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General and Plastic Surgery Devices; Reclassification of the Absorbable Hemostatic Device
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[Federal Register: October 31, 2006 (Volume 71, Number 210)]
[Proposed Rules]
[Page 63728-63732]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr31oc06-23]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 878
[Docket No. 2006N-0362]
General and Plastic Surgery Devices; Reclassification of the
Absorbable Hemostatic Device
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
reclassify the absorbable hemostatic device intended to produce
hemostasis from class III (premarket approval) into class II (special
controls). FDA is proposing this reclassification in accordance with
the Federal Food, Drug, and Cosmetic Act (the act). Elsewhere in this
issue of the Federal Register, FDA is announcing the availability of a
draft guidance document that would serve as the special control if FDA
reclassifies this device.
DATES: Submit written comments by January 29, 2007. See section X of
this document for the proposed effective date of a final rule based on
this proposed rule.
ADDRESSES: You may submit comments, identified by Docket No. 2006N-
0362, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following ways:
? Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
? Agency Web site: http://www.fda.gov/dockets/ecomments.
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
Submit written submissions in the following ways:
[[Page 63729]]
? 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.
To ensure more timely processing of comments, FDA is no longer
accepting comments submitted to the agency by e-mail. FDA encourages
you to continue to submit electronic comments by using the Federal
eRulemaking Portal or the agency Web site, as described in the
Electronic Submissions portion of this paragraph.
Instructions: All submissions received must include the agency name
and Docket No. for this rulemaking. All comments received may be posted
without change to http://www.fda.gov/ohrms/dockets/default.htm,
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.fda.gov/ohrms/dockets/default.htm
and insert the docket number(s), 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: David Krause, Center for Devices and
Radiological Health (HFZ-410), Food and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20850, 301-594-3090, ext. 141.
SUPPLEMENTARY INFORMATION:
I. Regulatory Authorities
The act, as amended by the Medical Device Amendments of 1976 (the
1976 amendments) (Public Law 94-295), the Safe Medical Devices Act of
1990 (SMDA) (Public Law 101-629), and the Food and Drug Administration
Modernization Act of 1997 (FDAMA) (Public Law 105-115), among other
amendments, established a comprehensive system for the regulation of
medical devices intended for human use. Section 513 of the 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).
The 1976 amendments broadened the definition of ``device'' in
section 201(h) of the act (21 U.S.C. 321(h)) to include certain
articles that were once regulated as drugs. Under the 1976 amendments,
Congress classified all transitional devices, i.e., those devices
previously regulated as new drugs, including the absorbable hemostatic
device, into class III. SMDA amended section 520(l) of the act (21
U.S.C. 360j(l)) to direct FDA to collect certain safety and
effectiveness information from the manufacturers of transitional
devices still remaining in class III to determine whether the devices
should be reclassified into class II (special controls) or class I
(general controls). The legislative history of the SMDA reflects
congressional concern that many transitional devices were being
overregulated in class III (H. Rept. 808, 101st Cong., 2d sess. 26-27
(1990); S. Rept. 513, 101st Cong., 2d sess. 27 (1990)).
Accordingly, in the Federal Register of November 14, 1991 (56 FR
57960), FDA issued an order under section 520(l)(5)(A) of the act,
requiring manufacturers of transitional devices, including the
absorbable hemostatic device (21 CFR 878.4490), to submit to FDA a
summary of and a citation to any information known or otherwise
available to them respecting the devices, including adverse safety or
effectiveness information, which had not been submitted under section
519 of the act (21 U.S.C. 360i).
Manufacturers were to submit the summaries and citations to FDA by
January 13, 1992. However, because of misunderstandings and
uncertainties regarding the information required by the order, and
whether the order applied to certain manufacturers' devices, many
transitional class III device manufacturers failed to comply with the
reporting requirement by January 13, 1992. Consequently, in the Federal
Register of March 10, 1992 (57 FR 8462), FDA extended the reporting
period to March 31, 1992.
Section 520(l)(5)(B) of the act provides that, after the issuance
of an order requiring manufacturers to submit any information known or
otherwise available respecting the devices, but before December 1,
1992, FDA was to publish regulations either leaving transitional class
III devices in class III or reclassifying them into class I or II.
