[Federal Register Volume 76, Number 56 (Wednesday, March 23, 2011)]
[Proposed Rules]
[Pages 16350-16353]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-6621]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2010-N-0029]
Medical Devices; Ovarian Adnexal Mass Assessment Score Test
System; Labeling; Black Box Restrictions
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
the regulation classifying ovarian adnexal mass assessment score test
systems to restrict these devices so that a prescribed warning
statement that addresses a risk identified in the special controls
guidance document must be in a black box and must appear in all
labeling, advertising, and promotional material. The black box warning
mitigates the risk to health associated with off-label use as a
screening test, stand-alone diagnostic test, or as a test to determine
whether or not to proceed with surgery. Elsewhere in this issue of the
Federal Register, FDA is announcing a final rule that classifies the
ovarian adnexal mass assessment score test system into class II
(special controls).
DATES: Submit either electronic or written comments by May 23, 2011.
ADDRESSES: You may submit comments, identified by Docket No. FDA-2010-
N-0029, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Written Submissions
Submit written submissions in the following ways:
Fax: 301-827-6870.
Mail/Hand delivery/Courier (for paper, disk, or CD-ROM
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
Instructions: All submissions received must include the Agency name
and Docket No. FDA-2010-N-0029. All comments received may be posted
without change to http://www.regulations.gov, including any personal
information provided. For additional information on submitting
comments, see the ``Comments'' heading of the SUPPLEMENTARY INFORMATION
section of this document.
Docket: For access to the docket to read background documents or
comments received, go to http://www.regulations.gov and insert the
docket number, found in brackets in the heading of this document, into
the ``Search'' box and follow the prompts and/or go to the Division of
Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Scott McFarland, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, rm. 5543, Silver Spring, MD 20993-0002, 301-
796-6217.
SUPPLEMENTARY INFORMATION:
I. What is the background of this proposed rule?
A. Ovarian Adnexal Mass Assessment Score Test System
An ovarian adnexal mass assessment score test system measures one
or more analytes in serum and combines the values into a single score
that is then used to determine the likelihood that the pre-surgical
adnexal mass in a woman not yet referred to an oncologist, is
malignant. An ovarian adnexal mass assessment score test system is
intended for use in those patients for whom surgery is planned, and
should not be used to decide whether or not a patient should receive
surgery. The test is used in conjunction with a clinical and
radiological evaluation of the patient by physicians in determining
whether the patient should be referred to a gynecologic oncologist for
surgery.
B. Identified Risk to Health
The ovarian adnexal mass assessment score test system is not
indicated for use as a screening or diagnostic test for ovarian cancer.
Off-label use of the test (e.g., in patients who are not already
[[Page 16351]]
identified as needing surgery for pelvic mass or without reference to
an independent clinical/radiological evaluation of the patient), may
lead to a high frequency of unnecessary further testing and surgery due
to false positive results, or to delay in tumor diagnosis due to false
negative results.
II. Why is FDA proposing to require black box warnings on ovarian
adnexal mass assessment score test system labeling, advertising, and
promotional material?
FDA has determined that in order to provide reasonable assurance of
safety and effectiveness, it is necessary to restrict the ovarian
adnexal mass assessment score test system to sale, distribution, and
use with labeling, advertising, and promotional material that bears a
warning statement in a black box that alerts users to the risk
associated with off-label use as a screening test, stand-alone
diagnostic test, or as a test to determine whether or not to proceed
with surgery. While FDA is establishing as a special control ``Guidance
for Industry and FDA Staff; Class II Special Controls Guidance
Document: Ovarian Adnexal Mass Assessment Score Test System'' which
recommends a black box warning to address the risk of off-label use,
FDA believes it is necessary to require this warning in labeling and
advertising by restricting the device under section 520(e) of the
Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360j(e)). A
notice of availability of this special controls guidance document is
published elsewhere in this issue of the Federal Register.
In cases in which class II and class III devices have significant
risks that would make the devices unsafe if used inappropriately, FDA
believes the risks need to be explained in warning statements placed in
a black box that is displayed prominently in the labeling, advertising,
and promotional material to ensure awareness by the end user. Awareness
of these important risks by the end user enables these devices to be
used safely. In this case, a prominent black box warning, which alerts
the user to the limitations of this device, is necessary in all
labeling, advertising, and promotional materials to allow ovarian
adnexal mass assessment score test system devices to be used safely.
The proposed prominent black box warning would read as follows:
[GRAPHIC] [TIFF OMITTED] TP23MR11.000
III. What is the legal authority for this proposed rule?
FDA is issuing this proposed rule under the authority of section
520(e) of the FD&C Act, which authorizes FDA to restrict sale,
distribution, and use of devices upon certain conditions. FDA is also
issuing this proposed rule under general device and administrative
provisions of the FD&C Act (sections 501, 510, 513, 515, 520, and 701
(21 U.S.C. 351, 360, 360c, 360e, 360j, and 371, respectively)).
