[Federal Register Volume 79, Number 183 (Monday, September 22, 2014)]
[Proposed Rules]
[Pages 56532-56538]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-22453]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 890

[Docket No. FDA-2000-N-0158]


Reclassification of Iontophoresis Devices Intended for Any Other 
Purposes

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed order.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to 
reclassify iontophoresis devices intended for any other purposes, a 
preamendments class III device, into class II (special controls), and 
to amend the device identification. FDA is proposing this 
reclassification on its own initiative based on new information. This 
action implements certain statutory requirements.

DATES: Submit either electronic or written comments by December 22, 
2014. See section XII for the proposed effective date of a final order 
based on this proposed order.

ADDRESSES: You may submit comments by any of the following methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following ways:
     Mail/Hand delivery/Courier (for paper submissions): 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Docket No. 
(FDA-2000-N-0158) for this rulemaking. All comments received may be 
posted without change to http://www.regulations.gov, 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.regulations.gov and insert the 
docket number, 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: Michael Ryan, Center for Devices and 
Radiological Health, Food and Drug Administration,10903 New Hampshire 
Ave., Bldg. 66, Rm. 1615, Silver Spring, MD 20993-0002, 301-796-6283.

SUPPLEMENTARY INFORMATION: 

I. Background--Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended 
by the Medical Device Amendments of 1976 (the 1976 amendments) (Pub. L. 
94-295), the Safe Medical Devices Act of 1990 (Pub. L. 101-629), the 
Food and Drug Administration Modernization Act of 1997 (Pub. L. 105-
115), the Medical Device User Fee and Modernization Act of 2002 (Pub. 
L. 107-250), the Medical Devices Technical Corrections Act (Pub. L. 
108-214), the Food and Drug Administration Amendments Act of 2007 (Pub. 
L. 110-85), and the Food and Drug Administration Safety and Innovation 
Act (FDASIA) (Pub. L. 112-144), among other amendments, established a 
comprehensive system for the regulation of medical devices intended for 
human use. Section 513 of the FD&C Act (21 U.S.C. 360c) established 
three categories (classes) of devices, reflecting 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).
    Section 513(a)(1) of the FD&C Act defines class II devices as those 
devices for which the general controls by themselves are insufficient 
to provide reasonable assurance of safety and effectiveness, but for 
which there is sufficient information to establish special controls to 
provide such assurance.
    Under section 513 of the FD&C Act, devices that were in commercial 
distribution before the enactment of the 1976 amendments, May 28, 1976 
(generally referred to as preamendments devices), are classified after 
FDA has: (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 
automatically classified by section 513(f) of the FD&C Act into class 
III without any FDA rulemaking process. Those devices remain in class 
III and require premarket approval unless, and until, the device is 
reclassified into class I or II or FDA issues an administrative order 
finding the device to be substantially equivalent, in accordance with 
section 513(i) of the FD&C 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 FD&C Act (21 U.S.C. 
360(k)) and part 807 (21 CFR part 807).
    On July 9, 2012, FDASIA was enacted. Section 608(a) of FDASIA 
amended section 513(e) of the FD&C Act, changing the process for 
reclassifying a device from rulemaking to an administrative order. 
Section 513(e) of the FD&C Act governs reclassification of classified 
preamendments devices. This

[[Page 56533]]

