isolates derived from clinical samples. Furthermore, some of these reagents consist ofListeriasp. Antisera conjugated to a fluorescent dye (immunofluorescent reagents) used for identificationListeriasp. directly from clinical samples. Identification helps diagnose listeriosis, a disease caused by a bacterium of the genuslisteria,and provides epidemiological information on diseases caused by these microorganisms.Listeria monocytogenes,the most common human pathogen of this genus, it causes meningitis (inflammation of the meninges) and meningoencephalitis (inflammation of the brain and meninges) and is often fatal if left untreated. A second form of human listeriosis is an intrauterine infection in pregnant women, resulting in a high mortality rate of babies before or after birth.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2311, January 14, 2000]

(a)ID.Lymphocytic Choriomeningitis Virus Serologic Reagents are kits consisting of antigens and antisera used in serologic tests to detect antibodies to Lymphocytic Choriomeningitis Virus in serum. Identification aids in the diagnosis of lymphocytic choriomeningitis virus infection and provides epidemiological information about diseases caused by these viruses. Lymphocytic choriomeningitis viruses usually cause mild cerebral meningitis (inflammation of the lining of the brain) and occasionally mild pneumonia, but in rare cases they can cause serious illness or even death from complications of cerebral meningitis and pneumonia.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2311, January 14, 2000]

(a)ID.A microorganism identification clinical mass spectrometer system is a qualitative in vitro diagnostic device intended for the identification of cultured microorganisms from human samples. The device consists of an ionization source, a mass analyzer and a spectral database. The device is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infections.

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

(1) Submission of pre-market notifications must include detailed documentation for device software, including, but not limited to, stand-alone software applications and hardware-based devices that contain software.

(2) The submission of pre-market notifications must include the database implementation methodology, design parameters and quality assurance protocols.

(3) A detailed explanation of the interpretation of the results and the acceptance criteria must be included on the 21 CFR 809.10(b)(9) compliant label of the device.

(4) As part of the risk management activities performed as part of your design controls 21 CFR 820.30, you must document an appropriate end-user device training program that is offered as part of your efforts to mitigate operational risk wrong instrument.

(5) The pre-market notification submission shall include details of the relevant end-user device training program that will be offered during the device's commercialization.

[82 FR 49101, oct. 24, 2017]

(a)ID.A multiplex nucleic acid assay for the identification of microorganisms and resistance markers from positive blood cultures is an in vitro qualitative device for the simultaneous detection and identification of nucleic acids from microorganisms from blood cultures that are positive by Gram stain or other microbiological stains. The device recognizes specific nucleic acid sequences used to identify microorganisms and antimicrobial resistance. This device aids in the diagnosis of bloodstream infections when used in conjunction with other clinical and laboratory findings. However, the device is not a replacement for traditional susceptibility testing and culture methods.

(b)Classification.Class II (special controls). The specific control for this device is the FDA guidance document titled Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures. See § 866.1(e) for policy document availability.

[80 FR 30154, May 27, 2015]

(a)ID. mycobacterial tuberculosisImmunofluorescent reagents are devices consisting of antisera conjugated to a fluorescent dye used for identification.mycobacterial tuberculosisdirectly from clinical samples. Identification helps diagnose tuberculosis and provides epidemiological information about this disease.mycobacterial tuberculosisIt is the most common causative agent of human tuberculosis, a chronic infectious disease characterized by the formation of tubercles (small rounded nodules) and tissue necrosis (destruction) and usually occurs in the lungs.

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

(a)ID.In vitro diagnostics based on nucleic acids for the detection ofmycobacterial tuberculosisNucleic acid-based qualitative in vitro diagnostics for detection are complex in respiratory specimensmycobacterial tuberculosisComplex nucleic acids extracted from human respiratory samples. These devices are not multiplexed and are intended to aid in the diagnosis of pulmonary tuberculosis when used in conjunction with clinical and laboratory findings. These products do not include products designed to detect the presence of mutations in the body associated with drug resistance. Respiratory specimens may include sputum (induced or expectorated), bronchial specimens (eg, bronchoalveolar lavage or bronchial aspirate), or tracheal aspirates.

(b)Classification.Class II (special controls). The specific control for this device is the FDA document titled Class II Special Controls Guideline: Nucleic Acid-Based In Vitro Diagnostic Devices for the Detection ofmycobacterial tuberculosisComplex in Respiratory Specimens.” See § 866.1(e) for the availability of the policy document.

[79 FR 31027, May 30, 2014]

(a)ID.In vitro diagnostics based on nucleic acids for the detection ofmycobacterial tuberculosis(MTB complex) and MTB complex antibiotic resistance-associated gene mutations in respiratory samples are qualitative nucleic acid-based devices that detect the presence of MTB complex-associated nucleic acid sequences in respiratory samples. These devices are intended to aid in the diagnosis of pulmonary tuberculosis and the selection of an initial treatment regimen when used in conjunction with clinical and other laboratory findings. These devices do not provide confirmation of antibiotic susceptibility because other resistance mechanisms may exist, which may be associated with a lack of clinical response to treatment other than those recognized by the device.

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

(1) Das FDA-Document mit dem Titel „Class II Special Controls Guidelines: Nucleic Acid-Based In Vitro Diagnostic Devices for the Detection ofmycobacterial tuberculosisComplex and genetic mutations associated with antibiotic resistance in respiratory samples, addressing specific risk mitigation for detection of the MTB complex. See §866.1(e) for document availability.

(2) The following points, which try to mitigate the specific risks of the detection of genetic mutations associated with antimicrobial resistance of the MTB complex:

(i) The device must contain an external positive assay control, if applicable. Acceptable positive test controls include MTB complex isolates that contain one or more antibiotic resistance-associated target sequences recognized by the instrument.

(ii) The product must include internal controls, where applicable. An acceptable internal control may include human nucleic acid co-extracted with an MTB complex containing nucleic acid sequences associated with antibiotic resistance and primers that amplify human housekeeping genes (eg, RNaseP, β-actin).

(iii) The intended use of the product should include a description of the level of resistance to the antimicrobials targeted for testing, ie h the specific drugs and/or classes of drugs.

(iv) The specific performance characteristics section of the product label shall contain information on the specificity of the assay oligonucleotides for detecting mutations associated with antibiotic resistance of the MTB complex and any information indicating the potential for non-specific binding (eg, BLAST search).

(v) To demonstrate the performance of the device, you must:

(A) Preanalytical studies that evaluate:

(1)Frozen samples.When frozen specimens are used in product performance studies or when there is a product statement for the use of frozen specimens for testing, the effect of freezing specimens prior to testing and the effect of multiple freeze/thaw cycles on strains sensitive and resistant to antibiotics. of the BTT complex.

(2)Nucleic acid extraction methods.Extraction methods should be consistent with those used in MTB complex nucleic acid detection devices and confirm that the detection of genetic mutations associated with antibiotic resistance is not compromised.

(B) Analytical studies that analyze:

(1)detection limit.The detection limit should be determined on the most challenging matrix (eg, sputum) claimed for use with the device. The detection limit should be determined with antibiotic resistant and sensitive strains of the MTB complex. Antibiotic resistant strains should be those with well-characterized genetic mutations associated with antibiotic resistance.

(2)Analytical reactivity (inclusivity).Testing should be performed to assess the ability of the device to detect genetic mutations associated with antibiotic resistance in a variety of strains of the MTB complex. Isolates used for testing must be well characterized. The characterization of the isolates must be carried out using standardized reference methods recognized by an accredited scientific body and appropriate for the strain line.

(3)Internal laboratory precision tests (repeatability).Internal precision studies, where applicable, should include at least one antibiotic-resistant and one antibiotic-susceptible MTB complex strain.

(4) Between laboratory reproducibility tests.The protocol for the reproducibility study may vary slightly depending on the test format; However, the panel must contain at least one antibiotic resistant and one antibiotic sensitive MTB complex strain.

(C) Clinical studies. The clinical performance of the device should be demonstrated by conducting prospective clinical studies in subjects with culture-confirmed active tuberculosis. Studies should attempt to recruit subjects at risk of antibiotic-resistant MTB complexes; However, it may be necessary to include additional antibiotic resistant contrived and retrospective samples. Clinical trials should compare device results with phenotypic drug susceptibility testing and genotypic reference methods. The genotypic reference method will be a polymerase chain reaction-based method using different primers than the experimental device and confirmed by bidirectional sequencing.

[79 FR 63036, October. 22, 2014]

(a)ID. mycoplasmasp. Serological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.mycoplasmasp. in the serum. Furthermore, some of these reagents consist ofmycoplasmasp. Antisera conjugated to a fluorescent dye (immunofluorescent reagents) used for identificationmycoplasmasp. directly from clinical samples. Identification helps diagnose diseases caused by bacteria of the genusmycoplasmaand provides epidemiological information on diseases caused by these microorganisms.mycoplasmasp. they are associated with inflammatory diseases of the urinary and respiratory tracts, the genitals and the mouth. The impact of the infection on humansmicoplasma pneumoniaethey range from an inapparent infection to mild or severe illness of the upper respiratory tract, ear infection, and bronchial pneumonia.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2311, January 14, 2000]

(a)ID.Mumps virus serology reagents consist of antigens and antisera used in serology tests to detect antibodies to the mumps virus in serum. In addition, some of these reagents consist of antisera conjugated to a fluorescent dye (immunofluorescent reagents) that are used in serologic tests to identify mumps virus from tissue culture isolates derived from clinical specimens. Identification helps diagnose mumps and provides epidemiological information about mumps. Mumps is an acute contagious disease, particularly in children, characterized by an enlargement of one or both of the parotid glands (glands near the ear), although other organs may also be affected.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2311, January 14, 2000]

(a)ID. Neisseriasp. Direct serological test reagents are devices consisting of antigens and antisera used in serological tests for the identificationNeisseriasp. of cultured isolates. Furthermore, some of these reagents consist ofNeisseriasp. Antisera conjugated to a fluorescent dye (immunofluorescent reagents) that can be used to detect the presence ofNeisseriasp. directly from clinical samples. Identification helps diagnose diseases caused by bacteria of the genusNeisseria,B. epidemic of cerebrospinal meningitis, meningococcal disease, and gonorrhea, and also provides epidemiological information on diseases caused by these microorganisms. The product does not include products for the detection of human gonorrhea by indirect methods such as B. the detection of antibodies or oxidase produced by gonococcal organisms.

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

(a)ID.Norovirus serological reagents are devices consisting of antigens and antisera used in serological tests to detect the presence of norovirus antigens in stool samples. These devices aid in the diagnosis of norovirus infection in an individual patient with symptoms of acute gastroenteritis when the individual patient has an epidemiological association with other patients with symptoms of acute gastroenteritis and/or aid in the identification of norovirus as the etiology of an outbreak sharp. gastroenteritis in patients with an epidemiological association with symptoms of acute gastroenteritis.

(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 the limitations in §866.9. The special control is the FDA guidance document titled Class II Special Controls Guidance Document: Norovirus Serology Reagents. See §866.1(e) for the availability of this guidance document.

[76 FR 14274, March 9, 2012, amended 84 FR 71800, December 30, 2019]

(a)ID.Parainfluenza virus serological reagents are devices consisting of antigens and antisera that are used in serological tests to detect antibodies to parainfluenza viruses in serum. Identification helps diagnose parainfluenza virus infections and provides epidemiologic information about illnesses caused by these viruses. Parainfluenza viruses cause a variety of respiratory illnesses ranging from the common cold to pneumonia.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID.APlasmodioSpecies Antigen Detection Assay is a device that uses antibodies to detect malaria parasite-specific antigens, including histidine-rich protein 2 (HRP2)-specific antigens and pan-malaria antigens in human whole blood. These devices are used to test samples from people who show signs and symptoms of malaria infection. Detection of these antigens aids in the clinical laboratory diagnosis of malaria caused by the four types of malaria that can infect humans:Plasmodium falciparum,Plasmodium vivax,Oval Plasmodium, yPlasmodium malariaeand help in the differential diagnosis ofPlasmodium falciparumInfections by other, less virulentPlasmodioSpecies. The device is intended to be used in conjunction with other clinical laboratory findings.

(b)Classification.Class II (special controls). The special control is the FDA guidance document titled "Class II Special Controls Guidance Document:PlasmodioSpecies antigen detection assays.” See §866.1(e) for the availability of this guidance document.

[73 FR 29054, May 20, 2008]

(a)ID.Poliovirus serological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies to poliovirus in serum. In addition, some of these reagents consist of fluorescent dye-conjugated poliovirus antisera (immunofluorescence reagents) that are used to identify poliovirus from clinical specimens or from tissue cultures isolated from clinical specimens. Identification helps diagnose poliomyelitis (polio) and provides epidemiological information about this disease. Polio is an acute infectious disease that, in its severe form, affects the central nervous system and leads to atrophy (weakening) of muscle groups, causing shrinkage and permanent deformity.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)Identification. protectionsp. (Weil-Felix) Serological reagents are devices consisting of antigens and antisera, including antisera conjugated with a fluorescent dye (immunofluorescent reagents), derived from the bacteriumvulgar protectionIt is used in agglutination tests (a type of antigen-antibody reaction) to detect antibodies against rickettsia (virus-like bacteria) in serum. Test results help diagnose diseases caused by bacteria of the genusRickettsiaand provide epidemiological information on these diseases. Rickettsiae are generally transmitted by arthropods (eg, ticks and mosquitoes) and cause human infections characterized by rash and fever (eg, typhoid fever, spotted fever, Q fever, and trench fever).

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID. pseudomonassp. Serological reagents are devices consisting of antigens and antisera, including antisera conjugated to a fluorescent dye (immunofluorescent reagents), used for identificationPseudomonassp. from clinical specimens or from culture isolates derived from clinical specimens. Identification helps diagnose diseases caused by bacteria of the genusPseudomonas. Pseudomonas aeruginosaIt is one of the leading causes of hospital infections and has been linked to urinary tract infections, eye infections, burn and wound infections, blood poisoning, abscesses, and meningitis (inflammation of the lining of the brain).Pseudomonas pseudomalleicauses melioidosis, a chronic pneumonia.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59227, Nov. 3, 1998]

(a)ID.Rabies virus immunofluorescent reagents are devices consisting of rabies virus antisera conjugated to a fluorescent dye used to detect rabies virus in specimens collected from animals suspected of having rabies. Identification helps diagnose rabies in patients exposed to animal bites and provides epidemiological information about rabies. Rabies is an acute infectious disease of the central nervous system that, if undiagnosed, can be fatal. The disease is commonly transmitted to humans through the bite of a rabid animal.

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

(a)ID.Reovirus serological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies to reovirus in serum. Identification helps diagnose reovirus infections and provides epidemiological information about diseases caused by these viruses. Reoviruses are thought to cause only mild respiratory and gastrointestinal illness.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID.Respiratory syncytial virus serologic reagents are devices consisting of antigens and antisera used in serologic tests to detect antibodies to respiratory syncytial virus in serum. In addition, some of these reagents consist of respiratory syncytial virus antisera conjugated with a fluorescent dye (immunofluorescence reagents) and are used to identify respiratory syncytial virus in clinical specimens or in tissue cultures isolated from clinical specimens. Identification helps diagnose respiratory syncytial virus infections and provides epidemiological information about diseases caused by these viruses. Respiratory syncytial viruses cause a variety of respiratory infections, including the common cold, pharyngitis, and childhood bronchopneumonia.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.Rhinovirus serological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies to rhinovirus in serum. Identification helps diagnose rhinovirus infections and provides epidemiological information about diseases caused by these viruses. Rhinoviruses cause colds.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID.Rickettsia serology reagents are products consisting of antigens and antisera used in serology tests to detect antibodies to Rickettsia in serum. In addition, some of these reagents consist of antisera to Rickettsia conjugated to a fluorescent dye (immunofluorescence reagents), which are used to directly detect Rickettsia in clinical specimens. Identification helps diagnose diseases caused by virus-like bacteria of the genusRickettsiaand provides epidemiological information on these diseases. Rickettsiae are generally transmitted by arthropods (eg, ticks and mosquitoes) and cause human infections characterized by rash and fever (eg, typhoid fever, spotted fever, Q fever, and trench fever).

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.Rubella virus serological reagents are devices consisting of antigens and antisera that are used in serological tests to detect antibodies to rubella virus in serum. Identification helps diagnose rubella (German measles) or confirm a person's immune status from previous infections or vaccinations, and provides epidemiological information about rubella. Newborns infected with rubella virus in utero can be born with multiple birth defects (rubella syndrome).

(b)Classification.Class II Controls specific to this device are:

(1) National Committee for Clinical Laboratory Standards:

(i) 1/LA6 "Detection and Quantification of Rubella IgG Antibodies: Evaluation and Performance Criteria for Multi-Component Test Products, Sample Handling, and Use of Test Products in the Clinical Laboratory, October 1997"

(ii) 1/LA18 "Specifications for immunological tests for infectious diseases, December 1994",

(iii) D13 "Agglutination Properties, Methodology, Limitations, and Clinical Validation, October 1993"

(iv) EP5 „Precision Performance Evaluation of Clinical Chemistry Devices, February 1999“ and

(v) EP10 "Preliminary Assessment of the Linearity of Quantitative Clinical Laboratory Methods, May 1998"

(2) Centers for Disease Control:

(i) low titer rubella standard,

(ii) reference panel of well-characterized rubella sera and

(3) International Rubella Standard of the World Health Organization.

[47 FR 50823, Nov. 9, 1982, as amended 52 FR 17734, May 11, 1987; 65 FR 17144, March 31, 2000]

(a)ID.Rubella (Measles) Virus Serological Reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies to rubella virus in serum. Identification helps diagnose measles and provides epidemiological information about the disease. Measles is an acute, highly infectious disease of the respiratory and reticuloendothelial tissues, particularly in children, characterized by a confluent, patchy rash.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)IDENTIFICATION. salmonellasp. Serological reagents are devices consisting of antigens and antisera used in serological tests for the identificationsalmonellasp. of cultured isolates derived from clinical samples. In addition, some of these reagents consist of antisera conjugated to a fluorescent dye (immunofluorescent reagents) that are used for identification.salmonellasp. directly from clinical samples or culture isolates derived from clinical samples. Identification helps diagnose salmonellosis caused by bacteria of the genussalmonellaand provides epidemiological information on this disease. Salmonellosis is characterized by high fever ("enteric fever"), severe diarrhea, and seizures.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59227, Nov. 3, 1998]

(a)ID. schistosomesp. Serological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.schistosomesp. in the serum. Identification helps diagnose schistosomiasis, which is caused by parasitic flatworms of the genusschistosome.Schistosomiasis is characterized by a variety of acute and chronic infections. Acute infection is characterized by fever, allergic symptoms, and diarrhea. Chronic effects are usually severe and are caused by fibrous degeneration of tissue around parasite ova deposited in the liver, lungs, and central nervous system. Schistosomes can also cause schistosomal dermatitis (eg, swimmer's itch), a skin condition characterized by intense itching.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID. Serratiesp. Serological reagents are devices consisting of antigens and antisera used in serological tests for the identificationserrated edgesp. of cultured isolates. Identification helps diagnose diseases caused by bacteria of the genusserrated edgeand provides epidemiological information on these diseases.serrated edgesp. occasionally they are associated with gastroenteritis (food poisoning) and wound 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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID. Shigelasp. Serological reagents are devices consisting of antigens and antisera, including antisera conjugated with a fluorescent dye (immunofluorescent reagents), used in serological tests for the identificationShigellasp. of cultured isolates. Identification helps diagnose shigellosis caused by bacteria of the genusShigellaand provides epidemiological information on this disease. Shigellosis is characterized by abdominal pain, cramps, diarrhea, and fever.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59227, Nov. 3, 1998]

(a)ID. Sporothrix schenckiiSerological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.Sporothrix schenckiiin the serum. Identification helps diagnose sporotrichosis caused by a fungus belonging to the genusesporothrixand provides epidemiological information on this disease. Sporotrichosis is a chronic tumor-like infection primarily of the skin.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID. staphylococcus aureusSerological reagents are devices consisting of antigens and antisera used in serological tests to detect enterotoxin (toxin that attacks the intestines) that produces staphylococci from isolated cultures. Identification aids in the diagnosis of diseases caused by this genus of bacteria.staphand provides epidemiological information on these diseases. certain tribes ofstaphylococcus aureusproduce an enterotoxin while growing in meat, dairy, or baked goods. After ingestion, this enterotoxin is absorbed from the intestine, causing destruction of the intestinal lining (gastroenteritis).

