[Federal Register: May 30, 2008 (Volume 73, Number 105)]
[Rules and Regulations]
[Page 31027-31033]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr30my08-9]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 878
[Docket No. FDA-2006-P-0140] (formerly 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: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is reclassifying the
device type, tissue adhesive for the topical approximation of skin,
from class III (premarket approval) into class II (special controls).
Tissue adhesives for non-topical uses 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 guidance document
entitled ``Class II Special Controls Guidance Document: Tissue Adhesive
for the Topical Approximation of Skin'' that will serve as the special
control for the reclassified device type.
DATES: This final rule is effective June 30, 2008.
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 not
appropriately regulated 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 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
[[Page 31028]]
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. By notice published 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, but did not publish the regulations before
December 1, 1993.
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), identified certain
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 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 transfer. In a January 19, 1982,
preamble to a proposed rule classifying other devices (47 FR 2810),
``tissue adhesive for use in general surgery,'' was identified as a
transitional device, but listed under injectable silicone. Since
enactment of the 1976 amendments, FDA has approved several PMAs 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 type, under review for
reclassification, in previous notices as ``tissue adhesive for use in
general surgery''; however, FDA is now revising the name and
identification to more accurately identify the device type. The device,
reclassified into class II, would be:
Tissue adhesive for the topical approximation of skin. A tissue
adhesive for the topical approximation of skin is a device 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 issuing 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 type. The Panel discussed the device
type 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.
Accordingly, in the Federal Register of July 3, 2007 (72 FR 36398),
FDA issued a proposed rule to reclassify the device, tissue adhesive
for the topical approximation of skin, from class III (premarket
approval) into class II (special controls). Tissue adhesive for non-
topical uses would remain in class III and continue to require PMAs.
V. Comments
FDA invited interested persons to comment on the proposed rule by
September 4, 2007. FDA received two comments on the proposed rule. The
following is a summary of the comments and FDA's responses. Elsewhere
in this issue of the Federal Register, portions of the comments which
address only the draft guidance document are addressed in the notice of
availability announcing the special controls guidance document.
(Comment 1) One comment supported the reclassification of tissue
adhesives. The comment noted that the tissue adhesives approved by FDA
have had a long history of safety. The comment suggested that tissue
adhesives made of other cyanoacrylates with different alkyl groups may
have additional benefits for patients. The comment also said that bench
testing is more useful than clinical testing to evaluate substantial
equivalence due to the many uncontrolled variables. The comment said
that manufacturers of new tissue adhesives should be permitted to
market their devices through a premarket notification if they are able
to demonstrate that their devices are substantially equivalent to the
marketed predicate devices.
(Response) FDA agrees that these type devices should be
reclassified and intends that manufacturers who are able to demonstrate
substantial equivalence to marketed devices within the reclassified
generic type will be permitted to market their devices.
(Comment 2) One comment objected that FDA improperly designated the
tissue adhesive for the topical approximation of skin as a transitional
device. The comment said that the tissue adhesive for the topical
approximation of skin does not meet the definition of a transitional
device in section 520(l) of the act. The comment noted that an NDA for
a tissue adhesive was submitted before the enactment of the 1976
amendments but was subsequently withdrawn before the enactment date.
The comment said that, in order for the device to be a transitional
device, it is necessary for an IND to have been in effect or for an NDA
to have been pending or approved on the enactment date. The comment
said that tissue adhesives are devices automatically classified into
class III under section 513(f)(1) of the act.
(Response) Section 520(l)(1)(B) provides that a device is a
transitional
[[Page 31029]]
device if ``an application [under section 505(b) of the act was filed
on or before the enactment date [of the Medical Device Amendments of
1976] and with respect to which no order of approval or refusing to
approve had been issued on such date* * *.'' The comment agrees that an
application was filed before the enactment date. It is also clear that
no order of approval or refusing to approve had been issued before the
enactment date. The plain words of the statute do not require that an
application be pending on the date of enactment. As noted previously,
FDA published a document on January 19, 1982 identifying, among other
devices, tissue adhesives as transitional devices. FDA did not receive
any objections to this designation until the comment on this proposed
rule. Furthermore, even if the device would be considered a
postamendments device under section 513(f) of the act, the procedures
that FDA followed would be sufficient to reclassify the device. FDA did
not follow ``truncated procedures'' to reclassify the device under the
transitional device provisions. FDA referred the petition to an
advisory panel that made a recommendation after holding an open public
meeting. FDA published the panel recommendation along with the proposed
rule and provided interested persons 60 days to comment on the
proposal. The criteria for reclassifying a device into class II are
identical for transitional devices under section 520(l) of the act and
postamendments devices under section 513(f) of the act.
