[Federal Register Volume 74, Number 195 (Friday, October 9, 2009)]
[Rules and Regulations]
[Pages 52136-52138]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-24432]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2009-N-0119]


Medical Devices; Immunology and Microbiology Devices; 
Classification of Respiratory Viral Panel Multiplex Nucleic Acid Assay

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
classification of the respiratory viral panel multiplex nucleic acid 
assay into class II (special controls). The special controls that will 
apply to the device are three guidance documents entitled: ``Class II 
Special Controls Guidance Document: Respiratory Viral Panel Multiplex 
Nucleic Acid Assay,'' as applicable, ``Class II Special Controls 
Guidance Document: Testing for Human Metapneumovirus (hMPV) Using 
Nucleic Acid Assays,'' and as applicable,``Class II Special Controls 
Guidance Document: Testing for Detection and Differentiation of 
Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.'' The 
agency classified the device into class II (special controls) in order 
to provide a reasonable assurance of safety and effectiveness of the 
device. Elsewhere in this issue of the Federal Register, FDA is 
announcing the availability of the guidance documents that will serve 
as the special controls for this device.

DATES: This final rule is effective November 9, 2009. The 
classification was effective January 3, 2008.

FOR FURTHER INFORMATION CONTACT: Zivana Tezak, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, rm. 5550, Silver Spring, MD 20993, 301-796-6204.

SUPPLEMENTARY INFORMATION:

I. What Is the Background of This Rulemaking?

    In accordance with section 513(f)(1) of the Federal Food, Drug, and 
Cosmetic Act (the 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 (the amendments), 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 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 act (21 
U.S.C. 360(k) and part 807 (21 CFR part 807) of FDA's regulations.
    Section 513(f)(2) of the act provides that any person who submits a 
premarket notification under section 510(k) of the act for a device 
that has not previously been classified may, within 30 days after 
receiving an order classifying the device in class III under section 
513(f)(1), request FDA to classify the device under the criteria set 
forth in section 513(a)(1). FDA shall, within 60 days of receiving such 
a request, classify the device by written order. This classification 
shall be the initial classification of the device. Within 30 days after 
the issuance of an order classifying the device, FDA must publish a 
notice in the Federal Register announcing such classification (section 
513(f)(2) of the act).
    In accordance with section 513(f)(1) of the act, FDA issued an 
order on November 30, 2007, classifying the Luminex Molecular 
Diagnostics, Inc., xTAG\TM\ RVP (Respiratory Viral Panel) as 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 that was 
subsequently reclassified into class I or class II. On December 1, 
2007, Luminex Molecular Diagnostics, Inc., submitted a petition 
requesting classification of the xTAG\TM\ RVP under section 513(f)(2) 
of the act. The manufacturer recommended that the device be classified 
into class II.
    In accordance with section 513(f)(2) of the act, FDA reviewed the 
petition in order to classify the device under the criteria for 
classification set forth in section 513(a)(1) of the act. Devices are 
to be classified 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 petition, FDA determined that the Luminex 
Molecular Diagnostics, Inc., xTAG\TM\ RVP can be classified in class II 
with the establishment of special controls. FDA believes these special 
controls, in addition to general controls, will provide reasonable 
assurance of safety and effectiveness of the device.
    The device is assigned the generic name ``respiratory viral panel 
multiplex nucleic acid assay.'' It is identified as a qualitative in 
vitro diagnostic device that is intended to simultaneously detect and 
identify multiple viral nucleic acids extracted from human respiratory 
specimens or viral culture. The detection and identification of a 
specific viral nucleic acid from individuals exhibiting signs and 
symptoms of respiratory infection aids in the diagnosis of respiratory 
viral infection when used in conjunction with other clinical and 
laboratory findings.

[[Page 52137]]

    Respiratory illness caused by various commonly circulating 
respiratory viruses (e.g., Influenza A, RSV) can cause high morbidity 
and mortality, particularly in at-risk populations such as the elderly 
and the very young. Therefore, FDA has identified the following issues 
of safety or effectiveness requiring special controls for a respiratory 
viral panel multiplex nucleic acid assay, i.e. potential risks to 
health associated with this assay. These include (1) Failure of the 
device to perform as indicated, leading to inaccurate results or lack 
of results and (2) incorrect interpretation of results; both of these 
potential risks may lead to incorrect patient management decisions. For 
example, a false positive result could lead to unnecessary or 
inappropriate treatment for the misidentified viral illness, as well as 
delayed treatment of the actual infection, which may potentially be a 
more serious infection caused by bacteria or other pathogens. A false 
negative result could lead to failure to provide a diagnosis and the 
correct treatment, and may contribute to unnecessary treatment. A lack 
of result could lead to delayed diagnosis and inadequate treatment. 
Additionally, for assays that both detect Influenza A and differentiate 
between Influenza A subtypes, if a specimen yields a positive test 
result for Influenza A, but produces negative test results for all 
specific influenza A subtypes intended to be differentiated (i.e., H1 
or H3), then local, state or federal public health authorities should 
be notified to determine whether the specimen represents a novel strain 
of Influenza A, in accordance with the Morbidity and Mortality Weekly 
Report (http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5613a4.htm and 
http://www.cste.org/ps/2007pdfs/novelfluanndssjan10final23.pdf).\1\ 
Therefore, inaccurate results for influenza types and subtypes included 
in the respiratory viral panel may lead to inappropriate public health 
responses. Failure to interpret assay results in the context of the 
other laboratory results and the clinical presentation could lead to 
inappropriate or delayed treatment. The virus or viruses detected may 
not necessarily be the cause of the clinical symptoms, therefore 
positive assay results do not rule out bacterial co-infection, or co-
infection with other viruses.
---------------------------------------------------------------------------

