[Federal Register Volume 60, Number 192 (Wednesday, October 4, 1995)]
[Proposed Rules]
[Pages 51946-51962]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-24686]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 888
[Docket No. 95N-0176]
Orthopedic Devices: Classification, Reclassification, and
Codification of Pedicle Screw Spinal Systems
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
classify certain unclassified preamendments pedicle screw spinal
systems into class II (special controls), and to reclassify certain
postamendments pedicle screw spinal systems from class III (premarket
approval) to class II. FDA is also issuing for public comment the
recommendations of the Orthopedic and Rehabilitation Devices Panel (the
Panel) concerning the classification of pedicle screw spinal systems,
and the agency's tentative findings on the Panel's recommendations.
After considering any public comments on the Panel's recommendations
and FDA's proposed classification, in addition to any other relevant
information that bears on this action, FDA will publish a final
regulation classifying the device. This action is being taken because
the agency believes that there is sufficient information to establish
special controls that will provide reasonable assurance of its safety
and effectiveness.
DATES: Written comments by January 2, 1996.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, rm. 1-23, 12420 Parklawn Dr.,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Mark N. Melkerson, 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. Highlights of the Proposal
II. Background
III. Recommendations of the Orthopedic and Rehabilitation Devices
Panel
IV. FDA's Tentative Findings
V. Summary of Data Upon Which FDA's Findings are Based
VI. References
VII. Environmental Impact
VIII. Analysis of Impacts
IX. Comments
I. Highlights of the Proposal
FDA is issuing for public comment several recommendations of the
Panel concerning the classification of pedicle screw spinal systems.
The Panel recommended that FDA classify into class II the unclassified
preamendments pedicle screw spinal system intended for the treatment of
severe spondylolisthesis (grades 3 and 4) of the fifth lumbar vertebra
in patients receiving fusion by autogenous bone graft having implants
attached to the lumbar and sacral spine with removal of the implant
after the attainment of a solid fusion. The Panel also recommended that
FDA reclassify the postamendments pedicle screw spinal system intended
for degenerative spondylolisthesis and spinal trauma from class III to
class II. For all other indications, pedicle screw spinal systems are
considered postamendments class III devices for which premarket
approval is required. The Panel made its recommendations after
reviewing information presented at two public meetings on August 20,
1993 and July 23, 1994, and after reviewing information which was
solicited in response to an April 3, 1995, letter. FDA is also issuing
for public comment its tentative findings on the Panel's
recommendations. FDA is proposing to expand the intended uses of the
device identified by the Panel to include pedicle screw spinal systems
intended to provide immobilization and stabilization of spinal segments
as an adjunct to fusion in the treatment of acute and chronic
instabilities and deformities, including spondylolisthesis, fractures
and dislocations, scoliosis, kyphosis, and spinal tumors. Finally, FDA
is proposing to codify the classification of both the preamendments and
the postamendments device in one regulation. Comments received in
response to this proposed rule, along with other relevant information
that the agency may obtain, will be relied upon by the agency in
formulating a final position on each of the foregoing issues and
provide the basis for a final agency regulation.
II. Background
The Federal Food, Drug, and Cosmetic Act (the act), as amended by
the Medical Device Amendments of 1976 (the 1976 amendments) and the
Safe Medical Devices Act of 1990 (the SMDA) 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 are as follows: Class I, general controls; class II,
special controls; and class III, premarket approval. Devices that were
in commercial distribution before May 28, 1976 (the date of enactment
of the amendments) are classified under section 513 of the act (21
U.S.C. 360c) 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. A device that is first offered for commercial
distribution after May 28, 1976, and is substantially equivalent to a
device classified under this scheme, is also classified into the same
class as the device to which it is substantially equivalent.
A device that was not in commercial distribution prior to May 28,
1976, and that is not substantially equivalent to a preamendments
device, is classified by statute into class III without any FDA
rulemaking proceedings. The agency determines whether new devices are
substantially equivalent to previously offered devices by means of the
premarket notification procedure in section 510(k) of the act (21
U.S.C. 360(k)) and part 807 of the regulations (21 CFR part 807).
The pedicle screw spinal system intended for indications other than
severe spondylolisthesis is a postamendment device classified into
class III under section 513 (f) of the act (21 U.S.C. 360c(f)). In
accordance with sections 513(e) and (f) of the act and 21 CFR 860.134,
based on new information with respect to the device, FDA, on its own
initiative, is proposing to reclassify this device from class III to
class II when intended to provide immobilization and stabilization of
spinal segments as an adjunct to fusion in the treatment of acute and
chronic instabilities and deformities, including spondylolisthesis,
fractures and dislocations, scoliosis, kyphosis, and
[[Page 51947]]
spinal tumors. Such intended uses encompass both degenerative
spondylolisthesis and spinal trauma. In addition, FDA is proposing to
classify the preamendments pedicle screw spinal system intended for the
treatment of severe spondylolisthesis into class II, in accordance with
section 513(d) of the act and 21 CFR 860.84.
FDA is proposing to place the pedicle screw spinal system in class
II because it believes that there is sufficient information to
establish special controls to provide reasonable assurance of its
safety and effectiveness.
Two categories of spinal fixation implants that were in commercial
distribution prior to the date of enactment of the amendments have been
classified into class II: Posterior hook-rod fixation devices
(classification: 21 CFR 888.3050, Spinal interlaminal fixation
orthosis) and anterior plate-screw-cable fixation devices
(classification: 21 CFR 888.3060, Spinal intervertebral body fixation
orthosis). In addition, bone plates and screws were placed into class
II when intended for general orthopedic use in long bone fracture
fixation (classifications: 21 CFR 888.3030, Single/multiple component
metallic bone fixation appliances and accessories). However, bone
plates and screws were considered postamendments class III devices when
incorporated into pedicle screw spinal systems. This proposal does not
affect the classification of those devices.
Pedicle screw spinal systems include a broad category of multiple
component implants. The first premarket notification submission
(510(k)) for a multiple component device system intended for attachment
to the spine via the pedicles of the vertebrae was submitted to FDA for
marketing clearance in 1984. FDA determined that the device was not
substantially equivalent to the following devices: (1) Single/multiple
component metallic bone fixation appliances and accessories intended
for long bone fracture fixation; and (2) interlaminal spinal fixation
device systems that attached to the spine via sublaminar wiring or
interlaminal hooks. FDA's decision was based on the fact that the
sponsor had not established that there was a preamendments device
incorporating pedicle screw components and that the device posed
potential risks not exhibited by other spinal fixation systems, such as
a greater chance of neurological deficit due to imprecise screw
placement or the event of a screw failure; pedicle fracture during
placement of screws; soft tissue damage or inadequate fusion due to
bending or fracture of device components; and greater risk of
pseudarthrosis due to instability of the device design. Because they
were not found to be substantially equivalent to a preamendments
device, these systems were automatically classified into class III
under section 513(f)(1) of the act.
In 1985, in response to another 510(k), FDA determined that the
interlaminal spinal fixation device (i.e., rods and hooks and/or
sublaminar wires) with screws attached to the sacrum was substantially
equivalent to the class II interlaminal spinal fixation device with
hooks supported on a rod threaded into the iliac crests (21 CFR
888.3050). However, when the same device was fixed to the pedicles, FDA
determined that the device was not substantially equivalent to the
spinal interlaminal fixation orthosis (21 CFR 888.3050) and is
therefore a postamendments class III device.
Clinical investigations of pedicle screw spinal systems under
investigational device exemption (IDE) protocols began in 1985. No
premarket approval application has been brought before the advisory
panel or approved to date.
By mid-1992, FDA discovered that the use of pedicle screw spinal
systems outside of approved IDE studies was widespread, and that
pedicle screw fixation was considered to be the standard of care by the
surgical community. To obtain guidance in resolving this issue in the
best interests of the public health, FDA convened an advisory panel
meeting on August 20, 1993, to review the available information
pertaining to the safety and effectiveness of the device. Mechanical
testing data, summaries of clinical studies conducted under FDA-
approved IDE protocols, and presentations by experts in the field were
presented to the Panel. After reviewing the information, the Panel
concluded that pedicle screw spinal devices appear to be safe and
effective when used as adjuncts to spinal fusion procedures, but that
additional clinical information was needed in order to determine what
regulatory controls should be required to provide reasonable assurance
of their safety and effectiveness.
During a February 1993 meeting, FDA requested the orthopedic
professional societies and spinal implant manufacturers to submit to
FDA all available valid scientific data on the performance of pedicle
screw spinal devices. In response, the Spinal Implant Manufacturers
Group (SIMG) was formed to provide the financing for a nationwide study
of the pedicle screw device. The SIMG consists of representatives from
the American Academy of Orthopedic Surgeons, the Scoliosis Research
Society, the North American Spine Society, the American Association of
Neurological Surgeons, the Congress of Neurological Surgeons, and 25
manufacturers of spinal implant systems. The Scientific Committee of
the SIMG, consisting of surgeons and scientists, was formed
specifically to develop and implement a uniform research protocol to
gather clinical experience from the use of the device. FDA also
provided extensive input into the design of the study protocol. With
the permission of individual IDE sponsors, FDA's scientific staff
provided the Scientific Committee with information about current IDE
clinical investigations, the types of diagnostic groups being studied,
the patient inclusion and exclusion criteria utilized, the outcome
variables under study, and insight into the types of problems
encountered with these studies. FDA also made recommendations regarding
the feasibility of various study designs, including an historical
cohort model. Finally, FDA provided the Scientific Committee with
extensive advice regarding statistical analysis of the data, validation
of data, reduction of study bias, and sample size calculations. The
Scientific Committee then conducted a nationwide historical cohort
study according to this research protocol.
The Panel met on August 20, 1993, and July 22, 1994, in open public
meetings to discuss the postamendments pedicle screw spinal system. At
the July 22, 1994, meeting, new information was presented to the Panel
by FDA and others, and recommendations were solicited from the Panel
regarding the classification of pedicle screw spinal systems. During
this meeting, the Panel heard testimony from FDA, the medical and
scientific communities, manufacturers, and the public regarding the
safety and effectiveness of the device. At this meeting, the SIMG
presented clinical data from its nationwide ``Historical Cohort Study
of Pedicle Screw Fixation in Thoracic, Lumbar, and Sacral Spinal
Fusions'' (Cohort study). FDA presented a comprehensive review of the
medical literature, an analysis of the Cohort study conducted by the
SIMG, and a summary of the clinical data that had been released by IDE
sponsors. Presentations of two meta-analyses of the literature
pertaining to the clinical performance of the device were given by
spinal surgeons. In addition, 38 persons gave presentations during the
public comment portion of the panel meeting. Patients who had had
spinal fusion
[[Page 51948]]
surgery with pedicle screw instrumentation gave personal testimonies of
their experiences with the device, citing both successes and failures.
Several litigation attorneys, representing patients involved in class
action lawsuits against spinal implant manufacturers, addressed the
Panel with their views. Five spine surgeons gave their professional
opinions regarding the usefulness of the pedicle screw device in their
practices. Three surgeons representing spinal professional societies
presented their societies' viewpoints.
At the conclusion of the July 22, 1994, meeting, the Panel
recommended that FDA reclassify the generic type of device from class
III into class II when intended for the treatment of degenerative
spondylolisthesis and spinal trauma. The Panel recommended further that
FDA adopt special controls as deemed necessary by FDA under
513(a)(1)(B) of the act, and that FDA assign a low priority for the
establishment of a performance standard for this generic type of device
under section 514 of the act (21 U.S.C. 360d).
Since 1986, a number of manufacturers have sought to demonstrate
that the pedicle screw spinal system is a preamendments device, that
is, that it was commercially available prior to May 28, 1976, the
enactment date of the 1976 amendments. In a 510(k) dated December 22,
1994, Sofamor Danek, Inc., provided sufficient evidence of the
preamendments commercial distribution of a spinal system that utilized
pedicle screws. In a letter to Sofamor Danek, Inc., dated January 20,
1995, FDA acknowledged that sufficient evidence now exists documenting
that pedicle screw spinal systems were commercially available prior to
May 28, 1976. The preamendments pedicle screw spinal fixation device
system consisted of hooks, spinal rods, threaded sacral rods, and
pedicle screws connected to the rods with wire. The device was intended
only for lumbar and sacral spine fusions using autogenous bone graft in
patients with severe spondylolisthesis (grades 3 and 4) with removal of
the device after spinal fusion was achieved. On January 20, 1995, the
first postamendments pedicle screw spinal system was found to be
substantially equivalent to the preamendments device. Based on this new
information, FDA has determined that the pedicle screw spinal system is
an unclassified preamendments device when indicated for autogenous bone
graft fusions of the fifth lumbar vertebra to the sacrum in patients
with severe spondylolisthesis (grades 3 and 4) at L5-S1 with
removal of the device after fusion has been achieved. In a letter,
dated April 3, 1995, FDA asked the Panel to provide its recommendations
on the classification of this preamendments device. The Panel
unanimously recommended that the preamendments pedicle screw spinal
system be classified into class II when intended for autogenous bone
graft fusions of the fifth lumbar vertebra to the sacrum in patients
with severe spondylolisthesis (grades 3 and 4) at L5-S1 with
removal of the device after fusion has been achieved.
In this document, FDA is publishing the recommendations of the
Panel with respect to classification of the preamendments device and
reclassification of the postamendments device. FDA is also proposing to
classify both the preamendments and postamendments devices into class
II, and to codify them in one regulation.
III. Recommendations of the Orthopedic and Rehabilitation Devices
Palen
The Orthopedic and Rehabilitation Devices Panel, an FDA advisory
panel, made the following recommendations regarding the classification
of the pedicle screw spinal system:
(1) Identification. A pedicle screw spinal system is a multiple
component device, made of alloys such as 316L stainless steel (Ref.
11), 316LVM stainless steel (Ref. 11), 22Cr-13Ni-5Mn stainless steel
(Ref. 12), unalloyed titanium (Ref. 9), and Ti-6Al-4V (Ref. 10), that
allows the surgeon to build an implant system to fit the patient's
anatomical and physiological requirements. A spinal implant assembly
consists of anchors (e.g., bolts, hooks, and screws); interconnection
mechanisms incorporating nuts, screws, sleeves, or bolts; longitudinal
members (e.g., plates, rods, and plate/rod combinations); and
transverse connectors. The device is used primarily in the treatment of
acute and chronic instabilities and deformities, such as trauma, tumor,
or degenerative spondylolisthesis.
(2) Classification recommendation. Class II (special controls). The
Panel recommended that the establishment of a performance standard be
low priority.
(3) Summary of reasons for recommendation. The Orthopedic and
Rehabilitation Devices Panel recommended that pedicle screw spinal
systems be classified into class II because the Panel believed that
general controls by themselves are insufficient to provide reasonable
assurance of the safety and effectiveness of the device, but that there
is sufficient information to establish special controls to provide such
assurance. The Panel also believed that premarket approval is not
necessary to provide reasonable assurance of the safety and
effectiveness of the device. The Panel believed that public information
demonstrates that the risks to health have been characterized and can
be controlled. The Panel also believed that the relationship between
these risks and the device's performance parameters have been
established and are sufficiently understood to assure the safety and
effectiveness of the device. Furthermore, the Panel recognized that
there exist voluntary standards and test methods with respect to the
production of the device.
(4) Summary of data on which the recommendation is based. The
Orthopedics and Rehabilitation Devices Panel based its recommendation
on the Panel members' personal knowledge of, and clinical experience
with, the device and presentations at the open panel meeting. The Panel
noted that, based upon clinical data from the Cohort study, IDE
clinical investigations, and the literature, pedicle screw spinal
systems performed at least equivalent to, and in some instances
superior to, currently available class II anterior and posterior spinal
fixation devices, as well as to treatments not utilizing internal
fixation devices for degenerative spondylolisthesis and trauma.
The Panel noted that, based on the Cohort study, clinical
investigations under IDE protocols and studies available from the
scientific literature, the use of pedicle screw spinal systems, when
intended for the treatment of degenerative spondylolisthesis and spinal
trauma, produced statistically significantly higher spinal fusion rates
than when no fixation or nonpedicle screw spinal fixation was used. In
addition, the Panel believed that these studies demonstrated
statistically significant improvements in patients' clinical outcomes
in terms of pain, function, and neurologic status. The Panel believed
that these studies demonstrated significant technical and clinical
advantages from the use of the device (Ref. 66).
According to the Panel, the mechanical testing data presented at
the August 20, 1993, panel meeting demonstrated that pedicle screw
spinal systems exhibit adequate mechanical strength, rigidity, and
fatigue resistance for the expected length of time required to
stabilize the spine to allow fusion to occur (Ref. 65).
The Panel concluded that the data presented at the July 22, 1994,
panel meeting provided clinical evidence that the device was effective
in stabilizing
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the spine in spinal fusions for degenerative spondylolisthesis and
spinal trauma. The Panel also determined that the incidence rates of
device breakage, deformation, and loosening were similar to those of
commercially available device systems and that the rates were
clinically acceptable. The types of device-related complications for
pedicle screw spinal systems reported to FDA under the MedWatch device
reporting program were comparable to those reported in clinical studies
and the medical literature for commercially available spinal systems
and included broken screws, neurologic injuries, and nonunions (Ref.
66).
The Panel did not find support in the literature or in clinical
data for use of the device in the treatment of low back pain. The Panel
specifically recommended that low back pain should not be included in
the indications for use of the device until clinical data justify its
inclusion (Ref. 66).
