Screws-Medical, Surgical, Bone etc.

Classification and Reclassification of Pedicle Screws

Orthopedic Devices: Classification and
Reclassification of Pedicle Screw Spinal
Systems
[Federal Register: July 27, 1998 (Volume 63,
Number 143)]
[Rules and Regulations]
[Page 40025-40041]

From the Federal Register Online via GPO
Access [wais.access.gpo.gov]
[DOCID:fr27jy98-7]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 888
[Docket No. 95N-0176]
RIN 0910-ZA12

Orthopedic Devices: Classification and
Reclassification of
Pedicle Screw Spinal Systems

Agency: Food and Drug Administration,
HHS.

Action: Final rule.
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SUMMARY: The Food and Drug Administration
(FDA) is classifying certain previously
unclassified preamendments pedicle screw
spinal systems into class II (special
controls) and reclassifying certain
postamendments pedicle screw spinal systems
from class III (premarket approval) to class
II. FDA is taking this action because it
believes that special controls would provide
reasonable assurance of safety and
effectiveness. This action is being taken
under the Federal Food, Drug, and Cosmetic
Act (the act), as amended by the Medical
Device Amendments of 1976 (the 1976
amendments), the Safe Medical Devices Act of
1990 (the SMDA), and the Food and Drug
Administration Modernization Act of 1997
(FDAMA).
EFFECTIVE DATE: August 26, 1998.
FOR FURTHER INFORMATION CONTACT: Aric D.
Kaiser, Center for Devices and Radiological
Health (HFZ-410), Food and Drug
Administration, 9200 Corporate Blvd.,
Rockville, MD 20850, 301-594-2036.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Background
II. Regulatory History of the Device
III. Summary of the Final Rule
IV. Proposed Rule Clarifications
V. Analysis of Comments and FDA's Response
A. Issues Relating to the Recommendations
of the Panel, FDA's Tentative Findings, and
Summary of the Data Upon Which FDA's Findings
Were Based
B. Issues Relating to Information
Published in the 1994
Supplementary Issue of the Journal Spine
(vol. 20S, 1994)
C. Issues Relating to the January 1995,
510(k) Substantial
Equivalence Determination for a Pedicle Screw
Spinal System Intended for Severe
Spondylolisthesis
D. Issues Relating to Misstatements or
False Statements
Appearing in the Proposed Rule
E. Issues Relating to the FDA's Issuance
of Regulations
F. Responses to Comments Which Contained
Clinical Data
G. Requests for Additional Pedicle Screw
Clinical Trials and Data Analyses
H. Issues Relating to Indications for Use
I. Issues Relating to Special Controls
J. Other Issues
K. Labeling of Bone Screws
L. Review of New Pedicle Screw Spinal
System 510(k)'s
M. Review of New Information Published and
Submitted After
Publication of the Proposed Rule: Pedicle
Screw and Related
Literature and MedWatch and MDR System
Reports
VI. References
VII. Environmental Impact
VIII. Analysis of Impacts
I. Background
The act (21 U.S.C. 331 et seq.), as
amended by the 1976 amendments (Pub. L.
94-295), the SMDA (Pub. L. 101-629), and
FDAMA (Pub. L. 105-
115), established a comprehensive system for
the regulation of medical devices intended
for human use. Section 513 of the act (21
U.S.C. 360c) established three categories
(classes) of devices, depending on 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 of the act, devices
that were in commercial distribution before
May 28, 1976 (the date of enactment of the
1976 amendments), 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
classified automatically by statute (section
513(f) of the act) into class III without any
FDA rulemaking process. Those devices remain
in class III and require premarket approval,
unless and until: (1) The device is
reclassified into class I or II; (2) FDA
issues an order classifying the device into
class I or II in accordance with new section
513(f)(2) of the act, as amended by FDAMA; or
(3) FDA issues an order finding the device to
be substantially equivalent, in accordance
with section 513(i) of the act, to a
predicate device that does not require
premarket approval. The agency determines
whether new devices are substantially
equivalent to previously offered devices by
means of premarket notification procedures in
section 510(k) of the act (21
U.S.C. 360(k)) and part 807 of the
regulations (21 CFR part 807). A
preamendments device that has been classified
into class III may
be marketed, by means of premarket
notification procedures, without submission
of a premarket approval application (PMA)
until FDA promulgates a final regulation
under section 515(b) of the act (21
U.S.C. 360e(b)) requiring premarket approval.
