[Federal Register Volume 69, Number 189 (Thursday, September 30, 2004)]
[Rules and Regulations]
[Pages 58258-58260]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-22011]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 862

[Docket No. 2004P-0354]


Medical Devices; Clinical Chemistry and Clinical Toxicology 
Devices; Classification of Sirolimus Test System Devices

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is classifying the 
sirolimus test system device 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: Sirolimus Test 
Systems.'' The device is intended to measure sirolimus levels in whole 
blood as an aid to managing therapy for transplant patients receiving 
sirolimus, an immunosuppressive drug. 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 the special 
control for this device.

DATES: This rule becomes effective November 1, 2004. The classification 
was effective July 28, 2004.

FOR FURTHER INFORMATION CONTACT: Avis Danishefsky, Center for Devices 
and Radiological Health (HFZ-440), Food and Drug Administration, 2098 
Gaither Rd., Rockville, MD 20850, 301-594-1243, ext. 161.

SUPPLEMENTARY INFORMATION:

I. Background

    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 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. 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 document 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 a 
document on June 15, 2004, classifying the Microgenics CEDIA Sirolimus 
Assay 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 June 16, 2004, Microgenics Corp. submitted a petition requesting 
classification of the Microgenics CEDIA Sirolimus Assay under section 
513(f)(2) of the act. The manufacturer recommended that the device be 
classified into class II.
    In accordance with 513(f)(2) of the act, FDA reviewed the petition 
in order to classify the device under the criteria for classification 
set forth in 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 Microgenics CEDIA Sirolimus Assay 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 sirolimus test system and 
is identified as a device intended to quantitatively determine 
sirolimus concentrations in whole blood. Measurements are used as an 
aid in management of transplant patients receiving therapy with 
sirolimus.
    FDA has identified no direct risks to health related to use of 
sirolimus test systems. However, FDA has identified improper patient 
management, which involves failure of the test to perform as indicated 
or error in interpretation of results, as an indirect risk to health 
related to use of this device. For example, a falsely low sirolimus 
measurement could contribute to a decision to raise the sirolimus dose 
above that which is necessary for therapeutic benefit. This could 
result in increased risk in the form of thrombocytopenia, leukopenia, 
anemia, or hyperlipidemia. A falsely high sirolimus measurement could 
contribute to a decision to decrease the dose below

[[Page 58259]]

that which is necessary for immunosuppression. This could result in 
increased risk of rejection of the transplanted organ. Since optimal 
ranges for sirolimus may vary depending on the metabolite cross-
reactivity of the specific assay, as well as on clinical factors, use 
of assay results to adjust a treatment regimen without consideration of 
such factors could also lead to improper patient management. Therefore, 
in addition to the general controls of the act, the device is subject 
to special controls, identified as the guidance document entitled 
``Class II Special Controls Guidance Document: Sirolimus Test 
Systems.''
    The class II special controls guidance document also provides 
information on how to meet premarket (510(k)) submission requirements 
for the device, including recommendations on validation of performance 
characteristics and labeling. FDA believes that following the class II 
special controls guidance document generally addresses the risks to 
health identified in the previous paragraph. Therefore, on July 28, 
2004, FDA issued an order to the petitioner classifying the device into 
class II. FDA is codifying this classification by adding 21 CFR 
862.3840.
    Following the effective date of this final classification rule, any 
firm submitting a 510(k) premarket notification for a sirolimus test 
system 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, FDA has 
determined that premarket notification is necessary to provide 
reasonable assurance of safety and effectiveness. FDA review of 
performance characteristics, test methodology, and labeling to satisfy 
requirements of Sec.  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 sirolimus test system they intend to 
market, 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.

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 $110 million. 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 under the Paperwork 
Reduction Act of 1995 is not required.

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 Microgenics Corp., dated June 16, 2004.

List of Subjects in 21 CFR Part 862

    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 
862 is amended as follows:

PART 862--CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES

0
1. The authority citation for 21 CFR part 862 continues to read as 
follows:

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

0
2. Section 862.3840 is added to subpart D to read as follows:


Sec.  862.3840  Sirolimus test system.

    (a) Identification. A sirolimus test system is a device intended to 
quantitatively determine sirolimus concentrations in whole blood. 
Measurements are used as an aid in management of transplant patients 
receiving therapy with sirolimus.
    (b) Classification. Class II (special controls). The special 
control is FDA's guidance document entitled ``Class II Special Controls 
Guidance Document: Sirolimus Test Systems.'' See Sec.  862.1(d) for the 
availability of this guidance document.


[[Page 58260]]


    Dated: September 21, 2004.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 04-22011 Filed 9-29-04; 8:45 am]
BILLING CODE 4160-01-S