[Federal Register Volume 71, Number 210 (Tuesday, October 31, 2006)]
[Proposed Rules]
[Pages 63728-63732]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-18324]


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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draft guidance document that would serve as the special control if FDA 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