Reclassification of classified
preamendments devices is governed by section
513(e) of the act. This section provides that
FDA may, by
rulemaking, reclassify a device (in a
proceeding that parallels the initial
classification proceeding) based upon ``new
information.눼 The reclassification can be
initiated by FDA or by the petition of an
interested person. The term ``new
information,눼 as used in section 513(e) of
the act, 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 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 regulatory action where the
reevaluation is made in light of newly
available regulatory authority (see Bell v.
Goddard, supra, 366 F.2d at 181; Ethicon,
Inc. v. FDA, 762
F. Supp. 382, 389-91 (D.D.C. 1991)), in light
of changes in ``medical science.'' (See
Upjohn v. Finch, supra, 422 F.2d at 951.)
Regardless of whether data before the agency
are past or new data, the ``new information''
on which any reclassification is based is
required to consist ``valid scientific
evidence,눼 as defined in section 513(a)(3)
of the act and Sec. 860.7(c)(2) (21 CFR
860.7(c)(2)). (See, e.g., General Medical Co.
v. FDA, 770 F.2d 214 (D.C. Cir. 1985);
Contact Lens Assoc. v. FDA, 766 F.2d 592
(D.C. Cir.), cert. denied, 474 U.S. 1062
(1985).) FDA relies upon ``valid scientific
evidence눼 in the classification process to
determine the level of
[[Page 40026]]
regulation for devices. For the purpose of
reclassification, 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 act (21 U.S.C. 360j(c).)
II. Regulatory History of the Device
Consistent with the act and the regulation,
FDA referred the proposed classification and
reclassification of pedicle screw spinal
systems to the Orthopedic and Rehabilitation
Devices Panel (the Panel), an FDA advisory
committee, for its recommendation on the
requested classification and change in
classification.
The Panel reviewed complication type and
rate data present in the literature, a
meta-analysis of the literature; a
nationwide, retrospective Cohort study of
patients treated with the devices;\1\ and a
review of publicly released investigational
device exemptions (IDE) data from patients
treated with pedicle screw spinal systems.
The Panel recommended that the postamendments
pedicle screw spinal systems intended to
treat spinal fracture and degenerative
spondylolisthesis of the thoracic, lumbar,
and sacral spine, be reclassified from class
III into class II.
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\1\ The Cohort study was an open,
nonblinded, historical Cohort study designed
to recruit the maximum number of surgeons to
provide clinical data on patients who had
undergone spinal fusion surgery. Three
hundred fourteen surgeons were recruited
through announcements at professional society
meetings and direct mailings to professional
society memberships. Only clinical data from
spinal fusion surgeries intended to treat
degenerative spondylolisthesis or spinal
trauma (fracture) that were performed between
January 1, 1990, and December 31, 1991, were
used in the analysis. This was done in an
effort to maximize the number of patients
with a minimum of 24 months followup. Data
from 3,498 patients were collected.
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In January, 1995, a manufacturer was able
to demonstrate
preamendments status for pedicle screw spinal
systems intended to provide immobilization
and stabilization of spinal segments as an
adjunct to spinal fusion in the treatment of
grades 3 or 4 severe spondylolisthesis at the
fifth lumbar-first sacral (L5-
S1) spinal level. In an April
1995, homework assignment, FDA requested that
the Panel recommend a classification for this
unclassified preamendments device. The Panel
recommended that the unclassified
preamendments pedicle screw spinal systems
intended to provide immobilization and
stabilization of spinal segments as an
adjunct to spinal fusion in the treatment of
grades 3 or 4 severe spondylolisthesis at the
L5-S1 spinal level be
classified into class II.
In the Federal Register of October 4, 1995
(60 FR 51946), FDA published a proposed rule
to classify certain unclassified
preamendments pedicle screw spinal systems
(for use in certain types of severe
spondylolisthesis ) into class II, to
reclassify certain postamendments pedicle
screw spinal systems (for use in fracture and
other conditions) from class III to class II,
and to retain in class III other
postamendments pedicle screw spinal systems.
