[Federal Register Volume 71, Number 66 (Thursday, April 6, 2006)]
[Proposed Rules]
[Pages 17390-17394]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-4962]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 878

[Docket No. 2006N-0109]


General and Plastic Surgery Devices; Reclassification of the 
Topical Oxygen Chamber for Extremities

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 topical oxygen chamber for extremities (TOCE) from class 
III (premarket approval) into class II (special controls). The device 
is intended to surround a patient's limb and apply humidified oxygen to 
aid healing of chronic skin ulcers such as bedsores. Elsewhere in this 
issue of the Federal Register, FDA is publishing a notice of 
availability of the draft guidance document that the agency proposes to 
use as a special control for the device.

DATES: Submit written or electronic comments by July 5, 2006. See 
section VIII of this document for the proposed effective date of a 
final rule based on this proposed rule.

ADDRESSES: You may submit comments, identified by Docket No. 2006N-
0109, 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.

[[Page 17391]]

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(s). and Regulatory Information Number (RIN) (if a RIN 
number has been assigned) 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 detailed 
instructions on submitting comments and additional information on the 
rulemaking process, 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: Charles N. Durfor, Center for Devices 
and Radiological Health (HFZ-410), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 301-594-3090, ext. 134.

SUPPLEMENTARY INFORMATION:

I. Background

A. Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 301 
et seq.), as amended by (among other amendments) the Medical Device 
Amendments of 1976 (the 1976 amendments) (Public Law 94-295) and the 
Safe Medical Devices Act (SMDA) (Public Law 101-629) 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).
    Under section 513 of the act, devices that were in commercial 
distribution before May 28, 1976 (the date of enactment of the 1976 
amendments), generally referred to as preamendments devices, are 
classified after FDA has taken the following steps: (1) Received a 
recommendation from a device classification panel (an FDA advisory 
committee); (2) published the panel's recommendation for comment, along 
with a proposed regulation classifying the device; and (3) published a 
final regulation classifying the device. FDA has classified most 
preamendments devices under these procedures.
    Devices that were not in commercial distribution prior to May 28, 
1976, generally referred to as postamendments devices, are classified 
automatically by statute (section 513(f) of the act) into class III 
without any FDA rulemaking process. Postamendments devices require 
premarket approval, unless FDA issues an order finding the device to be 
substantially equivalent, in accordance with section 513(i) of the act, 
to a predicate device that does not require premarket approval. The 
agency determines whether new devices are substantially equivalent to 
predicate devices by means of premarket notification procedures in 
section 510(k) of the act (21 U.S.C. 360(k)) and 21 CFR part 807) of 
the regulations.
    A preamendments device that has been classified into class III may 
be marketed, by means of premarket notification procedures, without 
submission of a premarket approval application (PMA) until FDA issues a 
final regulation under section 515(b) of the act (21 U.S.C. 360e(b)) 
requiring premarket approval.
    In 1990, the SMDA added section 515(i) to the act. This section 
requires FDA to issue an order to manufacturers of preamendments class 
III devices for which no final regulation requiring the submission of 
PMAs has been issued to submit to the agency a summary of, and a 
citation to, any information known or otherwise available to them 
respecting such devices, including adverse safety and effectiveness 
information that has not been submitted under section 519 of the act 
(21 U.S.C. 360i). Section 519 of the act requires manufacturers, 
importers, and device user facilities to submit adverse event reports 
of certain device-related events and reports of certain corrective 
actions taken. Section 515(i) of the act also directs FDA to either 
revise the classification of the device into class I or class II or 
require the device to remain in class III and establish a schedule for 
the issuance of a rule requiring the submission of PMAs for those 
devices.
    In the Federal Register of May 6, 1994 (59 FR 23731), FDA announced 
the availability of a document setting forth its strategy for 
implementing the provisions of the SMDA that require FDA to review the 
classification of preamendments class III devices. Under this plan, the 
agency divided preamendments class III devices into the following three 
groups: Group 1 devices are devices that FDA believes raise significant 
questions of safety and/or effectiveness, but are no longer used or are 
in very limited use; group 2 devices are devices that FDA believes have 
a high potential for being reclassified into class II; and group 3 
devices are devices that FDA believes are not likely candidates for 
reclassification.
    In the Federal Register of August 14, 1995 (60 FR 41986), FDA 
published an order for Group 2 preamendment class III devices, 
including the TOCE, requiring the submission of safety and 
effectiveness information in accordance with the preamendments class 
III strategy to implement section 515(i) of the act (515(i) summary). 
The order describes in detail the format for submitting the type of 
information required by section 515(i) of the act so that the 
information submitted would clearly support reclassification or 
indicate that the device should be retained in class III. This order 
was updated in the Federal Register of June 13, 1997 (62 FR 32355).
    Reclassification of classified preamendments devices is governed by 
section 513(e) of the act. This section provides that FDA may, by 
rulemaking, reclassify a device based upon ``new information.'' The 
reclassification can be initiated by FDA or by the petition of an 
interested person. The term ``new information,'' as used in section 
513(e) of the act, 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).)