(Comment 3) One comment said that FDA failed to instruct the panel
on the appropriate legal standard for reclassification. The comment
said that the panel transcript and briefing memorandum show that FDA
did not instruct the panel that a reclassification recommendation must
be based on valid scientific evidence.
(Response) FDA disagrees. The panel was instructed properly. FDA
conducts training sessions prior to the panel meeting for panel members
before they undertake their duties. Training for panels considering the
reclassification of a transitional device type consists of procedures
for the reclassification of a device type, including a transitional
device type, and the appropriate regulatory controls for each class of
device. Moreover, it is FDA's responsibility to make reclassification
decisions after receiving a panel recommendation. In accordance with
Sec. 860.7(c)(1) (21 CFR 860.7(c)(1)) the agency relied on valid
scientific evidence in determining that special controls, in addition
to general controls, would provide reasonable assurance of the safety
and effectiveness of the device.
(Comment 4) One comment said that FDA did not identify an
appropriate generic type of device that could be reclassified. The
comment said that existing tissue adhesives are significantly different
in composition and could not be combined into a single generic type of
device. The comment also said there is insufficient publicly available
formulation and manufacturing information to establish a generic type
of device. Finally, the comments said that even minor differences in
product composition can affect the performance of the device.
(Response) FDA disagrees with this comment. The FDA classification
regulations (21 CFR 860.3(i)) define generic type of device as ``a
grouping of devices that do not differ significantly in purpose,
design, materials, energy source, function, or any other feature
related to safety and effectiveness, and for which similar regulatory
controls are sufficient to provide reasonable assurance of safety and
effectiveness.'' It is not necessary that devices be identical in order
to fit within the same generic type. FDA believes that there is
sufficient publicly available information from currently marketed
tissue adhesives to show that they do not differ significantly in
design, materials, and function and that similar regulatory controls
are sufficient to provide reasonable assurance of their safety and
effectiveness. A manufacturer who wishes to market a new device will
need to show in a premarket notification that its device is
substantially equivalent in safety and effectiveness to a marketed
predicate device.
(Comment 5) Two comments said that there was insufficient valid
scientific evidence to support the reclassification. One comment noted
that three of the articles submitted are not reports of prospective
clinical trials. The comment described one of the articles as a general
discussion of tissue adhesives, the second article as a brief
description of one facility's 6-month experience with tissue adhesives,
and the third article as a retrospective review of eight different
clinical studies. The comment further said the 6 FDA-designated
representative articles that discuss prospective clinical studies
involve limited numbers of subjects with a total of 60 to 100 subjects
in each study.
(Response) FDA disagrees with this comment. FDA regulations (Sec.
860.7(b)(2)) define valid scientific evidence as:
``* * *evidence from well-controlled investigations, partially
controlled studies, studies and objective trials without matched
controls, well-documented case histories conducted by qualified
experts, and reports of significant human experience with a marketed
device, from which it can fairly and responsibly be concluded by
qualified experts that there is reasonable assurance of the safety and
effectiveness of a device under its conditions of use. The evidence
required may vary according to the characteristics of the device, its
conditions of use, the existence and adequacy of warnings and other
restrictions, and the extent of experience with its use. Isolated case
reports, random experience, reports lacking sufficient details to
permit scientific evaluation, and unsubstantiated opinions are not
regarded as valid scientific evidence to show safety or effectiveness*
* *.''
FDA believes that the evidence on the record falls within this
definition of valid scientific evidence. The shortcomings of the
information alleged by the comment do not take this information out of
the category of valid scientific evidence. Literature available to FDA
and the Panel included over 1,500 published articles that reported on
the use of multiple adhesives in over 5,900 procedures (over 5,500
patients), with more than half evaluated in prospective randomized
trials. The study protocols included primary endpoints such as
cosmesis, dehiscence, and healing time for the topical skin
approximations. As defined in Sec. 860.7(c)(2), randomized prospective
trials and peer-reviewed literature constitute valid scientific
evidence.