The proposed rule reflected FDA's belief that
the clinical outcomes and
complications described in the literature,
clinical data, and MDR and MedWatch
surveillance data bases,\2\ described patient
risks and benefits of pedicle screw spinal
systems comparable to other class II spinal
fixation devices and that special controls
have been identified which would provide a
reasonable assurance of safety and
effectiveness,
i.e., compliance with material standards,
mechanical testing standards,
biocompatibility standards, and special
labeling requirements. Initially, FDA
provided for interested persons to submit
comments on the proposal by January 2, 1996.
Subsequently, in the Federal Register of
December 29, 1995 (60 FR 67345), FDA extended
the comment period until March 4, 1996, in
response to several requests for extension of
the comment period.
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\2\ MDR and MedWatch data bases are two
reporting systems that FDA uses to track
adverse events, e.g., injuries, deaths, and
device malfunctions, related to medical
devices. The information consists of a
combination of mandatory and/or voluntary
adverse event reports from manufacturers,
distributors, user facilities, healthcare
professionals, as well as consumers.
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FDA received 4,060 comments in response
to the proposed rule. These comments were
submitted by physicians, patients, lawyers,
device manufacturers, trade associations, and
other interested parties. The overwhelming
majority of these comments were in favor of
the proposed rule, although some comments
were opposed to the proposed rule, and a few
were both in favor of some aspects of the
proposed rule and opposed to others.
In response to comments received on the
proposed rule, FDA reanalyzed the
meta-analysis of the literature, the Cohort
study, and the publicly released IDE data for
the indications of spinal fractures and
degenerative spondylolisthesis. The
reanalysis of the meta-analysis of the
literature consisted of a review of the
summary data and conclusions from the
original, published analysis. The review of
the Cohort study consisted of an audit (Ref.
1) of a structured sample of all 377 patients
enrolled by 21 of the 314 participating
surgeons, a reanalysis (Ref. 2) of all of the
data from the audit, and a comparison to the
data from unaudited surgeons. The Division of
Bioresearch Monitoring (BIMO) in the Office
of Compliance performed the data audit, while
the Office of Device Evaluation and the
Office of Surveillance and Biometrics
performed the reanalyses. This audit found
records were incomplete and investigators had
not followed the protocol. In review of the
audit, the agency concluded that the
disparities and irregularities were
consistent, with respect to both type and
scope, with other audits of similar studies.
After careful reanalysis of the potential
impact of the ``problem눼 records, the agency
concluded that they could not account for the
favorable results reported in this study.
The review of the Cohort study in the
context of the audit findings yielded results
that supported the safety and effectiveness
of these devices. For spinal fracture,
pedicle screw spinal systems presented risks
and benefits that were comparable to those
presented by nonpedicle screw instrumented
spinal fusion. The devices used in the
comparison group are class II medical
devices. For spondylolisthesis, the review in
the context of the audit findings described
an advantage for pedicle screw spinal systems
with regard to the clinical outcome
parameters of fusion and improvement in
neurological status when compared to
noninstrumented spinal fusions. For the other
parameters that were analyzed, e.g., pain,
function, and reoperation rate, pedicle screw
spinal systems did not always demonstrate an
advantage compared to noninstrumented spinal
fusion. When compared to instrumented spinal
fusions, however, results among pedicle screw
spinal system patients for these parameters
were not statistically equivalent and not
worse. Thus, FDA has concluded that the
results from the review of the Cohort study
are consistent with those reported in the
literature and the publicly released IDE
data.
The reanalysis of the meta-analysis of
the literature describing experience with
pedicle screw spinal systems in treating
spinal fracture and degenerative
spondylolisthesis found that pedicle screw
spinal systems present risks and benefits
that are comparable to those presented by
nonpedicle screw spinal systems and
noninstrumented spinal fusions. For
degenerative spondylolisthesis, the
reanalysis found
[[Page 40027]]
that patient results with pedicle screw
spinal systems were comparable to those with
noninstrumented spinal fusions; it did not
find a clinically significant improvement in
results at followup obtained with
instrumented spinal fusions over
noninstrumented spinal fusions.