    \1\ (FDA has verified the Web site addresses, but FDA is not 
responsible for any subsequent changes to the Web sites after this 
document publishes in the Federal Register.)
---------------------------------------------------------------------------

    FDA believes the class II special controls guidance documents will 
help mitigate potential risks by providing recommendations for 
performance evaluation, labeling, and measures to address the effects 
of ancillary reagents (specific reagents required under instructions 
for use of the assay but not provided) on safety and effectiveness of 
respiratory viral panel multiplex nucleic acid assays. The guidance 
documents also provide information on how to meet premarket (510(k)) 
submission requirements for the device. FDA believes that following the 
class II special controls guidance documents generally addresses the 
risks to health identified in the previous paragraph. Therefore, on 
January 3, 2008, FDA issued an order to the petitioner classifying the 
device into class II. FDA is codifying this classification by adding 21 
CFR 866.3980.
    Any firm submitting a 510(k) premarket notification for a 
respiratory viral panel multiplex nucleic acid assay will need to 
address the issues covered in the special controls guidances. However, 
the firm need only show that its device meets the recommendations of 
the guidances, or in some other way provides equivalent assurance of 
safety and effectiveness.
    Section 510(m) of the act provides that FDA may exempt a class II 
device from the premarket notification requirements under section 
510(k) of the 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, however, FDA has 
determined that premarket review of the system's key performance 
characteristics, test methodology, labeling, and other requirements as 
outlined in Sec.  807.87, will provide reasonable assurance that 
acceptable levels of performance for both safety and effectiveness will 
be addressed before marketing clearance. Thus, 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 
respiratory viral panel multiplex nucleic acid assay they intend to 
market.

II. What Is the Environmental Impact of This Rule?

    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.

III. What Is the Economic Impact of This Rule?

    FDA has examined the impacts of the final rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and 
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive 
Order 12866 directs agencies to assess all costs and benefits of 
available regulatory alternatives and, when regulation is necessary, to 
select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The agency believes that 
this final rule is not a significant regulatory action under the 
Executive order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because classification of these devices into class 
II will relieve manufacturers of the device of the cost of complying 
with the premarket approval requirements of section 515 of the act (21 
U.S.C. 360e), and may permit small potential competitors to enter the 
marketplace by lowering their costs, the agency certifies that the 
final rule will not have a significant economic impact on a substantial 
number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $130 million, using the most current (2007) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
final rule to result in any 1-year expenditure that would meet or 
exceed this amount.

IV. Does This Final Rule Have Federalism Implications?

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. Section 4(a) of the Executive order 
requires agencies to ``construe * * * a Federal statute to preempt 
State law only where the statute contains an express preemption 
provision or there is some other clear evidence that the Congress 
intended preemption of State law, or where the

[[Page 52138]]

exercise of State authority conflicts with the exercise of Federal 
authority under the Federal statute.'' Federal law includes an express 
preemption provision that preempts certain state requirements 
``different from or in addition to'' certain federal requirements 
applicable to devices. 21 U.S.C. 360k; Medtronic v. Lohr, 518 U.S. 470 
(1996); Riegel v. Medtronic, 128 S. Ct. 999 (2008). The special 
controls established by this final rule create ``requirements'' for 
specific medical devices under 21 U.S.C. 360k, even though product 
sponsors have some flexibility in how they meet those requirements. 
(Papike v. Tambrands, Inc., 107 F.3d 737, 740-42 (9th Cir. 1997)).

V. How Does This Rule Comply With the Paperwork Reduction Act of 1995?

    This final rule establishes as special controls three guidance 
documents 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 no. 
0910-0120. The collections of information in 21 CFR part 801 and 21 CFR 
809.10, regarding labeling, have been approved under OMB control no. 
0910-0485.

VI. What References Are on Display?

    The following reference has been placed on display in the Division 
of Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.

    1. Petition from Luminex Molecular Diagnostics, Inc., dated 
December 1, 2007.

List of Subjects in 21 CFR Part 866

    Medical devices.

0
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. Section 866.3980 is added to subpart D to read as follows:


Sec.  866.3980   Respiratory viral panel multiplex nucleic acid assay.

    (a) Identification. A respiratory viral panel multiplex nucleic 
acid assay is a qualitative in vitro diagnostic device intended to 
simultaneously detect and identify multiple viral nucleic acids 
extracted from human respiratory specimens or viral culture. The 
detection and identification of a specific viral nucleic acid from 
individuals exhibiting signs and symptoms of respiratory infection aids 
in the diagnosis of respiratory viral infection when used in 
conjunction with other clinical and laboratory findings. The device is 
intended for detection and identification of a combination of the 
following viruses:
    (1) Influenza A and Influenza B;
    (2) Influenza A subtype H1 and Influenza A subtype H3;
    (3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial 
Virus subtype B;
    (4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
    (5) Human Metapneumovirus;
    (6) Rhinovirus; and
    (7) Adenovirus.
    (b) Classification. Class II (special controls). The special 
controls are:
    (1) FDA's guidance document entitled ``Class II Special Controls 
Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid 
Assay;''
    (2) For a device that detects and identifies Human Metapneumovirus, 
FDA's guidance document entitled ``Class II Special Controls Guidance 
Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid 
Assays;'' and
    (3) For a device that detects and differentiates Influenza A 
subtype H1 and subtype H3, FDA's guidance document entitled ``Class II 
Special Controls Guidance Document: Testing for Detection and 
Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic 
Acid Assays.'' See Sec.  866.1(e) for the availability of these 
guidance documents.

    Dated: October 1, 2009.
Jeffrey Shuren,
Acting Director, Center for Devices and Radiological Health.
[FR Doc. E9-24432 Filed 10-8-09; 8:45 am]
BILLING CODE 4160-01-S