[Federal Register Volume 81, Number 251 (Friday, December 30, 2016)]
[Rules and Regulations]
[Pages 96366-96374]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-31670]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 888
[Docket No. FDA-2014-N-1205]
Orthopedic Devices; Reclassification of Pedicle Screw Systems,
Henceforth To Be Known as Thoracolumbosacral Pedicle Screw Systems,
Including Semi-Rigid Systems
AGENCY: Food and Drug Administration, HHS.
ACTION: Final order.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is issuing a final
order to reclassify pedicle screw systems, a preamendments class III
device (regulated under product code NKB), into class II (special
controls), renaming the device ``thoracolumbosacral pedicle screw
systems''; reclassify dynamic stabilization systems, a subtype of
pedicle screw systems regulated under product code NQP when used as an
adjunct to fusion, into class II (special controls), renaming this
device subtype ``semi-rigid systems''; and clarify the device
identification of pedicle screw systems to more clearly delineate
between rigid pedicle screw systems and semi-rigid systems. FDA is
finalizing this action based on a reevaluation of information
pertaining to the device type.
DATES: This order is effective on December 30, 2016. See further
discussion in section V, ``Implementation Strategy.''
FOR FURTHER INFORMATION CONTACT: Constance P. Soves, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 1437, Silver Spring, MD 20993, 301-796-
6951, [email protected].
SUPPLEMENTARY INFORMATION:
I. Background--Regulatory Authorities
The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended
by the Medical Device Amendments of 1976 (the 1976 amendments) (Pub. L.
94-295), the Safe Medical Devices Act of 1990 (Pub. L. 101-629), the
Food and Drug Administration Modernization Act of 1997 (Pub. L. 105-
115), the Medical Device User Fee and Modernization Act of 2002 (Pub.
L. 107-250), the Medical Devices Technical Corrections Act (Pub. L.
108-214), the Food and Drug Administration Amendments Act of 2007 (Pub.
L. 110-85), and the Food and Drug Administration Safety and Innovation
Act (FDASIA) (Pub. L. 112-144), among other amendments, established 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) of the FD&C Act, devices that were in
commercial distribution before the enactment of the 1976 amendments,
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.
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) 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 part 807 (21 Code of Federal Regulations (CFR) part 807).
A preamendments device that has been classified into class III and
devices found substantially equivalent by means of premarket
notification (510(k)) procedures to such a preamendments device or to a
device within that type (both the preamendments and substantially
equivalent devices are referred to as preamendments class III devices)
may be marketed without submission of a premarket approval application
(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.
[[Page 96367]]
Under section 515(i)(2) of the FD&C Act, FDA has the authority to
issue an administrative order revising the proposed classification of a
device for which FDA has classified as a class III device and for which
no administrative order has been issued calling for PMAs under section
515(b) of the FD&C Act, so that the device is classified into class I
or class II, after issuance of a proposed order, a meeting of a device
classification panel, and consideration of the comments of a proposed
order. In determining whether to revise the proposed classification of
a device or to require a device to remain in class III, FDA applies the
criteria set forth in section 513(a) of the FD&C Act. Section
513(a)(1)(B) of the FD&C Act defines class II devices as those devices
for which the general controls in section 513(a)(1)(A) by themselves
are insufficient to provide reasonable assurance of safety and
effectiveness, but for which there is sufficient information to
establish special controls to provide a reasonable assurance of safety
and effectiveness of a device.
On July 9, 2012, FDASIA was enacted. Section 608(a) of FDASIA
amended section 513(e) of the FD&C Act, changing the mechanism for
reclassifying a device from rulemaking to an administrative order.
Section 513(e) of the FD&C Act provides that FDA may, by
administrative order, reclassify a device based upon ``new
information.'' FDA can initiate a reclassification under section 513(e)
or an interested person may petition FDA to reclassify a preamendments
device. The term ``new information,'' as used in section 513(e),
includes information developed as a result of a reevaluation of the
data before the Agency when the device was originally classified, as
well as information not presented, not available, or not developed at
that time. (See, e.g., Holland-Rantos Co. v. United States Department
of Health, Education, and Welfare, 587 F.2d 1173, 1174 n.1 (D.C. Cir.
1978); Upjohn v. Finch, 422 F.2d 944 (6th Cir. 1970); Bell v. Goddard,
366 F.2d 177 (7th Cir. 1966).)
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 authority (see Bell, 366 F.2d at 181;
Ethicon, Inc. v. FDA, 762 F.Supp. 382, 388-391 (D.D.C. 1991)), or in
light of changes in ``medical science'' (Upjohn, 422 F.2d at 951).
Whether data before the Agency are old or new data, the ``new
information'' to support reclassification under section 513(e) 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 Mfrs. Ass'n 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 513(e)(1) of the FD&C Act sets forth the process for
issuing a final reclassification order. Specifically, prior to the
issuance of a final order reclassifying a 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 to a public docket.
FDA published a proposed order to propose different classifications
for rigid pedicle screw systems and semi-rigid systems (SRSs) in the
Federal Register of November 12, 2014 (79 FR 67105) (2014 Proposed
Order). Moreover, as explained in section II of the 2014 Proposed
Order, on May 22, 2013, FDA held a classification meeting of the
Orthopedic and Rehabilitation Devices Panel (the 2013 Panel) to discuss
pedicle screw systems, which include rigid pedicle screw systems and
SRSs. FDA received and has considered all the comments on the 2014
Proposed Order, as discussed in section III. Therefore, FDA has met the
requirements under sections 513(e)(1) and 515(i)(2) of the FD&C Act.
II. Device Description
Pedicle screw systems consist of multiple component devices made
from a variety of materials that allow the surgeon to build an implant
system to fit the patient's anatomical and physiological requirements.