The reanalysis of the publicly available
IDE data supports the Panel's recommendation
for the classification and reclassification
of pedicle screw spinal systems intended to
treat spinal fractures and severe
spondylolisthesis. It also supports the use
of pedicle screw spinal systems when intended
to provide immobilization and stabilization
of spinal segments in skeletally mature
patients as an adjunct to fusion for the
treatment of the following acute and chronic
instabilities or deformities of the thoracic,
lumbar, and sacral spine: degenerative
spondylolisthesis with objective evidence of
neurologic impairment, fractures,
dislocations, scoliosis, kyphosis, spinal
tumors, and failed previous fusion
(pseudarthrosis).
When all of these data are viewed in
conjunction with the medical literature and
the MDR and MedWatch surveillance data, no
new issues relating to the safety or
effectiveness of pedicle screw spinal systems
are raised. Therefore, the agency has
concluded that these data provide valid
scientific evidence that certain special
controls in conjunction with the general
controls applicable to all devices, will
provide a reasonable assurance of the safety
and effectiveness of pedicle screw spinal
systems for L5-S1 use
and for use at other levels for the treatment
of degenerative spondylolisthesis with
objective evidence of neurologic impairment.
The agency also reviewed whether the
Panel was properly
constituted. Investigation of alleged
undisclosed and unwaived conflicts of
interest held by Panel members found either
no omissions of current interests or
omissions of minor interests for all but one
of the Panel members. The agency has
concluded that the minor omissions are
insignificant and do not constitute a
financial conflict of interest that would
credibly influence the members' actions in
forming the Panel's recommendations.
The agency has found that one voting Panel
member did have
significant undisclosed financial conflicts.
However, because the recommendation of the
Panel, both in the July 23, 1994, meeting and
on the subsequent homework assignment, was
unanimous and this individual was not
controlling, or unduly influential, of the
votes of the other Panel members and was not
necessary to constitute a quorum, after
expunging the participation of this Panel
member, FDA has concluded that this Panel,
both in the meeting and on the subsequent
homework assignment, was a valid scientific
Panel to make recommendations to the agency.
The agency's reanalysis of these data has
confirmed its original conclusion, reflected
in the proposed rule, that the risks and
benefits of pedicle screw spinal systems are
comparable to those of other class II spinal
fixation devices. FDA's decision to classify
and reclassify these devices into class II is
based upon valid scientific evidence
establishing that the special controls
described above, along with the general
controls applicable to all devices under the
act, provide a reasonable assurance of the
safety and effectiveness of pedicle screw
spinal systems.
III. Summary of the Final Rule
In this final rule, FDA is classifying
into class II the
unclassified preamendments pedicle screw
spinal systems intended for treatment of
severe spondylolisthesis (grades 3 and 4) of
the L5-S1 vertebra in
skeletally mature patients receiving fusion
by autogenous bone graft having implants
attached to the lumbar and sacral spine with
removal of the implants after the attainment
of a solid fusion. In addition, FDA is
reclassifying into
class II the postamendments class III pedicle
screw spinal systems intended to provide
immobilization and stabilization of spinal
segments in skeletally mature patients as an
adjunct to fusion in the treatment of the
following acute and chronic instabilities or
deformities of the thoracic, lumbar, and
sacral spine: Degenerative spondylolisthesis
with objective evidence of neurologic
impairment, fracture, dislocation, scoliosis,
kyphosis, spinal tumor, and failed previous
fusion (pseudarthrosis). Pedicle screw spinal
systems intended for any other uses are
considered postamendments class III devices
for which premarket approval is required. The
following four special controls apply to the
devices being classified and reclassified
into class II: (1) Compliance with materials
standards, (2) compliance with mechanical
testing standards of performance, (3)
compliance with biocompatibility standards,
and (4) adherence to labeling requirements.