(Comment 6) One comment said that the performance parameters for
the device described in the proposal are incomplete. The comment said
that missing performance parameters include adherence and endurance
(how long the product will remain intact once applied); the ability to
potentiate infection; the ability to maintain a microbial barrier; and
how the skin reacts to the stabilizing agents. The comment also said
that publicly available scientific literature does not yield ranges of
values that would constitute acceptable performance on required tests
to demonstrate that performance parameters are met.
(Response) FDA disagrees with this comment. FDA believes that the
FDA recommendations for premarket notifications in the special controls
guidance as well as general controls will adequately address all
appropriate performance parameters. Manufacturers who are proposing the
introduction of a new tissue adhesive will need to demonstrate
substantial equivalence to a
[[Page 31030]]
legally marketed predicate device in all safety and effectiveness
aspects before FDA will issue a substantial equivalence order. All
manufacturers submitting 510(k)s will need to demonstrate the
performance characteristics of the device related to adhesive strength,
(i.e., tensile strength, shear strength, peel adhesion strength, and
impact strength); hydrolytic degradation (i.e., the amount of
formulation additives, monomer impurities, and degradation products);
heat of polymerization; shelf life; and biocompatibility. FDA believes
that these performance characteristics will directly or indirectly
address the performance parameters identified in the comment. Where
these performance characteristics are shown sufficiently different from
currently legally marketed devices, the special controls guidance
document indicates that FDA may conclude additional animal testing or
clinical assessment is necessary, see sections 10, ``Animal Testing,''
and 11, ``Clinical Studies.''
(Comment 7) A comment said that FDA has failed to fully identify
the risks to health presented by these devices. A comment said that FDA
unduly relied upon Medical Device Reports (MDRs) to identify the risks
to health and that the MDR system is inadequate to fully identify the
risks. A comment said that risks not identified include pain, stinging,
or burning upon application, delayed wound healing or tissue toxicity,
patients picking off the adhesive, and necrosis.
All of these effects are intrinsic to the risk of adverse tissue
reaction and chemical burns except for patient ``picking off
adhesive.'' Although foreseeable, it is not intended for patients to
``pick off'' the adhesive and therefore is not considered a risk to
health associated with the intended or otherwise correct use of the
device. A comment further said that the risks identified by FDA are not
supported by valid scientific evidence because they are developed from
the MDR system.
(Repsonse) FDA disagrees with this comment. FDA believes that it
has fully identified the significant risks to health presented by these
devices. As noted in the proposal, FDA did not rely solely upon the MDR
reports to identify the risks to health presented by these devices. FDA
also considered the information presented in the petition,
presentations at the panel meeting, and the panel recommendation.
(Comment 8) A comment also said that the proposed special controls
are inadequate to eliminate or mitigate the risks associated with
tissue adhesives. A comment also said that FDA did not present
sufficient valid scientific evidence to support the proposed special
controls because almost half of the articles relate to a single device
and, therefore, cannot support reclassification of a generic type of
device.
(Response) FDA disagrees with the comment. FDA believes that a
premarket notification that adequately addresses the recommendations of
the special control guidance and adherence to the general controls of
the act will mitigate the risks to health associated with these devices
and provide reasonable assurance of the safety and effectiveness of the
device. In the premarket notification review process, FDA will assure
that the device intended for marketing is at least as safe and
effective as the legally marketed predicate device. FDA believes that
there is adequate valid scientific evidence on the record about all
legally marketed tissue adhesives to establish and reclassify a generic
type of device. Although many of the articles relate to a single
device, there is substantial evidence concerning other marketed devices
and that evidence, as well as the remainder of the evidence on the
record, provides adequate valid scientific evidence to reclassify a
generic type of device.
(Comment 9) One comment stated that bench testing as described in
the special controls guidance document is more informative and
introduces fewer variables than do animal or clinical studies in
evaluating these devices.
(Response) FDA agrees, in general, that animal studies and clinical
trials for these devices may not be the most appropriate means to
evaluate these devices. FDA intends to request animal or clinical data
only when appropriate.
(Comment 10) One comment asked whether the device is subject to
current good manufacturing practices (CGMPs).
(Response) When the device is reclassified into class II, it
remains subject to the requirements of good manufacturing practices
(GMPs) under the Quality System Regulation in part 820 (21 CFR part
820). For more information on the scope of applicability of the Quality
System Regulation, please see Sec. 820.1, Scope.
