[Federal Register Volume 89, Number 98 (Monday, May 20, 2024)]
[Rules and Regulations]
[Pages 43743-43747]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-10895]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 886
[Docket No. FDA-2018-N-3074]
Ophthalmic Devices; Reclassification of Ultrasound
Cyclodestructive Device
AGENCY: Food and Drug Administration, HHS.
ACTION: Final amendment; final order.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
issuing a final order reclassifying the ultrasound cyclodestructive
device, a postamendments class III device (product code LZR), into
class II (special controls), subject to premarket notification. FDA is
also establishing special controls that are necessary to provide a
reasonable assurance of safety and effectiveness of the device. FDA is
finalizing this reclassification on its own initiative based on valid
scientific evidence. For this class II device, instead of a premarket
approval application, manufacturers may submit a premarket
notification, i.e., a 510(k) submission, and obtain FDA clearance of
the device before marketing it.
DATES: This order is effective June 20, 2024.
FOR FURTHER INFORMATION CONTACT: Claudine Krawczyk, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 1238, Silver Spring, MD 20993, 301-796-
6860, [email protected].
SUPPLEMENTARY INFORMATION:
I. Background--Regulatory Authorities
The Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended,
establishes 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 general controls),
and class III (premarket approval and general controls).
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)(1) 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 (1) FDA
reclassifies the device into class I or class II; or (2) 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 previously marketed devices by
means of the procedures in section 510(k) of the FD&C Act (21 U.S.C.
360(k)) and our implementing regulations (part 807, subpart E (21 CFR
part 807, subpart E)).
[[Page 43744]]
A postamendments device that has been initially classified into
class III under section 513(f)(1) of the FD&C Act may be reclassified
into class I or class II under section 513(f)(3) of the FD&C Act (21
U.S.C. 360c(f)(3)). Section 513(f)(3) provides that FDA, acting by
administrative order, can reclassify the device into class I or class
II on its own initiative, or in response to a petition from the
manufacturer or importer of the device. To change the classification of
the device, the new class must have sufficient regulatory controls to
provide reasonable assurance of the safety and effectiveness of the
device for its intended use.
Reevaluation of the data previously before the Agency is an
appropriate basis for subsequent action where the reevaluation is made
in light of changes in ``medical science'' (Upjohn v. Finch, 422 F.2d
944, 951 (6th Cir. 1970); Ethicon, Inc. v. FDA, 762 F. Supp. 382, 388-
391 (D.D.C. 1991)). Whether data before the Agency are old or new, the
data to support reclassification under section 513(f)(3) 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)).
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 520(h)(4) of the FD&C Act provides
that FDA may use, for reclassification of a device, certain information
in a PMA 6 years after the application has been approved. This includes
information from clinical and preclinical tests or studies that
demonstrate the safety and effectiveness of the device, but it does not
include the descriptions of methods of manufacture and product
composition and other trade secrets.
Section 510(m) of the FD&C Act provides that FDA may exempt a class
II device from the requirements under section 510(k) of the FD&C Act if
FDA determines that a 510(k) is not necessary to provide reasonable
assurance of the safety and effectiveness of the device type.
On September 25, 2018, FDA published a proposed order in the
Federal Register to reclassify the ultrasound cyclodestructive device
(product code LZR) (83 FR 48403, the ``proposed order''). The period
for public comment on the proposed order closed on November 26, 2018.
FDA received and has considered comments on the proposed order, as
discussed in Section II of this document.
II. Comments on the Proposed Order and FDA Responses
A. Introduction
FDA received fewer than 10 public comments on the proposed order.
These comments came from individual and anonymous commenters. The
majority of the comments supported the proposed reclassification of
ultrasound cyclodestructive devices.
We describe and respond to the comments in section II.B. The order
of the comments and our response to them is purely for organizational
purposes and does not signify the comment's value or importance nor the
order in which comments were received. Certain comments are grouped
together under a single number because the subject matter is similar.
