[Federal Register: May 9, 2007 (Volume 72, Number 89)]
[Rules and Regulations]               
[Page 26290-26291]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09my07-6]                         


[[Page 26290]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. 2007N-0136]

 
Medical Devices; Immunology and Microbiology Devices; 
Classification of Gene Expression Profiling Test System for Breast 
Cancer Prognosis

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is classifying gene 
expression profiling test systems for breast cancer prognosis 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: Gene Expression Profiling Test System for Breast 
Cancer Prognosis.'' 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 final rule is effective June 8, 2007. The classification 
was effective February 6, 2007.

FOR FURTHER INFORMATION CONTACT: Reena Philip, Center for Devices and 
Radiological Health (HFZ-440), Food and Drug Administration, 2098 
Gaither Rd., Rockville, MD 20850, 240-276-1286.

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) 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 (section 513(f)(2) of the act).
    In accordance with section 513(f)(1) of the act, FDA issued an 
order on January 19, 2007, classifying the Agendia BV, MAMMAPRINT 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 which was 
subsequently reclassified into class I or class II. Agendia BV 
submitted a petition dated January 22, 2007, requesting classification 
of the MAMMAPRINT under section 513(f)(2) of the act. FDA filed the 
petition on January 30, 2007. 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 Agendia 
BV, MAMMAPRINT 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 ``gene expression profiling 
test system for breast cancer prognosis.'' It is identified as a device 
that measures the ribonucleic acid (RNA) expression level of multiple 
genes and combines this information to yield a signature (pattern or 
classifier or index) to aid in prognosis of previously diagnosed breast 
cancer.
    A gene expression profiling test system for breast cancer prognosis 
is intended to provide prognostic information to aid in clinical 
evaluation of breast cancer patients. Failure of this device to perform 
as indicated may lead to erroneous test results. False positive results 
will misclassify the patient into a higher risk group and false 
negative results will misclassify the patient into a lower risk group. 
Misclassification of cancer recurrence risk may lead to incorrect 
prognosis with attendant psychological distress, inaccurate counseling, 
and suboptimal patient care.
    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 premarket (510(k)) 
submission requirements for the device. FDA believes that following the 
class II special controls guidance document generally addresses the 
risks to health identified in the previous paragraph. Therefore, on 
February 6, 2007, FDA issued an order to the petitioner classifying the 
device into class II. FDA is codifying this classification by adding 
Sec.  866.6040.
    Following the effective date of this final classification rule, any 
firm submitting a 510(k) premarket notification for a gene expression 
profiling test system for breast cancer prognosis 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 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,

[[Page 26291]]

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 gene expression profiling test system for breast 
cancer prognosis 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, 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 $122 million, using the most current (2005) 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 collections of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

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 Agendia BV, dated January 22, 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:

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

0
2. Section 866.6040 is added to subpart G to read as follows:


Sec.  866.6040  Gene expression profiling test system for breast cancer 
prognosis.

    (a) Identification. A gene expression profiling test system for 
breast cancer prognosis is a device that measures the ribonucleic acid 
(RNA) expression level of multiple genes and combines this information 
to yield a signature (pattern or classifier or index) to aid in 
prognosis of previously diagnosed breast cancer.
    (b) Classification. Class II (special controls). The special 
control is FDA's guidance document entitled ``Class II Special Controls 
Guidance Document: Gene Expression Profiling Test System for Breast 
Cancer Prognosis.'' See Sec.  866.1(e) for the availability of this 
guidance document.

    Dated: May 1, 2007.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. E7-8871 Filed 5-8-07; 8:45 am]

BILLING CODE 4160-01-S