(Comment 11) One comment said the bench testing using American
Society for Testing and Materials (ASTM) methods described in the
guidance does not correlate to device performance in the clinical
setting because the ASTM methods do not include acceptance criteria.
(Response) Although FDA agrees these methods do not include
acceptance criteria, FDA disagrees with the premise that these methods
are inadequate. The methods described in these standards allow direct
comparison of performance characteristics between devices. For those
devices where the data demonstrate equivalent performance
characteristics, no additional clinical testing would be necessary.
Where the performance characteristics are shown by bench testing to be
sufficiently different from those of currently legally marketed
devices, the special controls guidance document indicates that FDA may
conclude additional animal testing or clinical assessment is necessary.
See sections 10. Animal Testing and 11. Clinical Studies.
(Comment 12) One comment suggested that heat of polymerization
studies recommended in the guidance are not appropriate for materials
that cure by non-exothermic mechanisms. The second part of the comment
said that FDA should set an upper limit on the amount of heat generated
by exothermic mechanisms because of the possibility of burns.
(Response) FDA agrees, in part, with this comment. Heat of
polymerization studies are not appropriate methods for evaluating the
performance characteristics of materials that cure by non-exothermic
mechanisms. As stated in section 5 of the special controls guidance
document, a manufacturer proposing to use materials that cure by non-
exothermic mechanisms will need to identify the risks specific to those
devices by conducting a risk analysis and will need to address the
risks identified. FDA disagrees with the second part of the comment.
FDA has set no upper threshold for the heat of polymerization because
FDA believes the unique properties of each material approved to date
require a case-by-case evaluation of the heat generated by
polymerization. Addressing this property is intrinsic to addressing the
risk of chemical burns, which is one of the risks to health identified
in the special controls guidance document.
(Comment 13) One comment said that testing the applicator based on
the force to express and that moisture vapor transmission testing are
not relevant. The comment also suggested that, depending on the design
of the applicator and its components, applicator functionality may be a
more relevant test.
(Response) FDA agrees and has revised the guidance accordingly.
(Comment 14) A comment said that clinical trials are necessary to
effectively evaluate critical performance parameters. One comment said
that the record fails to reveal any new valid
[[Page 31031]]
scientific evidence that demonstrates a diminished need for clinical
testing.
(Response) FDA generally disagrees with the comment. In accordance
with the ``least burdensome'' provision of section 513(i)(1)(D) of the
act, FDA believes that the special controls guidance document
recommends the submission of the minimum information that is necessary
to making substantial equivalence determinations. In some cases,
submission of reports from bench and animal testing and conformance to
designated standards may be sufficient to demonstrate substantial
equivalence. FDA also states in the special controls guidance that it
may recommend the submission of clinical evidence in a premarket
notification if the proposed device is dissimilar to the legally
marketed predicate device in material formulation, technology, or
intended use.
FDA believes that new information includes information developed as
a result of a re-evaluation of the data before the agency when the
device was originally classified, as well as information not presented,
not available, or not developed at that time. (See e.g., Holland Rantos
v. United States Department of Health, Education, and Welfare, 587 F.2d
1173, 1174 n.1 (D.C. Cir. 1978); Upjohn v. Finch, 422 F.2d 944 (6th
Cir. 1970); Bell v. Goddard, 366 F.2d 177 (7th Cir. 1966).) Re-
evaluation of the data previously before the agency is an appropriate
basis for subsequent regulatory action where the re-evaluation is made
in light of newly available regulatory authority (see Bell v. Goddard,
supra, 366 F.2d at 181; Ethicon, Inc. v. FDA, 762 F.Supp. 382, 389-91
(D.D.C. 1991)), or in light of changes in ``medical science.'' (See
Upjohn v. Finch, supra, 422 F.2d at 951.) FDA believes that the
information in the reclassification petition together with information
presented at the panel meeting and the history of use of the device as
known to the panel and FDA is sufficient new information to justify the
reclassification.
(Comment 15) One comment said that the premarket notification and
GMP requirements will not provide reasonable assurance of the safety
and effectiveness of these devices. The comment said that there is no
coherent generic type of device that would permit meaningful
substantial equivalence comparisons and determinations. The comment
also said the premarket notification review process does not afford the
same level of manufacturing review as the premarket approval process.
