82_FR_50283 82 FR 50075 - Medical Devices; Immunology and Microbiology Devices; Classification of the Aquaporin-4 Autoantibody Immunological Test System

82 FR 50075 - Medical Devices; Immunology and Microbiology Devices; Classification of the Aquaporin-4 Autoantibody Immunological Test System

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 82, Issue 208 (October 30, 2017)

Page Range50075-50077
FR Document2017-23489

The Food and Drug Administration (FDA or we) is classifying the Aquaporin-4 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 Aquaporin-4 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.

Federal Register, Volume 82 Issue 208 (Monday, October 30, 2017)
[Federal Register Volume 82, Number 208 (Monday, October 30, 2017)]
[Rules and Regulations]
[Pages 50075-50077]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2017-23489]



[[Page 50075]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2017-N-5870]


Medical Devices; Immunology and Microbiology Devices; 
Classification of the Aquaporin-4 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 Aquaporin-4 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 Aquaporin-4 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 30, 2017. The classification was 
applicable on April 25, 2016.

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 Aquaporin-4 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. 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 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 July 2, 2015, KRONUS, Inc. submitted a request for De Novo 
classification of the KRONUS Aquaporin-4 Autoantibody (AQP4Ab) 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.
    Therefore, on April 25, 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 866.5665. We have named 
the generic type of device Aquaporin-4 autoantibody immunological test 
system, and it is identified as a device that consists of reagents used 
to measure by immunochemical techniques autoantibodies in human serum 
samples that react with Aquaporin-4 (AQP4Ab). The measurements aid in 
the diagnosis of neuromyelitis optica and neuromyelitis optica spectrum 
disorders, in conjunction with other clinical, laboratory, and 
radiological (e.g., magnetic resonance imaging) findings.
    FDA has identified the following risks to health associated 
specifically with this type of device and the measures

[[Page 50076]]

required to mitigate these risks in table 1.

  Table 1--Aquaporin-4 Autoantibody Immunological Test System Risks and
                           Mitigation Measures
------------------------------------------------------------------------
                                            Mitigation measures/21 CFR
            Identified risks                         section
------------------------------------------------------------------------
Inaccurate test results that provide     Special controls (1), (2), and
 false positive or false negative         (3) (21 CFR 866.5665(b)(1); 21
 results can lead to improper patient     CFR 866.5665(b)(2); and 21 CFR
 management.                              866.5665(b)(3)).
Failure to correctly interpret test      Special controls (1)(iii), (2),
 results can lead to false positive or    and (3) (21 CFR
 false negative results.                  866.5665(b)(1)(iii); 21 CFR
                                          866.5665(b)(2); and 21 CFR
                                          866.5665(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) 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

0
1. The authority citation for part 866 continues to read as follows:

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


0
2. Add Sec.  866.5665 to subpart F to read as follows:


Sec.  866.5665   Aquaporin-4 autoantibody immunological test system.

    (a) Identification. An Aquaporin-4 autoantibody immunological test 
system is a device that consists of reagents used to measure by 
immunochemical techniques autoantibodies in human serum samples that 
react with Aquaporin-4 (AQP4Ab). The measurements aid in the diagnosis 
of neuromyelitis optica (NMO) and neuromyelitis optica spectrum 
disorders (NMOSD) in conjunction with other clinical, laboratory, and 
radiological (e.g., magnetic resonance imaging) 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 device description including:
    (A) A detailed description of all components including all required 
ancillary reagents in the test;
    (B) If applicable, a detailed description of instrumentation and 
equipment, including illustrations or photographs of non-standard 
equipment or manuals;
    (C) If applicable, detailed documentation of the device software, 
including, but not limited to, standalone software applications and 
hardware-based devices that incorporate software;
    (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 
specified testing procedures;
    (E) Detailed specifications for sample collection, processing, and 
storage;
    (F) A detailed description of methodology and assay procedure;
    (G) A description of how the assay cutoff (the medical decision 
point between positive and negative) was established and validated as 
well as supporting data; and
    (H) Detailed specification of the criteria for test results 
interpretation and reporting.
    (ii) Detailed information demonstrating the performance 
characteristics of the device, including:
    (A) Device precision/reproducibility data generated from within-
run, between-run, between-day, between-lot, between-site, and total 
precision for multiple nonconsecutive days, as applicable. A well 
characterized panel of patient samples or pools from the indicated 
population that covers the device measuring range must be used.
    (B) Device linearity data generated from samples covering the 
device 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.
    (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 indications of use. A well-characterized 
panel of patient samples from the indicated population covering the 
device measuring range must be used.