section provides that FDA may, by administrative order, reclassify a 
device based upon ``new information.'' FDA can initiate a 
reclassification under section 513(e) of the FD&C Act or an interested 
person may petition FDA to reclassify a preamendments device. The term 
``new information,'' as used in section 513(e) of the FD&C Act, 
includes information developed as a result of a reevaluation 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).)
    Reevaluation of the data previously before the Agency is an 
appropriate basis for subsequent regulatory action where the 
reevaluation 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, 389-391 (D.D.C. 1991)) or in light of changes in ``medical 
science'' (see Upjohn v. Finch, supra, 422 F.2d at 951). Whether data 
before the Agency are past or new data, the ``new information'' to 
support reclassification under section 513(e) must be ``valid 
scientific evidence,'' as defined in 21 CFR 860.7(c)(2). (See, e.g., 
General Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens 
Mfrs. Assoc. v. FDA, 766 F.2d 592 (D.C. Cir.), cert. denied, 474 U.S. 
1062 (1986).)
    FDA relies upon ``valid scientific evidence'' in the classification 
process to determine the level of regulation for devices. To be 
considered in the reclassification process, 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 
premarket approval application (PMA). (See section 520(c) of the FD&C 
Act (21 U.S.C. 360j(c)).)
    Section 513(e)(1) of the FD&C Act sets forth the process for 
issuing a final reclassification order. Specifically, prior to the 
issuance of a final order reclassifying a device, the following must 
occur: (1) Publication of a proposed reclassification order in the 
Federal Register; (2) a meeting of a device classification panel 
described in section 513(b) of the FD&C Act; and (3) consideration of 
comments to a public docket.
    In accordance with section 513(e)(1) of the FD&C Act, the Agency is 
proposing, based on new information that has come to the Agency's 
attention, to reclassify iontophoresis devices intended for any other 
purposes because general controls and special controls are sufficient 
to provide a reasonable assurance of safety and effectiveness. 
Therefore, this order proposes to reclassify iontophoresis devices 
intended for any other purposes into class II (special controls) and to 
amend the device identification.
    Section 510(m) of the FD&C Act provides that a class II device may 
be exempted from the premarket notification requirements under section 
510(k) of the FD&C Act, if the Agency determines that premarket 
notification is not necessary to assure the safety and effectiveness of 
the device. FDA has determined that premarket notification is necessary 
to assure the safety and effectiveness of iontophoresis devices 
intended for any other purposes.

II. Regulatory History of the Device

    On August 28, 1979, FDA published a proposed rule for 
classification of all iontophoresis devices in the Federal Register (44 
FR 50520). This proposed classification was based on recommendations 
made during three panel meetings in 1978, of the Physical Medicine 
Panel; the Ear, Nose, and Throat Panel; and the Dental Products Panel. 
The 1979 rule proposed that iontophoresis devices should have a split 
classification; iontophoresis devices intended for diagnosis of cystic 
fibrosis, anesthetizing the intact tympanic membrane, and dental 
application of fluoride to the teeth would be class II, and 
iontophoresis devices intended for any other purposes would be class 
III. A second meeting of the Physical Medicine Panel in 1979 (the 1979 
Panel) agreed with FDA's proposed rule, finding insufficient evidence 
of safety and effectiveness of iontophoresis except in the uses 
proposed for class II regulation. The 1979 Panel recommended that 
iontophoresis devices for general drug delivery and hyperhidrosis be 
classified in class III.
    The Agency agreed with the 1979 Panel that insufficient information 
existed to determine that general controls would provide reasonable 
assurance of the safety and effectiveness and that insufficient 
information existed to establish a performance standard to provide this 
assurance when the device was used for any purpose other than the three 
uses proposed for class II regulation. However, FDA also regulates 
drugs for safety and effectiveness and, at the time, the Agency was 
unaware of any drug that had labeling providing adequate directions for 
its use with an iontophoresis device for the dental application of 
fluoride or the anesthetizing of the intact tympanic membrane. 
Therefore, in order to prevent conflicting regulatory requirements 
between the Center for Devices and Radiological Health (CDRH) and the 
Center for Drug Evaluation and Research (CDER), CDRH determined that 
iontophoresis devices for the dental application of fluoride or the 
anesthetizing of the intact tympanic membrane should be classified into 
class III.
    On November 23, 1983, FDA published a final rule in the Federal 
Register classifying iontophoresis devices with a split classification 
(48 FR 53032 at 53045). The final rule revised the information that had 
been presented in the proposed rule to omit the dental application of 
fluoride and anesthetizing the intact tympanic membrane from the class 
II uses. The rule classified iontophoresis devices into class II when 
intended to induce sweating for use in the diagnosis of cystic fibrosis 
or for other uses if the labeling of the drug intended for use with the 
device bears adequate directions for the device's use with that drug 
(Sec.  890.5525(a) (21 CFR 890.5525(a)). The rule classified 
iontophoresis devices into class III when intended for any other 
purposes (Sec.  890.5525(b)), but did not establish an effective date 
of requirement for premarket approval.
    On August 22, 2000, FDA published a proposed rule in the Federal 
Register (65 FR 50949) (the August 2000 proposed rule) to amend the 
iontophoresis regulation to remove paragraph (b), the class III 
identification, such that only paragraph (a) of the regulation, the 
class II identification, would remain. In this rule, FDA stated that it 
believed it had made an error in the original classification and that 
there were no iontophoresis devices on the market prior to the Medical 
Device Amendments of 1976 (preamendments devices) that met the class 
III identification. Although several devices had been cleared under 
this regulation between 1976 and the publication of the proposed rule, 
FDA believed that those devices could meet the definition of a class II 
iontophoresis device with modifications to their labeling. Any device 
that could not meet the class II definition (i.e., for any other use 
than the diagnosis of cystic fibrosis or with a specific drug approved 
for iontophoretic delivery) would require submission of a PMA.
    FDA received seven comments in response to the August 2000 proposed