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID. streptococcisp. Exoenzyme reagents are devices used to identify antibodies againststreptococcisp. exoenzyme in serum. Identification helps diagnose diseases caused by bacteria of the genusstreptococciand 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 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.

[47 FR 50823, Nov. 9, 1982, changed to 61 FR 1119, Jan. 16, 1996; 66 FR 38792, July 25, 2001]

(a)ID. streptococcisp. Serological reagents are devices consisting of antigens and antisera (except streptococcal exoenzyme reagents, which are made from enzymes secreted by streptococci) used in serological tests for identificationstreptococcisp. of cultured isolates derived from clinical samples. Identification helps diagnose diseases caused by bacteria of the genusstreptococciand 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 I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter, subject to section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID. toxoplasma gondiiSerological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.Toxoplasma gondiiin the serum. In addition, some of these reagents consist of antisera conjugated to a fluorescent dye (immunofluorescent reagents) that are used for identification.Toxoplasma gondiiof clinical samples. Identification helps diagnose toxoplasmosis, which is caused by the parasitic protozoanToxoplasma gondiiand provides epidemiological information on this disease. Congenital toxoplasmosis is characterized by lesions in the central nervous system that, if left undetected and untreated, can cause brain damage, blindness, and fetal death. The disease is characterized in children by inflammation of the brain and spinal cord.

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

(a)Identification Treponema paleNontreponemal test reagents are kits consisting of antigens derived from nontreponemal sources (sources not directly associated with treponemal organisms) and control sera (standardized sera to which test results are compared) used in serologic tests used to Identify reagin, an antibody- like agent that is produced by the reaction of treponemal microorganisms with body tissue. Identification helps diagnose syphilis caused by microorganisms of the genusTreponemaand provides epidemiological information on syphilis.

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

(a)Identification Treponema paleTreponemal test reagents are kits consisting of antigens, antisera, and any control reagents (standardized reagents against which test results are compared) derived from treponemal sources and used in the Fluorescent Treponemal Antibody Absorption Assay (FTA- ABS).treponema blasImmobilization Test (T.P.I.) and other Treponema tests to identify antibodies againsttreponema blasdirectly from infecting treponemal organisms in the serum. Identification helps diagnose syphilis caused by bacteria of the genusTreponemaand provides epidemiological information on syphilis.

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

(a)ID. Trichinella spiralisSerological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.Trichinella spiralisin the serum. Identification helps diagnose trichinosis caused by parasitic roundworms of the genusTrichinellaand provides epidemiological information on trichinosis. Trichinosis is caused by eating undercooked affected meat, particularly pork, and is characterized by fever, muscle weakness, and diarrhea.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.Avaginal trichomonasThe nucleic acid assay is a device consisting of primers, probes, enzymes, and controls for the amplification and detection of Trichomonas nucleic acids in endocervical swabs, vaginal swabs, and female urine specimens from women symptomatic of vaginitis, cervicitis, or urethritis and/or or to help diagnose trichomoniasis in asymptomatic women. Detection of Trichomonas nucleic acids, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of trichomoniasis caused byvaginal trichomonas.

(b)Classification.Class II (special controls). Special controls are described in the FDA guidance document titled Class II Special Controls Guideline: Nucleic Acid Amplification Assays for the Detection ofTrichomonas vaginalis;Guidelines for Food and Drug Administration and Industry Personnel.” See § 866.1(e) for information on how to obtain this document.

[80 FR 46192, August 4, 2015]

(a)ID. trypanosomesp. Serological reagents are devices consisting of antigens and antisera used in serological tests to detect antibodies.tripanosomasp. in the serum. Identification helps diagnose trypanosomiasis, a disease caused by parasitic protozoa of the genustripanosoma.Trypanosomiasis in adults is a chronic condition characterized by fever, chills, headache, and vomiting. The involvement of the central nervous system results in a typical syndrome of sleeping sickness: physical exhaustion, inability to eat, wasting away of tissues and, finally, death. Chagas disease, an acute form of trypanosomiasis in children, most often affects the central nervous system and heart muscle.

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

(a)ID.Varicella Zoster Virus Serological Reagents are products consisting of antigens and antisera used in serological tests to detect antibodies to Varicella Zoster in serum. Identification helps diagnose diseases caused by the varicella-zoster virus and provides epidemiological information about these diseases. Chickenpox is a mild and highly contagious disease that mainly affects children. Zoster (shingles) is the recurrent form of the disease that occurs in adults previously infected with varicella-zoster viruses. Zoster is the response (characterized by a rash) of the partially immune host to reactivation of the varicella virus that is latent in the patient's body.

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

(a)ID.A quality control material tested for clinical microbiology assays is a device indicated for use in a test system to assess test precision or to detect analytical bias that may arise from reagent or analytical instrument variations. This type of device consists of single or multiple microbiological analytes to be used for qualitative or quantitative assays.

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

(1) The submission of pre-market notifications shall include detailed product description documentation and information on the composition of the quality control material, including, where applicable:

(i) content analysis;

(ii) expected values;

(iii) analysis;

(iv) Basis matriz;

(v) Aggregate Components;

(vi) information on safety and handling; Y

(vii) Detailed instructions for use.

(2) Submission of premarket notifications must include detailed documentation, including lineage data and detailed study protocols and a plan for statistical analysis to determine performance, including:

(i) Description of the evaluation and validation process.

(ii) Description of the protocols used to determine stability.

(iii) Data line to establish precision/reproducibility.

(iv) Assessment of matrix effects and significant differences between quality control material and typical patient samples, as appropriate, for conditions known to cause analytical errors or affect assay performance.

(v) When applicable, identification or definition of traceability or relationship with a national or international standard reference material and/or method.

(vi) Where appropriate, detailed documentation on studies for substitute controls.

(3) The provision of premarket notifications must include a reasonable mitigation (eg, a real-time stability program) of the risk of false results due to possible changes in assays identified in the labeling of the compliant device with 21 CFR 809.10.

(4) Your 21 CFR 809.10 compliant label must include:

(i) The intended use of your labeling under 21 CFR 809.10(a)(2) and (b)(2) must include:

(A) Analyte(s) of the control material tested;

(B) whether the material is intended for quantitative or qualitative testing;

(C) indication of whether the material is a surrogate control; Y

(D) The system(s), instrument(s), or test(s) for which the quality control material is intended.

(ii) The intended use on the label that complies with 21 CFR 809.10(a)(2) and (b)(2) must include the following statement: "This product is not intended to replace manufacturer's controls shipped with the device ".

(iii) A statement of qualification stating: "Quality control materials must be used in accordance with local, state, and federal regulations and accreditation requirements."

[82 FR 34850, Jul 27, 2017]

(a)ID. Vibrio choleraeSerological reagents are devices used in the agglutination test (an antigen-antibody clumping reaction) for the identificationVibrio choleraeof cultured isolates derived from clinical samples. Identification helps diagnose cholera caused by the bacteriaVibrio choleraeand provides epidemiological information on cholera. Cholera is an acute infectious disease characterized by severe diarrhea with extreme fluid and electrolyte (salt) deficiency, vomiting, muscle cramps, and exhaustion. If left untreated, severe dehydration can lead to shock, kidney failure, cardiovascular collapse, and death.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59227, Nov. 3, 1998]

(a)ID.West Nile virus serological reagents are products consisting of antigens and antisera for the detection of IgM antibodies to West Nile virus in human serum from individuals exhibiting signs and symptoms of viral meningitis/encephalitis. Screening 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 an FDA guidance titled Class II Special Controls Guidance Document: Serological Reagents for Laboratory Diagnosis of West Nile Virus. See §866.1(e) for the availability of this guidance document.

[68 FR 61745, October. 30, 2003]

(a)ID.Dengue virus serological reagents are products consisting of antigens and antibodies for the detection of dengue virus and dengue antibodies in people with signs and symptoms of dengue or dengue hemorrhagic fever. The detection aids in the clinical laboratory diagnosis of dengue fever or dengue hemorrhagic fever caused by dengue viruses.

(b)Classification.Class II (special controls). The special control is the FDA guideline titled Class II Special Controls Guideline: Dengue Virus Serological Reagents. See § 866.1(e) for policy document availability.

[79 FR 31023, May 30, 2014]

(a)ID.Dengue Virus Nucleic Acid Amplification Test Reagents are devices consisting of primers, probes, enzymes, and controls for the amplification and detection of dengue virus serotypes 1, 2, 3, or 4 from ribonucleic acid. (RNA) virus in human serum and plasma. have signs and symptoms compatible with dengue (mild or severe). Identification of dengue virus serotypes 1, 2, 3, or 4 in human serum and plasma (sodium citrate) collected from human dengue patients provides epidemiologic information for surveillance of circulating dengue virus.

(b)Classification.Class II (special controls). The special control is the FDA guideline titled Class II Special Control Guideline: Dengue Virus Nucleic Acid Amplification Test Reagents. See § 866.1(e) for policy document availability.

[79 FR 53609, Sept. 10, 2014]

(a)ID.The in vitro HIV drug resistance genotyping assay is a device consisting of nucleic acid reagent primers and probes together with software to predict drug resistance/susceptibility based on the results obtained with these primers and probes. . Its objective is to detect HIV genomic mutations that confer resistance to certain antiretroviral drugs as an aid in the monitoring and treatment of HIV infection.

(b)Classification.Class II (special controls). The specific control for this device is the FDA guidance document titled Class II Special Controls Guidance Document: In Vitro HIV Drug Resistance Genotyping Assay. See §866.1(e) for the availability of this guidance document.

[72 FR 44382, August 8, 2007]

(a)ID.The HIV Drug Resistance Genotyping Assay using Next Generation Sequencing (NGS) technology is a prescription in vitro diagnostic device designed to detect mutations in the HIV genome that confer resistance to certain antiretroviral drugs. The device is intended to be used as an aid in the control and treatment of HIV infection.

(b)Classification.Class II (special controls). The specific 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 have been detected, the appropriate clinical indications for the purpose of the test, the type of sample and the specific population(s) for which the device is intended.

(ii) State that the device is not intended to be used as an aid in the diagnosis of HIV infection or to confirm the presence of HIV infection or to screen donors of blood, plasma or human cells, tissues and HIV-based products. cells and tissues. .

(2) The mark must contain:

(i) A detailed description of the device, including, but not limited to, all procedures from patient sample collection to final result reporting, all device components, control elements involved in the test procedure, instrument requirements and reagents required for use, but not provided with the device contains.

(ii) Performance characteristics of analytical studies and all anticipated sample types.

(iii) A list of specific mutations detected.

(iv) Name and version of the standardized database used for sequence comparison and result derivation.

(v) A detailed explanation of the interpretation of the test results, including the acceptance criteria for evaluating the validity of a test.

(vi) A disclaimer that the device should be used in conjunction with medical history and other laboratory findings. The results of this test must be interpreted by a physician or his equivalent.

(vii) A disclaimer that the failure to demonstrate drug resistance mutations does not exclude the possibility of a genetic mutation.

(viii) A disclaimer identifying relevant genetic mutations contained in the standardized database of HIV genomic sequences used for comparison and results, but not detected by the test.

(ix) A qualifying statement that the detection of a genomic drug resistance mutation may not be correlated with phenotypic gene expression.

(x) A disclaimer that the test will not detect all genetic mutations associated with antiviral drugs.

(xi) A restriction statement listing the types of HIV for which testing is not intended, if applicable.

(3) Verification and validation of the device must include:

(i) Design of primer sequences and rationale for sequence selection.

(ii) Calculation path from the raw data collected to the reported result.

(iii) Detailed documentation of analytical studies including, but not limited to, cut-off characterization, analytical sensitivity, inclusiveness, reproducibility, interference, cross-reactivity, instrument and method transfer/cross-contamination, stability, and sample handling for all claimed genomic data . mutations in the intended use.

(iv) Precision studies encompassing all claimed genomic mutations in the intended use.

(v) Detailed documentation of a multi-site clinical study to assess the sensitivity and specificity of the device. Clinical study subjects must represent the intended population for the intended use, and device results for all stated purposes for the intended use must be compared with Sanger sequencing or other methods deemed acceptable by the FDA. Drug resistance-associated mutations with a frequency of at least 20 percent must demonstrate mutations in greater than 90 percent of at least 10 repeats for each of the drug classes examined.

(vi) Documentation that variant calling is performed at a coverage level that supports positive detection of all declared genomic mutations in the intended use.

(vii) Detailed documentation of limit of detection (LoD) studies evaluating device performance by testing at least 100 HIV-positive clinical samples, including samples with analyte concentrations near clinical decision points and near LoD .

(A) The LoD for the device should be determined using at least 10 HIV-1 group M genotypes, if applicable. For mutations with a frequency greater than 20 percent, a detection rate at 1*LoD greater than or equal to 95 percent must be demonstrated.

(B) The LoD of gene mutations with a frequency of less than 20 percent should be determined.

(viii) A predefined bioinformatics analysis (BAP) pipeline of HIV genotyping. The BAP must adequately describe the bioinformatics analysis of the sequencing data, including but not limited to read alignment, variant calling, assembly, genotyping, quality control, and final results reporting.

(ix) A clear description of the selection and use of the standardized database used for sequence comparison and derivation of results.

(4) Premarket notices must include the information in paragraphs (b)(3)(i) through (ix) of this section.

[85 FR 7217, February 7, 2020]

(a)ID.Human Immunodeficiency Virus (HIV) Diagnostic and Complementary Serological Tests are prescription devices for the qualitative detection of HIV antigens and/or the detection of antibodies to HIV in human body fluids or tissues. The tests are intended to aid in the diagnosis of HIV infection and should only be used by professionals. Test results should be interpreted in conjunction with other relevant clinical and laboratory findings. These tests are not intended to monitor patient status or to test donors of blood or blood products or human cells, tissues, and cell and tissue-based products (HCT/Ps).

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

(1) For all diagnostic and complementary HIV serological tests

(i) The marking shall include:

(A) Intended use indicating that the device is not intended for screening of donor blood or blood products or HCT/Ps.

(B) A detailed explanation of the principles of operation and procedures for conducting the test.

(C) A detailed explanation of the interpretation of the results and the recommended actions to be taken based on the results.

(D) Constraints that must be updated to reflect current clinical practice and disease presentation and treatment. Limitations must include, among other things, statements that state:

(1) The matrices with which the device has been approved and that use of this test kit with sample types other than those specifically approved for this device may result in inaccurate test results.

(2) The test is not intended to monitor people receiving treatment for HIV infection.

(3) A sample with a reactive result should be further evaluated according to current guidelines.

(4) All test results should be interpreted in conjunction with the individual's clinical presentation, history, and other laboratory findings.

(5) A non-reactive test result does not exclude the possibility of HIV exposure or infection. Non-reactive results in this assay may be due to analyte concentrations below the detection limit of this assay.

(ii) Verification and validation of the device must include:

(A) Detailed description of the device, including device components, ancillary reagents required but not provided, and an explanation of the methodology. Additional information appropriate to the technology should be included, such as the amino acid sequence of the antigens and the design of the capture antibodies.

(B) For instruments with assay calibrators, the design of all primary, secondary, and subsequent quantitation standards used for calibration and their traceability to a reference material. In addition, analytical tests should be performed after the release of a new lot of the standard material used for instrument release or when transitioning to a new calibration standard.

(C) Detailed documentation of analytical performance studies performed in accordance with the technology, sample types tested, and intended use of the device, including, but not limited to, limit of blank, limit of detection, cut-off determination, precision, endogenous and exogenous interferences, cross-reactivity, carryover, quality control, matrix equivalence, and stability of samples and reagents. Specimens selected for use in analytical studies or used in preparation of samples for use in analytical studies must be derived from subjects with clinically relevant circulating genotypes in the United States.

(D) Multi-site reproducibility study involving testing of three independent production lots.

(E) The analytical sensitivity of the test must be equal to or better than that of other approved or approved tests. Specimens tested should include an appropriate number and type of specimens, including true clinical specimens near the lower limit of detection. The analytical specificity of the test must be equal to or better than that of other approved or approved tests. Samples should include an appropriate number and type of samples from patients with different underlying diseases or infections and from patients with possible endogenous interference.

(F) Detailed documentation of the performance of a multisite clinical study. Performance must be tested relative to an FDA approved or approved comparator. This study should be performed using samples from patients with an adequate number of HIV positive and negative samples in the corresponding risk categories. Additional subgroups or types should be validated using an appropriate number and type of samples. Samples may be a combination of fresh and stored samples, obtained from within and outside of the United States, as needed. The study design, including the number of samples tested, must be sufficient to meet the following criteria:

(1) The clinical sensitivity of the test must have a lower limit of the 95 percent confidence interval greater than or equal to 99 percent.

(2) The clinical specificity of the test must have a lower limit of the 95 percent confidence interval greater than or equal to 99 percent.

(G) Strategies for detecting new strains, types, subtypes, genotypes, and genetic mutations as they emerge.

(H) Risk analysis and management strategies, such as B. Failure modes and effects analysis and/or hazard analysis and critical control point summaries and their impact on test performance.

(I) Final release criteria to be used for manufactured test lots, with adequate evidence that lots released at the extremes of the specifications meet the stated analytical and clinical performance and stability requirements.

(J) All stability protocols, including acceptance criteria.

(K) Appropriate and acceptable procedures for evaluating customer complaints and other device information that will determine when to submit a medical device report.

(L) Premarket Notices must include the information contained in paragraphs (b)(1)(ii)(A) ​​through (K) of this Section.

(iii) Manufacturers must file a record of all complaints. The record of each complaint, if any, must include the following information: Nature of the fact (z.B.,false negative/false non-reactive or false positive/false reactive), lot, date, population, and whether or not the complaint was reported under part 803 of this chapter (Notification of medical devices). The protocol must be submitted annually on the launch anniversary for 5 years after the launch of a traditional premarket notification.

(2) If the test is designed for point-of-care (PoC) use, the following special controls apply in addition to those listed in paragraph (b)(1) of this Section:

(i) PoC labeling must include a statement that the test is designed for PoC use.

(ii) The PoC marking must contain the following information in addition to the indication of the intended use:

(A) That the test should be distributed to clinical laboratories that have an adequate quality assurance program in place, including planned routine activities that provide reasonable confidence that quality requirements will be met and that ensure that operators receive the training material and use it.

(B) That the test is for the exclusive use of a representative of a clinical laboratory.

(C) Instructions for individuals to receive "Notice of Subject Information" prior to sample collection and related 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) Label instructions should indicate that reactive results are considered preliminary and should be confirmed in accordance with current guidelines.

(v) Verification and validation of the device for PoC use must include:

(A) Detailed documentation of the performance of a multi-site clinical study conducted at eligible PoC sites. Performance must be tested relative to an FDA approved or approved comparator. This study should be performed using samples from patients with an adequate number of HIV positive and negative samples in the corresponding risk categories. Claims for subsets or additional types must be validated against an appropriate number and type of templates. Samples may be a combination of fresh and stored samples, obtained from within and outside of the United States, as needed. If the test is intended solely for PoC use, the test need only meet the performance criteria in paragraphs (b)(2)(v)(A)(1) y (2) of this section and not the criteria in paragraph (b)(1)(ii)(F) of this section:

(1) The clinical sensitivity of the test must have a lower limit of the 95 percent confidence interval greater than or equal to 98 percent.

(2) The clinical specificity of the test must have a lower limit of the 95 percent confidence interval greater than or equal to 98 percent.

(B) Premarket notices must include the information contained in paragraph (b)(2)(v)(A) of this Section.

(3) If the test is intended for adjunctive use other than use as an aid in initial diagnosis, use the following specific controls in addition to those listed in paragraphs (b)(1) and (2) of this section, as appropriate . :

(i) The label must include a statement that the test is designed as a supplemental test to confirm the presence of HIV antibodies or antigens in specimens that have been shown to be repeatedly reactive in a diagnostic screening test.

(ii) Validation and verification of the product for ancillary use must include a clinical study, including samples that were initially reactive and repeatedly reactive in one diagnostic test, but were negative or equivocal in another confirmatory test. Transmissions of premarket notifications must include this information.

(4) If the test is intended to be a supplemental test only, the following special controls are required in addition to those listed in paragraphs (b)(1) and (2) of this Section, except as specified in paragraphs (b)(1)(ii)(F) and (b)(2)(v)(A) of this section apply where applicable:

(i) The label must include a statement that the test is designed as a supplemental test to confirm the presence of HIV antibodies or antigens in specimens that have been shown to be repeatedly reactive in a diagnostic screening test.

(ii) The label must clearly indicate that the test is not intended for primary diagnosis or is not intended to be a first line test.