Such a spinal implant assembly may consist of a combination of hooks,
screws, longitudinal members (e.g., plates, rods, plate/rod
combinations), transverse or cross connectors, and interconnection
mechanisms (e.g., rod-to-rod connectors, offset connectors). Rigid
pedicle screw systems provide immediate rigid fixation to the spinal
column as an adjunct to spinal fusion procedures.
Since the 1998 classification (63 FR 40025, July 27, 1998), changes
in technological characteristics have occurred, leading to the
emergence of a new type of pedicle screw system, SRSs, previously
referred to as dynamic stabilization systems (DSSs). SRSs are a subset
of the pedicle screw systems regulated under Sec. 888.3070 (21 CFR
888.3070). SRSs are defined as systems that contain one or more non-
uniform and/or non-metallic longitudinal elements (e.g., polymer cords,
moveable screw heads, springs) that allow more motion or flexibility
(e.g., bending, rotation, translation) compared to rigid systems and do
not provide immediate rigid fixation to the spinal column as an adjunct
to spinal fusion procedures.
In the 2014 Proposed Order, FDA proposed to modify the
identification language from the way it is presently written in Sec.
888.3070(a) and sought comments on the means of providing distinction
between rigid pedicle screw systems and pedicle screw systems that
allow more motion or flexibility. As discussed in section III, FDA
received several comments suggesting that Sec. 888.3070 separate SRSs,
which may allow for more flexibility than traditional rigid pedicle
screw systems but still facilitate fusion, from truly ``dynamic''
systems that are intended for non-fusion use. Truly dynamic systems
intended for non-fusion use are postamendments devices that are outside
the scope of this regulatory action. FDA agrees with these comments and
has modified the identification language from the way it is presently
written in Sec. 888.3070(a) to include SRSs.
FDA has also, on its own initiative, renamed ``pedicle screw spinal
system'' as ``thoracolumbosacral pedicle screw system'' to clearly
distinguish these devices from posterior cervical screw systems, which
are not intended to be covered by Sec. 888.3070.
III. Public Comments in Response to the Proposed Order
In response to the 2014 Proposed Order, FDA received 15 comments
from industry, trade organizations, professional societies, and
individuals. Certain comments are grouped together under a single
number 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 or importance or the order in
which it was submitted. The comments that follow are grouped into those
that pertain to rigid pedicle screw systems and those that pertain to
SRSs.
[[Page 96368]]
A. Rigid Pedicle Screw Systems
Of the 15 comments received, several specifically referenced the
proposal to reclassify rigid pedicle screw systems when intended to
provide immobilization and stabilization of spinal segments in the
thoracic, lumbar, and sacral spine as an adjunct to fusion in the
treatment of degenerative disc disease (DDD) and spondylolisthesis
(other than either severe spondylolisthesis (grades 3 and 4) at L5-S1
or degenerative spondylolisthesis with objective evidence of neurologic
impairment). Some commenters agreed with the recommendation to
reclassify these as class II devices (special controls), most of whom
specifically stated that they agreed with the Agency that general and
special controls can provide reasonable assurance of the safety and
effectiveness of rigid pedicle screw systems.
(Comment 1) Some commenters did not agree with the proposal to
reclassify rigid pedicle screw systems to class II (special controls).
One comment stated that labeling special controls are not appropriate
risk mitigations and that clinical data should be required for these
devices. Another comment noted that adverse events have been identified
for rigid pedicle screw systems, and the final comment noted varied
results in clinical literature, specifically citing a 1990 study by
Matsuzaki et al. that found a 5.7 percent screw breakage rate (Ref. 1).
(Response 1) FDA disagrees that rigid pedicle screw systems for
treatment of DDD and spondylolisthesis (other than either severe
spondylolisthesis (grades 3 and 4) at L5-S1 or degenerative
spondylolisthesis with objective evidence of neurologic impairment)
should remain in class III. The Agency believes the labeling special
controls proposed to inform users of the technological features of the
device (including identification of device materials and the principles
of device operation), intended use and indications for use (including
levels of fixation), identification of magnetic resonance compatibility
status, cleaning and sterilization instructions, and detailed
instructions of each surgical step (including device removal) are
appropriate to help mitigate the identified risks to health that may
result from improper use of rigid pedicle screw systems. The Agency
does not believe clinical data are necessary for rigid pedicle screw
systems indicated for treatment of DDD and spondylolisthesis (other
than either severe spondylolisthesis (grades 3 and 4) at L5-S1 or
degenerative spondylolisthesis with objective evidence of neurologic
impairment). Clinical data from use of rigid pedicle screw systems for
these indications were presented to the 2013 Panel to support
reclassification to class II. Furthermore, non-clinical methods used to
evaluate these devices have been demonstrated to adequately mitigate
risks to health. FDA still retains the ability to request appropriate
performance testing, including clinical data for individual devices
with a different indication for use and/or different technological
features that do not raise different questions of safety and
effectiveness as compared to a predicate device, to demonstrate that
the individual devices are as safe and effective as the predicate
device, if necessary. FDA acknowledges that rigid pedicle screw
systems, like all medical devices, have risks to health, as evidenced
by the adverse events noted by one commenter, and the breakage rate
identified in the 1990 Matsuzaki et al. study cited by another
commenter (Ref. 1). On May 22, 2013, FDA held the 2013 Panel meeting to
discuss the current classification of rigid pedicle screw systems for
treatment of degenerative disc disease and spondylolisthesis other than
either severe spondylolisthesis (grades 3 and 4) at L5-S1 or
degenerative spondylolisthesis with objective evidence of neurologic
impairment, which are currently class III indications (Ref. 2). FDA is
not aware of evidence that indicates there is a higher rate of screw
fracture for the class III indications, which is the focus of this
reclassification effort, compared to the class II indications. The 2013
Panel discussed the adverse events and clinical literature associated
with rigid pedicle screw systems for all indications, and recommended
that traditional, rigid pedicle screw systems as an adjunct to fusion
for the treatment of DDD and spondylolisthesis other than severe grades
3 or 4, or degenerative spondylolisthesis with objective evidence of
neurologic impairment be reclassified as class II (special controls).
