49102 Federal Register / Vol. 82, No. 204 / Tuesday, October 24, 2017 / Rules and Regulations 

(5) Premarket notification 

submissions must include details on the 

appropriate end user device training 

program that will be offered while 

marketing the device. 

Dated: October 19, 2017. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2017–23022 Filed 10–23–17; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 866 

[Docket No. FDA–2017–N–5651] 

Medical Devices; Immunology and 

Microbiology Devices; Classification of 

the Zinc Transporter 8 Autoantibody 

Immunological Test System 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final order. 

SUMMARY: The Food and Drug 

Administration (FDA or we) is 

classifying the zinc transporter 8 

autoantibody immunological test 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 

zinc transporter 8 autoantibody 

immunological test 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 October 

24, 2017. The classification was 

applicable on August 20, 2014. 

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, 

steven.tjoe@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Upon request, FDA has classified the 

zinc transporter 8 autoantibody 

immunological test 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 (21 

U.S.C. 360c(a)(1)). 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 May 21, 2014, finding the KRONUS 

Zinc Transporter 8 Autoantibody 

(ZnT8Ab) ELISA Assay 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 June 16, 2014, KRONUS Market 

Development Associates, Inc., submitted 

a request for De Novo classification of 

the KRONUS Zinc Transporter 8 

Autoantibody (ZnT8Ab) ELISA Assay. 

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. 


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Federal Register / Vol. 82, No. 204 / Tuesday, October 24, 2017 / Rules and Regulations 49103 

Therefore, on August 20, 2014, 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 866.5670. We 

have named the generic type of device 

zinc transporter 8 autoantibody 

immunological test system, and it is 

identified as a device that consists of 

reagents used to measure, by 

immunochemical techniques, the 

autoantibodies in human serum samples 

that react with Zinc Transporter 8 

(ZnT8). The measurements aid in the 

diagnosis of Type 1 diabetes mellitus 

(autoimmune mediated diabetes) in 

conjunction with other clinical and 

laboratory findings. 

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—ZINC TRANSPORTER 8 AUTOANTIBODY IMMUNOLOGICAL TEST SYSTEM RISKS AND MITIGATION MEASURES

Identified risks Mitigation measures/21 CFR section 

Inaccurate test results that provide false positive or false negative results can lead to improper patient management.Special controls (1), (2), and (3) (21 CFR 866.5670(b)(1), 21 CFR 

866.5670(b)(2), and 21 CFR 866.5670(b)(3)). 

Failure to correctly interpret test results can lead to false positive or 

false negative results.

Special controls (1)(iii), (2), and (3) (21 CFR 866.5670(b)(1)(iii), 21 

CFR 866.5670(b)(2), and 21 CFR 866.5670(b)(3)). 

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). 

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, the collections of 

information in 21 CFR part 820 have 

been approved under OMB control 

number 0910–0073, 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 

■ 1. The authority citation for part 866 

continues to read as follows: 

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

360j, 360l, 371. 

■ 2. Add § 866.5670 to subpart F to read 

as follows: 

§ 866.5670 Zinc transporter 8 autoantibody 

immunological test system. 

(a) Identification. A zinc transporter 8 

autoantibody immunological test system 

is a device that consists of reagents used 

to measure, by immunochemical 

techniques, the autoantibodies in 

human serum samples that react with 

Zinc Transporter 8 (ZnT8). The 

measurements aid in the diagnosis of 

Type 1 diabetes mellitus (autoimmune 

mediated diabetes) in conjunction with 

other clinical and laboratory findings. 

(b) Classification. Class II (special 

controls). The special controls for this 

device are: 

(1) Premarket notification 

submissions must include the following 

information: 

(i) A detailed description of the 

device that includes: 

(A) A detailed description of all 

components in the test system, 

including a description of the assay 

components in the kit and all required 

ancillary reagents; 

(B) A detailed description of 

instrumentation and equipment, and 

illustrations or photographs of nonstandard equipment or methods if 

applicable; 

(C) Detailed documentation of the 

device software, including, but not 

limited to, standalone software 

applications and hardware-based 

devices that incorporate software where 

applicable; 

(D) 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; 

(E) Detailed specifications for sample 

collection, processing, and storage; 

(F) A detailed description of 

methodology and assay procedure; and 

(G) Detailed specification of the 

criteria for test results interpretation and 

reporting. 