(iii) Product validation and verification must include a clinical study involving specimens that were initially reactive and repeatedly reactive in a diagnostic test, but were negative or equivocal in a confirmatory test. Transmissions of premarket notifications must include this information.

(5) When the test is intended to discriminate between different types of HIV, the following specific controls shall apply in addition to those set forth in paragraphs (b)(1) through (4) of this Section:

(i) The label must include a statement that the test is intended to confirm preliminary results of a diagnostic test and to differentiate between different types of HIV.

(ii) The interpretation of the results in the labeling should include instructions to the user on how to interpret the results, including non-typable results and co-infection results.

(iii) The validation and verification of the product must include the evaluation of the analytical and clinical sensitivity and specificity for each of the types, strains and subtypes of HIV to be differentiated. Transmissions of premarket notifications must include this information.

[87 FR 29665, May 16, 2022]

(a)ID.Human Immunodeficiency Virus (HIV) Nucleic Acid Diagnostic and Complementary Tests (NAT) are prescription devices for the qualitative detection of HIV nucleic acid in human body fluids or tissues. The tests are intended to aid in the diagnosis of HIV infection and should only be used by professionals. Test results should be interpreted in conjunction with other relevant clinical and laboratory findings. These tests are not intended to monitor a patient's condition or to test donors of blood or blood products or human cells, tissues, or cell-based or tissue-based products (HCT/Ps).

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

(1) For all NAT diagnostic and/or supplementary HIV tests

(i) The marking shall include:

(A) Intended use indicating that the device is not intended for screening of donor blood or blood products or HCT/Ps.

(B) A detailed explanation of the principles of operation and procedures for conducting the test.

(C) A detailed explanation of the interpretation of the results and the recommended actions to be taken based on the results.

(D) Constraints that must be updated to reflect current clinical practice and disease presentation and treatment. Limitations must include, among other things, statements that state:

(1) The matrices with which the device has been approved and that use of this test kit with sample types other than those specifically approved for this device may result in inaccurate test results.

(2) The test is not intended to monitor people receiving treatment for HIV infection.

(3) A sample with a reactive result should be further evaluated according to current guidelines.

(4) All test results should be interpreted in conjunction with the individual's clinical presentation, history, and other laboratory findings.

(5) A non-reactive test result does not exclude the possibility of HIV exposure or infection. Non-reactive results in this assay may be due to analyte concentrations below the detection limit of this assay.

(ii) Verification and validation of the device must include:

(A) Detailed description of the device, including device components, ancillary reagents required but not provided, and an explanation of the methodology. Additional information appropriate to the technology should be included, such as: B. the design of primers and probes.

(B) For instruments with assay calibrators, the design and nature of all primary, secondary, and subsequent quantitation standards used for calibration and their traceability to a reference material. In addition, analytical tests should be performed after the release of a new lot of the standard material used for instrument release or when transitioning to a new calibration standard.

(C) Detailed documentation of analytical performance studies performed in accordance with the technology, sample types tested, and intended use of the device, including, but not limited to, limit of blank, limit of detection, cut-off determination, precision, endogenous and exogenous interferences, cross-reactivity, carryover, quality control, matrix equivalence, and stability of samples and reagents. Specimens selected for use in analytical studies or used in preparation of samples for use in analytical studies must be derived from subjects with clinically relevant circulating genotypes in the United States. The effect of each claimed nucleic acid isolation and purification method on detection should be evaluated.

(D) Multi-site reproducibility study involving testing of three independent production lots.

(E) The analytical sensitivity of the test must be equal to or better than that of other approved or approved tests. Specimens tested should include an appropriate number and type of specimens, including true clinical specimens near the lower limit of detection. The analytical specificity of the test must be equal to or better than that of other approved or approved tests. Samples should include an appropriate number and type of samples from patients with different underlying diseases or infections and from patients with possible endogenous interference.

(F) Detailed documentation of the performance of a multisite clinical study. Performance must be tested relative to an FDA approved or approved comparator. This study should be performed using appropriate patient samples with an adequate number of HIV positive and negative samples in the corresponding risk categories. Subtypes, strains or additional types should be validated using an appropriate number and type of samples. Samples may be a combination of fresh and stored samples, obtained from within and outside of the United States, as needed. The study design, including the number of samples tested, must be sufficient to meet the following criteria:

(1) The clinical sensitivity of the test must have a lower limit of the 95 percent confidence interval greater than or equal to 99 percent.

(2) The clinical specificity of the test must have a lower limit of the 95 percent confidence interval greater than or equal to 99 percent.

(G) Strategies for detecting new strains, types, subtypes, genotypes, and genetic mutations as they emerge.

(H) Risk analysis and management strategies, such as B. Failure modes and effects analysis and/or hazard analysis and critical control point summaries and their impact on test performance.

(I) Final release criteria to be used for manufactured test lots, with adequate evidence that lots released at the extremes of the specifications meet the stated analytical and clinical performance and stability requirements.

(J) All stability protocols, including acceptance criteria.

(K) Reasonable and acceptable procedures for evaluating customer complaints and other product information that will determine when a medical device report must be filed.

(L) Premarket Notices must include the information contained in paragraphs (b)(1)(ii)(A) ​​through (K) of this Section.

(iii) Manufacturers must file a record of all complaints. The record of each complaint, if any, must include the following information: Nature of the fact (z.B.,false negative/false non-reactive or false positive/false reactive), lot, date, population, and whether or not the complaint was reported under part 803 of this chapter (Notification of medical devices). The protocol must be submitted annually on the launch anniversary for 5 years after the launch of a traditional premarket notification.

(2) If the test is designed for point-of-care (PoC) use, the following special controls apply in addition to those listed in paragraph (b)(1) of this Section:

(i) PoC labeling must include a statement that the test is designed for PoC use.

(ii) The PoC marking must contain the following information in addition to the indication of the intended use:

(A) That the test should be distributed to clinical laboratories that have an adequate quality assurance program in place, including planned routine activities that provide reasonable confidence that quality requirements will be met and that ensure that operators receive the training material and use it.

(B) That the test is for the exclusive use of a representative of a clinical laboratory.

(C) Instructions for individuals to receive "Notice of Subject Information" prior to sample collection and related 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) Label instructions should indicate that reactive results are considered preliminary and should be confirmed in accordance with current guidelines.

(v) Verification and validation of the device for PoC use must include:

(A) Detailed documentation of a well conducted multisite clinical study at appropriate PoC sites. Performance must be tested relative to an FDA approved or approved comparator. This study should be performed using samples from patients with an adequate number of HIV positive and negative samples in the corresponding risk categories. Claims for subsets or additional types must be validated against an appropriate number and type of templates. Samples may be a combination of fresh and stored samples, obtained from within and outside of the United States, as needed. If the test is intended solely for PoC use, the test need only meet the performance criteria in paragraphs (b)(2)(v)(A)(1) y (2) of this section and not the criteria in paragraph (b)(1)(ii)(F) of this section:

(1) The clinical sensitivity of the test must have a lower limit of the 95 percent confidence interval greater than or equal to 98 percent.

(2) The clinical specificity of the test must have a lower limit of the 95 percent confidence interval greater than or equal to 98 percent.

(B) Premarket notices must include the information contained in paragraph (b)(2)(v)(A) of this Section.

(3) If the test is intended for adjunctive use other than use as an aid in initial diagnosis, use the following specific controls in addition to those listed in paragraphs (b)(1) and (2) of this section, as appropriate . :

(i) The label must include a statement that the test is designed as a supplemental test to confirm the presence of HIV viral nucleic acid in specimens that have been repeatedly shown to be reactive in a diagnostic screening test.

(ii) Validation and verification of the product for ancillary use must include a clinical study, including samples that were initially reactive and repeatedly reactive in a diagnostic test, but were negative or equivocal in a confirmatory test. Transmissions of premarket notifications must include this information.

(4) If the test is intended to be a supplemental test only, the following special controls are required in addition to those listed in paragraphs (b)(1) and (2) of this Section, except as specified in paragraphs (b)(1)(ii)(F) and (b)(2)(v)(A) of this section apply where applicable:

(i) The label must include a statement that the test is designed as a supplemental test to confirm the presence of HIV viral nucleic acid in specimens that have been repeatedly shown to be reactive in a diagnostic screening test.

(ii) The label must clearly indicate that the test is not intended for primary diagnosis or is not intended to be a first line test.

(iii) Product validation and verification must include a clinical study involving specimens that were initially reactive and repeatedly reactive in a diagnostic test, but were negative or equivocal in a confirmatory test. Transmissions of premarket notifications must include this information.

(5) When the test is intended to discriminate between different types of HIV, the following specific controls shall apply in addition to those set forth in paragraphs (b)(1) through (4) of this Section:

(i) The label must include a statement that the test is intended to confirm preliminary results and to differentiate between different types of HIV.

(ii) The interpretation of the results in the labeling should include instructions to the user on how to interpret the results, including non-typable results and co-infection results.

(iii) The validation and verification of the product must include the evaluation of the analytical and clinical sensitivity and specificity for each of the types, strains and subtypes of HIV to be differentiated. Transmissions of premarket notifications must include this information.

[87 FR 29667, May 16, 2022]

(a)ID.A Nucleic Acid-Based Device for the Amplification, Detection, and Identification of Microbial Pathogens Directly from Whole Blood Specimens is an in vitro qualitative device intended for the amplification, detection, and identification of microbial nucleic acid sequences from patients with suspected infections. from the bloodstream. This device is intended to aid in the diagnosis of bloodstream infections when used in conjunction with clinical signs and symptoms and other laboratory findings.

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

(1) Submission of premarket notifications must include detailed product description documentation, including product 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) Submission of premarket notifications must include detailed documentation of the following analytical and clinical performance studies: analytical sensitivity (limit of detection), reactivity, inclusiveness, precision, reproducibility, interference, cross-reactivity, carryover, and cross-contamination .

(3) Detailed documents of a clinical study must be attached to the prior notice submission. The study, conducted in a study population consistent with the intended use population, shall compare the performance of the device with the results obtained from accepted reference methods.

(4) Submission of pre-market notifications must include detailed documentation for device software, including but not limited to software applications and hardware-based devices containing software.

(5) The labeling of the device must contain limitations regarding the need for culture confirmation of negative samples, when applicable.

(6) A detailed explanation of the interpretation of the results and the acceptance criteria shall be included on the 21 CFR 809.10(b)(9) compliant label of the device.

(7) The pre-market notification submission must include details of an end-user device training program that may be offered during the device's commercialization.

(8) As part of the risk management activities performed as part of your design controls 21 CFR 820.30, you must document an appropriate end-user device training program that is offered as part of your efforts to mitigate operational risk incorrect device. .

[82 FR 47967, oct. 16, 2017]

(a)ID.A device for the detection and identification of nucleic acids of microbial pathogens in cerebrospinal fluid is an in vitro qualitative device intended for the detection and identification of nucleic acid sequences associated with microbes from patients with suspected meningitis or encephalitis. A device for the detection and identification of nucleic acids from microbial pathogens 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 specific controls for this device are:

(1) Submission of premarket notifications must include detailed product description documentation, including product 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 of the following analytical studies: analytical sensitivity (limit of detection), inclusiveness, reproducibility, interference, cross-reactivity, and sample stability.

(3) Detailed documents of a clinical study must be attached to the prior notice submission. The study, conducted in a study population consistent with the intended use population, should compare the performance of the device with the results obtained from accepted comparative methods.

(4) Submission of pre-market notifications must include detailed documentation for device software, including but not limited to software applications and hardware-based devices containing software.

(5) The statement of intended use on the product label shall include a statement that the product is intended to be used in conjunction with the standard supply culture.

(6) A detailed explanation of the interpretation of the results and the acceptance criteria shall be included on the 21 CFR 809.10(b)(9) compliant label of the device.

(7) The device label must include a qualification that negative results do not exclude the possibility of central nervous system infection.

(8) The product label shall contain a qualification that the results of the device should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

(9) The product label must contain a qualification that positive results do not mean that the organism detected is infectious or the causative agent of clinical symptoms.

(10) As part of the risk management activities performed as part of your design controls 21 CFR 820.30, you must document an appropriate end-user device training program that is offered as part of your efforts to mitigate operational risk incorrect device. .

[82 FR 48763, oct. 20, 2017]

(a)ID.A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device designed for the simultaneous detection and identification of multiple viral nucleic acids extracted from human respiratory specimens or viral cultures. Detection and identification of a specific viral nucleic acid from individuals displaying 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 designed for the 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 viruses;

(5) human metapneumovirus;

(6) rhinoviruses; water

(7) Adenovirus.

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

(1) Leitliniendokument der FDA mit dem Titel „Class II special controls guidance document: Respiratory viral panel multiplex nucleic acid assay“;

(2) For a device that detects and identifies human metapneumovirus, the FDA guidance document titled Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays; Y

(3) For a device that detects and differentiates influenza A H1 subtype and H3 subtype, the FDA guidance document entitled "Guidance Document on Class II Special Controls: Tests for Detection and Differentiation of Subtypes of influenza A virus by multiplex nucleic acid assays". See § 866.1(e) for the availability of these guides.

[74 FR 52138, October. 9, 2009]

(a)ID.A device for the detection and identification of microorganisms and associated resistance markers nucleic acids directly from respiratory samples is an in vitro diagnostic device for the detection and identification of microorganisms and associated resistance markers in respiratory samples collected from patients with signs or symptoms of Respiratory infection. The device is designed to aid in the diagnosis of a respiratory infection along with clinical signs and symptoms and other laboratory findings. These devices do not provide confirmation of antibiotic susceptibility because resistance mechanisms other than those recognized by the device may exist.

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

(1) The intended use for the 21 CFR 809.10 mark must include a detailed description of what the device detects, the nature of the results provided to the user, the appropriate clinical indications for use of the test, and the population(s)( es) specific(s)(es) for which the device is intended.

(2) The labeling required by 21 CFR 809.10(b) must include the following:

(i) A detailed description of the instrument, including all instrument components, controls incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology, including methods of processing of preanalytical samples.

(ii) Performance characteristics of analytical studies, including, but not limited to, limit of detection, inclusivity, reproducibility, cross-reactivity, interfering substances, competitive inhibition, carryover/cross-contamination, stability of the sample and linearity, as appropriate.

(iii) A qualifying statement that the device will be used in conjunction with the medical history, signs and symptoms, and the 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 the acceptance criteria for all quality control tests.

(v) A qualifying statement that negative results for microorganisms do not exclude the possibility of infection and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

(vi) Where applicable, a qualifying statement that the microorganisms detected may not be the cause of a lower respiratory tract infection and may indicate colonization or normal respiratory flora.

(vii) Where applicable, a qualifying statement that the detection of resistance markers cannot be unequivocally associated with specific microorganisms and that the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora.

(viii) A qualifying statement, where applicable, that the detection of antibiotic resistance markers may not be correlated with phenotypic gene expression.

(3) Labeling per 21 CFR 809.10(b) and any test report generated by the device must include a qualifying statement that negative resistance marker results do not indicate susceptibility of the detected microorganism.

(4) The verification and validation of the design will include:

(i) Performance characteristics of clinical studies, including prospective (sequential) samples and additional characterized samples, as appropriate. The study must be conducted in a study population consistent with the intended use population and compare device performance with results obtained from an FDA-accepted reference method and/or an FDA-accepted comparator method. Clinical study results must include the clinical study protocol (including a pre-defined statistical analysis plan, if applicable), the clinical study report, and the results of all statistical analyses.

(ii) A detailed description of the device including:

(A) Detailed description of the assay methodology, including, but not limited to, primer/probe sequences, primer/probe design, and rationale for target sequence selection, if applicable.

(B) Algorithm used to generate a final result from raw data (for example, how raw signals are converted to a reported result).

(iii) A detailed description of the device software, including, but not limited to, validation activities and results.

(iv) As part of risk management activities, a suitable training program should be provided for end-user devices to mitigate the risk of failure due to user error.

[84 FR 9228, March 14, 2019]

(a)ID.A nucleic acid-based multiplex assay with gastrointestinal microorganisms is qualitativein vitroDiagnostic device for the simultaneous detection and identification of multiple gastrointestinal microbial nucleic acids extracted from human stool samples. The device recognizes specific nucleic acid sequences to identify organisms and determine the presence of toxin genes. 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 multiplex nucleic acid-based assay of gastrointestinal microorganisms also aids in the detection and identification of outbreaks associated with acute gastroenteritis.

(b)Classification.Class II (special controls). Special controls are described in the FDA guidance document titled Class II Special Controls Guideline: Multiplex Nucleic Acid-Based Assays of Gastrointestinal Organisms for the Detection and Identification of Organisms and Toxin Genes from Stool Specimens human. See § 866.1(e) for policy document availability.

[80 FR 67314, Nov. 2, 2015]

(a)ID.RNA Preanalytical Systems are devices used to collect, store, and transport patient samples and to stabilize intracellular RNA in samples for subsequent isolation and purification of intracellular RNA for RT-PCR used in in-house molecular diagnostic tests. vitro.

(b)Classification.Class II (special controls). The Special Control is the FDA guidance document titled Class II Special Controls Guidance Document: RNA Preanalytical Systems (RNA Collection, Stabilization, and Purification System for RT-PCR Used in Molecular Diagnostic Tests). See §866.1(e) for the availability of this guidance document.

[70 FR 49863, August 25, 2005]

(a)ID.A complement reagent is a device consisting of complement, a natural serum protein of warm-blooded animals such as guinea pigs, which can be included as part of serological test kits used to diagnose 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.

[47 FR 50823, November 9, 2001, modified 66 FR 38792, July 25, 2001]

(a)ID.The clinical immunoelectrophoresis kit with its power supply is a device used to separate protein molecules. Immunoelectrophoresis is a procedure in which a complex mixture of proteins is placed on an agar gel and the different proteins are separated under the influence of an electric current based on their relative mobility. The separated proteins are then allowed to diffuse through the agar to a multispecific antiserum, allowing precipitation and visualization of the separated complexes.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID.The Power Supply Clinical Immunofluorometer Kit is a device used to measure the fluorescence of fluorochrome-labeled antigen-antibody complexes. The concentration of these complexes can be measured using reflected light. A beam of light is passed through a solution in which a fluorochrome has selectively bound to suspended serum protein-antibody molecules. The amount of light emitted by the fluorochrome tag is detected by a photodetector, which converts the light energy into electrical energy. The amount of electrical energy is recorded on a reading system, such as a digital voltmeter or chart recorder. This electrical reading is called a fluorescence reading and is used to measure the concentration of antigen-antibody complexes.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID.The clinical immunonephelometer kit with its power supply is a device that measures the light scattering of antigen-antibody complexes. The concentration of these complexes can be measured using reflected light. A light beam passing through a solution is scattered by the suspended particles. The amount of light is detected by a photodetector, which converts light energy into electrical energy. The amount of electrical energy is recorded on a reading system, such as a digital voltmeter or chart recorder. This electrical reading is called a light-scattering reading and is used to measure the concentration of antigen-antibody complexes. This generic device type includes devices with different types of light sources, such as laser devices.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID.A clinical Ouchterlony agar plate is a device containing an agar gel that is used to study antigen-antibody reactions. In immunodiffusion, antibodies and antigens migrate toward each other through a gel that originally did not contain either of these reagents. When the reagents come into contact with each other, they combine to form a precipitate that becomes trapped and immobilized in the gel matrix.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID.An automated FISH enumeration system is a device consisting of an automated scanning microscope, an image analysis system, and custom software applications for FISH assays. This device is intended for in vitro diagnostic use in FISH assays to aid in the detection, enumeration, and sorting of cells based on detection of cell color, size, and shape, and in the detection and enumeration of FISH signals in Formalin nuclei provided in the paraffin-embedded interface-fixed human tissue samples.

(b)Classification.Class II (special controls). The special control is the FDA guidance document titled Class II Special Controls Guidance Document: Automated Fluorescencein the placeHybridization Enumeration Systems (FISH).” See §866.1(e) for the availability of this guidance document.

[70 FR 14534, March 23, 2005]

(a)ID.An automated indirect immunofluorescence microscope and software-based system is a device that acquires, analyzes, stores, and displays digital images of indirect immunofluorescence slides. It is intended to be used as an aid in determining antibody status in clinical specimens. The apparatus may include a fluorescence microscope with a light source, a motorized microscope stage, dedicated instrument controls, a camera, a computer, a sample processor, or other hardware components. The instrument can use software to acquire and process fluorescence signals, mechanisms to store and transmit data, or assay-specific algorithms to suggest results. Results generated with the device must be confirmed by a trained operator.

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

(1) Device labeling must relate to legally marketed assays intended for use with the device.

