Document ID: FDA-2018-N-3074-0001
Agency: fda
Document Type: Proposed Rule
Title: Ophthalmic Devices; Reclassification of Ultrasound Cyclodestructive Device
Posted Date: 2018-09-25T04:00Z

[Federal Register Volume 83, Number 186 (Tuesday, September 25, 2018)]
[Proposed Rules]
[Pages 48403-48408]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-20763]

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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: Proposed order.

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SUMMARY: The Food and Drug Administration (FDA) is issuing this 
proposed order to reclassify the ultrasound cyclodestructive device, a 
postamendments class III device (regulated under product code LZR), 
into class II (special controls), subject to premarket notification. 
FDA is also identifying the proposed special controls that the Agency 
believes are necessary to provide a reasonable assurance of safety and 
effectiveness of the device. FDA is proposing this reclassification on 
its own initiative based on new information. If finalized, this order 
will reclassify these devices from class III to class II (special 
controls) and reduce regulatory burdens as these types of devices will 
no longer be required to submit a premarket approval application (PMA) 
but can instead submit a less burdensome premarket notification 
(510(k)) before marketing their device.

DATES: Submit either electronic or written comments on the proposed 
order by November 26, 2018. Please see section XI for the proposed 
effective date when the new requirements apply and for the proposed 
effective date of a final order based on this proposed order.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before November 26, 2018. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of November 26, 2018. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery 
service acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the

[[Page 48404]]

instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2018-N-3074 for ``Ophthalmic Devices; Reclassification of 
Ultrasound Cyclodestructive Device.'' Received comments, those filed in 
a timely manner (see ADDRESSES), will be placed in the docket and, 
except for those submitted as ``Confidential Submissions,'' publicly 
viewable at https://www.regulations.gov or at the Dockets Management 
Staff between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Hina Pinto, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 1652, Silver Spring, MD 20993, 301-796-6351, 
[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 class III 
(premarket approval).
    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, 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 21 CFR part 807.
    A postamendments device that has been initially classified in 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. Section 
513(f)(3) of the FD&C Act provides that FDA acting by 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 proposed 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 newly available regulatory authority (see Bell v. Goddard, 
366 F.2d 177, 181 (7th Cir. 1966); Ethicon, Inc. v. FDA, 762 F. Supp. 
382, 388-391 (D.D.C. 1991)), or in light of changes in ``medical 
science'' (Upjohn v. Finch, 422 F.2d 944, 951 (6th Cir. 1970)). Whether 
data before the Agency are old or new, the ``new information'' to 
support reclassification under section 513(f)(3) of the FD&C Act 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 Assoc. 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 
510(m) of the FD&C Act provides that a class II device may be exempted 
from the 510(k) premarket notification requirements, if the Agency 
determines that premarket notification is not necessary to

[[Page 48405]]

reasonably assure the safety and effectiveness of the device.

II. Regulatory History of the Devices

    On June 30, 1988, FDA approved the first and only ultrasound 
cyclodestructive device through its PMA process under section 515 of 
the FD&C Act (21 U.S.C. 360e). On August 10, 1988 (53 FR 30101), FDA 
announced a PMA order for Sonocare Inc.'s Model CST-100 Therapeutic 
Ultrasound System (Sonocare CST-100) (Ref. 1). As of the date of 
issuance of this proposed order, the Sonocare CST-100 is the only PMA 
approved by FDA for this device type.