FDA agrees with the 2013 Panel's recommendation for
reclassification. The Agency believes, as stated in the 2014 Proposed
Order, that the risks of rigid pedicle screw systems as an adjunct to
fusion for the treatment of DDD and spondylolisthesis other than severe
grades 3 or 4, or degenerative spondylolisthesis with objective
evidence of neurologic impairment, are sufficiently understood based on
valid scientific evidence, which enables FDA to establish special
controls to provide reasonable assurance of safety and effectiveness of
rigid pedicle screw systems.
(Comment 2) One commenter provided an additional recommendation for
the identification language for rigid pedicle screw systems.
Specifically, to more completely characterize components that may be
used as a part of these systems, the commenter suggested adding
sublaminar wires and cables to the list of components of these systems.
(Response 2) FDA disagrees with this proposed edit to the
identification language. These additional components, while often used
in conjunction with pedicle screw systems, are classified under a
separate classification regulation and, therefore, are not appropriate
to include under Sec. 888.3070. However, in review of this
information, FDA acknowledges that hooks (currently listed in the
identification language for pedicle screw systems) are also classified
under a separate classification regulation. Therefore, the Agency has
also taken the opportunity to remove ``hooks'' from the revised
identification language for rigid pedicle screw systems.
(Comment 3) One commenter recommended removing design
characteristics as a special control because this should be a
requirement of all premarket notifications. This commenter also
recommended removing the word ``rigid'' from the identification.
(Response 3) FDA disagrees with the recommendation of this
commenter to remove design characteristics as a special control. FDA
considers this special control critical to help differentiate
technological features for rigid pedicle screw systems from SRSs.
Similarly, inclusion of the word ``rigid'' in the identification
language is necessary to distinguish between these and SRSs.
(Comment 4) One commenter recommended revising the biocompatibility
special control to state ``compliance with biocompatibility
standards.''
(Response 4) FDA disagrees with this comment and has determined
that it is most appropriate not to reference consensus standards within
special controls because relevant standards are subject to change over
time. The special controls as worded allow for additional mechanisms by
which manufacturers can meet the requirements to ensure conformity.
(Comment 5) One commenter recommended removing ``wear'' from the
list of potential means by which a device could fail.
[[Page 96369]]
(Response 5) The risk of wear was raised at the 2013 Panel,
specifically in the context of SRSs. FDA still considers there to be a
potential for wear in traditional rigid systems as well and, therefore,
has elected not to modify the definition of device failure accordingly.
(Comment 6) One commenter suggested editorial revisions to the
risks and descriptive text associated with risks as outlined in the
2014 Proposed Order.
(Response 6) These edits were not considered to substantively
change the intended meaning of the risks and associated mitigations
and, therefore, FDA will not accept these suggested edits in this final
order.
(Comment 7) One commenter provided several proposed edits that
would impact Sec. 888.3070(b)(1). Additionally, this commenter
provided other editorial recommendations to the language from the 2014
Proposed Order.
(Response 7) While FDA agrees with the proposed modifications that
would impact Sec. 888.3070(b)(1), these will require a separate
regulatory action because this section of the regulation is outside the
scope of the call for information under section 515(i) of the FD&C Act.
Edits that were proposed to the language from the 2014 Proposed Order
did not materially impact the language within this final order.
In reviewing the 2014 Proposed Order, the comments received, and
the 2013 Panel's recommendations, FDA is also making minor
modifications to the identification for thoracolumbosacral pedicle
screw systems. The identification for rigid pedicle screw systems will
be revised from ``longitudinal members (e.g., plates, rods, plate/rod
combinations)'' to ``longitudinal members (e.g., plates, rods including
dual diameter rods, plate/rod combinations)'' as the latter statement
clarifies that dual diameter rods would be considered to be part of
rigid systems rather than as ``non-uniform longitudinal elements''
specified under the definition of SRSs.
B. SRSs
1. Identification
In the 2014 Proposed Order, FDA solicited comments to revise the
identification language for pedicle screw spinal systems to distinguish
between rigid pedicle screw systems and DSSs (now termed SRSs).
(Comment 8) While most commenters did not specifically comment on
the proposed up-classification of SRSs to class III, approximately half
of the comments suggested revisions to the definition of SRSs. These
suggestions propose separating SRSs, which may allow for more
flexibility than traditional rigid pedicle screw systems but still
facilitate fusion, from truly ``dynamic'' systems that are intended for
non-fusion use. Truly dynamic systems are postamendments devices that
are outside the scope of this regulatory action.
(Response 8) FDA agrees with these comments and will henceforth
refer to these systems as SRSs in this final order under Sec.
880.3070(b)(3).
(Comment 9) Several commenters provided alternative identification
language to FDA's initially proposed definition of DSSs, now termed
SRSs, which was as follows: ``Dynamic stabilization systems are defined
as systems that contain one or more non-uniform and/or non-metallic
longitudinal elements (e.g., polymer cords, moveable screw heads,
springs) that allow more motion or flexibility (e.g., bending,
rotation, translation) compared to rigid pedicle screw systems and do
not provide immediate rigid fixation to the spinal column as an adjunct
[to] fusion.'' While most commenters agreed with the language that
these systems ``allow more motion or flexibility,'' there were several
comments that disagreed with the technological features called out
within this definition (i.e., non-uniform and/or non-metallic). For
example, one commenter provided the case that an undersized metallic
rod may allow for more flexibility than a larger non-metallic rod.