Subsequently, as permitted by section 520(l)(5)(C) of the act, in the
Federal Register of November 30, 1992 (57 FR 56586), the agency
published a notice extending the period for issuing such regulations
until December 1, 1993. Due to limited resources, FDA was unable to
publish the regulations before the December 1, 1993, deadline.
II. Regulatory Background of the Device
In the Federal Register of December 16, 1977 (42 FR 63472), FDA
identified the absorbable hemostatic agent and dressing as a
transitional device that is a class III device that FDA previously
regulated as a drug and for which premarket approval was immediately
required. Since enactment of the 1976 amendments, FDA has approved
numerous premarket approval (PMA) applications and PMA supplements
authorizing the commercial distribution of new absorbable hemostatic
agents and dressings in the United States.
Absorbable hemostatic products that include biological products or
drug components are combination products as defined in 21 CFR 3.2(e).
When the device component is responsible for the primary mode of action
of the absorbable hemostatic product, it is assigned to CDRH for
premarket review and regulation. If the absorbable hemostatic device is
reclassified, these combination products will be subject to premarket
notification [510(k)]
requirements.
III. Description of the Device
The current identification of the device states that an
``absorbable hemostatic agent or dressing is a device intended to
produce hemostasis by accelerating the clotting process of blood. It is
absorbable.'' Absorbable hemostatic devices are primarily applied
during surgical procedures in order to control bleeding that is not
readily controlled via conventional means, such as cautery or ligation.
At other times, an absorbable hemostatic device may be applied due to
the inaccessibility of a site to conventional hemostatic methods.
FDA is proposing the following device name and identification based
on the agency's review to more accurately identify the device: An
absorbable hemostatic device is an absorbable device that is placed in
the body during surgery to produce hemostasis by accelerating the
clotting process of blood.
IV. Recommendation of the Panel
At a July 8, 2002, public meeting of FDA's General and Plastic
Surgery Devices Panel (the Panel), the Panel requested that the agency
provide information on the potential content of a class II special
controls guidance document for the absorbable hemostatic device. The
Panel requested this information to enable them to make an appropriate
recommendation on possible reclassification of the device (Ref. 1).
[[Page 63730]]
At a July 24, 2003, public meeting of the Panel, the agency
presented the possible content of a class II special controls guidance
for the absorbable hemostatic device (Ref. 2). The Panel unanimously
recommended that the absorbable hemostatic device be reclassified from
class III into class II and recommended that a class II guidance
document be the special control for the device. The Panel based the
recommendations on the information provided by FDA, the presentations
to the panel by manufacturers and FDA, the Panel's deliberations at the
meeting, and their personal experience with the device.
V. Risks to Health
After considering the information in the panel's recommendation, as
well as the published literature and Medical Device Reports, FDA has
evaluated the risks to health associated with use of the absorbable
hemostatic device and determined that the following risks to health are
associated with its use.
A. Uncontrolled Bleeding
The absorbable hemostatic device is intended for use during
surgical procedures as an adjunct to hemostasis when conventional means
fail to produce hemostasis or are impractical. Patients receiving
antiplatelet/anticoagulation therapy have increased blood clotting
times. This increase in blood clotting time occurs even when an
absorbable hemostatic device is used during the surgical procedure to
control bleeding. Failure to completely control bleeding can lead to
death or severe injury.
B. Hematoma
If small amounts of bleeding persist following the application of
an absorbable hemostatic device, the accumulation of blood behind the
device will form a hematoma. The hematoma may press on soft tissue and
cause soft tissue or nerve damage. A hematoma may also result in
infection (see section V.C of this document).
C. Infection
An absorbable hemostatic device may serve as a nidus for infection
and abscess formation. Absorbable hemostatic devices are manufactured
from collagen, gelatin, or oxidized regenerated cellulose; some
collagen and gelatin hemostatic devices may contain FDA-licensed bovine
thrombin. Bacteria can grow on these device materials. For example, the
use of absorbable hemostatic devices in nasal surgery has caused toxic
shock syndrome.
D. Wound Dehiscence
The use of an absorbable hemostatic device near sites of skin
incision closures has interfered with the healing of the incision. This
interference is due to mechanical interposition of the device and is
not due to intrinsic interference with the wound healing process.