[[Page 50077]]

    (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 well-characterized patient samples covering the 
device measuring range.
    (K) Clinical performance must be established by comparing data 
generated by testing samples from the indicated population and the 
differential diagnosis or non-target disease groups with the device to 
the clinical diagnostic standard.
    (1) The diagnosis of NMO and NMOSD must be based on clinical 
findings, laboratory tests (e.g., serological tests), and radiological 
tests (e.g., magnetic resonance imaging).
    (2) The differential diagnosis or non-target disease group must 
include the applicable diseases or conditions, including but not be 
limited to the following: Multiple sclerosis, stroke, Lyme disease, 
shingles, syphilis, human immunodeficiency virus, hepatitis B, 
tuberculosis, Srgen's syndrome, systemic lupus erythematous, systemic 
vasculitis, sarcoidosis, Graves' disease, Hashimoto's disease, Type I 
diabetes, rheumatoid arthritis, Addison's disease, and myasthenia 
gravis.
    (3) Diagnosis of diseases or conditions for the differential or 
non-target disease groups must be based on established diagnostic 
criteria and clinical evaluation.
    (4) For all samples, the diagnostic clinical criteria and the 
demographic information must be collected and provided.
    (5) The clinical validation results must demonstrate clinical 
sensitivity and clinical specificity for the test values based on the 
presence or absence of NMO and NMOSD.
    (6) The data must be summarized in tabular format comparing the 
interpretation of results to the disease status.
    (L) 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) The device's 21 CFR 809.10(b) compliant labeling must include 
warnings relevant to the device including:
    (i) A warning statement that reads ``The device is for use by 
laboratory professionals in a clinical laboratory setting''; and
    (ii) A warning statement that reads ``The device is not to be used 
as a stand-alone device but as an adjunct to other clinical 
information. A diagnosis of Neuromyelitis Optica (NMO) and 
Neuromyelitis Optica Spectrum Disorders (NMOSD) should not be made on a 
single test result. The clinical symptoms, results from physical 
examination, laboratory tests (e.g., serological tests), and 
radiological tests (e.g. Magnetic Resonance Imaging), when appropriate, 
should always be taken into account when considering the diagnosis of 
NMO and NMOSD.''
    (3) The device's 21 CFR 809.10(b) compliant labeling must include a 
detailed 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 24, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-23489 Filed 10-27-17; 8:45 am]
 BILLING CODE 4164-01-P



                                                              Federal Register / Vol. 82, No. 208 / Monday, October 30, 2017 / Rules and Regulations                                           50075