Similar arguments were also made at the 2013 Panel, where the
challenges of defining these systems based upon technological
characteristics were also discussed. Accordingly, several commenters
proposed modifications to the identification language of these systems
based solely on intended use (i.e., not intended for immediate rigid
fixation, or intended to allow more motion or flexibility compared to
rigid systems). Two commenters did not specifically provide alternate
language; however, these commenters provided data from clinical and
non-clinical studies to support the argument that rods manufactured
from polyetheretherketone (PEEK) perform similarly to traditional
metallic rods (Refs. 3 to 5). Qi et al. demonstrated that subjects
undergoing single posterolateral fusion with either titanium rods or
PEEK rods showed no difference in adjacent segment disease, spinal
alignment, or clinical outcomes (Ref. 3). A biomechanical study by
Sengupta et al. shows similar restriction in range of motion for PEEK
rods compared to both the traditional metallic rods and another SRS
device (Ref. 4). Kurtz et al. collected and analyzed explanted PEEK and
traditional metallic rods and concluded that the PEEK rod retrievals
showed similar wear patterns compared to traditional rigid rods (Ref.
5). These commenters also used terminology to distinguish these types
of systems (i.e., ``semi-rigid systems''), which are used as an adjunct
to fusion, from ``non-rigid'' or ``flexible'' systems, which are
``intended for dynamic stabilization'' of the spine. An additional
commenter also cited a cadaver study, which similarly showed that PEEK
rods resulted in comparable stability to traditional metallic systems
(Ref. 6).
(Response 9) In response to these comments, FDA has revised this
identification to remove reference to ``non-metallic'' components and
has also captured devices with less stiff materials (i.e., ``features
that allow more motion or flexibility compared to rigid systems''). FDA
has also elected to alter the terminology used to identify these
systems that ``allow more motion or flexibility'' when used as an
adjunct to fusion as SRSs. This is also consistent with comments made
at the 2013 Panel, in which the distinction between ``semi-rigid'' and
``dynamic'' systems was discussed. The features that may result in a
device being classified as an SRS may include, but are not limited to,
polymer cords, moveable screw heads, or springs. ``Dynamic
stabilization systems'' for use in non-fusion procedures remain a
postamendments class III device requiring PMAs.
2. Classification
In the 2014 Proposed Order, which was issued pursuant to sections
513(e)(1) and 515(i)(2) of the FD&C Act, FDA initially recommended that
SRSs be classified into class III and require PMAs. Some commenters
agreed with FDA's class III recommendation and other commenters
proposed that SRSs be classified into class II.
(Comment 10) One comment agreed that SRSs for non-fusion uses
should remain in class III, but SRSs used as an adjunct to fusion
should be classified as class II. The commenter described that ``[w]e
believe that this matter arose after two [SRS] products from two
different manufacturers were recalled in 2008 and 2009. These two
recalled devices created FDA concern over the entire category of [SRS],
calling into question whether preclinical testing alone is sufficient
to predict clinical outcomes for these devices. Other SRSs have not
been recalled, nor are there significant safety concerns with these
other [SRSs].'' Another commenter conducted a Medical Device Reporting
(MDR)
[[Page 96370]]
analysis, which separated out PEEK rods from other SRSs to demonstrate
a similarity in reporting of adverse events associated with PEEK rods
to that of traditional metallic rods.
Commenters specifically recommend that PEEK, or carbon-fiber
reinforced PEEK, should remain in class II. This is based on several
reported studies that demonstrate similarities in safety profiles and
effectiveness outcomes for these devices as compared to devices
incorporating traditional metallic rods, as also described previously
in Comment 9 (Refs. 3 to 5). Two non-clinical literature articles
provided in response to the proposed order demonstrate similar behavior
between systems with PEEK rods and those with titanium rods.
Commenters also provided references to clinical studies using SRSs
(Refs. 7 to 9). Each of these studies demonstrates fusion rates within
a range deemed to be clinically acceptable in single- or multilevel
posterolateral fusion using PEEK rod constructs.
(Response 10) Based on these comments to the proposed order and to
corroborate findings from the literature following the 2013 Panel
meeting, FDA conducted an additional MDR analysis of SRSs excluding the
two recalled systems, as well as an MDR analysis of PEEK rods alone.
A search of the Manufacturer and User Facility Device Experience
database was conducted to identify the relevant MDRs and identify the
types of adverse events reported for pedicle screw spinal systems on or
before October 17, 2016. Results from this MDR analysis demonstrated
that the same types of adverse events are present in the same relative
incidence for SRS devices as noted in traditional rigid pedicle screw
systems (i.e., the most common adverse events are device breakage,
revision, and pain in all groups). FDA believes this evidence
demonstrates that SRS devices have the same risks to health as rigid
pedicle screw systems.
FDA additionally conducted an independent survey of literature
published after the 2013 Panel related to the use of SRSs as an adjunct
to fusion to assess current surgical practice and reported treatment
outcome. FDA's literature search captured the articles identified
previously in the comments as well as articles pertaining to additional
SRS designs that have been cleared for marketing in the United States
(Refs. 10 and 11). While only a subset of the 16 SRSs that have
currently been determined to be substantially equivalent are
represented in the literature, a wide range of currently cleared SRS
designs is represented by this subset. The data demonstrated similar
safety profiles for SRSs compared to traditional rigid pedicle screw
systems. The adverse events reported in the literature for SRSs are
similar to those cited in the Executive Summary for the 2013 Panel
Meeting for traditional rigid pedicle screw systems used in currently
class III indications that we proposed to reclassify to Class II rods
(Ref. 2). Typical adverse events included pseudarthrosis, reoperation,
screw loosening, and screw breakage. There were no reports of breakage
of the longitudinal members of any of the SRSs studied.