[[Page 56534]]

rule (see Docket No. FDA-2000-N-0158). Several comments disagreed with 
FDA's assertion that no class III preamendments iontophoresis devices 
existed. Two comments asserted that the assumption that there are 
differences between different iontophoresis devices that would warrant 
linking a particular device to a particular drug is in error, and 
suggested that FDA should consider reclassification of iontophoresis 
devices into either class I or class II as drug delivery systems 
comparable to syringes and pumps. In contrast, another comment rejected 
what it perceived as the implication that all iontophoresis drug 
delivery systems were the same and that any iontophoresis device could 
be relabeled to reference any drug approved for iontophoretic 
administration, whether or not the drug had actually been tested for 
use with that particular device.
    As a result of these comments, FDA withdrew the August 2000 
proposed rule on November 4, 2004 (69 FR 64266). In the same issue of 
the Federal Register, FDA also published a notice of its intent to 
initiate a proceeding to reclassify class III iontophoresis devices 
intended for any other purposes into class II (special controls) (69 FR 
64313).
    In 2009, FDA published an order in the Federal Register under 
section 515(i) of the FD&C Act (21 U.S.C. 360e(i)) to call for 
information on the remaining class III 510(k) devices (74 FR 16214, 
April 9, 2009). FDA received 10 submissions regarding iontophoresis 
devices in response to that order (see Docket No. FDA-2009-M-0101). One 
response stated that the company was only a repackager/relabeler of the 
device and did not have a recommended classification or information on 
safety and effectiveness. The remaining nine responses were all from 
manufactures of iontophoresis devices. Eight of the manufacturers 
recommended that the devices be reclassified into class II with special 
controls. The other manufacturer provided only safety and effectiveness 
information and did not recommend a classification. The risks to health 
identified by the manufacturers are included as part of the discussion 
in section V.
    On February 21, 2014, FDA held a classification panel meeting of 
the Orthopaedic and Rehabilitation Devices Panel (the 2014 Panel) in 
accordance with section 513(b) of the FD&C Act to discuss the 
reclassification of iontophoresis devices intended for any other 
purposes (Ref. 1). This device classification panel meeting discussed 
the relevant data and information described in this order, the risks to 
health for iontophoresis devices intended for any other purposes, 
whether they should be reclassified or remain in class III, and 
possible special controls for these devices if reclassified into class 
II. The Panel believed that iontophoresis devices intended for any 
other purposes present a potential unreasonable risk of illness or 
injury and recommended that general controls alone are not sufficient 
to ensure the safety and effectiveness of these devices. In 
deliberating whether sufficient information exists to establish special 
controls for these devices, the Panel voiced significant concerns over 
possible systemic effects that might be produced by some drugs, 
particularly fentanyl, or by misuse of drugs. The Panel consensus was 
that if this issue could be addressed, sufficient information exists to 
establish special controls for these devices that would mitigate the 
risks to health identified by FDA and the Panel, and that special 
controls, in combination with general controls, could provide a 
reasonable assurance of safety and effectiveness and these devices 
could be classified in class II.
    In order to address the Panel's concerns regarding systemic effects 
of the delivered drug, FDA is proposing to amend the identification of 
iontophoresis devices intended for any other purposes to clarify that 
devices intended to deliver specific drugs that may have adverse 
systemic effects, like fentanyl, are not considered part of this 
regulatory classification, and that only iontophoresis devices not 
labeled for use with a specific drug, or labeled for use with a non-
drug solution, are included. An iontophoresis device intended to 
deliver a specific drug with systemic effects, such as fentanyl, would 
be regulated as a combination product in CDER under section 503(g) of 
the FD&C Act (21 U.S.C. 353(g)) and Sec.  3.2(e) (21 CFR 3.2(e)) or 
under Sec.  890.5525(a)) (the iontophoresis regulation). FDA believes 
this will also help clarify the difference between the two regulatory 
subsets of iontophoresis devices. In addition, FDA is proposing a 
special control that will require iontophoresis device manufacturers to 
include labeling warnings regarding adverse systemic effects.

