[Federal Register Volume 81, Number 143 (Tuesday, July 26, 2016)]
[Rules and Regulations]
[Pages 48703-48707]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-17609]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 890
[Docket No. FDA-2000-N-0158]
Physical Medicine Devices; Reclassification of Iontophoresis
Device Intended for Any Other Purposes
AGENCY: Food and Drug Administration, HHS.
ACTION: Final order.
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SUMMARY: The Food and Drug Administration (FDA) is issuing a final
order to reclassify iontophoresis devices intended for any other
purposes, which are preamendments class III devices (regulated under
product code EGJ), into class II (special controls) and to amend the
device identification to clarify that devices intended to deliver
specific drugs are not considered part of this regulatory
classification.
DATES: This order is effective on July 26, 2016.
FOR FURTHER INFORMATION CONTACT: Jismi Johnson, Center for Devices and
Radiological Health, 10903 New Hampshire Ave., Bldg. 66, Rm. 1524,
Silver Spring, MD 20993, 301-796-6424, [email protected].
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
[[Page 48704]]
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).
Under section 513(d) 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.
A preamendments device that has been classified into class III and
devices found substantially equivalent by means of premarket
notification procedures (510(k)) to such a preamendments device or to a
device within that type (both the preamendments and substantially
equivalent devices are referred to as preamendments class III devices)
may be marketed without submission of a premarket approval application
(PMA) until FDA issues a final order under section 515(b) of the FD&C
Act (21 U.S.C. 360e(b)) requiring premarket approval or until the
device is subsequently reclassified into class I or class II.
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 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 mechanism for
reclassifying a device under that section from rulemaking to an
administrative order.
Section 513(e) of the FD&C Act governs reclassification of
classified devices. This section provides that FDA may, by
administrative order, reclassify a device based on ``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), 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 Co. 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 action where the reevaluation is made
in light of newly available authority (see Bell, 366 F.2d at 181;
Ethicon, Inc. v. FDA, 762 F.Supp. 382, 388-391 (D.D.C. 1991)), or in
light of changes in ``medical science'' (Upjohn, 422 F.2d at 951).
Whether data before the Agency are old or new data, the ``new
information'' to support reclassification under section 513(e) must be
``valid scientific evidence,'' as defined in section 513(a)(3) of the
FD&C Act and 21 CFR 860.7(c)(2). (See, e.g., General Medical Co. v.
FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens Association v. FDA,
766 F.2d 592 (D.C. Cir. 1985), 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
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 order to reclassify a device under that section.
Specifically, prior to the issuance of a final order reclassifying a
device, the following must occur: (1) Publication of a proposed 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.
II. Regulatory History of the Device
FDA presented the complete regulatory history of these devices in
the proposed order to reclassify iontophoresis devices for any other
purposes, published in the Federal Register of September 22, 2014 (79
FR 56532) (the ``proposed order''). The following are the most relevant
pieces of the regulatory history of these devices. On August 28, 1979,
the Agency published a proposed rule (44 FR 50520) for classification
of all iontophoresis devices. On November 23, 1983, FDA issued a final
rule in the Federal Register (48 FR 53032 at 53045) classifying
iontophoresis devices into two different classes based on the device's
intended use. Specifically, 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 only when 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))).
These devices are currently under product code KTB. 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. These devices are currently
under product code EGJ. In 2009, FDA published an order under section
515(i) of the FD&C Act (the ``515(i) Order'') requiring manufacturers
of remaining class III devices for which regulations requiring PMAs had
not been issued, including iontophoresis devices (Sec. 890.5525(b)),
to submit a summary of information concerning those devices by August
7, 2009 (74 FR 16214, April 9, 2009).
As discussed in the proposed order, FDA considered the available
information on iontophoresis devices intended for any other purposes
and concluded that these devices, which are prescription devices, could
be reclassified to class II, subject to the special controls identified
in the
[[Page 48705]]
proposed order, because there was sufficient information that these
special controls, along with general controls, would provide reasonable
assurance of safety and effectiveness. As required by section 513(e)(1)
of the of the FD&C Act, FDA convened a meeting of a device
classification panel described in section 513(b) of the FD&C Act,
specifically the Orthopaedic and Rehabilitation Devices Panel (the 2014
Panel), to discuss whether iontophoresis devices intended for any other
purposes should be reclassified or remain in class III on February 21,
2014 (Ref. 1). Please see the proposed order for additional information
on the 2014 Panel. Ultimately, the panel concluded that sufficient
information exists to establish special controls for these devices, and
that special controls in combination with general controls could
provide a reasonable assurance of safety and effectiveness; and thus,
iontophoresis devices for any other purposes could be classified in
class II.
FDA received and has considered three sets of comments on this
proposed order, as discussed in section III of this document.
Therefore, FDA has met the requirements for issuing a final order under
section 513(e)(1) of the FD&C Act. FDA is not aware of new information
since the 2014 Panel meeting that would provide a basis for a different
recommendation or finding.