IV. Proposed Rule Clarifications
FDA is taking this opportunity to clarify
that neither well- controlled investigations
nor valid scientific evidence relating to
pedicle screw spinal systems intended for use
in the cervical spine is available and,
therefore, the safety and effectiveness of
these devices for this intended use have not
been demonstrated. As a result, pedicle screw
spinal systems intended for use in the
cervical spine are excluded from this
classification and reclassification and are
considered postamendments class III devices
for which premarket approval is required.
In addition, although not specifically
stated in the preamble to the proposed rule,
all valid scientific evidence reviewed by the
Panel and FDA were obtained from skeletally
mature populations. To date, the safety and
effectiveness of pedicle screw spinal systems
in pediatric populations have not been
demonstrated. Consequently, pedicle screw
spinal systems intended for use in pediatric
populations are postamendments class III
devices for which premarket approval is
required.
V. Analysis of Comments and FDA's Response
A. Issues Relating to the Recommendations of
the Panel, FDA's Tentative Findings, and
Summary of the Data Upon Which FDA's Findings
Were Based
1. Several comments believed that valid
scientific evidence was not presented to the
Panel or used in formulating the proposed
rule. These comments argued that only
prospective, randomized, concurrently-
controlled clinical trials constitute valid
scientific evidence and that anything else is
insufficient to support device
reclassification.
FDA disagrees that only data from
prospective, randomized,
concurrently-controlled clinical trials can
constitute valid scientific evidence.
Although prospective, randomized,
concurrently controlled clinical trials have
the potential to produce the most convincing
and reliable data, e.g., all sources of bias
have been reduced to a minimum, such clinical
trials are not the only type of study that
can produce data adequate to support a
determination that there is reasonable
assurance that a device is safe and effective
for its conditions for use. In fact, Sec.
860.7(c)(2) defines valid scientific evidence
as
* *evidence from well-controlled
investigations, partially
controlled studies, studies and objective
trials without matched controls,
well-documented case histories conducted by
qualified experts, and reports of significant
human experience with a marketed device, from
which it can fairly and responsibly be
concluded by qualified experts that there is
reasonable assurance of the safety and
effectiveness of a device under
[[Page 40028]]
its conditions of use. The evidence may vary
according to the characteristics of the
device, the existence and adequacy of
warnings and other restrictions, and the
extent of experience with
its use * * *.
From this definition, it is clear that there
is a hierarchy of data that fits the
definition of valid scientific and that,
while well- controlled, prospective clinical
trials are at the top of the hierarchy, they
are not the only source of data that may
support a determination regarding reasonable
assurance of safety and effectiveness for
purposes of classifying and/or reclassifying
a device.
FDA also disagrees that valid scientific
evidence was not presented to the Panel or
used in support of the proposed rule. The
three sources of data presented to the Panel
and used in support of the proposed rule
were: (1) Reformatted IDE data, (2) a
meta-analysis of the literature, and (3) the
Cohort study. The reformatted IDE data
represent data from well-controlled
investigations, while the meta-analysis of
the literature and the Cohort study represent
studies and objective trials without matched
controls or well-documented case histories or
reports of significant human experience. All
three sources of data used in support of the
classification and reclassification of
pedicle screw spinal systems clearly fall
within the definition of valid scientific
evidence in Sec. 860.7(c)(2).
2. One comment objected that, in addition
to not being valid scientific evidence, the
three sources of data, i.e., the
meta-analysis of the literature, the
reformatted IDE data and the Cohort study,
were flawed.
The comment noted the following
deficiencies with the meta- analysis:
FDA previously determined that
the available literature on pedicle screw
spinal systems could not be used to support
device reclassification.
FDA disagrees. FDA made that statement
prior to January, 1993, when no adequate
analysis of pedicle screw literature had been
provided to the agency. FDA believes that,
while individual literature articles
describing the use of pedicle screw spinal
systems would be insufficient to support
reclassification of a device, group analysis
of relevant articles may be adequate,
especially where, as here, the group analysis
is considered in conjunction with other
supporting data. Furthermore, after noting
the limitations of the individual studies
reported in the literature, FDA concluded
that the literature, taken as a whole and
used in conjunction with the other sources of
data, provided adequate information to
support the reclassification of pedicle screw
spinal systems intended to treat degenerative
spondylolisthesis with objective evidence of
neurologic impairment or spinal trauma.

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