III. Device Description

    Iontophoresis is a noninvasive transdermal delivery method in which 
a substance bearing a charge is propelled through the skin by an 
electric current. Iontophoresis devices generally consist of a 
controller, active and return electrode(s), and a power supply used to 
deliver currents to transport drugs, soluble salts, ionic solutions, or 
other drugs into the body for medical purposes as an alternative to 
hypodermic injections. Iontophoresis systems consist of the 
iontophoresis device and the drug or other solution to be administered. 
If the system is marketed as a complete product that includes both a 
device and drug component, then it would be regulated as a drug-device 
combination product (see Sec.  3.2(e)), and CDER would have the lead 
jurisdictional authority because the primary mode of action of the 
combination product is attributable to the drug component (see Sec.  
3.2(m) and 21 CFR 3.4(a)). Alternatively, if the device component is 
marketed separately from a drug, or as a complete system with a non-
drug solution, then it would be regulated as a medical device by CDRH.
    The iontophoresis classification regulation is split into two 
parts, as described previously. Iontophoresis devices intended for use 
in the diagnosis of cystic fibrosis or for use with a specific drug 
that has been approved for delivery by iontophoresis are class II 
devices regulated under Sec.  890.5525(a). These devices are not the 
subject of this proposed order. Iontophoresis devices intended for any 
other purposes are currently class III devices regulated under Sec.  
890.5525(b). ``Any other purposes'' means that these devices are not 
intended for use in the diagnosis of cystic fibrosis and not indicated 
for use with a specific drug; that is, these devices are intended for 
general iontophoretic delivery of drugs that are approved for that 
route of administration. This device subset also includes devices 
indicated for use with specific non-drug solutions, such as tap water 
(e.g., for treatment of hyperhidrosis). FDA is proposing in this order 
to reclassify iontophoresis devices intended for any other purposes 
from class III to class II. FDA is also proposing in this order to 
amend the device identification in order to clarify the difference 
between the two subsets of iontophoresis devices in Sec.  890.5525, to 
emphasize that iontophoresis devices intended and labeled for use with 
specific drugs are regulated under Sec.  890.5525(a), and to clarify 
that these are prescription devices in accordance with Sec.  801.109 
(21 CFR 801.109).

IV. Proposed Reclassification

    FDA is proposing that iontophoresis devices intended for any other 
purposes be reclassified from class III to class II (special controls). 
FDA is also proposing, in response to the concerns voiced by the 2014 
Orthopaedic and Rehabilitation Devices Classification Panel regarding 
adverse systemic effects of drug delivery via iontophoresis

[[Page 56535]]

devices, to amend the identification of these devices to clarify that 
iontophoresis devices intended for any other purposes do not include 
devices labeled for use with specific drugs. In this proposed order, 
the Agency has identified special controls under section 513(a)(1)(B) 
of the FD&C Act that, if finalized, together with general controls 
(including prescription use restrictions) applicable to the devices, 
would provide reasonable assurance of their safety and effectiveness. 
Absent the special controls identified in this proposed order, general 
controls applicable to the device are insufficient to provide 
reasonable assurance of the safety and effectiveness of the device. FDA 
believes that iontophoresis devices may benefit patients by improving 
the noninvasive transdermal delivery of drugs or other solutions 
intended to treat various medical ailments or issues.
    Therefore, in accordance with sections 513(e) and 515(i) of the 
FD&C Act and Sec.  860.130 (21 CFR 860.130), based on new information 
with respect to the devices and taking into account the public health 
benefit of the use of the device and the nature and known incidence of 
the risks of the device, FDA, on its own initiative, is proposing to 
reclassify this preamendments class III device into class II. FDA 
believes that this new information is sufficient to demonstrate that 
the proposed special controls can effectively mitigate the risks to 
health identified in section V, and that these special controls, 
together with general controls (including prescription use 
restrictions), will provide a reasonable assurance of safety and 
effectiveness for iontophoresis devices intended for any other 
purposes.
    Section 510(m) of the FD&C Act authorizes the Agency to exempt 
class II devices from premarket notification (510(k)) requirements. FDA 
has considered iontophoresis devices intended for any other purposes 
and has determined that the device does require premarket notification 
(510(k)). Therefore, the Agency does not intend to exempt this proposed 
class II device from premarket notification (510(k)) submission 
requirements as provided for under section 510(m) of the FD&C Act.