IV. What is the environmental impact of this proposed rule?
FDA has determined under 21 CFR 25.34(b) and (f) 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.
V. What is the economic impact of this proposed rule?
FDA has examined the impacts of the proposed 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 proposed rule is not a significant regulatory action as defined by
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 proposed rule would strengthen existing
cautions against misuse of a new product, the Agency proposes to
certify 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
proposed rule to result in any 1-year expenditure that would meet or
exceed this amount.
An ovarian adnexal mass assessment test system is a device that
measures one or more proteins in serum to yield a single result for the
likelihood that an adnexal pelvic mass in a woman is malignant. Such a
test would identify women whose planned gynecologic surgery would
benefit from referral to a gynecological oncologist, despite negative
results from other clinical and radiographic tests for ovarian cancer.
In considering the appropriate level of regulatory oversight for
this device, FDA concluded in classifying the device that general and
special controls to minimize the risk of false positive and false
[[Page 16352]]
negative results, and risks associated with improper off-label use
would provide a reasonable assurance of safety and effectiveness of the
ovarian adnexal mass assessment test system. The special controls
guidance recommends use of a black box warning to minimize these risks.
Without such a strong warning, ovarian adnexal mass assessment test
systems might be used as a screening test, stand-alone diagnostic test,
or as a test to determine whether or not to proceed with surgery. Off-
label use of the test or the use of test results without consideration
of other diagnostic testing and clinical assessment could pose a risk
for morbidity and mortality due to nonreferral for oncologic evaluation
and treatment.
In order to require the specific black box warning on labeling and
on all advertising and promotional materials for the device, FDA is
issuing this proposed rule under section 520(e) of the FD&C Act.
Through this action, the Agency proposes to require a black box warning
on product labeling, advertising, and promotional materials for ovarian
adnexal mass assessment test systems. This warning would make users
aware of the limitations of this device and the serious risks
associated with its misuse. With the proposed addition of this black
box warning to product labeling, advertising, and marketing materials,
the Agency concludes there would be a reasonable assurance of the
safety and effectiveness of ovarian adnexal mass assessment test
systems.
The economic impact of this proposed rule is expected to be very
small. We are aware of a single manufacturer producing a single product
that would be affected by this black box warning. The manufacturer
should be able to incorporate the warning in the course of developing
its product labeling. The admonition against off-label use for this
device already exists, so the addition of this type of warning is not
expected to have a significant effect on the market for this product.
The expected impact of this proposal on the market for this product
would be a reduction in off-label use among the small number of users
who would be undeterred by a less visible warning.
The Regulatory Flexibility Act requires Agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. This proposal would impose almost no cost on
manufacturers. The proposed black box warning would strengthen an
existing admonition against off-label use and would not significantly
affect usage. Impacts on any entities would be so small as to be
difficult to quantify. For these reasons, the Agency proposes to
certify that this rule would not have a significant economic impact on
a substantial number of small entities.
VI. How does the Paperwork Reduction Act of 1995 apply to this proposed
rule?
FDA concludes that labeling provisions of this proposed rule are
not subject to review by the Office of Management and Budget because
they do not constitute a ``collection of information'' under the
Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). Rather, the
black box warning on all labeling, advertising, and promotional
materials for ovarian adnexal mass assessment score test system devices
is a ``public disclosure of information originally supplied by the
Federal Government to the recipient for the purpose of disclosure to
the public.'' (see 5 CFR 1320.3(c)(2)).
VII. What are the federalism impacts of this proposed rule?
FDA has analyzed this proposed 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 from 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)). If this proposed rule is made
final, the final rule would create a requirement under 21 U.S.C. 360k
for a black box warning statement that must appear in all advertising,
labeling, and promotional material for ovarian adnexal mass assessment
score test systems.
VIII. How do you submit comments on this proposed rule?
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) either electronic or written comments regarding this
document. It is only necessary to send one set of comments. It is no
longer necessary to send two copies of mailed comments. Identify
comments with the docket number found in brackets in the heading of
this document. Received comments may be seen in the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday.
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, FDA proposes
to amend 21 CFR part 866 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. In Sec. 866.6050 of subpart G, add new paragraph (c) to read as
follows:
Sec. 866.6050 Ovarian adnexal mass assessment score test system.
* * * * *
(c) Black Box Warning. Under section 520(e) of the Federal Food,
Drug, and Cosmetic Act these devices are subject to the following
restriction: A warning statement must be placed in a black box and must
appear in all advertising, labeling, and promotional material for these
devices. That warning statement must read:
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[GRAPHIC] [TIFF OMITTED] TP23MR11.001
Dated: March 16, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-6621 Filed 3-22-11; 8:45 am]
BILLING CODE 4160-01-P