[Federal Register Volume 83, Number 1 (Tuesday, January 2, 2018)]
[Rules and Regulations]
[Pages 20-22]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-28262]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 864

[Docket No. FDA-2017-N-6780]


Medical Devices; Hematology and Pathology Devices; Classification 
of the Whole Slide Imaging 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 whole slide imaging 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 whole slide 
imaging 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.

[[Page 21]]


DATES: This order is effective January 2, 2018. The classification was 
applicable on April 12, 2017.

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 whole slide imaging 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 (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 (see 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 (21 U.S.C. 360(k) and part 807 (21 CFR part 807).
    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 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

    On December 1, 2016, Philips Medical Systems Nederland B.V. 
submitted a request for De Novo classification of the Philips 
IntelliSite Pathology Solution (PIPS). 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 the general controls, will 
provide reasonable assurance of the safety and effectiveness of the 
device.
    Therefore, on April 12, 2017, FDA issued an order to the requester 
classifying the device into class II. FDA is codifying the 
classification of the device by adding 21 CFR 864.3700. We have named 
the generic type of device the whole slide imaging system, and it is 
identified as an automated digital slide creation, viewing, and 
management system intended as an aid to the pathologist to review and 
interpret digital images of surgical pathology slides. The system 
generates digital images that would otherwise be appropriate for manual 
visualization by conventional light microscopy.
    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--Whole Slide Imaging System Risks and Mitigation Measures
------------------------------------------------------------------------
                                            Mitigation measures/21 CFR
            Identified risk                          Section
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Inaccurate or missing results leading    General controls;
 to, for example, incorrect diagnosis.   Special control (1) (21 CFR
                                          864.3700(b)(1)); and,
                                         Special control (2) (21 CFR
                                          864.3700(b)(2)).
Delayed results........................  General controls;
                                         Special control (1) (21 CFR
                                          864.3700(b)(1)); and,
                                         Special control (2) (21 CFR
                                          864.3700(b)(2)).
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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. 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 
the guidance document ``De Novo Classification Process (Evaluation of 
Automatic Class III Designation)'' have been approved under OMB control 
number 0910-0844; the collections of information in 21 CFR part 814, 
subparts A through E, regarding premarket approval, have been approved 
under OMB control number 0910-0231; the collections of information in 
part 21 CFR 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 864

    Blood, Medical devices, Packaging and containers.

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

PART 864--HEMATOLOGY AND PATHOLOGY DEVICES

0
1. The authority citation for part 864 is revised to read as follows:

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


0
2. Add Sec.  864.3700 to subpart D to read as follows:


Sec.  864.3700  Whole slide imaging system.

    (a) Identification. The whole slide imaging system is an automated 
digital slide creation, viewing, and management system intended as an 
aid to the pathologist to review and interpret digital images of 
surgical pathology slides. The system generates digital images that 
would otherwise be appropriate for manual visualization by conventional 
light microscopy.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Premarket notification submissions must include the following 
information:
    (i) The indications for use must specify the tissue specimen that 
is intended to be used with the whole slide imaging system and the 
components of the system.
    (ii) A detailed description of the device and bench testing results 
at the component level, including for the following, as appropriate:
    (A) Slide feeder;
    (B) Light source;
    (C) Imaging optics;
    (D) Mechanical scanner movement;
    (E) Digital imaging sensor;
    (F) Image processing software;
    (G) Image composition techniques;
    (H) Image file formats;
    (I) Image review manipulation software;
    (J) Computer environment; and
    (K) Display system.
    (iii) Detailed bench testing and results at the system level, 
including for the following, as appropriate:
    (A) Color reproducibility;
    (B) Spatial resolution;
    (C) Focusing test;
    (D) Whole slide tissue coverage;
    (E) Stitching error; and
    (F) Turnaround time.
    (iv) Detailed information demonstrating the performance 
characteristics of the device, including, as appropriate:
    (A) Precision to evaluate intra-system and inter-system precision 
using a comprehensive set of clinical specimens with defined, 
clinically relevant histologic features from various organ systems and 
diseases. Multiple whole slide imaging systems, multiple sites, and 
multiple readers must be included.
    (B) Reproducibility data to evaluate inter-site variability using a 
comprehensive set of clinical specimens with defined, clinically 
relevant histologic features from various organ systems and diseases. 
Multiple whole slide imaging systems, multiple sites, and multiple 
readers must be included.
    (C) Data from a clinical study to demonstrate that viewing, 
reviewing, and diagnosing digital images of surgical pathology slides 
prepared from tissue slides using the whole slide imaging system is 
non-inferior to using an optical microscope. The study should evaluate 
the difference in major discordance rates between manual digital (MD) 
and manual optical (MO) modalities when compared to the reference 
(e.g., main sign-out diagnosis).
    (D) A detailed human factor engineering process must be used to 
evaluate the whole slide imaging system user interface(s).
    (2) Labeling compliant with 21 CFR 809.10(b) must include the 
following:
    (i) The intended use statement must include the information 
described in paragraph (b)(1)(i) of this section, as applicable, and a 
statement that reads, ``It is the responsibility of a qualified 
pathologist to employ appropriate procedures and safeguards to assure 
the validity of the interpretation of images obtained using this 
device.''
    (ii) A description of the technical studies and the summary of 
results, including those that relate to paragraphs (b)(1)(ii) and (iii) 
of this section, as appropriate.
    (iii) A description of the performance studies and the summary of 
results, including those that relate to paragraph (b)(1)(iv) of this 
section, as appropriate.
    (iv) A limiting statement that specifies that pathologists should 
exercise professional judgment in each clinical situation and examine 
the glass slides by conventional microscopy if there is doubt about the 
ability to accurately render an interpretation using this device alone.

    Dated: December 26, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-28262 Filed 12-29-17; 8:45 am]
 BILLING CODE 4164-01-P