The Panel believed that the primary risks to health associated with
pedicle screw spinal systems are similar to those associated with other
class II spinal implant devices. The Panel believed that both clinical
and nonclinical parameters need to be controlled to provide reasonable
assurance of the safety and effectiveness of the device. The primary
nonclinical parameters affecting safety and effectiveness are: (1)
Biocompatibility of the materials used in the manufacture of the
device; (2) device design; (3) device durability; (4) device strength,
and (5) device rigidity. The primary measures of clinical effectiveness
of the device are: (1) Fusion, (2) pain relief, (3) functional
improvement, and (4) neurologic status. These concerns are the same as
those associated with commercially available class II devices,
including posteriorly placed interlaminal spinal fixation orthoses (21
CFR 888.3050) and anteriorly placed spinal intervertebral body fixation
orthoses (21 CFR 888.3060).
The Panel reviewed the medical literature pertaining to the use of
pedicle screw spinal systems in the treatment of severe
spondylolisthesis (Refs. 5, 6, 14, 27, 28, 29, 30, 48, 52, 68, 81, 82,
83, 84, 92, 93, 147, 155, 159, 168, 169, 175, and 188) and determined
that the risks associated with the device are no different than those
associated with the use of the preamendments class II spinal fixation
devices or those associated with pedicle screw spinal systems intended
for the treatment of other acute or chronic instabilities and
deformities. The Panel concluded that the effectiveness of the device
is related to its mechanical strength and rigidity, which have been
demonstrated to be superior to existing class II devices.
(5) Risks to health. The following risks are associated with the
pedicle screw spinal system: (a) Mechanical failure. The screw may bend
or fracture, loosen or pull-out, the plate or rod may bend or fracture,
the connector may slip resulting in loss of fixation and loss of
reduction; (b) soft tissue injury. The risks of tissue injury include
screw over-penetration of the vertebral body with associated injury to
major blood vessels or viscera; pedicle fracture; nerve root injury;
spinal cord injury; cauda equina injury; dural tear or cerebrospinal
fluid leak; blood vessel injury; and bowel injury; (c) pseudarthrosis.
The risk of nonunion, or pseudarthrosis, signifies failure of bony
fusion and persistent instability; and (d) need for reoperation. The
risk of a possible reoperation includes reoperation for infection or
bleeding; revision surgery; removal of device components for device
failure, or symptomatic, painful, or prominent hardware; and
reoperations for other reasons not related to fusion, such as nerve
root decompression. In addition, there are theoretical risks, such as
device-related osteoporosis, metal allergy, particulate debris, and
metal toxicity, for which no reliable human data exist.
A. Safety and Effectiveness: Nonclinical
1. Biocompatibility of Materials
The biocompatibility of stainless steel and titanium metal alloys
used in the fabrication of pedicle screw spinal systems has been
investigated extensively with in vitro testing, implantation studies,
mechanical testing, toxicological testing, corrosion testing, and
clinical trials. These alloys have been demonstrated to be reasonably
safe for human usage under a variety of conditions. (Refs. 23, 33, 67,
105, 111, 134, 135, 179, 180, 182, and 197).
Stainless steels, such as 316 L, 316 LVM, and 22Cr-13Ni-5Mn alloys,
are susceptible to some degree of crevice, pitting, and stress
corrosion. The presence of corrosion products can produce a localized
chronic inflammatory response with granuloma formation, macrophage
engorgement with particulate matter, and focal areas of necrosis (Refs.
41, 67, 76, 111, 167, 179, and 197). Metallic ion species from leaching
or corrosion can produce allergic responses (Refs. 61, 67, 120, and
148). These are recognized and well-described tissue reactions to
stainless steel implants and metal ions. Nevertheless, stainless steels
have been used extensively with great clinical success for the
fabrication of surgical implants, including bone plates, bone screws,
and intramedullary rods. The biocompatibility of stainless steels has
been regarded as acceptable for implants at various anatomic locations
under different pathophysiologic conditions (Refs. 38, 67, 105, 134,
135, 157, 158, 165, 179, and 181).
The corrosion resistance of commercially pure (CP) titanium and Ti-
6Al-4V alloy has been well-documented through in vitro testing,
implantation studies, toxicological testing, corrosion testing, and
clinical trials. Titanium and its alloys are susceptible to wear as
well as corrosion, and thus may cause black discoloration of
surrounding tissues and induce aseptic local fibrosis (Refs. 33, 42,
115, 121, 129, 139, 197, and 198). In the soft tissue surrounding
titanium alloy orthopedic implants, T-lymphocytes in association with
macrophages have been observed, implying an immunological response to
the debris (Ref. 103). Macrophage release of bone-resorbing mediators
in association with titanium wear debris has also been demonstrated
(Ref. 85). The significance of these observations regarding the
biologic and toxicologic effects of titanium ions and wear particles in
spinal fusion is uncertain since these tissue reactions have been
observed only in closed joint systems, such as hip replacements (Refs.
121 and 129). Despite these tissue responses, CP titanium and titanium
alloys are still considered relatively safe biomaterials, and may be
effectively used with minimal risk when not used as the articulating
surface, which leads to the generation of large amounts of wear debris
(Refs. 42, 121, 129, 139, 196, 197, and 198). Titanium and its alloys
have been used extensively as implant materials since the mid-1960's
for the fabrication of implants such as bone plates, bone screws, and
hip implants (Refs. 105, 129, 182, 196, 197, and 198).
All available metallic implant materials are imperfect
biomaterials. In the trade-off between the theoretical risks arising
from metal ion release, corrosion products, and wear debris, and the
known benefits of these materials, it appears that both stainless steel
and titanium alloys are acceptable for human implantation in the spinal
environment.
The Panel believed that the biocompatibility specifications of
existing voluntary standards provide reasonable assurance of the safety
and effectiveness of devices manufactured of
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metals and metallic alloys (Refs. 65 and 66).
2. Mechanical Properties of the Device
It has been demonstrated that the multiple component pedicle screw
spinal systems perform as well as other commercially available spinal
fixation device systems in various modes and frequencies of loading
(Refs. 8, 21, 45, 63, 67, 71, 73, 77, 98, 99, 100, 136, 137, 138, 142,
143, 144, 146, and 184).
Sufficient test methods exist to enable the evaluation of fatigue
strengths and tensile, torsional, and bending strengths of the pedicle
screw spinal fixation systems to assure its safety and effectiveness
during the period of time needed for fusion to occur (Refs. 8, 13, 21,
45, 66, 72, and 78). There is adequate mechanical testing data for the
pedicle screw spinal system for which clinical data was presented at
the July 22, 1994, panel meeting. For example, one of the pedicle
screw-plate systems had a static bending strength of 807.8 N, stiffness
of 123.7 KN/M, and flexibility of 8.18 x 10-3 M/KN (Ref. 45). In
cyclic fatigue testing, the same system endured 10 6 cycles with a
400 N load, 10 6 cycles with a 500 N load, and 212,960 cycles with
a 600 N load (Ref. 45). Pedicle screw-rod systems have reported static
bending strengths ranging from 544.9 to 1,289 N, stiffnesses ranging
from 136.9 to 153.2 KN/M, and flexibilities ranging from 6.53 to 7.32
( x 10-3) M/KN (Ref. 45). In cyclic fatigue testing, the pedicle
screw-rod fixation device systems have endured 10 6 cycles with a
400 N load, 202,769 to 10 6 cycles with a 500 N load, and 135,017
to 799,544 cycles with a 600 N load (Ref. 45).
B. Safety and Effectiveness: Clinical
The Panel based its recommendations on valid scientific evidence
from the Cohort study, IDE clinical investigations, and the medical
literature. These data sources allowed the Panel to evaluate the safety
and effectiveness of pedicle screw spinal systems in terms of
mechanical failure, soft tissue injury, pseudarthrosis, reoperation,
fusion, pain, function, and neurologic status, as well as other
potential harmful and beneficial effects of these devices.
Representatives of the SIMG presented the results of the Cohort
study at the July 22, 1994, panel meeting. The Cohort study was an
open, nonblinded, historical cohort study (Ref. 201). It was designed
to recruit a maximum number of surgeons who would voluntarily
participate by collecting clinical data on patients who had undergone
spinal fusions. Physicians were recruited through announcements at
professional society meetings and direct mailings to professional
society memberships. Clinical data were collected from medical records
of patients who had undergone spinal fusions during the period January
1, 1990, to December 31, 1991. This window was chosen to allow an
adequate number of patients with a theoretical minimum followup of 2
years up to the time of the study onset. The concurrent control groups
consisted of patients with identical entry criteria who had been
operated on during the same time window (1/1/90-12/31/91). These
control patients were either fused without instrumentation
(noninstrumented) or were fused and instrumented with a control device
(nonpedicle screw instrumentation). The data collection protocol was
identical to that used for the study group.
Three hundred fourteen surgeons voluntarily participated in this
study and contributed a total of 3,500 patients: 2,685 patients in the
Degenerative Spondylolisthesis group and 815 patients in the Fracture
(spinal trauma) group. In the Degenerative Spondylolisthesis group, the
2,685 patients were stratified by treatment: 2,177 patients were
treated with pedicle screw instrumented fusions, 51 patients with
nonpedicle screw instrumented fusion, and 457 patients with
noninstrumented fusion. Similarly, in the Fracture group, the 815
patients were stratified by treatment: 587 patients were treated with
pedicle screw instrumented fusions, 221 patients with nonpedicle screw
instrumented fusion, and 7 patients with noninstrumented fusion.
Data from three clinical evaluation periods were collected from
each patient record: Preoperatively, immediately postoperatively, and
at the final evaluation which ranged from six months to two years
postoperatively. The preoperative data included the patient's age,
gender, weight, primary diagnosis, involved levels, identification of
known prognostic variables (e.g., prior back surgery), and levels of
pain, function, and neurologic status. Information regarding the
operative procedure included the date of operation, type of bone
grafting (if any), the levels instrumented and fused, the name of the
pedicle screw device, and the number of each of the relevant components
(e.g., rods, screws, connectors). Data collected at the final
evaluation time point included the date of the last clinical and
radiographic evaluations; fusion status; the date fusion was first
diagnosed; maintenance of alignment; and neurologic, functional, and
pain assessments. Intraoperative and postoperative adverse events and
the incidence and cause of reoperations were recorded.
Ten prospective IDE clinical trials for multiple indications were
analyzed. Five studies involving the treatment of degenerative
spondylolisthesis (n = 268) and two studies involving the treatment of
spinal fracture (n = 27) were compared to the results of the Cohort
study and were presented to the Panel (Ref. 66).
A comprehensive search of the English-language medical literature
from 1984 to the present was performed. One hundred one articles
pertained to clinical performance of pedicle screw devices and were
selected for inclusion in this review (Ref. 66). Only articles
appearing in peer-reviewed journals were included. Meta-analyses of the
medical literature for degenerative spondylolisthesis and spinal trauma
were conducted and presented (Refs. 51, 66, and 119).
These data were analyzed and presented at the July 22, 1994, panel
meeting.
1. Mechanical Failure
The Cohort study provided the incidence of mechanical device
failures related to treatment with pedicle screw spinal systems,
nonpedicle screw instrumentation, and noninstrumented fusion (Refs. 66
and 201). For the fracture group (n = 586), the pedicle screw group had
a mechanical failure rate of 9.7 percent, compared to a 1.9 percent
failure rate in the nonpedicle screw group. For the pedicle screw
group, the incidence of screw fracture was 6.7 percent, screw loosening
2.1 percent, rod/plate fracture 0.3 percent, and connector loosening
(slippage) 0.2 percent. For the nonpedicle screw group (n = 221), the
incidence of rod/plate fracture was 0.9 percent, hook pull-out 0.5
percent, and connector slippage 0.5 percent
For the degenerative spondylolisthesis group, the device mechanical
failure rate was 7.8 percent in the pedicle screw group (n = 2,153).
The most frequent events for the pedicle screw group were screw
loosening (2.8 percent), screw fractures (2.6 percent), rod or plate
fractures (0.7 percent), and connector loosening (slippage) (0.7
percent). Mechanical device failures were not possible in the
noninstrumented group because a surgical technique, not an instrument
technique, was utilized.
The overall incidence of mechanical device failures in the IDE
clinical investigations (n = 2,431) was 0.7 to 3.7 percent (mean = 1.2
percent) (Ref. 66). For all investigational pedicle screw
[[Page 51951]]
spinal systems reported, the incidence of rod/plate fractures for
degenerative spondylolisthesis was 0.0 to 7.1 percent (mean = 1.5
percent), for fractures 0.0 percent, for degenerative disc disease 0.0
to 4.0 percent (mean = 1.1 percent), for scoliosis 0.0 to 9.1 percent
(mean = 0.9 percent), for failed back syndrome 0.0 to 2.7 percent (mean
= 0.3 percent), and for spinal stenosis 0.0 to 7.7 percent (mean = 5.0
percent) (Ref. 66). The incidence of screw fractures for degenerative
spondylolisthesis was 0.0 to 18.6 percent (mean = 6.2 percent), for
fractures 20.0 to 28.6 percent (mean = 22.2 percent), for degenerative
disc disease 0.0 to 2.7 percent (mean = 0.6 percent), for scoliosis 1.8
percent, for failed back syndrome 0.0 to 3.4 percent (mean = 2.4
percent), and for spinal stenosis 0.0 to 14.3 percent (mean = 3.0
percent). The incidence of screw loosening or pull-out for degenerative
spondylolisthesis was 0.0 to 9.3 percent (mean = 0.9 percent), for
fractures 0.0 to 5.0 percent (mean = 3.7 percent), for degenerative
disc disease 0.0 to 7.4 percent (mean = 0.7 percent), for scoliosis 0.0
to 3.5 percent (mean = 1.8 percent), for failed back syndrome 0.0 to
12.1 percent (mean = 1.6 percent), and for spinal stenosis 0.0 percent.
The incidence of connector loosening was 0.0 percent for degenerative
spondylolisthesis, fractures, scoliosis, and spinal stenosis, 0.0 to
2.1 percent (mean = 0.4 percent) for degenerative disc disease, and 0.1
percent for failed back syndrome.
A low rate of mechanical failure of pedicle screw fixation devices,
when used in multiple indications, is further documented by the medical
literature (Refs. 3, 5, 19, 22, 24, 32, 35, 37, 43, 47, 50, 58, 59, 60,
73, 77, 79, 87, 89, 90, 94, 95, 107, 109, 110, 113, 116, 122, 125, 150,
151, 152, 162, 163, 164, 173, 183, 185, 186, 187, 191, 192, 193, and
203). A meta-analysis of 58 clinical studies revealed no differences
between pedicle screw fixation (n = 641), hook-rod fixation (n = 1128),
anterior fixation (n = 255), and sublaminar wire-rod fixation (n = 48)
groups in the rate of mechanical device failures (Refs. 51 and 119).
Survivorship analysis of pedicle screw device failures (defined as
screw bending or breaking, infection, device loosening, rod or plate
hardware problems, or neurologic complication requiring device removal)
in patients treated for spondylolisthesis, postlaminectomy instability,
pseudarthrosis, trauma, scoliosis, and tumor demonstrated a 90 percent
survival of the instrumentation at 20 months, and 80 percent survival
at 5 to 10 years (Ref. 124). The cumulative survivorship at 1 year was
84.0 percent and 91.3 percent for two devices used in the treatment of
patients diagnosed with degenerative isthmic spondylolisthesis,
degenerative segmental instability, and degenerative lumbar scoliosis
(Ref. 26). Survivorship analysis performed on thoracolumbar burst
fractures treated with pedicle screw fixation also demonstrated high
survival rates for the implants: 100 percent at 22.4 months and 75
percent from 22.4 to 32 months (54).
2. Soft Tissue Injury
The incidence of device-related soft tissue injuries associated
with the use of pedicle screw spinal systems for both degenerative
spondylolisthesis and fracture groups is comparable to that associated
with nonpedicle screw instrumented fusions and noninstrumented fusions
(Refs. 66 and 201). Clinical studies have documented 0.1 percent and
0.2 percent rates of vascular injuries related to the use of pedicle
screw spinal systems for the degenerative spondylolisthesis and
fracture groups, respectively, and no visceral (intestinal) injuries
for those groups. There were no differences found between treatment
groups for intraoperative and postoperative neurological injuries,
including nerve root and spinal cord injuries, as well as new radicular
pain. For the degenerative spondylolisthesis and fracture groups,
intraoperative nerve root injuries occurred in 0.4 percent and 0.2
percent of cases, respectively; intraoperative spinal cord injuries
occurred in 0.1 percent and 0.2 percent of cases, respectively;
postoperative radicular pain or deficits in 4.8 percent and 0.9 percent
of cases, respectively; intraoperative device-related dural tears in
0.1 percent and 0.7 percent of cases, respectively; and postoperative
dural tears or leaks in 0.3 percent and 0.0 percent of cases,
respectively (Refs. 66 and 201).
The data released from the IDE clinical investigations reported an
overall vascular injury rate of 0.7 percent; an intraoperative nerve
root injury rate of 0.1 percent; a wound infection rate of 3.7 percent;
a postoperative radicular pain or deficit rate of 2.2 percent; and a
rate of postoperative dural tears or leaks of 0.8 percent. In these
investigations, intraoperative spinal cord injuries did not occur (Ref.
66).
