[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]


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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.

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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Federal Register, FDA is announcing the availability of a draft 
guidance document that would serve as the special control if FDA 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.
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           Identified risk              Recommended mitigation  measures
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Unintentional Bonding or Product       Bench Testing
 Leaks into Eyes                       Labeling
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Wound Dehiscence                       Bench Testing
                                       Shelf-Life Testing
                                       Animal Testing
                                       Labeling
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Adverse Tissue Reaction and Chemical   Biocompatibility
 Burns                                 Animal Testing
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Infection                              Bench Testing
                                       Sterility
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Applicator Malfunction                 Bench Testing
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Delayed Polymerization                 Bench Testing
                                       Animal Testing
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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

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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