16292 Federal Register / Vol. 76, No. 56 / Wednesday, March 23, 2011 / Rules and Regulations 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 866 

[Docket No. FDA–2011–N–0026] 

Medical Devices; Immunology and 

Microbiology Devices; Classification of 

Ovarian Adnexal Mass Assessment 

Score Test System 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final rule. 

SUMMARY: The Food and Drug 

Administration (FDA) is classifying the 

ovarian adnexal mass assessment score 

test system into class II (special 

controls). The special control that will 

apply to these devices is the guidance 

document entitled ‘‘Guidance for 

Industry and FDA Staff; Class II Special 

Controls Guidance Document: Ovarian 

Adnexal Mass Assessment Score Test 

System.’’ The Agency is classifying these 

devices into class II (special controls) 

because special controls, in addition to 

general controls, will provide a 

reasonable assurance of safety and 

effectiveness of these devices and there 

is sufficient information to establish 

special controls. 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 these devices. 

DATES: Effective Date: April 22, 2011. 

The classification was effective 

September 11, 2009. 

FOR FURTHER INFORMATION CONTACT: 

Donna Roscoe, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, rm. 5540, Silver Spring, 

MD 20993–0002, 301–796–6183. 

SUPPLEMENTARY INFORMATION: 

I. Legal Authority 

The Federal Food, Drug, and Cosmetic 

Act (FD&C Act) (21 U.S.C. 301 et seq.), 

as amended by the Medical Device 

Amendments of 1976 (the 1976 

amendments) (Pub. L. 94–295), the Safe 

Medical Devices Act of 1990 (the 

SMDA) (Pub. L. 101–629), and the Food 

and Drug Administration Modernization 

Act (the FDAMA) (Pub. L. 107–250) 

established a comprehensive system for 

the regulation of medical devices 

intended for human use. Section 513 of 

the FD&C Act (21 U.S.C. 360c) 

established three categories (classes) of 

devices, depending on the regulatory 

controls needed to provide reasonable 

assurance of their safety and 

effectiveness. The three categories of 

devices are class I (general controls), 

class II (special controls), and class III 

(premarket approval). 

FDA refers to devices that were not in 

commercial distribution before May 28, 

1976 (the date of enactment of the 1976 

amendments), as postamendments 

devices. Postamendments devices are 

classified automatically by statute 

(section 513(f) of the FD&C Act into 

class III without any FDA rulemaking 

process. These devices remain in class 

III and require premarket approval, 

unless: (1) FDA reclassifies the device 

into class I or II; (2) FDA issues an order 

classifying the device into class I or 

class II in accordance with section 

513(f)(2) of the FD&C Act; or (3) FDA 

issues an order finding the device to be 

substantially equivalent, under section 

513(i), 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 FD&C Act (21 

U.S.C. 360(k)) and part 807 of the 

regulations (21 CFR part 807). 

A person may market a 

preamendments device that has been 

classified into class III through 

premarket notification procedures, 

without submission of a premarket 

approval application (PMA) until FDA 

issues a final regulation under section 

515(b) of the FD&C Act (21 U.S.C. 

360e(b)) requiring premarket approval. 

Reclassification of postamendments 

devices is governed by section 513(f)(3) 

of the FD&C Act, formerly section 

513(f)(2). This section provides that 

FDA may initiate the reclassification of 

a device classified into class III under 

section 513(f)(1) of the FD&C Act, or the 

manufacturer or importer of a device 

may petition the Secretary for the 

issuance of an order classifying the 

device in class I or class II. FDA’s 

regulations in 21 CFR 860.134 set forth 

the procedures for the filing and review 

of a petition for reclassification of such 

class III devices. In order to change the 

classification of the device, it is 

necessary that the proposed new class 

have sufficient regulatory controls to 

provide reasonable assurance of the 

safety and effectiveness of the device for 

its intended use. 