The medical literature documents a low incidence of soft tissue
injuries related directly to the device when used in the treatment of
fractures (Refs. 46, 49, 74, 106, 127, and 153), degenerative
spondylolisthesis (Refs. 26, 27, 37, 49, 60, 113, 183, 185, 187, 191,
and 192), isthmic spondylolisthesis (Ref. 147), degenerative disc
disease (Refs. 47, 60, 113, 183, 187, 191, and 192), deformities (Ref.
25), scoliosis (Refs. 43 and 116), tumors (Ref. 126), spinal stenosis
(Ref. 173), and multiple diagnoses (Refs. 112 and 122). A meta-analysis
of the medical literature for treatment of degenerative
spondylolisthesis and fracture demonstrates no differences in the rates
of intraoperative and postoperative adverse events related to soft
tissue injuries among pedicle screw fixation, hook-rod fixation,
anterior fixation, and sublaminar wire-rod fixation treatment groups (p
< 0.05)="" (refs.="" 51="" and="" 119).="" these="" soft="" tissue="" injuries="" appear="" to="" be="" related="" to="" the="" surgical="" procedure,="" rather="" than="" the="" device="" itself.="" misdirected="" pedicle="" screws="" can="" cause="" pedicle="" fracture,="" screw="" cutout,="" or="" screw="" penetration="" of="" the="" pedicle,="" potentially="" causing="" nerve="" root="" or="" spinal="" cord="" injuries,="" dural="" tears,="" or="" canal="" stenosis="" (refs.="" 152,="" 166,="" 171,="" and="" 189).="" meticulous="" surgical="" technique="" and="" attention="" to="" detail="" appear="" to="" minimize="" these="" adverse="" events="" (refs.="" 24,="" 47,="" 60,="" 79,="" 90,="" and="" 190).="" pedicle="" screws="" too="" large="" for="" the="" pedicle="" diameter="" can="" cause="" pedicle="" fracture.="" likewise,="" over="" penetration="" of="" pedicle="" screws="" through="" the="" vertebral="" body="" from="" pedicle="" screws="" too="" long="" for="" the="" anterior-posterior="" dimensions="" of="" the="" vertebrae="" can="" cause="" retroperitoneal="" vascular="" or="" visceral="" injury="" (refs.="" 101,="" 106,="" and="" 204).="" thus,="" selection="" of="" the="" appropriate="" size="" of="" the="" pedicle="" screw="" is="" critical="" to="" prevent="" these="" injuries="" (refs.="" 64="" and="" 190).="" operative="" technique="" guidelines="" have="" been="" developed="" to="" assure="" accurate="" placement="" of="" pedicle="" screws="" and="" minimize="" operative="" complications="" (refs.="" 16,="" 56,="" 149,="" 164,="" and="" 172).="" in="" addition,="" the="" relevant="" surgical="" anatomy="" of="" the="" thoracic,="" lumbar,="" and="" sacral="" spine,="" including="" the="" pedicle="" dimensions="" and="" orientation,="" as="" well="" as="" surrounding="" soft="" tissue="" structures,="" have="" been="" thoroughly="" described="" in="" the="" medical="" literature="" (refs.="" 7,="" 15,="" 20,="" 57,="" 62,="" 64,="" 69,="" 75,="" 87,="" 88,="" 91,="" 101,="" 102,="" 106,="" 117,="" 131,="" 132,="" 133,="" 141,="" 145,="" 156,="" 161,="" 166,="" 171,="" 176,="" 177,="" 189,="" 190,="" 195,="" 199,="" and="" 204).="" 3.="" pseudarthrosis="" in="" the="" cohort="" study,="" radiographic="" data="" were="" available="" to="" determine="" the="" fusion="" status="" for="" 1,794="" patients="" in="" the="" pedicle="" screw="" group="" and="" 382="" patients="" in="" the="" noninstrumented="" group="" for="" the="" treatment="" of="" degenerative="" spondylolisthesis,="" and="" 506="" patients="" in="" the="" pedicle="" screw="" group="" and="" 184="" patients="" in="" the="" nonpedicle="" screw="" group="" for="" the="" treatment="" of="" fracture.="" there="" was="" a="" statistically="" significant="" reduction="" in="" [[page="" 51952]]="" the="" incidence="" of="" pseudarthrosis="" in="" the="" degenerative="" spondylolisthesis="" group="" when="" treated="" with="" pedicle="" screw="" fixation="" (3.7="" percent)="" compared="" to="" treatment="" without="" instrumentation="" (17.0="" percent)="" (p="">< 0.001).="" however,="" there="" was="" no="" significant="" difference="" in="" the="" incidence="" of="" pseudarthrosis="" associated="" with="" the="" use="" of="" pedicle="" screw="" fixation="" in="" treating="" fractures="" (1.8="" percent)="" compared="" to="" treatment="" with="" nonpedicle="" screw="" fixation="" devices="" (3.3="" percent)="" (p="0.18)" (refs.="" 66="" and="" 201).="" in="" the="" data="" released="" from="" the="" ide="" clinical="" investigations,="" the="" incidence="" of="" pseudarthrosis="" for="" degenerative="" spondylolisthesis="" was="" 0.0="" to="" 44.0="" percent="" (mean="12.6" percent),="" for="" fractures="" 10.0="" to="" 14.3="" percent="" (mean="11.1" percent),="" for="" degenerative="" disc="" disease="" 0.0="" to="" 37.0="" percent="" (mean="8.4" percent),="" for="" scoliosis="" 0.0="" to="" 36.4="" percent="" (mean="3.7" percent),="" for="" ``failed="" back="" syndrome''="" 0.0="" to="" 47.2="" percent="" (mean="12.6" percent),="" and="" for="" spinal="" stenosis="" 5.1="" to="" 14.3="" percent="" (mean="13.0" percent)="" (ref.="" 66).="" the="" medical="" literature="" similarly="" documents="" a="" low="" incidence="" of="" pseudarthrosis="" in="" those="" treated="" with="" pedicle="" screw="" spinal="" systems="" for="" fractures="" (refs.="" 3,="" 17,="" 34,="" 35,="" 36,="" 47,="" 80,="" 153,="" and="" 154),="" degenerative="" spondylolisthesis="" (refs.="" 32,="" 37,="" 96,="" 125,="" 173,="" and="" 174),="" deformities="" (ref.="" 25),="" degenerative="" spondylosis="" (refs.="" 22,="" 24,="" 169,="" and="" 194),="" degenerative="" disc="" disease="" (ref.="" 205),="" and="" tumor="" (refs.="" 50="" and="" 126).="" survivorship="" analysis="" for="" pseudarthrosis="" demonstrated="" a="" 98="" percent="" fusion="" rate="" at="" one="" year,="" 97="" percent="" at="" 12="" to="" 20="" months,="" 96="" percent="" at="" 21="" to="" 30="" months,="" and="" 93="" percent="" at="" 31="" to="" 40="" months="" (ref.="" 124).="" 4.="" reoperation="" reoperations="" were="" necessary="" in="" 17.6="" percent="" and="" 23.2="" percent="" of="" cases,="" respectively,="" for="" the="" degenerative="" spondylolisthesis="" and="" fracture="" groups="" in="" the="" cohort="" study="" (refs.="" 66="" and="" 201).="" device="" removals="" constituted="" the="" vast="" majority="" of="" reoperation="" procedures:="" 270="" of="" 379="" (71.2="" percent)="" patients="" with="" reoperations="" in="" the="" degenerative="" spondylolisthesis="" group,="" and="" 109="" of="" 136="" (80.1="" percent)="" patients="" with="" reoperations="" in="" the="" fracture="" group.="" most="" device="" removals="" were="" performed="" for="" pain,="" irritation,="" or="" prominence="" of="" the="" device="" (6.3="" percent="" and="" 7.2="" percent="" in="" the="" degenerative="" spondylolisthesis="" and="" fracture="" groups,="" respectively).="" only="" a="" small="" percentage="" of="" the="" devices="" were="" removed="" for="" device="" failure="" (0.6="" percent="" and="" 1.5="" percent="" in="" the="" degenerative="" spondylolisthesis="" and="" fracture="" groups,="" respectively).="" in="" the="" data="" released="" from="" the="" ide="" clinical="" investigations,="" the="" rates="" of="" reoperations="" reported="" for="" degenerative="" spondylolisthesis="" were="" 1.4="" to="" 13.2="" percent="" (mean="5.0" percent),="" for="" fractures="" 10.0="" to="" 14.3="" percent="" (mean="11.1" percent),="" for="" degenerative="" disc="" disease="" 1.4="" to="" 10.5="" percent="" (mean="2.3" percent),="" for="" scoliosis="" 2.3="" percent,="" for="" failed="" back="" syndrome="" 1.1="" to="" 8.8="" percent="" (mean="1.6" percent),="" and="" for="" spinal="" stenosis="" 5.1="" to="" 5.6="" percent="" (mean="5.0" percent)="" (ref.="" 66).="" the="" medical="" literature="" documents="" rates="" of="" device-related="" and="" nondevice="" related="" reoperations="" of="" 7.0="" percent="" to="" 24="" percent="" for="" pedicle="" screw="" fixation="" cases="" for="" a="" variety="" of="" conditions="" (refs.="" 50,="" 60,="" 86,="" and="" 173).="" meta-analysis="" of="" the="" literature="" demonstrated="" that="" the="" reoperation="" rate="" for="" the="" treatment="" of="" fractures="" with="" pedicle="" screw="" spinal="" systems="" (5.8="" percent)="" are="" comparable="" to="" the="" reoperation="" rates="" associated="" with="" hook-="" rod="" devices="" (8.9="" percent)="" and="" anterior="" devices="" (2.7="" percent)="" (refs.="" 51="" and="" 119).="" 5.="" fusion="" comparing="" the="" degenerative="" spondylolisthesis="" and="" fracture="" groups="" in="" the="" cohort="" study,="" patients="" treated="" with="" pedicle="" screw="" fixation="" had="" a="" significantly="" higher="" fusion="" rate="" (89.1="" percent="" and="" 88.5="" percent,="" respectively)="" than="" the="" nonpedicle="" (70.8="" percent="" and="" 81.0="" percent)="" and="" noninstrumented="" (70.4="" percent="" and="" 50.5="" percent)="" groups="" (p="">< 0.0001).="" using="" actuarial="" analysis,="" the="" time-adjusted="" rates="" of="" fusion="" for="" the="" degenerative="" spondylolisthesis="" group="" demonstrated="" that="" treatment="" with="" pedicle="" screw="" fixation="" was="" associated="" with="" a="" significantly="" greater="" rate="" of="" fusion="" than="" treatment="" with="" no="" instrumentation="" (82.5="" percent="" versus="" 74.5="" percent,="" p="">< 0.001).="" the="" time-adjusted="" rates="" of="" fusion="" for="" the="" fracture="" patient="" group="" demonstrated="" that="" there="" was="" no="" significant="" difference="" in="" the="" rates="" of="" fusion="" when="" comparing="" pedicle="" screw="" fixation="" and="" nonpedicle="" screw="" fixation.="" for="" the="" degenerative="" spondylolisthesis="" group,="" the="" rate="" of="" fusion="" was="" higher="" in="" those="" treated="" with="" pedicle="" screw="" fixation="" than="" in="" those="" treated="" without="" instrumentation="" at="" every="" time="" interval="" beyond="" 3="" months.="" these="" rates="" are="" evidence="" that="" fusion="" occurs="" faster="" in="" the="" pedicle="" group="" (refs.="" 66="" and="" 201).="" in="" the="" data="" released="" from="" clinical="" investigations="" performed="" under="" ide's,="" fusion="" rates="" associated="" with="" pedicle="" screw="" spinal="" systems="" were="" comparable="" to="" those="" associated="" with="" nonpedicle="" screw="" instrumentation="" and="" noninstrumentation.="" the="" fusion="" rates="" in="" patients="" with="" pedicle="" screw="" fixation="" were="" 82.1="" to="" 89.5="" percent="" (mean="87.8" percent)="" in="" the="" treatment="" of="" degenerative="" spondylolisthesis,="" 71.4="" to="" 80.0="" percent="" (mean="77.8" percent)="" for="" fractures,="" 82.9="" to="" 93.1="" percent="" (mean="85.9" percent)="" for="" degenerative="" disc="" disease,="" 96.5="" percent="" for="" scoliosis,="" 88.6="" to="" 94.7="" percent="" (mean="91.9" percent)="" for="" ``failed="" back="" syndrome,''="" and="" 85.7="" to="" 92.3="" percent="" (mean="91.3" percent)="" for="" spinal="" stenosis="" (ref.="" 66).="" a="" high="" incidence="" of="" successful="" fusion="" after="" pedicle="" screw="" fixation="" is="" documented="" in="" the="" medical="" literature.="" the="" fusion="" rates="" for="" the="" treatment="" of="" spinal="" deformity="" was="" 100="" percent="" (ref.="" 86);="" for="" low="" back="" syndrome="" 100="" percent="" (ref.="" 109);="" for="" postlaminectomy="" instability="" 94="" percent="" (ref.="" 113);="" for="" fracture="" 88.5="" percent="" to="" 100="" percent="" (refs.="" 55,="" 66,="" 80,="" and="" 201);="" for="" postsurgical="" failed="" back="" syndrome="" 91.6="" percent="" (ref.="" 173);="" for="" pseudarthrosis="" 80="" percent="" to="" 94="" percent="" (refs.="" 113="" and="" 186);="" for="" degenerative="" spondylosis="" 87="" percent="" to="" 100="" percent="" (refs.="" 22,="" 169,="" 185,="" and="" 187);="" for="" spinal="" stenosis="" 96="" percent="" to="" 100="" percent="" (refs.="" 113,="" 163,="" and="" 173);="" for="" scoliosis="" 100="" percent="" (ref.="" 163);="" for="" spondylolisthesis="" 78="" percent="" to="" 100="" percent="" (refs.="" 27,="" 37,="" 49,="" 96,="" 113,="" 125,="" and="" 173);="" and="" for="" multiple="" diagnoses="" 77="" percent="" to="" 100="" percent="" (refs.="" 49,="" 95,="" 110,="" 183,="" 192,="" 200,="" and="" 202).="" a="" randomized="" prospective="" trial="" comparing="" pedicle="" screw="" fixation="" with="" noninstrumented="" fusion="" demonstrated="" a="" significant="" improvement="" in="" the="" rate="" of="" successful="" fusion="" when="" pedicle="" fixation="" was="" utilized="" (94="" percent="" fusion="" rate="" with="" rigid="" pedicle="" screw="" instrumentation="" versus="" 65="" percent="" without="" instrumentation)="" (ref.="" 202).="" meta-analyses="" of="" the="" medical="" literature="" compared="" the="" treatment="" outcomes="" with="" pedicle="" screw="" fixation="" with="" three="" types="" of="" class="" ii="" spinal="" fixation="" systems,="" i.e.,="" posterior="" hook-rod="" devices,="" anterior="" instrumentation,="" and="" sublaminar="" wire-rod="" instrumentation.="" for="" thoracolumbar="" spine="" fractures,="" patients="" treated="" with="" pedicle="" screw="" fixation="" had="" a="" significantly="" higher="" rate="" of="" successful="" fusion="" (99.4="" percent)="" than="" those="" treated="" with="" hook-rod="" fixation="" (96.9="" percent)="" or="" anterior="" fixation="" (94.8="" percent),="" p="">< 0.05="" (ref.="" 51).="" there="" were="" no="" significant="" differences="" in="" the="" fusion="" rates="" for="" patients="" with="" degenerative="" spondylolisthesis="" treated="" with="" pedicle="" screw="" fixation="" (93="" percent)="" and="" those="" treated="" with="" hook-rod/sublaminar="" wire-rod="" fixation="" (96="" percent)="" or="" anterior="" fixation="" (94="" percent)="" (ref.="" 119).="" 6.="" pain="" for="" the="" degenerative="" spondylolisthesis="" patients="" in="" the="" cohort="" study,="" the="" rate="" of="" improvement="" in="" back="" pain="" was="" significantly="" greater="" in="" the="" pedicle="" group="" (91.5="" percent)="" when="" compared="" to="" the="" noninstrumented="" group="" (84.0="" percent),="" p="">< 0.001.="" in="" contrast,="" the="" [[page="" 51953]]="" rate="" of="" back="" pain="" improvement="" was="" greater="" in="" the="" nonpedicle="" group="" (95.2="" percent)="" than="" the="" pedicle="" group="" (90.1="" percent)="" for="" the="" fracture="" patient="" group,="" p="">< 0.023.="" the="" rate="" of="" improvement="" in="" leg="" pain="" was="" significantly="" greater="" in="" those="" degenerative="" spondylolisthesis="" patients="" treated="" with="" pedicle="" screw="" fixation="" (91.5="" percent)="" than="" those="" treated="" without="" instrumentation="" (88.2="" percent),="" p="">< 0.027.="" there="" were="" comparable="" improvements="" in="" pain="" in="" patients="" treated="" with="" pedicle="" screw="" fixation="" (90.1="" percent)="" and="" nonpedicle="" screw="" instrumented="" fusion="" (95.2="" percent)="" for="" the="" fracture="" patient="" group="" (refs.