III. Public Comments in Response to the Proposed Order
In response to the proposed order, FDA received three sets of
comments from various stakeholders. The comments and FDA's responses to
the comments are summarized as follows.
(Comment 1) One comment requested that iontophoresis devices
intended for any other purposes remain classified in class III, and
that FDA call for PMAs for these products. The commenter disagreed that
general controls and special controls are sufficient to provide a
reasonable assurance of safety and effectiveness because of, among
other reasons, the commenter located, at the time of the 2014 Panel
meeting, 40 adverse event reports for a 5-year period that implicated
device malfunction, 12 of which include burns, in a search of the
Manufacturer and User Facility Device Experience (MAUDE) database for
iontophoresis devices intended for any other purposes. The commenter
stated that manufacturing inspections during the PMA process would help
ensure that iontophoresis devices are constructed properly and,
therefore, be less likely to cause third degree burns and other
injuries.
(Response) FDA disagrees that iontophoresis devices intended for
any other purposes should remain in class III and require PMA approval.
As discussed in section V, ``Risks to Health,'' of the proposed order,
these devices have certain risks to health; however, the Agency
believes that those risks can be mitigated by the special controls. For
example, the special controls include performance testing that will
mitigate the risks of burns, insufficient or excessive drug delivery,
and/or infection. Performance testing using a drug approved for
iontophoretic delivery, or a solution, identified in the labeling, will
ensure that device malfunction or use error is minimized. Additionally,
performance testing will ensure that iontophoresis devices intended for
any other purposes maintain a safe pH level to minimize burns from a
large electrical current density or highly acidic solution. Based on
FDA's review of the MAUDE database, the number of adverse event reports
identified for iontophoresis devices intended for any other purposes
has decreased over the last several years, supporting that the risk of
injury is low. Furthermore, in the past decade, there have been no
recalls for iontophoresis devices intended for any other purposes.
(Comment 2) In addition, the commenter expressed concern that the
special control requiring a labeling warning about adverse systemic
effects was an insufficient safeguard because clinicians and patients
may not see or read the label.
(Response) FDA takes issue with this statement. As stated in the
proposed order, iontophoresis devices are restricted to patient use
only upon the authorization of a practitioner licensed by law to
administer or use the device and the device identification in Sec.
890.5525(b) has been revised to clarify that these are prescription
devices in accordance with Sec. 801.109 (21 CFR 801.109). Per Sec.
801.109(c), a prescription device, including iontophoresis devices
intended for any other purposes, must include labeling that describes
the indications and other information for use, such as methods,
frequency and duration of administration, any relevant hazards,
contraindications, side effects, and precautions under which the
practitioners can use the device safely. Accordingly, clinicians will
have access to and be aware of the warnings and precautions in the
labeling, and as such, clinicians should be adequately informed of the
risks associated with these devices. The clinician can inform the
patients of the relevant risks. Therefore, the warning and precaution
statements are an appropriate mitigation. FDA believes, therefore, that
the special controls identified in this final order, in combination
with general controls, will adequately mitigate the risks identified
for iontophoresis devices intended for any other purposes and will
provide a reasonable assurance of safety and effectiveness. 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. As such, it is
appropriate to reclassify these devices from class III (PMA) to class
II (special controls). This is also the conclusion supported by the
2014 Panel.
(Comment 3) Two comments supported the reclassification of
iontophoresis from class III to class II when these devices are
intended for any other purposes. One comment, although overall
supportive of reclassification, disagreed with the modified
identification language and special controls. This comment asserted
that the special controls, by requiring testing using a drug approved
for iontophoretic delivery and labeling that contains language
referring the user of the device to approved drug labeling, would
create different regulatory paradigms for Sec. 890.5525(a) and (b),
such that a new drug application (NDA) and 510(k) are needed for
iontophoresis devices falling under paragraph (b) of the regulation,
and that a 510(k) is needed for paragraph (a), although the devices are
similar. The commenter uses iontophoresis devices that deliver
pilocarpine for the diagnosis of cystic fibrosis, regulated under Sec.
890.5525(a), as an example of this inconsistency.
(Response) To the extent the commenter is raising issues related to
products regulated under Sec. 890.5525(a), such products are not the
subject of this reclassification; and as such, are not addressed here.
However, we do note that the commenter's statement about two different
regulatory paradigms is incorrect. As stated previously in this
document and in the proposed order, whether an iontophoresis device
falls into Sec. 890.5525(a) or (b), any drug that is intended to be
used with these devices is required to have marketing authorization for
iontophoretic administration of that drug. FDA intends to consider
addressing the regulation of iontophoresis devices under Sec.
890.5525(a) through a separate process.
In addition, iontophoresis devices intended for any other purposes
regulated under Sec. 890.5525(b) will need to comply with the
applicable special
[[Page 48706]]
controls prior to entering the market. ``Any other purposes'' means
that these devices are neither intended for use in the diagnosis of
cystic fibrosis nor for use with a specific drug. Devices for any other
purposes may include those intended for general iontophoretic delivery
of drugs that are approved for that route of administration or intended
for use with specific solutions. One example of an iontophoretic device
for ``any other purposes'' is one indicated for use with tap water for
treatment of hyperhidrosis.