B. Description of Comments and FDA Response
(Comment 1) The majority of commenters supported the proposed
reclassification of ultrasound cyclodestructive devices. One commenter
stated that decreasing the regulatory burden (through reclassification
of the device from class III into class II) for ultrasound
cyclodestructive devices will hopefully allow increased access of the
devices for patients. The commenter further stated that having stricter
manufacturing and regulatory controls during the initial years of
device use (as a class III device) and then decreasing the controls
should not result in an increase of known medical incidents. Another
commenter stated that there is sufficient information to establish
special controls which can provide a reasonable assurance of safety and
effectiveness.
(Response 1) FDA agrees with the comments. Based on the available
information (including valid scientific evidence), as discussed in the
proposed order, and consideration of the comments received on the
proposed order, FDA has determined that reclassification of ultrasound
cyclodestructive devices into class II is appropriate because there is
sufficient information to establish special controls for the device
that, together with general controls, will provide for reasonable
assurance of safety and effectiveness. The Agency believes that
reclassification of ultrasound cyclodestructive devices under this
final order will reduce the regulatory burden on manufacturers, while
still providing reasonable assurance of safety and effectiveness.
Specifically, reclassifying this type of device from class III into
class II will reduce regulatory burdens on industry because instead of
submission of a PMA, manufacturers may submit a less burdensome
premarket notification (i.e., a 510(k) submission) and obtain FDA
clearance of the device before marketing it.
Additionally, FDA agrees that there is sufficient information to
establish special controls and that the special controls required in
this final order, along with general controls, provide a reasonable
assurance of safety and effectiveness for these devices for their
intended use. FDA has identified the probable risks to health in
section V of the proposed order, and the Agency has determined, in
finalizing the proposed order after considering the comments received,
that the special controls in this final order will mitigate such risks
to health.
(Comment 2) A commenter stated that ultrasound cyclodestructive
devices should be reclassified into class II, similarly to devices
indicated for use in conventional refractory glaucoma treatment
modalities (e.g., implantable aqueous shunts and valves,
cyclocryotherapy, laser transcleral cyclophotocoagulation), all of
which are regulated as class II devices subject to 510(k) requirements.
The commenter stated that it also concurred with the definition of
refractory glaucoma described in the proposed order and claimed that
the definition is consistent with current medical practice for the
management of the disease and with other device treatment modalities
cleared by FDA (e.g., implantable aqueous shunts).
(Response 2) This comment is supportive of the reclassification.
The term ``refractory glaucoma'' in the proposed order refers to the
intended use population for the device: ``patients who are refractory
to or are poor candidates for laser or surgical treatment and fail to
achieve target intraocular pressures on maximally tolerated drug
therapy'' (83 FR 48403 at 48405, Section III, Device Description).
Although we explained what we meant by ``refractory glaucoma'' in the
preamble of the proposed order (as mentioned by the commenter), we did
not include that clarification in the proposed codified text. Upon
consideration of this comment, however, FDA believes clarifying in the
codified text what we mean by
[[Page 43745]]
``refractory glaucoma'' would be helpful in reducing ambiguity in the
codified text and reducing the potential for misunderstanding of the
intended use population, which is specific to the population that was
treated in the studies supporting the only PMA approved by FDA for a
device within the device type being reclassified under this final
order. Retaining the proposed codified language may incorrectly
indicate that this classification applies to types of laser treatments
for glaucoma that were developed after the approval of this PMA.
Therefore, FDA is revising the device identification language in the
codified text of the final order from ``. . . and that is intended for
treatment of refractory glaucoma'' to ``. . . and that is intended for
treatment of glaucoma patients who . . . are refractory to, or are poor
candidates for, Argon laser trabeculoplasty or traditional filtering
surgery and . . . had failures on maximally tolerated drug therapy.''
(Comment 3) A commenter requested clarification concerning the
classification of certain conventional glaucoma treatment modalities
mentioned at the end of section III of the proposed order;
specifically, the commenter indicated that trabeculectomy and some
incisional glaucoma surgeries do not involve a class II medical device
and noted that class I manual ophthalmic instruments are used to
perform some of these surgeries.