(2) Premarket notices must include the following information:

(i) A detailed description of the device, including:

(A) A detailed description of the instruments and equipment and, where applicable, illustrations or photographs of non-standard equipment or methods;

(B) detailed documentation for the Software, including, without limitation, stand-alone software applications and hardware-based devices containing Software, as applicable;

(C) A detailed description of the appropriate internal and external quality controls that are recommended or provided. The description should identify those control elements that are integrated into the recommended test procedures;

(D) Detailed description and specifications for sample preparation, processing, and storage, if applicable;

(E) Methodology and protocols to detect fluorescence and visualize the results; Y

(F) Detailed specification of the criteria for interpreting and reporting test results.

(ii) Data demonstrating the performance of the device, which will include:

(A) A comparative study of the results obtained with the conventional manual method (dhreference standard), the device and the reading of the digital image without the help of the software, using the same set of patient samples in each case. The study must use a legally marketed assay designed for use with the device. Patient samples should be from the specific assay population for the intended use and from the differential diagnosis population. Samples must also cover the measurement range of the assay, if applicable;

(B) Clinical device performance determined by comparing device results at various US sites to the clinical diagnostic standard used in the United States using patient samples from the trial-specific intended use population and the differential diagnosis population. Clinical diagnostic criteria and demographic information must be collected and provided for all samples. Clinical validation should be based on determination of clinical sensitivity and clinical specificity from test results (z.B.,Fluorescence-based antibody status, including pattern and titer, if applicable) compared to the clinical diagnosis of the subject from whom the clinical sample was obtained. Data should be summarized in tabular form, comparing the result generated by automatic, manual, and digital-only interpretation with disease status;

(C) Instrument precision/reproducibility data generated from intra-run, between-run, between-day, between-lot, between-operator, between-instrument, between-site, and total precision for multiple non-consecutive days (if applicable) Multiple operators, multiple instruments and multiple locations. A well-characterized panel of patient samples or groups from the specific trial population suitable for the intended use should be used;

(D) device linearity data generated from patient samples and covering the measurement range of the assay, if applicable;

(E) Analytical sensitivity data for the device, including limit of blank, limit of detection, and limit of quantification, if applicable;

(F) device specific test limit, if applicable;

(G) Analytical specificity data of the device including, where appropriate, the interference of endogenous and exogenous substances;

(H) device-to-instrument transfer data, if applicable;

(I) device stability data, including real-time stability at different storage times and temperatures, if applicable; Y

(J) Traceability information to a reference material and description of the value assignment of calibrators and controls, if applicable.

(iii) Identification of the risk mitigation elements used by the product, including a description of any additional procedures, methods and practices incorporated into the instructions for use that mitigate the risks associated with the tests.

(3) Your 21 CFR 809.10 compliant label must include:

(i) a warning stating "The device is intended for use by a trained operator in a clinical laboratory setting";

(ii) a warning stating "All software-based results must be confirmed by the trained operator";

(iii) a warning statement that reads "This device is to be used only with the reagents specified for use with the device"; Y

(iv) A description of the protocol and performance studies conducted pursuant to paragraph (b)(2)(ii) of this Section and a summary of the results, if any.

[82 FR 52648, November 14, 2017, modified 86 FR 20283, April 19, 2021]

(a)ID.A radial immunodiffusion plate for clinical use is a device consisting of a plastic plate on which agar gel containing antiserum is placed. In radial immunodiffusion, antigens migrate through a gel that originally contains specific antibodies. When the reagents come into contact with each other, they combine to form a precipitate that becomes trapped and immobilized in the gel matrix.

(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.

[47 FR 50823, November 9, 1982, modified 66 FR 38792, July 25, 2001]

(a)ID.The clinical use rocket immunoelectrophoresis kit is a device used to perform a specific test on proteins by a method called rocket immunoelectrophoresis. In this procedure, an electrical current causes protein in solution to migrate through an agar gel containing specific antisera. The protein precipitates with the antisera in a rocket-like pattern, giving the device its name. The height of the peak (or the area under the peak) is proportional to the concentration of the protein.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID.A carrier gel for clinical use is a device consisting of an agar or agarose preparation that is used to measure various types of protein molecules or parts thereof by various immunochemical techniques, such as immunoelectrophoresis, immunodiffusion, or chromatography.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 54 FR 25047, Jun. 12, 1989; 66 FR 38792, July 25, 2001]

(a)ID.An albumin immunoassay system is a device consisting of reagents used to measure albumin (a plasma protein) in serum and other body fluids using immunochemical techniques. Measuring albumin helps diagnose kidney and intestinal diseases.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59227, Nov. 3, 1998]

(a)ID.A prealbumin immunoassay system is a device consisting of reagents used to measure prealbumin (a plasma protein) in serum and other body fluids using immunochemical techniques. Measurement of serum prealbumin levels may be useful in assessing the patient's nutritional status.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.A human allotypic marker immunoassay system is a device consisting of reagents used to identify, by immunochemical techniques, inherited human allotypic protein markers (such as the nGm, nA2m, and Km allotypes) in serum and other body fluids. The identification can be used in the study of population genetics.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.AAlfaThe -1-antichymotrypsin immunological test system is a device consisting of reagents used for measurement with immunochemical techniquesAlfa-1-antichymotrypsin (a protein) in serum, other body fluids, and tissues.Alfa-1-Antichymotrypsin helps protect tissues from proteolytic (protein-splitting) enzymes released during infection.

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

(a)ID.An antimitochondrial antibody immunoassay system is a device consisting of the reagents used to measure antimitochondrial antibodies in human serum by immunochemical techniques. The measurements help diagnose diseases that produce a spectrum of autoantibodies (antibodies against the body's own tissues), such as B. primary biliary cirrhosis (degeneration of liver tissue) and chronic active hepatitis (inflammation of the liver).

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

(a)ID.An antinuclear antibody immunological test system is a device consisting of reagents used to measure, by immunochemical techniques, autoimmune antibodies in serum, other body fluids and tissues that react with cell nuclei (molecules present in the nucleus of a cell), such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements help diagnose systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjogren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands) . ) and systemic sclerosis (chronic hardening and shrinking of many body tissues).

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

(a)ID.An antiparietal antibody immunoassay system is a device consisting of reagents used to measure, by immunochemical techniques, specific antibodies against gastric parietal cells in serum and other body fluids. Gastric parietal cells are the cells found in the stomach that make a protein that allows the body to absorb vitamin B12. The measurements help diagnose vitamin B12 deficiency (or pernicious anemia), atrophic gastritis (inflammation of the stomach), and autoimmune connective tissue diseases (diseases that develop when the body produces antibodies against its own tissues).

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

(a)ID.An anti-smooth muscle antibody immunoassay system is a device consisting of reagents used to measure, by immunochemical techniques, anti-smooth muscle antibodies (antibodies to non-striated involuntary muscle) in serum. The measurements help diagnose chronic hepatitis (inflammation of the liver) and autoimmune connective tissue diseases (diseases caused by antibodies produced against the body's own tissue).

(b)classificationClass II (performance standards).

(a)ID.AAlfa-1-Antitrypsin Immunoassay System is a device consisting of reagents used for measurement by immunochemical techniquesAlfa-1-antitrypsin (a plasma protein) in serum, other body fluids, and tissues. The measurements help diagnose various diseases, including liver cirrhosis in adolescents and adults. Also,Alfa-1-antitrypsin deficiency has been linked to pulmonary emphysema.

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

(a)ID.A Bence Jones Protein Immunoassay System is a device consisting of reagents used to measure Bence Jones proteins in urine and plasma using immunochemical techniques. Immunoglobulin molecules are normally composed of pairs of polypeptide chains (subunits) of unequal size (light chains and heavy chains) linked by multiple disulfide bonds. Some cancers involve the proliferation of a plasma cell (antibody-producing cell) with excessive production of a specific type of light chain (monoclonal light chain). These free and homogeneous light chains, not associated with an immunoglobulin molecule, can be found in urine and plasma and have been termed Bence Jones proteins. Measuring Bence Jones proteins and seeing that they are monoclonal helps diagnose multiple myeloma (malignant proliferation of plasma cells), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins by cells of the spleen and bone marrow), leukemia ( cancer of the blood) that form organs) and lymphomas (cancer of the lymphatic tissue).

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

(a)ID.ABeta-Immune Globulin Test System is a device consisting of reagents used to measure beta-globulins (serum protein) in serum and other body fluids by immunochemical techniques.Beta-Globulin proteins includeBeta-lipoprotein, transferrin, glycoproteins and complement and are rarely associated with specific pathological disorders.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.A human milk immunoassay system is a device consisting of the reagents used to measure proteins in human milk through immunochemical techniques.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001]

(a)ID.A fecal calprotectin immunological test system is ain vitroDiagnostic device composed of reagents used for the quantitative determination of fecal calprotectin in human stool samples by immunochemical methods. The device is intended forin vitrodiagnostic use as an aid in the diagnosis of inflammatory bowel disease (IBD), particularly Crohn's disease and ulcerative colitis, and as an aid in distinguishing IBD from irritable bowel syndrome.

(b)Classification.Class II (special controls). The specific control for these devices is the FDA guidance document titled Class II Special Controls Guidance Document: Fecal Calprotectin Immunoassay Systems. See §866.1(e) for the availability of this guidance document.

[71 FR 42598, Jul 27, 2006]

(a)ID.A carbonic anhydrase B and C immunoassay system is a device consisting of reagents used to measure specific carbonic anhydrase protein molecules in serum and other body fluids by immunochemical techniques. Measurements of carbonic anhydrase B and C help diagnose abnormal hemoglobin metabolism.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.A ceruloplasmin immunoassay system is a device consisting of reagents used to measure ceruloplasmin (serum copper-binding protein) in serum, other body fluids, or tissues by immunochemical techniques. Ceruloplasmin measurements help diagnose disorders of copper metabolism.

(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 the limitations in §866.9.

[47 FR 50823, November 9, 1982, modified 84 FR 71800, December 30, 2019]

(a)ID.A Cohn Fraction II immunological test system is a device consisting of reagents containing or using that fraction of plasma that contains gamma globulin proteins, predominantly of the IgG class. The device can be used as a coprecipitate in radioimmunoassay methods, as a starting material for IgG subclass purification, and to reduce non-specific adsorption of plasma proteins in immunoassay techniques. Measurement of these proteins helps diagnose any disease related to abnormal levels of IgG gammaglobulins, such as agammaglobulinemia or multiple myeloma.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001]

(a)ID.A colostrum immunoassay system is a device consisting of reagents used to measure specific proteins in colostrum through immunochemical techniques. Colostrum is a substance secreted by the mammary glands during pregnancy and until the production of breast milk begins 1 to 5 days after birth.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001]

(a)ID.An immunological test system for complement components is a device consisting of the reagents used to measure the complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8 and C9 in serum or other body with immunochemical techniques. fluids and tissues. Complement is a group of serum proteins that destroy infectious agents. Measurements of these proteins help diagnose immunological disorders, particularly those associated with deficiencies in complement components.

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

[47 FR 50823, Nov. 9, 1982, amended 53 FR 11253, Apr. 6, 1988]

(a)ID.A complement C1 inhibitor (inactivator) immunoassay system is a device consisting of reagents used to measure complement C1 inhibitor (a plasma protein) in serum by immunochemical techniques. Complement inhibitor C1 is normally found in plasma and blocks the action of the C1 component of complement (a group of serum proteins that destroy infectious agents). Measurement of complement C1 inhibitor helps diagnose hereditary angioneurotic edema (increased blood vessel permeability leading to tissue swelling) and a rare form of angioedema associated with lymphoma (cancer of the lymph nodes).

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

(a)ID.A complement C3b inactivator immunoassay system is a device consisting of reagents used to measure complement C3b inactivator (a plasma protein) in serum by immunochemical techniques. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement inactivator C3b helps diagnose inherited antibody dysfunction.

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

(a)ID.A C-reactive protein immunological test system is a device consisting of reagents used to measure C-reactive protein in serum and other body fluids by immunochemical techniques. Measurement of C-reactive protein helps assess the extent of damage to body tissues.

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

(a)ID.An owndin B factor immunoassay system is a device consisting of reagents used to measure owndin B factor in serum and other body fluids by immunochemical techniques. Deposition of owndin factor B in body tissues, or a corresponding reduction in owndin factor B levels in serum and other body fluids, is evidence for the involvement of the alternative pathway to the classical pathway of complement activation ( a group of plasma proteins that cause the destruction of non-self cells). Measurement of owndin factor B helps to diagnose various kidney diseases, e.g. B. chronic glomerulonephritis (inflammation of the glomeruli of the kidney), lupus nephritis (kidney disease associated with a multisystem autoimmune disease, systemic lupus erythematosus) as well as various skin diseases, e.g. B. Dermatitis herpetiformis (presence of skin blisters that burn and itch) and pemphigus vulgaris (large skin blisters). Other diseases in which the alternative pathway of complement activation is involved are rheumatoid arthritis, sickle cell anemia, and gram-negative bacteremia.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59227, Nov. 3, 1998]

(a)ID.A factor XIII, A, S immunoassay system is a device consisting of reagents used to measure factor XIII (a blood coagulation factor) in platelets (A) or serum (S) by immunochemical techniques. Measurements of factor XIII, A, S aid in the diagnosis and treatment of certain bleeding disorders that result from a deficiency of this factor.

(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 section 866.9. This exception does not apply to factor deficiency tests, which are classified under section 864.7290 of this chapter.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.A ferritin immunoassay system is a device consisting of reagents used to measure ferritin (a protein that stores iron) in serum and other body fluids using immunochemical techniques. Ferritin measurements help diagnose diseases that affect iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia.

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

(a)ID.A fibrinopeptide A immunological test system is a device consisting of reagents used to measure fibrinopeptide A (a blood clotting factor) in plasma and other body fluids by immunochemical techniques. Measurement of fibrinopeptide A may be useful in diagnosing and treating certain blood clotting disorders.

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

(a)ID.A Cohn Fraction IV immunological test system is a device that consists primarily of or measures this fraction of plasma proteins.Alfa-yBeta-Globulins used as raw material for the manufacture of cigarAlfa-oBeta-globulins. measurement ofAlfa-oBeta-Globulins help diagnose many diseases, such as Wilson's disease (an inherited disease that affects the liver and brain), Tangier's disease (absence ofAlfa-1-lipoprotein), malnutrition, iron deficiency anemia, red blood cell disorders, and kidney 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.

[47 FR 50823, Nov. 9, 1982; 47 FR 56846, December 21, 1982, as amended 59 FR 63007, December 7, 1994; 66 FR 38793, July 25, 2001]

(a)ID.A Cohn Fraction V Immunoassay System is a device that consists of or measures a fraction of plasma that predominantly contains albumin (a plasma protein). This test helps diagnose conditions where albumin levels may be low, e.g. B. nephrosis (kidney disease), proteinuria (protein in the urine), gastroenteropathy (disease of the stomach and small intestine), rheumatoid arthritis, and viral 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 the limitations in §866.9.

[47 FR 50823, Nov. 9, 1982, as amended 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001]

(a)ID.An immunological test system for free secretory components is a device consisting of reagents used to measure free secretory components (usually part of the secretory IgA antibody molecule) in body fluids by immunochemical techniques. Measurement of the free secretory component (protein molecules) helps diagnose recurrent lung infections and other hypogammaglobulinemic (low antibody levels) conditions.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59227, Nov. 3, 1998]

(a)ID.AAlfa-The immunoglobulin test system is a device consisting of reagents used for measurement by immunochemical techniques.Alfa-Globulin (a serum protein) in serum and other body fluids. measure ofAlfa-Globulin can be useful in diagnosing inflammatory lesions, infections, severe burns, and a variety of other conditions.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.AAlfa-The 1-Glycoprotein Immunoassay System is a device consisting of reagents used for measurement by immunochemical techniques.Alfa-1-glycoproteins (a group of plasma proteins found in theAlfa-1 group in electrophoresis) in serum and other body fluids. measurement ofAlfa-1-Glycoproteins can help diagnose collagen (connective tissue) diseases, tuberculosis, infections, widespread cancers, and diabetes.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.AAlfaThe -2-glycoprotein immunological test system is a device consisting of reagents used for measurement by immunochemical techniquesAlfa-2-glycoproteins (a group of plasma proteins found in theAlfa-Group 2 in electrophoresis) in serum and other body fluids. measure ofAlfaThe -2 glycoproteins help diagnose some cancers and genetically inherited deficiencies of these plasma proteins.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.ABeta-2-Glycoprotein I Immunological Test System is a device consisting of reagents used for measurement by immunochemical techniquesBeta-2-Glycoprotein I (a serum protein) in serum and other body fluids. measure ofBeta-2-Glycoprotein I helps diagnose hereditary deficiency of this serum protein.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.ABetaThe -2-Glycoprotein III Immunoassay System is a device consisting of reagents used for measurement by immunochemical techniquesBeta-2-Glycoprotein III (a serum protein) in serum and other body fluids. measure ofBeta-2-Glycoprotein III helps diagnose inherited deficiency of this serum protein and a variety of other disorders.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.A haptoglobin immune test system is a device consisting of reagents used to measure haptoglobin (a protein that binds to hemoglobin, the oxygen-carrying pigment in red blood cells) in serum using immunochemical techniques. Measurement of haptoglobin can help diagnose hemolytic disorders (diseases in which red blood cells break down and release hemoglobin) associated with the formation of hemoglobin-haptoglobin complexes and certain kidney diseases.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59227, Nov. 3, 1998]

(a)ID.A hemoglobin immunological test system is a device consisting of reagents used to measure various types of free hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body fluids using immunochemical techniques. Free hemoglobin measurements help diagnose various blood diseases, including sickle cell anemia, Fanconi anemia (a rare inherited disease), aplastic anemia (the bone marrow does not make enough blood cells), and leukemia (cancer of the blood-forming 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 the limitations in §866.9.

[47 FR 50823, November 9, 1982, modified 84 FR 71800, December 30, 2019]

(a)ID.A hemopexin immunoassay system is a device consisting of reagents used to measure hemopexin (a serum protein that binds heme, a component of hemoglobin) in serum using immunochemical techniques. Measurement of hemopexin helps diagnose various hematologic disorders such as: B. hemolytic anemia (anemia due to reduced in vivo survival of mature red blood cells and the inability of the bone marrow to compensate for their reduced lifespan) and sickle cell anemia.

(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 section 866.9.

[47 FR 50823, Nov. 9, 1982, amended 63 FR 59227, Nov. 3, 1998]

(a)ID.A hypersensitivity pneumonitis immunological test system is a device consisting of reagents used to measure, by immunochemical techniques, serum immunoglobulin antibodies that specifically react with organic powder derived from animal or fungal protein sources. When these antibodies react with such dusts in the lungs, the immune complexes precipitate and trigger an inflammatory reaction (hypersensitivity pneumonitis). Measurement of these immunoglobulin G antibodies helps diagnose hypersensitivity pneumonitis and other allergic airway diseases.

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

(a)ID.An immunoglobulin A, G, M, D, and E immunoassay system is a device consisting of reagents used to measure immunoglobulins A, G, M, D, and E (serum antibodies) in serum by immunochemical techniques. Measurement of these immunoglobulins helps diagnose abnormal protein metabolism and the body's lack of ability to resist infectious agents.

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

(a)ID.An immunoglobulin G (specific Fab fragment) immunoassay system is a device consisting of reagents used to measure, by immunochemical techniques, the antigen-binding fragment Fab resulting from the degradation of immunoglobulin G antibodies in urine, serum and other bodily fluids. Measurement of immunoglobulin G Fab fragments helps diagnose lymphoproliferative disorders such as multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased production of immunoglobulin by cells of the spleen and marrow bone) and lymphoma (tumor of the lymphatic 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 the limitations in §866.9.

[47 FR 50823, Nov. 9, 1982, changed to 61 FR 1119, Jan. 16, 1996; 66 FR 38793, July 25, 2001]

(a)ID.An immunoglobulin G (specific Fc fragment) immunological test system is a device consisting of the reagents used to measure the Fc fragment (containing carbohydrates) of immunoglobulin G (resulting from the breakdown of immunoglobulin G antibodies) is used in urine, serum and immunochemical procedures other body fluids. Measurement of immunoglobulin G-Fc fragments helps to diagnose abnormalities that produce antibodies against plasma cells, e.g. B. Gamma heavy chain 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.

