Document ID: FDA-2017-N-5881-0001
Agency: fda
Document Type: Rule
Title: Medical Devices; Immunology and Microbiology Devices; Classification of the Automated Indirect Immunofluorescence Microscope and Software-Assisted System
Posted Date: 2017-11-14T05:00Z

[Federal Register Volume 82, Number 218 (Tuesday, November 14, 2017)]
[Rules and Regulations]
[Pages 52647-52649]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-24585]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2017-N-5881]

Medical Devices; Immunology and Microbiology Devices; 
Classification of the Automated Indirect Immunofluorescence Microscope 
and Software-Assisted System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA or we) is classifying 
the automated indirect immunofluorescence microscope and software-
assisted system into class II (special controls). The special controls 
that apply to the device type are identified in this order and will be 
part of the codified language for the automated indirect 
immunofluorescence microscope and software-assisted system's 
classification. We are taking this action because we have determined 
that classifying the device into class II (special controls) will 
provide a reasonable assurance of safety and effectiveness of the 
device. We believe this action will also enhance patients' access to 
beneficial innovative devices, in part by reducing regulatory burdens.

DATES: This order is effective November 14, 2017. The classification 
was applicable on April 9, 2015.

FOR FURTHER INFORMATION CONTACT: Steven Tjoe, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 4550, Silver Spring, MD 20993-0002, 301-796-5866, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the automated indirect 
immunofluorescence microscope and software-assisted system as class II 
(special controls), which we have determined will provide a reasonable 
assurance of safety and effectiveness. In addition, we believe this 
action will enhance patients' access to beneficial innovation, in part 
by reducing regulatory burdens by placing the device into a lower 
device class than the automatic class III assignment.
    The automatic assignment of class III occurs by operation of law 
and without any action by FDA, regardless of the level of risk posed by 
the new device. Any device that was not in commercial distribution 
before May 28, 1976, is automatically classified as, and remains 
within, class III and requires premarket approval unless and until FDA 
takes an action to classify or reclassify the device (see 21 U.S.C. 
360c(f)(1)). We refer to these devices as ``postamendments devices'' 
because they were not in commercial distribution prior to the date of 
enactment of the Medical Device Amendments of 1976, which amended the 
Federal Food, Drug, and Cosmetic Act (the FD&C Act).
    FDA may take a variety of actions in appropriate circumstances to 
classify or reclassify a device into class I or II. We may issue an 
order finding a new device to be substantially equivalent under section 
513(i) of the FD&C Act (21 U.S.C. 360c(i)) to a predicate device that 
does not require premarket approval. We determine whether a new device 
is substantially equivalent to a predicate by means of the procedures 
for premarket notification under section 510(k) of the FD&C Act and 
part 807 (21 U.S.C. 360(k) and 21 CFR part 807, respectively).
    FDA may also classify a device through ``De Novo'' classification, 
a common name for the process authorized under section 513(f)(2) of the 
FD&C Act. Section 207 of the Food and Drug Administration Modernization 
Act of 1997 established the first procedure for De Novo classification 
(Pub. L. 105-115). Section 607 of the Food and Drug Administration 
Safety and Innovation Act modified the De Novo application process by 
adding a second procedure (Pub. L. 112-144). A device sponsor may 
utilize either procedure for De Novo classification.
    Under the first procedure, the person submits a 510(k) for a device 
that has not previously been classified. After receiving an order from 
FDA classifying the device into class III under section 513(f)(1) of 
the FD&C Act, the person then requests a classification under section 
513(f)(2).
    Under the second procedure, rather than first submitting a 510(k) 
and then a request for classification, if the person determines that 
there is no legally marketed device upon which to base a determination 
of substantial equivalence, that person requests a classification under 
section 513(f)(2) of the FD&C Act.
    Under either procedure for De Novo classification, FDA is required 
to classify the device by written order within 120 days. The 
classification will be according to the criteria under section 
513(a)(1) of the FD&C Act. Although the device was automatically placed 
within class III, the De Novo classification is considered to be the 
initial classification of the device.
    We believe this De Novo classification will enhance patients' 
access to beneficial innovation, in part by reducing regulatory 
burdens. When FDA classifies a device into class I or II via the De 
Novo process, the device can serve as a predicate for future devices of 
that type, including for 510(k)s (see 21 U.S.C. 360c(f)(2)(B)(i)). As a 
result, other device sponsors do not have to submit a De Novo request 
or premarket approval application (PMA) in order to market a 
substantially equivalent device (see 21 U.S.C. 360c(i), defining 
``substantial equivalence''). Instead, sponsors can use the less-
burdensome 510(k) process, when necessary, to market their device.

