Federal Register / Vol. 87, No. 14 / Friday, January 21, 2022 / Rules and Regulations 3203 

APPENDIX A TO PART 11—FEE

SCHEDULE FOR FY 2022—Continued 

State County Fee/acre/yr 

Pierce ................ 380.82 

San Juan ........... 167.58 

Skagit ................ 179.51 

Skamania .......... 214.10 

Snohomish ........ 342.58 

Spokane ............ 66.06 

Stevens ............. 27.80 

Thurston ............ 210.52 

Wahkiakum ........ 85.15 

Walla Walla ....... 44.85 

Whatcom ........... 297.60 

Whitman ............ 30.94 

Yakima .............. 48.82 

West Virginia ..... Barbour .............. 63.52 

Berkeley ............ 145.52 

Boone ................ 63.63 

Braxton .............. 55.88 

Brooke ............... 76.86 

Cabell ................ 96.96 

Calhoun ............. 49.60 

Clay ................... 46.85 

Doddridge .......... 57.92 

Fayette .............. 79.25 

Gilmer ................ 35.83 

Grant ................. 71.33 

Greenbrier ......... 70.90 

Hampshire ......... 81.73 

Hancock ............ 124.44 

Hardy ................. 87.41 

Harrison ............. 68.12 

Jackson ............. 60.15 

Jefferson ............ 159.78 

Kanawha ........... 105.58 

Lewis ................. 58.76 

Lincoln ............... 50.14 

Logan ................ 67.31 

Marion ............... 80.64 

Marshall ............. 70.38 

Mason ................ 66.11 

McDowell ........... 168.56 

Mercer ............... 68.42 

Mineral ............... 75.85 

Mingo ................. 30.36 

Monongalia ........ 123.24 

Monroe .............. 72.42 

Morgan .............. 142.39 

Nicholas ............. 71.14 

Ohio ................... 98.59 

Pendleton .......... 61.21 

Pleasants ........... 62.79 

Pocahontas ....... 51.01 

Preston .............. 74.73 

Putnam .............. 77.97 

Raleigh .............. 100.90 

Randolph ........... 65.97 

Ritchie ............... 49.11 

Roane ................ 52.51 

Summers ........... 61.81 

Taylor ................ 83.66 

Tucker ............... 77.89 

Tyler .................. 52.04 

Upshur ............... 71.96 

Wayne ............... 54.66 

Webster ............. 62.55 

Wetzel ............... 52.42 

Wirt .................... 49.19 

Wood ................. 90.68 

Wyoming ........... 91.06 

Wisconsin .......... Adams ............... 120.55 

Ashland ............. 59.99 

Barron ................ 91.82 

Bayfield .............. 58.84 

Brown ................ 228.13 

Buffalo ............... 105.81 

Burnett ............... 73.13 

Calumet ............. 211.46 

Chippewa .......... 95.58 

Clark .................. 108.98 

Columbia ........... 156.51 

Crawford ............ 85.40 

APPENDIX A TO PART 11—FEE

SCHEDULE FOR FY 2022—Continued 

State County Fee/acre/yr 

Dane .................. 221.26 

Dodge ................ 156.94 

Door ................... 127.75 

Douglas ............. 52.66 

Dunn .................. 96.70 

Eau Claire ......... 122.65 

Florence ............ 67.86 

Fond du Lac ...... 195.37 

Forest ................ 65.15 

Grant ................. 126.67 

Green ................ 145.74 

Green Lake ....... 153.61 

Iowa ................... 130.62 

Iron .................... 91.33 

Jackson ............. 102.05 

Jefferson ............ 165.27 

Juneau .............. 99.47 

Kenosha ............ 203.43 

Kewaunee ......... 150.92 

La Crosse .......... 133.93 

Lafayette ............ 160.51 

Langlade ............ 87.87 

Lincoln ............... 87.04 

Manitowoc ......... 183.26 

Marathon ........... 127.59 

Marinette ........... 104.12 

Marquette .......... 112.15 

Menominee ........ 46.62 

Milwaukee ......... 239.76 

Monroe .............. 106.53 

Oconto ............... 111.88 

Oneida ............... 109.17 

Outagamie ......... 193.54 

Ozaukee ............ 176.01 

Pepin ................. 104.04 

Pierce ................ 124.07 

Polk ................... 94.99 

Portage .............. 110.11 

Price .................. 66.04 

Racine ............... 206.30 

Richland ............ 90.13 

Rock .................. 176.95 

Rusk .................. 66.73 

Sauk .................. 112.98 

Sawyer .............. 69.63 

Shawano ........... 125.20 

Sheboygan ........ 177.08 

St. Croix ............ 125.90 

Taylor ................ 78.82 

Trempealeau ..... 106.29 

Vernon ............... 104.30 

Vilas ................... 158.79 

Walworth ........... 186.19 

Washburn .......... 84.00 

Washington ....... 189.41 

Waukesha ......... 147.89 

Waupaca ........... 121.28 

Waushara .......... 113.62 

Winnebago ........ 187.21 

Wood ................. 88.92 

Wyoming ............ Albany ............... 10.74 

Big Horn ............ 23.35 

Campbell ........... 8.32 

Carbon ............... 8.08 

