[Federal Register Volume 68, Number 211 (Friday, October 31, 2003)]
[Rules and Regulations]
[Pages 62007-62008]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-27392]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. 2003D-0221]


Medical Devices; Immunology and Microbiology Devices; 
Classification of the Endotoxin Assay

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is classifying the 
endotoxin assay into class II (special controls). 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 amendments), the Safe Medical Devices Act of 
1990 (SMDA), the Food and Drug Administration Modernization Act of 1997 
(FDAMA), and the Medical Device User Fee and Modernization Act of 2002 
(MDUFMA). The agency is classifying this 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 a guidance document 
that will serve as the special control for the device.

DATES: This rule is effective December 1, 2003.

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, 301-594-2096.

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 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 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 21 CFR part 807 of the FDA 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 
issuing an order classifying the device, FDA will publish a notice in 
the Federal Register announcing the classification.
    On April 14, 2003, FDA received a petition submitted under section 
513(f)(2) of the act by the Devices and Diagnostics Consulting Group, 
Inc., seeking an evaluation of the automatic class III designation of 
its ``endotoxin activity assay.'' In accordance with section 513(f)(1) 
of the act, FDA issued an order classifying the device 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 that was 
subsequently reclassified into class I or II. After reviewing 
information submitted in the petition, FDA determined that the 
endotoxin activity assay could be classified in class II under the 
generic name, endotoxin assay, with the establishment of special 
controls. This device is intended to measure endotoxin activity as an 
aid in the risk assessment on the first day of the patient's admission 
to the intensive care unit (ICU). FDA believes that class II special 
controls, in addition to the general controls, will provide reasonable 
assurance of the safety and effectiveness of the device.
    FDA has identified the risk to health associated specifically with 
this type of device as improper patient management. Therefore, in 
addition to the general controls of the act, the device is subject to a 
special controls guidance document entitled ``Class II Special Controls 
Guidance Document: Endotoxin Assay.'' FDA believes this special 
controls guidance document will reasonably assure the safety and 
effectiveness of this type of device.
    The class II special controls guidance provides information on how 
to meet

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premarket notification submission (510(k)) requirements for the device, 
including recommendations for labeling and performance studies. FDA 
believes manufacturers of the device that adhere to the class II 
special controls guidance will address the potential risk to health 
identified in the previous paragraph.
    Following the effective date of this final classification rule, any 
firm submitting a 510(k) for an endotoxin assay will need to address 
the issues covered in the special controls guidance document. However, 
the firm need only show that its device meets the recommendations of 
the guidance or in some other way provides equivalent assurances of 
safety and effectiveness.
    Section 510(m) of the act provides that FDA may exempt a class II 
device from the premarket notification requirement 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, FDA has 
determined that premarket notification is necessary to provide 
reasonable assurance of safety and effectiveness and, therefore, the 
device is not exempt from the premarket notification requirements. The 
endotoxin assay is a device that uses serological techniques in whole 
blood. The device is intended for use in conjunction with other 
laboratory findings and clinical assessment of the patient to aid in 
the risk assessment of critically ill patients for progression to 
severe sepsis. FDA review of performance characteristics and labeling 
will ensure that acceptable levels of performance for both safety and 
effectiveness are addressed before marketing clearance. Thus, persons 
who intend to market this device must submit to FDA a 510(k) containing 
information on the endotoxin assay before marketing the device.
    On June 16, 2003, FDA issued an order classifying the endotoxin 
activity assay and substantially equivalent devices of this generic 
type into class II. FDA identifies this generic type of device as an 
endotoxin assay, which is intended for the use of serological 
techniques in whole blood. The device is intended for use in 
conjunction with other laboratory findings and clinical assessment of 
the patient to aid in the risk assessment of critically ill patients 
for progression to severe sepsis. The order also stated the endotoxin 
activity assay is intended for use only on the first day of admission 
to the ICU.
    FDA is codifying the classification of this device by adding 21 CFR 
866.3610. The order also identifies a special control applicable to 
this device, a guidance document entitled ``Class II Special Controls 
Guidance Document: Endotoxin Assay.'' Elsewhere in this issue of the 
Federal Register, FDA is announcing the availability of a guidance 
document that will serve as the special control for 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.

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 (2 U.S.C. 1501 et seq.). 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 consistent with the regulatory philosophy and 
principles identified in the Executive order. In addition, the final 
rule is not a significant regulatory action as defined by the Executive 
order and so it is not subject to review 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. FDA knows of only one manufacturer of this type of 
device. Classification of these devices in 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, therefore, certifies that the final 
rule will not have a significant impact on a substantial number of 
small entities. In addition, this final rule will not impose costs of 
$100 million or more on either the private sector or State, local, and 
tribal governments in the aggregate and, therefore, a summary statement 
of analysis under section 202(a) of the Unfunded Mandates Reform Act is 
not required.

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 under the Paperwork 
Reduction Act of 1995 is not required.

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 866.3610 is added to subpart D to read as follows:


866.3610  Endotoxin assay.

    (a) Identification. An endotoxin assay is a device that uses 
serological techniques in whole blood. The device is intended for use 
in conjunction with other laboratory findings and clinical assessment 
of the patient to aid in the risk assessment of critically ill patients 
for progression to severe sepsis.
    (b) Classification. Class II (special controls). The special 
control for this device is the FDA guidance entitled ``Class II Special 
Controls Guidance Document: Endotoxin Assay.'' See Sec.  866.1(e) for 
the availability of this guidance document.

    Dated: October 17, 2003.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 03-27392 Filed 10-30-03; 8:45 am]
BILLING CODE 4160-01-S