51558 Federal Register / Vol. 82, No. 214 / Tuesday, November 7, 2017 / Rules and Regulations 

and Cosmetic Act unless added color is 

authorized by such standards. 

(d) Labeling requirements. The label 

of the color additive and of any 

mixtures prepared therefrom intended 

solely or in part for coloring purposes 

must conform to the requirements of 

§ 70.25 of this chapter. 

(e) Exemption from certification. 

Certification of this color additive is not 

necessary for the protection of the 

public health, and, therefore, batches 

thereof are exempt from the certification 

requirements of section 721(c) of the 

Federal Food, Drug, and Cosmetic Act. 

Dated: November 1, 2017. 

Anna K. Abram, 

Deputy Commissioner for Policy, Planning, 

Legislation, and Analysis. 

[FR Doc. 2017–24194 Filed 11–6–17; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 862 

[Docket No. FDA–2017–N–4394] 

Medical Devices; Clinical Chemistry 

and Clinical Toxicology Devices; 

Classification of the Total 25- 

Hydroxyvitamin D Mass Spectrometry 

Test System 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final order. 

SUMMARY: The Food and Drug 

Administration (FDA, the Agency, or 

we) is classifying the total 25- 

hydroxyvitamin D mass spectrometry 

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 total 25- 

hydroxyvitamin D mass spectrometry 

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 November 

7, 2017. The classification was 

applicable on May 18, 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, 

steven.tjoe@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Upon request, FDA has classified the 

total 25-hydroxyvitamin D mass 

spectrometry 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 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 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 March 20, 2017, AB Sciex LLC 

submitted a request for De Novo 

classification of the Vitamin D 200M 

Assay for the Topaz System. 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 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 


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Federal Register / Vol. 82, No. 214 / Tuesday, November 7, 2017 / Rules and Regulations 51559 

assurance of the safety and effectiveness 

of the device. 

Therefore, on May 18, 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 862.1840. We 

have named the generic type of device 

total 25-hydroxyvitamin D mass 

spectrometry test system, and it is 

identified as a device intended for use 

in clinical laboratories for the 

quantitative determination of total 25- 

hydroxyvitamin D (25–OH–D) in serum 

or plasma to be used in the assessment 

of vitamin D sufficiency. 

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—TOTAL 25-HYDROXYVITAMIN D MASS SPECTROMETRY TEST SYSTEM RISKS AND MITIGATION MEASURES

Identified risk Mitigation measures 

Clinical action based on falsely elevated inaccurate Vitamin D results 

may lead to unnecessary supplementation of Vitamin D.

General controls; Special control (1) (21 CFR 862.1840(b)(1)); and, 

Special control (2) (21 CFR 862.1840(b)(2)). 

Clinical action based on falsely low inaccurate Vitamin D results may 

lead to a delay in supplementation of Vitamin D.

General controls; Special control (1) (21 CFR 862.1840(b)(1)); and, 

Special control (2) (21 CFR 862.1840(b)(2)). 

Clinical action based on uninterpretable results due to lack of established device specific reference range values for the representative 

population.

General controls; and, Special control (3) (21 CFR 862.1840(b)(3)). 

Clinical action based on the misinterpretation of Vitamin D2 or Vitamin 

D3 results as total Vitamin D results.

General controls; and, Special control (4) (21 CFR 862.1840(b)(4)). 

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). 

Section 510(m)(2) of the FD&C Act 

provides that FDA may exempt a class 

II device from the premarket notification 

requirements under section 510(k) if, 

after notice of our intent to exempt and 

consideration of comments, we 

determine by order that premarket 

notification is not necessary to provide 

reasonable assurance of safety and 

effectiveness of the device. We believe 

this may be such a device. The notice 

of intent to exempt the device from 

premarket notification requirements is 

published elsewhere in this issue of the 

Federal Register. 

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, 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 862 

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 862 is 

amended as follows: 

PART 862—CLINICAL CHEMISTRY 

AND CLINICAL TOXICOLOGY 

DEVICES 

■ 1. The authority citation for part 862 

continues to read as follows: 

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

360j, 360l, 371. 