E. Foreign Body Reactions
The absorbable hemostatic device has been associated with foreign
body reactions involving fluid accumulation due to encapsulation of the
device. Such encapsulated devices have resulted in granuloma formation,
inflammation, and edema, which may require surgical removal.
F. Immunologic Reactions
Absorbable hemostatic devices are composed of animal or plant
derived proteins and/or polysaccharides. These devices are made of
bovine collagen, porcine and bovine gelatin, and regenerated oxidized
cellulose; some may also include FDA-licensed bovine thrombin as a
combination product component. Some patients are allergic to these
animal or plant-derived materials. Patients allergic to bovine thrombin
containing hemostatic devices may form antibodies to bovine Factor
Va that may cross react with human Factor Va
resulting in a potentially fatal coagulopathy.
G. Adhesion Formation
An absorbable hemostatic device, in the presence of coagulated
blood and tissue fluid, often leads to scarring and adhesion formation
in the weeks and months following the surgical procedure. The surgical
procedure itself may result in scarring and adhesion formation.
H. Failure to be Absorbed
Absorbable hemostatic devices are readily degraded by enzymatic and
hydrolytic action. Occasionally, an absorbable hemostatic device may
lodge in an area with low enzymatic and hydrolytic activity. In such
instances, it may not be efficiently absorbed. Subsequently, it may
become encapsulated and exert pressure on soft tissue requiring
surgical removal.
I. Interference With Methylmethacrylate Adhesives
Some types of absorbable hemostatic devices have been reported to
reduce the strength of methylmethacrylate adhesives used to fixate
orthopedic prosthetic devices to bone.
J. Aspiration Into Blood Salvage System Filters
Fragments of an absorbable hemostatic device may pass through blood
salvage system filters and occlude the systems or the patient's
vasculature.
K. Embolization
Absorbable hemostatic devices used near moderate to large blood
vessels may result in embolization of the blood vessel. Such
embolization has been associated with severe adverse effects, including
fever, duodenal and pancreatic infarct, embolization of lower extremity
vessels, pulmonary embolization, splenic abscess, necrosis, asterixis,
and death.
L. Paralysis/Nerve Damage/Tissue Necrosis
Absorbable hemostatic devices absorb liquid and swell to varying
degrees, up to 35 to 40 times their weight in liquid. This absorption
of liquid is accompanied by a concomitant swelling of the device.
VI. Summary of the Reasons for the Reclassification
FDA believes that the absorbable hemostatic device should be
reclassified into class II because special controls, in addition to
general controls, would provide reasonable assurance of the safety and
effectiveness of the device and because there is sufficient information
to establish special controls to provide such assurance.
In addition to the potential risks to health associated with use of
the absorbable hemostatic device described in section V of this
document, there is reasonable knowledge of the benefits of the device.
Specifically, the absorbable hemostatic device may prevent extended
bleeding, reduce surgical morbidity due to blood loss, and reduce the
need for transfusions.
VII. Special Controls
In addition to general controls, FDA believes that the draft
guidance document entitled ``Class II Special Controls Guidance:
Absorbable Hemostatic Device'' (the class II special controls guidance
document) is an adequate special control to address the risks to health
associated with the use of the device described in section V of this
document. FDA believes that the class II special controls guidance
document, which incorporates voluntary consensus standards and
describes labeling recommendations, addresses the Panel's concerns.
Elsewhere in this issue of the Federal Register, FDA is publishing a
notice of availability of the draft class II special
[[Page 63731]]
controls guidance document that the agency would use as the special
control for this device.
The draft class II special controls guidance document sets forth
the information FDA believes should be included in premarket
notification submissions (510(k)s) for the absorbable hemostatic
device. FDA has identified the risks to health associated with the use
of the device in the first column of table 1 of this document and the
recommended mitigation measures identified in the class II special
controls guidance document in the second column of table 1. FDA
believes that addressing these risks to health in a 510(k) in the
manner identified in the class II special controls guidance document,
or in an acceptable alternative manner, is necessary to provide
reasonable assurance of the safety and effectiveness of the device.
Table 1.
