[Federal Register Volume 88, Number 61 (Thursday, March 30, 2023)]
[Rules and Regulations]
[Pages 18990-18993]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-06565]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 888

[Docket No. FDA-2021-N-0309]


Effective Date of Requirement for Premarket Approval Applications 
for Spinal Spheres for Use in Intervertebral Fusion Procedures

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is issuing a 
final order to require the filing of a premarket approval application 
(PMA) for spinal spheres for use in intervertebral fusion procedures, 
an unclassified, preamendments device following the classification of 
the device into class III.

DATES: This order is effective on May 1, 2023. Anyone who wishes to 
market spinal spheres for use in intervertebral fusion procedures will 
need to submit a PMA prior to the last day of the 30th calendar month 
beginning after the month in which the classification of the device in 
class III became effective. See section IX for the effective date of 
the final order. See section VI of this document for more information 
about submitting a PMA.

FOR FURTHER INFORMATION CONTACT: Constance Soves, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Rm. 1656, Silver Spring, MD 20993-0002, 301-
796-6951, [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).
    Under section 513(d)(1) of the FD&C Act, devices that were in 
commercial distribution before the enactment of the Medical Device 
Amendments of 1976 (the 1976 amendments) (Pub. L. 94-295), on May 28, 
1976, (generally referred to as ``preamendments devices''), are 
classified after FDA has: (1) received a recommendation from a device 
classification panel (an FDA advisory committee); (2) published the 
panel's recommendation for comment, along with a proposed regulation 
classifying the device; and (3) published a final regulation 
classifying the device. FDA has classified most preamendments devices 
under these procedures.
    A person may market a preamendments device that has been classified 
into class III through premarket notification procedures, without 
submission of a PMA, until FDA issues a final order under section 
515(b) of the FD&C Act (21 U.S.C. 360e(b)) requiring premarket 
approval.
    Section 515(f) of the FD&C Act provides an alternative pathway for 
meeting the premarket approval requirement. Under section 515(f), 
manufacturers may meet the premarket approval requirement if they file 
a notice of completion of a product development protocol (PDP) approved 
under section 515(f)(4) of the FD&C Act and FDA declares the PDP 
completed under section 515(f)(6)(B) of the FD&C Act. Accordingly, the 
manufacturer of a preamendments class III device may comply with a call 
for PMAs by filing a PMA or a notice of completion of a PDP. In 
practice, however, the option of filing a notice of completion of a PDP 
has rarely been used. For simplicity, although the PDP option remains 
available to manufacturers in response to a final order under section 
515(b) of the FD&C Act, this document will refer only to the 
requirement for filing and obtaining approval of a PMA.
    Section 515(b)(1) of the FD&C Act sets forth the process for 
issuing a final order. Specifically, prior to the issuance of a final 
order requiring premarket approval for a preamendments class III 
device, the following must occur: (1) publication of a proposed order 
in the Federal Register; (2) a meeting of a device classification panel 
described in section 513(b) of the FD&C Act; and (3) consideration of 
comments from all

[[Page 18991]]

