[Federal Register Volume 72, Number 127 (Tuesday, July 3, 2007)]
[Proposed Rules]
[Pages 36398-36401]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-12797]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 878
[Docket No. 2006P-0071]
General and Plastic Surgery Devices; Reclassification of the
Tissue Adhesive for Topical Approximation of Skin Device
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is proposing to
reclassify the device, tissue adhesive for the topical approximation of
skin, from class III (premarket approval) into class II (special
controls). Tissue adhesives for non-topical uses would remain in class
III and continue to require premarket approval applications (PMAs). 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Federal Register, FDA is announcing the availability of a draft
guidance document that would serve as the special control if FDA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 September 4, 2007. See section IX 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. 2006P-
0071, 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:
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: George J. Mattamal, Center for Devices
and Radiological Health (HFZ-410), Food and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20850, 240-276-3619.
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, 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, which included tissue
adhesives for use in general surgery (47 FR 2810, January 19, 1982), 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, that 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
regarding whether the order applied to certain manufacturers' devices,
many transitional class III device manufacturers failed to comply
[[Page 36399]]
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
Transitional devices, those devices formerly regulated as drugs,
were classified into class III by the statute and premarket approval
was immediately required (section 520(l) of the act). The Federal
Register of December 16, 1977 (42 FR 63472), listed transitional
devices and stated the following: ``The lists contained in this notice
may not be an exhaustive inventory of products subject to section
520(l) of the act.'' This notice did not specifically list ``Tissue
Adhesives.'' The investigational new drug (IND) and new drug
applications (NDAs) for products classified as transitional devices
were shortly thereafter transferred to FDA's Center for Devices and
Radiological Health (formerly the Bureau of Medical Devices).
Applications for tissue adhesives were included in this list of
products transferred. (FDA did list ``injectable silicone'' as a
transitional device in the Federal Register of December 16, 1977. In
the January 19, 1982, Federal Register notice (47 FR 2810) ``tissue
adhesive for use in general surgery,'' was included as a transitional
device under ``injectable silicone.'' This was a typographical error as
``tissue adhesives'' are not a subcategory of ``injectable silicone.'')
Since enactment of the 1976 amendments, FDA has approved several
premarket approval (PMA) applications and PMA supplements authorizing
the commercial distribution of tissue adhesives in the United States.
III. Description of the Device
FDA has referred to this device, under review for reclassification,
in previous notices as ``tissue adhesive for use in general surgery;''
however, FDA is proposing in this notice to revise the name and
identification to more accurately identify the device. Under the
proposal, the device proposed for reclassification into class II, would
be: Tissue adhesives for the topical approximation of skin. Tissue
adhesives for the topical approximation of skin devices, which may
contain cyanoacrylate as the active ingredient, are intended for
topical closure of surgical incisions, including laparoscopic
incisions, and simple traumatic lacerations that have easily
approximated skin edges. Tissue adhesives for the topical approximation
of skin may be used in conjunction with, but not in place of, deep
dermal stitches.
FDA is also proposing the following identification for the devices
that will remain in class III: A tissue adhesive for non-topical use,
including adhesives intended for use in the embolization of brain
arteriovenous malformation or ophthalmic surgery, is a device used for
adhesion of internal tissues and vessels.
IV. Recommendation of the Panel
On February 9, 2006, Regulatory & Clinical Research Institute, Inc.
(RCRI), Minneapolis MN, submitted a petition (Docket No. 2006P-0071) to
FDA to reclassify tissue adhesive for soft tissue approximation from
``Class III to Class II (special controls)'' (Ref. 1). On May 15, 2006,
the petitioner amended its petition to include several references from
the scientific literature cited in the original petition (Ref. 2). On
July 18, 2006, the petitioner again amended its petition to clarify
that the use it was proposing for reclassification was only the topical
approximation of skin (Ref. 3).
In response to the petition, FDA consulted with the FDA's General
and Plastic Surgery Devices Panel (the Panel), regarding
reclassification of this device. The Panel discussed the device at an
August 25, 2006, public meeting and unanimously recommended that the
tissue adhesive for the topical approximation of skin be reclassified
from class III into class II. The Panel also recommended that a class
II guidance document, which the Panel thought should include several
voluntary consensus standards, be the special control for the device.
The Panel based the recommendations on the information provided by FDA;
the presentations to the panel by the petitioner, other manufacturers,
and FDA; the Panel's deliberations at the meeting; and the Panel's
personal experience with the use of devices for the topical
approximation of skin. The Panel did not consider the reclassification
of any other use of tissue adhesives.
V. Risks to Health
After considering the information in the petition, the information
presented at the Panel meeting, the Panel's recommendation, and Medical
Device Reports, FDA has evaluated the risks to health associated with
use of the tissue adhesive for the topical approximation of skin and
determined that the following risks to health are associated with its
use.
A. Unintentional Bonding or Product Leaks Into Eyes
Without adequate protection of the patient's eye, the adhesive may
inadvertently leak onto the eyelids when tissue adhesive is used on the
skin near the patient's eye, for example on the brow or forehead. If
this occurs, this can lead to sealing the eyelids shut and can require
surgical intervention to remove the adhesive and any bound skin.
B. Wound Dehiscence
Wound dehiscence, the subsequent separation of the edges of the
wound, i.e., incision or laceration, during recovery is a risk of all
surgical procedures and treatments of traumatic wounds. Complications
can arise as a result of wound dehiscence, which include re-sealing the
wound and surgical revision of the wound with adhesive or sutures.