V. Risks to Health

    After considering available information, including a comprehensive 
review of relevant literature and the recommendations of the 2014 
Orthopaedic and Rehabilitation Devices Classification Panel (Ref. 1), 
FDA has determined that the following risks to health are associated 
with the use of iontophoresis devices intended for any other purposes.
     Electric shock: Electrical shock hazards may pose a hazard 
to both operators and users. Excessive leakage current from the device 
could result in injury, or a malfunction of the device could result in 
electrical shock. Possible adverse events include cardiac events such 
as arrhythmias and cardiac arrest.
     Burns: Patient or user burns could result from a large 
electrical current density or a highly acidic solution.
     Insufficient or excessive delivery of drug or solution: 
Device malfunction (such as inaccurate current measurement), use error, 
or inadequate information on the drug or solution being used may result 
in inappropriate drug or solution delivery.
     Interference with other medical devices: Electromagnetic 
interference could interfere with other devices in the treatment 
environment, such as pacemakers implanted in either the patient or 
user.
     Adverse tissue reactions: Device materials that are not 
biocompatible may either directly or through the release of their 
material constituents or through a reaction with the ionic solution: 
(1) Produce adverse local or systemic effects such as contact 
dermatitis and scarring, (2) be carcinogenic, or (3) produce adverse 
reproductive and developmental effects. Although medical devices may 
have myriad biocompatibility issues, the biocompatibility concerns from 
iontophoresis devices are likely limited to skin reactions.
     Infection: Infection can occur from use of a non-sterile 
iontophoresis device, or from improper device design or use error. This 
risk is particularly relevant for devices used in the ear.
     Ear Trauma (when used in the ear): Use error or improper 
device design can lead to ear trauma, when used in the ear. This 
includes perforation of the tympanic membrane and middle or inner ear 
injuries.

VI. Summary of Reasons for Reclassification

    Based on the comments from the 2014 Panel meeting and FDA's 
assessment of new, valid scientific data related to the health benefits 
and risks associated with iontophoresis devices intended for any other 
purposes, FDA is proposing that these devices should be reclassified 
from class III to class II because sufficient information exists to 
establish specials controls, which, in addition to general controls, 
would provide a reasonable assurance of safety and effectiveness of the 
device, and because general controls themselves are insufficient to 
provide a reasonable assurance of its safety and effectiveness.
    FDA does not believe that iontophoresis devices not intended for 
use with a specific drug or solution are life-supporting or life-
sustaining, or for a use which is of substantial importance in 
preventing impairment of human health. FDA does believe these devices 
may present a potential unreasonable risk of illness or injury, as a 
review of the relevant clinical literature indicates. However, FDA 
believes that special controls, in combination with general controls, 
would provide reasonable assurance of safety and effectiveness.