III. Device Description

    An ultrasound cyclodestructive device is a postamendments device 
classified into class III under section 513(f)(1) of the FD&C Act. An 
ultrasound cyclodestructive device is indicated for the treatment of 
refractory glaucoma; it is intended for 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. The device is designed to reduce intraocular pressure by 
producing a series of lesions in the ciliary body and trabecular 
meshwork induced by high intensity focused ultrasound (HIFU) energy. 
Different technologies, such as laser cyclodestruction to lower 
intraocular pressure, have been studied since the 1970s (Refs. 2 and 
3), which increases FDA's knowledge base for devices used to treat this 
condition. As stated earlier in section II, FDA has approved only one 
ultrasound cyclodestructive device through its PMA process under 
section 515 of the FD&C Act (Ref. 4). More recently, reports in the 
literature indicate that the HIFU technology has been modified and 
currently studied in Europe for treatment of refractory glaucoma (Refs. 
5 to 8). Based upon our review experience and consistent with the FD&C 
Act and FDA's regulations, FDA believes that these devices should be 
reclassified from class III into class II because there is sufficient 
information to establish special controls that can provide reasonable 
assurance of the device's safety and effectiveness.
    Conventional refractory glaucoma treatment modalities include 
implantable aqueous shunts and valves, trabeculectomy and other 
incisional glaucoma surgeries, cyclocryotherapy, as well as laser 
transcleral cyclophotocoagulation. FDA currently regulates all of the 
devices indicated for these procedures in a refractory glaucoma 
population as class II devices, subject to 510(k) requirements.

IV. Proposed Reclassification

    On April 29, 2015, FDA published a document in the Federal Register 
entitled ``Retrospective Review of Premarket Approval Application 
Devices; Striking the Balance Between Premarket and Postmarket Data 
Collection,'' in which FDA announced plans to consider reclassifying 
ultrasound cyclodestructive devices identified with the LZR product 
code from class III to class II (80 FR 23798) and requested comments. 
FDA received no adverse comments regarding our proposed intent for LZR.
    In accordance with section 513(f)(3) of the FD&C Act and 21 CFR 
part 860, subpart C, FDA is proposing to reclassify this postamendments 
class III device into class II. FDA believes that there is sufficient 
information available to FDA through peer-reviewed literature and 
knowledge of similar devices to establish special controls that would 
effectively mitigate the risks to health identified in section V. 
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 is proposing to create a separate classification regulation for 
ultrasound cyclodestructive devices that will be reclassified from 
class III to II. Under this proposed order, if finalized, the 
ultrasound cyclodestructive devices will be identified as a 
prescription device. As such, the prescription device must satisfy 
prescription labeling requirements (see Sec.  801.109 (21 CFR 801.109), 
Prescription devices). 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 Sec.  801.5 
(21 CFR 801.5), as long as the conditions of Sec.  801.109 are met 
(referring to 21 U.S.C. 352(f)(1)). In this proposed order, if 
finalized, the Agency has identified the special controls under section 
513(a)(1)(B) of the FD&C Act that, together with general controls, will 
provide a reasonable assurance of the safety and effectiveness for 
ultrasound cyclodestructive devices.
    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 device. For this type of device, FDA has 
determined that premarket notification is necessary for ultrasound 
cyclodestructive devices to provide reasonable assurance of safety and 
effectiveness. Therefore, the Agency does not intend to exempt these 
proposed class II devices from 510(k) requirements. Persons who intend 
to market this type of device must submit to FDA a 510(k) and receive 
clearance prior to marketing the device.
    This proposal, if finalized, will decrease regulatory burden and 
will reduce private costs and expenditures required to comply with 
Federal regulations. Specifically, regulated industry will no longer 
have to submit a PMA but can instead submit a 510(k) to the Agency for 
review prior to marketing their device. A 510(k) is a less burdensome 
pathway to market a device, which typically results in a more timely 
premarket review compared to a PMA and reduces the regulatory burden in 
addition to providing more timely access of these types of devices to 
patients.

V. Risks to Health

    After considering the information available to FDA through the 
review submission, peer-reviewed literature, and knowledge of other 
technologies indicated to treat the same refractory glaucoma patient 
population (such as aqueous shunt and cryotherapy), FDA determined that 
the probable risks to health associated with the use of ultrasound 
cyclodestructive devices for treatment of refractory glaucoma are as 
follows:
     Thermal Injury. Exposure of the ocular tissue to the HIFU 
energy causes thermal damage of the tissue. The misdirection or 
misalignment of the beam may cause temperature elevation in the non-
target ocular tissues and overall ocular tissue damage. Unsuitable 
power and duration of the beam may also result in temperature 
elevation, which may cause corneoscleral lesions including scleral 
thinning, corneal ectasia and perforation, eyelid burns, corneal burns, 
clouding of the cornea (haze) and lens (cataract formation), and 
retinal and choroidal lesions.
     Physical Injury. Exposure of the ocular tissue to the HIFU 
energy can cause physical damage to the ocular tissue due to cavitation 
or other mechanical effects. These injuries could be caused by the 
suboptimal selection of the treatment parameters, misalignment/
displacement of the probe during the treatment, device malfunction, or 
other factors affecting stability of treatment. For example, 
insonification of the zonular fibers may cause elongation or rupture of 
ligaments, which can lead to a displacement of the lens.

