CFR - Code of Federal Regulations Title 21

The information on this page is current as of Dec 22, 2023.

For the most up-to-date version of CFR Title 21, go to the Electronic Code of Federal Regulations (eCFR).

[Code of Federal Regulations]

[Title 21, Volume 8]

[CITE: 21CFR866]

TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER H - MEDICAL DEVICES

PART 866 IMMUNOLOGY AND MICROBIOLOGY DEVICES

Subpart E - Immunology Laboratory Equipment and Reagents

Sec. 866.4070 RNA Preanalytical Systems.

(a) Identification. RNA Preanalytical Systems are devices intended to collect, store, and transport patient specimens, and stabilize intracellular RNA from the specimens, for subsequent isolation and purification of the intracellular RNA for RT-PCR used in in vitro molecular diagnostic testing.

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

[70 FR 49863, Aug. 25, 2005]

Sec. 866.4100 Complement reagent.

(a) Identification. A complement reagent is a device that consists of complement, a naturally occurring serum protein from any warm-blooded animal such as guinea pigs, that may be included as a component part of serological test kits used in the diagnosis of disease.

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

[47 FR 50823, Nov. 9, 2001, as amended at 66 FR 38792, July 25, 2001]

Sec. 866.4500 Immunoelectrophoresis equipment.

(a) Identification. Immunoelectrophoresis equipment for clinical use with its electrical power supply is a device used for separating protein molecules. Immunoelectrophoresis is a procedure in which a complex protein mixture is placed in an agar gel and the various proteins are separated on the basis of their relative mobilities under the influence of an electric current. The separated proteins are then permitted to diffuse through the agar toward a multispecific antiserum, allowing precipitation and visualization of the separate 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 at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001]

Sec. 866.4520 Immunofluorometer equipment.

(a) Identification. Immunofluorometer equipment for clinical use with its electrical power supply is a device used to measure the fluorescence of fluorochrome-labeled antigen-antibody complexes. The concentration of these complexes may be measured by means of reflected light. A beam of light is passed through a solution in which a fluorochrome has been selectively attached to serum protein antibody molecules in suspension. The amount of light emitted by the fluorochrome label is detected by a photodetector, which converts light energy into electrical energy. The amount of electrical energy registers on a readout system such as a digital voltmeter or a recording chart. This electrical readout is called the fluorescence value 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 at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001]

Sec. 866.4540 Immunonephelometer equipment.

(a) Identification. Immunonephelometer equipment for clinical use with its electrical power supply is a device that measures light scattering from antigen-antibody complexes. The concentration of these complexes may be measured by means of reflected light. A beam of light passed through a solution is scattered by the particles in suspension. The amount of light is detected by a photodetector, which converts light energy into electrical energy. The amount of electrical energy registers on a readout system such as a digital voltmeter or a recording chart. This electrical readout is called the light-scattering value and is used to measure the concentration of antigen-antibody complexes. This generic type of device includes devices with various kinds of light sources, such as laser 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 at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001]

Sec. 866.4600 Ouchterlony agar plate.

(a) Identification. An ouchterlony agar plate for clinical use is a device containing an agar gel used to examine antigen-antibody reactions. In immunodiffusion, antibodies and antigens migrate toward each other through gel which originally contained neither of these reagents. As the reagents come in contact with each other, they combine to form a precipitate that is trapped in the gel matrix and is immobilized.

(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 at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001]

Sec. 866.4700 Automated fluorescence in situ hybridization (FISH) enumeration systems.

(a) Identification. An automated FISH enumeration system is a device that consists of an automated scanning microscope, image analysis system, and customized software applications for FISH assays. This device is intended for in vitro diagnostic use with FISH assays as an aid in the detection, counting and classification of cells based on recognition of cellular color, size, and shape, and in the detection and enumeration of FISH signals in interphase nuclei of formalin-fixed, paraffin-embedded human tissue specimens.

(b) Classification. Class II (special controls). The special control is FDA's guidance document entitled "Class II Special Controls Guidance Document: Automated Fluorescence in situ Hybridization (FISH) Enumeration Systems." See § 866.1(e) for the availability of this guidance document.

[70 FR 14534, Mar. 23, 2005]

Sec. 866.4750 Automated indirect immunofluorescence microscope and software-assisted system.