="" 66="" and="" 201).="" clinical="" investigations="" performed="" under="" ide="" protocols="" have="" demonstrated="" rates="" of="" improvement="" in="" pain="" ranging="" from="" 79.1="" to="" 89.3="" percent="" (mean="85.7" percent)="" in="" the="" treatment="" of="" degenerative="" spondylolisthesis,="" 70.0="" to="" 85.0="" percent="" (mean="74.1" percent)="" for="" fractures,="" 71.7="" to="" 86.2="" percent="" (mean="78.2" percent)="" for="" degenerative="" disc="" disease,="" 44.2="" percent="" for="" scoliosis,="" 72.4="" to="" 81.6="" percent="" (mean="76.8" percent)="" for="" failed="" back="" syndrome,="" and="" 71.4="" to="" 84.6="" percent="" (mean="82.6" percent)="" for="" spinal="" stenosis="" (ref.="" 66).="" the="" medical="" literature="" also="" documents="" successful="" outcomes="" for="" pain="" in="" patients="" treated="" with="" pedicle="" screw="" fixation="" with="" success="" rates="" ranging="" from="" 67="" percent="" to="" 100="" percent="" (refs.="" 2,="" 19,="" 27,="" 37,="" 80,="" 86,="" 95,="" 97,="" 109,="" 110,="" and="" 147).="" a="" meta-analysis="" of="" these="" data="" showed="" that="" the="" 83.3="" percent="" rate="" of="" improvement="" in="" pain="" for="" patients="" treated="" with="" pedicle="" screw="" instrumentation="" was="" comparable="" to="" the="" 83.3="" percent="" rate="" for="" hook-rod="" instrumentation="" and="" the="" 77.0="" percent="" rate="" for="" anterior="" instrumentation="" in="" the="" treatment="" of="" fractures="" (ref.="" 51).="" similarly,="" the="" rate="" of="" satisfactory="" clinical="" (pain="" and="" function)="" outcomes="" in="" patients="" treated="" for="" degenerative="" spondylolisthesis="" with="" pedicle="" screw="" instrumentation="" was="" 85.7="" percent,="" which="" was="" comparable="" to="" those="" treated="" with="" nonpedicle="" screw="" instrumentation="" (89.6="" percent)="" or="" noninstrumented="" fusions="" (89.6="" percent)="" (refs.="" 51="" and="" 119).="" 7.="" function="" in="" the="" cohort="" study,="" data="" on="" functional="" status="" was="" available="" from="" 2,132="" patients="" in="" the="" pedicle="" screw="" group="" and="" 451="" patients="" in="" the="" noninstrumented="" group="" for="" the="" treatment="" of="" degenerative="" spondylolisthesis,="" and="" from="" 569="" patients="" in="" the="" pedicle="" screw="" group="" and="" 211="" patients="" in="" the="" nonpedicle="" screw="" group="" for="" the="" treatment="" of="" fracture.="" in="" the="" degenerative="" spondylolisthesis="" group,="" there="" was="" a="" significantly="" greater="" incidence="" of="" functional="" improvement="" associated="" with="" the="" use="" of="" pedicle="" screw="" fixation="" (90.4="" percent)="" compared="" to="" treatment="" without="" instrumentation="" (86.7="" percent)="" (p="">< 0.02).="" in="" contrast,="" in="" the="" fracture="" group,="" there="" was="" a="" significantly="" lower="" incidence="" of="" functional="" improvement="" associated="" with="" the="" use="" of="" pedicle="" screw="" fixation="" (87.9="" percent)="" compared="" to="" treatment="" with="" nonpedicle="" screw="" fixation="" (93.4="" percent)="" (p="">< 0.027)="" (refs.="" 66="" and="" 201).="" in="" the="" ide="" clinical="" investigations,="" the="" rate="" of="" functional="" status="" improvement="" for="" degenerative="" spondylolisthesis="" treated="" with="" pedicle="" screw="" instrumentation="" was="" 79.1="" to="" 86.8="" percent="" (mean="84.4" percent),="" fractures="" 75.0="" to="" 85.7="" percent="" (mean="77.8" percent),="" degenerative="" disc="" disease="" 74.1="" to="" 75.7="" percent="" (mean="75.4" percent),="" scoliosis="" 34.9="" percent,="" failed="" back="" syndrome="" 69.3="" to="" 73.6="" percent="" (mean="71.6" percent)="" and="" spinal="" stenosis="" 71.4="" to="" 74.4="" percent="" (mean="73.9" percent)="" (ref.="" 66).="" in="" the="" medical="" literature,="" the="" rate="" of="" successful="" functional="" outcomes="" in="" the="" treatment="" of="" spinal="" stenosis="" was="" 78="" percent="" (ref.="" 173);="" isthmic="" spondylolisthesis="" 90.9="" percent="" (ref.="" 147);="" postsurgical="" failed="" back="" syndrome="" 80.2="" percent="" (ref.="" 173);="" degenerative="" disc="" disease="" 60="" percent="" (ref.="" 206);="" and="" low="" back="" pain="" 72="" percent="" (ref.="" 109).="" a="" meta-="" analysis="" of="" these="" data="" showed="" that="" the="" 82.0="" percent="" rate="" of="" improvement="" in="" functional="" outcomes="" of="" patients="" treated="" with="" pedicle="" screw="" instrumentation="" was="" comparable="" to="" the="" 74.8="" percent="" rate="" for="" hook-rod="" instrumentation="" and="" the="" 73.2="" percent="" rate="" for="" anterior="" instrumentation="" in="" the="" treatment="" of="" fractures="" (ref.="" 51).="" 8.="" neurologic="" status="" in="" the="" cohort="" study,="" in="" the="" degenerative="" spondylolisthesis="" group,="" the="" rate="" of="" improvement="" of="" spinal="" cord="" neurologic="" function="" was="" comparable="" for="" those="" treated="" with="" pedicle="" screw="" fixation="" (3.6="" percent)="" and="" those="" treated="" with="" noninstrumented="" fusion="" (1.2="" percent).="" for="" the="" fracture="" group,="" there="" were="" no="" significant="" differences="" in="" the="" rates="" of="" improvement="" of="" spinal="" cord="" neurological="" assessments="" between="" the="" pedicle="" screw="" (13.3="" percent)="" and="" nonpedicle="" screw="" instrumentation="" (13.0="" percent)="" groups="" (p="">< 0.91)="" (refs.="" 66="" and="" 201).="" for="" the="" degenerative="" spondylolisthesis="" group,="" the="" rate="" of="" root="" status="" improvement="" by="" one="" grade="" or="" more="" was="" significantly="" greater="" in="" patients="" treated="" with="" pedicle="" screw="" fixation="" (36.8="" percent)="" than="" in="" patients="" treated="" without="" instrumentation="" (29.2="" percent),="" or="" with="" nonpedicle="" screw="" fixation="" (25.5="" percent),="" p="">< 0.002.="" in="" the="" fracture="" group,="" the="" rates="" of="" improvement="" in="" root="" neurological="" assessments="" were="" comparable="" in="" the="" pedicle="" screw="" instrumented="" group="" (24.1="" percent)="" and="" the="" nonpedicle="" screw="" instrumented="" group="" (18.2="" percent)="" (p="">< 0.08)="" (refs.="" 66="" and="" 201).="" in="" the="" ide="" clinical="" investigations,="" there="" was="" improved="" neurological="" root="" status="" in="" 11.8="" to="" 32.6="" percent="" of="" patients="" (mean="19.3" percent)="" with="" degenerative="" spondylolisthesis,="" in="" 7.5="" to="" 30.7="" percent="" of="" patients="" (mean="17.6" percent)="" with="" degenerative="" disc="" disease,="" in="" 12.2="" to="" 32.2="" percent="" of="" patients="" (mean="20.5" percent)="" with="" failed="" back="" syndrome,="" in="" 5.8="" percent="" of="" patients="" with="" scoliosis,="" in="" 28.6="" percent="" of="" patients="" with="" spinal="" stenosis,="" and="" in="" 14.3="" percent="" of="" patients="" with="" fracture="" (ref.="" 66).="" improvement="" in="" the="" neurological="" status="" of="" patients="" treated="" with="" pedicle="" screw="" fixation="" in="" the="" medical="" literature="" ranged="" from="" 18.8="" percent="" to="" 100="" percent,="" and="" was="" found="" to="" be="" comparable="" to="" that="" resulting="" from="" nonpedicle="" screw="" instrumented="" fusions="" and="" noninstrumented="" fusions="" (refs.="" 39,="" 49,="" 55,="" 80,="" 107,="" 153,="" 154,="" and="" 164).="" meta-analysis="" of="" the="" literature="" for="" the="" treatment="" of="" thoracolumbar="" fractures="" demonstrated="" a="" statistically="" higher="" rate="" of="" neurologic="" improvement="" in="" the="" anterior="" instrumentation="" (51.4="" percent)="" and="" hook-rod="" instrumentation="" (40.7="" percent)="" treatment="" groups="" compared="" to="" the="" pedicle="" screw="" instrumentation="" group="" (24.3="" percent)="" (p="">< 0.05).="" however,="" the="" pedicle="" screw="" treatment="" group="" had="" a="" significantly="" greater="" proportion="" of="" neurologically="" intact="" (frankel="" e)="" preoperative="" neurological="" profiles="" compared="" to="" all="" other="" treatment="" groups="" and,="" hence,="" no="" potential="" for="" neurological="" recovery="" (ref.="" 51).="" there="" were="" no="" significant="" differences="" between="" treatment="" groups="" in="" the="" number="" of="" patients="" who="" were="" neurologically="" worse="" or="" who="" had="" neurological="" complications="" (ref.="" 51).="" 9.="" potential="" effects="" on="" bone="" density="" experimental="" work="" has="" demonstrated="" decreased="" pedicle="" screw="" fixation="" strength="" in="" bone="" with="" decreased="" bone="" mineral="" density="" (refs.="" 40="" and="" 167),="" and="" care="" must="" be="" taken,="" therefore,="" in="" patients="" with="" osteoporosis="" (ref.="" 170).="" animal="" studies="" have="" demonstrated="" significant="" device-related="" decrease="" in="" bone="" density="" following="" arthrodesis="" with="" rigid="" spinal="" instrumentation="" (ref.="" 123).="" however,="" rates="" of="" successful="" fusion="" increase="" with="" increased="" mechanical="" rigidity="" of="" the="" spinal="" fixation="" systems="" used="" to="" stabilize="" the="" spine.="" the="" significance="" of="" these="" findings="" in="" the="" clinical="" setting="" has="" not="" been="" resolved.="" [[page="" 51954]]="" 10.="" potential="" benefits="" of="" pedicle="" screw="" spinal="" systems="" the="" number="" of="" motion="" segments="" in="" fracture="" patients="" that="" were="" required="" to="" be="" fused="" when="" using="" pedicle="" screw="" fixation="" has="" been="" reported="" to="" be="" half="" that="" required="" when="" using="" hook-rod="" and="" sublaminar="" wire-rod="" instrumentation="" (refs.="" 77,="" 109,="" 154,="" and="" 203).="" this="" reduction="" in="" the="" number="" of="" spinal="" segments="" fused="" preserves="" motion="" at="" the="" adjacent="" motion="" segments,="" particularly="" at="" the="" important="" caudal="" levels="" of="" the="" spine.="" in="" these="" same="" publications,="" the="" authors="" reported="" that,="" when="" using="" pedicle="" screw="" spinal="" systems,="" the="" frequency="" of="" disc="" degeneration="" at="" levels="" adjacent="" to="" the="" fused="" segments="" was="" found="" to="" occur="" at="" rates="" comparable="" to="" those="" occurring="" in="" hook-rod="" and="" sublaminar="" wire-rod="" instrumentation="" systems.="" the="" rigid,="" segmental,="" three-column="" fixation="" achieved="" with="" pedicle="" screw="" fixation="" allowed="" successful="" fixation="" of="" severely="" unstable="" spines="" in="" cases="" of="" tumor="" (refs.="" 31,="" 77,="" 94,="" and="" 114),="" severe="" fracture-="" dislocation="" (refs.="" 2,="" 4,="" 17,="" 35,="" 46,="" 53,="" 58,="" 59,="" 73,="" 107,="" 108,="" 128,="" 130,="" 140,="" 153,="" 154,="" 160,="" and="" 178),="" deformities="" (ref.="" 25),="" pseudarthrosis="" (ref.="" 104),="" severe="" spondylolisthesis="" (refs.="" 27,="" 77,="" and="" 175),="" and="" instability="" following="" extensive="" laminectomy="" (refs.="" 113="" and="" 118).="" two="" authors="" reported="" that="" posterior="" distraction="" achievable="" with="" pedicle="" screw="" instrumentation="" may="" allow="" greater="" fracture="" reduction="" and="" spinal="" canal="" decompression,="" and="" may="" improve="" neurological="" recovery="" (refs.="" 70="" and="" 203).="" iv.="" fda's="" tentative="" findings="" fda="" agrees="" with="" the="" orthopedic="" and="" rehabilitation="" devices="" panel's="" recommendation="" and="" is="" proposing="" that="" the="" pedicle="" screw="" spinal="" system="" intended="" for="" the="" treatment="" of="" degenerative="" spondylolisthesis,="" severe="" spondylolisthesis,="" and="" spinal="" trauma="" be="" classified="" into="" class="" ii.="" fda="" believes="" that="" there="" exists="" sufficient="" information="" to="" develop="" special="" controls="" which="" will="" provide="" reasonable="" assurance="" of="" the="" safety="" and="" effectiveness="" of="" these="" devices.="" fda="" believes="" that="" appropriate="" special="" controls="" should="" include="" mechanical="" testing="" standards="" of="" performance,="" special="" labeling="" requirements,="" and="" postmarket="" surveillance.="" fda="" also="" believes="" that="" premarket="" approval="" is="" not="" necessary="" to="" provide="" reasonable="" assurance="" of="" the="" safety="" and="" effectiveness="" of="" the="" device.="" the="" data="" demonstrate="" that="" the="" use="" of="" pedicle="" screw-based="" instrumentation="" in="" the="" treatment="" of="" degenerative="" spondylolisthesis="" and="" fractures="" results="" in="" significantly="" higher="" fusion="" rates,="" improved="" clinical="" outcomes,="" and="" comparable="" complication="" rates="" when="" compared="" with="" treatment="" with="" no="" instrumentation="" or="" with="" currently="" available="" preamendments="" class="" ii="" spinal="" devices="" (see="" section="" iii.b.="" of="" this="" document).="" the="" data="" also="" demonstrate="" that="" the="" use="" of="" pedicle="" screw-based="" instrumentation="" in="" the="" treatment="" of="" severe="" spondylolisthesis="" results="" in="" equivalent="" or="" higher="" fusion="" rates,="" similar="" clinical="" outcomes,="" and="" comparable="" complication="" rates="" when="" compared="" with="" treatment="" with="" no="" instrumentation="" or="" with="" currently="" available="" preamendments="" class="" ii="" spinal="" devices="" (refs.="" 5,="" 6,="" 14,="" 27,="" 28,="" 29,="" 30,="" 48,="" 52,="" 68,="" 81,="" 82,="" 83,="" 84,="" 92,="" 93,="" 147,="" 155,="" 159,="" 168,="" 169,="" 175,="" and="" 188).="" v.="" summary="" of="" data="" upon="" which="" fda's="" findings="" are="" based="" a.="" clinical="" and="" mechanical="" data="" fda="" analyzed="" the="" medical="" literature="" pertaining="" to="" pedicle="" screw="" spinal="" systems="" and="" presented="" its="" findings="" at="" the="" july="" 22,="" 1994,="" advisory="" panel="" meeting="" (ref.="" 66).="" the="" literature="" pertaining="" to="" the="" clinical="" performance="" of="" pedicle="" screw="" spinal="" systems="" is="" extensive="" and="" describes="" clinical="" indications="" for="" use,="" descriptions="" of="" surgical="" techniques,="" definitions="" of="" clinical="" endpoints="" and="" outcome="" variables="" used="" to="" evaluate="" safety="" and="" effectiveness,="" and="" descriptions="" of="" the="" types,="" and="" estimates="" of="" the="" frequencies,="" of="" device-related="" complications.="" the="" literature="" pertaining="" to="" the="" mechanical="" characteristics="" of="" pedicle="" screw-based="" spinal="" instrumentation="" is="" also="" extensive="" and="" provides="" considerable="" data="" on="" the="" device="" materials,="" strength,="" and="" other="" mechanical="" characteristics="" of="" the="" device="" (see="" section="" ii.a.2.