[[Page 48406]]

     Post-treatment injury. Post-treatment injury from use of 
the device may include intraocular inflammation (e.g., iritis, 
uveitis), increased intraocular pressure in the immediate post-
treatment period, ciliary body hemorrhage, persistent or transient low 
pressure, decreased visual acuity, worsening glaucoma, phthisis, pain/
discomfort, corneal edema, hyphema, retinal and choroidal 
complications, etc.
     Electrical shock. While in operation, the device may 
discharge electricity that could shock the user. Electrical shock can 
be caused by use error or device malfunction.
     Electromagnetic interference. While in operation, 
electromagnetic interferences from other devices operated in the same 
environment may cause the device to malfunction, which could result in 
patient's injury. In addition, the device may interfere with other 
electrically powered devices, causing them to malfunction.
     Ocular irritation and corneal infections. Inadequate 
biocompatibility of the eye contact components of the device can lead 
to irritation of the ocular tissue. Inappropriately sterilized or 
reprocessed eye contact components of the device can lead to 
inflammation and corneal infections.

VI. Summary of Reasons for Reclassification

    FDA believes that the ultrasound cyclodestructive devices for 
treatment of refractory glaucoma should be reclassified from class III 
to class II in light of available information about the effectiveness 
of these devices. There is sufficient information to establish special 
controls for ultrasound cyclodestructive devices, in addition to 
general controls, which can provide reasonable assurance of safety and 
effectiveness of the device, as general controls themselves are 
insufficient to provide reasonable assurance of its safety and 
effectiveness. FDA believes that the risks to health associated with 
ultrasound cyclodestructive devices for treatment of refractory 
glaucoma can be mitigated with special controls and that these 
mitigations will provide a reasonable assurance of its safety and 
effectiveness.
    Based on a reconsideration of the available information and data, 
FDA believes that there is valid scientific evidence of effectiveness 
for ultrasound cyclodestructive devices to reduce intraocular pressure 
intended for treatment of refractory glaucoma using ultrasound.

VII. Summary of Data Upon Which the Reclassification Is Based

    FDA believes that the identified special controls, in addition to 
general controls, are necessary to provide reasonable assurance of 
safety and effectiveness of these devices. Taking into account the 
probable health benefits 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 postamendments class III device into 
class II. FDA has considered and analyzed the following information: An 
inclusive search of the Agency's Manufacturer and User Facility Device 
Experience (MAUDE) database, which shows no adverse events for 
ultrasound cyclodestructive device type; no recalls have been received 
for this device type; other technologies indicated to treat the same 
refractory glaucoma patient population, such as aqueous shunt and 
cryotherapy, and currently regulated as class II devices to compare the 
probable risks (i.e., between the rate and severity of the adverse 
events associated with these class II technologies and ultrasound 
cyclodestructive procedures); and peer-reviewed publications (Refs. 5 
to 12) to identify probable device risks (e.g., the types and rates of 
adverse events) and mitigation strategies.