[[Page 17392]]

    Re-evaluation of the data previously before the agency is an 
appropriate basis for subsequent regulatory action where the 
reevaluation is made in light of changes in ``medical science.'' (See 
Upjohn v. Finch, supra, 422 F.2d at 951.) However, regardless of 
whether data before the agency are past or new data, the ``new 
information'' upon which reclassification under section 513(e) of the 
act is based must consist of ``valid scientific evidence,'' as defined 
in section 513(a)(3) of the act and 21 CFR 860.7(c)(2). FDA relies upon 
``valid scientific evidence'' in the classification process to 
determine the level of regulation for devices. For the purpose of 
reclassification, the valid scientific evidence upon which the agency 
relies must be publicly available. Publicly available information 
excludes trade secret and/or confidential commercial information, e.g., 
the contents of a pending PMA. (See section 520(c) of the act (21 
U.S.C. 360j(c)).)

B. Device Description

    The TOCE is currently identified as a device intended to surround 
hermetically a patient's limb and apply humidified oxygen topically at 
a pressure slightly greater than atmospheric pressure to aid healing of 
chronic skin ulcers or bed sores.

C. Regulatory History of the Device

    In 1988, the agency issued a final rule classifying this device 
into class III (53 FR 23856, June 24, 1988). In the preamble to the 
classification final rule, FDA cited two documents that found little 
scientific evidence to support the safety and effectiveness of the 
device. FDA stated that there was a potential for widespread use of the 
device in the treatment of skin sores in the elderly and infirm. FDA 
concluded that the device presented a potential unreasonable risk of 
illness or injury to these patients if there were not adequate data to 
assure its safety and effectiveness. In addition, FDA found that the 
device was purported or represented to be for a use, the treatment of 
decubitus ulcers, that was of substantial importance in preventing 
impairment of human health. Accordingly, the agency classified the 
device into class III.
    In August 1997, in response to FDA's order for the submission of 
information on the TOCE, two manufacturers submitted 515(i) summaries 
of safety and effectiveness information to the agency for the TOCE 
(Refs. 1 and 2). These 515(i) summaries recommended that the device be 
reclassified into class II and provided information to assist FDA in 
reclassifying the device. FDA referred the 515(i) submissions to the 
General and Plastic Surgery Devices Panel (GPS Panel) for their 
recommendation on the requested reclassification.
    At a public meeting on November 17, 1998, the GPS Panel recommended 
that the device be retained in class III (Ref. 3). The GPS Panel based 
their recommendation on the information in the 515(i) submissions of 
safety and effectiveness information; the information provided by FDA; 
testimony presented at the meeting by manufacturers of the device, a 
physician user of the device, and FDA; and the Panel's deliberations at 
the meeting.
    The GPS Panel believed that the effectiveness of the TOCE remained 
unestablished. The Panel also concluded that special controls, in 
addition to general controls, were insufficient to provide a reasonable 
assurance of the safety and effectiveness of the device and that there 
was insufficient information, primarily a lack of effectiveness 
information, to establish special controls. Accordingly, the GPS panel 
recommended premarket approval to provide reasonable assurance of the 
device's effectiveness. The Panel recommended that the call for 
premarket approval be of low priority to allow manufacturers of the 
device sufficient time to conduct studies that would establish the 
effectiveness of the device.

II. Proposed Rule

    As discussed in more detail in the following paragraph, FDA is 
proposing to reclassify the TOCE from class III to class II (special 
controls). FDA believes that new information now exists to establish 
special controls, that, in addition to the general controls, will 
provide a reasonable assurance of the safety and effectiveness of this 
device.
    In addition, FDA is proposing minor revisions to the device 
description (see 21 CFR 878.5650) intended to more accurately describe 
this device type. FDA is proposing to remove the term hermetically and 
to clarify that bedsores are chronic skin ulcers. FDA proposes to 
identify the TOCE as follows: A topical oxygen chamber for extremities 
is a device that is intended to surround a patient's limb and apply 
humidified oxygen topically at a pressure slightly greater than 
atmospheric pressure to aid healing of chronic skin ulcers such as 
bedsores.