■ 2. Add § 862.1840 to subpart B to read 

as follows: 

§ 862.1840 Total 25-hydroxyvitamin D 

mass spectrometry test system. 

(a) Identification. A total 25- 

hydroxyvitamin D mass spectrometry 

test system is a device intended for use 

in clinical laboratories for the 

quantitative determination of total 25- 

hydroxyvitamin D (25–OH–D) in serum 

or plasma to be used in the assessment 

of vitamin D sufficiency. 

(b) Classification. Class II (special 

controls). The special controls for this 

device are: 

(1) The device must have initial and 

annual standardization verification by a 

certifying vitamin D standardization 

organization deemed acceptable by 

FDA. 

(2) The 21 CFR 809.10(b) compliant 

labeling must include detailed 

descriptions of performance testing 

conducted to evaluate precision, 

accuracy, linearity, interference, 

including the following: 

(i) Performance testing of device 

precision must, at a minimum, use 

intended sample type with Vitamin D 

concentrations at medically relevant 

decision points. At least one sample in 

the precision studies must be an 

unmodified patient sample. This testing 

must evaluate repeatability and 

reproducibility using a protocol from an 

FDA-recognized standard. 

(ii) Performance testing of device 

accuracy must include a minimum of 

115 serum or plasma samples that span 

the measuring interval of the device and 

compare results of the new device to 

results of a reference method or a legally 

marketed standardized mass 

spectrometry based vitamin D assay. 

The results must be described in the 21 

CFR 809.10(b)(12) compliant labeling of 

the device. 

(iii) Interference from vitamin D 

analogs and metabolites including 

vitamin D2, vitamin D3, 1- 

hydroxyvitamin D2, 1-hydroxyvitamin 

D3, 3-Epi-25-Hydroxyvitamin D2, 3-Epi25-Hydroxyvitamin D3, 1,25- 

Dihydroxyvitamin D2, 1,25- 

Dihydroxyvitamin D3, 3-Epi-1,25- 

Dihydroxyvitamin D2, and 3-Epi-1,25- 

Dihydroxyvitamin D3, 25, 26- 

Dihydroxyvitamin-D3, 24 (R), 25- 

dihydroxyvitamin-D3, 23 (R), 25- 

dihydroxyvitamin-D3 must be described 

in the 21 CFR 809.10(b)(7) compliant 

labeling of the device. 

(3) The 21 CFR 809.10(b) compliant 

labeling must be supported by a 

reference range study representative of 


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51560 Federal Register / Vol. 82, No. 214 / Tuesday, November 7, 2017 / Rules and Regulations 

the performance of the device. The 

study must be conducted using samples 

collected from apparently healthy male 

and female adults at least 21 years of age 

and older from at least 3 distinct 

climatic regions within the United 

States in different weather seasons. The 

ethnic, racial, and gender background of 

this study population must be 

representative of the U.S. population 

demographics. 

(4) The results of the device as 

provided in the 21 CFR 809.10(b) 

compliant labeling and any test report 

generated must be reported as only total 

25-hydroxyvitamin D. 

Dated: October 31, 2017. 

Lauren Silvis, 

Chief of Staff. 

[FR Doc. 2017–24161 Filed 11–6–17; 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–4341] 

Medical Devices; Immunology and 

Microbiology Devices; Classification of 

the Genetic Health Risk Assessment 

System 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final order. 

SUMMARY: The Food and Drug 

Administration (FDA, the Agency, or 

we) is classifying the genetic health risk 

assessment 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 genetic health 

risk assessment 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 November 

7, 2017. The classification was 

applicable on April 6, 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, 

steven.tjoe@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Upon request, FDA has classified the 

genetic health risk assessment 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 section 513(f)(1) of the Federal 

Food, Drug, and Cosmetic Act (the 

FD&C Act) (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 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. 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 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 June 28, 2016, 23andMe, Inc. 

submitted a request for De Novo 

classification of the 23andMe Personal 

Genome Service (PGS) Test. 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. 


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