VIII. Proposed Special Controls

    FDA believes that the following special controls, together with 
general controls, are necessary and sufficient to mitigate the risks to 
health described in section V and provide a reasonable assurance of 
safety and effectiveness for ultrasound cyclodestructive devices.
     Non-clinical performance testing of device features and 
characteristics will demonstrate:
    [cir] The ability of the device to deposit controllable HIFU energy 
to the target area to evoke the required level of thermal lesion.
    [cir] The design and geometry of the HIFU transducer and the output 
characteristics of the HIFU generator, including operating frequency 
and power, produce a small focal zone and a steep transition of energy 
deposition between the focal zone and the untreated areas. In addition, 
the total acoustic power radiated by the transducer(s), spatial 
distribution of the ultrasound field (including compressional and 
rarefactional pressure), and spatial peak, temporal-average intensity 
will be evaluated. This may be accomplished by demonstrating compliance 
with the standard International Electrotechnical Commission (IEC) 
Technical Specification (TS) 62556: Ultrasonics--Field 
characterization--Specification and measurement of field parameters for 
high intensity therapeutic ultrasound (HITU) transducers and systems. 
Thermal and physical (due to potential cavitation of gas bubbles) 
safety analyses will also be evaluated.
    [cir] The appropriate alignment and focusing of the ultrasound beam 
to the target tissue to minimize unintended damage to adjacent ocular 
tissues.
    [cir] The function of all safety features built into the device, 
including the energy monitoring system.
     Clinical performance data will validate device performance 
and characterize ocular tissue thermal injuries, physical injury, and 
postoperative adverse events by establishing the treatment parameters 
for which the device is safe and effective.
     Electrical safety testing will minimize the risk of 
electrical shock, thermal or physical injury to the patient and 
healthcare provider. This may be accomplished by demonstrating 
compliance with FDA-recognized consensus standard American National 
Standards Institute (ANSI)/Association for the Advancement of Medical 
Instrumentation (AAMI) 60601-1: Medical electrical equipment, Part 1: 
General requirements for basic safety and essential performance.
     Electromagnetic compatibility testing ensures that 
electromagnetic interferences do not cause device malfunction. It can 
also provide assurance that electromagnetic interferences generated by 
the device do not affect the other devices operated in the same 
environment. This may be accomplished by demonstrating compliance with 
FDA-recognized consensus standard IEC 60601-1-2: Medical electrical 
equipment, Part 1-2: General requirements for safety. If the device 
incorporates radiofrequency (RF) wireless technology to perform medical 
functions and/or communicates medical data, testing will mitigate the 
risks associated with interference or degradation when using RF 
wireless technology. This may be accomplished by demonstrating 
compliance with FDA-recognized consensus standard AAMI TIR69: Risk 
Management of Radio-frequency Wireless Coexistence for Medical Devices 
and Systems (risk assessment) and ANSI/Institute of Electrical and 
Electronics Engineers (IEEE) C63.27: American National Standard for 
Evaluation of Wireless Coexistence (coexistence testing).
     Software verification, validation, and hazard analysis is 
necessary to

[[Page 48407]]

mitigate the risks of thermal and physical injury and ensures that 
software performs as intended and potential software malfunctions do 
not impact the safety or effectiveness of the device. If the device 
incorporates internet network connectivity, testing will demonstrate 
that cybersecurity concerns are mitigated (e.g., data integrity, 
unauthorized access, etc.).
     Biocompatibility evaluation can help mitigate the risk of 
ocular irritation and corneal infection by ensuring that the patient-
contacting components of the device are safe for contact with skin and 
ocular tissue.
     Sterilization validation, for devices provided sterile, 
and/or cleaning validation, for devices or components that are 
reusable, help mitigate the risk of inflammation and corneal infections 
(e.g., keratitis).
     The labeling will also include necessary information to 
ensure safe and effective use of the ultrasound cyclodestructive device 
and minimize probability of the ocular treatment-related adverse 
events. Labeling needs to include sufficient information that will help 
the patient and healthcare provider make an informed decision regarding 
treatment-related adverse effects of the ultrasound cyclodestructive 
treatment. For example, the labeling needs to include information 
regarding the most common reported treatment-related injuries, which 
may include intraocular inflammation (e.g., iritis, uveitis) and 
increased intraocular pressure in the immediate post-treatment period. 
Adverse event information related to ciliary body hemorrhage, 
persistent low pressure, decreased visual acuity, worsening glaucoma, 
phthisis, pain/discomfort, transient low pressure, corneal edema, 
hyphema, retinal complications (such as cystoid macula edema), and 
choroidal effusion or detachment need to be discussed. The labeling 
will mitigate the risk associated with the intraoperative events, such 
as pain/discomfort, and postoperative adverse events by providing 
appropriate clinical information along with mitigation strategies 
(e.g., retrobulbar or peribulbar anesthesia). Specifically, device 
labeling must include:
    [cir] Appropriate warnings and precautions to ensure safe and 
effective use of the device and minimize potential device malfunctions 
and user errors.
    [cir] A summary of the clinical evaluation pertinent to use of the 
device, including study outcomes and adverse events.
    [cir] Information regarding procedure parameters, proper 
positioning of the HIFU transducer and its coupling with the eye, and 
typical course of treatment to ensure the user can safely operate the 
device.
    [cir] Validated reprocessing instructions to ensure the safe use of 
reusable device components.
    [cir] Safety information regarding electrical safety and 
electromagnetic compatibility to minimize risks to the patient and 
users.
    Table 1 shows how FDA believes the risks to health identified and 
described in section V will be mitigated by the proposed special 
controls. This reclassification order and the identified special 
controls, if finalized, would provide sufficient detail regarding FDA's 
requirements to reasonably assure safety and effectiveness of 
ultrasound cyclodestructive devices.