FDAMA added section 513(f)(2) to the 

FD&C Act which addresses 

classification of postamendments 

devices. Section 513(f)(2) of the FD&C 

Act provides that, upon receipt of a ‘‘not 

substantially equivalent’’ determination, 

a 510(k) applicant may request FDA to 

classify a postamendments device into 

class I or class II. Within 60 days from 

the date of such a written request, FDA 

must classify the device by written 

order. If FDA classifies the device into 

class I or II, the applicant has then 

received clearance to market the device 

and it can be used as a predicate device 

for other 510(k)s. It is expected that this 

process will be used for low risk 

devices. This process does not apply to 

devices that have been classified by 

regulation into class III—i.e., 

preamendments class III devices, or 

class III devices for which a PMA is 

appropriate. 

II. Classification 

In accordance with section 513(f)(1) of 

the FD&C Act, FDA issued an order on 

July 16, 2009, classifying the 

Vermillion, Inc. OVA1TM Test into 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 class II. On 

July 22, 2009, Vermillion, Inc., 

submitted a petition requesting 

classification of the OVA1TM Test under 

section 513(f)(2) of the FD&C Act. The 

manufacturer recommended that the 

device be classified into class II (Ref. 1). 

In accordance with section 513(f)(2) of 

the FD&C Act, FDA reviewed the 

petition in order to classify the device 

under the criteria for classification set 

forth in section 513(a)(1). FDA classifies 

devices 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, 

the FDA determined that the device can 

be classified into class II with the 

establishment of special controls. FDA 

believes these special controls will 

provide reasonable assurance of the 

safety and effectiveness of the device. 

The device is assigned the generic 

name ovarian adnexal mass assessment 

score test system, and it is identified as 

a device that measures one or more 

proteins in serum or plasma. It yields a 

single result for the likelihood that an 

adnexal pelvic mass in a woman, for 

whom surgery is planned, is malignant. 

The test is for adjunctive use, in the 

context of a negative primary clinical 

and radiological evaluation, to augment 

the identification of patients whose 

gynecologic surgery requires oncology 

expertise and resources. 


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Federal Register / Vol. 76, No. 56 / Wednesday, March 23, 2011 / Rules and Regulations 16293 

III. Risks to Health 

FDA has identified the risks to health 

associated with this type of device as a 

false negative result, a false positive 

result, and off-label use as a screening 

test, stand-alone diagnostic test, or as a 

test to determine whether or not to 

proceed with surgery. Failure of the 

system to perform as indicated could 

lead to inaccurate risk assessment and 

improper management of patients with 

ovarian malignancies. Specifically, a 

falsely low ovarian adnexal mass score 

could result in a determination that the 

patient may not have ovarian 

malignancy, which could lead to less 

than optimal surgical expertise and 

resources. A falsely high ovarian 

adnexal mass score could result in a 

determination that the patient may have 

ovarian malignancy which could lead to 

inappropriate surgical decisions and 

unnecessary patient anxiety. Off-label 

use of the test, including use of test 

results as a stand-alone diagnostic 

without consideration of other 

diagnostic testing and clinical 

assessment, could also pose a risk for 

morbidity and mortality due to nonreferral for oncologic evaluation and 

treatment. 

FDA believes that the special controls 

guidance document, in addition to 

general controls, addresses the risks to 

health identified above and provides 

reasonable assurance of the safety and 

effectiveness of the device. Therefore, 

on September 11, 2009, FDA issued an 

order to the petitioner classifying the 

device into class II. FDA is codifying 

this device by adding § 866.6050. 

IV. 510(k) Premarket Notification 

Following the effective date of this 

final classification rule, any firm 

submitting a 510(k) premarket 

notification for ovarian adnexal mass 

assessment score 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 FD&C Act 

provides that FDA may exempt a class 

II device from the premarket notification 

requirements under section 510(k), 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 because 

of the risks of false positives and 

negatives and off label use that 

premarket notification is necessary to 

provide 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 ovarian adnexal 

mass assessment score test system they 

intend to market. 

V. 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. 

VI. Analysis of Impacts 

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 (Pub. L. 