                                             DEPARTMENT OF HEALTH AND                                within, class III and requires premarket                 We believe this De Novo classification
                                             HUMAN SERVICES                                          approval unless and until FDA takes an                will enhance patients’ access to
                                                                                                     action to classify or reclassify the device           beneficial innovation, in part by
                                             Food and Drug Administration                            (see 21 U.S.C. 360c(f)(1)). We refer to               reducing regulatory burdens. When FDA
                                                                                                     these devices as ‘‘postamendments                     classifies a device into class I or II via
                                             21 CFR Part 866                                         devices’’ because they were not in                    the De Novo process, the device can
                                             [Docket No. FDA–2017–N–5870]                            commercial distribution prior to the                  serve as a predicate for future devices of
                                                                                                     date of enactment of the Medical Device               that type, including for 510(k)s (see 21
                                             Medical Devices; Immunology and                         Amendments of 1976, which amended                     U.S.C. 360c(f)(2)(B)(i)). As a result, other
                                             Microbiology Devices; Classification of                 the Federal Food, Drug, and Cosmetic                  device sponsors do not have to submit
                                             the Aquaporin-4 Autoantibody                            Act (the FD&C Act).                                   a De Novo request or premarket
                                             Immunological Test System                                  FDA may take a variety of actions in               approval application in order to market
                                                                                                     appropriate circumstances to classify or              a substantially equivalent device (see 21
                                             AGENCY:    Food and Drug Administration,                reclassify a device into class I or II. We            U.S.C. 360c(i), defining ‘‘substantial
                                             HHS.                                                    may issue an order finding a new device               equivalence’’). Instead, sponsors can use
                                             ACTION:   Final order.                                  to be substantially equivalent under                  the less-burdensome 510(k) process,
                                                                                                     section 513(i) of the FD&C Act (21                    when necessary, to market their device.
                                             SUMMARY:    The Food and Drug                           U.S.C. 360c(i)) to a predicate device that
                                             Administration (FDA or we) is                                                                                 II. De Novo Classification
                                                                                                     does not require premarket approval.
                                             classifying the Aquaporin-4                             We determine whether a new device is                     On July 2, 2015, KRONUS, Inc.
                                             autoantibody immunological test system                  substantially equivalent to a predicate               submitted a request for De Novo
                                             into class II (special controls). The                   by means of the procedures for                        classification of the KRONUS
                                             special controls that apply to the device               premarket notification under section                  Aquaporin-4 Autoantibody (AQP4Ab)
                                             type are identified in this order and will              510(k) of the FD&C Act and part 807 (21               ELISA Assay. FDA reviewed the request
                                             be part of the codified language for the                                                                      in order to classify the device under the
                                                                                                     U.S.C. 360(k) and 21 CFR part 807,
                                             Aquaporin-4 autoantibody                                                                                      criteria for classification set forth in
                                                                                                     respectively).
                                             immunological test system’s                                                                                   section 513(a)(1) of the FD&C Act. We
                                                                                                        FDA may also classify a device
                                             classification. We are taking this action                                                                     classify devices into class II if general
                                                                                                     through ‘‘De Novo’’ classification, a
                                             because we have determined that                                                                               controls by themselves are insufficient
                                                                                                     common name for the process
                                             classifying the device into class II                                                                          to provide reasonable assurance of
                                                                                                     authorized under section 513(f)(2) of the             safety and effectiveness, but there is
                                             (special controls) will provide a                       FD&C Act. Section 207 of the Food and
                                             reasonable assurance of safety and                                                                            sufficient information to establish
                                                                                                     Drug Administration Modernization Act                 special controls that, in combination
                                             effectiveness of the device. We believe                 of 1997 established the first procedure
                                             this action will also enhance patients’                                                                       with the general controls, provide
                                                                                                     for De Novo classification (Pub. L. 105–              reasonable assurance of the safety and
                                             access to beneficial innovative devices,                115). Section 607 of the Food and Drug
                                             in part by reducing regulatory burdens.                                                                       effectiveness of the device for its
                                                                                                     Administration Safety and Innovation                  intended use (see 21 U.S.C.
                                             DATES: This order is effective October                  Act modified the De Novo application
                                             30, 2017. The classification was                                                                              360c(a)(1)(B)). After review of the
                                                                                                     process by adding a second procedure                  information submitted in the request,
                                             applicable on April 25, 2016.                           (Pub. L. 112–144). A device sponsor                   we determined that the device can be
                                             FOR FURTHER INFORMATION CONTACT:                        may utilize either procedure for De                   classified into class II with the
                                             Steven Tjoe, Center for Devices and                     Novo classification.                                  establishment of special controls. FDA
                                             Radiological Health, Food and Drug                         Under the first procedure, the person              has determined that these special
                                             Administration, 10903 New Hampshire                     submits a 510(k) for a device that has                controls, in addition to general controls,
                                             Ave., Bldg. 66, Rm. 4550, Silver Spring,                not previously been classified. After                 will provide reasonable assurance of the
                                             MD 20993–0002, 301–796–5866,                            receiving an order from FDA classifying               safety and effectiveness of the device.
                                             steven.tjoe@fda.hhs.gov.                                the device into class III under section                  Therefore, on April 25, 2016, FDA
                                             SUPPLEMENTARY INFORMATION:                              513(f)(1) of the FD&C Act, the person                 issued an order to the requestor
                                                                                                     then requests a classification under                  classifying the device into class II. FDA
                                             I. Background                                           section 513(f)(2).                                    is codifying the classification of the
                                               Upon request, FDA has classified the                     Under the second procedure, rather                 device by adding 21 CFR 866.5665. We
                                             Aquaporin-4 autoantibody                                than first submitting a 510(k) and then               have named the generic type of device
                                             immunological test system as class II                   a request for classification, if the person           Aquaporin-4 autoantibody
                                             (special controls), which we have                       determines that there is no legally                   immunological test system, and it is
                                             determined will provide a reasonable                    marketed device upon which to base a                  identified as a device that consists of
                                             assurance of safety and effectiveness. In               determination of substantial                          reagents used to measure by
                                             addition, we believe this action will                   equivalence, that person requests a                   immunochemical techniques
                                             enhance patients’ access to beneficial                  classification under section 513(f)(2) of             autoantibodies in human serum samples
                                             innovation, in part by reducing                         the FD&C Act.                                         that react with Aquaporin-4 (AQP4Ab).
                                             regulatory burdens by placing the                          Under either procedure for De Novo                 The measurements aid in the diagnosis
                                             device into a lower device class than the               classification, FDA is required to                    of neuromyelitis optica and
                                             automatic class III assignment.                         classify the device by written order                  neuromyelitis optica spectrum
                                               The automatic assignment of class III                 within 120 days. The classification will
nlaroche on DSK9F9SC42PROD with RULES