     Table 1--Risks to Health and Mitigation Measures for Ultrasound
                        Cyclodestructive Devices
------------------------------------------------------------------------
  Identified risk to health               Mitigation measures
------------------------------------------------------------------------
Thermal Injury...............  Non-clinical performance testing,
                                Clinical performance data, Electrical
                                Safety, Electromagnetic compatibility,
                                Software verification, validation, and
                                hazard analysis, Labeling.
Physical Injury..............  Non-clinical performance testing,
                                Clinical performance data, Electrical
                                safety, Electromagnetic compatibility,
                                Software verification, validation, and
                                hazard analysis, Labeling.
Post-treatment Injury........  Non-clinical performance testing,
                                Clinical performance data, Software
                                verification, validation, and hazard
                                analysis, Labeling.
Electrical Shock.............  Electrical safety, Labeling.
Electromagnetic Interference.  Electromagnetic compatibility, Labeling.
Ocular Irritation and Corneal  Biocompatibility evaluation, Sterility/
 Infections.                    reprocessing validation, Labeling.
------------------------------------------------------------------------

    In addition, FDA is proposing to limit these devices to 
prescription use under Sec.  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 and Sec.  801.5, as long as the 
conditions of Sec.  801.109 are met (referring to 21 U.S.C. 352(f)(1)). 
Under 21 CFR 807.81, the device would continue to be subject to 510(k) 
requirements.
    This reclassification order and the identified special controls, if 
finalized, would provide sufficient detail regarding FDA's requirements 
to reasonably assure safety and effectiveness of ultrasound 
cyclodestructive devices for the treatment of refractory glaucoma. As 
discussed below, the reclassification will be codified in 21 CFR 
886.5350. FDA believes that adherence to the proposed special controls, 
in addition to the general controls, is necessary to provide a 
reasonable assurance of the safety and effectiveness of the devices.

IX. 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.

X. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed order contains no new 
collections of information. Therefore, clearance by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(PRA) (44 U.S.C. 3501-3520) is not required. This proposed order refers 
to previously approved collections of information found in FDA 
regulations. These collections of information are subject to review by 
OMB under the PRA. The collections of information in 21 CFR 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.

XI. Proposed Effective Date

    FDA proposes that any final order based on this proposal become 
effective 30 days after the date of its publication in the Federal 
Register.

XII. References

    The following references are on display at the Dockets Management 
Staff (see ADDRESSES), and are available for viewing by interested 
persons between

[[Page 48408]]

9 a.m. and 4 p.m., Monday through Friday; these are not available 
electronically at https://www.regulations.gov as they are copyrighted 
or are available through the website address. FDA has verified the 
website addresses, as of the date this document publishes in the 
Federal Register, but websites are subject to change over time.