III. Risks to Health

    After considering the information in the 515(i) submissions for the 
two devices, the GPS Panel's recommendation, the published literature, 
and Medical Device Reports, FDA has evaluated the risks to health 
associated with use of the TOCE and determined that the following risks 
to health are associated with its use.

A. Infection

    If the device cannot be sterilized, an infection can occur. FDA 
also notes that some TOCEs are for single patient use and some are for 
multiple patient use. If a TOCE for multiple patient use cannot be 
adequately sterilized between use in multiple patients, there is a high 
potential for transmission of infection between patients because these 
patients are already immunologically compromised.

B. Fire and Explosion

    The risk of fire and explosion is common to all devices that are 
used in an atmosphere of pure oxygen.

C. Local Tissue Damage

    The therapeutic topical oxygen pressure range, which is only 
slightly above atmospheric pressure, is very narrow and is critical to 
maintain. Excessive topical oxygen pressure (higher than 22 millimeters 
of mercury) can occlude local arterial circulation, decreasing local 
tissue circulation, which could cause local tissue damage.

D. Adverse Tissue Reaction

    Adverse tissue reaction is a risk common to all devices that 
contact compromised skin. Incompatible materials or impurities in the 
materials may increase the severity of a local tissue reaction or cause 
a system tissue reaction.

E. Electrical Shock

    Electrical shock is also a risk common to electrical devices that 
contact compromised skin.

IV. Summary of the Reasons for the Reclassification

    FDA believes that the TOCE should be reclassified into class II 
because special controls, in addition to general controls, can be 
established to provide reasonable assurance of the safety and 
effectiveness of the device. In addition, there is now experience in 
the clinical community and adequate effectiveness information 
sufficient to establish special controls to provide such assurance.

V. Summary of the Data Upon Which the Reclassification is Based

    New information has become available since the 1998 GPS Panel 
meeting on the clinical effectiveness of the device. Specifically, 
three recent studies (two prospective and one

[[Page 17393]]

retrospective) report safe use and adequate healing of wounds using the 
TOCE. Two studies compared standard wound care with TOCE treatment for 
gangrenous or necrotic wounds (Refs. 4 and 5), and the third study 
evaluated the clinical effectiveness of TOCE treatment of chronic 
ulcers, post-surgical wounds, and acute trauma-induced wounds (Ref. 6). 
These three studies demonstrated adequate healing for an acceptable 
number of wounds. Investigators reported no complications related to 
TOCE use in these three studies.

VI. Special Controls

    FDA believes that the draft guidance document entitled ``Class II 
Special Controls Guidance: Topical Oxygen Chamber for Extremities'' 
(draft special controls guidance document), in addition to general 
controls, can be an adequate special control to address the risks to 
health associated with the use of the TOCE device described in section 
III of this document. FDA agrees with the GPS Panel that in 1998 the 
effectiveness of the TOCE was not established. FDA now believes that 
the new information cited previously (Refs. 4 to 6) provides sufficient 
supporting evidence regarding effectiveness. Thus, the agency now 
believes that the draft special controls guidance document, which 
incorporates voluntary consensus standards, device performance testing, 
and labeling, addresses the GPS Panel's concerns. Elsewhere in this 
issue of the Federal Register, FDA is publishing a notice of 
availability of the draft guidance document that the agency intends to 
use as the special control for this device.
    The draft special controls guidance document contains specific 
recommendations for device performance testing and other information 
that should be included in a premarket notification (510(k)) 
submission. For example, the draft special controls guidance document 
addresses the following issues: sterility, fire and explosion control, 
oxygen pressure control, biocompatibility, electrical safety testing, 
and labeling. In the following table 1, FDA has identified the risks to 
health associated with the use of the device in the first column and 
the recommended mitigation measures identified in the draft special 
controls guidance document in the second column. These recommendations 
will also help ensure that the device has appropriate performance 
characteristics and labeling for its use. Following the effective date 
of any final reclassification rule based on this proposal, any firm 
submitting a 510(k) submission for this device will need to address the 
issues covered in the draft special controls guidance document. 
However, the firm need only show that its device meets the 
recommendations of the draft special controls guidance document or in 
some other way provides equivalent assurances of safety and 
effectiveness.

