Document ID: FDA-2017-N-4394-0001
Agency: fda
Document Type: Rule
Title: Medical Devices; Clinical Chemistry and Clinical Toxicology Devices;
Classification of the Total 25-Hydroxyvitamin D Mass Spectrometry Test System
Posted Date: 2017-11-07T05:00Z

[Federal Register Volume 82, Number 214 (Tuesday, November 7, 2017)]
[Rules and Regulations]
[Pages 51558-51560]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-24161]

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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.

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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, 
[email protected].

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

[[Page 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
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            Identified risk                    Mitigation measures
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Clinical action based on falsely         General controls; Special
 elevated inaccurate Vitamin D results    control (1) (21 CFR
 may lead to unnecessary                  862.1840(b)(1)); and, Special
 supplementation of Vitamin D.            control (2) (21 CFR
                                          862.1840(b)(2)).
Clinical action based on falsely low     General controls; Special
 inaccurate Vitamin D results may lead    control (1) (21 CFR
 to a delay in supplementation of         862.1840(b)(1)); and, Special
 Vitamin D.                               control (2) (21 CFR
                                          862.1840(b)(2)).
Clinical action based on                 General controls; and, Special
 uninterpretable results due to lack of   control (3) (21 CFR
 established device specific reference    862.1840(b)(3)).
 range values for the representative
 population.
Clinical action based on the             General controls; and, Special
 misinterpretation of Vitamin D2 or       control (4) (21 CFR
 Vitamin D3 results as total Vitamin D    862.1840(b)(4)).
 results.
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    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

0
1. The authority citation for part 862 continues to read as follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.

0
2. Add Sec.  862.1840 to subpart B to read as follows:

Sec.  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-Epi-25-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

[[Page 51560]]

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