Federal Register / Vol. 82, No. 218 / Tuesday, November 14, 2017 / Rules and Regulations 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 assayspecific 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 realtime 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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 876 

[Docket No. FDA–2017–N–6289] 

Medical Devices; GastroenterologyUrology Devices; Classification of the 

Prostatic Artery Embolization Device 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final order. 

SUMMARY: The Food and Drug 

Administration (FDA or we) is 

classifying the prostatic artery 

embolization 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 prostatic artery 

embolization 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, in part by reducing regulatory 

burdens. 

DATES: This order is effective November 

14, 2017. The classification was 

applicable on June 21, 2017. 

FOR FURTHER INFORMATION CONTACT: 

Benjamin Fisher, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. G108, Silver Spring, 

MD 20993–0002, 301–796–0245, 

Benjamin.Fisher@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Upon request, FDA has classified the 

prostatic artery embolization 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, 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 to a 

predicate device that does not require 

premarket approval (see 21 U.S.C. 

360c(i)). We determine whether a new 

device is substantially equivalent to a 

predicate by means of the procedures 


jstallworth on DSKBBY8HB2PROD with RULES
52650 Federal Register / Vol. 82, No. 218 / Tuesday, November 14, 2017 / Rules and Regulations 

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 (21 U.S.C. 360c(f)(2)). 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 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 pre-market 

approval 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 August 5, 2016, BioSphere 

Medical, S.A., submitted a request for 

De Novo classification of the 

Embosphere® Microspheres. FDA 

reviewed the request 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 generals 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 June 21, 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 876.5550. We 

have named the generic type of device 

prostatic artery embolization device, 

and it is identified as an intravascular 

implant intended to occlude the 

prostatic arteries to prevent blood flow 

to the targeted area of the prostate, 

resulting in a reduction of lower urinary 

tract symptoms related to benign 

prostatic hyperplasia. This does not 

include cyanoacrylates and other 

embolic agents which act by in situ 

polymerization or precipitation, or 

embolization devices used in 

neurovascular applications (see 21 CFR 

882.5950). 

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—PROSTATIC ARTERY EMBOLIZATION DEVICE RISKS AND MITIGATION MEASURES

Identified risks Mitigation measures 

Adverse tissue reaction ............................................................................ Biocompatibility evaluation.

Infection .................................................................................................... Sterilization validation, Shelf-life validation, Non-clinical performance 

testing, and Labeling. 

Non-target ischemia ................................................................................. Clinical data, Non-clinical performance testing, and Labeling. 

Urinary retention ....................................................................................... Labeling. 

Post-prostatic artery embolization syndrome (nausea, vomiting, regional 

pain, non-infectious fever, minor hematuria, or hematochezia).

Labeling. 

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 

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 part 21 CFR part 814, 

subparts A through E, regarding 

premarket approval, have been 

approved under OMB control number 

0910–0231; the collections of 


jstallworth on DSKBBY8HB2PROD with RULES
Federal Register / Vol. 82, No. 218 / Tuesday, November 14, 2017 / Rules and Regulations 52651 

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 

part 801, regarding labeling, have been 

approved under OMB control number 

0910–0485. 

List of Subjects in 21 CFR Part 876 

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 876 is 

amended as follows: 

PART 876—GASTROENTEROLOGY– 

UROLOGY DEVICES 

■ 1. The authority citation for part 876 

continues to read as follows: 

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

360j, 360l, 371. 

■ 2. Add § 876.5550 to subpart F to read 

as follows: 

§ 876.5550 Prostatic artery embolization 

device. 

(a) Identification. A prostatic artery 

embolization device is an intravascular 

implant intended to occlude the 

prostatic arteries to prevent blood flow 

to the targeted area of the prostate, 

resulting in a reduction of lower urinary 

tract symptoms related to benign 

prostatic hyperplasia. This does not 

include cyanoacrylates and other 

embolic agents which act by in situ 

polymerization or precipitation, or 

embolization devices used in 

neurovascular applications (see 21 CFR 

882.5950). 

(b) Classification. Class II (special 

controls). The special controls for this 

device are: 

(1) The device must be demonstrated 

to be biocompatible. 

(2) Non-clinical performance testing 

must demonstrate that the device 

performs as intended under anticipated 

conditions of use. The following 

performance characteristics must be 

tested: 

(i) Evaluation of suitability for 

injection through catheters intended for 

use in embolization; and 

(ii) Evaluation of the size distribution 

of the device. 

(3) Performance data must support the 

sterility and pyrogenicity of the device. 

(4) Performance data must support the 

shelf life of the device by demonstrating 

continued sterility, package integrity, 

and device functionality over the 

identified shelf life. 