="" of="" this="" document).="" review="" of="" publicly="" released="" ide="" clinical="" investigation="" data="" from="" annual="" reports="" (ref.="" 65),="" as="" well="" as="" data="" released="" by="" the="" study="" sponsors="" (ref.="" 66),="" provided="" fda="" clinical="" data="" from="" controlled="" investigations="" on="" clinical="" and="" radiographic="" outcomes,="" fusion="" rates,="" and="" device-related="" complication="" rates.="" review="" of="" the="" medwatch="" and="" medical="" device="" reporting="" (mdr)="" data="" bases,="" fda's="" device="" problem="" reporting="" systems,="" provided="" information="" regarding="" the="" types="" of="" device-related="" complications="" associated="" with="" the="" use="" of="" spinal="" instrumentation="" devices.="" the="" complications="" associated="" with="" pedicle="" screw="" spinal="" systems="" reported="" to="" fda="" were="" comparable="" to="" those="" associated="" with="" the="" use="" of="" commercially="" available="" class="" ii="" spinal="" fixation="" devices="" (ref.="" 66).="" the="" cohort="" study="" data,="" submitted="" to="" the="" agency="" by="" the="" scientific="" committee="" and="" presented="" to="" the="" panel="" at="" the="" july="" 22,="" 1994,="" meeting,="" provided="" data="" from="" a="" large="" cohort="" of="" patients="" with="" spinal="" fusions="" (refs.="" 66="" and="" 201).="" fda="" evaluated="" the="" cohort="" study="" and="" identified="" a="" number="" of="" shortcomings="" in="" the="" study="" design.="" fda="" found="" that="" the="" cohort="" study="" design="" has="" weaknesses="" inherent="" in="" all="" retrospective="" studies,="" including="" concerns="" of="" possible="" selection="" bias;="" comparability="" of="" the="" treatment="" groups;="" differences="" in="" the="" diagnostic="" inclusion="" criteria;="" treatment="" differences,="" including="" differences="" in="" surgeon="" skill="" and="" experience,="" surgical="" procedures,="" devices,="" and="" postoperative="" care;="" differences="" in="" outcome="" measurement="" and="" reporting;="" and="" the="" degree="" of="" completeness="" of="" medical="" records="" (ref.="" 66).="" in="" addition,="" fda="" found="" that="" a="" significant="" number="" of="" cases="" did="" not="" complete="" the="" 2-year="" followup="" period="" required="" for="" ide="" clinical="" trials="" and="" that="" several="" issues="" regarding="" the="" pooling="" of="" data="" were="" not="" addressed="" (ref.="" 66).="" however,="" many="" of="" these="" weaknesses="" were="" anticipated="" in="" the="" planning="" phase="" of="" the="" study="" and="" steps="" were="" taken="" to="" minimize="" these="" potential="" problems.="" fda="" has="" determined="" that,="" despite="" its="" weaknesses,="" the="" cohort="" study="" was="" conducted="" in="" a="" scientifically="" sound="" manner="" (ref.="" 66).="" the="" investigation="" provided="" adequate="" numbers="" of="" cases,="" followup="" times,="" clinical="" performance="" data,="" and="" complication="" rate="" data="" to="" permit="" assessment="" of="" the="" safety="" and="" effectiveness="" of="" the="" device.="" in="" addition,="" fda="" has="" determined="" that="" the="" data="" meet="" the="" criteria="" for="" valid="" scientific="" evidence="" found="" in="" 21="" cfr="" 860.7(c)(2),="" that="" is,="" they="" are="" from="" 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="" its="" conditions="" of="" use.="" under="" this="" regulation,="" the="" evidence="" may="" vary="" according="" to="" the="" characteristics="" of="" the="" device,="" its="" conditions="" of="" use,="" the="" existence="" and="" adequacy="" of="" warnings="" and="" other="" restrictions,="" and="" the="" extent="" of="" experience="" with="" its="" use.="" fda="" recognizes="" that="" the="" design="" and="" intent="" of="" the="" cohort="" study="" was="" to="" investigate="" two="" demanding="" clinical="" situations="" rather="" than="" merely="" two="" diagnostic="" groups.="" the="" investigation="" of="" this="" device="" for="" these="" two="" diagnostic="" entities="" constituted="" a="" ``worst="" case="" scenario.''="" fda="" has="" concluded="" that="" these="" entities="" represented="" the="" extremes="" [[page="" 51955]]="" of="" acute="" and="" chronic="" instabilities="" and="" deformities.="" therefore,="" fda="" had="" strongly="" recommended="" that="" the="" study="" design="" be="" limited="" to="" degenerative="" spondylolisthesis="" and="" spinal="" fracture="" in="" order="" to="" produce="" a="" more="" meaningful="" investigation="" (ref.="" 66).="" these="" entities="" were="" well-recognized="" and="" easily="" definable="" diagnoses="" with="" established="" radiographic="" findings,="" clinical="" symptomatology,="" surgical="" indications,="" and="" treatment="" outcomes.="" these="" two="" diagnoses="" were="" expected="" to="" yield="" homogeneous="" patient="" groups="" in="" terms="" of="" recognized="" prognostic="" variables.="" more="" importantly,="" these="" diagnostic="" groups="" were="" recognized="" to="" be="" mechanically="" demanding="" and="" clinically="" challenging="" situations="" that="" would="" rigorously="" test="" the="" device.="" the="" fracture="" group,="" which="" included="" fractures="" and="" fracture-="" dislocations,="" represented="" the="" extreme="" of="" spinal="" instability,="" and="" was="" often="" accompanied="" by="" neurologic="" deficit,="" deformity,="" pain,="" and="" severe="" functional="" loss.="" the="" degenerative="" spondylolisthesis="" group="" represented="" chronic="" instability="" with="" deformity="" from="" degenerative="" disease.="" fda="" believes="" that="" the="" following="" special="" controls,="" in="" combination="" with="" the="" general="" controls="" applicable="" under="" the="" act,="" would="" provide="" reasonable="" assurance="" of="" the="" safety="" and="" effectiveness="" of="" pedicle="" screw="" spinal="" systems:="" (1)="" compliance="" with="" materials="" standards,="" such="" as="" astm="" f136,="" f138,="" and="" f1314="" (serve="" to="" control="" risks="" of="" implant="" breakage,="" particulate="" debris,="" and="" metal="" toxicity);="" (2)="" compliance="" with="" mechanical="" testing="" standards,="" such="" as="" astm="" ps-5-94,="" (serves="" to="" control="" risks="" of="" implant="" breakage,="" loss="" of="" fixation,="" loss="" of="" alignment,="" and="" loss="" of="" reduction);="" (3)="" compliance="" with="" biocompatibility="" testing="" standards,="" such="" as="" ``tripartite="" biocompatibility="" guidance="" for="" medical="" devices''="" (9/86)="" and="" international="" standards="" organization="" (iso)="" 10993-1="" (serve="" to="" control="" biocompatibility="" concerns,="" such="" as="" metal="" toxicity="" and="" long-term="" theoretical="" risks="" of="" carcinogenicity);="" and="" (4)="" compliance="" with="" special="" labeling="" requirements="" (serve="" to="" control="" risks="" such="" as="" nerve="" root="" or="" spinal="" cord="" injury,="" dural="" tears,="" vascular="" injury,="" visceral="" injury,="" pedicle="" fracture,="" vertebral="" body="" penetration,="" pseudarthrosis,="" and="" loss="" of="" fixation="" and="" alignment,="" by="" adequately="" warning="" physicians="" of="" potential="" risks="" related="" to="" the="" use="" of="" the="" device).="" for="" example,="" the="" following="" labeling="" would="" be="" required:="" warning:="" the="" safety="" and="" effectiveness="" of="" pedicle="" screw="" spinal="" systems="" have="" not="" been="" determined="" for="" spinal="" conditions="" other="" than="" those="" with="" significant="" mechanical="" instability="" or="" deformity="" requiring="" fusion="" with="" instrumentation.="" these="" include="" significant="" mechanical="" instability="" secondary="" to="" spondylolisthesis,="" vertebral="" fractures="" and="" dislocations;="" scoliosis,="" kyphosis,="" spinal="" tumors,="" and="" pseudarthrosis="" resulting="" from="" previously="" unsuccessful="" fusion="" attempts.="" warning:="" implantation="" of="" pedicle="" screw="" spinal="" systems="" is="" a="" technically="" demanding="" surgical="" procedure="" with="" a="" significant="" potential="" risk="" of="" serious="" injury="" to="" patients.="" this="" procedure="" should="" only="" be="" performed="" by="" surgeons="" with="" adequate="" training="" and="" experience="" in="" both="" the="" specific="" surgical="" technique="" and="" use="" of="" the="" specific="" products="" to="" be="" implanted.="" (5)="" conduction="" of="" postmarket="" surveillance="" (pms)="" studies="" for="" pedicle="" screw="" spine="" systems="" as="" a="" mechanism="" to="" address="" issues="" related="" to="" device="" specific="" design="" differences,="" surgical="" techniques,="" and="" device="" usage.="" because="" complications="" most="" frequently="" occur="" intraoperatively="" or="" early="" post-operatively,="" yet="" important="" common="" complications="" occur="" late="" post-="" operatively,="" a="" potential="" pms="" study="" design="" might="" include="" the="" first="" 1000="" subjects="" evaluated="" for="" intraoperative="" and="" early="" complications="" and="" the="" first="" 100="" subjects="" evaluated="" for="" a="" minimum="" of="" 2="" years="" for="" late="" complications.="" the="" agency="" invites="" comments="" on="" special="" controls,="" including="" labeling="" statements,="" which="" are="" appropriate="" to="" mitigate="" the="" risks="" from="" use="" of="" these="" devices="" as="" they="" are="" proposed="" to="" be="" reclassified.="" b.="" indications="" for="" use="" spinal="" instability="" is="" defined="" in="" terms="" of="" real="" or="" potential="" neural="" dysfunction="" as="" measured="" by="" the="" degree="" of="" structural="" damage="" to="" the="" vertebral="" column.="" instability="" has="" also="" been="" defined="" in="" terms="" of="" fracture="" patterns="" or="" neurologic="" deficit="" (refs.="" 17="" and="" 58),="" or="" excessive="" sagittal="" plane="" translation="" on="" flexion-extension="" radiographs="" or="" spondylolisthesis="" (ref.="" 19).="" spinal="" deformities="" include="" structural="" deformities,="" such="" as="" scoliosis,="" kyphosis,="" lordosis,="" and="" severe="" spondylolisthesis.="" fusion="" of="" the="" thoracic,="" lumbar,="" and="" sacral="" spine="" is="" often="" necessary="" in="" the="" treatment="" of="" disorders="" that="" involve="" instability="" and="" deformity.="" fusion="" provides="" permanent="" stabilization="" of="" the="" involved="" unstable="" motion="" segments="" and="" correction="" of="" structural="" deformities,="" and="" prevents="" the="" long-term="" sequelae="" of="" these="" disorders.="" clinically,="" all="" entities="" that="" require="" fusion,="" either="" to="" treat="" acute="" or="" chronic="" instability="" or="" to="" correct="" a="" spinal="" deformity,="" may="" be="" indications="" for="" the="" use="" of="" adjunctive="" spinal="" instrumentation.="" spinal="" instrumentation,="" including="" anterior="" instrumentation="" systems="" and="" posterior="" hook-rod,="" sublaminar="" wire-rod,="" or="" pedicle="" screw-based="" instrumentation="" systems,="" is="" used="" as="" an="" adjunct="" to="" fusion="" by="" immobilizing="" and="" stabilizing="" the="" involved="" vertebral="" motion="" segments="" until="" fusion="" occurs.="" successful="" fusion="" is="" dependent="" on="" the="" maintenance="" of="" spinal="" alignment="" and="" elimination="" of="" motion="" at="" the="" fusion="" site.="" spinal="" instrumentation="" systems="" are="" simply="" contrivances="" that="" promote="" fusion="" by="" providing="" immobilization="" and="" stabilization="" between="" intervertebral="" motion="" segments.="" mechanically,="" the="" stabilization="" of="" the="" involved="" motion="" segments="" and="" maintenance="" of="" alignment="" are="" accomplished="" by="" all="" types="" of="" spinal="" instrumentation="" systems="" by="" attaching="" anchors="" to="" vertical="" supporting="" members="" (ref.="" 13).="" the="" posterior="" hook-rod="" and="" posterior="" sublaminar="" wire-rod="" device="" systems="" provide="" mechanical="" stabilization="" of="" the="" vertebrae="" with="" longitudinal="" rods="" attached="" to="" the="" laminae="" or="" spinous="" processes="" via="" hooks="" or="" wires.="" the="" anterior="" plate-screw-cable="" fixation="" devices="" provide="" stabilization="" with="" longitudinal="" plates="" or="" cables="" attached="" to="" the="" vertebral="" bodies="" via="" screws="" placed="" anteriorly="" or="" laterally.="" similarly,="" pedicle="" screw="" spinal="" systems="" provide="" stabilization="" of="" vertebrae="" with="" longitudinal="" plates="" or="" rods="" attached="" to="" the="" vertebral="" bodies="" via="" screws="" through="" the="" pedicles.="" mechanical="" testing="" has="" demonstrated="" that="" the="" pedicle="" screw="" spinal="" systems="" has="" equivalent="" or="" superior="" mechanical="" characteristics,="" such="" as="" static="" and="" fatigue="" strength,="" when="" compared="" to="" asti="" class="" ii="" posterior="" hook-rod="" and="" anterior="" plate-screw-cable="" spinal="" devices="" (see="" section="" iii.a.2.="" of="" this="" document).="" in="" addition,="" the="" rigidity="" of="" the="" vertebrae="" instrumented="" with="" pedicle="" screw="" spinal="" systems="" is="" greater="" than="" when="" instrumented="" with="" the="" other="" device="" systems="" (see="" section="" iii.a.2.="" of="" this="" document).="" in="" vivo="" studies="" have="" demonstrated="" that="" the="" strength="" of="" the="" fusion="" is="" directly="" related="" to="" the="" rigidity="" of="" the="" spinal="" instrumentation="" (ref.="" 123).="" clinical="" studies="" also="" have="" verified="" that="" the="" rate="" of="" successful="" fusion="" is="" related="" to="" the="" rigidity="" of="" the="" spinal="" instrumentation="" (ref.="" 202).="" fda="" believes="" that="" the="" indications="" for="" use="" of="" asti="" devices,="" as="" described="" in="" 21="" cfr="" 888.3050="" and="" 888.3060,="" are="" comparable="" to="" the="" proposed="" indications="" for="" pedicle="" screw="" spinal="" systems.="" currently,="" the="" class="" ii="" asti="" posterior="" hook-rod,="" sublaminar="" wire-rod,="" sacral="" screw-="" rod,="" and="" iliac="" screw-rod="" fixation="" devices,="" ``spinal="" interlaminal="" fixation="" orthoses,''="" are="" used="" to="" ``straighten="" and="" immobilize="" the="" spine="" to="" allow="" bone="" grafts="" to="" unite="" and="" fuse="" the="" vertebrae="" together''="" (21="" cfr="" 888.3050).="" the="" intended="" use="" is="" ``primarily="" in="" the="" treatment="" of="" scoliosis="" (a="" lateral="" curvature="" of="" the="" spine),="" but="" it="" also="" may="" [[page="" 51956]]="" be="" used="" in="" the="" treatment="" of="" fracture="" or="" dislocation="" of="" the="" spine,="" grades="" 3="" and="" 4="" of="" spondylolisthesis="" (a="" dislocation="" of="" the="" spinal="" column),="" and="" lower="" back="" syndrome.''