(ii) Information that demonstrates the 

performance characteristics of the 

device, including: 

(A) 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. A well characterized panel 

of patient samples or pools from the 

intended use population that covers the 

device measuring range must be used; 

(B) Device linearity data generated 

from patient samples covering the assay 

measuring range if applicable; 

(C) Information on traceability to a 

reference material and description of 

value assignment of calibrators and 

controls if applicable; 

(D) Device analytical sensitivity data, 

including limit of blank, limit of 

detection and limit of quantitation if 

applicable; 

(E) Device analytical specificity data, 

including interference by endogenous 

and exogenous substances, as well as 

cross-reactivity with samples derived 

from patients with other autoimmune 

diseases or conditions; 

(F) Device instrument carryover data 

when applicable; 

(G) Device stability data including 

real-time stability under various storage 

times and temperatures; 


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49104 Federal Register / Vol. 82, No. 204 / Tuesday, October 24, 2017 / Rules and Regulations 

(H) Specimen stability data, including 

stability under various storage times, 

temperatures, freeze-thaw, and transport 

conditions where appropriate; 

(I) Method comparison data generated 

by comparison of the results obtained 

with the device to those obtained with 

a legally marketed predicate device with 

similar indication of use. Patient 

samples from the intended use 

population covering the device 

measuring range must be used; 

(J) Specimen matrix comparison data 

if more than one specimen type or 

anticoagulant can be tested with the 

device. Samples used for comparison 

must be from patient samples covering 

the device measuring range; 

(K) A description of how the assay 

cut-off (the medical decision point 

between positive and negative) was 

established and validated as well as 

supporting data; 

(L) Clinical performance must be 

established by comparing data generated 

by testing samples from the intended 

use population and the differential 

diagnosis groups with the device to the 

clinical diagnostic standard. The 

diagnosis of Type 1 diabetes mellitus 

must be based on clinical history, 

physical examination, and laboratory 

tests, such as one or more pancreatic or 

insulin autoantibody test. Because the 

intended use population for Type 1 

diabetes mellitus includes subjects less 

than 18 years old, samples from 

representative numbers of these subjects 

must be included. Representative 

numbers of samples from all age strata 

must also be included. The differential 

diagnosis groups must include, but not 

be limited to the following: Type 2 

diabetes mellitus; metabolic syndrome; 

latent autoimmune diabetes in adults; 

other autoimmune diseases such as 

celiac disease (without a concomitant 

diagnosis of Type 1 diabetes mellitus), 

systemic lupus erythematosus, 

rheumatoid arthritis, and Hashimoto’s 

thyroiditis; infection; renal disease; and 

testicular cancer. Diseases for the 

differential groups must be based on 

established diagnostic criteria and 

clinical evaluation. For all samples, the 

diagnostic clinical criteria and the 

demographic information must be 

collected and provided. The clinical 

validation results must demonstrate 

clinical sensitivity and clinical 

specificity for the test values based on 

the presence or absence of Type 1 

diabetes mellitus. The data must be 

summarized in tabular format 

comparing the interpretation of results 

to the disease status; and 

(M) Expected/reference values 

generated by testing an adequate 

number of samples from apparently 

healthy normal individuals. 

(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. 