(Response 3) FDA notes that this final order only applies to
ultrasound cyclodestructive devices. Nevertheless, to clarify, the
commenter is correct in that the manual ophthalmic instruments (e.g.,
trabeculotomes, cannulas, etc.) are class I devices, not subject to
510(k) requirements, and are indicated ``to aid or perform ophthalmic
surgical procedures.'' However, FDA notes that these manual ophthalmic
instruments regulated under 21 CFR 886.4350 are not indicated
specifically to treat glaucoma patients.
(Comment 4) A commenter requested clarification on the device
identification description in the proposed order. Specifically, the
commenter stated that not all ultrasound cyclodestructive devices have
been shown to create additional lesions in the trabecular meshwork and
recommended that the device identification paragraph be revised
accordingly.
(Response 4) FDA agrees that not all ultrasound cyclodestructive
devices create lesions in the trabecular meshwork and that an edit to
the device identification paragraph (a) of proposed Sec. 886.5350 is
appropriate. Specifically, FDA has modified the device identification
paragraph (a) of Sec. 886.5350 in the final order so that it reads:
``An ultrasound cyclodestructive device is a prescription device that
reduces intraocular pressure by producing a series of lesions in the
ciliary body and/or trabecular meshwork induced by high intensity
focused ultrasound (HIFU) energy . . .'' (italics added in this
preamble discussion to highlight the change).
(Comment 5) A commenter requested the special controls in the
proposed order to reference IEC 60601-2-62 Medical electrical
equipment--Part 2-62: Particular requirements for the basic safety and
essential performance of high intensity therapeutic ultrasound (HITU)
equipment since it is recognized by FDA and is relevant to the
reclassification of these devices.
(Response 5) FDA acknowledges that IEC 60601-2-62 has been
recognized by FDA (79 FR 38919, Jul. 9, 2014) and is relevant to
ultrasound cyclodestructive devices.\1\ This standard includes methods
of thermal and mechanical safety analysis. FDA agrees that
manufacturers may rely on this FDA-recognized standard to comply with
some of the special controls identified in this final order. However,
IEC-60601-2-62 is not the sole methodology for complying with some of
the special controls identified in this final order. Therefore, no
change has been made to reference IEC 60601-2-62 in the special
controls.
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\1\ See the current FDA database of Recognized Consensus
Standards, available at https:\\www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm.
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(Comment 6) A commenter did not agree with the reclassification of
ultrasound cyclodestructive devices from class III into class II due to
the potential adverse events caused by the use of the device.
Specifically, the commenter raised concerns related to the ultrasound
cyclodestructive devices causing lesions, thermal damage of the ocular
tissue, possible temperature elevation with use of the device causing
corneoscleral lesions, intraocular inflammation, ciliary body
hemorrhage, decreased visual acuity and worsening glaucoma.
(Response 6) The commenter raised important concerns regarding
potential adverse effects secondary to the exposure to unsafe level of
HIFU energy. The proposed order adequately discusses these and other
risks to health associated with use of the device, including thermal
injury, physical injury, post-treatment injury, electrical shock,
electromagnetic interference, ocular irritation, and corneal
infections. As stated in Response 1 and in section III of this
document, based on the available information (including valid
scientific evidence), as discussed in the proposed order, and
considering the comments received on the proposed order, FDA has
determined that reclassification of ultrasound cyclodestructive devices
into class II is appropriate because there is sufficient information to
establish special controls for the device, that together with general
controls, will provide reasonable assurance of safety and
effectiveness. For example, the special control under Sec.