affected stakeholders, including patients, payors, and providers.
    Section 515(b)(2) of the FD&C Act provides that a proposed order to 
require premarket approval shall contain: (1) the proposed order; (2) 
proposed findings with respect to the degree of risk of illness or 
injury designed to be eliminated or reduced by requiring the device to 
have an approved PMA and the benefit to the public from the use of the 
device; (3) an opportunity for the submission of comments on the 
proposed order and the proposed findings; and (4) an opportunity to 
request a change in the classification of the device based on new 
information relevant to the classification of the device.
    Section 515(b)(3) of the FD&C Act provides that FDA shall, after 
the close of the comment period on the proposed order,\1\ consideration 
of any comments received, and a meeting of a device classification 
panel described in section 513(b) of the FD&C Act, issue a final order 
to require premarket approval or publish a document terminating the 
proceeding together with the reasons for such termination. If FDA 
terminates the proceeding, FDA is required to initiate reclassification 
of the device under section 513(e) of the FD&C Act, unless the reason 
for termination is that the device is a banned device under section 516 
of the FD&C Act (21 U.S.C. 360f).
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    \1\ In December 2019, FDA began adding the term ``Proposed 
amendment'' to the ``ACTION'' caption for these documents to 
indicate that they ``amend'' the Code of Federal Regulations. This 
editorial change was made in accordance with the Office of the 
Federal Register's 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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    A preamendments class III device may be commercially distributed 
without a PMA until 90 days after FDA issues a final order requiring 
premarket approval for the device, or 30 months after the 
classification of the device in class III under section 513 of the FD&C 
Act becomes effective, whichever is later (section 501(f)(2)(B) of the 
FD&C Act (21 U.S.C. 351(f)(2)(B)). Elsewhere in this issue of the 
Federal Register, FDA is classifying spinal spheres for use in 
intervertebral fusion procedures (spinal spheres) to class III. 
Therefore, a PMA for spinal spheres for use in intervertebral fusion 
procedures must be filed within the 30-month period because that is the 
later of the two time periods. If a PMA is not filed in a timely manner 
for such devices, then the device would be deemed adulterated under 
section 501(f) of the FD&C Act.
    Also, a preamendments device subject to the order process under 
section 515(b) of the FD&C Act is not required to have an approved 
investigational device exemption (IDE) (see part 812 (21 CFR part 812)) 
contemporaneous with its interstate distribution until the date 
identified by FDA in the final order requiring the filing of a PMA for 
the device. At that time, an IDE is required only if a PMA has not been 
filed. If the manufacturer, importer, or other sponsor of the device 
submits an IDE application and FDA approves it, the device may be 
distributed for investigational use. If a PMA is not filed by the later 
of the two dates, and the device is not distributed for investigational 
use under an IDE, the device is deemed adulterated within the meaning 
of section 501(f)(1)(A) of the FD&C Act and subject to enforcement 
action.

II. Regulatory History of the Devices

    After the enactment of the Medical Device Amendments of 1976, FDA 
undertook an effort to identify and classify all preamendments devices, 
in accordance with section 513(d) of the FD&C Act. FDA issued a 
proposed rule for classification of 77 generic types of orthopedic 
devices in the Federal Register of September 4, 1987 (52 FR 33686). 
However, spinal spheres for use in intervertebral fusion procedures 
were not identified in this effort. Subsequently and consistent with 
the FD&C Act, FDA held a panel meeting on December 12, 2013, regarding 
the classification of spinal sphere devices for use in intervertebral 
fusion procedures (Ref. 1). Spinal sphere devices, intended for use in 
fusion procedures, are no longer used due to the widespread adoption of 
intervertebral body fusion devices (``interbody cages''). Unlike spinal 
sphere devices, interbody cages generally possess different features to 
engage with vertebral endplates, allowing them to resist migration and 
subsidence, and features that allow for the packing of graft material, 
facilitating bone growth into and through the device.
    Elsewhere in this issue of the Federal Register, FDA is issuing a 
rule to classify unclassified, preamendments spinal spheres for use in 
intervertebral fusion procedures into class III. A PMA, in addition to 
general controls, will provide reasonable assurance of the safety and 
effectiveness of the device. The rule establishes the identification, 
classification, and regulatory controls for spinal spheres.
    Spinal spheres for use in intervertebral fusion procedures are 
unclassified preamendments devices. These devices have been subject to 
premarket review through a 510(k) submission and have been cleared for 
marketing if FDA considers the device to be substantially equivalent to 
a legally marketed predicate in accordance with section 513(i) of the 
FD&C Act. To date, FDA has cleared six spinal sphere devices from four 
manufacturers.

III. Dates New Requirements Apply

    FDA is issuing a rule for classification of spinal spheres, into 
class III elsewhere in this issue of the Federal Register. In 
accordance with sections 501(f)(2)(B) and 515(b) of the FD&C Act, FDA 
requires that a PMA be filed with the Agency for spinal sphere devices 
by the last day of the 30th calendar month beginning after the month in 
which the classification of the device in class III became effective. 
An applicant whose product was legally in commercial distribution 
before May 28, 1976, or whose product has been found to be 
substantially equivalent to such a product, will be permitted to 
continue marketing such class III product during FDA's review of the 
PMA, provided that a PMA is filed in a timely manner. FDA intends to 
review any PMA for the device within 180 days. FDA cautions that under 
section 515(d)(1)(B)(i) of the FD&C Act, the Agency may not enter into 
an agreement to extend the review period for a PMA beyond 180 days, 
unless the Agency finds that ``. . . the continued availability of the 
device is necessary for the public health.''
    If a PMA for a class III device is not filed with FDA within 30 
months after the classification of the device into class III, 
commercial distribution of the device must cease. The device may be 
distributed for investigational use, only if the requirements of the 
IDE regulations in part 812 are met. The requirements for 
investigational use of significant risk devices include submitting an 
IDE application to FDA for review and approval. An approved IDE is 
required to be in effect before an investigation of the device may be 
initiated or continued under 21 CFR 812.30. FDA, therefore, recommends 
that IDE applications be submitted to FDA at least 30 days before the 
date a PMA is required to be filed to avoid interrupting 
investigations.

