26290 Federal Register / Vol. 72, No. 89 / Wednesday, May 9, 2007 / Rules and Regulations 

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. 

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 

§ 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 § 807.87, will provide 

reasonable assurance that acceptable 

levels of performance for both safety 

and effectiveness will be addressed 

before marketing clearance. Thus, 


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Federal Register / Vol. 72, No. 89 / Wednesday, May 9, 2007 / Rules and Regulations 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. 

■ 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 

■ 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. 

■ 2. Section 866.6040 is added to 

subpart G to read as follows: 

§ 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 

§ 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 

DEPARTMENT OF THE INTERIOR 

Office of Surface Mining Reclamation 

and Enforcement 

30 CFR Part 935 

[OH–251–FOR] 

Ohio Regulatory Program 

AGENCY: Office of Surface Mining 

Reclamation and Enforcement, Interior. 

ACTION: Final rule; approval of 

amendment. 

SUMMARY: We are approving an 

amendment to the Ohio regulatory 

program (the ‘‘Ohio program’’) under 

the Surface Mining Control and 

Reclamation Act of 1977 (SMCRA or the 

Act). This amendment is intended to 

remove certain Conflict of Interest 

provisions from the approved Ohio 

program that were previously approved 

by OSM but have not been promulgated 

by Ohio through their rulemaking 

process. 

EFFECTIVE DATE: May 9, 2007. 

FOR FURTHER INFORMATION CONTACT: Mr. 

George Rieger, Chief, Pittsburgh Field 

Division, Telephone: (717) 782–4036. 

E-mail: grieger@osmre.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background on the Ohio Program 

II. Submission of the Amendment 

III. OSM’s Findings 

IV. Summary and Disposition of Comments 

V. OSM’s Decision 

VI. Procedural Determinations 

I. Background on the Ohio Program 

Section 503(a) of the Act permits a 

State to assume primacy for the 

regulation of surface coal mining and 

reclamation operations on non-Federal 

and non-Indian lands within its borders 

by demonstrating that its program 

includes, among other things, ‘‘a State 


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