[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]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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).
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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
[[Page 18993]]
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