="" (an="" exclusion="" of="" lower="" back="" syndrome="" is="" addressed="" below).="" the="" class="" ii="" asti="" anterior="" plate-screw-="" cable="" fixation="" devices,="" ``spinal="" intervertebral="" body="" fixation="" orthosis,''="" are="" ``used="" to="" apply="" a="" force="" to="" a="" series="" of="" vertebrae="" to="" correct="" `sway="" back,'="" scoliosis="" (lateral="" curvature="" of="" the="" spine),="" or="" other="" conditions''="" (21="" cfr="" 888.3060).="" scoliosis="" is="" a="" three-plane="" spinal="" deformity,="" but="" should="" also="" be="" considered="" a="" growth="" abnormality="" and="" a="" chronic="" instability.="" the="" predominant="" feature="" in="" scoliosis="" is="" a="" lateral="" curvature="" of="" the="" thoracic="" and="" lumbar="" vertebrae="" in="" the="" coronal="" plane,="" but="" is="" also="" accompanied="" by="" sagittal="" plane="" and="" rotational="" deformities.="" untreated="" severe="" scoliosis="" can="" cause="" severe="" cosmetic="" deformity,degenerative="" facet="" joint="" and="" intervertebral="" disc="" disease,="" paraplegia,="" right="" heart="" failure,="" and="" death,="" and="" can="" compromise="" pulmonary="" function.="" spinal="" fractures="" and="" dislocations="" result="" in="" loss="" of="" bony="" or="" ligamentous="" integrity="" that="" cause="" spinal="" instability.="" untreated="" traumatic="" spinal="" instability="" may="" lead="" to="" progressive="" spinal="" deformity,="" nonunion,="" pain,="" progressive="" neurologic="" deficit,="" and="" traumatic="" spinal="" stenosis.="" spondylolisthesis,="" whether="" degenerative="" or="" severe,="" is="" generally="" regarded="" as="" a="" chronic="" instability="" caused="" by="" loss="" of="" the="" structural="" integrity="" of="" posterior="" element="" structures,="" such="" as="" the="" pars="" interarticularis,="" as="" well="" as="" the="" intervertebral="" disc.="" spondylolisthesis="" results="" in="" a="" chronic,="" sometimes="" progressive,="" anterior="" subluxation="" of="" the="" superior="" vertebra="" over="" the="" inferior="" vertebra.="" this="" may="" be="" a="" result="" of="" congenital="" vertebral="" anomalies="" (e.g.,="" deficiency="" of="" the="" facets),="" acquired="" defects="" (e.g.,="" traumatic="" pars="" defects,="" pedicle="" or="" facet="" fractures),="" metabolic="" bone="" diseases="" (e.g.,="" osteogenesis="" imperfecta,="" osteoporosis),="" or="" degenerative="" processes="" (e.g.,="" degenerative="" disc="" disease).="" spondylolisthesis="" may="" cause="" severe="" back="" and="" leg="" pain,="" postural="" deformity,="" gait="" abnormalities="" due="" to="" hamstring="" tightness,="" and="" progressive="" neurologic="" deficits.="" fda="" believes="" that,="" for="" the="" purposes="" of="" device="" classification,="" all="" of="" the="" above="" indications="" can="" be="" categorized="" as="" acute="" and="" chronic="" instabilities="" and="" deformities.="" lower="" back="" syndrome="" is="" an="" ill-defined="" disorder="" and="" is="" not="" considered="" to="" be="" included="" in="" the="" indications="" of="" acute="" and="" chronic="" instabilities="" and="" deformities.="" sway="" back,="" an="" obsolete="" term="" for="" lordosis,="" is="" a="" congenital="" or="" developmental="" sagittal="" plane="" deformity.="" although="" 21="" cfr="" 888.3060="" states="" that="" the="" asti="" device="" is="" also="" indicated="" for="" ``other="" conditions''="" that="" were="" not="" specified,="" the="" ``other="" conditions''="" involve="" instability="" or="" a="" deformity="" in="" which="" fusion="" is="" indicated.="" both="" of="" these="" asti="" devices="" are="" used="" as="" adjuncts="" to="" spinal="" fusion,="" providing="" immobilization="" and="" stabilization="" of="" the="" spinal="" segments="" while="" fusion="" takes="" place.="" except="" for="" this="" ill-defined="" ``lower="" back="" syndrome,''="" all="" these="" indications="" constitute="" acute="" and="" chronic="" instabilities="" or="" deformities.="" the="" common="" purpose="" of="" the="" treatment="" of="" these="" clinical="" entities="" is="" to="" prevent="" the="" short-term="" and="" long-term="" sequelae="" of="" instability="" and="" deformity,="" such="" as="" progressive="" neurologic="" deficit,="" severe="" pain,="" severe="" cosmetic="" deformity,="" pulmonary="" and="" cardiovascular="" compromise,="" and="" even="" death.="" acute="" and="" chronic="" instabilities="" or="" deformities="" therefore="" include="" scoliosis,="" fractures,="" dislocations,="" and="" spondylolisthesis,="" but="" may="" also="" include="" spinal="" tumors,="" pseudarthrosis,="" as="" well="" as="" kyphotic="" deformities.="" an="" extensive="" laminectomy="" for="" spinal="" stenosis,="" foraminal="" stenosis,="" or="" other="" indications="" may="" cause="" iatrogenic="" spinal="" instability="" by="" removing="" critical="" stabilizing="" posterior="" element="" structures="" (refs.="" 78="" and="" 118).="" benign="" and="" malignant="" tumors="" cause="" instability="" of="" the="" spine="" by="" compromising="" the="" structural="" integrity="" of="" the="" anterior,="" middle,="" or="" posterior="" columns="" of="" the="" spine="" (refs.="" 31,="" 94,="" 114,="" 118,="" and="" 126).="" segmental="" defects="" or="" loss="" of="" posterior="" elements="" following="" tumor="" resection="" require="" instrumentation="" and="" fusion="" to="" reestablish="" spinal="" stability="" and="" prevent="" neurologic="" injury.="" the="" pathogenesis="" of="" kyphosis="" deformities="" are="" fracture,="" inflammation,="" tumor,="" congenital="" malformation,="" and="" laminectomy="" (refs.="" 25,="" 36,="" and="" 118).="" the="" goal="" of="" treatment="" is="" immediate="" and="" long-term="" stability,="" nerve="" and="" cord="" decompression,="" and="" correction="" of="" angulation.="" pseudarthrosis,="" or="" failure="" to="" achieve="" a="" successful="" fusion,="" causes="" symptomatic="" instability="" at="" the="" motion="" segment="" (refs.="" 104,="" 169,="" and="" 202).="" fda="" believes="" that="" sufficient="" clinical="" data="" exist="" to="" justify="" including="" other="" indications="" such="" as="" scoliosis,="" spinal="" tumors,="" and="" failed="" previous="" fusion="" attempts="" (pseudarthrosis)="" in="" the="" intended="" use="" of="" the="" pedicle="" screw="" spinal="" system.="" the="" medical="" literature="" and="" data="" from="" ide="" clinical="" investigations="" demonstrate="" that="" the="" device="" can="" effectively="" stabilize="" the="" spine="" and="" adequately="" maintain="" spinal="" alignment="" while="" fusion="" takes="" place,="" and="" provide="" adequate="" evidence="" that="" the="" device="" can="" safely="" and="" effectively="" treat="" these="" conditions="" (ref.="" 66).="" fda="" believes="" that="" the="" risks="" associated="" with="" the="" use="" of="" pedicle="" screw="" spinal="" systems="" intended="" to="" provide="" immobilization="" and="" stabilization="" of="" spinal="" segments="" as="" an="" adjunct="" to="" fusion="" in="" the="" treatment="" of="" these="" acute="" and="" chronic="" instabilities="" and="" deformities="" are="" similar="" to="" those="" of="" the="" commercially="" available="" device="" systems="" (21="" cfr="" 888.3050="" and="" 888.3060)="" and="" that="" these="" rates="" are="" clinically="" acceptable="" (ref.="" 66).="" fda="" believes="" that="" the="" clinical="" data="" from="" the="" ide="" clinical="" investigations="" and="" the="" medical="" literature="" adequately="" support="" the="" safety="" and="" effectiveness="" of="" pedicle="" screw="" spinal="" systems="" for="" these="" additional="" indications="" (ref.="" 66).="" moreover,="" fda="" recognizes="" that="" these="" indications="" for="" use="" are="" similar="" to="" those="" of="" commercially="" available="" class="" ii="" spinal="" fixation="" devices,="" such="" as="" the="" spinal="" interlaminal="" fixation="" orthosis="" classified="" under="" 21="" cfr="" 888.3050="" and="" the="" spinal="" intervertebral="" body="" fixation="" orthosis="" classified="" under="" 21="" cfr="" 888.3060.="" fda="" believes="" the="" medical="" literature="" is="" also="" supportive="" of="" the="" use="" of="" pedicle="" screw="" spinal="" systems="" in="" the="" treatment="" of="" acute="" and="" chronic="" instabilities="" and="" deformities.="" as="" described="" above="" in="" section="" iii.b.="" of="" this="" document,="" the="" rates="" of="" clinical="" complications="" related="" to="" the="" use="" of="" pedicle="" screw="" spinal="" systems="" in="" the="" treatment="" of="" acute="" and="" chronic="" instabilities="" and="" deformities="" are="" comparable="" to="" those="" for="" existing="" class="" ii="" devices="" in="" terms="" of="" mechanical="" failures="" (refs.="" 3,="" 5,="" 19,="" 22,="" 24,="" 32,="" 35,="" 37,="" 43,="" 47,="" 50,="" 51,="" 58,="" 59,="" 60,="" 73,="" 77,="" 79,="" 87,="" 89,="" 90,="" 94,="" 95,="" 107,="" 109,="" 110,="" 113,="" 116,="" 122,="" 125,="" 150,="" 151,="" 152,="" 162,="" 163,="" 164,="" 173,="" 183,="" 185,="" 186,="" 187,="" 191,="" 192,="" 193,="" and="" 205),="" soft="" tissue="" injuries="" (refs.="" 25,="" 26,="" 27,="" 37,="" 46,="" 47,="" 49,="" 60,="" 74,="" 106,="" 112,="" 113,="" 126,="" 127,="" 147,="" 153,="" 183,="" 185,="" 187,="" 191,="" and="" 192),="" pseudarthrosis="" (refs.="" 3,="" 17,="" 22,="" 24,="" 25,="" 32,="" 34,="" 35,="" 36,="" 37,="" 47,="" 50,="" 80,="" 96,="" 125,="" 126,="" 153,="" 154,="" 169,="" 173,="" 174,="" 194,="" and="" 205),="" and="" reoperation="" rates="" (refs.="" 50,="" 51,="" 60,="" 74,="" 86,="" 119,="" and="" 173).="" the="" clinical="" performance="" is="" also="" comparable="" to="" existing="" spinal="" devices="" in="" terms="" of="" fusion="" rates="" (refs.="" 1,="" 22,="" 27,="" 37,="" 49,="" 55,="" 66,="" 80,="" 86,="" 95,="" 96,="" 109,="" 110,="" 113,="" 125,="" 163,="" 169,="" 173,="" 183,="" 185,="" 186,="" 187,="" 192,="" 200,="" 201,="" and="" 202),="" rates="" of="" successful="" pain="" (refs.="" 2,="" 18,="" 25,="" 27,="" 37,="" 80,="" 86,="" 95,="" 97,="" 109,="" 110,="" and="" 147),="" function="" (refs.="" 51,="" 109,="" 119,="" 147,="" 173,="" and="" 206),="" and="" neurological="" outcomes="" (refs.="" 39,="" 49,="" 55,="" 80,="" 90,="" 107,="" 153,="" 154,="" and="" 164).="" fda="" also="" recognizes="" the="" unique="" benefits="" of="" pedicle="" screw="" spinal="" systems="" compared="" to="" existing="" spinal="" instrumentation="" systems="" in="" the="" treatment="" of="" certain="" conditions="" involving="" severe="" instability="" or="" deformity.="" the="" rigid,="" segmental,="" three-column="" fixation="" achieved="" with="" pedicle="" [[page="" 51957]]="" screw="" instrumentation="" allows="" successful="" fixation="" of="" severely="" unstable="" spines="" in="" cases="" of="" tumor="" (refs.="" 31,="" 77,="" 94,="" and="" 114),="" severe="" fracture-="" dislocation="" (refs.="" 2,="" 4,="" 17,="" 35,="" 46,="" 53,="" 58,="" 59,="" 73,="" 107,="" 108,="" 128,="" 130,="" 140,="" 153,="" 154,="" 160,="" and="" 178),="" and="" severe="" spondylolisthesis="" (refs.="" 5,="" 27,="" 77,="" 81,="" 82,="" 83,="" 147,="" 169,="" and="" 175).="" in="" addition,="" the="" pedicle="" screw="" spinal="" systems="" provide="" the="" only="" means="" of="" posterior="" attachment="" of="" instrumentation="" in="" cases="" of="" iatrogenic="" instability="" in="" which="" the="" absence="" of="" the="" posterior="" elements="" precludes="" the="" use="" of="" existing="" posterior="" instrumentation="" systems,="" which="" require="" laminae="" or="" spinous="" processes="" for="" attachment="" to="" the="" spine="" (refs.="" 113="" and="" 118).="" fda="" did="" not="" find="" sufficient="" literature="" or="" other="" clinical="" data="" to="" support="" use="" of="" the="" device="" in="" the="" treatment="" of="" low="" back="" pain.="" fda="" has="" determined="" that="" low="" back="" pain="" and="" other="" conditions="" not="" categorized="" as="" an="" acute="" or="" chronic="" instability="" or="" deformity="" should="" not="" be="" included="" in="" the="" indications="" for="" use="" unless="" further="" data="" justify="" their="" inclusion.="" thus,="" if="" the="" device="" has="" such="" indications="" for="" use,="" the="" device="" is="" a="" class="" iii="" device.="" c.="" associated="" risks="" the="" risks="" associated="" with="" the="" use="" of="" pedicle="" screw="" spinal="" systems="" include="" implant="" breakage,="" loss="" of="" fixation,="" nerve="" root="" or="" spinal="" cord="" injury,="" dural="" tears,="" vascular="" injury,="" visceral="" injury,="" pedicle="" fracture,="" vertebral="" body="" penetration,="" pseudarthrosis,="" loss="" of="" alignment="" or="" reduction,="" and="" symptomatic="" hardware="" requiring="" removal.="" fda="" has="" determined="" that="" these="" risks="" are="" comparable="" to="" those="" associated="" with="" the="" use="" of="" the="" existing="" class="" ii="" spinal="" fixation="" devices="" described="" in="" secs.="" 888.3050="" 888.3060.="" fda="" agrees="" with="" the="" panel="" that="" the="" risks="" to="" health="" associated="" with="" the="" use="" of="" the="" device="" are="" reasonably="" well="" understood="" and="" can="" be="" adequately="" controlled="" through="" the="" application="" of="" special="" controls.="" vi.="" references="" the="" following="" references="" have="" been="" placed="" on="" display="" in="" the="" dockets="" management="" branch="" (address="" above)="" and="" may="" be="" seen="" by="" interested="" persons="" from="" 9="" a.m.="" to="" 4="" p.m.,="" monday="" through="" friday.="" 1.="" abdu,="" w.="" a.,="" r.="" g.="" wilber,="" and="" s.="" e.="" emery,="" ``pedicular="" transvertebral="" screw="" fixation="" of="" the="" lumbosacral="" spine="" in="" spondylolisthesis.="" a="" new="" technique="" for="" stabilization,''="" spine,="" 19(6):710-715,="" 1994.="" 2.="" aebi,="" m.,="" ``correction="" of="" degenerative="" scoliosis="" of="" the="" lumbar="" spine.="" a="" preliminary="" report,''="" clinical="" orthopaedics="" and="" related="" research,="" 232:80-86,="" 1988.="" 3.="" aebi,="" m.,="" c.="" etter,="" t.="" kehl,="" and="" j.="" thalgott,="" ``stabilization="" of="" the="" lower="" thoracic="" and="" lumbar="" spine="" with="" the="" internal="" spinal="" skeletal="" fixation="" system.="" indications,="" techniques,="" and="" first="" results="" of="" treatment,''="" spine,="" 12(6):544-551,="" 1987.="" 4.="" an,="" h.="" s.,="" a.="" vaccaro,="" j.="" m.="" cotler,="" and="" s.="" lin,="" ``low="" lumbar="" burst="" fractures.="" comparison="" among="" body="" cast,="" harrington="" rod,="" luque="" rod,="" and="" steffee="" plate,''="" spine,="" 16(8,="" suppl.):440-444,="" 1991.="" 5.="" ani,="" n.,="" l.="" keppler,="" r.="" s.="" biscup,="" and="" a.="" d.="" steffee,="" ``reduction="" of="" high-grade="" slips="" (grades="" iii-iv)="" with="" vsp="" instrumentation.