(2) Your 21 CFR 809.10(a) compliant 

label and 21 CFR 809.10(b) compliant 

labeling must include warnings relevant 

to the assay including: 

(i) A warning statement that reads, 

‘‘The device is for use by laboratory 

professionals in a clinical laboratory 

setting’’; 

(ii) A warning statement that reads, 

‘‘The test is not a stand-alone test but an 

adjunct to other clinical information. A 

diagnosis of Type 1 diabetes mellitus 

should not be made on a single test 

result. The clinical symptoms, results 

on physical examination, and laboratory 

tests (e.g., serological tests), when 

appropriate, should always be taken 

into account when considering the 

diagnosis of Type 1 diabetes mellitus 

and Type 2 diabetes mellitus’’; 

(iii) A warning statement that reads, 

‘‘Absence of Zinc T8 autoantibody does 

not rule out a diagnosis of Type 1 

diabetes mellitus’’; and 

(iv) A warning statement that reads, 

‘‘The assay has not been demonstrated 

to be effective for monitoring the stage 

of disease or its response to treatment.’’ 

(3) Your 21 CFR 809.10(b) compliant 

labeling must include a description of 

the protocol and performance studies 

performed in accordance with 

paragraph (b)(1)(ii) of this section and a 

summary of the results. 

Dated: October 18, 2017. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2017–22995 Filed 10–23–17; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HOMELAND 

SECURITY 

Coast Guard 

33 CFR Part 117 

[Docket No. USCG–2017–0048] 

RIN 1625–AA09 

Drawbridge Operation Regulation; 

Reynolds Channel, Lawrence, NY 

AGENCY: Coast Guard, DHS. 

ACTION: Temporary final rule. 

SUMMARY: The Coast Guard is modifying 

the operating schedule that governs the 

Atlantic Beach Bridge across Reynolds 

Channel, mile 0.4 at Lawrence, New 

York. This action is necessary to allow 

for an unexpected delay in the 

reconstruction and painting of the 

bascule leaves. A temporary deviation 

was previously granted for a length of 

180 days. As the Coast Guard may not 

approve extensions beyond that allotted 

timeframe nor approve back-to-back or 

sequential deviations, it is necessary to 

issue this rule in order to allow the 

bridge owner to complete the remaining 

work items. 

DATES: This rule is effective without 

actual notice from October 24, 2017 

until 11:59 p.m. on November 13, 2017. 

For the purposes of enforcement, actual 

notice will be used from 12:01 on 

October 14, 2017 until October 24, 2017. 

ADDRESSES: To view documents 

mentioned in this preamble as being 

available in the docket, go to http://

www.regulations.gov, type USCG–2017– 

0048 in the ‘‘SEARCH’’ box and click 

‘‘SEARCH.’’ Click on Open Docket 

Folder on the line associated with this 

rulemaking. 

FOR FURTHER INFORMATION CONTACT: If 

you have questions on this interim rule, 

call or email James M. Moore, Bridge 

Management Specialist, U.S. Coast 

Guard; telephone 202–372–1518, email 

James.M.Moore2@uscg.mil. 

SUPPLEMENTARY INFORMATION: 

I. Table of Abbreviations 

CFR Code of Federal Regulations 

DHS Department of Homeland Security 

FR Federal Register 

OMB Office of Management and Budget 

NPRM Notice of Proposed Rulemaking 

§ Section 

U.S.C. United States Code 

II. Background Information and 

Regulatory History 

On April 6, 2017, we published a 

temporary deviation entitled, 

‘‘Drawbridge Operation Regulation; 

Atlantic Beach Bridge, Reynolds 

Channel, Lawrence, NY’’ in the Federal 

Register (see 82 FR 06735). Although we 

did not request public comments, 

outreach conducted with mariners 

utilizing the waterway indicated no 

objections to the temporary deviation. 

No complaints have been submitted 

during the current temporary deviation. 

The Coast Guard is issuing this 

temporary interim rule without prior 

notice and opportunity to comment 

pursuant to authority under section 4(a) 

of the Administrative Procedure Act 

(APA) (5 U.S.C. 553(b)). This provision 

authorizes an agency to issue a rule 

without prior notice and opportunity to 

comment when the agency for good 

cause finds that those procedures are 

‘‘impracticable, unnecessary, or contrary 


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