(Response) FDA disagrees with this comment. FDA believes that the
premarket notification process, in conjunction with the special
controls guidance document and the general controls of the act,
including the GMP requirements, will provide reasonable assurance of
the safety and effectiveness of the device. A manufacturer will need to
show in a premarket notification that the device it intends to market
is at least as safe and effective as a legally marketed predicate
device. This provides a device to which meaningful comparisons can be
made. While the premarket notification review process does not include
a pre-clearance GMP inspection, manufacturers of new tissue adhesive
devices will still be required to be in compliance with the GMP
requirements at all times.
(Comment 16) One comment noted that tissue adhesives have been
considered significant risk devices under the investigational device
exemption rule (21 CFR 812.3(m)). The comment expressed concern that
reclassification into class II would result in these devices being
considered non-significant risk devices and expose patients in studies
involving newly developed tissue adhesives to risks without adequate
protection.
(Response) Reclassification of these devices into class II is not
inconsistent with the designation of these devices as significant risk
devices under the investigational device exemption regulations. In the
special controls guidance document, FDA states: ``If a clinical study
is needed to demonstrate substantial equivalence (i.e., conducted prior
to obtaining 510(k) clearance of the device), the study must be
conducted under the Investigational Device Exemptions (IDE) regulation,
21 CFR Part 812. FDA generally believes that this device is a
significant risk device as defined in 21 CFR 812.3(m). In addition to
the requirement of having an FDA-approved IDE, sponsors of such trials
must comply with the regulations governing institutional review boards
(21 CFR Part 56) and informed consent (21 CFR Part 50).''
VI. Risks to Health
After considering the information in the petition, the information
presented at the Panel meeting, the Panel's recommendation, and MDRs,
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,
which include re-sealing the wound and surgical revision of the wound
with adhesive or sutures, can arise as a result of wound dehiscence.
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 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.
[[Page 31032]]
VII. Summary of the Reasons for the Reclassification
FDA believes that a tissue adhesive for the topical approximation
of skin 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 a tissue adhesive for the topical skin approximation 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.
VIII. Special Controls
In addition to general controls, FDA believes that the 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 class II
special controls guidance document that is the special control for this
device.
The 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.--Risks to Health and Mitigation Measures
------------------------------------------------------------------------
Identified Risk Recommended Mitigation Measures
------------------------------------------------------------------------
Unintentional bonding or product leaks Bench testing
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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IX. FDA's Findings
As discussed previously in this document, FDA believes the tissue
adhesive for the topical approximation of skin can 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 reclassifying
the device into class II and establishing 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, for the
reasons discussed previously, 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.
X. Environmental Impact
The agency has determined under 21 CFR 25.34(b) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
XI. Analysis of Impacts
FDA has examined the impacts of the final rule under Executive
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), 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 final rule is not a significant regulatory action under the
Executive order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small
[[Page 31033]]
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 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 $127 million, using the most current (2006) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
rule to result in any 1-year expenditure that would meet or exceed this
amount.
XII. Federalism
FDA has analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has determined that the rule
does not contain policies that 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 has concluded
that the rule does not contain policies that have federalism
implications as defined in the Executive order and, consequently, a
federalism summary impact statement is not required.
XIII. Paperwork Reduction Act of 1995
This final rule contains no collections of information. Therefore,
clearance by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 is not required. Elsewhere in this
issue of the Federal Register, FDA is issuing a notice announcing the
guidance for the final rule. This guidance, ``Class II Special Controls
Guidance Document: Tissue Adhesive for the Topical Approximation of
Skin,'' references previously approved collections of information found
in FDA regulations.
XIV. References
The following references have been placed on display in the
Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville, MD 20852 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.
0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
878 is amended as follows:
PART 878--GENERAL AND PLASTIC SURGERY DEVICES
0
1. The authority citation for 21 CFR part 878 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Section 878.4010 is added to subpart E to read as follows:
Sec. 878.4010 Tissue adhesive.
(a) Tissue adhesive for the topical approximation of skin--(1)
Identification. A tissue adhesive for the topical approximation of skin
is a device 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 is FDA's ``Class II Special Controls Guidance
Document: ``Tissue Adhesive for the Topical Approximation of Skin.''
See Sec. 878.1(e) of this chapter for the availability of this
guidance document.
(b) Tissue adhesive 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 foradhesion 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 of this
chapter.
Dated: May 21, 2008.
Daniel G. Schultz,
Center for Devices and Radiological Health.
[FR Doc. E8-12078 Filed 5-29-08; 8:45 am]
BILLING CODE 4160-01-S