VII. Summary of Data Upon Which the Reclassification Is Based

    FDA believes that the identified special controls, in addition to 
general controls (including prescription use restrictions), are 
necessary to provide reasonable assurance of safety and effectiveness 
of these devices. Therefore, in accordance with sections 513(e) and 
515(i) of the FD&C Act and Sec.  860.130, based on new information with 
respect to the device and taking into account the public health 
benefit(s) of the use of the device and the nature and known incidence 
of the risk(s) of the device, FDA, on its own initiative, is proposing 
to reclassify this preamendments class III device into class II. The 
Agency has identified special controls that would provide reasonable 
assurance of their safety and effectiveness. FDA's review of the 
clinical literature has been previously summarized in the Executive 
Summary to the 2014 Panel meeting to discuss iontophoresis device 
classification (Ref. 1).
    In addition, the 2014 Panel reviewed and discussed recent 
information presented by FDA, a manufacturer of iontophoresis devices, 
and members of the public. This information included recent literature 
regarding the possible risks to health and a review of FDA's 
Manufacturer and User Facility Device Experience (MAUDE) database.
    The 2014 Panel agreed that iontophoresis devices not intended for 
use with specific drugs or solutions are not ``life-supporting or life-
sustaining, or of substantial importance in preventing impairment of 
human health.'' The 2014 Panel agreed on the potential risks to health 
identified by FDA with some proposed clarifications, which were 
incorporated in section V. However, the 2014 Panel also expressed 
concerns regarding adverse systemic effects that might potentially 
result from use of iontophoresis devices to deliver drugs such as 
fentanyl, repeated treatments with certain drugs, or

[[Page 56536]]

misuse. In order to address the Panel's concerns regarding systemic 
effects, FDA is proposing to amend the identification of iontophoresis 
devices intended for any other purposes to clarify that devices 
intended to deliver specific drugs that may have adverse systemic 
effects, like fentanyl, are not considered part of this regulatory 
classification. An iontophoresis device intended to deliver a specific 
drug with systemic effects, such as fentanyl, would be regulated as a 
combination product in CDER or under Sec.  890.5525(a). FDA believes 
this will help clarify the difference between the two regulatory 
subsets of iontophoresis devices. In addition, FDA is proposing a 
special control that will require iontophoresis device manufacturers to 
include labeling warnings regarding adverse systemic effects. Regarding 
the benefits of iontophoresis devices not intended for use with a 
specific drug or solution, the 2014 Panel indicated that they believe 
that the benefit provided by these devices outweigh the probable risks, 
as long as their concern about potential adverse systemic events could 
be addressed.
    Regarding classification, there was general panel consensus that 
iontophoresis devices not intended for use with a specific drug or 
solution should be class II devices subject to special controls, unless 
the devices were used to deliver a treatment with potential adverse 
systemic effects. The Panel believed that such devices should be class 
III. However, iontophoresis devices intended to deliver specific drugs 
are not included in this regulatory subset of iontophoresis devices, 
and are regulated separately under Sec.  890.5525(a) or as combination 
products in CDER. FDA believes that its proposal to amend the 
identification of iontophoresis devices regulated under Sec.  
890.5525(b), as well as its proposed special controls, will address the 
Panel's concern. There was general consensus among the Panel that if 
that concern could be addressed that the special controls identified by 
FDA were appropriate. The Panel agreed that general controls alone are 
not sufficient to provide reasonable assurance of the safety and 
effectiveness of these devices.

VIII. Proposed Special Controls

    FDA believes that the following special controls, in addition to 
general controls (including applicable prescription use restrictions), 
are sufficient to mitigate the risks to health described in section V:
    1. Performance testing must provide a reasonable assurance of 
safety and effectiveness of the device, including:
    a. Testing using a drug approved for iontophoretic delivery, or a 
non-drug solution if identified in the labeling;
    b. testing of the ability of the device to maintain a safe pH 
level; and
    c. if used in the ear, testing of the mechanical safety of the 
device.
    2. Labeling must include adequate instructions for use, including 
sufficient information for the health care provider to determine the 
device characteristics that affect delivery of the drug or solution and 
to select appropriate drug or solution dosing information for 
administration by iontophoresis. This includes the following:
    a. A description and/or graphical representation of the electrical 
output;
    b. a description of the electrode materials and pH buffer;
    c. when intended for general drug delivery, language referring the 
user to approved drug labeling to determine if the drug they intend to 
deliver is specifically approved for use with that type of device and 
to obtain relevant dosing information; and
    d. a detailed summary of the device-related and procedure-related 
complications pertinent to use of the device, and appropriate warnings 
and contraindications, including the following warning:

Warning: Potential systemic adverse effects may result from use of this 
device. Drugs or solutions delivered with this device have the 
potential to reach the blood stream and cause systemic effects. 
Carefully read all labeling of the drug or solution used with this 
device to understand all potential adverse effects and to ensure 
appropriate dosing information. If systemic manifestations occur, refer 
to the drug or solution labeling for appropriate action.