                                                                                                                                                           disorders, in conjunction with other
                                             occurs by operation of law and without                  be according to the criteria under                    clinical, laboratory, and radiological
                                             any action by FDA, regardless of the                    section 513(a)(1) of the FD&C Act.                    (e.g., magnetic resonance imaging)
                                             level of risk posed by the new device.                  Although the device was automatically                 findings.
                                             Any device that was not in commercial                   placed within class III, the De Novo                     FDA has identified the following risks
                                             distribution before May 28, 1976, is                    classification is considered to be the                to health associated specifically with
                                             automatically classified as, and remains                initial classification of the device.                 this type of device and the measures


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                                             50076            Federal Register / Vol. 82, No. 208 / Monday, October 30, 2017 / Rules and Regulations

                                             required to mitigate these risks in
                                             table 1.

                                                       TABLE 1—AQUAPORIN-4 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 re-            Special controls (1), (2), and (3) (21 CFR 866.5665(b)(1); 21 CFR
                                               sults can lead to improper patient management.                                       866.5665(b)(2); and 21 CFR 866.5665(b)(3)).
                                             Failure to correctly interpret test results can lead to false positive or            Special controls (1)(iii), (2), and (3) (21 CFR 866.5665(b)(1)(iii); 21
                                               false negative results.                                                              CFR 866.5665(b)(2); and 21 CFR 866.5665(b)(3)).