1. PMA Database Reference for Sonocare. Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?ID=319101.
2. Shields, M.B., ``Transcleral Diode Cyclophotocoagulation,'' in 
Chen, T.C. (ed.), ``Surgical Techniques in Ophthalmology: Glaucoma 
Surgery.'' Saunders Elsevier, 2008.
3. Chen, T.C., L.R. Pasquale, D.S. Walton, et al., ``Diode Laser 
Transcleral Cyclophotocoagulation.'' International Ophthalmology 
Clinics, 39(1):169-176, 1999.
4. Muratore, R.A., ``History of the Sonocare CST-100: The First FDA-
Approved HIFU Device.'' Therapeutic Ultrasound, 809:508-512, 2006.
5. Melamed, S., M. Goldenfeld, D. Cotlear, et al., ``High-Intensity 
Focused Ultrasound Treatment in Refractory Glaucoma Patients: 
Results at 1 Year of Prospective Clinical Study.'' European Journal 
of Ophthalmology, 25(6):483-489, 2015.
6. Aptel, F., T. Charrel, C. Labon, et al., ``Miniaturized High-
Intensity Focused Ultrasound Device in Patients with Glaucoma: A 
Clinical Pilot Study.'' Investigative Ophthalmology and Visual 
Science, 52 (12):8747-8753, 2011.
7. Aptel, F. and C. Lafon, ``Therapeutic Applications of Ultrasound 
in Ophthalmology.'' International Journal of Hyperthermia, 
28(4):405-418, 2012.
8. Mastropasqua, R., V. Fasanella, A. Mastropasqua, et al., ``High-
Intensity Focused Ultrasound Circular Cyclocoagulation in Glaucoma: 
A Step Forward for Cyclodestruction?'' Journal of Ophthalmology, 
(2017), 1-14, 2017.
9. Burgess, SE, R.H. Silverman, D.J. Coleman, et al., ``Treatment of 
Glaucoma with High Intensity Focused Ultrasound.'' Ophthalmology, 
93:831-838, 1986.
10. Coleman, D.J., F.L. Lizzi, J. Driller, et al., ``Therapeutic 
Ultrasound in the Treatment of Glaucoma. II. Clinical 
Applications.'' Ophthalmology, 92:347-353, 1985.
11. Valtot, F., J. Kopel, and J. Haut, ``Treatment of Glaucoma with 
High Intensity Focused Ultrasound.'' International 
Ophthalmology,13:167-170, 1989.
12. Silverman, R.H., B. Vogelsang, M.J. Rondeau, et al., 
``Therapeutic Ultrasound for the Treatment of Glaucoma.'' American 
Journal of Ophthalmology, 111:327-337, 1991.

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, it is proposed that 21 CFR part 886 be 
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 subpart F to read as follows:

Sec.  886.5350  Ultrasound cyclodestructive device.

    (a) Identification. An ultrasound cyclodestructive device is a 
prescription device to reduce intraocular pressure by producing a 
series of lesions in the ciliary body and trabecular meshwork induced 
by high intensity focused ultrasound (HIFU) energy and that is intended 
for treatment of refractory glaucoma.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) The clinical performance data must demonstrate an adequate 
safety profile and an appropriate reduction in intraocular pressure in 
patients with refractory glaucoma and capture any 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;
    (ii) Thermal and physical safety characterization of the device; 
and
    (iii) Simulated use testing to validate that the device performs as 
intended under anticipated conditions of use, including eye movements 
and positioning error.
    (3) Analysis/testing must demonstrate electrical safety in the 
appropriate use-environment.
    (4) Analysis/testing must demonstrate electromagnetic compatibility 
(EMC), including wireless coexistence (if applicable) in the 
appropriate use-environment.
    (5) Software verification, validation, and hazard analysis must be 
performed commensurate with the level of concern of the device.
    (6) The patient-contacting components must be demonstrated to be 
biocompatible.
    (7) 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/reprocessing of these components.
    (8) 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 
technical specification 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: September 18, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-20763 Filed 9-24-18; 8:45 am]
 BILLING CODE 4164-01-P