II. De Novo Classification

    For this device, FDA issued an order on November 14, 2014, finding 
the NOVA View[supreg] Automated Fluorescence Microscope not 
substantially equivalent to a predicate not subject to PMA. Thus, the 
device remained in class III in accordance with section 513(f)(1) of 
the FD&C Act when we issued the order.
    On December 11, 2014, Inova Diagnostics, Inc. submitted a request 
for De Novo classification of the NOVA

[[Page 52648]]

View[supreg] Automated Fluorescence Microscope. FDA reviewed the 
request in order to classify the device under the criteria for 
classification set forth in section 513(a)(1) of the FD&C Act. We 
classify devices into class II if general controls by themselves are 
insufficient to provide reasonable assurance of safety and 
effectiveness, but there is sufficient information to establish special 
controls that, in combination with the general controls, provide 
reasonable assurance of the safety and effectiveness of the device for 
its intended use (see 21 U.S.C. 360c(a)(1)(B)). After review of the 
information submitted in the request, we determined that the device can 
be classified into class II with the establishment of special controls. 
FDA has determined that these special controls, in addition to general 
controls, will provide reasonable assurance of the safety and 
effectiveness of the device.
    Therefore, on April 9, 2015, FDA issued an order to the requestor 
classifying the device into class II. FDA is codifying the 
classification of the device by adding 21 CFR 866.4750. We have named 
the generic type of device automated indirect immunofluorescence 
microscope and software-assisted system, and it is identified as 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.
    FDA has identified the following risks to health associated 
specifically with this type of device and the measures required to 
mitigate these risks in table 1.

 Table 1--Automated Indirect Immunofluorescence Microscope and Software-
              Assisted System Risks and Mitigation Measures
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       Identified risks            Mitigation measures/21 CFR section
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Inaccurate test results that   Special controls (1), (2), and (3) (21
 provide false positive or      CFR 866.4750(b)(1); 21 CFR
 false negative results.        866.4750(b)(2); and 21 CFR
                                866.4750(b)(3)).
Failure to correctly           Special controls (1), (2)(i), (2)(ii)(A),
 interpret test results can     (2)(ii)(B), (2)(iii), and (3) (21 CFR
 lead to false positive or      866.4750(b)(1); 21 CFR
 false negative results.        866.4750(b)(2)(i); 21 CFR
                                866.4750(b)(2)(ii)(A); 21 CFR
                                866.4750(b)(2)(ii)(B); 21 CFR
                                866.4750(b)(2)(iii); and 21 CFR
                                866.4750(b)(3)).
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    FDA has determined that special controls, in combination with the 
general controls, address these risks to health and provide reasonable 
assurance of safety and effectiveness. In order for a device to fall 
within this classification, and thus avoid automatic classification in 
class III, it would have to comply with the special controls named in 
this final order. The necessary special controls appear in the 
regulation codified by this order. This device is subject to premarket 
notification requirements under section 510(k) of the FD&C Act.

III. Analysis of Environmental Impact

    The Agency has determined under 21 CFR 25.34(b) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

IV. Paperwork Reduction Act of 1995

    This final order establishes special controls that refer to 
previously approved collections of information found in other FDA 
regulations. These collections of information are subject to review by 
the Office of Management and Budget (OMB) under the Paperwork Reduction 
Act of 1995 (44 U.S.C. 3501-3520). The collections of information in 
part 807, subpart E, regarding premarket notification submissions have 
been approved under OMB control number 0910-0120 and the collections of 
information in 21 CFR parts 801 and 809, regarding labeling have been 
approved under OMB control number 0910-0485.

List of Subjects in 21 CFR Part 866

    Biologics, Laboratories, Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
866 is amended as follows:

PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES

0
1. The authority citation for part 866 continues to read as follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.

0
2. Add Sec.  866.4750 to subpart E to read as follows:

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 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

[[Page 52649]]

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.

    Dated: November 7, 2017.
Lauren Silvis,
Chief of Staff.
[FR Doc. 2017-24585 Filed 11-13-17; 8:45 am]
 BILLING CODE 4164-01-P