                                                FDA has determined that special                      PART 866—IMMUNOLOGY AND                                  (F) A detailed description of
                                             controls, in combination with the                       MICROBIOLOGY DEVICES                                  methodology and assay procedure;
                                             general controls, address these risks to                                                                         (G) A description of how the assay
                                             health and provide reasonable assurance                 ■ 1. The authority citation for part 866              cutoff (the medical decision point
                                             of safety and effectiveness. In order for               continues to read as follows:                         between positive and negative) was
                                             a device to fall within this classification,              Authority: 21 U.S.C. 351, 360, 360c, 360e,          established and validated as well as
                                             and thus avoid automatic classification                 360j, 360l, 371.                                      supporting data; and
                                             in class III, it would have to comply                                                                            (H) Detailed specification of the
                                                                                                     ■ 2. Add § 866.5665 to subpart F to read              criteria for test results interpretation and
                                             with the special controls named in this                 as follows:
                                             final order. The necessary special                                                                            reporting.
                                             controls appear in the regulation                       § 866.5665 Aquaporin-4 autoantibody                      (ii) Detailed information
                                             codified by this order. This device is                  immunological test system.                            demonstrating the performance
                                             subject to premarket notification                          (a) Identification. An Aquaporin-4                 characteristics of the device, including:
                                             requirements under section 510(k) of the                                                                         (A) Device precision/reproducibility
                                                                                                     autoantibody immunological test system
                                             FD&C Act.                                                                                                     data generated from within-run,
                                                                                                     is a device that consists of reagents used
                                                                                                                                                           between-run, between-day, between-lot,
                                             III. Analysis of Environmental Impact                   to measure by immunochemical
                                                                                                                                                           between-site, and total precision for
                                                                                                     techniques autoantibodies in human
                                                The Agency has determined under 21                                                                         multiple nonconsecutive days, as
                                                                                                     serum samples that react with
                                             CFR 25.34(b) that this action is of a type                                                                    applicable. A well characterized panel
                                                                                                     Aquaporin-4 (AQP4Ab). The                             of patient samples or pools from the
                                             that does not individually or                           measurements aid in the diagnosis of
                                             cumulatively have a significant effect on                                                                     indicated population that covers the
                                                                                                     neuromyelitis optica (NMO) and                        device measuring range must be used.
                                             the human environment. Therefore,                       neuromyelitis optica spectrum disorders
                                             neither an environmental assessment                                                                              (B) Device linearity data generated
                                                                                                     (NMOSD) in conjunction with other                     from samples covering the device
                                             nor an environmental impact statement                   clinical, laboratory, and radiological                measuring range, if applicable.
                                             is required.                                            (e.g., magnetic resonance imaging)                       (C) Information on traceability to a
                                             IV. Paperwork Reduction Act of 1995                     findings.                                             reference material and description of
                                                                                                        (b) Classification. Class II (special              value assignment of calibrators and
                                               This final order establishes special                  controls). The special controls for this
                                             controls that refer to previously                                                                             controls, if applicable.
                                                                                                     device are:                                              (D) Device analytical sensitivity data,
                                             approved collections of information                        (1) Premarket notification                         including limit of blank, limit of
                                             found in other FDA regulations. These                   submissions must include the following                detection, and limit of quantitation, if
                                             collections of information are subject to               information:                                          applicable.
                                             review by the Office of Management and                     (i) A detailed device description                     (E) Device analytical specificity data,
                                             Budget (OMB) under the Paperwork                        including:                                            including interference by endogenous
                                             Reduction Act of 1995 (44 U.S.C. 3501–                     (A) A detailed description of all                  and exogenous substances, as well as
                                             3520). The collections of information in                components including all required                     cross-reactivity with samples derived
                                             part 807, subpart E, regarding premarket                ancillary reagents in the test;                       from patients with other autoimmune
                                             notification submissions have been                         (B) If applicable, a detailed                      diseases or conditions.
                                             approved under OMB control number                       description of instrumentation and                       (F) Device instrument carryover data,
                                             0910–0120, the collections of                           equipment, including illustrations or                 when applicable.
                                             information in part 820 have been                       photographs of non-standard equipment                    (G) Device stability data, including
                                             approved under OMB control number                       or manuals;                                           real-time stability under various storage
                                             0910–0073, and the collections of                          (C) If applicable, detailed                        times and temperatures.
                                             information in 21 CFR parts 801 and                     documentation of the device software,                    (H) Specimen stability data, including
                                             809, regarding labeling have been                       including, but not limited to, standalone             stability under various storage times,
                                             approved under OMB control number                       software applications and hardware-                   temperatures, freeze-thaw, and transport
                                             0910–0485.                                              based devices that incorporate software;              conditions, where appropriate.
                                                                                                        (D) A detailed description of                         (I) Method comparison data generated
                                             List of Subjects in 21 CFR Part 866
                                                                                                     appropriate internal and external                     by comparison of the results obtained
                                               Biologics, Laboratories, Medical                                                                            with the device to those obtained with
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                                                                                                     quality controls that are recommended
                                             devices.                                                or provided. The description must                     a legally marketed predicate device with
                                               Therefore, under the Federal Food,                    identify those control elements that are              similar indications of use. A well-
                                             Drug, and Cosmetic Act and under                        incorporated into the specified testing               characterized panel of patient samples
                                             authority delegated to the Commissioner                 procedures;                                           from the indicated population covering
                                             of Food and Drugs, 21 CFR part 866 is                      (E) Detailed specifications for sample             the device measuring range must be
                                             amended as follows:                                     collection, processing, and storage;                  used.