(5) Clinical data must evaluate postembolization damage due to non-target 

embolization under anticipated use 

conditions. 

(6) The labeling must include: 

(i) Specific instructions on safe device 

preparation and use; 

(ii) The device shelf life; 

(iii) Data regarding urinary retention; 

and 

(iv) Data regarding post-prostatic 

artery embolization syndrome. 

Dated: November 7, 2017. 

Lauren Silvis, 

Chief of Staff. 

[FR Doc. 2017–24586 Filed 11–13–17; 8:45 am] 

BILLING CODE 4164–01–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 52 

[EPA–R03–OAR–2016–0369; FRL–9970–70– 

Region 3] 

Determination of Attainment by the 

Attainment Date for the 2008 Ozone 

National Ambient Air Quality Standard; 

District of Columbia, Maryland, and 

Virginia; Washington, DC-MD-VA Area 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: The Environmental Protection 

Agency (EPA) is making a final 

determination that the Washington, DC– 

MD–VA marginal ozone nonattainment 

area (the Washington Area) attained the 

2008 ozone national ambient air quality 

standard (NAAQS) by the July 20, 2016 

attainment date. This determination is 

based on complete, certified, and 

quality assured ambient air quality 

monitoring data for the Washington 

Area for the 2013–2015 monitoring 

period. The effect of this determination 

of attainment is that the Washington 

Area will not be bumped up or 

reclassified as a moderate 

nonattainment area. This determination 

of attainment is not equivalent to a 

redesignation, and the states in the 

Washington Area and the District of 

Columbia must meet the statutory 

requirements for redesignation in order 

to be redesignated to attainment. This 

determination is also not a clean data 

determination. This action is being 

taken under the Clean Air Act (CAA). 

DATES: This final rule is effective on 

December 14, 2017. 

ADDRESSES: EPA established a docket 

for this action under Docket ID Number 

EPA–R03–OAR–2016–0369. All 

documents in the docket are listed on 

the http://www.regulations.gov Web 

site. Although listed in the docket 

index, some information is not publicly 

available, e.g., confidential business 

information (CBI) or other information 

whose disclosure is restricted by statute. 

Certain other material, such as 

copyrighted material, is not placed on 

the Internet and will be publicly 

available only in hard copy form. 

Publicly available docket materials are 

available through http://

www.regulations.gov, or please contact 

the person identified in the FOR FURTHER

INFORMATION CONTACT section below for 

additional availability information. 

FOR FURTHER INFORMATION CONTACT: 

Gavin Huang, (215) 814–2042, or by 

email at huang.gavin@epa.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

On April 25, 2017 (82 FR 19011), EPA 

published a notice of proposed 

rulemaking (NPR) for the Washington 

Area. The Washington Area consists of 

the Counties of Calvert, Charles, 

Frederick, Montgomery, and Prince 

George’s in Maryland; the Counties of 

Arlington, Fairfax, Loudoun, and Prince 

William and the Cities of Alexandria, 

Fairfax, Falls Church, Manassas, and 

Manassas Park in Virginia; and the 

entirety of the District of Columbia. In 

the NPR, EPA proposed to determine, in 

accordance with its statutory obligations 

under section 181(b)(2)(A) of the CAA 

and the Provisions for Implementation 

of the 2008 Ozone National Ambient Air 

Quality Standards (40 CFR part 51, 

subpart AA), that the Washington Area 

attained the 2008 ozone NAAQS by the 

applicable attainment date of July 20, 

2016. 

II. EPA’s Evaluation 

Section 181(b)(2)(A) of the CAA 

requires that EPA determine whether an 

area has attained the NAAQS by its 

attainment date based on complete and 

certified air quality data from the three 

full calendar years preceding an area’s 

attainment date. The 2008 ozone 

NAAQS level is 0.075 parts per million 

(ppm). See 73 FR 16436 (March 27, 

2008). Consistent with the requirements 

contained in 40 CFR part 50, appendix 

P, EPA reviewed the ozone ambient air 

quality monitoring data for each 

monitoring site within the Washington 

Area for the monitoring period from 

2013 through 2015, as recorded in the 

Air Quality System (AQS) database. 

Federal, state, and local agencies 

responsible for ozone air monitoring 

networks supplied and quality assured 

the data. EPA determined that all the 

Washington Area monitoring sites with 

valid data had design values equal to or 

less than 0.075 ppm based on the 2013– 

2015 monitoring period. Therefore, 

based on 2013–2015 certified air quality 


jstallworth on DSKBBY8HB2PROD with RULES