[47 FR 50823, Nov. 9, 1982, changed to 61 FR 1119, Jan. 16, 1996; 66 FR 38793, July 25, 2001]

(a)ID.An immunoglobulin G (specific Fd fragment) immunoassay system is a device consisting of reagents used to measure the amino-terminus (antigen binding) (Fd fragment) of the heavy chain (one subunit) of the immunoglobulin antibody. Immunochemical techniques. serum molecules are used. Measurement of immunoglobulin G-Fd fragments helps diagnose abnormalities of antibody-forming cells in plasma.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001]

(a)ID.An immunoglobulin (light chain specific) immunoassay system is a device consisting of reagents used to measure the kappa and lambda types of light chain fractions of immunoglobulin molecules in serum, other body fluids, and tissues by immunochemical techniques. In some disease states, antibody-producing cells produce too many light chains. These free light chains, which are not associated with gamma globulin molecules, can be found in a patient's body fluids and tissues. Measuring different amounts of different types of light chains helps diagnose multiple myeloma (cancer of antibody-producing cells), lymphocytic neoplasia (cancer of lymphatic tissue), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins), and tissue diseases connective tissue such as rheumatoid arthritis or systemic lupus erythematosus.

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

(a)ID.A lactic acid dehydrogenase immunoassay system is a device consisting of reagents used to measure lactic acid dehydrogenase enzyme activity in serum by immunochemical techniques. Elevated levels of lactate dehydrogenase are found in a variety of disorders, including megaloblastic anemia (decreased number of mature red blood cells), myocardial infarction (heart disease), and some forms of leukemia (cancer of the blood-forming organs). ). However, the diagnostic utility of this device is limited due to the many conditions known to cause elevated lactic acid dehydrogenase levels.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.A lactoferrin immune test system is a device consisting of reagents used to measure lactoferrin (an iron-binding protein with the ability to inhibit the growth of bacteria) in serum, breast milk, other body fluids, and tissues by immunochemical techniques. Measuring lactoferrin can help diagnose an inherited deficiency of this protein.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2312, January 14, 2000]

(a)ID.AAlfa-1-Lipoprotein Immunological Test System is a device consisting of reagents used for measurement by immunochemical techniquesAlfa-1-lipoprotein (high-density lipoprotein) in serum and plasma. measure ofAlfa-1-lipoprotein can help diagnose Tangier disease (an inherited disorder of fat metabolism).

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

(a)ID.A Lipoprotein X Immunoassay System is a device consisting of reagents used to measure Lipoprotein X (a high-density lipoprotein) in serum and other body fluids by immunochemical techniques. Measuring lipoprotein X helps diagnose obstructive liver 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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2313, January 14, 2000]

(a)ID.A low-density lipoprotein immunological test system is a device consisting of reagents used to measure low-density lipoprotein in serum and other body fluids by immunochemical techniques. Measurement of serum low-density lipoproteins can help diagnose disorders of lipid (fat) metabolism and help identify youth at risk for cardiovascular disease.

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

(a)ID.AAlfaThe 2-macroglobulin immunological test system is a device consisting of reagents used for measurement by immunochemical techniques.Alfa-2-macroglobulin (a serum protein) in plasma. measure ofAlfa-2-macroglobulin can help diagnose blood coagulation disorders or clot lysis.

(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 the limitations in §866.9.

[47 FR 50823, November 9, 1982, modified 84 FR 71800, December 30, 2019]

(a)ID.ABetaThe 2-microglobulin immunoassay system is a device consisting of reagents used for measurement by immunochemical techniques.Beta-2-microglobulin (a protein molecule) found in serum, urine, and other body fluids. measure ofBeta-2-microglobulin helps diagnose active rheumatoid arthritis and kidney disease.

(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 the limitations in §866.9.

[47 FR 50823, November 9, 1982, modified 84 FR 71800, December 30, 2019]

(a)ID.An infectious mononucleosis immunological test system is a device consisting of reagents used to measure, by immunochemical techniques, the heterophile antibodies commonly associated with infectious mononucleosis in serum, plasma, and other body fluids. Measurements of these antibodies help diagnose infectious mononucleosis.

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

[47 FR 50823, Nov. 9, 1982; 47 FR 56846, Dec. 21, 1982]

(a)ID.A multiple autoantibody immune test system is a device consisting of reagents used to measure, by immunochemical techniques, autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measuring multiple autoantibodies helps diagnose autoimmune diseases (diseases that develop when autoantibodies damage the body's own tissues).

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

(a)ID.An Aquaporin-4 Autoantibody Immunotest System is a device consisting of reagents used to measure autoantibodies in human serum specimens that react with Aquaporin-4 (AQP4Ab) by immunochemical techniques. The measurements help diagnose neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) along with other clinical, laboratory, and radiological diagnoses (z.B.,MRI) findings.

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

(1) Premarket notices must include the following information:

(i) A detailed description of the device including:

(A) A detailed description of all components, including ancillary reagents required in the assay;

(B) If applicable, a detailed description of the instruments and equipment, including illustrations or photographs of non-standard equipment or manuals;

(C) Detailed documentation of device software, if any, including, but not limited to, stand-alone software applications and hardware-based devices that contain software;

(D) A detailed description of the appropriate internal and external quality controls that are recommended or provided. The description should identify those control elements that are integrated into the specified test procedures;

(E) Detailed specifications for sample collection, processing, and storage;

(F) A detailed description of the test methodology and procedure;

(G) A description of how the assay cut-off point (the medical decision point between positive and negative) was established and validated, and supporting data; Y

(H) Detailed specification of the criteria for interpreting and reporting test results.

(ii) Detailed information demonstrating the performance of the device, including:

(A) Instrument precision/reproducibility data generated from within-run, inter-run, inter-day, inter-lot, inter-site, and total precision for multiple non-consecutive days, where applicable. A well-characterized panel of patient samples or specified population groups covering the measurement range of the device should be used.

(B) Instrument linearity data generated from samples covering the measurement range of the instrument, if applicable.

(C) Information on traceability to a reference material and description of the value assignment of calibrators and controls, if applicable.

(D) Analytical sensitivity data for the device, including limit of blank, limit of detection, and limit of quantification, if applicable.

(E) Analytical specificity data for the device, including interference from endogenous and exogenous substances and cross-reactivity with specimens derived from patients with other autoimmune diseases or conditions.

(F) Transfer data from device to instrument, if applicable.

(G) Device stability data, including real-time stability at different storage times and temperatures.

(H) Sample stability data, including stability over various storage times, temperatures, freeze-thaw cycles, and transport conditions, as applicable.

(I) Method comparison data generated by comparing results obtained with the device to a legitimately marketed comparison device with similar indications for use. A well-characterized panel of patient samples from the specified population covering the measurement range of the device should be used.

(J) Sample matrix comparison data if more than one sample type or anticoagulant can be tested on the device. Samples used for comparison should come from well-characterized patient samples that cover the measurement range of the device.

(K) Clinical performance will be determined by comparing data generated by testing specimens from the specified population and differential diagnostic or non-target disease groups with the device in accordance with the clinical diagnostic standard.

(1) The diagnosis of NMO and NMOSD should be based on clinical findings, laboratory tests (z.B.,serological tests) and radiological tests (z.B.,magnetic resonance imaging).

(2) The group of differential diagnoses or non-target diseases must include applicable diseases or conditions, including, but not limited to, the following: multiple sclerosis, stroke, Lyme disease, shingles, syphilis, human immunodeficiency virus, hepatitis B, tuberculosis, Srgen B syndrome, systemic lupus erythematosus, systemic vasculitis, sarcoidosis, Graves' disease, Hashimoto's disease, type I diabetes, rheumatoid arthritis, Addison's disease, and myasthenia gravis.

(3) Diagnosis of diseases or conditions for differential or non-target disease groups should be based on established diagnostic criteria and clinical evaluation.

(4) Clinical diagnostic criteria and demographic information must be collected and provided for all samples.

(5) Clinical validation results must demonstrate clinical sensitivity and clinical specificity for the test values ​​based on the presence or absence of NMO and NMOSD.

(6) Data should be summarized in tabular form, comparing interpretation of results with disease status.

(L) Expected/reference values ​​generated by testing an appropriate number of specimens from apparently healthy and normal subjects.

(iii) Identification of the risk mitigation elements used by the product, including a description of any additional procedures, methods and practices incorporated into the instructions for use that mitigate the risks associated with the tests.

(2) Device labeling that complies with 21 CFR 809.10(b) must contain warning statements relevant to the device, including:

(i) a warning stating "The device is intended for use by laboratory personnel in a clinical laboratory setting"; Y

(ii) A warning stating: “The device is not to be used as a stand-alone device, but rather as a supplement to other clinical information. A diagnosis of neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) should not be based on a single test result Clinical symptoms, physical examination results, laboratory tests (z.B.,serological tests) and radiological tests (z.B.Magnetic resonance imaging), when appropriate, should always be taken into account when considering the diagnosis of NMO and NMOSD.

(3) Device labeling that complies with 21 CFR 809.10(b) shall include a detailed description of the protocol and performance studies conducted pursuant to paragraph (b)(1)(ii) of this section and a summary of the the results.

[82 FR 50076, October. 30, 2017]

(a)ID.A zinc transporter 8 autoantibody immunoassay is a device consisting of reagents used to measure autoantibodies in human serum samples that react with zinc transporter 8 (ZnT8) by immunochemical techniques. The measurements help diagnose type 1 diabetes mellitus (autoimmune diabetes) along with other clinical and laboratory findings.

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

(1) Premarket notices must include the following information:

(i) A detailed description of the device, including:

(A) A detailed description of all test system components, including a description of the test components in the kit and any required ancillary reagents;

(B) A detailed description of the instruments and equipment and, where applicable, illustrations or photographs of non-standard equipment or methods;

(C) Detailed documentation of device software, including, but not limited to, stand-alone software applications and hardware-based devices that may contain software;

(D) A detailed description of the appropriate internal and external quality controls that are recommended or provided. The description should identify those control elements that are integrated into the recommended test procedures;

(E) Detailed specifications for sample collection, processing, and storage;

(F) A detailed description of the test methodology and procedure; Y

(G) Detailed specification of the criteria for interpreting and reporting test results.

(ii) information that demonstrates the capabilities of the device, including:

(A) Instrument precision/reproducibility data generated from intra-run, inter-run, inter-day, inter-lot, inter-operator, inter-instrument, inter-site, and total precision for multiple non-consecutive days, where applicable. A well-characterized panel of patient samples or population groups of intended use covering the measurement range of the device should be used;

(B) device linearity data generated from patient samples and covering the measurement range of the assay, if applicable;

(C) Traceability information to a reference material and description of the value assignment of calibrators and controls, if applicable;

(D) Analytical sensitivity data for the device, including limit of blank, limit of detection, and limit of quantification, if applicable;

(E) Analytical specificity data for the device, including interference from endogenous and exogenous substances and cross-reactivity with specimens derived from patients with other autoimmune diseases or conditions;

(F) device-to-instrument transfer data, if applicable;

(G) device stability data, including real-time stability at various storage times and temperatures;

(H) Sample stability data, including stability over various storage times, temperatures, freeze-thaw cycles, and transport conditions, as applicable;

(I) Method comparison data generated by comparing results obtained with the device to a legitimately marketed comparison device with a similar indication for use. Patient samples should be taken from the intended population that covers the measurement range of the device;

(J) Sample matrix comparison data if more than one sample type or anticoagulant can be tested on the device. Samples used for comparison must be patient samples covering the measurement range of the device;

(K) a description of how the assay cut-off point (the medical decision point between positive and negative) was established and validated, and supporting data;

(L) Clinical performance will be determined by comparing data generated by testing samples from the intended use population and differential diagnosis groups with the standard clinical diagnostic device. Diagnosis of type 1 diabetes mellitus should be based on history, physical examination, and laboratory tests, such as B. based on one or more insulin or pancreatic autoantibody tests. Because the predicted population for type 1 diabetes mellitus includes subjects younger than 18 years of age, samples of a representative number of these subjects should be included. In addition, representative sample numbers from all age groups should be included. Differential diagnosis groups should include, among others: type 2 diabetes mellitus; Metabolic syndrome; latent autoimmune diabetes in adults; other autoimmune diseases such as celiac disease (without concomitant diagnosis of type 1 diabetes mellitus), systemic lupus erythematosus, rheumatoid arthritis, and Hashimoto's thyroiditis; Infection; kidney disease; and testicular cancer. Diseases for differential groups should be based on established diagnostic and clinical evaluation criteria. Clinical diagnostic criteria and demographic information must be collected and provided for all samples. Clinical validation results should demonstrate clinical sensitivity and clinical specificity for test values ​​based on the presence or absence of type 1 diabetes mellitus. Data should be summarized in tabular form, comparing interpretation of results with state of the art. the illness; Y

(M) Expected/reference values ​​generated by testing an appropriate number of specimens from apparently healthy and normal individuals.

(iii) Identification of the risk mitigation elements used by the product, including a description of any additional procedures, methods and practices incorporated into the instructions for use that mitigate the risks associated with the tests.

(2) Your 21 CFR 809.10(a) compliant label and 21 CFR 809.10(b) compliant label must include assay-relevant warnings, including:

(i) a warning stating: "The device is intended for use by laboratory personnel in a clinical laboratory setting";

(ii) A disclaimer stating: “The test is not a standalone test but a supplement to other clinical information. A diagnosis of type 1 diabetes mellitus should not be based on a single test result. Clinical symptoms, results of additional physical examinations and laboratory tests (z.B.,serological tests), where appropriate, should always be taken into account when considering the diagnosis of type 1 diabetes mellitus and type 2 diabetes mellitus”;

(iii) a warning stating: "The absence of zinc T8 autoantibodies does not exclude the diagnosis of type 1 diabetes mellitus"; Y

(iv) A cautionary statement stating: "The assay has not been shown to be effective in monitoring disease status or response to treatment."

(3) Your 21 CFR 809.10(b) compliant label must include a description of the protocol and performance studies conducted pursuant to paragraph (b)(1)(ii) of this section and a summary of the results.

[82 FR 49103, oct. 20, 2017]

(a)ID.A myoglobin immunoassay system is a device consisting of reagents used to measure myoglobin (an oxygen storage protein found in muscle) in serum and other body fluids using immunochemical techniques. The measurement of myoglobin helps in the rapid diagnosis of heart or kidney diseases.

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

(a)ID.A complete serum or plasma immunoassay system is a device consisting of reagents used to measure proteins in plasma or serum by immunochemical techniques. Plasma or serum protein measurements aid in the diagnosis of any disease related to abnormal plasma or serum protein levels, e.g. B. agammaglobulinemia, allergies, multiple myeloma, rheumatoid vasculitis, or hereditary angioedema.

(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.

[47 FR 50823, Nov. 9, 1982, as amended 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001]

(a)ID.A plasminogen immune test system is a device consisting of reagents used to measure plasminogen (an inactive substance from which plasmin, a blood clotting factor, is formed) in serum, other body fluids, and tissues by immunochemical techniques. Measurement of plasminogen levels can be helpful in diagnosing fibrinolytic (blood clotting) disorders.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2313, January 14, 2000]

(a)ID.A prothrombin immunoassay system is a device consisting of reagents used to measure prothrombin (coagulation factor II) in serum by immunochemical techniques. Measurements of the antigen-competent prothrombin level (ability to react with protein antibodies) help diagnose bleeding disorders.

(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 section 866.9. This exception does not apply to multipurpose systems for in vitro coagulation studies classified under §864.5425 of this chapter or prothrombin time tests classified under §864.7750 of this chapter.

[47 FR 50823, November 9, 1982, modified 65 FR 2313, January 14, 2000]

(a)ID.A radioallergosorbent immunoassay system is a device consisting of reagents used to measure allergenic antibodies specific to a particular allergen (antibodies that produce an allergic reaction) by immunochemical techniques. Measurement of antibodies against specific allergens can help diagnose asthma, allergies, and other lung diseases.

(b)Classification.Class II (special controls). The device, if designed to detect any of the allergens listed in Table 1 of this paragraph, is exempt from the premarket notification procedures in subpart E of Part 807 of this chapter, subject to the limitations of the Section 866.9.

[47 FR 50823, November 9, 1982, modified 84 FR 71800, December 30, 2019]

(a)ID.A tryptase test system is a device that helps diagnose systemic mastocytosis. It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of patients with suspected systemic mastocytosis in conjunction with other clinical and laboratory findings.

(b)Classification.Class II (special controls). The special control is the FDA guideline titled "Guide to Class II Special Controls: Tryptase Test System as an Aid in the Diagnosis of Systemic Mastocytosis." See §866.1(e) for document availability.

[79 FR 56010, Sept. 18, 2014]

(a)ID.A retinol-binding protein immunoassay system is a device consisting of reagents used to measure, by immunochemical techniques, retinol-binding protein that binds and transports vitamin A in serum and urine. Measuring this protein can help diagnose kidney disease and monitor kidney transplant patients.

(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 section 866.9.

[47 FR 50823, November 9, 1982, modified 65 FR 2313, January 14, 2000]

(a)ID.A rheumatoid factor immune test system is a device consisting of reagents used to measure levels of rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues by immunochemical techniques. Rheumatoid factor measurement can help diagnose rheumatoid arthritis.

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

(a)ID.el antiSaccharomyces cerevisiae(S. cerevisiae) The Antibody Test System (ASCA) is an in vitro diagnostic device consisting of the reagents used to measure antibodies against immunochemical techniques.S. cerevisiae(baker's or brewer's yeast) in human serum or plasma. detection ofS. cerevisiaeAntibodies can help diagnose Crohn's disease.

(b)Classification.Class II (special controls). Special control is the "Guide for Industry and FDA Reviewers: Class II Special Control Guidance Document for Anti-Saccharomyces cerevisiae(S. cerevisiae) Antibody Premarket Notifications (ASCA).“

[65 FR 70307, ​​​​Nov. 22, 2000]

(a)ID.A seminal fluid (semen) immunological test system is a device consisting of reagents used for legal purposes to identify and distinguish between animal and human sperm. The test results can be used as evidence in court in cases of suspected rape and other sexual crimes.

(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.

[54 FR 25047, June 12, 1989, modified 66 FR 38793, July 25, 2001]

(a)ID.An immunological test system for systemic lupus erythematosus (SLE) is a device consisting of the reagents used to measure, by immunochemical techniques, autoimmune antibodies in serum and other body fluids conjugated with double-stranded deoxyribonucleic acid (DNA) cellular nuclear or other respond components that are specifically diagnostic of SLE. Measurement of antibodies against double-stranded nuclear DNA helps diagnose SLE (a multisystem autoimmune disease in which tissues are attacked by the person's own antibodies).

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

(a)ID.A TBI Screening Test is a device consisting of reagents used to detect and measure biomarkers of brain injury in human samples. The measurements help evaluate patients with suspected mild traumatic brain injury along with other clinical information to help determine the need for head imaging based on the current standard of care.

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

(1) Labeling that complies with 21 CFR 809.10(b) must include detailed descriptions and results of performance tests performed to evaluate precision, accuracy, linearity, analytical sensitivity, interference, and cross-reactivity. This information must include:

(i) Device precision performance tests must use at least one unmodified clinical sample from the intended use population with a concentration of brain injury biomarkers close to the medical decision point. Contrived samples derived from pooling multiple samples or adding purified analytes can be used to cover the measurement range, but contrived samples must be prepared to mimic clinical samples as closely as possible. These tests must assess repeatability and reproducibility using an FDA-recognized standard protocol.

(ii) Device performance data must be supported by a clinical study and include:

(A) Data demonstrating the clinical validity, including clinical sensitivity and specificity, and the positive and negative predictive value of the test in the intended use population of patients with suspected mild traumatic brain injury (dhGlasgow Coma Score (GCS) of 13-15) or equivalent standard of care to determine the severity of traumatic brain injury (TBI).

(B) The study should be conducted with carriers and in environments representative of the types of carriers and environments for which the device is intended to be used.

(C) All eligible subjects must meet well-defined study inclusion and exclusion criteria, which define the intended use population. The prevalence of sick or injured subjects in the study population should reflect the prevalence of the device's intended use population, or alternatively, statistical measures should be used to account for any bias due to enrichment of subpopulations of the intended use population. .

(D) All eligible subjects must have had a head computed tomography (CT) scan or other appropriate clinical diagnostic standard used to determine the presence of an intracranial lesion as part of the standard of care and must also be evaluated for the device appropriate to be qualified. All clinical diagnostic standards used in the clinical study must be in accordance with standard clinical practice in the United States.

(E) Relevant demographic variables and baseline characteristics, including medical history and neurological history. In addition, the characteristics of the head injury, neurological evaluations, and physical evidence of trauma must be presented for each subject. This information includes, but is not limited to, the following: time from head injury, time from head injury to CT scan, time from head injury to blood draw, GCS score or equivalent , experience of loss of consciousness, presence of confusion, episodes of vomiting, features of post-traumatic amnesia, presence of post-traumatic seizures, drug or alcohol intoxication, mechanism of injury, type of acute intracranial injury, neurosurgical injury, and skull fracture.

