49098 Federal Register / Vol. 82, No. 204 / Tuesday, October 24, 2017 / Rules and Regulations 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 866 

[Docket No. FDA–2017–N–5657] 

Medical Devices; Immunology and 

Microbiology Devices; Classification of 

the Device To Detect and Measure 

Non-Microbial Analyte(s) in Human 

Clinical Specimens To Aid in 

Assessment of Patients With 

Suspected Sepsis 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final order. 

SUMMARY: The Food and Drug 

Administration (FDA or we) is 

classifying the device to detect and 

measure non-microbial analyte(s) in 

human clinical specimens to aid in 

assessment of patients with suspected 

sepsis 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 device to detect and measure 

non-microbial analyte(s) in human 

clinical specimens to aid in assessment 

of patients with suspected sepsis’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 February 20, 2016. 

FOR FURTHER INFORMATION CONTACT: 

Ryan Lubert, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 4545, Silver Spring, 

MD 20993–0002, 240–402–6357, 

Ryan.Lubert@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Upon request, FDA has classified the 

device to detect and measure nonmicrobial analyte(s) in human clinical 

specimens to aid in assessment of 

patients with suspected sepsis 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 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 

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 

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 March 4, 2015, B·R·A·H·M·S 

GmbH, part of Thermo Fisher Scientific, 

submitted a request for De Novo 

classification of the B·R·A·H·M·S PCT 

sensitive KRYPTOR. 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 February 20, 2016, 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 866.3215. We 

have named the generic type of device, 

device to detect and measure nonmicrobial analyte(s) in human clinical 

specimens to aid in assessment of 

patients with suspected sepsis, and it is 

identified as an in vitro device intended 

for the detection and qualitative and/or 

quantitative measurement of one or 

more non-microbial analytes in human 

clinical specimens to aid in the 


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Federal Register / Vol. 82, No. 204 / Tuesday, October 24, 2017 / Rules and Regulations 49099 

assessment of patients with suspected 

sepsis when used in conjunction with 

clinical signs and symptoms and 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—DEVICE TO DETECT AND MEASURE NON-MICROBIAL ANALYTE(S) IN HUMAN CLINICAL SPECIMENS TO AID IN

ASSESSMENT OF PATIENTS WITH SUSPECTED SEPSIS RISKS AND MITIGATION MEASURES

Identified risks Mitigation measures/21 CFR section 

Incorrect determination of procalcitonin (PCT) value, including false 

positives and false negatives, by the device can lead to improper patient management.

Special Controls (2), (3), and (7) (21 CFR 866.3215(b)(2); 21 CFR 

866.3215(b)(3); and 21 CFR 866.3215(b)(7)). 

Incorrect interpretation of device results by end user can lead to improper patient management.Special Controls (1), (4), (5), (6), and (7) (21 CFR 866.3215(b)(1); 21 

CFR 866.3215(b)(4); 21 CFR 866.3215(b)(5); 21 CFR 

866.3215(b)(6); and 21 CFR 866.3215(b)(7)). 

Manual calculation error of final results ................................................... Special Control (7) (21 CFR 866.3215(b)(7)). 

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, the collections of 

information in 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 § 866.3215 to subpart D to read 

as follows: 

§ 866.3215 Device to detect and measure 

non-microbial analyte(s) in human clinical 

specimens to aid in assessment of patients 

with suspected sepsis. 

(a) Identification. A device to detect 

and measure non-microbial analyte(s) in 

human clinical specimens to aid in 

assessment of patients with suspected 

sepsis is identified as an in vitro device 

intended for the detection and 

qualitative and/or quantitative 

measurement of one or more nonmicrobial analytes in human clinical 

specimens to aid in the assessment of 

patients with suspected sepsis when 

used in conjunction with clinical signs 

and symptoms and 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 device’s 

detailed Indications for Use statement 

describing what the device detects and 

measures, the results provided to the 

user, whether the measure is qualitative 

and/or quantitative, the clinical 

indications for which the test is to be 

used, and the specific population(s) for 

which the device use is intended. 

(2) Premarket notification 

submissions must include detailed 

documentation of the device 

description, including (as applicable), 

all device components, software, 

ancillary reagents required but not 

provided, explanation of the device 

principle and methodology, and for 

molecular devices include detailed 

documentation of the primer/probe 

sequence, design, and rationale for 

sequence selection. 

(3) Premarket notification 

submissions must include detailed 

documentation of applicable analytical 

studies, such as, analytical sensitivity 

(Limit of Detection, Limit of Blank, and 

Limit of Quantitation), precision, 

reproducibility, analytical measuring 

range, interference, cross-reactivity, and 

specimen stability. 

(4) Premarket notification 

submissions must include detailed 

documentation of a prospective clinical 

study or, if appropriate, results from an 

equivalent sample set. This detailed 

documentation must include the 

following information: 

(i) Results must demonstrate adequate 

device performance relative to a wellaccepted comparator. 

(ii) Clinical sample results must 

demonstrate consistency of device 

output throughout the device measuring 

range likely to be encountered in the 

Intended Use population. 

(iii) Clinical study documentation 

must include the original study protocol 

(including predefined statistical 

analysis plan), study report 

documenting support for the Indications 

for Use(s), and results of all statistical 

analyses. 

(5) Premarket notification 

submissions must include evaluation of 

the level of the non-microbial analyte in 

asymptomatic patients with 

demographic characteristics (e.g., age, 

racial, ethnic, and gender distribution) 

similar to the Intended Use population. 

(6) As part of the risk management 

activities performed under 21 CFR 

820.30 design controls, you must 

document an appropriate end user 

device training program that will be 


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49100 Federal Register / Vol. 82, No. 204 / Tuesday, October 24, 2017 / Rules and Regulations 

offered as part of your efforts to mitigate 

the risk of failure to correctly operate 

the instrument. 

(7) A detailed explanation of the 

interpretation of results and acceptance 

criteria must be included in the device’s 

21 CFR 809.10(b)(9) compliant labeling, 

and a detailed explanation of the 

interpretation of the limitations of the 

samples (e.g., collected on day of 

diagnosis) must be included in the 

device’s 21 CFR 809.10(b)(10) compliant 

labeling. 

Dated: October 18, 2017. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2017–22994 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–5290] 

Medical Devices; Immunology and 

Microbiology Devices; Classification of 

the Mass Spectrometer System for 

Clinical Use for the Identification of 

Microorganisms 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final order. 

SUMMARY: The Food and Drug 

Administration (FDA or we) is 

classifying the mass spectrometer 

system for clinical use for the 

identification of microorganisms 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 

mass spectrometer system for clinical 

use for the identification of 

microorganisms’ 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 21, 2013. 

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 

mass spectrometer system for clinical 

use for the identification of 

microorganisms 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 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 

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 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, 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 

On January 3, 2013, bioMe ́rieux, Inc. 

submitted a request for De Novo 

classification of the Vitek® MS. 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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