[Federal Register Volume 83, Number 201 (Wednesday, October 17, 2018)]
[Rules and Regulations]
[Pages 52313-52315]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-22694]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2018-N-3596]


Medical Devices; Immunology and Microbiology Devices; 
Classification of the Herpes Virus Nucleic Acid-Based Cutaneous and 
Mucocutaneous Lesion Panel

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA or we) is classifying 
the herpes virus nucleic acid-based cutaneous and mucocutaneous lesion 
panel 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 herpes virus nucleic acid-based cutaneous and 
mucocutaneous lesion panel'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 17, 2018. The classification was 
applicable on May 13, 2014.

FOR FURTHER INFORMATION CONTACT: Scott McFarland, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Rm. 4676, Silver Spring, MD, 20993-0002, 301-
796-6217, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Upon request, FDA has classified the herpes virus nucleic acid-
based cutaneous and mucocutaneous lesion panel as class II (special 
controls), which we have determined will provide a reasonable assurance 
of safety and effectiveness. In addition, we believe this action will 
enhance patients' access to beneficial innovation, in part by reducing 
regulatory burdens by placing the device into a lower device class than 
the automatic class III assignment.
    The automatic assignment of class III occurs by operation of law 
and without any action by FDA, regardless of the level of risk posed by 
the new device. Any device that was not in commercial distribution 
before May 28, 1976, is automatically classified as, and remains 
within, class III and requires premarket approval unless and until FDA 
takes an action to classify or reclassify the device (see 21 U.S.C. 
360c(f)(1)). We refer to these devices as ``postamendments devices'' 
because they were not in commercial distribution prior to the date of 
enactment of the Medical Device Amendments of 1976, which amended the 
Federal Food, Drug, and Cosmetic Act (FD&C Act).
    FDA may take a variety of actions in appropriate circumstances to 
classify or reclassify a device into class I or II. We may issue an 
order finding a new device to be substantially equivalent under section 
513(i) of the FD&C Act (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 (21 
U.S.C. 360(k)) and part 807 (21 CFR part 807).
    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 (Pub. L. 105-115) established the first procedure for De 
Novo classification. Section 607 of the Food and Drug Administration 
Safety and Innovation Act (Pub. L. 112-144) modified the De Novo 
application process by adding a second procedure. 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 (PMA) 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

    For this device, FDA issued an order on February 7, 2014, finding 
the Lyra\TM\ Direct HSV 1 + 2/VZV Assay not substantially equivalent to 
a predicate not subject to PMA. Thus, the device remained in class III 
in accordance with section 513(f)(1) of the FD&C Act when we issued the 
order.
    On February 21, 2014, Quidel Corporation submitted a request for De 
Novo classification of the Lyra\TM\ Direct HSV 1 + 2/VZV 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 May 13, 2014, FDA issued an order to the requestor 
classifying the device into class II. FDA

[[Page 52314]]

is codifying the classification of the device by adding 21 CFR 
866.3309. We have named the generic type of device herpes virus nucleic 
acid-based cutaneous and mucocutaneous lesion panel, and it is 
identified as a qualitative in vitro diagnostic device intended for the 
simultaneous detection and differentiation of different herpes viruses 
in cutaneous and mucocutaneous lesion samples from symptomatic patients 
suspected of Herpetic infections. Negative results do not preclude 
infection and should not be used as the sole basis for treatment or 
other patient management decisions. The assay is not intended for use 
in cerebrospinal fluid samples.
    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--Herpes Virus Nucleic Acid-Based Cutaneous and Mucocutaneous
               Lesion Panel Risks and Mitigation Measures
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            Identified risks                   Mitigation measures
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Risk of false results..................  Special controls (1) (21 CFR
                                          866.3309(b)(1)), (2) (21 CFR
                                          866.3309(b)(2)), and (3) (21
                                          CFR 866.3309(b)(3)).
Failure to correctly interpret test      Special controls (4) (21 CFR
 results.                                 866.3309(b)(4)) and (5) (21
                                          CFR 866.3309(b)(5)).
Failure to correctly operate the         Special controls (6) (21 CFR
 instrument.                              866.3309(b)(6)) and (7) (21
                                          CFR 866.3309(b)(7)).
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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. 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

    We have 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 and guidance. These collections of information are subject 
to review by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The collections 
of information in the guidance document ``De Novo Classification 
Process (Evaluation of Automatic Class III Designation)'' have been 
approved under OMB control number 0910-0844; the collections of 
information in 21 CFR part 814, subparts A through E, regarding 
premarket approval, have been approved under OMB control number 0910-
0231; 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 21 CFR part 
820, regarding quality system regulations, 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 21 CFR part 866 continues to read as 
follows:

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


0
2. Add Sec.  866.3309 to subpart D to read as follows:


Sec.  866.3309   Herpes virus nucleic acid-based cutaneous and 
mucocutaneous lesion panel.

    (a) Identification. A herpes virus nucleic acid-based cutaneous and 
mucocutaneous lesion panel is a qualitative in vitro diagnostic device 
intended for the simultaneous detection and differentiation of 
different herpes viruses in cutaneous and mucocutaneous lesion samples 
from symptomatic patients suspected of Herpetic infections. Negative 
results do not preclude infection and should not be used as the sole 
basis for treatment or other patient management decisions. The assay is 
not intended for use in cerebrospinal fluid samples.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Premarket notification submissions must include detailed 
documentation for the device description, including the device 
components, ancillary reagents required but not provided, and a 
detailed explanation of the methodology including primer design and 
selection.
    (2) Premarket notification submissions must include detailed 
documentation from the following analytical and clinical performance 
studies: Analytical sensitivity (Limit of Detection), reactivity, 
inclusivity, precision, reproducibility, interference, cross 
reactivity, carry-over, and cross contamination.
    (3) Premarket notification submissions must include detailed 
documentation of a clinical study using lesion samples in which Herpes 
Simplex Virus 1, Herpes Simplex Virus 2, or Varicella Zoster Virus DNA 
detection was requested. The study must compare the device performance 
to an appropriate well established reference method.
    (4) A detailed explanation of the interpretation of results and 
acceptance criteria must be included in the device's 21 CFR 
809.10(b)(9) compliant labeling.
    (5) The device labeling must include a limitation statement that 
reads: ``The device is not intended for use with cerebrospinal fluid or 
to aid in the diagnosis of HSV or VZV infections of the central nervous 
system (CNS).''
    (6) Premarket notification submissions must include quality 
assurance protocols and a detailed documentation for device software, 
including, but not limited to, standalone

[[Page 52315]]

software applications and hardware-based devices that incorporate 
software.
    (7) The risk management activities performed as part of the 
manufacturer's 21 CFR 820.30 design controls must document an 
appropriate end user device training program that will be offered as 
part of efforts to mitigate the risk of failure to correctly operate 
the instrument.

    Dated: October 12, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-22694 Filed 10-16-18; 8:45 am]
 BILLING CODE 4164-01-P


