[Federal Register Volume 71, Number 55 (Wednesday, March 22, 2006)]
[Rules and Regulations]
[Pages 14377-14379]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 06-2742]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. 2006N-0100]


Medical Devices; Immunology and Microbiology Devices; 
Classification of Reagents for Detection of Specific Novel Influenza A 
Viruses

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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

SUMMARY: The Food and Drug Administration (FDA) is classifying Reagents 
for detection of specific novel influenza A viruses into class II 
(special controls). Special controls that will apply to the device are 
the guidance document entitled, ``Class II Special Controls Guidance 
Document: Reagents for Detection of Specific Novel Influenza A 
Viruses'' and limitations of distribution of these reagents. The agency 
is taking this action in response to a petition submitted under the 
Federal Food, Drug, and Cosmetic Act (the act) as amended by the 
Medical Device Amendments of 1976, the Safe Medical Devices Act of 
1990, the Food and Drug Administration Modernization Act of 1997, and 
the Medical Device User Fee and Modernization Act of 2002. 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. Elsewhere in this issue of the Federal Register, FDA is 
publishing a notice of availability of a guidance document that is a 
special control for this device.

DATES: This rule becomes effective April 21, 2006. The classification 
was effective February 3, 2006.

FOR FURTHER INFORMATION CONTACT: Claudia Gaffey, Center for Devices and 
Radiological Health (HFZ-440), Food and Drug Administration, 2098 
Gaither Rd., Rockville, MD 20850, 240-276-0496.

SUPPLEMENTARY INFORMATION:

I. Background

    In accordance with section 513(f)(1) of 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

[[Page 14378]]

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 previously marketed 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) of the act, request FDA to classify the device under the 
criteria set forth in section 513(a)(1) of the act. 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 (513(f)(2) of the act).
    In accordance with section 513(f)(1) of the act, FDA issued a 
notice on January 26, 2006, classifying the Centers for Disease Control 
and Prevention (CDC)'s Influenza A/H5 (Asian lineage) Virus Real-time 
RT-PCR Primer and Probe Set in class III, because it was not 
substantially equivalent to a class I or class II 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 January 26, 
2006, CDC submitted a petition requesting classification of the 
Influenza A/H5 (Asian lineage) Virus Real-time RT-PCR Primer and Probe 
Set 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 CDC's 
Influenza A/H5 (Asian lineage) Virus Real-time RT-PCR Primer and Probe 
Set 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, ``Reagents for 
detection of specific novel influenza A viruses.'' The Influenza A/H5 
(Asian lineage) Virus Real-time RT-PCR Primer and Probe Set is intended 
for the in vitro qualitative detection of Influenza A/H5 (Asian 
lineage) virus RNA either directly in patient respiratory specimens or 
in viral cultures for the presumptive laboratory identification of 
Influenza A/H5 (Asian lineage) virus. Testing with the Influenza A/H5 
(Asian lineage) Virus Real-time RT-PCR Primer and Probe Set should be 
used in conjunction with other laboratory testing and clinical 
observations for the following indications: (1) Providing 
epidemiological information for the surveillance of human infection 
with Influenza A/H5 (Asian lineage) virus; (2) identifying patients who 
may be infected with Influenza A/H5 (Asian lineage) virus based on 
clinical and epidemiological risk factors.
    FDA has identified the risks to health associated with this type of 
device as improper patient management and public health response, 
laboratory-acquired infection, and potential influenza A virus 
reassortment. Failure of testing with reagents for detection of 
specific novel influenza A viruses to correctly identify a specific 
novel influenza A virus, or failure to properly interpret test results 
obtained with these reagents, could lead to incorrect patient 
management decisions and inappropriate public health responses. Also, 
the use of reagents for detection of specific novel influenza A viruses 
without appropriate biosafety equipment and containment could result in 
laboratory-acquired infection and viral reassortment.
    The class II special controls guidance document provides 
information on how to meet premarket (510(k)) submission requirements 
for the device, including recommendations on validation of performance 
characteristics and labeling. It also addresses postmarket measures to 
assure the continued safety and effectiveness of the device by 
identifying changes in performance that may result from mutation in the 
virus that the device is intended to detect or changes in the 
prevalence of human infection. FDA believes that following the class II 
special controls guidance document and the additional special control 
specified in the classification regulation generally addresses the 
risks to health identified in the previous paragraph. Therefore, on 
February 3, 2006, FDA issued an order to the petitioner classifying the 
device into class II. FDA is codifying this classification by adding 
Sec.  866.3332.
    Following the effective date of this final classification rule, any 
firm submitting a 510(k) premarket notification for reagents for 
detection of specific novel influenza A viruses will need to address 
the issues covered in the special controls guidance, which contains 
recommendations for the contents of premarket notification submissions 
including performance testing, labeling, and postmarket data collection 
and analysis; and will have to limit distribution of these reagents to 
laboratories with: (1) Experienced personnel who have training in 
standardized molecular testing procedures and expertise in viral 
diagnosis, and (2) appropriate biosafety equipment and containment. 
However, regarding the issues covered in the special controls guidance, 
the firm need only show that its device meets the recommendations of 
the guidance 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 notification is necessary because FDA review 
of performance characteristics, test methodology, and labeling to 
satisfy requirements of 21 CFR 807.87(e), 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 containing information on the reagents for 
detection of specific novel influenza A viruses before marketing the 
device.

II. 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.

[[Page 14379]]

III. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866, 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 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 $115 million, using the most current (2003) 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. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does not contain policies that have substantial direct effects on the 
States, on the relationship between the National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, the agency has concluded 
that the rule does not contain policies that have federalism 
implications as defined in the Executive Order and, consequently, a 
federalism summary impact statement is not required.

V. Paperwork Reduction Act of 1995

    This final rule contains no collections of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) is not required. FDA concludes 
that the special controls guidance document contains information 
collection provisions that are subject to review and clearance by OMB 
under the PRA. Elsewhere in this issue of the Federal Register, FDA is 
publishing a notice announcing the availability of the guidance 
document entitled, ``Class II Special Controls Guidance Document: 
Reagents for Detection of Specific Novel Influenza A Viruses''; the 
notice contains an analysis of the paperwork burden for the guidance.

VI. Reference

    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 CDC, dated January 26, 2006.

List of Subjects in 21 CFR Part 866

    Biologics, Laboratories, 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 866.3332 is added to subpart D to read as follows:


Sec.  866.3332  Reagents for detection of specific novel influenza A 
viruses.

    (a) Identification. Reagents for detection of specific novel 
influenza A viruses are devices that are intended for use in a nucleic 
acid amplification test to directly detect specific virus RNA in human 
respiratory specimens or viral cultures. Detection of specific virus 
RNA aids in the diagnosis of influenza caused by specific novel 
influenza A viruses in patients with clinical risk of infection with 
these viruses, and also aids in the presumptive laboratory 
identification of specific novel influenza A viruses to provide 
epidemiological information on influenza. These reagents include 
primers, probes, and specific influenza A virus controls.
    (b) Classification. Class II (special controls). The special 
controls are:
    (1) FDA's guidance document entitled ``Class II Special Controls 
Guidance Document: Reagents for Detection of Specific Novel Influenza A 
Viruses.'' See Sec.  866.1(e) for information on obtaining this 
document.
    (2) The distribution of these devices is limited to laboratories 
with experienced personnel who have training in standardized molecular 
testing procedures and expertise in viral diagnosis, and appropriate 
biosafety equipment and containment.

    Dated: March 10, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 06-2742 Filed 3-21-06; 8:45 am]
BILLING CODE 4160-01-S