(F) Each CT scan or other imaging result must be evaluated independently and blindly by at least two board-certified radiologists to determine if it is positive or negative, defined by the presence or absence of acute intracranial lesions. This independent review should be done without access to device test results. Before performing the review, the criteria and procedures for evaluating the images, including the mechanism for establishing consensus, should be established.

(G) All clinical specimens should be tested with the subject's device blinded to the subject's TBI status and neurological lesion status.

(H) Details should be given on how to deal with missing values ​​in the data.

(I) In the case of deposited clinical samples, the conditions and duration of storage must be reported. In addition, a sample stability study during storage should be performed to demonstrate the integrity of archived clinical samples. Samples evaluated during assay test development should not be used to determine the clinical validity of assays.

(iii) Verification of device analytical specificity performance should include the most commonly reported concomitant medications present in samples from the intended use population. In addition, endogenous analytes that may cross-react should be tested at the highest concentration reported in samples from the intended use population.

(iv) Expected Values/Reference Values ​​generated by testing a statistically reasonable number of specimens from apparently healthy and normal subjects.

(2) Marking in accordance with 21 CFR 809.10(a) and (b) must include the following restrictions:

(i) A qualifying statement that this device is not intended to be used as a stand-alone device, but rather as an adjunct to other clinical information to aid in the evaluation of patients being considered for standard neuroimaging.

(ii) A qualifying statement that reads: “A negative result is generally associated with the absence of acute intracranial lesions. Appropriate imaging is required to diagnose acute intracranial injuries.”

(iii) Where applicable, a qualifying statement that reads "This device is intended for use by laboratory professionals in a clinical laboratory setting."

[83 FR 27701, June 14, 2018]

(a)ID.A total cerebrospinal fluid immunological test system is a device consisting of reagents used to measure total protein in cerebrospinal fluid by immunochemical techniques. Measurement of cerebrospinal fluid protein can help diagnose multiple sclerosis and other diseases of the nervous system.

(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.

[47 FR 50823, Nov. 9, 1982, changed to 61 FR 1119, Jan. 16, 1996; 66 FR 38793, July 25, 2001]

(a)ID.A thyroid autoantibody immunoassay system is a device consisting of reagents used to measure thyroid autoantibodies (antibodies produced against the body's own tissues) by immunochemical techniques. Measurement of thyroid autoantibodies can help diagnose certain thyroid disorders, such as Hashimoto's disease (chronic lymphocytic thyroiditis), nontoxic goiter (enlarged thyroid gland), Graves' disease (enlarged thyroid gland with bulging eyeballs) and cancer of the thyroid gland.

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

(a)ID.A transferrin immunoassay system is a device consisting of reagents used to measure transferrin (a serum protein that binds and transports iron) in serum, plasma, and other body fluids using immunochemical techniques. Measuring transferrin levels helps diagnose malnutrition, acute inflammation, infection, and red blood cell disorders such as iron deficiency anemia.

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

(a)ID.an interAlfaThe trypsin inhibitor immunological test system is a device consisting of the reagents used to test, using immunochemical techniques, the inter-AlfaTrypsin (a protein) inhibitor in serum and other body fluids. measure ofAlfaTrypsin inhibitors can help diagnose inflammation and acute 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 section 866.9.

[47 FR 50823, Nov. 9, 1982, as amended 53 FR 11253, Apr. 6, 1988; 65 FR 2313, January 14, 2000]

(a)ID.The CFTR Gene Mutation Detection System is a device used to simultaneously detect and identify a number of mutations and variants in the CFTR gene. It is designed as an aid in diagnostic confirmation testing in people with suspected cystic fibrosis (CF), in carrier identification, and in newborn screening. This device is not intended for use in stand-alone diagnosis, prenatal diagnosis, preimplantation, or population screening.

(b)Classification.Class II (special controls). The special control is the FDA guidance document titled Class II Special Controls Guidance Document: CFTR Gene Mutation Detection System. See §866.1(e) for the availability of this guidance document.

[70 FR 61738, October. 26, 2005]

(a)ID.Quality control material for cystic fibrosis nucleic acid assays. A quality control kit for cystic fibrosis nucleic acid assays is a device designed to monitor the reliability of a test system by detecting analytical bias such as that caused by variations in reagents or instruments used in genetic testing. . This type of device includes recombinant, synthetic, and cell line-based DNA controls.

(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 the limitations in §866.9. The special control is the FDA guidance document titled Class II Special Controls Guidance Document: Quality Control Material for Cystic Fibrosis Nucleic Acid Assays. See §866.1(e) for the availability of this guidance document.

[72 FR 1176, January 10, 2007, as amended at 84 FR 71811, December 30, 2019]

(a)ID.A newborn screening test for SCID is a prescription device that measures T-cell receptor cleavage circle (TREC) DNA obtained from blood samples dried on filter paper using a chain reaction-based assay. polymerase to aid in the detection of neonates to SCID. Presumptive positive results should be followed by confirmatory diagnostic tests. This test is not designed as a diagnostic test or to detect syndromes similar to SCID, such as DiGeorge syndrome or Omenn syndrome. It is also not designed to detect less acute SCID syndromes, such as leaky SCID or SCID variants.

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

(1) Premarket notices must include the following information:

(i) The intended purpose must state:

(A) The test is not intended for diagnostic purposes or to detect SCID-like syndromes such as DiGeorge syndrome or Omenn syndrome; Y

(B) The test is not designed to detect less acute SCID syndromes such as B. Leaky SCID or SCID variants.

(ii) A detailed description of each test component, including:

(A) A detailed description of the test components, all required reagents, instruments, and equipment, including illustrations or photographs of non-standard equipment or methods;

(B) Detailed documentation for device software, including, but not limited to, stand-alone software applications and hardware-based devices that contain software;

(C) Specifications for the filter paper to be properly labeled for in vitro diagnostic use, to be used in sample collection, and how it will be used in sample collection validation. These specifications should include: descriptive properties of the filter paper, instructions on how a laboratory should select the appropriate filter paper, chemical properties of the filter paper, interference problems related to chemicals in the filter paper, absorption properties of the filter paper, perforations size, absorption capacity, verification of the homogeneity of the punch, diameter of the circle for the aliquot of the dried blood stain, absorption time, physical composition and number and size of the punches to be tested;

(D) Methodology and protocols for detecting T-cell receptor cleavage circles and methods for determining results. The cut-off point must be selected before conducting clinical and analytical studies;

(E) A description of the results along with sample reports. Sample reports should include the scale used in reporting the results (z.B.,TREC copies/[micro]L) and the range of values ​​to be output; Y

(F) A description of the appropriate internal and external controls that are recommended or provided. The description should identify the control elements involved in the test procedure.

(iii) information demonstrating the performance characteristics of the test, including:

(A) Data demonstrating the clinical validity of the device using prospectively or retrospectively obtained well-characterized clinical samples representative of the intended use population. At least 10-15 confirmed positive samples should be obtained from more than 1 site, including relevant comments, and a diagnosis of SCID by flow cytometry or clinically significant information on the subject's condition should be obtained at one year or more. Additional samples should have been obtained that are characterized by other disorders that may be found when examining samples with low or absent REBT (z.B.,other T-cell lymphopenia) to complement the range of results. The clinical validation study must have a predetermined clinical decision point (dhCut-off point to differentiate between positive and negative results). The results should be summarized in tabular form, comparing the interpretation of the results with the reference method. Point estimates should be provided along with two-sided 95 percent confidence intervals for positive percent agreement, negative percent agreement, and overall percent agreement. Data should include retest rate, pre-retest false-positive rate, final false-positive rate, and false-negative rate;

(B) Instrument reproducibility data generated using at least three sites, at least two of which must be remote sites, with two operators at each site. Each site must perform a minimum of five analyzes per operator on five non-consecutive days to assess at least six different relevant TREC concentrations that span and are well distributed across the measurement range and include the clinical breakpoint. Samples should include cord blood and cord blood diluted with ABO-compatible adult blood samples. Identical samples from the same panel of samples must be tested at each site. Each sample must be tested in triplicate and contains controls tested in triplicate. Results should be reported as standard deviation and percent coefficient of variation for each level tested. Results should also be shown as dichotomous variables around the cut-off point. The total variation should be divided into the sum of the within-laboratory and between-laboratory variations with predetermined acceptance criteria and 95 percent confidence intervals for all data. Pre-established acceptance criteria must be provided and followed;

(C) Device precision data using clinical samples to assess intra-lot, inter-lot, intra-assay, between-assay and total variation. A range of sample TREC values ​​should include samples within the measurement range, samples above and below the measurement range, and very close samples above and below the cut-off value. At least three replicates of each sample should be tested with controls and calibrators in accordance with the instrument instructions for use. The precision study should use well-characterized samples with different batches, instruments, and operators. The results will be summarized in tabular form. Pre-established acceptance criteria must be provided and followed;

(D) The linearity of the test should be demonstrated using a dilution panel of clinical samples. The dilution sample range should include samples within the measurement range, samples above and below the measurement range, and samples very close above and below the cut-off value. The results of the regression analysis should be summarized in tabular form and fitted to a linear regression model with the results of individual measurements against dilution factors. Pre-established acceptance criteria must be provided and followed;

(E) Analytical sensitivity data for the device, including limit of blank, limit of detection, and limit of quantification;

(F) device-specificity data, including interference, carryover, cross-contamination, and in silico analysis of potential off-target genomic sequences;

(G) Instrument stability data, including real-time stability of samples at different storage times, temperatures, and freeze-thaw conditions. A separate transport stability study should be performed;

(H) Lot-to-lot reproducibility study of each filter paper validated with the test. The lot-to-lot study must include at least three lots of each blood card validated with the test and run on five non-consecutive days. The sample panel should consist of samples with different TREC values ​​and should include samples within the measurement range, samples above and below the measurement range, and samples closely above and below the cutoff. Multiple punches should be made on each card to demonstrate the homogeneity of the analyte in the dried blood spot. Comparability of test performance for each filter paper must be demonstrated. The stability and storage of TREC-DNA must be demonstrated on each blood sample card. The results of the batch-to-batch study should be summarized with the mean, standard deviation, and percent coefficient of variation presented in tabular form. Data should be calculated for Within Run, Between Run, Within Batch, and Between Batch. Data should be provided to demonstrate the agreement between the results of different filter papers. Study acceptance criteria must be provided and followed; Y

(I) Where applicable, a thermal cycler reproducibility study will be performed with thermal cyclers from three independent thermal cycler manufacturers. The sample panel should consist of samples with different TREC values ​​and should include samples within the measurement range, samples above and below the measurement range, and samples very close above and below the cut-off value. The study should be performed using three lots of filter paper and performed over five non-consecutive days. The results of the thermal cycler reproducibility study should be summarized in tabular form with the mean, standard deviation, and percent coefficient of variance reported. Data should be calculated for study results within a run, between runs, within a batch, between batches and between manufacturers of thermal cyclers. Study acceptance criteria must be provided and followed.

(iv) Identification of risk mitigation elements used by your device, including a description of additional procedures, methods, and practices embedded in the instructions for use that mitigate the risks associated with testing.

(2) Your § 809.10 compliant label must include:

(i) A disclaimer stating: “This test is not intended for diagnostic use, prenatal or preimplantation testing, or for the detection of SCID-like syndromes such as DiGeorge syndrome or Omenn syndrome. It is also not designed to detect less acute SCID syndromes, such as leaky SCID or variant SCID.";

(ii) a disclaimer stating "Test results are intended to be used in conjunction with other clinical and diagnostic findings that meet professional standards of practice, including confirmation by alternative methods and clinical evaluation, as appropriate."

(iii) a description of the performance studies referred to in paragraph (b)(1)(iii) and a summary of the results; Y

(iv) A description of the filter paper specifications required for the test.

[82 FR 50079, October. 30, 2017]

(a)ID.The Autosomal Recessive Carrier Gene Mutation Detection System is an in vitro qualitative molecular diagnostic system for the genotyping of clinically relevant variants in genomic DNA isolated from human samples intended for prescription or non-prescription use. The device is designed for the detection of carriers of autosomal recessive diseases in adults of childbearing age. The device is not intended for copy number variation, cytogenetic, or biochemical testing.

(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 the restrictions of section 866.9, except section 866.9(c)(2). The genetic mutation detection system for the screening of autosomal recessive carriers must comply with the following specific controls:

(1) If the product is offered without a prescription, the manufacturer of the product must provide the potential purchaser or actual recipient of a test report with information on how to access a board-certified clinical molecular geneticist or equivalent physician for pre- and follow-up . -up assistance Advice after the test.

(2) The device must use a collection device that is FDA-cleared, approved, or classified as 510(k)-exempt with an indication for in vitro diagnostic use in DNA testing.

(3) The product label shall include a prominent hyperlink to the manufacturer's public website where the manufacturer makes the information mentioned in this section publicly available. The manufacturer's home page, as well as the main part of the manufacturer's website dealing with the device, must contain a conspicuously placed hyperlink to the web page containing this information and allow unrestricted viewing access. If the Device can be purchased from the website or tests using the device can be ordered from the website, the same information must be available on the device ordering web page or provided in a prominent and publicly available hyperlink on the website. device ordering page online. Any changes to the device that could significantly affect its safety or effectiveness would require new data or information to support those changes, which should also be posted on the manufacturer's website. The information must contain:

(i) A detailed description of the device including:

(A) Gene (or list of genes if more than one is present) and variants detected by the test (using standardized nomenclature, Human Genome Organization (HUGO) nomenclature and coordinates).

(B) Scientifically proven clinical validity of each variant detected and reported by the test, identified in peer-reviewed journal articles, authoritative abstracts of the literature such as Genetics Home Reference (http://ghr.nlm.nih.gov/), GeneReviews (http://www.ncbi.nlm.nih.gov/books/NBK1116/) or similar summaries of valid scientific evidence and/or recommendations from professional bodies, including:

(1) genotype-phenotype information for the reported mutations.

(2) Relevant American College of Medical Genetics (ACMG) or American Congress of Obstetricians and Gynecologists (ACOG) guidelines that recommend tests for the specific genes and variants that the test detects, and recommended populations if available. If not available, a statement that professional guidelines do not currently recommend testing for that specific gene or variant.

(3) Table of the expected prevalence of the carrier state in the major ethnic and racial populations and in the general population.

(C) The type of sample (z.B.,saliva, whole blood), matrix and volume.

(D) Test steps and technology used.

(E) Specification of reagents, instruments and auxiliary equipment required.

(F) Specification of sample collection, processing, storage, and preparation methods.

(G) Specification of risk mitigation elements and description of additional procedures, methods, and practices incorporated into IFUs that mitigate risks associated with testing.

(H) Information about the probability of failing a test (z.B.,failed quality control) based on data from clinical samples, description of scenarios in which a test may fail (dhlow sample volume, low DNA concentration, etc.), how to notify clients and what follow-up actions to take.

(I) Specification of criteria for interpreting and reporting test results.

(ii) information that demonstrates the capabilities of the device, including:

(A) Precision (method comparison) of study results for each sample type claimed.

(1) The precision of the device should be evaluated using fresh clinical specimens collected and processed according to the instructions for use of the device. When this is not practical, fresh clinical samples can be substituted or supplemented by archived clinical samples. Archived samples must have been previously collected, stored appropriately, and randomly selected in accordance with the instrument's instructions for use. In some cases, the use of artificial samples or samples from human cell lines may also be appropriate; samples from artificial or human cell lines should closely mimic clinical samples and provide an unbiased assessment of device precision.

(2) Precision should be assessed against bi-directional sequencing or other FDA-identified methods as appropriate. Performance criteria for both the comparison method and the device should be predefined and appropriate for the intended use of the test. Detailed and appropriate study protocols should be submitted.

(3) Information provided includes the number and type of samples broken down by clinically relevant variant compared to two-way sequencing or other FDA-identified methods as appropriate. Precision, defined as positive percent agreement (PPA) and negative percent agreement (NPA), should be measured; Point estimates of precision must be greater than 99 percent (both per variant reported and overall) and the uncertainty of the point estimate must be presented using the 95 percent confidence interval. Clinical samples must contain homozygous wild-type and heterozygous genotypes. The number of clinical samples for each reported variant to be included in the precision study should be based on the prevalence of the variant. For common variants (greater than 0.1 percent allele frequency in the ethnically relevant population), at least 20 distinct heterozygous clinical samples should be tested. For rare variants (less than or equal to 0.1 percent allele frequency in the ethnically relevant population), at least three distinct heterozygous mutant samples should be tested. Any no calls (dhno result) or invalid calls (z.B.,failure of quality control) in the study should be included in the results of the precision study and reported separately. Variants with a PPA or NPA point estimate of less than 99 percent (false test results compared to two-way sequencing or other methods identified by the FDA as appropriate) may not be included in test claims and reports. Precision measurements generated from clinical samples vs. artificial samples or cell lines must be submitted separately. Results should be summarized and tabulated by sample and genotype. The PPP point estimate should be calculated as the number of positive results divided by the number of samples known to harbor variants (mutations) with "no calls" or invalid calls. The NPA point estimate should be calculated for each reported variant as the number of negative results divided by the number of wild-type samples tested with no "no call" or invalid calls. Point estimates should be calculated along with two-sided 95 percent confidence intervals.

(4) Provide information on the clinical positive predictive value (PPV) and negative predictive value (NPV) of the carrier state (and for each variant, if possible) in each population. Specifically, to calculate the PPV and NPV, estimate the test coverage (TC) and the percentage of subjects with variant(s) included in the device among all carriers: PPV = (PPA * TC * Ï? )/(PPP * TC * Ï? + (1 – NPA) * (1 – Ï?)) and NPV = (NPA * (1 – Ï?))/(NPA * (1 – Ï?) + (1 – ?) ?PPA* TC) * Ï ?) where PPA and NPA in any of paragraphs (b)(3)(ii)(A)(4)(yo) or in Paragraph (b)(3)(ii)(A)(4)(yo) of this section and Ï? is the prevalence of carriers in the population (pretest risk of being a carrier of the disease).

(yo) For point estimates of PPP and NPA less than 100 percent, use the estimates calculated in the PPV and NPV calculations.

(yo) Point estimates of 100 percent may be subject to large uncertainty. If these variants are measured using highly multiplexed technology, calculate the random error rate for the entire device and integrate this rate into the PPA and NPA estimate as calculated previously. Then use these calculated estimates in the PPV and NPV calculations. This type of precision study is useful to determine that there is no systematic error in this type of device.

(B) Precision (reproducibility): Precision data should be generated using multiple instruments, multiple operators, multiple non-consecutive days, and multiple lots of reagents. The swatch panel must contain swatches with the claimed swatch type (z.B.Saliva samples) containing different genotypes (dhwild type, heterozygous). Performance criteria must be predefined. A detailed study protocol should be prepared before the study and followed afterward. The rate of "failed quality control" should be indicated. It must be clearly documented whether the results were generated from clinical samples, contrived samples, or cell lines. The results of the study should indicate, in tabular form, the variants tested in the study and the number of replicates for each variant, as well as the test conditions examined (dhnumber of runs, days, instruments, reagent lots, operators, samples/type, etc.). The study must include all nucleic acid extraction steps of the claimed sample or matrix type, unless a separate extraction study is performed for the claimed sample type. If the device is to be used in more than one laboratory, different laboratories must be included in the precision study (and reproducibility must be evaluated). The percentage of "no calls" or invalid calls, if any, in the study should be reported as part of the precision (reproducibility) study results.

(C) Analytical Specificity Data: Data should be generated evaluating the impact of potential endogenous and exogenous interfering substances relevant to the sample type on assay performance, assessment of cross-reactivity of alleles, and cross-reactive pseudogenes known, and evaluation of cross-reactivity. pollution.

(D) Analytical Sensitivity Data: Data must be generated showing the minimum amount of DNA that will allow the test to be performed accurately in 95 percent of runs.

(E) Instrument Stability Data: The manufacturer must establish upper and lower limits for input nucleic acid and sample stability that achieve the stated precision and reproducibility. The data supporting such claims should be described.

(F) Sample Type and Matrix Comparison Data: Sample and matrix type comparison data should be generated if more than one type of sample or anticoagulant can be tested on the instrument, including failure rates for the different types shows.