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                                                              Federal Register / Vol. 82, No. 208 / Monday, October 30, 2017 / Rules and Regulations                                          50077

                                                (J) Specimen matrix comparison data,                    (ii) A warning statement that reads                FOR FURTHER INFORMATION CONTACT:
                                             if more than one specimen type or                       ‘‘The device is not to be used as a stand-            Caryl Giuliano, Center for Devices and
                                             anticoagulant can be tested with the                    alone device but as an adjunct to other               Radiological Health, Food and Drug
                                             device. Samples used for comparison                     clinical information. A diagnosis of                  Administration, 10903 New Hampshire
                                             must be from well-characterized patient                 Neuromyelitis Optica (NMO) and                        Ave., Bldg. 66, Rm. 5664, Silver Spring,
                                             samples covering the device measuring                   Neuromyelitis Optica Spectrum                         MD 20993–0002, 301–796–2478,
                                             range.                                                  Disorders (NMOSD) should not be made                  caryl.giuliano@fda.hhs.gov.
                                                (K) Clinical performance must be                     on a single test result. The clinical                 SUPPLEMENTARY INFORMATION:
                                             established by comparing data generated                 symptoms, results from physical
                                                                                                     examination, laboratory tests (e.g.,                  I. Background
                                             by testing samples from the indicated
                                             population and the differential                         serological tests), and radiological tests               Upon request, FDA has classified the
                                             diagnosis or non-target disease groups                  (e.g. Magnetic Resonance Imaging),                    newborn screening test for SCID as class
                                             with the device to the clinical                         when appropriate, should always be                    II (special controls), which we have
                                             diagnostic standard.                                    taken into account when considering                   determined will provide a reasonable
                                                (1) The diagnosis of NMO and                         the diagnosis of NMO and NMOSD.’’                     assurance of safety and effectiveness. In
                                             NMOSD must be based on clinical                            (3) The device’s 21 CFR 809.10(b)                  addition, we believe this action will
                                             findings, laboratory tests (e.g.,                       compliant labeling must include a                     enhance patients’ access to beneficial
                                             serological tests), and radiological tests              detailed description of the protocol and              innovation, in part by reducing
                                             (e.g., magnetic resonance imaging).                     performance studies performed in                      regulatory burdens by placing the
                                                (2) The differential diagnosis or non-               accordance with paragraph (b)(1)(ii) of               device into a lower device class than the
                                             target disease group must include the                   this section and a summary of the                     automatic class III assignment.
                                             applicable diseases or conditions,                      results.                                                 The automatic assignment of class III
                                             including but not be limited to the                       Dated: October 24, 2017.                            occurs by operation of law and without
                                             following: Multiple sclerosis, stroke,                  Anna K. Abram,
                                                                                                                                                           any action by FDA, regardless of the
                                             Lyme disease, shingles, syphilis, human                                                                       level of risk posed by the new device.
                                                                                                     Deputy Commissioner for Policy, Planning,
                                             immunodeficiency virus, hepatitis B,                    Legislation, and Analysis.
                                                                                                                                                           Any device that was not in commercial
                                             tuberculosis, Srgen’s syndrome,                                                                               distribution before May 28, 1976, is
                                                                                                     [FR Doc. 2017–23489 Filed 10–27–17; 8:45 am]
                                             systemic lupus erythematous, systemic                                                                         automatically classified as, and remains
                                                                                                     BILLING CODE 4164–01–P
                                             vasculitis, sarcoidosis, Graves’ disease,                                                                     within, class III and requires premarket
                                                                                                                                                           approval unless and until FDA takes an
                                             Hashimoto’s disease, Type I diabetes,
                                                                                                                                                           action to classify or reclassify the device
                                             rheumatoid arthritis, Addison’s disease,                DEPARTMENT OF HEALTH AND
                                                                                                                                                           (see 21 U.S.C. 360c(f)(1)). We refer to
                                             and myasthenia gravis.                                  HUMAN SERVICES
                                                                                                                                                           these devices as ‘‘postamendments
                                                (3) Diagnosis of diseases or conditions