The fusion rates of SRSs compare favorably to fusion rates of
traditional systems for treatment of low-grade spondylolisthesis and
DDD, which range from 78 to 100 percent and which the 2013 Panel deemed
to be clinically acceptable to support reclassification for these
indications (see the 2013 Panel Executive Summary for additional
information (Ref. 2)). Based upon the currently available information,
FDA agrees with the Panel's assessment that a fusion rate within the
range of 78 to 100 percent would be clinically acceptable. Although the
information presented to the 2013 Panel was limited in both the number
of subjects and the number of SRSs represented, additional information
that FDA received and considered after the 2013 Panel meeting supports
FDA's determination that there is sufficient information to revise the
proposed classification of SRSs from class III to II. FDA believes that
the range of fusion rates found clinically acceptable by the 2013 Panel
could serve as a performance parameter for providing reasonable
assurance of safety and effectiveness for the device type based on the
valid scientific evidence but due to some variability (e.g., design and
material used) among individual devices, FDA has determined that
clinical data are needed to demonstrate that each device with its
specific characteristics (e.g., design and material used) and
conditions of use meets that parameter. FDA believes that fusion rates
higher than the current clinically acceptable range may be achieved
with improvement in technology and, thus, may consider that factor in
evaluating clinical data submitted from firms.
Based upon the information provided in response to the proposed
order, and including additional analyses of the literature and MDRs
since the 2013 Panel, FDA has determined that the risks to health are
not substantially different from traditional rigid pedicle screw spinal
systems. As discussed previously and in the 2014 Proposed Order, FDA
agreed with the 2013 Panel that there is valid scientific evidence on
the safety of rigid pedicle screw systems. FDA has also determined, as
discussed previously, that an evaluation of additional MDR data and
additional clinical literature provide valid scientific evidence
regarding the safety of SRS devices for fusion (Refs. 3 to 11).
Whereas non-clinical performance testing appropriately mitigates
the risks to health for rigid pedicle screw systems, non-clinical
special controls are not sufficient to mitigate the risks to health,
specifically, the risk of pseudarthrosis resulting in additional
surgical procedures, for SRS devices. Non-clinical performance testing
(such as standardized test methods or biomechanical testing of
cadaveric specimens) does not adequately differentiate between
different SRS technologies nor predict the ability to achieve spinal
fusion with a particular SRS. While some SRSs can be tested using the
typical bench testing as a means of comparing performance of
traditional rigid pedicle screw systems (e.g., per ASTM F1717-15,
``Standard Test Methods for Spinal Implant Constructs in a
Vertebrectomy Model''), this testing may result in lower bending
stiffness for SRSs than similarly sized uniform metallic rods (Ref.
12). Testing in accordance with ASTM F1717-15 is not typically used to
evaluate SRS technologies as significant modifications to the test
standards are often necessary to conduct the test. Given that the
systems have not typically been tested in accordance with the accepted
consensus standard and as standardized acceptance criteria for SRS
technologies undergoing this testing have not been developed, it is
challenging to solely use the results of non-clinical performance
testing for comparison purposes to rigid pedicle screw systems.
While clinical data as a special control was not specifically
mentioned in the comments, the 2013 Panel discussed the ability for
clinical data to distinguish between successful and unsuccessful SRS
device designs. FDA believes that clinical performance data would
adequately mitigate the risks to health for SRS devices, particularly
the risk of pseudarthrosis resulting in additional surgical procedures.
In addition, there is sufficient valid scientific evidence showing that
the device type is effective for use as an adjunct to fusion, when the
fusion rate is within a clinically acceptable range, as discussed
previously. FDA therefore believes there is sufficient information to
establish special controls that, in
[[Page 96371]]
addition to general controls, can provide a reasonable assurance of
safety and effectiveness for SRSs. Table 1 summarizes how FDA believes
the risks to health identified for SRSs can be mitigated by special
controls, including clinical performance data.
Table 1--Risks to Health and Mitigation Measures for SRSs
------------------------------------------------------------------------
Identified risks to health Mitigation method
------------------------------------------------------------------------
Device failure............... Design characteristics; Non-clinical
performance testing; Labeling.
Failure of bone implant Design characteristics; Biocompatibility
interface. evaluation; Non-clinical performance
testing; Labeling.
Tissue injury................ Labeling.
Adverse tissue reaction...... Design characteristics; Biocompatibility
evaluation; Sterility; Labeling.
Device malposition........... Labeling.
Pseudarthrosis............... Non-clinical performance testing;
Clinical performance testing; Labeling.
------------------------------------------------------------------------
As discussed in FDA's response to Comment 1, the risks to health
and associated mitigation measures for rigid pedicle screw systems
remain unchanged from those listed in table 1 of the 2014 Proposed
Order.
3. SRS as Class II Device
As stated previously, FDA has reevaluated all of the valid
scientific evidence for SRSs in finalizing this order. As described in
the proposed order and in section I of this order, FDA has satisfied
the requirements under section 515(i)(2) of the FD&C Act for revising
the proposed classification for SRSs. Under section 515(i)(2) of the
FD&C Act, FDA has the authority to issue an administrative order
revising the proposed classification of a device for which FDA has
classified as a class III device and for which no administrative order
has been issued calling for PMAs under section 515(b) of the FD&C Act,
so that the device is classified into class I or class II, after
issuance of a proposed order, a meeting of a device classification
panel, and consideration of the comments of a proposed order. In
determining whether to revise the proposed classification of a device
or to require a device to remain in class III, FDA applies the criteria
set forth in section 513(a) of the FD&C Act. Section 513(a)(1)(B) of
the FD&C Act defines class II devices as those devices for which the
general controls in section 513(a)(1)(A) by themselves are insufficient
to provide reasonable assurance of safety and effectiveness, but for
which there is sufficient information to establish special controls to
provide a reasonable assurance of safety and effectiveness of a device.