    3. Appropriate analysis/testing must demonstrate electromagnetic 
compatibility, electrical safety, thermal safety, and mechanical 
safety. The requirement would, in concert with other special controls, 
help ensure the mitigation of cardiac events and discomfort, pain, and 
tenderness resulting from burns to the skin due to excessive energy 
deposition. In addition, this requirement would ensure the device does 
not interfere with other electrical equipment or medical devices and 
would also ensure that both operators and users are properly protected 
from electrical hazards such as electrical shock.
    4. Appropriate software verification, validation, and hazard 
analysis must be performed. This requirement would help mitigate the 
risk of insufficient or excessive delivery of drugs or non-drug 
solutions.
    5. The elements of the device that may contact the patient must be 
demonstrated to be biocompatible. These devices can contact users' and 
patients' skin directly; therefore, a demonstration of biocompatibility 
would mitigate the risks of skin reactions. Conditions of device 
operation, such as application of electrical current, may influence 
biocompatibility and should be considered in any biocompatibility 
determination.
    6. The elements of the device that may contact the patient must be 
assessed for sterility to ensure the risk of infection is mitigated.
    7. Performance data must support the shelf life of the elements of 
the device that may be affected by aging by demonstrating continued 
package integrity and device functionality over the stated shelf life.
    Table 1 shows how FDA believes that the risks to health identified 
in section V can be mitigated by the proposed special controls. Under 
Sec.  807.81 (21 CFR 807.81), these devices would also continue to be 
subject to 510(k) notification requirements.

  Table 1--Health Risks and Mitigation Measures for Sec.   890.5525(b)
                          Iontophoresis Devices
------------------------------------------------------------------------
              Identified risk                    Mitigation measures
------------------------------------------------------------------------
Burns.....................................  Performance Testing.
                                            Electrical Safety Testing.
                                            Shelf Life Testing.
                                            Labeling.
Electrical Shock..........................  Electrical Safety Testing.
                                            Shelf Life Testing.
                                            Labeling.
Insufficient or Excessive Delivery........  Performance Testing.
                                            Software Verification,
                                             Validation and Hazards
                                             Analysis.
                                            Labeling.
Interference with Other Medical Devices...  Electromagnetic
                                             Compatibility Testing.
                                            Labeling.
Adverse Tissue Reactions..................  Biocompatibility.
Infection.................................  Sterility.
                                            Shelf Life Testing.
Ear Trauma (only when used in the ear)....  Performance Testing.
                                            Labeling.
------------------------------------------------------------------------

    In addition, iontophoresis devices are restricted to patient use 
only upon the authorization of a practitioner licensed by law to 
administer or use the device. (Proposed Sec.  890.5525(b); Sec.  
801.109 (Prescription devices)). Under Sec.  807.81,

[[Page 56537]]

these devices would continue to be subject to 510(k) notification 
requirements.

IX. 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.

X. Paperwork Reduction Act of 1995

    This proposed order refers to currently approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collections of information in part 807, subpart E, have been approved 
under OMB control number 0910-0120; the collections of information in 
21 CFR part 814, subpart B, have been approved under OMB control number 
0910-0231; and the collections of information under 21 CFR part 801 
have been approved under OMB control number 0910-0485. In addition, FDA 
concludes that the labeling statement proposed in this order does not 
constitute a ``collection of information'' under the PRA. Rather, the 
labeling statement is ``public disclosure(s) of information originally 
supplied by the Federal government to the recipient for the purpose of 
disclosure to the public . . .'' (5 CFR 1320.3(c)(2)).
    No burden shift is associated with the reclassification of the 
device. This is currently a class III device for which manufacturers 
must submit a premarket notification (510(k)). This order proposes to 
reclassify the device into class II, therefore, respondents would 
continue to submit a premarket notification.

XI. Codification of Orders

    Prior to the amendments by FDASIA, section 513(e) of the FD&C Act 
provided for FDA to issue regulations to reclassify devices. Although 
section 513(e) of the FD&C Act as amended requires FDA to issue final 
orders rather than regulations, FDASIA also provides for FDA to revoke 
previously issued regulations by order. FDA will continue to codify 
classifications and reclassifications in the Code of Federal 
Regulations (CFR). Changes resulting from final orders will appear in 
the CFR as changes to codified classification determinations or as 
newly codified orders. Therefore, under section 513(e)(1)(A)(i), as 
amended by FDASIA, in this proposed order we are proposing to revoke 
the requirements in Sec.  890.5525(b)(1) related to the classification 
of iontophoresis devices not intended for use with a specific drug as 
class III devices and to codify their reclassification into class II 
(special controls).