="" report="" of="" a="" series="" of="" 41="" cases,''="" spine,="" 16(6,="" suppl.):302-310,="" 1991.="" 6.="" apel,="" d.="" m.,="" m.="" a.="" lorenz,="" and="" m.="" r.="" zindrick,="" ``symptomatic="" spondylolisthesis="" in="" adults:="" four="" decades="" later,="" spine,="" 14:345-348,="" 1989.="" 7.="" asher,="" m.="" a.,="" and="" w.="" e.="" strippgen,="" ``anthropometric="" studies="" of="" the="" human="" sacrum="" relating="" to="" dorsal="" transsacral="" implant="" designs,''="" clinical="" orthopaedics="" and="" related="" research,="" 203:58-62,="" 1986.="" 8.="" ashman,="" r.="" b.,="" j.="" g.="" birch,="" l.="" b.="" bone,="" j.d.="" corin,="" j.="" a.="" herring,="" c.="" e.="" johnston,="" j.="" f.="" ritterbush,="" and="" j.="" w.="" roach,="" ``mechanical="" testing="" of="" spinal="" instrumentation,''="" clinical="" orthopaedics="" and="" related="" research,="" 227:113-125,="" 1988.="" 9.="" astm="" f67-89="" standard="" specification="" for="" unalloyed="" titanium="" for="" surgical="" implant="" applications.="" 10.="" astm="" f136-92="" standard="" specification="" for="" wrought="" titanium-6al-4v="" eli="" alloy="" for="" surgical="" implant="" applications.="" 11.="" astm="" f138-92="" standard="" specification="" for="" stainless="" steel="" bar="" and="" wire="" for="" surgical="" implants="" (special="" quality).="" 12.="" astm="" f1314-90="" standard="" specification="" for="" wrought="" nitrogen="" strengthened,="" high="" manganese,="" high="" chromium="" stainless="" steel="" bar="" and="" wire="" for="" surgical="" implants.="" 13.="" astm="" ps-5-94="" static="" and="" dynamic="" test="" method="" for="" spinal="" implant="" assemblies="" in="" a="" corpectomy="" model.="" 14.="" balderston,="" r.="" a.,="" and="" d.="" s.="" bradford,="" ``technique="" for="" achievement="" and="" maintenance="" of="" reduction="" for="" severe="" spondylolisthesis="" using="" spinous="" process="" traction="" wiring="" and="" external="" fixation="" of="" the="" pelvis,''="" spine,="" 10:376-382,="" 1985.="" 15.="" banta,="" iii,="" c.="" j.,="" a.="" g.="" king,="" e.="" j.="" dabezies,="" and="" r.="" l.="" liljeberg,="" ``measurement="" of="" effective="" pedicle="" diameter="" in="" the="" spine,''="" orthopedics,="" 12(7):939-942,="" 1989.="" 16.="" bednar,="" d.,="" ``experience="" with="" the="" `fixateur="" interne':="" initial="" clinical="" results,''="" journal="" of="" spinal="" disorders,="" 5(1):93-96,="" 1992.="" 17.="" benson,="" d.="" r.,="" j.="" k.="" burkus,="" p.="" x.="" montesano,="" t.="" b.="" sutherland,="" and="" r.f.="" mclain,="" ``unstable="" thoracolumbar="" and="" lumbar="" burst="" fractures="" treated="" with="" the="" ao="" fixateur="" interne,''="" journal="" of="" spinal="" disorders,="" 5(3):335-343,="" 1992.="" 18.="" bernard,="" t.="" n.,="" and="" c.="" e.="" seibert,="" ``pedicle="" diameter="" determined="" by="" computed="" tomography.="" its="" relevance="" to="" pedicle="" screw="" fixation="" in="" the="" lumbar="" spine,''="" spine,="" 17(6s):="" 160-163,="" 1992.="" 19.="" bernhardt,="" m.,="" d.="" e.="" swartz,="" p.="" l.="" clothiaux,="" r.="" r.="" crowell,="" and="" a.="" a.="" white,="" iii,="" ``posterolateral="" lumbar="" and="" lumbosacral="" fusion="" with="" and="" without="" pedicle="" screw="" internal="" fixation,''="" clinical="" orthopaedics="" and="" related="" research,="" 284,="" 1109-115,="" 1992.="" 20.="" berry,="" j.="" l.,="" j.="" m.="" moran,="" w.="" s.="" berg,="" and="" a.="" d.="" steffee,="" ``a="" morphometric="" study="" of="" human="" lumbar="" and="" selected="" thoracic="" vertebrae,''="" spine,="" 12(4):362-367,="" 1987.="" 21.="" beynnon,="" b.="" d.,="" m.="" h.="" krag,="" m.="" h.="" pope,="" j.="" w.="" frymoyer,="" and="" l.="" d.="" haugh,="" ``fatigue="" evaluation="" of="" a="" new="" spinal="" implant,''="" asme,="" advances="" in="" bioengineering,="" 56-57,="" 1986="" 22.="" bhojraj,="" s.="" y.,="" and="" s.="" g.="" archik,="" ``early="" results="" of="" unconventional="" pedicular="" screw-plate="" fixations.="" the="" indian="" experience,''="" spine,="" 16(10):1192-1195,="" 1991.="" 23.="" bidez,="" m.,="" l.="" lucas,="" j.="" lemmons,="" and="" j.="" ward,="" ``corrosion-wear="" phenomenon="" associated="" with="" spinal="" instrumentation,''="" transcripts="" of="" the="" society="" for="" biomaterials,="" p.="" 86,="" san="" antonio,="" tx,="" 1985.="" 24.="" blumenthal,="" s.,="" and="" k.="" gill,="" ``complications="" of="" the="" wiltse="" pedicle="" screw="" fixation="" system,''="" spine,="" 18(13):1867-1871,="" 1993.="" 25.="" bohm,="" h.,="" j.="" harms,="" r.="" donk,="" and="" k.="" zielke,="" ``correction="" and="" stabilization="" of="" angular="" kyphosis,''="" clinical="" orthopaedics="" and="" related="" research,="" 258:56-61,="" 1990.="" 26.="" boos,="" n.,="" d.="" marchesi,="" and="" m.="" aebi,="" ``survivorship="" analysis="" of="" pedicular="" fixation="" systems="" in="" the="" treatment="" of="" degenerative="" disorders="" of="" the="" lumbar="" spine:="" a="" comparison="" of="" cotrel-dubousset="" instrumentation="" and="" the="" ao="" internal="" fixator,''="" journal="" of="" spinal="" disorders,="" 5(4):403-409,="" 1992.="" 27.="" boos,="" n.,="" d.="" marchesi,="" k.="" zuber,="" and="" m.="" aebi,="" ``treatment="" of="" severe="" spondylolisthesis="" by="" reduction="" and="" pedicular="" fixation.="" a="" 4-6="" year="" follow-up="" study,''="" spine,="" 18(12):1655-1661,="" 1993.="" 28.="" bradford,="" d.="" s.,="" ``treatment="" of="" severe="" spondylolisthesis.="" a="" combined="" approach="" for="" reduction="" and="" stabilization,''="" spine,="" 4:423-="" 429,="" 1979.="" 29.="" bradford,="" d.="" s.,="" and="" o.="" boachie-adjei,="" ``treatment="" of="" severe="" spondylolisthesis="" by="" anterior="" and="" posterior="" reduction="" and="" stabilization,''="" journal="" of="" bone="" and="" joint="" surgery,="" 72a:1060-1066,="" 1990.="" 30.="" bradford,="" d.="" s.,="" and="" y.="" gotfried,="" ``staged="" salvage="" reconstruction="" of="" grade-iv="" and="" v="" spondylolisthesis,''="" journal="" of="" bone="" and="" joint="" surgery,="" 69a:191-202,="" 1987.="" 31.="" bridwell,="" k.="" h.,="" a.="" b.="" jenny,="" t.="" saul,="" k.="" m.="" rich,="" and="" r.="" l.="" grubb,="" ``posterior="" segmental="" spinal="" instrumentation="" (pssi)="" with="" posterolateral="" decompression="" and="" debulking="" for="" metastatic="" thoracic="" and="" lumbar="" spine="" disease.="" limitations="" of="" the="" technique,''="" spine,="" 13(12):1383-1393,="" 1988.="" [[page="" 51958]]="" 32.="" bridwell,="" k.="" h.,="" t.="" a.="" sedgewick,="" m.="" f.="" o'brien,="" l.="" g.="" lenke,="" and="" c.="" baldus,="" ``the="" role="" of="" fusion="" and="" instrumentation="" in="" the="" treatment="" of="" degenerative="" spondylolisthesis="" with="" spinal="" stenosis,''="" journal="" of="" spinal="" disorders,="" 6(6):461-472,="" 1993.="" 33.="" brown,="" s.="" a.,="" and="" k.="" merritt,="" ``fretting="" corrosion="" of="" plates="" and="" screws:="" an="" in="" vitro="" test="" method,''="" in="" corrosion="" and="" degradation="" of="" implant="" materials:="" second="" symposium.="" astm="" special="" technical="" publication="" 859,="" edited="" by="" fraker,="" a.c.="" and="" griffin,="" c.d.,="" pp.="" 105-="" 116.="" ann="" arbor,="" 1985.="" 34.="" carl,="" a.="" l.,="" s.="" g.="" tromanhauser,="" and="" d.="" j.="" roger,="" ``pedicle="" screw="" instrumentation="" for="" thoracolumbar="" burst="" fractures="" and="" fracture-dislocations,''="" spine,="" 17(8,="" suppl.):317-324,="" 1992.="" 35.="" chang,="" k.-w.,="" ``a="" reduction-fixation="" system="" for="" unstable="" thoracolumbar="" burst="" fractures,''="" spine,="" 17:879-886,="" 1992.="" 36.="" chang,="" k.-w.,="" ``oligosegmental="" correction="" of="" post-traumatic="" thoracolumbar="" angular="" kyphosis,''="" spine,="" 18(13):1909-1915,="" 1993.="" 37.="" chang,="" k.-w.,="" and="" p.="" c.="" mcafee,="" ``degenerative="" spondylolisthesis="" and="" degenerative="" scoliosis="" treated="" with="" a="" combination="" segmental="" rod-="" plate="" and="" transpedicular="" screw="" instrumentation="" system:="" a="" preliminary="" report,''="" journal="" of="" spinal="" disorders,="" 1(4):247-256,="" 1989.="" 38.="" cigada,="" a.,="" g.="" rondelli,="" b.="" vicentini,="" m.="" giacomazzi,="" and="" a.="" roos,="" ``duplex="" stainless="" steels="" for="" osteosynthesis="" devices,''="" journal="" of="" biomedical="" materials="" research,="" 23:1087-1095,="" 1989.="" 39.="" cigliano,="" a.,="" r.="" de="" falco,="" e.="" scarano,="" g.="" russo,="" and="" g.="" profeta,="" ``a="" new="" instrumentation="" system="" for="" the="" reduction="" and="" posterior="" stabilization="" of="" unstable="" thoracolumbar="" fractures,''="" neurosurgery,="" 30(2):208-217,="" 1992.="" 40.="" coe,="" j.="" d.,="" k.="" e.="" warden,="" m.="" a.="" herzig,="" and="" p.="" c.="" mcafee,="" ``influence="" of="" bone="" mineral="" density="" on="" the="" fixation="" of="" thoracolumbar="" implants.="" a="" comparative="" study="" of="" transpedicular="" screws,="" laminar="" hooks,="" and="" spinous="" process="" wires,''="" spine,="" 15="" (9):902-907,="" 1990.="" 41.="" coleman,="" d.="" l.,="" r.="" n.="" king,="" and="" j.="" d.="" andrade,="" ``the="" foreign="" body="" reaction:="" a="" chronic="" inflammatory="" response,''="" journal="" of="" biomedical="" materials="" research,="" 8:199-211,="" 1974.="" 42.="" cook,="" s.="" d.,="" r.="" l.="" barrack,="" g.="" c.="" baffes,="" a.="" j.="" t.="" clemow,="" p.="" serekian,="" n.="" dong,="" and="" m.="" a.="" kester,="" ``wear="" and="" corrosion="" of="" modular="" interfaces="" in="" total="" hip="" replacements,''="" clinical="" orthopaedics="" and="" related="" research,="" 298:80-88,="" 1994.="" 43.="" cotrel,="" y.,="" j.="" dubousset,="" and="" m.="" guillaumat,="" ``new="" universal="" instrumentation="" in="" spinal="" surgery,''="" clinical="" orthopaedics="" and="" related="" research,="" 227:10-23,="" 1988.="" 44.="" covenry,="" f.="" r.,="" m.="" a.="" minteer,="" r.="" w.="" smith,="" and="" s.="" m.="" emerson,="" ``fracture-dislocation="" of="" the="" dorsal-lumbar="" spine.="" acute="" operative="" stabilization="" by="" harrington="" instrumentation,''="" spine,="" 3:160-166,="" 1978.="" 45.="" cunningham,="" b.="" w.,="" j.="" c.="" sefter,="" y.="" shono,="" and="" p.="" c.="" mcafee,="" ``static="" and="" cyclic="" biomechanical="" analysis="" of="" pedicle="" screw="" spinal="" constructs,''="" spine,="" 18:1677-1688,="" september,="" 1993.="" 46.="" daniaux,="" h.,="" p.="" seykora,="" a.="" genelin,="" t.="" land,="" and="" a.="" kathrein,="" ``application="" of="" posterior="" plating="" and="" modifications="" in="" thoracolumbar="" spine="" injuries.="" indication,="" techniques,="" and="" results,''="" spine,="" 16="" (suppl.):125-133,="" 1991.="" 47.="" davne,="" s.="" h.,="" and="" d.="" l.="" myers,="" ``complications="" of="" lumbar="" spinal="" fusion="" with="" transpedicular="" instrumentation,''="" spine,="" 16(6,="" suppl.):184-189,="" 1992.="" 48.="" dewald,="" r.="" l.,="" m.="" m.="" faut,="" r.="" f.="" taddonio,="" and="" m.="" g.="" neuwirth,="" ``severe="" lumbosacral="" spondylolisthesis="" in="" adolescents="" and="" children.="" reduction="" and="" staged="" circumferential="" fusion,''="" journal="" of="" bone="" and="" joint="" surgery,="" 63a:619-626,="" 1981.="" 49.="" dick,="" w.,="" ``the="" `fixateur="" interne'="" as="" a="" versatile="" implant="" for="" spine="" surgery,''="" spine,="" 12(9):882-900,="" 1987.="" 50.="" dickman,="" c.="" a.,="" r.="" g.="" fessler,="" m.="" macmillan,="" and="" r.="" w.="" haid,="" ``transpedicular="" screw-rod="" fixation="" of="" the="" lumbar="" spine:="" operative="" technique="" and="" outcome="" in="" 104="" cases,''="" journal="" of="" neurosurgery,="" 77:860-870,="" 1992.="" 51.="" dickman,="" c.="" a.,="" m.="" a.="" yahiro,="" h.="" t.="" c.="" lu,="" and="" m.="" n.="" melkerson,="" ``surgical="" treatment="" alternatives="" for="" fixation="" of="" unstable="" fractures="" of="" the="" thoracic="" and="" lumbar="" spine:="" a="" meta-analysis,''="" spine,="" 19="" (suppl.):="" 2266s-2273s,="" 1994.="" 52.="" dimar,="" j.="" r.,="" and="" g.="" hoffman,="" ``grade="" 4="" spondylolisthesis:="" two-="" stage="" therapeutic="" approach="" of="" anterior="" vertebrectomy="" and="" anterior-="" posterior="" fusion,="" orthopaedic="" review,="" 15(8):504-509,="" 1986.="" 53.="" doerr,="" t.="" e.,="" p.="" x.="" montesano,="" k.="" burkus,="" and="" d.="" r.="" benson,="" ``spinal="" canal="" decompression="" in="" traumatic="" thoracolumbar="" burst="" fractures:="" posterior="" distraction="" rods="" versus="" transpedicular="" screw="" fixation,''="" journal="" of="" spinal="" disorders,="" 5(4):403-411,="" 1991.="" 54.="" ebelke,="" d.="" k.,="" m.="" a.="" asher,="" j.="" r.="" neff,="" and="" d.="" p.="" kraker,="" ``survivorship="" analysis="" of="" vsp="" spine="" instrumentation="" in="" the="" treatment="" of="" thoracolumbar="" and="" lumbar="" burst="" fractures,''="" spine,="" 16="" (suppl.):428-432,="" 1991.="" 55.="" esses,="" s.="" i.,="" ``the="" ao="" spinal="" internal="" fixator,''="" spine,="" 14="" (4):373-378,="" 1989.="" 56.="" esses,="" s.="" i.,="" and="" d.="" r.="" bednar,="" ``the="" spinal="" pedicle="" screw:="" techniques="" and="" systems,''="" orthopaedic="" review,="" 18(6):676682,="" 1989.="" 57.="" esses,="" s.="" i.,="" d.="" j.="" botsford,="" r.="" j.="" huler,="" and="" w.="" rauschning,="" ``surgical="" anatomy="" of="" the="" sacrum.="" a="" guide="" for="" rational="" screw="" fixation,''="" spine,="" 16(6="" suppl.):283-288,="" 1991.="" 58.="" esses,="" s.="" i.,="" d.="" j.="" botsford,="" and="" j.="" p.="" kostuik,="" ``evaluation="" of="" surgical="" treatment="" for="" burst="" fractures,''="" spine,="" 15="" (7):667-673,="" 1990.="" 59.="" esses,="" s.="" i.,="" d.="" j.="" botsford,="" t.="" wright,="" d.="" bednar,="" and="" s.="" bailey,="" ``operative="" treatment="" of="" spinal="" fractures="" with="" the="" ao="" internal="" fixator,''="" spine,="" 16="" (suppl.):146-="" 150,="" 1991.="" 60.="" esses,="" s.="" i.,="" b.="" l.="" sachs,="" and="" v.="" dreyzin,="" ``complications="" associated="" with="" the="" technique="" of="" pedicle="" screw="" fixation.="" a="" selected="" survey="" of="" abs="" members,''="" spine,="" 18="" (15):2231-2239,="" 1993.="" 61.="" evans,="" e.="" m.,="" m.="" a.="" r.="" freeman,="" and="" a.="" j.="" miller,="" and="" b.="" vernon-="" roberts,="" ``metal="" sensitivity="" as="" a="" cause="" of="" bone="" necrosis="" and="" loosening="" of="" the="" prosthesis="" in="" total="" joint="" replacement,''="" journal="" of="" bone="" and="" joint="" surgery,="" 56b:626-642,="" 1974.="" 62.="" farcy,="" j-p.="" c.,="" b.="" a.="" rawlins,="" and="" s.="" d.="" glassmam,="" ``technique="" and="" results="" of="" fixation="" to="" the="" sacrum="" with="" iliosacral="" screws,''="" spine,="" 17(6="" suppl.):190-195,="" 1992.