FDA has reviewed all of the initial procedures, scientific
information presented at the 2013 Panel meeting, comments received from
both the 2014 Proposed Order and 2009 Final Order under section
515(i)(1) of the FD&C Act calling for information on preamendment
devices (74 FR 16214, April 9, 2009) for consideration of the
classification of SRS devices under section 513(a) of the FD&C Act and
has initiated revision of the proposed classification of the device
under section 515(i)(2) of the FD&C Act.
The discussion at the 2013 Panel for SRSs was limited, as
acknowledged by 2013 Panel members, by the small number of studies
available at that time and reports in the MDRs regarding SRSs for
fusion. Given limitations of the available data, in literature and MDR
analysis, the 2013 Panel concluded that insufficient evidence was
available to establish special controls. Although FDA recommended, and
the 2013 Panel agreed, that a call for PMAs was the necessary measure
to mitigate the risks to health for SRSs and ensure a reasonable
assurance of safety and effectiveness, FDA has since reassessed the
scientific evidence based upon comments received and additional
information, reevaluating the scientific evidence presented at the 2013
Panel meeting to reconsider FDA's prior position regarding the
necessary controls to provide reasonable assurance of safety and
effectiveness for SRSs. Based on FDA's reevaluation of the available
body of evidence, FDA has determined that sufficient information exists
regarding the risks and benefits of SRSs for FDA to determine that
general and special controls can provide reasonable assurance of the
safety and effectiveness of the device type and, thus, revising the
proposed classification for these devices from class III to II under
section 515(i)(2) of the FD&C Act is appropriate.
Also, at the 2013 Panel meeting, the panel did discuss the
feasibility of clinical data as being able to potentially distinguish
between successful and non-successful SRS designs, without specifically
discussing what level of data would be necessary. After further review
of the scientific literature and comments, FDA believes that clinical
performance data as a special control would adequately mitigate the
risks to health for SRS devices, particularly the risk of
pseudarthrosis resulting in additional surgical procedures (see
response to Comment 10 in section II.B.2).
Upon reevaluation of the scientific evidence and additional
information, FDA has determined that SRS devices do not have the degree
of risk of illness or injury designed to be eliminated or reduced by
requiring the device to have an approved PMA under section 515(b)(2) of
the FD&C Act. In addition, the level of scientific evidence evaluated
has allowed FDA to determine that SRSs can be classified as class II
with the establishment of special controls because sufficient valid
scientific evidence exists to determine that general controls, in
combination with special controls, are sufficient to provide a
reasonable assurance of safety and effectiveness. FDA has determined
that revision of the proposed classification of SRSs under section
515(i)(2) of the FD&C Act will allow these devices to be classified in
class II subject to a clinical performance data special control. As a
result, instead of calling for PMAs for SRSs, FDA is finalizing this
order to revise the proposed classification for SRS devices from class
III to class II (special controls) following reassessment of all
relevant scientific evidence and comments received from the 2014
Proposed Order. FDA believes the clinical performance data special
control and other special controls, together with general controls, are
sufficient to provide a reasonable assurance of safety and
effectiveness for SRS devices.
IV. The Final Order
Under sections 513(e) and 515(i) of the FD&C Act, FDA is adopting
its findings as published in the preamble to the proposed order with
the modifications discussed in section II of this final order. FDA is
issuing this final order to reclassify rigid pedicle screw systems and
to revise classification of SRSs when intended to provide
[[Page 96372]]
immobilization and stabilization of spinal segments in the thoracic,
lumbar, and sacral spine as an adjunct to fusion in the treatment of
DDD and spondylolisthesis (other than either severe spondylolisthesis
(grades 3 and 4) at L5-S1 or degenerative spondylolisthesis with
objective evidence of neurologic impairment) when used as an adjunct to
fusion from class III to class II and establish special controls for
all SRSs by revising part 888. Rigid pedicle screw systems when
intended to provide immobilization and stabilization of spinal segments
in the thoracic, lumbar, and sacral spine as an adjunct to fusion in
the treatment of DDD and spondylolisthesis (other than either severe
spondylolisthesis (grades 3 and 4) at L5-S1 or degenerative
spondylolisthesis with objective evidence of neurologic impairment) and
SRSs for any indication must comply with the special controls
identified in this order (see Section V, ``Implementation Strategy'').
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 devices. FDA has determined that premarket
notification is necessary to provide reasonable assurance of safety and
effectiveness of rigid pedicle screw systems and SRSs when intended to
provide immobilization and stabilization of spinal segments in the
thoracic, lumbar, and sacral spine as an adjunct to fusion in the
treatment of DDD and spondylolisthesis (other than either severe
spondylolisthesis (grades 3 and 4) at L5-S1 or degenerative
spondylolisthesis with objective evidence of neurologic impairment).
Therefore, these device types are not exempt from premarket
notification requirements.
Following the effective date of this final order, firms marketing
rigid pedicle screw systems when intended to provide immobilization and
stabilization of spinal segments in the thoracic, lumbar, and sacral
spine as an adjunct to fusion in the treatment of DDD and
spondylolisthesis (other than either severe spondylolisthesis (grades 3
and 4) at L5-S1 or degenerative spondylolisthesis with objective
evidence of neurologic impairment) and SRSs for any indication must
comply with the special controls set forth in this order (see section
V, ``Implementation Strategy'').
V. Implementation Strategy
The special controls identified in this final order are effective
as of the date of publication of this order, December 30, 2016. Both
rigid pedicle screw systems and SRSs covered by this order must comply
with the special controls following the effective date of the order.