(Comment 4) The commenter also requested clarification on the
identified risk of infection and the special control that states the
patient-contacting elements of the device must be assessed for
sterility.
(Response) FDA believes that patient-contacting elements should be
assessed for sterility if the device is labeled as sterile, and has
clarified the special control in question (Sec. 890.5525(b)(2)(vi)) to
specify such.
IV. The Final Order
Based on the information discussed previously and in the preamble
to the proposed order, the comments on the proposed order, a review of
the MAUDE database, a review of current scientific literature, and
panel deliberations (see the 2014 Panel transcript (Ref. 1)), FDA
concludes that special controls, in conjunction with general controls,
will provide reasonable assurance of the safety and effectiveness of
iontophoresis devices intended for any other purposes. Under section
513(e) of the FD&C Act, FDA is adopting its findings as published in
the preamble to the proposed order, with the modification of the
special control pertaining to sterility (Sec. 890.5525(b)(2)(vi)) to
clarify that only devices labeled as sterile must have their patient-
contacting elements assessed for sterility. FDA is issuing this final
order to reclassify iontophoresis devices intended for any other
purposes from class III to class II and establish special controls by
revising Sec. 890.5525(b).
As noted previously, the identification for Sec. 890.5525(b) has
been clarified to specify that devices intended to deliver specific
drugs, including those drugs that may have adverse systemic effects,
like fentanyl, are not considered part of this regulatory
classification (Sec. 890.5525(b)(1)).
Following the effective date of this final order, firms submitting
a premarket notification (510(k)) for iontophoresis devices intended
for any other purposes must comply with the applicable mitigation
measures set forth in the codified special controls. This includes
firms who are required to submit a new 510(k) under Sec. 807.81(a)(3)
because the device is about to be significantly changed or modified.
Additionally, a firm whose device was legally in commercial
distribution before May 28, 1976, or whose device has been found to be
substantially equivalent to such a device, must also comply with the
special controls to remain legally on the market.
Section 510(m) of the FD&C Act provides that FDA may exempt a class
II device from the premarket notification requirements under section
510(k) of the FD&C Act if FDA determines that premarket notification is
not necessary to provide reasonable assurance of the safety and
effectiveness of the devices. FDA has determined that premarket
notification is necessary to provide reasonable assurance of safety and
effectiveness of iontophoresis devices intended for any other purposes,
and therefore, this device type is not exempt from premarket
notification requirements.
V. Analysis of 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.
VI. Paperwork Reduction Act of 1995
This final order refers to previously 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; and the collections of information
under part 801 have been approved under OMB control number 0910-0485.
In addition, FDA concludes that the labeling statement codified in
this order does not constitute a ``collection of information'' under
the PRA. Rather, the labeling statement is a public disclosure 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)).
VII. 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) as amended requires FDA to issue final orders rather
than regulations, FDASIA also provides for FDA to revoke previously
promulgated 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) of the
FD&C Act, as amended by FDASIA, in this final order, we are revoking
the requirements in Sec. 890.5525(b) related to the classification of
iontophoresis devices intended for any other purposes as class III
devices and codifying the reclassification of iontophoresis device
intended for any other purposes into class II (special controls).
VIII. Reference
The following reference is on display in the Division of Dockets
Management (HFA-305) Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, and is available for viewing by
interested persons between 9 a.m. and 4 p.m., Monday through Friday; it
is also available electronically at http://www.regulations.gov. FDA has
verified the Web site address, as of the date this document publishes
in the Federal Register, but Web sites are subject to change over time.
1. The panel transcript and other meeting materials for the February
21, 2014, Orthopedic and Rehabilitation Devices Panel are available
on FDA's Web site 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, part 890 is
amended as follows:
PART 890--PHYSICAL MEDICINE DEVICES
0
1. The authority citation for part 890 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
0
2. In Sec. 890.5525 revise paragraph (b) and remove paragraph (c) to
read as follows:
Sec. 890.5525 Iontophoresis device.
* * * * *
[[Page 48707]]
(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, or a specific drug is not specified in the labeling of the
iontophoresis device.
(2) Classification. Class II (special controls). The device is
classified as class II. The special controls for this device are:
(i) The following performance testing must be conducted:
(A) Testing using a drug approved for iontophoretic delivery, or a
solution, if identified in the labeling, to demonstrate safe use of the
device as intended;
(B) Testing of the ability of the device to maintain a safe pH
level; and
(C) If used in the ear, testing of the device to demonstrate
mechanical safety.
(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 drug labeling approved for iontophoretic delivery 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.
(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, for devices labeled as sterile.
(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: July 20, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-17609 Filed 7-25-16; 8:45 am]
BILLING CODE 4164-01-P