886.5350(b)(2)(i) of this final order requires, among other things,
characterization of the total acoustic power radiated by the
transducers, and Sec. 886.5350(b)(2)(ii) requires characterization of
the thermal and physical safety of the device. Any new device would
have to show substantial equivalence to a legally marketed predicate
device, which would include a comparison with respect to intended use
and technology, and the supporting data submitted must demonstrate,
among other things, that the device is as safe and effective as a
legally marketed device. In addition, the special controls described in
Sec. 886.5350(b)(1) of this final order require clinical performance
data to demonstrate an appropriate reduction in intraocular pressure in
glaucoma patients who (1) are refractory to, or are poor candidates
for, Argon laser trabeculoplasty or traditional filtering surgery and
(2) have failures on maximally tolerated drug therapy. The submitted
clinical performance data would also specifically need to include
evaluation of all adverse events observed during clinical use, which
would include not only adverse events observed when the device is in
use but also during the post-treatment period, such as any ocular
tissue thermal injuries, physical injuries, inflammation, etc. FDA has
provided a minor revision to the proposed codified language to delete
reference to an ``adequate safety profile'' in the special control to
require more specifically ``an evaluation of all adverse events
observed during clinical use.'' FDA has determined this change will
establish the same reasonable assurance of safety and effectiveness for
the device, while giving sponsors a more specific instruction on how to
demonstrate the device's safety. Therefore, FDA believes that thermal
damage, inflammation, and the other concerns identified by the
commenter would be mitigated both by the comparison of the
technological characteristics and performance of the
[[Page 43746]]
device to a legally marketed predicate device and by device compliance
with the special controls, including the clinical and non-clinical
performance testing special controls established by this final order.
FDA, on its own initiative, has made non-substantive changes to the
codified language to improve organization and clarity. For example,
``analysis/testing'' has been changed to ``analysis or testing'' to
indicate that one or the other may be conducted as appropriate, and the
special control for simulated use testing has been shifted out from
under the non-clinical performance testing special control umbrella.
III. The Final Order
FDA is adopting its findings under section 513(f)(3) of the FD&C
Act, as published on September 25, 2018, in the preamble to the
proposed order (83 FR 48403).\2\ FDA is issuing this final order to
reclassify ultrasound cyclodestructive devices from class III into
class II and to establish special controls by revising 21 CFR part 886.
In this final order, the Agency has identified the special controls
under section 513(a)(1)(B) of the FD&C Act that, along with general
controls, provide a reasonable assurance of the safety and
effectiveness for ultrasound cyclodestructive devices.
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\2\ FDA notes that the ``ACTION'' caption for this final order
is styled as ``Final amendment; final order,'' rather than ``Final
order.'' Beginning in December 2019, this editorial change was made
to indicate that the document ``amends'' the Code of Federal
Regulations. The change was made in accordance with the Office of
Federal Register's (OFR) interpretations of the Federal Register Act
(44 U.S.C. chapter 15), its implementing regulations (1 CFR 5.9 and
parts 21 and 22), and the Document Drafting Handbook.
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FDA has determined that requiring 510(k) submission is necessary to
reasonably assure the safety and effectiveness of the ultrasound
cyclodestructive devices and, therefore, the Agency is not exempting
this class II device from 510(k) submission requirements as provided
under section 510(m) of the FD&C Act. Thus, under sections 510(k) and
513(f) and (i) of the FD&C Act, persons who intend to market this
device type must submit a 510(k) notification containing information on
the ultrasound cyclodestructive device that they intend to market and
must obtain FDA clearance of the device prior to marketing it.
The device is assigned the generic name ultrasound cyclodestructive
device, and it is identified as a prescription device that reduces
intraocular pressure by producing a series of lesions in the ciliary
body and/or trabecular meshwork induced by high intensity focused
ultrasound (HIFU) energy and that is intended for treatment of glaucoma
in patients who (1) are refractory to, or are poor candidates for,
Argon laser trabeculoplasty or traditional filtering surgery and (2)
have failures on maximally tolerated drug therapy.
Under this final order, the ultrasound cyclodestructive device is a
prescription use device under Sec. 801.109 (21 CFR 801.109).