These complications have the potential to delay the patient's recovery.
C. Adverse Tissue Reaction and Chemical Burns
Tissue adhesive may be associated with adverse tissue reactions,
including allergy, inflammation, foreign body reactions, erythema
(redness), granuloma, and the exacerbation of asthma. In addition,
fumes given off by the adhesive before or during polymerization can
cause chemical burns.
D. Infection
Infection of the skin or soft tissue is a risk to health associated
with all surgical procedures and wound treatment. If the tissue
adhesive is not properly sterilized, it may contribute to an increased
risk of infection.
E. Applicator Malfunction
Inadequate packaging of the device or user error when opening the
packaging can result in damage to the applicator and subsequent
malfunction. If an applicator malfunctions, surgery may be extended,
resulting in additional time
[[Page 36400]]
under anesthesia, or treatment may be delayed. In addition, if the
adhesive is packaged in a glass container, lacerations to the user or
the patient may result if the glass breaks.
F. Delayed Polymerization
Polymerization of the adhesive may be delayed, resulting in
compromise of the wound, additional time under anesthesia, or delayed
treatment.
VI. Summary of the Reasons for the Reclassification
FDA believes that the tissue adhesive for the topical approximation
of skin 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. FDA believes
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 tissue adhesive for the topical skin
approximation device described in section V of this document, there is
reasonable knowledge of the benefits of the device. Specifically, the
tissue adhesive for the topical approximation of skin may prevent
extended bleeding in the repair of surgical incisions and traumatic
lacerations, promote healing of approximated wound edges, and reduce
pain and recovery time.
VII. Special Controls
In addition to general controls, FDA believes that the draft
guidance document entitled ``Class II Special Controls Guidance
Document: Tissue Adhesive for the Topical Approximation of Skin'' (the
class II special controls guidance document) is a special control
adequate 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,
in addition to general controls, provides reasonable assurance of the
safety and effectiveness of the device. Elsewhere in this issue of the
Federal Register, FDA is publishing a notice of availability of the
draft class II special 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 tissue adhesive for the
topical approximation of skin. 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.
------------------------------------------------------------------------
Identified risk Recommended mitigation measures
------------------------------------------------------------------------
Unintentional Bonding or Product Bench Testing
Leaks into Eyes Labeling
------------------------------------------------------------------------
Wound Dehiscence Bench Testing
Shelf-Life Testing
Animal Testing
Labeling
------------------------------------------------------------------------
Adverse Tissue Reaction and Chemical Biocompatibility
Burns Animal Testing
------------------------------------------------------------------------
Infection Bench Testing
Sterility
------------------------------------------------------------------------
Applicator Malfunction Bench Testing
------------------------------------------------------------------------
Delayed Polymerization Bench Testing
Animal Testing
------------------------------------------------------------------------
VIII. FDA's Findings
As discussed previously in this document, FDA believes the tissue
adhesive for the topical approximation of skin 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. Tissue adhesives for non-topical use will remain in
class III and continue to require PMAs.
Section 510(m) of the act (21 U.S.C. 360) 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 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 when it is used for
the topical approximation of skin, 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 (21 U.S.C.
360e). 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
[[Page 36401]]
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 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 new
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.
This proposed rule designates a guidance document as a special
control. 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 that draft guidance document
entitled ``Class II Special Controls Guidance Document: Tissue Adhesive
for the Topical Approximation of Skin,'' which 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. Regulatory & Clinical Research Institute, Inc. (RCRI),
reclassification petition, Docket No. 2006P-0071, Minneapolis MN,
February 9, 2006.
2. Regulatory & Clinical Research Institute, Inc.,
reclassification petition, Docket No. 2006P-0071, Minneapolis MN,
May 15, 2006.
3. Regulatory & Clinical Research Institute, Inc.,
reclassification petition, Docket No. 2006P-0071, Minneapolis MN,
July 18, 2006.
4. General and Plastic Surgery Devices Panel, Transcript, pp.
199 to 207, August 25, 2006.
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 878.4010 is added to subpart E to read as follows:
Sec. 878.4010 Tissue adhesive.
(a) Tissue adhesives for the topical approximation of skin--(1)
Identification. Tissue adhesives for the topical approximation of skin
are intended for topical closure of surgical incisions, including
laparoscopic incisions, and simple traumatic lacerations that have
easily approximated skin edges. Tissue adhesives for the topical
approximation of skin may be used in conjunction with, but not in place
of, deep dermal stitches.
(2) Classification. Class II (special controls). The special
control for this device isEFDA's ``Class II Special Controls Guidance
Document: ``Tissue Adhesive for the Topical Approximation of Skin.''
See Sec. 878.1(e) for the availability of this guidance document.
(b) Tissue adhesives for non-topical use--(1) Identification. A
tissue adhesive for non-topical use, including adhesives intended for
use in the embolization of brain arteriovenous malformation or for use
in ophthalmic surgery, is a device used for adhesion of internal
tissues and vessels.
(2) Classification. Class III (premarket approval). As of May 28,
1976, an approval under section 515 of the act is required before this
device may be commercially distributed. See Sec. 878.3.
Dated: June 22, 2007.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. E7-12797 Filed 7-2-07; 8:45 am]
BILLING CODE 4160-01-S