[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

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``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]
BILLING CODE 4164-01-P