[Federal Register Volume 73, Number 98 (Tuesday, May 20, 2008)]
[Rules and Regulations]
[Pages 29052-29054]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-11263]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2008-N-0231]


Medical Devices; Immunology and Microbiology Devices; 
Classification of Plasmodium Species Antigen Detection Assays

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is classifying 
Plasmodium species antigen detection assays into class II (special 
controls). The special control that will apply to the device is the 
guidance document entitled ``Class II Special Controls Guidance 
Document: Plasmodium Species Antigen Detection Assays.'' 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 
announcing the availability of the guidance document that will serve as 
the special control for this device.

DATES: This rule is effective June 19, 2008. The classification was 
effective June 13, 2007.

FOR FURTHER INFORMATION CONTACT: Freddie M. Poole, Center for Devices 
and Radiological Health (HFZ-440), Food and Drug Administration, 2098 
Gaither Rd., Rockville, MD 20850, 240-276-0712.

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 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 
this classification (section 513(f)(2) of the act).
    In accordance with section 513(f)(1) of the act, FDA issued an 
order on February 22, 2007, classifying the Binax NOW[supreg] Malaria 
Test in 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 March 22, 2007, Binax, Inc., submitted a petition requesting 
classification of the Binax NOW[supreg] Malaria Test under section 
513(f)(2) of the act. The manufacturer recommended that the device be 
classified into class II (Ref. 1).
    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 Binax 
NOW[supreg] Malaria Test 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 ``Plasmodium species 
antigen detection assays.'' It is identified as a device that employs 
antibodies for the detection of specific malaria parasite antigens, 
including histidine-rich protein-2 (HRP2) specific antigens, and pan 
malarial antigens in human whole blood. These devices are used for 
testing specimens from individuals who have signs and symptoms 
consistent with malaria infection. The detection of these antigens aids 
in the clinical laboratory diagnosis of malaria caused by the four 
malaria species capable of infecting humans: Plasmodium falciparum, 
Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae, and aids 
in the differential diagnosis of P. falciparum infections from other 
less virulent Plasmodium species. The device is intended for use in 
conjunction with other clinical laboratory findings.
    FDA has identified the following risks to health associated with 
the device. Failure of the test to perform as indicated may lead to 
improper patient management and/or inappropriate public health 
responses. For example, false negative results may lead to delays in 
providing, or even failure to provide, definitive diagnosis and 
appropriate treatment. A false positive test result may subject 
individuals to unnecessary and/or inappropriate treatment for malaria, 
and failure to appropriately diagnose and treat the actual disease 
condition. The unnecessary use of alternative drugs, such as quinine, 
mefloquine and artemisinin, typically used in high resistance areas 
outside the United States, is problematic because these drugs are less 
safe than the first and second line treatments.
    In addition, malaria is a significant public health issue and is a 
reportable disease to the Centers for Disease Control and Prevention. 
Local and state health departments are required to conduct case 
investigations upon receiving a report of a malaria infection. A false 
positive test result could place an undue burden on local and state 
health department resources and could also lead to unnecessary public 
health actions (e.g., unnecessary or inappropriate treatment and 
management of others in the community). On the other hand, a false 
negative result could lead to a delay in recognition of increased 
transmission of the parasitic infection.
    An error in interpretation of results could also pose a risk, 
especially decisions about treatment without confirmation of negative 
results by

[[Page 29053]]

microscopy, which is more sensitive than antigen detection assays for 
detecting malaria parasites in blood.

            Table 1.--Risks to Health and Mitigation Measures
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          Identified Risks                   Mitigation Measures
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Failure of the assay to perform      Section 6. of the guidance--
 properly, i.e., false negative or    Performance Characteristics
 false positive results which can    Section 7. of the guidance--
 lead to improper patient             Labeling
 management and/or inappropriate
 public health responses
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Failure to properly interpret test   Section 6. of the guidance--
 results                              Performance Characteristics
                                     Section 7. of the guidance--
                                      Labeling
------------------------------------------------------------------------

    FDA believes the class II special controls guidance document 
generally addresses the risks to health identified in the previous 
paragraphs. FDA believes the class II special controls guidance 
document will aid in mitigating potential risks by providing 
recommendations on labeling and validation of performance 
characteristics. The guidance document also provides information on how 
to meet 510(k) premarket notification submission requirements for the 
device. FDA believes that the special controls, in addition to general 
controls, address the risks to health identified previously and provide 
reasonable assurances of the safety and effectiveness of the device 
type. Therefore, on June 13, 2007, FDA issued an order to the 
petitioner classifying the device into class II (Ref. 2). FDA is 
codifying this classification by adding 21 CFR 866.3402.
    Following the effective date of this final classification rule, any 
firm submitting a premarket notification submission for a Plasmodium 
species antigen detection assay will need to address the issues covered 
in the special controls guidance. However, 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 to provide a 
reasonable assurance of the safety and effectiveness of the device and, 
therefore, this type of device 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 Plasmodium species 
antigen detection assays 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 as defined by 
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 this device into class II 
will relieve manufacturers 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 $127 million, using the most current (2006) 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. 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. How Does This Rule Comply With the Paperwork Reduction Act of 1995?

    This final rule contains no new information collection provisions. 
Therefore, clearance by the Office of Management and Budget (OMB) under 
the Paperwork Reduction Act of 1995 is not required.

VI. What References Are on Display?

    The following references have 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 Binax, Inc., dated March 22, 2007.
    2. Order classifying Binax NOW[reg] Malaria Test, dated June 13, 
2007.

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:


[[Page 29054]]


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

0
2. Section 866.3402 is added to subpart D to read as follows:


Sec.  866.3402  Plasmodium species antigen detection assays.

    (a) Identification. A Plasmodium species antigen detection assay is 
a device that employs antibodies for the detection of specific malaria 
parasite antigens, including histidine-rich protein-2 (HRP2) specific 
antigens, and pan malarial antigens in human whole blood. These devices 
are used for testing specimens from individuals who have signs and 
symptoms consistent with malaria infection. The detection of these 
antigens aids in the clinical laboratory diagnosis of malaria caused by 
the four malaria species capable of infecting humans: Plasmodium 
falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium 
malariae, and aids in the differential diagnosis of Plasmodium 
falciparum infections from other less virulent Plasmodium species. The 
device is intended for use in conjunction with other clinical 
laboratory findings.
    (b) Classification. Class II (special controls). The special 
control is FDA's guidance document entitled ``Class II Special Controls 
Guidance Document: Plasmodium species Antigen Detection Assays.'' See 
Sec.  866.1(e) for the availability of this guidance document.

    Dated: April 30, 3008.
Daniel G. Schultz,
Director, Center for Devices and Radiological Health.
[FR Doc. E8-11263 Filed 5-19-08; 8:45 am]
BILLING CODE 4160-01-S