                                                                                                     Food and Drug Administration                          devices’’ because they were not in
                                             for the differential or non-target disease
                                                                                                                                                           commercial distribution prior to the
                                             groups must be based on established
                                                                                                     21 CFR Part 866                                       date of enactment of the Medical Device
                                             diagnostic criteria and clinical
                                                                                                                                                           Amendments of 1976, which amended
                                             evaluation.                                             [Docket No. FDA–2017–N–5924]                          the Federal Food, Drug, and Cosmetic
                                                (4) For all samples, the diagnostic                                                                        Act (the FD&C Act).
                                             clinical criteria and the demographic                   Medical Devices; Immunology and                          FDA may take a variety of actions in
                                             information must be collected and                       Microbiology Devices; Classification of               appropriate circumstances to classify or
                                             provided.                                               the Newborn Screening Test for Severe                 reclassify a device into class I or II. We
                                                (5) The clinical validation results                  Combined Immunodeficiency Disorder                    may issue an order finding a new device
                                             must demonstrate clinical sensitivity                   AGENCY:    Food and Drug Administration,              to be substantially equivalent under
                                             and clinical specificity for the test                   HHS.                                                  section 513(i) of the FD&C Act (21
                                             values based on the presence or absence                                                                       U.S.C. 360c(i)) to a predicate device that
                                                                                                     ACTION:   Final order.
                                             of NMO and NMOSD.                                                                                             does not require premarket approval.
                                                (6) The data must be summarized in                   SUMMARY:   The Food and Drug                          We determine whether a new device is
                                             tabular format comparing the                            Administration (FDA or we) is                         substantially equivalent to a predicate
                                             interpretation of results to the disease                classifying the newborn screening test                by means of the procedures for
                                             status.                                                 for severe combined immunodeficiency                  premarket notification under section
                                                (L) Expected/reference values                        disorder (SCID) into class II (special                510(k) of the FD&C Act and part 807 (21
                                             generated by testing an adequate                        controls). The special controls that                  U.S.C. 360(k) and 21 CFR part 807,
                                             number of samples from apparently                       apply to the device type are identified               respectively).
                                             healthy normal individuals.                             in this order and will be part of the                    FDA may also classify a device
                                                (iii) Identification of risk mitigation              codified language for the newborn                     through ‘‘De Novo’’ classification, a
                                             elements used by the device, including                  screening test for SCID’s classification.             common name for the process
                                             description of all additional procedures,               We are taking this action because we                  authorized under section 513(f)(2) of the
                                             methods, and practices incorporated                     have determined that classifying the                  FD&C Act. Section 207 of the Food and
                                             into the directions for use that mitigate               device into class II (special controls)               Drug Administration Modernization Act
                                             risks associated with testing.                          will provide a reasonable assurance of                of 1997 established the first procedure
                                                (2) The device’s 21 CFR 809.10(b)                    safety and effectiveness of the device.               for De Novo classification (Pub. L. 105–
                                             compliant labeling must include                         We believe this action will also enhance              115). Section 607 of the Food and Drug
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                                             warnings relevant to the device                         patients’ access to beneficial innovative             Administration Safety and Innovation
                                             including:                                              devices, in part by reducing regulatory               Act modified the De Novo application
                                                (i) A warning statement that reads                   burdens.                                              process by adding a second procedure
                                             ‘‘The device is for use by laboratory                   DATES: This order is effective October                (Pub. L. 112–144). A device sponsor
                                             professionals in a clinical laboratory                  30, 2017. The classification was                      may utilize either procedure for De
                                             setting’’; and                                          applicable on December 15, 2014.                      Novo classification.


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Document Created: 2017-10-28 00:28:47
Document Modified: 2017-10-28 00:28:47
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionRules and Regulations
ActionFinal order.
DatesThis order is effective October 30, 2017. The classification was applicable on April 25, 2016.
ContactSteven 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]
FR Citation82 FR 50075 
CFR AssociatedBiologics; Laboratories and Medical Devices

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