(iii) When the device is offered without a prescription, including where test results are provided directly to the consumer, the manufacturer must conduct a study to assess user understanding of the device labeling and testing procedure and provide a brief summary Summary of the results of the study. The following elements should be included in the user study:

(A) The test manufacturer shall conduct pre-test and post-test user comprehension studies to assess the user's ability to understand the potential results of a carrier test and their clinical significance. The comprehension test questions should directly assess the material presented to the user in the test reports.

(B) The test manufacturer shall make available to actual and potential recipients of test reports a bearer test training module. The module will define terms used in test reports and explain the meaning of bearer status.

(C) The user study must meet the following criteria:

(1) Study participants must be a statistically verified and demographically diverse population (determined using methods such as quota sampling) that is representative of the population of intended users. In addition, users must be of different ages and educational levels and have no previous experience with the test or its manufacturer. These factors must be clearly defined in the inclusion and exclusion criteria.

(2) All sources of bias (z.B.,non-responders) should be pre-defined and accounted for in the study results in terms of responders and non-responders.

(3) Tests should follow a format in which users have a limited time to complete the studies (for example, a single-visit site survey format with a limit on the maximum time a participant has to complete the tests ).

(4) Users should be randomly assigned to study arms. Test reports provided to users must: define the condition tested and associated symptoms; explain the purpose and limitations of the test; explain the relevant ethnic groups in relation to the tested variant; Explain the status of the carrier and the relevance to the ethnicity of the wearer; and provide links to additional information related to situations where the user has concerns about their test results or would like follow-up information, as indicated on the test label. The study is designed to assess participants' ability to understand the following comprehension concepts: limitations, purpose, and test results.

(5) Study participants should be untrained and naive about the subject of the study test and only receive the materials that will be available to them when the test is commercialized.

(6) The user comprehension study must meet predefined primary endpoints, including an overall comprehension rate of at least 90 percent or higher (dhChoose the correct answer) for each comprehension concept to show that the educational module and test reports are suitable for over-the-counter use.

(D) A summary of the user comprehension study must be provided that contains the following:

(1) Reporting results provided for each gene/variant/ethnicity tested.

(2) Statistical methods to analyze all data sets.

(3) completion rate, non-responder rate, and reasons for nonresponse/exclusion of data, and a summary table of comprehension rates for understanding concepts (test purpose, test scores, limitations of the test, ethnic relevance to test scores, etc.) for each study report.

(4) Your 21 CFR 809.10 compliant label and any generated test report must include the following warnings and disclaimers, as applicable:

(i) A disclaimer stating "The test is for the detection of autosomal recessive carriers in adults of childbearing age only."

(ii) A statement detailing, in plain language, the genetic coverage of the test, including, where applicable, information on variants not interrogated by the test and the proportion of reported diseases that are not related to the genes being tested ( is related. For example, where applicable, the statement should include a disclaimer that the test does not or may not detect all genetic variants associated with the genetic disease and that the absence of one variant tested does not exclude the presence of other genetic variants that may be disease related. Or, where appropriate, the statement should include a disclaimer that the basis of the disease for which genetic carrier status is being tested is unknown or considered non-heritable in a significant number of people who have the disease, and so on. successively. a negative test result does not exclude the possibility that the offspring may be affected by the disease. The statement would have to include any other caveats necessary to convey to consumers exactly how informative the carrier status test is.

(iii) For prescription tests, the following warnings, stating:

(A) "The results of this test are intended for interpretation by a board-certified clinical molecular geneticist or equivalent expert and should be used in conjunction with other available clinical and laboratory information."

(B) "This device is not intended for disease diagnosis, prenatal testing of fetuses, risk assessment, prognostic or presymptomatic testing, susceptibility testing, or newborn screening."

(iv) For over-the-counter tests, a statement that says: “This test is not intended to diagnose any disease or tell you about your risk of developing any disease in the future. This test alone is also not meant to tell you anything about the health of your fetus or your newborn's risk of developing a particular disease later in life."

(v) For over-the-counter tests, the following warnings, which read:

(A) “This test is not a substitute for visits to a health care provider. It is recommended that you contact a healthcare provider if you have any questions or concerns about your results.”

(B) “The test does not diagnose any health problems. Results should be used with other clinical information for medical purposes.”

(C) "The laboratory may not be able to process your sample. The probability that the laboratory will not be able to process your saliva sample may be up to [true percentage probability]."

(D) "Your ethnicity may affect the interpretation of your genetic health results."

(vi) For a positive result on an over-the-counter test, when the positive predictive value for a given population is less than 50 percent and greater than 5 percent, an alert is displayed stating "The positive result you received could have misled". to identify Consider genetic counseling and follow-up testing.”

(vii) For a positive result on an over-the-counter test, if the positive predictive value for a given population is less than 5 percent, a warning that reads "The positive result you received is highly likely to be false due to rarity of this variant Consider genetic counseling and follow-up testing."

(5) Tests conducted to comply with paragraph (b)(3) of this section shall demonstrate that the device meets or exceeds each of the following performance specifications:

(i) Accuracy must be shown to be equal to or greater than 99 percent for both PPA and NPA. Variants with a PPA or NPA point estimate of less than 99 percent (false test results compared to two-way sequencing or other methods identified by the FDA as appropriate) may not be included in test claims and reports.

(ii) The precision yield (reproducibility) must meet or exceed 99 percent for positive and negative results.

(iii) The User Comprehension Study must achieve User Comprehension scores of 90 percent or higher for each comprehension concept.

(6) Distribution of this device, other than the sampling device described in paragraph (b)(2) of this section, is restricted to the manufacturer, subsidiaries of the manufacturer, and laboratories covered by the Laboratory Improvement Amendments Clinical.

[80 FR 65630, Oct. 27, 2015, amended 82 FR 51570, Nov. 7, 2017]

(a)ID.A genetic health risk assessment system is an in vitro qualitative molecular diagnostic system designed to detect variants in genomic deoxyribonucleic acid (DNA) isolated from human samples and provide users with information about their genetic risk of developing a disease for help them choose their own Lifestyle Support and/or discussions with a naturopath. This rating system is designed for over-the-counter use. This device does not determine an individual's overall risk of developing a disease.

(b)Classification.Class II (special controls). The genetic health risk assessment system if you previously received a marketing authorization from the FDA for the first time (z.B.,510(k) Authorization) for the genetic health risk assessment system (a “genetic health risk assessment system after review by the FDA”) is exempt from the premarket notification procedures in the Part 807, Subpart E of this chapter, subject to the limitations in §866.9. The device must comply with the following specific controls:

(1) Unless otherwise noted, 21 CFR 809.10 compliant labeling and all pre-sale generated pages and test reports must include:

(i) A section addressed to users that provides the following information:

(A) The qualification statement explaining that this test provides genetic risk information based on evaluation of specific genetic variants, but does not reflect a user's complete genetic profile. This test [may not] detect all genetic variants associated with a particular disease, and the absence of a tested variant does not exclude the presence of other genetic variants that may be associated with the disease.

(B) The qualifying statement that other companies offering a genetic risk test may detect different genetic variants for the same disease, so the user may obtain different results using a test from another company.

(C) The qualifying statement, which explains that other factors, such as environmental and lifestyle risk factors, may affect the risk of developing a particular disease.

(D) The qualifying statement, which explains that some people may be afraid of receiving health results from genetic testing. That's normal. If the potential user is very anxious, they should talk to their doctor or other healthcare professional before taking a sample for testing. This test does not replace a visit to a doctor or other health professional. Users should consult their physician or other healthcare professional if they have any questions or concerns about their test results or their current medical condition.

(E) Information on how to access a genetic counselor, board-certified clinical molecular geneticist, or equivalent healthcare professional about the results of a user test.

(F) The qualifying statement that this test is not intended to diagnose any disease, tell you anything about your current medical condition, or be used to make medical decisions, including whether to take any medication or how much medication to take. .

(G) A statement of qualification showing that the laboratory may not be able to process a sample and, if applicable, a description of the next steps to be taken by the manufacturer and/or customer.

(ii) A section in its 21 CFR 809.10 labeling and any test report generated, intended for healthcare professionals who can obtain test results from their patients with the following information:

(A) The qualifying statement that this test is not intended to diagnose any disease, determine medical treatment, or inform the user of their current medical condition.

(B) The qualification statement explaining that this test is intended to provide users with their genetic information to assist them in lifestyle choices and discussions with their physician or other healthcare professional.

(C) The qualification statement, which states that all diagnostic or treatment decisions should be based on evidence and/or other information you deem appropriate for your patient.

(2) Genetic testing must use an FDA-approved or 510(k)-exempt classified specimen collection device with an indication for in vitro diagnostic use in over-the-counter DNA testing.

(3) The device label shall include a hyperlink to the manufacturer's public website where the manufacturer makes the information referred to in paragraph (b)(3) of this Section available to the public. The manufacturer's home page, as well as the main part of the manufacturer's website dealing with the device, must contain a hyperlink to the web page containing this information and allow unrestricted viewing access. If the Device can be purchased on the Website or trials using the Device can be ordered on the Website, the same information must be available on the Device ordering web page or provided in a publicly accessible hyperlink on the Website. Device ordering website. Any changes to the device that could significantly affect its safety or effectiveness would require new data or information to support those changes, which should also be posted on the manufacturer's website. The information must contain:

(i) A list of the material provided to meet the requirements of paragraph (b)(3) of this Section and its location.

(ii) A section that highlights summary information that allows the user to understand how the test works and how to interpret the test results. This section must be written at least in simple language understandable to laymen and must contain the following:

(A) Consistent explanations of disease risk associated with all variants included in the test. In the case of different risk categories, the manufacturer must provide references that support the different risk categories. If there will be multiple test reports and multiple variants, the risk categories should be defined similarly to each other. For example, "increased risk" should be defined similarly between different test reports and different combinations of variants.

(B) Clear context for the user to understand the context in which the cited clinical performance data supports the reported risk. This includes, but is not limited to, all risks influenced by ethnicity, age, gender, environment and lifestyle.

(C) Materials that explain the key concepts and terminology used in the test, including:

(1)The definition:Scientific terms used in test reports.

(2)Pre-sale page:This page should contain information informing the user of what information the test will provide. This includes, but is not limited to, information about variants, the condition or disease associated with the variant(s), professional policy recommendations for general genetic risk testing, limitations associated with the test (z.B.,test does not detect all variants associated with the disease) and any precautions about the test that the user should consider before purchasing. If the test reports the risk of a life-threatening or irreversibly debilitating disease or condition for which there are few or no options to prevent, treat, or cure the disease, an acceptance section must be provided for the user. This subscription page must be provided for each disease that falls into this category and must contain specific information relevant to each test result. The login page should contain the following:

(yo) An option to accept or decline to receive that specific test result;

(yo) specifying the risk involved in determining that the user has the result of the specific genetic test;

(iii) professional guidelines recommending when genetic testing is or is not recommended for the associated target disease; Y

(IV) A recommendation to speak with a physician, genetic counselor, or equivalent professional before receiving test results.

(3)Frequently asked questions (FAQ) page:This page should contain specific information for each variant/disease pair reported. The information in this section must be scientifically valid and documented by relevant publications. The FAQ page should include the health/disease condition tested, the purpose of the test, the information the test does and does not provide, the relevance of race and ethnicity to the test results, information about the population for which it is most applicable, the significance of the results, other risk factors contributing to the disease, appropriate follow-up procedures, how the test results may affect the user's family, including children, and links to resources that provide additional information Offer.

(iii) a technical information section containing the following information:

(A) Gene(s) and variant(s) recognized by the test using standardized nomenclature, Human Genome Organization nomenclature and coordinates, and reference SNP numbers (rs#) from the polymorphism database of single nucleotide (dbSNP).

(B) Scientifically proven disease risk association of each variant detected and reported by the test. This risk association information will include:

(1) genotype-phenotype information for the reported variants.

(2) Table of expected frequency and risks of developing the disease in relevant ethnic populations and the general population.

(3) A statement of current professional guidelines for testing these specific genes and variants.

(yo) If professional guidelines are available, provide the recommendations in the professional guidelines for the gene, variant, and disease, when genetic testing should or should not be performed, and warnings to communicate when testing for a gene and variant in particular.

(yo) If scientific guidelines are not available, please provide a statement that scientific guidelines are not available for this specific gene(s) and variant(s).

(C) The type of sample (z.B.,saliva, capillary whole blood).

(D) Test steps and technology used.

(E) Specification of reagents, instruments and auxiliary equipment required.

(F) Specification of sample collection, processing, storage, and preparation methods.

(G) Specification of risk mitigation elements and description of additional procedures, methods, and practices incorporated into IFUs that mitigate risks associated with testing.

(H) Information about the probability of failing a test (dhpercentage of tests that failed QC) based on data from clinical samples, a description of scenarios in which a test may fail (dhlow sample volume, low DNA concentration, etc.), how users will be notified of a failed test, and the type of follow-up of a failed test that the user and manufacturer should take.

(I) Specification of criteria for interpreting and reporting test results.

(J) Information demonstrating the performance characteristics of the test, including:

(1) Accuracy of study results for each sample type claimed.

(yo) Assay precision should be assessed using fresh clinical specimens collected and processed in accordance with the assay instructions for use. When this is not practical, fresh clinical samples can be substituted or supplemented by archived clinical samples. Archived samples must have been collected in accordance with the instructions for use, stored properly, and randomly selected. In some limited circumstances, the use of artificial samples or samples from human cell lines may also be appropriate and used as an acceptable alternative. Samples from artificial or human cell lines are designed to mimic clinical samples as closely as possible and provide an unbiased assessment of device precision.

(yo) Precision should be assessed by comparison with two-way Sanger sequencing or other methods identified by the FDA as appropriate. Performance criteria for both the comparison method and the device must be predefined and appropriate for the intended use of the device. Detailed study protocols should be submitted.

(iii) Test samples must contain all genotypes to be included in tests and reports. The number of samples tested in the precision study for each variant reported should be based on the frequency of the variant, using the minimum number of samples specified in this paragraph or, if deemed appropriate and identified by FDA, a minimum number determined by a sample alternative. is method used. Where appropriate, the same samples can be used in tests to demonstrate test precision for multiple genotypes by generating sequence information at multiple genetic sites of interest. At least 20 unique samples representing the wild-type genotype must be tested. To test samples heterozygous for the reported variant(s), common variants (>0.1 percent variant frequency in the relevant population) should be tested with at least 20 unique samples. Rare variants (≥0.1 percent variant frequency in the relevant population) should be tested with at least three unique samples. To test specimens homozygous for the reported variant(s), variants with a variant frequency of ≥2 percent should be tested in a relevant population of at least 20 unique specimens. Variants with a frequency of < 2 percent and ≤ 0.5 percent in the relevant population should be tested with at least 10 individual samples. Variants with a frequency of <0.5 percent in the relevant population should be tested with at least three unique samples. If no variants with a frequency of <0.5 percent are found within the relevant population and no homozygous samples are tested, then the test results for this homozygous rare variant should not be reported to the user.

(IV) Precision study information must include the number and type of samples compared using two-way Sanger sequencing or other FDA-identified methods as appropriate. This information should be reported in tabular form and organized by clinically relevant variant, or using another FDA-identified method as appropriate. As an example of samples with different DD, Dd and dd genotypes, the following table presents data from the precision study in tabular form:

(v) Precision represents the closeness of agreement between the device results and the comparison results. Accuracy should be assessed by measuring various percentages of agreement (PA) of the device results with the comparator results and the percentage of invalid or no calls. Calculate the rate of non-calls and invalid calls for each comparator output as %Inv(DD) = A4/NDD, %Inv(Dd) = B4/NDd, %Inv(dd) = C4/Ndd. If it is not necessary to retest calls or invalid calls according to the instructions for use of the device, the final percentage of invalid calls or no calls should be reported. In the precision study results table, use only the final results (dhafter retesting the initial "no calls" or "invalid calls" if necessary according to the instructions for use). Samples that result in a "no call" or "invalid call" after retesting should not be included in final settlement calculations. If the percentages of "no calls" or "bad calls" are similar for each comparator output, combine these estimates as (A4 + B4 + C4)/(NDD + NDd + Ndd) and give a 95 percent confidence interval. bilateral cent. The percentage of final "no calls" or "invalid calls" should be clinically acceptable.

(vi) Point estimates of percent agreement for each genotype should be calculated as the number of correct tests for that genotype divided by the number of samples known to contain that genotype, excluding "no tests" or "invalid tests". The calculations should be done as follows:

(viii) For percentage matches for DD, Dd and dd (PA(DD|DD), PA(Dd|Dd) and PA(dd|dd)) as in paragraph (b)(3)(iii)(J)(1)(vi) of this section, two-sided 95 percent confidence intervals should be given. Precision point estimates for percent agreement for DD, Dd, and dd should be ≥ 99 percent per variant reported and overall. Any variant that has a point estimate for PA(DD|DD), PA(Dd|Dd), or PA(dd|dd) of <99 percent compared to bidirectional sequencing or other methods identified by the FDA as appropriate are disqualified. will be included in claims and test reports. Precision results for clinical samples compared to contrived samples or cell lines should be reported separately. Results must be summarized and tabulated by sample type and genotype, or reported using another FDA-identified method as appropriate (see paragraph (b)(3)(iii)(J)(1)(IV) of this section).

(viii) Information on the technical positive predictive value (TPPV) related to the analytical (technical) performance of the device for genotypes in each relevant subpopulation (z.B.,ethnicity, gender, age, geographic location, etc.). TPPV is the percentage of individuals with the genotype actually present among individuals whose test reports indicate that the genotype is present. The TPPV depends on the precision measures of the percentage agreement and the frequency of the genotypes in the subpopulation examined. f(DD) is the frequency of DD and f(Dd) is the frequency of Dd in the studied subpopulation; TPPV shall, as specified in paragraphs (b)(3)(iii)(J)(1)(ix) through (xi) of this section.

(ix) For variants where the point estimates of PA(DD|DD), PA(Dd|Dd), and PA(dd|dd) are less than 100%, use these point estimates in the TPPV calculations.

(X) Point estimates of 100 percent in the precision study can have a large uncertainty about the performance of the test in the population. If these variants are measured using highly multiplexed technology, calculate the random error rate for the entire device. The purpose of the precision study described in paragraph (b)(3)(iii)(J) of this section in these cases is more to establish that there is no systematic error in said equipment. In these cases, integrate this rate into the percent agreement calculation, as in paragraph (b)(3)(iii)(J)(1)(vi) of this section and include them in the TPPV calculations.

(xi) The TPPV for subpopulations with genotypic frequencies of f(dd), f(Dd) and f(DD) = 1 – f(dd) – f(Dd) in the subpopulation is calculated as follows:

(2) Precision and reproducibility data should be provided using multiple instruments, multiple operators, multiple non-consecutive days, and multiple reagent lots. The sample panel must contain samples of the claimed sample type (z.B.,saliva) representing all genotypes for each variant (z.B.,wild-type, heterozygous, and homozygous) or, if an alternate composition of the sample panel is identified as eligible by the FDA, a panel comprised of the FDA-identified eligible samples. In the run-up to the study, a detailed study protocol should be written, which should contain pre-defined acceptance criteria for performance results. The percentage of samples that did not pass the quality control must be reported (dhthe total number of replicate samples for which a sequence variant cannot be recovered (no withdrawals) or that do not meet sequencing quality control criteria divided by the total number of replicates tested). It must be clearly documented whether the results were generated from clinical samples, contrived samples, or cell lines. The results of the study should indicate the variants tested in the study and the number of replicates of each variant, as well as the conditions tested (dhnumber of runs, days, instruments, reagent lots, operators, samples/type, etc.). Results should be evaluated and presented in tabular form and stratified according to study parameters (z.B.,by location, instrument(s), reagent lot, operator, and sample variant). The study must include all extraction steps for the claimed sample or matrix type, unless a separate extraction reproducibility study is performed for the claimed sample type. If the device is to be used in more than one laboratory, different laboratories should be included in the reproducibility study and inter-site reproducibility should be assessed. Any null or invalid calls in the study should be reported as part of the precision and reproducibility study results.

(3)Analytical specificity data:Data should be provided evaluating the effect of potential endogenous and exogenous interferences on assay performance, including sample extraction and variant detection. The interference tested must include interference that is reasonably likely to be potentially relevant to the type of sample used with the device.

(4)Disturbing Variant Facts:Nucleotide mutations that can disrupt the technology must be identified and evaluated. Data must be provided to demonstrate the impact of the offending variants on the execution of successful calls. Alternatively, for each suspected interfering mutation for which no data supporting the effect of the interfering variant is presented, the manufacturer must identify the suspected interfering variants on the label and state that the effects that the interfering variants may have on Assay performance has not occurred by providing a statement that reads: "It is possible that the presence of [insert unique identifying information for the suspected interfering variant] in a sample could affect the performance of this assay. However, this has not been studied in any way on the performance of this test."