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Identified Risk Recommended Mitigation Measures
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Uncontrolled Bleeding Material and performance
characteristics, Animal testing,
Clinical testing, Labeling
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Hematoma Animal testing, Clinical testing,
Labeling
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Infection Animal testing, Sterility, Labeling
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Wound Dehiscence Labeling
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Foreign Body Reactions Animal testing, Biocompatibility, and
Labeling
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Immunological Reactions Animal testing, Biocompatibility,
Labeling
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Adhesion Formation Animal testing, Clinical testing
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Failure to be Absorbed Material and performance
characteristics, Animal testing,
Biocompatibility
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Interference with Animal testing, Labeling
Methylmethacrylate Adhesives
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Aspiration Into Blood Salvage Labeling
System Filters
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Embolization Labeling
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Paralysis/Nerve Damage/Tissue Labeling
Necrosis
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VIII. FDA's Findings
As discussed previously in this document, FDA believes the
absorbable hemostatic device should be reclassified into class II
because special controls, in addition to general controls, provide
reasonable assurance of the safety and effectiveness of the device and
because there is sufficient information to establish special controls
to provide such assurance. FDA, therefore, is proposing to reclassify
the device into class II and establish the draft class II special
controls guidance document as a special control for the device.
Section 510(m) of the act provides that a class II device may be
exempted from the premarket notification requirements under section
510(k) of the act, if the agency 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 believes that
premarket notification is necessary to provide reasonable assurance of
safety and effectiveness and, therefore, does not intend to exempt the
device from the premarket notification requirements.
IX. Effective Date
FDA proposes that any final regulation based on this proposal
become effective 30 days after its date of publication in the Federal
Register.
X. Environmental Impact
The agency has determined under 21 CFR 25.34(b) that this proposed
reclassification 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.
XI. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-602), 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 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. Reclassification of this device from class III to
class II will relieve manufacturers of the device of the cost of
complying with the premarket approval requirements in section 515 of
the act. Because reclassification will reduce regulatory costs with
respect to this device, the agency certifies that the proposed 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 $118 million, using the most current (2004) 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.
XII. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the proposed rule, if finalized, would not contain policies that would
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 tentatively concludes that the proposed rule
does not contain policies that have federalism implications as defined
in the Executive order and, consequently, a federalism summary impact
statement has not been prepared.
XIII. Paperwork Reduction Act of 1995
FDA tentatively concludes that this proposed rule contains no
collections of information. Therefore, clearance by the Office of
Management and Budget (OMB) under the Paperwork Reduction Act of 1995
(the PRA) (44 U.S.C. 3501-3520) is not required.
FDA also tentatively concludes that the draft special control
guidance document does not contain new information collection
provisions that are subject to review and clearance by OMB under the
PRA. Elsewhere in this issue of the Federal Register, FDA is publishing
a notice announcing the availability of the draft guidance document
entitled ''Class II Special Controls Guidance Document:
[[Page 63732]]
Absorbable Hemostatic Device''; the notice contains an analysis of the
paperwork burden for the draft guidance.
XIV. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper copy.
Comments are to be identified 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.
XV. References
The following references have been placed on display in the
Division of Dockets Management (see ADDRESSES) and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
1. General and Plastic Surgery Devices Panel, Transcript, pp. 80-
177, July 8, 2002.
2. General and Plastic Surgery Devices Panel, Transcript, July 24,
2003.
List of Subjects in 21 CFR Part 878
Medical devices.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 878 be amended as follows:
PART 878--GENERAL AND PLASTIC SURGERY DEVICES
1. The authority citation for 21 CFR Part 878 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
2. Section 878.4490 is revised to read as follows:
Sec. 878.4490 Absorbable hemostatic device.
(a) Identification. An absorbable hemostatic device is an
absorbable device that is placed in the body during surgery to produce
hemostasis by accelerating the clotting process of blood.
(b) Classification. Class II (special controls). The special
control for the device is FDA's ``Class II Special Controls Guidance
Document: Absorbable Hemostatic Device.'' See Sec. 878.1(e) for the
availability of this guidance document.
Dated: October 19, 2006.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. E6-18324 Filed 10-30-06; 8:45 am]
BILLING CODE 4160-01-S