XII. Proposed Effective Date

    FDA is proposing that any final order based on this proposed order 
become effective on the date of its publication in the Federal Register 
or at a later date if stated in the final order.

XIII. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments 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, and will be posted to the docket at http://www.regulations.gov.

XIV. Reference

    The following reference has 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, and is 
available electronically at http://www.regulations.gov. (FDA has 
verified the Web site address in this reference section, but we are not 
responsible for any subsequent changes to the Web site after this 
document publishes in the Federal Register.)

1. Meeting Materials for the February 21, 2014, meeting of the 
Orthopaedic and Rehabilitation Devices Panel, available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/OrthopaedicandRehabilitationDevicesPanel/ucm386335.htm.

List of Subjects in 21 CFR Part 890

    Medical devices, Physical medicine 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 890 be amended as follows:

PART 890--PHYSICAL MEDICINE DEVICES

0
1. The authority citation for 21 CFR part 890 continues to read as 
follows:

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

0
2. Amend Sec.  890.5525 by revising paragraph (b) and removing 
paragraph (c) to read as follows:


Sec.  890.5525  Iontophoresis device.

* * * * *
    (b) Iontophoresis device intended for any other purposes--(1) 
Identification. An iontophoresis device intended for any other purposes 
is a prescription device that is intended to use a current to introduce 
ions of drugs or non-drug solutions into the body for medical purposes 
other than those specified in paragraph (a) of this section, meaning 
that the device is not intended for use in diagnosis of cystic 
fibrosis, and a specific drug is not specified in the labeling of the 
iontophoresis device. Iontophoresis devices included in this 
classification may be intended to deliver non-drug solutions.
    (2) Classification. Class II (special controls). The special 
controls for this device are:
    (i) Performance testing must provide a reasonable assurance of 
safety and effectiveness of the device, including:
    (A) Testing using a drug approved for iontophoretic delivery, or a 
non-drug solution if identified in the labeling;
    (B) testing of the ability of the device to maintain a safe pH 
level; and
    (C) if used in the ear, testing of the mechanical safety of the 
device.
    (ii) Labeling must include adequate instructions for use, including 
sufficient information for the health care provider to determine the 
device characteristics that affect delivery of the drug or solution and 
to select appropriate drug or solution dosing information for 
administration by iontophoresis. This includes the following:
    (A) A description and/or graphical representation of the electrical 
output;
    (B) a description of the electrode materials and pH buffer;
    (C) when intended for general drug delivery, language referring the 
user to approved drug labeling to determine if the drug they intend to 
deliver is specifically approved for use with that type of device and 
to obtain relevant dosing information; and
    (D) a detailed summary of the device-related and procedure-related 
complications pertinent to use of the device, and appropriate warnings 
and contraindications, including the following warning:


[[Page 56538]]



Warning: Potential systemic adverse effects may result from use of this 
device. Drugs or solutions delivered with this device have the 
potential to reach the blood stream and cause systemic effects. 
Carefully read all labeling of the drug or solution used with this 
device to understand all potential adverse effects and to ensure 
appropriate dosing information. If systemic manifestations occur, refer 
to the drug or solution labeling for appropriate action.

    (iii) Appropriate analysis/testing must demonstrate electromagnetic 
compatibility, electrical safety, thermal safety, and mechanical 
safety.
    (iv) Appropriate software verification, validation, and hazard 
analysis must be performed.
    (v) The elements of the device that may contact the patient must be 
demonstrated to be biocompatible.
    (vi) The elements of the device that may contact the patient must 
be assessed for sterility.
    (vii) Performance data must support the shelf life of the elements 
of the device that may be affected by aging by demonstrating continued 
package integrity and device functionality over the stated shelf life.

    Dated: September 15, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-22453 Filed 9-19-14; 8:45 am]
BILLING CODE 4164-01-P