(5)Analytical Sensitivity Data:Data must be provided demonstrating the minimum amount of DNA that will allow the test to be performed correctly 95 percent of the time.

(6)Reagent stability:The manufacturer must evaluate the stability of the reagents using wild type, heterozygous and homozygous samples. Reagent stability data must demonstrate that the reagents maintain their stated precision and reproducibility. Data should be provided to support such claims.

(7)Sample Type and Matrix Comparison Data:Matrix and sample type comparison data should be generated if more than one sample type can be tested with this instrument, including failure rates for the different samples.

(K) Summary of clinical performance.

(1) Information must be provided to support the clinical performance of each variant reported by the test.

(2) Manufacturers should organize the information according to the specific combination of variants (z.B.,wild-type, heterozygous, homozygous, compound heterozygous, hemizygous genotypes). For each combination of variants, information should be provided in the clinical performance section to describe the clinical performance for the risk category (z.B.,no risk, higher risk). For each combination of variants, a summary of the key results must be provided in tabular form or using another method identified by the FDA as appropriate to provide the appropriate variant type, data source, definition of target condition (z.B.,target disease), clinical criteria to determine whether the target disease is present or absent, description of subjects with target disease present and target disease absent (exclusion or inclusion criteria), and technical procedure for genotyping. If available, information should be provided on the effect of the variant on the risk of a disease (lifetime risk or lifetime incidence) for an individual compared to the risk for the general population.

(yo) When odds ratios are available, using information on the distribution of genotypes among individuals lacking a target disease or in the general population, or information on risk variant frequencies and odds ratios, the likelihood ratios for the device corresponding values ​​are calculated along with 95 percent confidence intervals. Using information about the risk before the test (Ï?), an estimate of the likelihood ratio (LR), and a relationship between the risk after the test R as R/(1â??R) = LR-Ï?/ (1â ?? Ï?) , the post-test risk R must be calculated.

(yo) If available, the likelihood ratios (LRs) for the results of various tests must be presented in tabular form together with references to the source data or using another method identified by FDA as appropriate pursuant to paragraph (b)( 3)(iii)(K)(2) this section. When these values ​​are not directly available in the published literature, the likelihood ratios can be calculated separately, along with the 95 percent confidence interval, with references to the source data. Note that a minimum requirement for the existence of a variance effect on risk is that a corresponding LR be statistically greater than 1 (a lower limit of the two-sided 95 percent confidence interval is greater than 1). This means that the post-test risk is statistically higher than the pre-test risk (an observed value of the difference between the post-test and pre-test risk).

(L) Materials that explain the key concepts and terminology used in the test, including, but not limited to:

(1)The definition:Scientific terms used in test reports.

(2)Pre-sale page:This page should contain information that informs the user of what the test will return. This includes, but is not limited to, information about variants, the condition or disease associated with the variant(s), professional policy recommendations for general genetic risk testing, limitations associated with the test (z.B.,test does not detect all variants associated with the disease) and any precautions about the test that the user should consider before purchasing. If the test reports the risk of a life-threatening or irreversibly debilitating disease or condition for which there are few or no options to prevent, treat, or cure the disease, an acceptance section must be provided for the user. This subscription page must be provided for each disease that falls into this category and must contain specific information relevant to each test result. The login page should contain the following:

(yo) An option to accept or decline to receive that specific test result;

(yo) specifying the risk involved in determining that the user has the result of the specific genetic test;

(iii) professional guidelines recommending when genetic testing is or is not recommended for the associated target disease; Y

(IV) A recommendation to speak with a physician, genetic counselor, or equivalent professional before receiving test results.

(3) Frequently Asked Questions (FAQ) Page: This page should contain specific information for each variant/disease pair reported. The information in this section must be scientifically valid and documented by relevant publications. The FAQ page should include the health/disease condition being tested, the purpose of the test, the information the test does and does not provide, the relevance of race and ethnicity to the test results, information about the population for which it is most applicable, the significance of the results, other risk factors contributing to the disease, appropriate follow-up procedures, how the test results may affect the user's family, including children, and links to resources with additional information.

(M) User Understanding Study: Information must be provided on a study that assesses the understanding of the test procedure and results by potential test users.

(1) The test manufacturer must provide inexperienced User Understanding Study participants with a genetic risk education module prior to their participation in the User Understanding Study. The module will define the terms used in test reports and explain the meaning of genetic risk reports.

(2) The test manufacturer must perform user comprehension studies before and after the test. Comprehension test questions must involve direct assessment of a representative sample of the material presented to the user, as described in paragraph (b)(3)(ii) of this section.

(3) The manufacturer must provide justification from a physician and/or genetic counselor identifying the appropriate general and variant-specific concepts included in the material tested in the user comprehension study to ensure that all relevant concepts are included in the study.

(4) The user study must meet the following criteria:

(yo) Study participants must include a statistically sufficient sample size and a demographically diverse population (determined using methods such as quota sampling) that is representative of the population of intended users. In addition, study participants must be of different ages and educational levels and must have no previous experience with the test or its manufacturer. These factors must be well defined in the inclusion and exclusion criteria.

(yo) All sources of bias should be predefined and accounted for in the study results in terms of responders and nonresponders.

(iii) Tests should follow a format in which users have a limited time to complete the studies (for example, a single-visit site survey format with a limit on the maximum time a participant has to complete the tests ).

(IV) Users should be randomly assigned to study arms. User understanding study test reports provided to users should define the target condition to be tested and associated symptoms, explain the intended use and limitations of the test, explain relevant ethnicities in relation to the variant proven, genetic risks to health and relevance. to the user's ethnicity and assess participants' ability to grasp the following comprehension concepts: test limitations, purpose, appropriate action, test scores, and other factors that may affect test results.

(v) Study participants must be untrained, naive to the subject of the study, and given the label before beginning the user comprehension study.

(vi) The user comprehension study must meet predefined primary endpoints, including an overall comprehension rate of at least 90 percent or higher (dhChoose the correct answer) for each comprehension concept. Depending on the concept tested, other acceptance criteria may also be acceptable. Meeting or exceeding this general comprehension rating indicates that the materials presented to the user are appropriate for non-prescription use.

(viii) Analysis of user comprehension results should include the results related to the reports provided for each gene/variant/ethnicity tested, the statistical methods used to analyze all data sets, and the completion rate, non-responder rate and the reasons for non-response/exclusion of data. A summary table of comprehension rates for comprehension concepts (z.B.,test purpose, test scores, test limitations, relevance of race to test scores, etc.) for each study report should be included.

(4) The intended use of the device must not include the following instructions for use:

(i) prenatal tests;

(ii) determine predisposition to cancer when the test result may lead to prophylactic screening, confirmatory procedures, or treatment that may result in morbidity or mortality to the patient;

(iii) assess for the presence of genetic variants that affect the metabolism, exposure, response, risk of adverse events, dosing, or mechanisms of prescription or over-the-counter drugs; either

(iv) evaluation of the presence of deterministic dominant autosomal variants.

[82 FR 51561, November 7, 2017, modified 83 FR 25914, June 5, 2018]

(a)ID.A tumor-associated antigen immunoassay system is a device consisting of reagents used for the qualitative or quantitative measurement of tumor-associated antigens in serum, plasma, urine, or other body fluids by immunochemical techniques. This device is intended as an aid to monitor patients for disease progression or response to therapy, or to detect recurrent or residual disease.

(b)Classification.Class II (special controls). Tumor markers must comply with the following specific controls: (1) A guidance document titled "Guidance Document for Submitting Premarket Tumor-Associated Antigen (510(k)s) Notifications to the FDA" and ( 2) voluntary test performance standards issued by the National Committee for Clinical Laboratory Standards.

[62 FR 66005, December 17, 1997]

(a)ID.A system for selecting and counting immunomagnetic circulating cancer cells is a device composed of biological probes, fluorochromes, and other reagents; preservation and preparation devices; and a semi-automated analytical instrument for selecting and counting circulating cancer cells in a prepared whole blood sample. This device is intended for adjunctive use in monitoring or predicting cancer progression, response to therapy, and detection of recurrent disease.

(b)Classification.Class II (special controls). The specific control for this device is the FDA guidance document titled Class II Special Controls Guidance Document: Immunomagnetic Circulating Cancer Cell Enumeration and Selection System. See §866.1(e) for the availability of this guidance document.

[69 FR 26038, May 11, 2004]

(a)ID.An AFP-L3% Immunoassay System is an in vitro device consisting of reagents and an automated instrument used for the quantitative measurement of AFP and AFP-L3 subfraction in human serum by immunochemical techniques. The device is intended for in vitro diagnostic use to aid in the risk assessment of patients with chronic liver disease for the development of hepatocellular carcinoma in conjunction with other laboratory findings, imaging studies, and clinical evaluation.

(b)Classification.Class II (special controls). The special control is the FDA guidance document titled Class II Special Controls Guidance Document: AFP-L3% Immunoassay Systems. See §866.1(e) for the availability of this guidance document.

[70 FR 57749, October. 4, 2005]

(a)ID.A breast cancer prognostic gene expression profiling test system is a device that measures the ribonucleic acid (RNA) expression level of multiple genes and combines this information to obtain a signature (pattern, classifier, or index) for predict the prognosis of previously diagnosed breast cancer. .

(b)Classification.Class II (special controls). The special control is the FDA guidance document titled Class II Special Controls Guidance Document: Gene Expression Profiling Test System for Breast Cancer Prognosis. See §866.1(e) for the availability of this guidance document.

[72 FR 26291, May 9, 2007]

(a)ID.An ovarian/adnexal bulk test system is a device that measures one or more proteins in serum or plasma. It provides a single result for the probability that an adnexal mass is malignant in a woman scheduled for surgery. The test is designed for adjunctive use in the context of negative primary clinical and radiological evaluation to improve identification of patients whose gynecologic surgery requires oncologic expertise and resources.

(b)Classification.Class II (special controls). The specific control for this device is the FDA guidance document titled Class II Special Controls Guidance Document: Ovarian Adnexal Mass Assessment Scoring Test System. For the availability of this guide,ver§ 866.1(e).

(C)Black box warning.Pursuant to Section 520(e) of the Federal Food, Drug, and Cosmetic Act, these devices are subject to the following restriction: A warning notice must be placed in a black box and appear on all advertisements, labels, and materials promotions for these devices. This warning should say:

[76 FR 16294, Mar 23, 2011, changed to 76 FR 82131, Dec 30, 2011]

(a)ID.A BCR-ABL quantification test is presented as a reverse transcription quantitative polymerase chain reaction (RT-qPCR) test for the quantification of BCR-ABL1 expressed on the international scale (IS) and control transcripts on the Total RNA from whole blood of diagnosed patients. identified (9;22) positive patients with chronic myeloid leukemia (CML) during follow-up of treatment with tyrosine kinase inhibitors. This test is not intended to diagnose chronic myeloid leukemia.

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

(1) Premarket notices must include the following information:

(i) The indication for use should indicate the variant(s) for which the assay has been developed and validated, e.g. BCR-ABL e13a2 and/or e14a2.

(ii) A detailed description of each test component, including the following:

(A) A detailed description of the test components, all required reagents, instruments, and equipment, including illustrations or photographs of non-standard equipment or methods;

(B) Detailed documentation for device software, including, but not limited to, stand-alone software applications and hardware-based devices that contain software;

(C) Methodology and protocols for trial control procedures to enable international reporting;

(D) a description of the results, the analytical sensitivity of the assay, and the range of values ​​to be reported; Y

(E) A description of the appropriate internal and external controls that are recommended or provided. The description should identify the control elements involved in the test procedure.

(iii) information demonstrating the performance characteristics of the test, including:

(A) For threshold-based indications for use of such a generic predicate device, product performance data from a method comparison study with the predicate device or from a clinical study demonstrating clinical validity using well-characterized data obtained prospectively or retrospectively, where appropriate, clinical samples representative of the intended use population;

(B) For indications for use based on a threshold not established in a predicate device of this generic type, device performance data from a clinical study demonstrating clinical validity using well-characterized clinical samples obtained prospectively or retrospectively, and designed for their intended uses are representative. for population use;

(C) Instrument reproducibility data generated using at least three sites, at least two of which must be remote sites, with two operators at each site. Each site must perform a minimum of three runs per operator on non-consecutive days to test for at least five different concentrations of BCR-ABL that are distributed in the measurement area and are well distributed and contain MR3 (0.1 percent IS). Results will be reported as standard deviation and percent coefficient of variation for each level tested. Predetermined acceptance criteria must be provided and followed;

(D) device precision data using clinical samples to assess within-lot, between-lot, within-cycle, between-cycle, and total variation;

(E) Instrument linearity data using a dilution panel constructed from clinical samples;

(F) Analytical sensitivity data for the device, including limit of blank, limit of detection, and limit of quantification;

(G) device specificity data, including interferences and cross contamination; Y

(H) Instrument stability data, including real-time stability of samples at various storage times, temperatures, and freeze-thaw conditions.

(iv) Identification of risk mitigation elements used by your device, including a detailed description of additional procedures, methods, and practices incorporated into the instructions for use that mitigate the risks associated with testing your device.

(2) Your 21 CFR 809.10 compliant label must include:

(i) The intended use label of your complaint pursuant to 21 CFR 809.10(a)(2) and (b)(2) must include an intended use statement that reads: "This test is not intended to diagnose CML "; Y

(ii) A detailed description of the performance studies conducted to comply with paragraph (b)(1)(iii) of this Section and a summary of the results.

(3) Your instrument output must include International Scale (IS) results and your assay must include multi-point calibration controls traceable to a relevant international reference panel (z.B.,the International Genetic Reference Panel of the World Health Organization to quantify BCR-ABL mRNA).

[82 FR 50532, Nov. 1, 2017]

(a)ID.A next-generation sequencing (NGS)-based tumor profiling test is a qualitative in vitro diagnostic test intended for NGS analysis of tissue samples from malignant solid neoplasms to detect somatic mutations in a broad range of target genes to guide treatment of previously diagnosed patients. cancer patients by qualified medical professionals.

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

(1) Premarket notices must include the following information:

(i) A detailed description of any somatic mutation intended to be detected by the test that is adequately documented in accordance with paragraph (b)(1)(v) of this section and reported in the test results in accordance with paragraph paragraph (b)(2)(iv) of this section, including:

(A) A list of mutations that are cancer mutations with indications of clinical significance.

(B) If applicable, a list of mutations that are cancer mutations with possible clinical significance.

(ii) The indications must express:

(A) The test is indicated for previously diagnosed cancer patients.

(B) The proposed sample type(s) and matrix (z.B.,formalin-fixed, paraffin-embedded tumor tissue).

(C) Die Mutationstypen (z.B.,single nucleotide variant, insertion, deletion, copy number variation, or gene rearrangement) for which validation data have been provided.

(D) Name of test facility(ies), if applicable.

(iii) A detailed description of the device including:

(A) A description of the test in terms of genomic coverage as follows:

(1) Tabulated summary of all reported mutations, grouped by gene and target region within each gene, together with the specific cDNA and amino acid positions for each mutation.

(2) A description of any target region within a gene that cannot be reported and data to support such a conclusion.

(B) Specifications for sample requirements, including all sample collection equipment and preservatives, sample volume, minimum tumor content, sample handling, DNA extraction, and criteria for test metrics. quality and quantity of DNA required to perform the assay.

(C) A detailed description of all required test components, reagents, instruments, and software. Detailed documentation of device software, including, but not limited to, software applications and hardware-based devices that contain software.

(D) A detailed description of the methodology and protocols for each test step, including a description of the quality metrics, thresholds, and filters implemented at each test step to report the final result, and a description of metrics for execution. -failures, pattern failures, invalids, as appropriate.

(E) A list of links that the device makes available to the user or that the device accesses for internal or external information (z.B.,Decision rules or databases) that demonstrate the clinical significance of the test results to the panel or its members in accordance with paragraphs (b)(1)(v) and (b)(2)(vi) of this Section.

(F) A description of the recommended or provided internal and external control controls and procedures. The description should identify the control elements involved in the test procedure.

(iv) Information to demonstrate the analytical validity of the device according to the analytical performance characteristics assessed specifically for each gene/mutation or, when clinically and practically justified, using a representative approach based on other mutations of the same type, including:

(A) Data that reasonably support the intended type of sample (z.B.,formalin-fixed, paraffin-embedded tumor tissue), sample handling and nucleic acid purification protocol for specific tumor types or for a pan-tumor claim.

(B) A summary of the empirical evidence obtained to demonstrate how analytical quality metrics and thresholds were optimized.

(C) Device precision data using clinical samples to adequately assess intra-assay, inter-assay, and overall variability. Samples must cover all mutation types tested (both positive and negative samples) and contain samples close to the detection limit of the instrument. Precision should be assessed by agreement within replicates of the final assay result for each representative mutation, where applicable, and also supported by sequencing quality metrics for target regions across the panel.

(D) Description of protocols and/or data that adequately demonstrate the interchangeability of multiplexing barcodes and reagent lots.

(E) A description of the nucleic acid assay input concentration range and evidence to reasonably support the range.

(F) A description of the data that reasonably supports the limit of detection of the device.

(G) A description of the data to adequately support the accuracy of the device, using clinical specimens that represent the intended specimen type and range of tumor types, if applicable.

(1) Clinical samples tested to support the accuracy of the device must adequately represent the list of cancer mutations with evidence of clinical significance that the device purports to detect.

(2) For mutations designated as cancer mutations with evidence of clinical significance and based on evidence found in the intended sample type (z.B.,tumor tissue), but for a different type of analyte (z.B.,protein, RNA) and/or a measurement (z.B.,with score or copy number) and/or with an alternative technology (z.B.,IHC, RT-qPCR, FISH), the accuracy test should include clinically adequate agreement between the mutation results and the medically established biomarker test (z.B.,Evidence from an appropriately sized method comparison study with clinical samples from the target population).

(3) For qualitative DNA mutations not specified in paragraph (b)(1)(iv)(G)(2) of this section, precision studies should include wild-type and mutation-positive results.

(H) Appropriate Device Stability Information.

(v) Information that adequately supports the clinical relevance of the panel shall include:

(A) The criteria established what types and levels of evidence clinically validate a mutation as a cancer mutation with evidence of clinical significance versus a cancer mutation with potential clinical significance.

(B) For mutations representative of mutations designated as cancer mutations, with an indication of clinical significance, a description of the clinical evidence associated with such mutations, such as: B. Clinical evidence presented in professional guidelines, where applicable, with performance data method reference as described in paragraph (b)(1)(iv)(G) of this section.

(C) For all other mutations identified as cancer mutations of possible clinical significance, a description of the reason for the notification.

(2) Labeling that complies with 21 CFR 809.10 and all product information and test reports generated must include the following, as applicable:

(i) The statement of intended use must indicate:

(A) The test is indicated for previously diagnosed cancer patients.

(B) The proposed sample type(s) and matrix (z.B.,formalin-fixed, paraffin-embedded tumor tissue).

(C) Die Mutationstypen (z.B.,single nucleotide variant, insertion, deletion, copy number variation, or gene rearrangement) for which validation data have been provided.

(D) Name of test facility(ies), if applicable.

(ii) A description of the product and a summary of the results of performance studies conducted pursuant to paragraphs (b)(1)(iii), (b)(1)(iv), and (b)(1) (v)) of this Section.

(iii) A description of the applicable limitations of the test, including an adequate description of the level of evidence and/or differences between next-generation sequencing results for device-specific mutations validated with method comparison data with an established test medically in the same type of sample provided. and medically established test results (z.B.,as described in professional guidelines).

(iv) A list of all somatic mutations intended to be detected by the device that are identified in the test results under the following two categories, or equivalent designations where applicable: "Cancer Mutation Panel with Indication of Clinical Significance" or "Cancer mutation panel with potential clinical significance."

(v) For mutations reported in the category “Potentially Clinically Significant Cancer Mutation Panel”, a qualifying statement stating: “For mutations reported in [Potentially Clinically Significant Cancer Mutation Panel or equivalent designation], the Clinical relevance not demonstrated [with sufficient clinical evidence (z.B.,per professional guidelines) in accordance with paragraph (b)(1)(v) of this section] or with this test.”

(vi) For mutations in the category "Cancer Mutation Panel with Evidence of Clinical Significance" or equivalent, link(s) for clinicians to access internal or external information on decision rules or conclusions on the level of evidence of significance of the marker mentioned in paragraph (b)(1)(v) of this section.

[83 FR 28995, June 22, 2018]