Converse ........... 7.77 

Crook ................. 14.38 

Fremont ............. 18.72 

Goshen .............. 12.67 

Hot Springs ....... 9.12 

Johnson ............. 8.64 

Laramie ............. 12.46 

Lincoln ............... 26.86 

Natrona .............. 6.67 

Niobrara ............. 9.21 

Park ................... 21.95 

Platte ................. 12.90 

Sheridan ............ 17.98 

Sublette ............. 24.26 

Sweetwater ........ 4.35 

Teton ................. 59.49 

APPENDIX A TO PART 11—FEE

SCHEDULE FOR FY 2022—Continued 

State County Fee/acre/yr 

Uinta .................. 15.75 

Washakie ........... 17.18 

Weston .............. 9.83 

[FR Doc. 2022–01105 Filed 1–20–22; 8:45 am] 

BILLING CODE 6717–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 886 

[Docket No. FDA–2021–N–0993] 

Medical Devices; Ophthalmic Devices; 

Classification of the Retinal Diagnostic 

Software Device 

AGENCY: Food and Drug Administration, 

Department of Health and Human 

Services (HHS). 

ACTION: Final amendment; final order. 

SUMMARY: The Food and Drug 

Administration (FDA, Agency, or we) is 

classifying the retinal diagnostic 

software device 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 retinal 

diagnostic software device’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. 

DATES: This order is effective January 

21, 2022. The classification was 

applicable on April 11, 2018. 

FOR FURTHER INFORMATION CONTACT: 

Elvin Ng, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 1304, Silver Spring, 

MD 20993–0002, 240–402–4662, 

Elvin.Ng@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Upon request, FDA has classified the 

retinal diagnostic software device 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, by placing the 

device into a lower device class than the 

automatic class III assignment. 


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3204 Federal Register / Vol. 87, No. 14 / Friday, January 21, 2022 / Rules and Regulations 

1FDA notes that the ACTION caption for this 

final order is styled as ‘‘Final amendment; final 

order,’’ rather than ‘‘Final order.’’ Beginning in 

December 2019, this editorial change was made to 

indicate that the document ‘‘amends’’ the Code of 

Federal Regulations. The change was made in 

accordance with the Office of Federal Register’s 

(OFR) interpretations of the Federal Register Act (44 

U.S.C. chapter 15), its implementing regulations (1 

CFR 5.9 and parts 21 and 22), and the Document 

Drafting Handbook. 

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 

device 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 shall 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. 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 

section 513(f)(2)(B)(i)) of the FD&C Act). 

As a result, other device sponsors do not 

have to submit a De Novo request or 

premarket approval application to 

market a substantially equivalent device 

(see section 513(i) of the FD&C Act, 

defining ‘‘substantial equivalence’’). 

Instead, sponsors can use the lessburdensome 510(k) process, when 

necessary, to market their device. 

II. De Novo Classification 

On January 12, 2018, FDA received 

IDx, LLC’s request for De Novo 

classification of the IDx-DR. 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 11, 2018, FDA 

issued an order to the requester 

classifying the device into class II. In 

this final order, FDA is codifying the 

classification of the device by adding 21 

CFR 886.1100.1 We have named the 

generic type of device retinal diagnostic 

software device, and it is identified as 

a prescription software device that 

incorporates an adaptive algorithm to 

evaluate ophthalmic images for 

diagnostic screening to identify retinal 

diseases or conditions. 

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—RETINAL DIAGNOSTIC SOFTWARE DEVICE RISKS AND MITIGATION MEASURES

Identified risks Mitigation measures 

False positive results leading to additional unnecessary medical procedures.

• Diagnostic software failure ............................................

• Software failure ..............................................................

Clinical performance testing; Software verification, validation, and hazard analysis; and Protocol for technical specification changes. 

False negative results leading to delay of further evaluation 

or treatment.

• Diagnostic software failure ............................................

• Software failure ..............................................................

Clinical performance testing; Software verification, validation, and hazard analysis; Protocol for technical specification changes; and Labeling. 