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 this rule is 

deregulatory and imposes no new 

burdens, 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 $135 

million, using the most current (2009) 

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. 

A. Background 

An ovarian adnexal mass assessment 

test system is a device that measures 

one or more proteins in serum or plasma 

to yield a single result for the likelihood 

that an adnexal pelvic mass in a woman 

for whom surgery is planned is 

malignant. Such a test would identify 

women who would benefit from referral 

to a gynecological oncologist, despite 

negative results from other clinical and 

radiographic tests for ovarian cancer. 

The ovarian adnexal mass assessment 

test system device is currently classified 

into class III, the highest level of 

regulatory oversight. The device was 

initially placed in this classification 

automatically because there was no 

predicate device to which it could be 

found substantially equivalent. 

Manufacturers of ovarian adnexal mass 

assessment test systems, as makers of 

class III devices, bear all costs 

associated with premarket approval, 

including the cost of submitting the 

premarket approval application (PMA) 

and payment of user fees. The costs 

associated with the submission of the 

PMA are substantial, potentially 

reaching $1,000,000. 

We are aware of a single manufacturer 

producing a single product affected by 

this device classification. The 

manufacturer submitted a request for 

Evaluation of Automatic Class III 

Designation, recommending 

classification into class II. Placing this 

device in a classification with less 

burdensome regulatory requirements 

affects the current manufacturer and 

potentially affects others, encouraging 

future entry into this market. 

In response to the manufacturer 

request, FDA is classifying ovarian 

adnexal mass assessment test system 

devices into class II. Based on the 

experience of FDA reviewers, the 

Agency concludes that the ovarian 

adnexal mass assessment test system 

device would not be safe and effective 

under general controls. FDA has 

therefore chosen special controls to 

address the specific risks of false 

positives, false negatives, and off-label 

use. These special controls in addition 

to the application of general controls 

would be consistent with the principle 

of applying the least degree of 

regulatory control necessary to provide 

reasonable assurance of safety and 

effectiveness. The application of this 

intermediate level of regulatory 

oversight would be consistent with the 

treatment of other devices with similar 

risk profiles. 

The special controls recommend a 

black box warning to reduce the risks of 

off-label use. The Agency is separately 


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16294 Federal Register / Vol. 76, No. 56 / Wednesday, March 23, 2011 / Rules and Regulations 

proposing to require the application of 

the black box warning to labeling and 

advertising through notice and comment 

rulemaking. For the purposes of this 

analysis, we assume that this final rule 

will establish special controls with a 

reference to a black box warning 

regarding off-label use, but the analysis 

of the impact of the addition of the 

warning to the product label will be 

included in a separate rulemaking. 

B. Costs of the Final Rule 

This final rule is deregulatory. Device 

manufacturers currently subject to class 

III requirements will be subject to the 

less burdensome requirements for 

makers of class II devices. Through this 

classification, manufacturers of ovarian 

adnexal mass assessment test system 

devices will be relieved of the obligation 

to submit a PMA prior to marketing. The 

cost of submitting a PMA can reach 

$1,000,000, plus user fees of an 

additional $217,787 in FY 2010, 

increasing to $256,384 in 2012. This 

device classification will substantially 

reduce an existing burden on 

manufacturers of ovarian adnexal mass 

assessment test system devices. 

Considering the cost of submitting a 

PMA plus the relevant user fees, the 

reduction could be $1,000,000 per 

device. 

The Regulatory Flexibility Act 

requires Agencies to analyze regulatory 

options that would minimize any 

significant impact of a rule on small 

entities. Classification of the affected 

device into class II after it had 

automatically been placed in class III 

will relieve manufacturers of the cost of 

complying with the premarket approval 

requirements of section 515 of the FD&C 

Act. Because of the reduced burden, the 

Agency does not believe that this final 

rule will have a significant economic 

impact on a substantial number of small 

entities. 