IV. Device Subject to This Final Order

    A spinal sphere is a prescription device that is an implanted, 
solid, spherical device manufactured from metallic (e.g., cobalt-
chromium-molybdenum) or polymeric (e.g., polyetheretherketone) 
materials. They are intended to be inserted into the intervertebral 
disc space of the lumbar

[[Page 18992]]

spine following a discectomy in order to maintain disc space height and 
provide postoperative stabilization to the affected spinal segment 
during fusion procedures. The device is to be used with bone graft 
material. FDA currently regulates these unclassified devices as devices 
requiring a 510(k) submission under product code NVR.

V. Public Comments in Response to the Proposed Order

    In response to the proposed order, FDA received a total of five 
comments on the proposed order and they are supportive of the rule to 
classify spinal spheres to class III and the call for PMA for this 
device type. The comments and FDA responses to the comments are 
summarized in this section. Certain comments are grouped together 
because the subject matter of the comments is similar. The number 
assigned to each comment is purely for organizational purposes and does 
not signify the comment's value, importance, or the order in which it 
was received.
    (Comment 1) Commenters supported the requirement for PMA for spinal 
spheres and had no concern with the time period of 30 months after the 
effective date for PMA submission.
    (Response) FDA agrees. FDA has made no changes to the final order.
    (Comment 2) Although supportive of the classification of spinal 
spheres into class III and the call for PMA, a comment suggested it 
would ``promote efficiency'' to apply the proposed rule to all 
manufacturers of preamendments devices to be classified into class III. 
Additionally, the commenter requested that the effective date 
requirement for PMAs for spinal spheres be applied to all manufacturers 
of preamendments devices to be classified into class III. Finally, the 
commenter stated that the title of the rule should be revised to 
reflect a process by which all such preamendments devices would be 
classified into class III.
    (Response) FDA disagrees. FDA notes that under the FD&C Act, it is 
required to classify preamendments devices and establish the controls 
necessary to provide reasonable assurance of safety and effectiveness 
for devices based on each device type's intended use and following the 
public process established in section 513 of the FD&C Act. Each 
classification action for a preamendments device requires FDA to engage 
the appropriate classification panel and make a recommendation for 
classification specific to the facts and information relevant to the 
device at issue (see section 513(d) of the FD&C Act). The FD&C Act does 
not require that FDA classify all devices for class III at the same 
time. Nor can FDA apply the PMA requirement to devices that were not 
discussed at the panel meeting, summarized in the proposed rule, or 
that are not the subject of the proposed order to require PMAs. With 
the rule published elsewhere in the Federal Register, FDA is completing 
the classification of spinal spheres, which is the only device subject 
to the classification. FDA, therefore, cannot include other 
preamendments devices at this time and, as such, we will not change the 
title of the rule.
    (Comment 3) Commenters stated that FDA should consider extending 
the amount of time that manufacturers of spinal spheres preamendments 
devices are required to file PMAs. The commenters expressed concern 
that 30 months would not be sufficient to collect evidence needed to 
support safe and effective use of these devices.
    (Response) FDA disagrees. The 30-month time period to file for a 
PMA is dictated by statute (section 501(f)(2)(B) of the FD&C Act). 
Additionally, as described in the preamble to the proposed 
classification rule (86 FR 71191), there are safety concerns associated 
with these devices, including reoperation, pain and loss of function, 
infection, adverse tissue reaction, soft tissue injury, vertebral 
endplate injury, pseudarthrosis, implant migration and/or instability, 
and implant breakage during insertion. Because of these risks in 
combination with the fact that there are no devices currently marketed, 
FDA continues to consider the 30-month time period to be appropriate 
and reasonable.
    In the final order, we are revising the section number from Sec.  
888.3085 (21 CFR 888.3085) to 21 CFR 888.3083, because a De Novo was 
previously granted under Sec.  888.3085. No other substantive changes 
were made to the regulation.