(a) Identification. An automated indirect immunofluorescence microscope and software assisted system is a device that acquires, analyzes, stores, and displays digital images of indirect immunofluorescent slides. It is intended to be used as an aid in the determination of antibody status in clinical samples. The device may include a fluorescence microscope with light source, a motorized microscope stage, dedicated instrument controls, a camera, a computer, a sample processor, or other hardware components. The device may use fluorescent signal acquisition and processing software, data storage and transferring mechanisms, or assay specific algorithms to suggest results. A trained operator must confirm results generated with the device.

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

(1) The labeling for the device must reference legally marketed assays intended for use with the device.

(2) Premarket notification submissions must include the following information:

(i) A detailed description of the device that includes:

(A) A detailed description of instrumentation and equipment, and illustrations or photographs of non-standard equipment or methods, if applicable;

(B) Detailed documentation of the software, including, but not limited to, stand-alone software applications and hardware-based devices that incorporate software, if applicable;

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

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

(E) Methodology and protocols for detecting fluorescence and visualizing results; and

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

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

(A) A comparison study of the results obtained with the conventional manual method (i.e., reference standard), the device, and the reading of the digital image without aid of the software, using the same set of patient samples for each. The study must use a legally marketed assay intended for use with the device. Patient samples must be from the assay-specific intended use population and differential diagnosis population. Samples must also cover the assay measuring range, if applicable;

(B) Device clinical performance established by comparing device results at multiple U.S. sites to the clinical diagnostic standard used in the United States, using patient samples from the assay-specific intended use population and the differential diagnosis population. For all samples, the diagnostic clinical criteria and the demographic information must be collected and provided. Clinical validation must be based on the determination of clinical sensitivity and clinical specificity using the test results (e.g., antibody status based on fluorescence to include pattern and titer, if applicable) compared to the clinical diagnosis of the subject from whom the clinical sample was obtained. The data must be summarized in tabular format comparing the result generated by automated, manual, and digital only interpretation to the disease status;

(C) Device precision/reproducibility data generated from within-run, between-run, between-day, between-lot, between-operator, between-instruments, between-site, and total precision for multiple nonconsecutive days (as applicable) using multiple operators, multiple instruments and at multiple sites. A well-characterized panel of patient samples or pools from the associated assay specific intended use population must be used;

(D) Device linearity data generated from patient samples covering the assay measuring range, if applicable;

(E) Device analytical sensitivity data, including limit of blank, limit of detection, and limit of quantitation, if applicable;

(F) Device assay specific cutoff, if applicable;

(G) Device analytical specificity data, including interference by endogenous and exogenous substances, if applicable;

(H) Device instrument carryover data, if applicable;

(I) Device stability data including real-time stability under various storage times and temperatures, if applicable; and

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

(iii) Identification of risk mitigation elements used by the device, including description of all additional procedures, methods, and practices, incorporated into the directions for use that mitigate risks associated with testing.

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

(i) A warning statement that reads "The device is for use by a trained operator in a clinical laboratory setting";

(ii) A warning statement that reads "All software-aided results must be confirmed by the trained operator";

(iii) A warning statement that reads "This device is only for use with reagents that are indicated for use with the device"; and

(iv) A description of the protocol and performance studies performed in accordance with paragraph (b)(2)(ii) of this section and a summary of the results, if applicable.

[82 FR 52648, Nov. 14, 2017, as amended at 86 FR 20283, Apr. 19, 2021]

Sec. 866.4800 Radial immunodiffusion plate.

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

(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 at 66 FR 38792, July 25, 2001]

Sec. 866.4830 Rocket immunoelectrophoresis equipment.

(a) Identification. Rocket immunoelectrophoresis equipment for clinical use is a device used to perform a specific test on proteins by using a procedure called rocket immunoelectrophoresis. In this procedure, an electric current causes the protein in solution to migrate through agar gel containing specific antisera. The protein precipitates with the antisera in a rocket-shaped pattern, giving the name to the device. 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 at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001]

Sec. 866.4900 Support gel.

(a) Identification. A support gel for clinical use is a device that consists of an agar or agarose preparation that is used while measuring various kinds of, or parts of, protein molecules 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 at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001]

Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
Source: 47 FR 50823, Nov. 9, 1982, unless otherwise noted.