Operator failure to provide images that meet input quality 

specifications.

Labeling, Training, and Human factors validation testing. 


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Federal Register / Vol. 87, No. 14 / Friday, January 21, 2022 / Rules and Regulations 3205 

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. 

At the time of classification, retinal 

diagnostic software devices are for 

prescription use only. Prescription 

devices are exempt from the 

requirement for adequate directions for 

use for the layperson under section 

502(f)(1) of the FD&C Act (21 U.S.C. 

352(f)(1)) and 21 CFR 801.5, as long as 

the conditions of 21 CFR 801.109 are 

met. 

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 and 

guidance. 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. 3501–3521). 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 807, subpart E, 

regarding premarket notification 

submissions, have been approved under 

OMB control number 0910–0120; the 

collections of information in 21 CFR 

part 820, regarding quality system 

regulation, have been approved under 

OMB control number 0910–0073; and 

the collections of information in 21 CFR 

part 801, regarding labeling, have been 

approved under OMB control number 

0910–0485. 

List of Subjects in 21 CFR Part 886 

Medical devices, Ophthalmic goods 

and services. 

Therefore, under the Federal Food, 

Drug, and Cosmetic Act and under 

authority delegated to the Commissioner 

of Food and Drugs, 21 CFR part 886 is 

amended as follows: 

PART 886—OPHTHALMIC DEVICES 

■ 1. The authority citation for part 886 

continues to read as follows: 

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

360j, 360l, 371. 

■ 2. Add § 886.1100 to subpart B to read 

as follows: 

§ 886.1100 Retinal diagnostic software 

device. 

(a) Identification. A retinal diagnostic 

software device is a prescription 

software device that incorporates an 

adaptive algorithm to evaluate 

ophthalmic images for diagnostic 

screening to identify retinal diseases or 

conditions. 

(b) Classification. Class II (special 

controls). The special controls for this 

device are: 

(1) Software verification and 

validation documentation, based on a 

comprehensive hazard analysis, must 

fulfill the following: 

(i) Software documentation must 

provide a full characterization of 

technical parameters of the software, 

including algorithm(s). 

(ii) Software documentation must 

describe the expected impact of 

applicable image acquisition hardware 

characteristics on performance and 

associated minimum specifications. 

(iii) Software documentation must 

include a cybersecurity vulnerability 

and management process to assure 

software functionality. 

(iv) Software documentation must 

include mitigation measures to manage 

failure of any subsystem components 

with respect to incorrect patient reports 

and operator failures. 

(2) Clinical performance data 

supporting the indications for use must 

be provided, including the following: 

(i) Clinical performance testing must 

evaluate sensitivity, specificity, positive 

predictive value, and negative 

predictive value for each endpoint 

reported for the indicated disease or 

condition across the range of available 

device outcomes. 

(ii) Clinical performance testing must 

evaluate performance under anticipated 

conditions of use. 

(iii) Statistical methods must include 

the following: 

(A) Where multiple samples from the 

same patient are used, statistical 

analysis must not assume statistical 

independence without adequate 

justification. 

(B) Statistical analysis must provide 

confidence intervals for each 

performance metric. 

(iv) Clinical data must evaluate the 

variability in output performance due to 

both the user and the image acquisition 

device used. 

(3) A training program with 

instructions on how to acquire and 

process quality images must be 

provided. 

(4) Human factors validation testing 

that evaluates the effect of the training 

program on user performance must be 

provided. 

(5) A protocol must be developed that 

describes the level of change in device 

technical specifications that could 

significantly affect the safety or 

effectiveness of the device. 

(6) Labeling must include: 

(i) Instructions for use, including a 

description of how to obtain quality 

images and how device performance is 

affected by user interaction and user 

training; 

(ii) The type of imaging data used, 

what the device outputs to the user, and 

whether the output is qualitative or 

quantitative; 

(iii) Warnings regarding image 

acquisition factors that affect image 

quality; 

(iv) Warnings regarding interpretation 

of the provided outcomes, including: 

(A) A warning that the device is not 

to be used to screen for the presence of 

diseases or conditions beyond its 

indicated uses; 

(B) A warning that the device 

provides a screening diagnosis only and 

that it is critical that the patient be 

advised to receive followup care; and 

(C) A warning that the device does not 

treat the screened disease; 

(v) A summary of the clinical 

performance of the device for each 

output, with confidence intervals; and 

(vi) A summary of the clinical 

performance testing conducted with the 

device, including a description of the 

patient population and clinical 

environment under which it was 

evaluated. 

Dated: January 14, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–01147 Filed 1–20–22; 8:45 am] 

BILLING CODE 4164–01–P 


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