VI. PMA Requirements

    A PMA for spinal sphere devices for use in fusion procedures must 
include the information required by section 515(c)(1) of the FD&C Act. 
Such a PMA should also include a detailed discussion of the risks, as 
well as a discussion of the effectiveness of the product for which 
premarket approval is sought. In addition, a PMA must include all data 
and information on the following: (1) any risks known, or that should 
be reasonably known, to the applicant that have not been identified in 
this document; (2) the effectiveness of the device that is the subject 
of the application; and (3) full reports of all non-clinical and 
clinical information from investigations on the safety and 
effectiveness of the device for which premarket approval is sought.
    A PMA must include valid scientific evidence to demonstrate 
reasonable assurance of the safety and effectiveness of the spinal 
sphere for its intended use (see Sec.  860.7(c)(2) (21 CFR 
860.7(c)(2))). FDA defines valid scientific evidence in Sec.  
860.7(c)(2).
    To present reasonable assurance of safety and effectiveness of 
spinal sphere devices, FDA concludes that manufacturers should submit 
performance testing, including clinical trials of their product, to 
support PMA approval. Existing published clinical literature relevant 
to the product may also be leveraged as part of the PMA submission. In 
addition, FDA strongly encourages manufacturers to meet with the Agency 
early through the Q-Submission Program for any assistance in 
preparation of their PMA.

VII. 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.

VIII. Paperwork Reduction Act of 1995

    While this final order contains no collection of information, it 
does refer to previously approved FDA 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. 3501-3521) is not 
required for this order. The previously approved collections of 
information are subject to review by the OMB under the PRA. The 
collections of information in 21 CFR part 814, subparts A through E, 
have been approved under OMB control number 0910-0231; and the 
collections of information in part 812 have been approved under OMB 
control number 0910-0078.

IX. Effective Date

    This final order will become effective 30 days after its 
publication in the Federal Register.

X. Reference

    The following reference is on display at the Dockets Management 
Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 
1061, Rockville, MD 20852, 240-402-7500 and is available for viewing by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday; it 
also is available electronically at https://www.regulations.gov. FDA 
has verified the website addresses, as of the date this

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document publishes in the Federal Register, but websites are subject to 
change over time.

1. Orthopaedic and Rehabilitation Devices Panel--Classification of 
Spinal Sphere Devices Meeting, December 12, 2013, available at 
https://wayback.archive-it.org/7993/20170114044038/http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/OrthopaedicandRehabilitationDevicesPanel/UCM378083.pdf.

List of Subjects in 21 CFR Part 888

    Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act, and 
under authority delegated to the Commissioner of Food and Drugs, 21 CFR 
part 888 is amended as follows:

PART 888--ORTHOPEDIC DEVICES

0
1. The authority citation for part 888 continues to read as follows:

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


0
2. In Sec.  888.3083, add paragraph (c) to read as follows:


Sec.  888.3083  Spinal spheres for use in intervertebral fusion 
procedures.

* * * * *
    (c) Date premarket approval application (PMA) or notice of 
completion of product development protocol (PDP) is required. A PMA or 
notice of completion of a PDP is required to be filed with the Food and 
Drug Administration on or before October 30, 2025, for any spinal 
sphere for use in intervertebral fusion procedures as identified in 
paragraph (a) of this section that was in commercial distribution 
before May 28, 1976, or that has, on or before October 30, 2025, been 
found to be substantially equivalent to any spinal sphere device for 
use in intervertebral fusion procedures identified in paragraph (a) of 
this section, that was in commercial distribution before May 28, 1976. 
Any other spinal sphere device for use in intervertebral fusion 
procedures identified in paragraph (a) of this section shall have an 
approved PMA or declared completed PDP in effect before being placed in 
commercial distribution.

    Dated: March 24, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-06565 Filed 3-29-23; 8:45 am]
BILLING CODE 4164-01-P