Prescription devices are exempt from the requirement for adequate
directions for use for the layperson under section 502(f)(1) of the
FD&C Act (21 U.S.C. 352(f)(1)) and 21 CFR 801.5, as long as the
conditions of Sec. 801.109 are met. The device would continue to be
subject to the submission and device clearance requirements of sections
510(k) and 513 of the FD&C Act (21 U.S.C. 360(k) and 360c) and of part
807, subpart E.
IV. Analysis of Environmental Impact
We have 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.
V. Paperwork Reduction Act of 1995
This final administrative 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-
3521). The collections of information in 21 CFR part 812 have been
approved under OMB control number 0910-0078; the collections of
information in part 807, subpart E, have been approved under OMB
control number 0910-0120; and the collections of information under 21
CFR part 801 have been approved under OMB control number 0910-0485.
List of Subjects in 21 CFR Part 886
Medical devices, Ophthalmic goods and services.
Therefore, under the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 321 et seq., as amended) and under authority delegated to the
Commissioner of Food and Drugs, 21 CFR part 886 is amended as follows:
PART 886--OPHTHALMIC DEVICES
0
1. The authority citation for part 886 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 886.5350 to read as follows:
Sec. 886.5350 Ultrasound cyclodestructive device.
(a) Identification. An ultrasound cyclodestructive device is a
prescription device that reduces intraocular pressure by producing a
series of lesions in the ciliary body and/or trabecular meshwork
induced by high intensity focused ultrasound (HIFU) energy and that is
intended for treatment of glaucoma patients who:
(1) Are refractory to, or are poor candidates for, Argon laser
trabeculoplasty or traditional filtering surgery; and
(2) Had failures on maximally tolerated drug therapy.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) The clinical performance data must demonstrate an appropriate
reduction in intraocular pressure in glaucoma patients who:
(i) Are refractory to, or are poor candidates for, Argon laser
trabeculoplasty or traditional filtering surgery; and
(ii) Had failures on maximally tolerated drug therapy, and an
evaluation of all adverse events observed during clinical use.
(2) Non-clinical performance testing of device features and
characteristics must demonstrate that the device performs as intended
under anticipated conditions of use. The following performance
characteristics must be tested:
(i) Ultrasound field characteristics, which must include the total
acoustic power radiated by the transducer(s), the spatial distribution
of the ultrasound field (including compressional and rarefactional
pressure), and spatial-peak, temporal-average intensity; and
(ii) Thermal and physical safety characteristics of the device.
(3) Simulated use testing to validate that the device performs as
intended under anticipated conditions of use, including eye movements
and positioning error.
(4) Analysis or testing must demonstrate electrical safety in the
appropriate use environment.
(5) Analysis or testing must demonstrate electromagnetic
compatibility (EMC), including wireless coexistence (if applicable) in
the appropriate use-environment.
(6) Software verification, validation, and hazard analysis must be
performed commensurate with the level of concern of the device.
(7) The patient-contacting components must be demonstrated to be
biocompatible.
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(8) Performance data must demonstrate sterility of all patient-
contacting components labeled as sterile. If the device contains
reusable eye-contact components, the validation tests must demonstrate
adequate cleaning and reprocessing of these components.
(9) Labeling must include:
(i) A detailed description of the patient population for which the
device is indicated for use, as well as warnings, and precautions
regarding potential for device malfunction and use-error pertinent to
use of the device.
(ii) A detailed summary of the clinical testing, including study
outcomes and adverse events.
(iii) Information on how the device operates and the typical course
of treatment.
(iv) Description of all main components of the device including
HIFU generator, transducer(s), and controls. The labeling must include
the technical specifications of the device including, but not limited
to, treatment frequency, total acoustic power delivered by transducer,
treatment duration, treatment zone, site targeting, power requirements,
weight, and physical dimensions of the device.
(v) Where appropriate, validated methods and instructions for
reprocessing of any reusable components.
(vi) Safe-use conditions for electrical safety and electromagnetic
compatibility.
Dated: May 14, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-10895 Filed 5-17-24; 8:45 am]
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