                                 Table 1
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        Identified Risk              Recommended Mitigation Measures
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Infection                        Section 7: Sterility
                                 Section 12: Clinical Studies
                                 Section 13: Labeling
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Fire and Explosion               Section 8: Fire and Explosion Control
                                 Section 13: Labeling
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Local Tissue                     Section 9: Oxygen Pressure Control
 Damage
                                 Section 13: Labeling
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Adverse Tissue Reaction          Section 10: Biocompatibility
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Electrical Shock                 Section 11: Electrical Safety Testing
                                 Section 13: Labeling
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VII. FDA's Findings

    As discussed previously, FDA believes the TOCE should be 
reclassified into II because special controls, in addition to general 
controls, provide reasonable assurance of the safety and effectiveness 
of the devices, and there is sufficient information to establish 
special controls to provide such assurance. FDA, therefore, is 
proposing to reclassify the device into class II and establish the 
draft class II special controls guidance document as a special control 
for the device.
    Section 510(m) of the act provides that a class II device may be 
exempted from the premarket notification requirements under section 
510(k) of the act, if the agency determines that premarket notification 
is not necessary to provide reasonable assurance of the safety and 
effectiveness of the device. For this type of device, FDA has 
determined that premarket notification is necessary to provide 
reasonable assurance of safety and effectiveness and, therefore, the 
device is not exempt from the premarket notification requirements. FDA 
review of performance characteristics will provide reasonable assurance 
that acceptable levels of performance for both safety and effectiveness 
are addressed before marketing clearance. Thus, persons who intend to 
market this device must submit to FDA a 510(k) submission containing 
information on the TOCE and receive a substantial equivalence 
determination from the agency before marketing the device.

VIII. Proposed 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.

IX. 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.

X. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and 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 proposed rule is not a significant regulatory action as defined by 
the Executive order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Reclassification of this device from class III to 
class II will relieve all manufacturers of the device of the cost of 
complying with the premarket approval requirements of section 515 of 
the act. Because reclassification will reduce the regulatory costs with 
respect to this device, the agency certifies that the proposed rule 
will not have a significant economic impact on a substantial number of 
small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $115

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million, using the most current (2003) 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.

XI. 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.

XII. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no 
collections of information. Therefore, clearance by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(the PRA) (44 U.S.C. 3501-3520) is not required.
    FDA also tentatively concludes that the draft special controls 
guidance document does not contain new information collection 
provisions that are subject to review and clearance by OMB under the 
PRA. Elsewhere in this issue of the Federal Register, FDA is publishing 
a notice announcing the availability of the draft guidance document 
entitled ``Class II Special Controls Guidance: Topical Oxygen Chamber 
for Extremities''; the notice contains an analysis of the paperwork 
burden for the draft guidance.

XIII. Comments

    Interested persons may submit to the Division of Dockets Management 
Branch (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.

XIV. 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. 515(i) Submission submitted by Gaymar Industries, Inc., 
Orchard Park, NY, dated August 4, 1997, received August 11, 1997.
    2. 515(i) Submission submitted by Stephen's Medical Inc./Wound 
Cure, Inc., Northbrook, IL, dated August 11, 1997, received August 
12, 1997.
    3. General and Plastic Surgery Devices Panel, Transcript, 
November 17, 1998, pages 120-201.
    4. Heng, M.C.Y., J. Harker, V.B. Bardakjian, and H. Ayvazian, 
``Enhanced Healing and Cost-Effectiveness of Low Pressure Oxygen 
Therapy in Healing Necrotic Wounds: A feasibility study of 
technology transfer,'' Ostomy Wound Management, 46: 52-60, 2000.
    5. Heng, M.C.Y., J. Harker, G. Csathy, C. Marshall, J. Brazier, 
S. Socorro, and E.P. Gomez, ``Angiogenesis in Necrotic Ulcers 
Treated with Hyperbaric Oxygen,'' Ostomy Wound Management, 46: 18-
32, 2000.
    6. Kalliainen, L.K., G.M. Gordillo, R. Schlanger, and C.K. Sen, 
``Topical oxygen as an adjunct to wound healing: a clinical case 
series,'' Pathophysiology 9: 81-87, 2003.

List of Subjects in 21 CFR Part 878

    Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR part 878 be amended as follows:

PART 878--GENERAL AND PLASTIC SURGERY DEVICES

    1. The authority citation for 21 CFR part 878 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

    2. Section 878.5650 is revised in Subpart F to read as follows:


Sec.  878.5650  Topical oxygen chamber for extremities.

    (a) Identification. A topical oxygen chamber for extremities is a 
device that is intended to surround a patient's limb and apply 
humidified oxygen topically at a pressure slightly greater than 
atmospheric pressure to aid healing of chronic skin ulcers such as 
bedsores.
    (b) Classification. Class II (special controls). The special 
control for the device is FDA's ``Class II Special Controls Guidance: 
Topical Oxygen Chamber for Extremities.'' See Sec.  878.1(e) for the 
availability of this guidance document.

    Dated: March 27, 2006.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. E6-4962 Filed 4-5-06; 8:45 am]
BILLING CODE 4160-01-S