VII. Federalism 

FDA has analyzed this final rule in 

accordance with the principles set forth 

in Executive Order 13132. Section 4(a) 

of the Executive Order requires 

Agencies to ‘‘construe * * * a Federal 

statute to preempt State law only where 

the statute contains an express 

preemption provision or there is some 

other clear evidence that the Congress 

intended preemption of State law, or 

where the exercise of State authority 

conflicts with the exercise of Federal 

authority under the Federal statute.’’ 

Federal law includes an express 

preemption provision that preempts 

certain state requirements ‘‘different or 

in addition to’’ certain federal 

requirements applicable to devices. 21 

U.S.C. 360k; See Medtronic v. Lohr, 518 

U.S. 470 (1996); Riegel v. Medtronic, 

Inc., 552 U.S. 312 (2008). The special 

controls established by this rulemaking 

create ‘‘requirements’’ to address each 

identified risk to health presented by 

these specific medical devices under 21 

U.S.C. 360k, even though product 

sponsors may have flexibility in how 

they meet those requirements. Cf. 

Papike v. Tambrands, Inc., 107 F.3d 

737, 740–42 (9th Cir. 1997). 

VIII. Paperwork Reduction Act of 1995 

This final rule establishes as special 

controls a guidance document that 

refers to previously approved 

collections of information found in 

other FDA regulations. These 

collections of information are subject to 

review by the Office of Management and 

Budget under the Paperwork Reduction 

Act of 1995 (44 U.S.C. 3501–3520). 

Elsewhere in this issue of the Federal 

Register, FDA is publishing a notice 

announcing the availability of the 

guidance document entitled ‘‘Guidance 

for Industry and FDA Staff; Class II 

Special Controls Guidance Document: 

Ovarian Adnexal Mass Assessment 

Score Test System.’’ The notice contains 

an analysis of the paperwork burden for 

the guidance. 

IX. References 

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 Vermillion, Inc., for 

reclassification of the OVA1TM Test 

submitted July 22, 2009. 

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 866.6050 is added to 

subpart G to read as follows: 

§ 866.6050 Ovarian adnexal mass 

assessment score test system. 

(a) Identification. An ovarian/adnexal 

mass assessment test system is a device 

that measures one or more proteins in 

serum or plasma. It yields a single result 

for the likelihood that an adnexal pelvic 

mass in a woman, for whom surgery is 

planned, is malignant. The test is for 

adjunctive use, in the context of a 

negative primary clinical and 

radiological evaluation, to augment the 

identification of patients whose 

gynecologic surgery requires oncology 

expertise and resources. 

(b) Classification. Class II (special 

controls). The special control for this 

device is FDA’s guidance document 

entitled ‘‘Class II Special Controls 

Guidance Document: Ovarian Adnexal 

Mass Assessment Score Test System.’’ 

For the availability of this guidance 

document, see § 866.1(e). 

Dated: March 16, 2011. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2011–6620 Filed 3–22–11; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HOMELAND 

SECURITY 

Coast Guard 

33 CFR Part 117 

[Docket No. USCG–2011–0100] 

RIN 1625–AA09 

Drawbridge Operation Regulation; 

Buffalo Bayou, Mile 4.3, Houston, 

Harris County, TX 

AGENCY: Coast Guard, DHS. 

ACTION: Final rule. 

SUMMARY: The Coast Guard is removing 

the existing drawbridge operation 

regulation for the drawbridge across 

Buffalo Bayou, mile 4.3, Houston, Harris 

County, Texas. The bridge was replaced 

with a fixed bridge in 1991 and the 

operating regulation is no longer 

applicable or necessary. 

DATES: This rule is effective March 23, 

2011. 

ADDRESSES: Documents indicated in this 

preamble as being available in the 

docket, are part of docket USCG–2011– 

0100 and are available by going to 

http://www.regulations.gov, inserting 

USCG–2011–0100 in the ‘‘Keyword’’ 

box, and then clicking ‘‘Search.’’ This 

material is also available for inspection 

or copying at the Docket Management 

Facility (M–30), U.S. Department of 

Transportation, West Building Ground 


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