Specifically, devices subject to the special controls in this order
include rigid pedicle screw systems intended to provide immobilization
and stabilization of spinal segments in the thoracic, lumbar, and
sacral spine as an adjunct to fusion in the treatment of DDD and
spondylolisthesis (other than either severe spondylolisthesis (grades 3
and 4) at L5-S1 or degenerative spondylolisthesis with objective
evidence of neurologic impairment), and SRSs for any indication.
However, FDA does not intend to enforce compliance with the special
controls for currently legally marketed SRSs covered by this order
until June 28, 2018. The 30-month enforcement discretion period was
selected based on the following factors: (1) The 2014 Proposed Order
initially called for PMAs containing clinical performance data to be
submitted within a 30-month timeframe, and thus the request in this
final order for 510(k) amendments, which include submission of clinical
performance data as a special control, maintains the same expectation
of sponsors; and (2) the effectiveness endpoint of fusion for SRSs is
generally assessed at 1 to 2 years post-implantation, and thus if a new
study were to be initiated to collect clinical performance data, FDA
would expect the 30-month period to be appropriate for SRS and allow
sponsors sufficient time to enroll patients, conduct the study, and
analyze the data.
For those manufacturers who wish to continue to offer for sale
currently legally marketed SRSs covered by this order, FDA expects them
to submit an amendment to their previously cleared 510(k)s for the
devices by June 28, 2018 that demonstrates compliance with the special
controls. This approach is consistent with prior final orders for
reclassifications of preamendment devices in which special controls
requiring submission of clinical performance data were issued. An
amendment to a 510(k) will be added to the 510(k) file but will not
serve as a basis for a new substantial equivalence review. A submitted
510(k) amendment in this context will be used solely to demonstrate to
FDA that an SRS system is in compliance with the special controls. If a
510(k) amendment for the device is not submitted by June 28, 2018 or if
FDA determines that the amendment does not demonstrate compliance with
the special controls, then this compliance policy would not apply, and
FDA would intend to enforce compliance with these requirements. In that
case, the device is deemed adulterated under section 501(f)(1)(B) of
the FD&C Act (21 U.S.C. 351(f)(1)(B)) as of the date of FDA's
determination of noncompliance or June 28, 2018, whichever is sooner.
For rigid pedicle screw systems intended to provide immobilization
and stabilization of spinal segments in the thoracic, lumbar, and
sacral spine as an adjunct to fusion in the treatment of DDD and
spondylolisthesis (other than either severe spondylolisthesis (grades 3
and 4) at L5-S1 or degenerative spondylolisthesis with objective
evidence of neurologic impairment) and SRSs for any indication that
have not been legally marketed prior to December 30, 2016, or models
that have been legally marketed but are required to submit a new 510(k)
under 21 CFR 807.81(a)(3) because the device is about to be
significantly changed or modified, manufacturers must obtain 510(k)
clearance, among other relevant requirements, and demonstrate
compliance with the special controls included in this final order,
before marketing the new or changed device.
VI. 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.
VII. Paperwork Reduction Act of 1995
This final 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. 3501-3520). 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.
VIII. Codification of Orders
Prior to the amendments by FDASIA, section 513(e) of the FD&C Act
provided for FDA to issue regulations to reclassify devices. Although
section 513(e) as amended requires FDA to issue final orders rather
than regulations, FDASIA also provides for FDA to revoke previously
promulgated regulations by
[[Page 96373]]
order. FDA will continue to codify classifications and
reclassifications in the CFR. Changes resulting from final orders will
appear in the CFR as changes to codified classification determinations
or as newly codified orders. Therefore, pursuant to section
513(e)(1)(A)(i) of the FD&C Act, as amended by FDASIA, in this final
order, we are revoking the requirements in Sec. 888.3070 related to
the classification of rigid pedicle screw systems and SRSs when
intended to provide immobilization and stabilization of spinal segments
in the thoracic, lumbar, and sacral spine as an adjunct to fusion in
the treatment of DDD and spondylolisthesis (other than either severe
spondylolisthesis (grades 3 and 4) at L5-S1 or degenerative
spondylolisthesis with objective evidence of neurologic impairment) as
class III devices. We are codifying the reclassification of rigid
pedicle screw systems and SRSs when intended to provide immobilization
and stabilization of spinal segments in the thoracic, lumbar, and
sacral spine as an adjunct to fusion in the treatment of DDD and
spondylolisthesis (other than either severe spondylolisthesis (grades 3
and 4) at L5-S1 or degenerative spondylolisthesis with objective
evidence of neurologic impairment) into class II (special controls). In
addition, as set forth in the 2014 Proposed Order, FDA has separated
SRSs, a subtype of pedicle screw systems, from rigid pedicle screw
systems in the identification section of the classification regulation
(Sec. 888.3070(a)) and has established a separate subpart of the
classification regulation (Sec. 888.3070(b)(3)), which is applicable
to all SRSs regardless of indication.
IX. References
The following references are on display in the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, and are available for viewing by
interested persons between 9 a.m. and 4 p.m., Monday through Friday;
they are also available electronically at https://www.regulations.gov.
FDA has verified the Web site addresses, as of the date this document
publishes in the Federal Register, but Web sites are subject to change
over time.
1. Matsuzaki, H., Y. Tokuhashi, F. Matsumoto, et al., ``Problems and
Solutions of Pedicle Screw Fixation of Lumbar Spine,'' Spine,
15(11):1159-1165, 1990.
2. FDA's Orthopedic and Rehabilitation Devices Panel transcript and
other meeting materials are available on FDA's Web site at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm352525.htm.
3. Qi, L., M. Li, S. Zhang, et al., ``Comparative Effectiveness of
PEEK Rods Versus Titanium Alloy Rods in Lumbar Fusion: A Preliminary
Report,'' Acta Neurochirurgica, 155(7):1187-1193, 2013.
