[Federal Register Volume 80, Number 101 (Wednesday, May 27, 2015)]
[Rules and Regulations]
[Pages 30153-30155]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-12741]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2015-N-1072]


Medical Devices; Immunology and Microbiology Devices; 
Classification of Multiplex Nucleic Acid Assay for Identification of 
Microorganisms and Resistance Markers From Positive Blood Cultures

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA) is classifying 
multiplex nucleic acid assay for identification of microorganisms and 
resistance markers from positive blood cultures into class II (special 
controls). The special controls that will apply to this device are 
identified in this order and will be part of the codified language for 
the multiplex nucleic acid assay for identification of microorganisms 
and resistance markers from positive blood cultures. The Agency is 
classifying the device into class II (special controls) in order to 
provide a reasonable assurance of safety and effectiveness of the 
device.

DATES: This order is effective May 27, 2015. The classification was 
applicable June 26, 2012.

FOR FURTHER INFORMATION CONTACT: Kimberly J. Sconce, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Rm. 5506, Silver Spring, MD 20993-0002, 301-
796-6679.

SUPPLEMENTARY INFORMATION:

I. Background

    In accordance with section 513(f)(1) of the Federal Food, Drug, and 
Cosmetic Act (the FD&C Act) (21 U.S.C. 360c(f)(1)), devices that were 
not in commercial distribution before May 28, 1976 (the date of 
enactment of the Medical Device Amendments of 1976), generally referred 
to as postamendments devices, are classified automatically by statute 
into class III without any FDA rulemaking process. These devices remain 
in class III and require premarket approval, unless and until the 
device is classified or reclassified into class I or II, or FDA issues 
an order finding the device to be substantially equivalent, in 
accordance with section 513(i) of the FD&C Act, to a predicate device 
that does not require premarket approval. The Agency determines whether 
new devices are substantially equivalent to predicate devices by means 
of premarket notification procedures in section 510(k) of the FD&C Act 
(21 U.S.C. 360(k)) and part 807 (21 CFR part 807) of the regulations.
    Section 513(f)(2) of the FD&C Act, as amended by section 607 of the 
Food and Drug Administration Safety and Innovation Act (Pub. L. 112-
144, July 9, 2012), provides two procedures by which a person may 
request FDA to classify a device under the criteria set forth in 
section 513(a)(1). Under the first procedure, the person submits a 
premarket notification under section 510(k) of the FD&C Act for a 
device that has not previously been classified and, within 30 days of 
receiving an order classifying the device into class III under section 
513(f)(1) of the FD&C Act, the person requests a classification under 
section 513(f)(2). Under the second procedure, rather than first 
submitting a premarket notification under section 510(k) of the FD&C 
Act and then a request for classification under the first procedure, 
the person determines that there is no legally marketed device upon 
which to base a determination of substantial equivalence and requests a 
classification under section 513(f)(2) of the FD&C Act. If the person 
submits a request to classify the device under this second procedure, 
FDA may decline to undertake the classification request if FDA 
identifies a legally marketed device that could provide a reasonable 
basis for review of substantial equivalence with the device or if FDA 
determines that the device submitted is not of ``low-moderate risk'' or 
that general controls would be inadequate to control the risks and 
special controls to mitigate the risks cannot be developed.
    In response to a request to classify a device under either 
procedure provided by section 513(f)(2) of the FD&C Act, FDA will 
classify the device by written order within 120 days. This 
classification will be the initial classification of the device.
    In accordance with section 513(f)(1) of the FD&C Act, FDA issued an 
order on June 12, 2012, classifying the Verigene[supreg] Gram Positive 
Blood Culture Nucleic Acid Test (BC-GP) into class III, because it was 
not substantially equivalent to a device that was introduced or 
delivered for introduction into interstate commerce for commercial 
distribution before May 28, 1976, or a device which was subsequently 
reclassified into class I or class II. On June 15, 2012, Nanosphere, 
Inc., submitted a request for classification of Verigene[supreg] Gram 
Positive Blood Culture Nucleic Acid Test (BC-GP) under section 
513(f)(2) of the FD&C Act. The manufacturer recommended that the device 
be classified into class II.
    In accordance with section 513(f)(2) of the FD&C Act, 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. FDA 
classifies 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 to provide reasonable assurance of the safety and 
effectiveness of the device for its intended use. After review of the 
information submitted in the de novo request, FDA determined that the 
device can be classified into class II with the establishment of 
special controls. FDA believes these special controls, in addition to 
general controls, will provide reasonable assurance of the safety and 
effectiveness of the device.
    The device is assigned the generic name multiplex nucleic acid 
assay for identification of microorganisms and resistance markers from 
positive blood cultures, and it is identified as a qualitative in vitro 
device intended to simultaneously detect and identify microorganism 
nucleic acids from blood cultures that test positive by Gram stain or 
other microbiological stains. The device detects specific nucleic acid 
sequences for microorganism identification as well as for antimicrobial 
resistance. This device aids in the diagnosis of bloodstream infections 
when used in conjunction with other clinical and laboratory findings. 
However, the device does not replace traditional methods for culture 
and susceptibility testing.
    Multiplex nucleic acid assay for identification of microorganisms 
and resistance markers from positive blood cultures is a prescription 
device.
    FDA has identified the following risks to health associated with 
this type of device and the measures required to mitigate these risks 
in table 1:

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                               Table 1--Identified Risks and Required Mitigations
----------------------------------------------------------------------------------------------------------------
                         Identified risks                                       Required mitigations
----------------------------------------------------------------------------------------------------------------
False negative result............................................  The FDA document entitled ``Class II Special
                                                                    Controls Guideline: Multiplex Nucleic Acid
                                                                    Assay for Identification of Microorganisms
                                                                    and Resistance Markers from Positive Blood
                                                                    Cultures,'' which addresses this risk
                                                                    through: Device description containing the
                                                                    information specified in the special control
                                                                    guideline, performance characteristics, and
                                                                    labeling.
False positive result............................................  The FDA document entitled ``Class II Special
                                                                    Controls Guideline: Multiplex Nucleic Acid
                                                                    Assay for Identification of Microorganisms
                                                                    and Resistance Markers from Positive Blood
                                                                    Cultures,'' which addresses this risk
                                                                    through: Device description containing the
                                                                    information specified in the special control
                                                                    guideline, performance characteristics, and
                                                                    labeling.
Errors in interpretation.........................................  The FDA document entitled ``Class II Special
                                                                    Controls Guideline: Multiplex Nucleic Acid
                                                                    Assay for Identification of Microorganisms
                                                                    and Resistance Markers from Positive Blood
                                                                    Cultures,'' which addresses this risk
                                                                    through: Device description containing the
                                                                    information specified in the special control
                                                                    guideline, performance characteristics, and
                                                                    labeling.
----------------------------------------------------------------------------------------------------------------

    FDA believes that the measures set forth in the special controls 
guideline entitled ``Class II Special Controls Guideline: Multiplex 
Nucleic Acid Assay for Identification of Microorganisms and Resistance 
Markers from Positive Blood Cultures'' are necessary, in addition to 
general controls, to mitigate the risks to health described in table 1.
    Therefore, effective June 26, 2012, FDA issued an order to the 
requestor classifying the device into class II. FDA is codifying the 
classification of the device by adding Sec.  866.3365.

II. 510(k) Premarket Notification

    Following the effective date of this final classification order, 
any firm submitting a 510(k) premarket notification for this device 
type will need to comply with the special controls.
    Section 510(m) of the FD&C Act provides that FDA may exempt a class 
II device from the premarket notification requirements under section 
510(k) of the FD&C Act if FDA determines that premarket notification is 
not necessary to provide reasonable assurance of the safety and 
effectiveness of the device. For this type of device, FDA has 
determined that premarket notification is necessary to provide 
reasonable assurance of the safety and effectiveness of the device. 
Therefore, this device type is not exempt from premarket notification 
requirements. Persons who intend to market this type of device must 
submit to FDA a premarket notification, prior to marketing the device, 
which contains information about the multiplex nucleic acid assay for 
identification of microorganisms and resistance markers from positive 
blood cultures they intend to market.

III. 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 administrative 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 21 CFR parts 50 and 56 have been approved under OMB 
control number 0910-0755; the collections of information in 21 CFR part 
807, subpart E, regarding premarket notification submissions have been 
approved under OMB control number 0910-0120; the collections of 
information in 21 CFR parts 801 and 809 regarding labeling have been 
approved under OMB control number 0910-0485; the collections of 
information in 21 CFR part 812 regarding investigational device 
exemptions have been approved under OMB control number 0910-0078; the 
collections of information in 21 CFR part 820 regarding quality systems 
have been approved under OMB control number 0910-0073; and the 
collections of information regarding Requests for Feedback 
(``presubmissions'') have been approved under OMB control number 0910-
0756.

V. Clarifications to Special Controls Guidelines

    This special controls guideline reflects changes the Agency is 
making to clarify its position on the binding nature of special 
controls. The changes include referring to the document as a 
``guideline,'' as that term is used in section 513(a) of the FD&C Act, 
which the Secretary has developed and disseminated to provide a 
reasonable assurance of safety and effectiveness for class II devices, 
and not a ``guidance,'' as that term is used in 21 CFR 10.115. The 
guideline uses mandatory language to emphasize that firms must comply 
with special controls to legally market their class II devices. The 
guideline clarifies that firms will need either to: (1) Comply with the 
particular mitigation measures set forth in the special controls 
guideline or (2) use alternative mitigation measures, but demonstrate 
to the Agency's satisfaction that those alternative measures identified 
by the firm will provide at least an equivalent assurance of safety and 
effectiveness. These revisions do not represent a change in FDA's 
position about the binding effect of special controls, but rather are 
intended to address any possible confusion or misunderstanding.

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, 371.


0
2. Add Sec.  866.3365 to subpart D to read as follows:


Sec.  866.3365  Multiplex nucleic acid assay for identification of 
microorganisms and resistance markers from positive blood cultures.

    (a) Identification. A multiplex nucleic acid assay for 
identification of microorganisms and resistance markers from positive 
blood cultures is a qualitative in vitro device intended to 
simultaneously detect and identify microorganism nucleic acids from 
blood

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cultures that test positive by Gram stain or other microbiological 
stains. The device detects specific nucleic acid sequences for 
microorganism identification as well as for antimicrobial resistance. 
This device aids in the diagnosis of bloodstream infections when used 
in conjunction with other clinical and laboratory findings. However, 
the device does not replace traditional methods for culture and 
susceptibility testing.
    (b) Classification. Class II (special controls). The special 
control for this device is FDA's guideline document entitled ``Class II 
Special Controls Guideline: Multiplex Nucleic Acid Assay for 
Identification of Microorganisms and Resistance Markers from Positive 
Blood Cultures.'' For availability of the guideline document, see Sec.  
866.1(e).

    Dated: May 20, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-12741 Filed 5-26-15; 8:45 am]
 BILLING CODE 4164-01-P