(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 software may include 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.