4. Sengupta, D.K., B. Bucklen, P.C. McAfee, et al., ``The
Comprehensive Biomechanics and Load-Sharing of Semirigid PEEK and
Semirigid Posterior Dynamic Stabilization Systems,'' Advances in
Orthopedics, 2013. doi:10.1155/2013/745610 (Epub); available at
https://www.hindawi.com/journals/aorth/2013/745610/.
5. Kurtz, S.M., T.H. Lanman, G. Higgs, et al., ``Retrieval Analysis
of PEEK Rods for Posterior Fusion and Motion Preservation,''
European Spine Journal, 22(12):2752-2759, 2013.
6. Gornet, M.F., F.W. Chan, J.C. Coleman, et al., ``Biomechanical
Assessment of a PEEK Rod System for Semi-Rigid Fixation of Lumbar
Fusion Constructs,'' Journal of Biomechanical Engineering,
133(8):081009, 2011. doi: 10.1115/1.4004862.
7. Athanasakopoulos, M., A.F. Mavrogenis, G. Triantafyllopoulos, et
al., ``Posterior Spinal Fusion Using Pedicle Screws,'' Orthopedics,
36(7):e951-e957, 2013. doi: 10.3928/01477447-20130624-28.
8. Colangeli, S., G. Barbanti Brod[agrave]no, A. Gasbarrini, et al.,
``Polyetheretherketone (PEEK) Rods: Short-Term Results in Lumbar
Spine Degenerative Disease,'' Journal of Neurosurgical Sciences,
59(2):91-96, 2015.
9. De Iure, F., G. Bosco, M. Cappuccio, et al., ``Posterior Lumbar
Fusion by PEEK Rods in Degenerative Spine: Preliminary Report on 30
Cases,'' European Spine Journal, 21 Suppl 1:S50-54, 2012.
10. Ormond, D.R., L. Albert Jr., and K. Das, ``Polyetheretherketone
(PEEK) Rods in Lumbar Spine Degenerative Disease: A Case Series,''
Journal of Spine Disorders & Techniques, in press, 2012 (later
published in 2016 under Clinical Spine Surgery, 29(7):E371-E375,
2016).
11. Yang, M., C. Li, Z. Chen, et al., ``Short Term Outcome of
Posterior Dynamic Stabilization System in Degenerative Lumbar
Diseases,'' Indian Journal of Orthopaedics, 48(6):574-581, 2014.
12. ASTM F1717-15, ``Standard Test Methods for Spinal Implant
Constructs in a Vertebrectomy Model,'' July 2015; available at:
https://www.astm.org/Standards/F1717.htm.
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, 371.
0
2. Section 888.3070 is amended by revising the section heading and
paragraphs (a) and (b)(2), adding paragraph (b)(3), and removing
paragraph (c).
The revisions and addition read as follows:
Sec. 888.3070 Thoracolumbosacral pedicle screw system.
(a) Identification. (1) Rigid pedicle screw systems are comprised
of multiple components, made from a variety of materials that allow the
surgeon to build an implant system to fit the patient's anatomical and
physiological requirements. Such a spinal implant assembly consists of
a combination of screws, longitudinal members (e.g., plates, rods
including dual diameter rods, plate/rod combinations), transverse or
cross connectors, and interconnection mechanisms (e.g., rod-to-rod
connectors, offset connectors).
(2) Semi-rigid systems are defined as systems that contain one or
more of the following features (including but not limited to): Non-
uniform longitudinal elements, or features that allow more motion or
flexibility compared to rigid systems.
(b) * * *
(2) Class II (special controls), when a rigid pedicle screw system
is intended to provide immobilization and stabilization of spinal
segments in the thoracic, lumbar, and sacral spine as an adjunct to
fusion in the treatment of degenerative disc disease and
spondylolisthesis other than either severe spondylolisthesis (grades 3
and 4) at L5-S1 or degenerative spondylolisthesis with objective
evidence of neurologic impairment. These pedicle screw systems must
comply with the following special controls:
(i) The design characteristics of the device, including engineering
schematics, must ensure that the geometry and material composition are
consistent with the intended use.
(ii) Non-clinical performance testing must demonstrate the
mechanical function and durability of the implant.
(iii) Device components must be demonstrated to be biocompatible.
(iv) Validation testing must demonstrate the cleanliness and
sterility of, or the ability to clean and sterilize, the device
components and device-specific instruments.
[[Page 96374]]
(v) Labeling must include the following:
(A) A clear description of the technological features of the device
including identification of device materials and the principles of
device operation;
(B) Intended use and indications for use, including levels of
fixation;
(C) Identification of magnetic resonance (MR) compatibility status;
(D) Cleaning and sterilization instructions for devices and
instruments that are provided non-sterile to the end user; and
(E) Detailed instructions of each surgical step, including device
removal.
(3) Class II (special controls), when a semi-rigid system is
intended to provide immobilization and stabilization of spinal segments
in the thoracic, lumbar, and sacral spine as an adjunct to fusion for
any indication. In addition to complying with the special controls in
paragraphs (b)(2)(i) through (v) of this section, these pedicle screw
systems must comply with the following special controls:
(i) Demonstration that clinical performance characteristics of the
device support the intended use of the product, including assessment of
fusion compared to a clinically acceptable fusion rate.
(ii) Semi-rigid systems marketed prior to the effective date of
this reclassification must submit an amendment to their previously
cleared premarket notification (510(k)) demonstrating compliance with
the special controls in paragraphs (b)(2)(i) through (v) and paragraph
(b)(3)(i) of this section.
Dated: December 22, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-31670 Filed 12-29-16; 8:45 am]
BILLING CODE 4164-01-P