="" 63.="" fergusson,="" r.="" l.,="" a.="" f.="" tencer,="" p.="" woodward,="" and="" b.="" l.="" allen,="" ``biomechanical="" comparison="" of="" spinal="" fracture="" models="" and="" the="" stabilizing="" effects="" of="" posterior="" instrumentations,''="" spine,="" 13:453-="" 460,="" 1988.="" 64.="" ferree,="" b.="" a.,="" ``morphometric="" characteristics="" of="" pedicles="" of="" the="" immature="" spine,''="" spine,="" 17(6):887-891,="" 1992.="" 65.="" food="" and="" drug="" administration,="" orthopedic="" and="" rehabilitation="" devices="" advisory="" panel="" meeting="" transcripts.="" gaithersburg,="" md,="" august="" 20,="" 1993.="" 66.="" food="" and="" drug="" administration,="" orthopedic="" and="" rehabilitation="" devices="" advisory="" panel="" meeting="" transcripts.="" gaithersburg,="" md,="" july="" 22,="" 1994.="" 67.="" french,="" h.="" g.,="" s.="" d.="" cook,="" and="" r.="" j.="" haddad,="" jr.,="" ``correlation="" of="" tissue="" reaction="" to="" corrosion="" in="" osteosynthetic="" devices,''="" journal="" of="" biomedical="" materials="" research,="" 18:817-828,="" 1984.="" 68.="" gaines,="" r.="" w.,="" and="" w.="" k.="" nichols,="" ``treatment="" of="" spondyloptosis="" by="" two="" stage="" l5="" vertebrectomy="" and="" reduction="" of="" l4="" onto="" s1,''="" spine,="" 10:680-686,="" 1985.="" 69.="" george,="" d.="" c.,="" m.="" h.="" krag,="" c.="" c.="" johnson,="" m.="" e.="" van="" hal,="" l.="" d.="" haugh,="" and="" l.="" j.="" grobler,="" ``hole="" preparation="" for="" transpedicle="" screws.="" effect="" on="" pull-out="" strength="" from="" human="" cadaveric="" vertebrae,''="" spine,="" 16(2):180-184,="" 1991.="" 70.="" gertzbein,="" s.="" d.,="" p.="" j.="" crowe,="" m.="" fazl,="" m.="" schwartz,="" and="" d.="" rowed,="" ``canal="" clearance="" in="" burst="" fractures="" using="" the="" ao="" internal="" fixator,''="" spine,="" 17:558-560,="" 1992.="" 71.="" goel,="" v.="" k.,="" t.="" a.="" nye,="" c.="" r.="" clark,="" k.="" nishiyama,="" and="" j.="" n.="" weinstein,="" ``a="" technique="" to="" evaluate="" an="" internal="" spinal="" device="" by="" the="" use="" of="" the="" selspot="" system--an="" application="" to="" luque="" closed="" loop,''="" spine,="" 12:="" 150-159,="" 1987.="" 72.="" goel,="" v.="" k.,="" and="" j.="" n.="" weinstein,="" ``biomechanics="" of="" the="" spine--="" clinical="" and="" surgical="" perspective,''="" boca="" raton.="" crc="" press="" inc,="" 1989.="" 73.="" graziano,="" g.="" p.,="" ``cotrel-dubousset="" hook="" and="" screw="" combination="" for="" spine="" fractures,''="" journal="" of="" spinal="" disorders,="" 6(5):380-385,="" 1993.="" 74.="" greenfield,="" iii,="" r.="" t.,="" r.="" e.="" grant,="" and="" d.="" bryant,="" ``pedicle="" screw="" fixation="" in="" the="" management="" of="" unstable="" thoracolumbar="" spine="" injuries,''="" orthopaedic="" review,="" 21(6):701-706,="" 1992.="" 75.="" grob,="" d.,="" f.="" magerl,="" and="" d.="" p.="" mcgowan,="" ``to="" the="" editor,''="" spine,="" 13:251,="" 1988.="" [[page="" 51959]]="" 76.="" gruen,="" t.="" a.,="" and="" h.="" c.="" amstutz,="" ``a="" failed="" vitallium/stainless="" steel="" total="" hip="" replacement:="" a="" case="" report="" with="" histological="" and="" metallurgical="" examination,''="" journal="" of="" biomedical="" materials="" research,="" 9:465-477,="" 1975.="" 77.="" gurr,="" k.="" r.,="" and="" p.="" c.="" mcafee,="" ``cotrel-dubousset="" instrumentation="" in="" adults.="" a="" preliminary="" report,''="" spine,="" 13(5):510-="" 520,="" 1988.="" 78.="" gurr,="" k.="" r.,="" p.="" c.="" mcafee,="" and="" c.="" m.="" shih,="" ``biomechanical="" analysis="" of="" posterior="" instrumentation="" systems="" after="" decompressive="" laminectomy,''="" journal="" of="" bone="" and="" joint="" surgery,="" 70-a:1182-1191,="" 1988.="" 79.="" guyer,="" d.="" w.,="" l.="" l.="" wiltse,="" and="" r.="" d.="" peek,="" ``the="" wiltse="" pedicle="" screw="" fixation="" system,''="" orthopedics,="" 11(10):1455-="" 1460,="" 1988.="" 80.="" hardaker,="" w.="" t.,="" w.="" a.="" cook,="" a.="" h.="" friedman,="" and="" r.="" d.="" fitch,="" ``bilateral="" transpedicular="" decompression="" and="" harrington="" rod="" stabilization="" in="" the="" management="" of="" severe="" thoracolumbar="" burst="" fractures,''="" spine,="" 17:162-171,="" 1992.="" 81.="" harrington,="" p.="" r.,="" and="" j.="" h.="" dickson,="" ``spinal="" instrumentation="" in="" the="" treatment="" of="" severe="" progressive="" spondylolisthesis,''="" clinical="" orthopaedics="" and="" related="" research,="" 117:157-163,="" 1976.="" 82.="" harrington,="" p.="" r.,="" and="" h.="" s.="" tullos,="" ``reduction="" of="" severe="" spondylolisthesis="" in="" children,''="" southern="" medical="" journal,="" 62:1-7,="" 1969.="" 83.="" harrington,="" p.="" r.,="" and="" h.="" s.="" tullos,="" ``spondylolisthesis="" in="" children.="" observations="" and="" surgical="" treatment,''="" clinical="" orthopaedics="" and="" related="" research,="" 79:75-84,="" 1971.="" 84.="" harris,="" i.="" e.,="" and="" s.="" l.="" weinstein,="" ``long-term="" follow-up="" of="" patients="" with="" grade="" iii="" and="" iv="" spondylolisthesis.="" treatment="" with="" and="" without="" posterior="" fusion,''="" journal="" of="" bone="" and="" joint="" surgery,="" 69a:960-969,="" 1987.="" 85.="" haynes,="" d.="" r.,="" s.="" d.="" rogers,="" b.="" hay,="" m.="" j.="" pearcy,="" and="" d.="" w.="" howie,="" ``the="" differences="" in="" toxicity="" and="" release="" of="" bone-resorbing="" mediators="" induced="" by="" titanium="" and="" cobalt-chromium-alloy="" wear="" particles,''="" journal="" of="" bone="" and="" joint="" surgery,="" 75a:825-833,="" 1993.="" 86.="" hehne,="" h.="" j.,="" k.="" zielke,="" and="" h.="" bohm,="" ``polysegmental="" lumbar="" osteotomies="" and="" transpedicle="" fixation="" for="" correction="" of="" long-curved="" kyphotic="" deformities="" in="" ankylosing="" spondylitis,''="" clinical="" orthopaedics="" and="" related="" research,="" 258:49-55,="" 1990.="" 87.="" henstorf,="" j.="" e.,="" r.="" w.="" gaines,="" and="" a.="" d.="" steffee,="" ``transpedicular="" fixation="" of="" spinal="" disorders="" with="" steffee="" plates,''="" surgical="" rounds="" for="" orthopaedics,="" march="" 1987.="" 88.="" hertlein,="" h.,="" t.="" mittelmeier,="" m.="" schurmann,="" and="" g.="" lob,="" ``anterior="" transpedicular="" instrumentation="" of="" the="" lumbar="" spine:="" an="" anatomical="" study,''="" j.="" spinal="" disorders,="" 5(3):330-334,="" 1992.="" 89.="" hirabayashi,="" s.,="" k.="" kumano,="" and="" t.="" kuroki,="" ``cotrel-dubousset="" pedicle="" screw="" system="" for="" various="" spinal="" disorders.="" merits="" and="" problems,''="" spine,="" 16(11):1298-1304,="" 1991.="" 90.="" horowitch,="" a.,="" r.="" d.="" peek,="" j.="" c.="" thomas,="" jr.,="" e.="" h.="" widell,="" p.="" p.="" dimartino,="" c.="" w.="" spencer,="" iii,="" j.="" weinstein,="" and="" l.="" l.="" wiltse,="" ``the="" wiltse="" pedicle="" screw="" fixation="" system.="" early="" clinical="" results,''="" spine,="" 14(4):461-476,="" 1989.="" 91.="" hou,="" s.,="" r.="" hu,="" and="" y.="" shi,="" ``pedicle="" morphology="" of="" the="" lower="" thoracic="" and="" lumbar="" spine="" in="" a="" chinese="" population,''="" spine,="" 18(13):1850-1855,="" 1993.="" 92.="" johnson,="" j.="" r.,="" and="" e.="" o.="" kirwan,="" ``the="" long-term="" results="" of="" fusion="" in="" situ="" for="" severe="" spondylolisthesis,''="" journal="" of="" bone="" and="" joint="" surgery,="" 65b:43-46,="" 1983.="" 93.="" jones,="" a.="" a.="" m.,="" p.="" c.="" mcafee,="" r.="" a.="" robinson,="" s.="" j.="" zinreich,="" and="" h.="" wang,="" ``failed="" arthrodesis="" of="" the="" spine="" for="" severe="" spondylolisthesis.="" salvage="" by="" interbody="" arthrodesis,''="" journal="" of="" bone="" and="" joint="" surgery,="" 70a:25-30,="" 1988.="" 94.="" jonsson,="" b.,="" l.="" sjostrom,="" h.="" jonsson,="" jr.,="" and="" g.="" karlstrom,="" ``surgery="" for="" multiple="" myeloma="" of="" the="" spine.="" a="" retrospective="" analysis="" of="" 12="" patients,''="" acta="" orthopaedica="" scandinavica,="" supplementum,="" 63(2):192-194,="" 1992.="" 95.="" kabins,="" m.="" b.,="" j.="" n.="" weinstein,="" k.="" f.="" spratt,="" e.="" m.="" found,="" v.="" k.="" goel,="" j.="" woody,="" and="" h.="" a.="" sayre,="" ``isolated="" l4-l5="" fusions="" using="" the="" variable="" screw="" placement="" system:="" unilateral="" versus="" bilateral,''="" journal="" of="" spinal="" disorders,="" 5(1):39-49,="" 1992.="" 96.="" kamioka,="" y.,="" and="" h.="" yamamoto,="" ``lumbar="" trapezoid="" plate="" for="" lumbar="" spondylolisthesis.="" a="" clinical="" study="" on="" preoperative="" and="" postoperative="" instability,''="" spine,="" 15(11):1198,="" 1203,="" 1990.="" 97.="" knight,="" r.="" q.,="" d.="" p.="" k.="" chan,="" j.="" r.="" devanny,="" and="" j.="" r.="" dimao,="" ``influence="" of="" pedicle="" fixation="" on="" postoperative="" pain,''="" journal="" of="" spinal="" disorders,="" 6(2):141-145,="" 1993.="" 98.="" kornblatt,="" m.="" d.,="" m.="" p.="" casey,="" and="" r.="" r.="" jacobs,="" ``internal="" fixation="" in="" lumbosacral="" spine="" fusion--a="" biomechanical="" and="" clinical="" study,''="" clinical="" orthopaedics="" and="" related="" research,="" 203:141-150,="" 1986.="" 99.="" kostiuk,="" j.="" p.,="" b.="" maki,="" p.,="" hasell,="" and="" g.="" fernie,="" ``a="" dynamic="" loading="" apparatus="" for="" the="" controlled="" evaluation="" of="" spinal="" fixation="" devices,''="" transcripts="" of="" the="" scoliosis="" research="" society,="" 1983.="" 100.="" krag,="" m.="" h.,="" b.="" d.="" beynnon,="" m.="" h.="" pope,="" j.="" w.="" frymoyer,="" l.="" d.="" haugh,="" and="" d.="" l.="" weaver,="" ``an="" internal="" fixator="" for="" posterior="" application="" to="" short="" segments="" of="" the="" thoracic,="" lumbar,="" or="" lumbosacral="" spine--design="" and="" testing,''="" clinical="" orthopaedics="" and="" related="" research,="" 203:75-98,="" 1986.="" 101.="" krag,="" m.="" h.,="" m.="" e.="" van="" hal,="" and="" b.="" d.="" beynnon,="" ``placement="" of="" transpedicular="" vertebral="" screws="" close="" to="" anterior="" vertebral="" cortex.="" description="" of="" methods,''="" spine,="" 14(8):879-883,="" 1989.="" 102.="" krag,="" m.="" h.,="" d.="" l.="" weaver,="" b.="" d.="" beynnon,="" and="" l.="" d.="" haugh,="" ``morphometry="" of="" the="" thoracic="" and="" lumbar="" spine="" related="" to="" transpedicular="" screw="" placement="" for="" surgical="" spinal="" fixation,''="" spine,="" 13(1):27-32,="" 1988.="" 103.="" lalor,="" p.="" a.,="" p.="" a.="" revell,="" a.="" b.="" gray,="" s.="" wright,="" g.="" t.="" railton,="" and="" m.="" a.="" r.="" freeman,="" ``sensitivity="" to="" titanium,''="" journal="" of="" bone="" and="" joint="" surgery,="" 75b:25-28,="" 1991.="" 104.="" lauerman,="" w.="" c.,="" d.="" s.="" bradford,="" j.="" w.="" ogilvie,="" and="" e.="" e.="" transfeldt,="" ``results="" of="" lumbar="" pseudarthrosis="" repair,''="" journal="" of="" spinal="" disorders,="" 5(2):149-157,="" 1992.="" 105.="" lemmons,="" j.="" e.,="" k.="" m.="" w.="" niemann,="" and="" a.="" b.="" weiss,="" ``biocompatibility="" studies="" on="" surgical="" grade="" titanium,="" cobalt-="" and="" iron-based="" alloys,''="" journal="" of="" biomedical="" materials="" research,="" 7:549-553,="" 1976.="" 106.="" licht,="" n.="" j.,="" d.="" e.="" rowe,="" and="" l.="" m.="" ross,="" ``pitfalls="" of="" pedicle="" screw="" fixation="" in="" the="" sacrum.="" a="" cadaver="" model,''="" spine,="" 17(8):892-="" 896,="" 1992.="" 107.="" lindsey,="" r.="" w.,="" and="" w.="" dick,="" ``the="" fixateur="" interne="" in="" the="" reduction="" and="" stabilization="" of="" thoracolumbar="" spine="" fractures="" in="" patients="" with="" neurologic="" deficit,''="" spine,="" 16="" (suppl.):140-145,="" 1991.="" 108.="" lindsey,="" r.="" w.,="" w.="" dick,="" s.="" nunchuck,="" and="" g.="" zach,="" ``residual="" intersegmental="" spinal="" mobility="" following="" limited="" pedicle="" fixation="" of="" thoracolumbar="" spine="" fractures="" with="" the="" fixateur="" interne,''="" spine,="" 18(4):474-477,="" 1993.="" 109.="" lorenz,="" m.,="" m.="" zindrick,="" p.="" schwaegler,="" l.="" vrbos,="" m.="" a.="" collatz,="" r.="" behal,="" and="" r.="" cram,="" ``a="" comparison="" of="" single-="" level="" fusions="" with="" and="" without="" hardware,''="" spine,="" 16(8,="" suppl.):455-458,="" 1991.="" 110.="" louis,="" r.,="" ``fusion="" of="" the="" lumbar="" and="" sacral="" spine="" by="" internal="" fixation="" with="" screw="" plates,''="" clinical="" orthopaedics="" and="" related="" research,="" 203:18-57,="" 1986.="" 111.="" lucas,="" l.="" c.,="" l.="" j.="" bearden,="" and="" j.="" e.="" lemmons,="" ``ultrastructural="" examination="" of="" in="" vitro="" and="" in="" vivo="" cells="" exposed="" to="" elements="" from="" type="" 316l="" stainless="" steel,''="" in="" corrosion="" and="" degradation="" of="" implant="" materials:="" second="" symposium,="" astm="" special="" technical="" publication="" 859,="" edited="" fraker,="" a.="" c.="" and="" griffin,="" c.="" d.="" pp.="" 208-222.="" ann="" arbor,="" 1985.="" 112.="" luque,="" e.="" r.,="" ``interpeduncular="" segmental="" fixation,''="" clinical="" orthopaedics="" and="" related="" research,="" 203:54-57,="" 1986.="" 113.="" macmillan,="" m.,="" r.="" cooper,="" and="" r.="" haid,="" ``lumbar="" and="" lumbosacral="" fusions="" using="" cotrel-dubousset="" pedicle="" screws="" and="" rods,''="" spine,="" 19(4):430-434,="" 1994.="" 114.="" magerl,="" f.,="" and="" m.="" f.="" coscia,="" ``total="" posterior="" vertebrectomy="" of="" the="" thoracic="" or="" lumbar="" spine,''="" clinical="" orthopaedics="" and="" related="" research,="" 232:62-69,="" 1988.="" 115.="" maloney,="" w.="" j.,="" r.="" l.="" smith,="" f.="" castro,="" and="" d.="" j.="" schurman,="" ``fibroblast="" response="" to="" metallic="" debris="" in="" vitro,''="" journal="" of="" bone="" and="" joint="" surgery,="" 75a:="" 835-844,="" 1993.="" 116.="" marchesi,="" d.g.,="" and="" m.="" aebi,="" ``pedicle="" fixation="" devices="" in="" the="" treatment="" of="" adult="" lumbar="" scoliosis,''="" spine,="" 17(8,="" suppl.):304-309,="" 1992.="" [[page="" 51960]]="" 117.="" marchesi,="" d.="" g.,="" m.="" michel,="" g.="" l.="" lowery,="" and="" m.="" aebi,="" ``anterior="" transpedicular="" fixation="" of="" the="" lower="" thoracic="" and="" lumbar="" spine.="" experimental="" verification="" using="" a="" new="" direction="" finder,''="" spine,="" 18(4):461-465,="" 1993.="" 118.="" marchesi,="" d.g.,="" j.="" s.="" thalgott,="" and="" m.="" aebi,="" ``application="" and="" results="" of="" the="" ao="" internal="" fixation="" system="" in="" nontraumatic="" indications,''="" spine,="" 16(3,="" suppl.):162-169,="" 1991.="" 119.="" mardjetko,="" s.="" m.,="" p.="" j.="" connolly,="" and="" s.="" shott,="" ``degenerative="" lumbar="" spondylolisthesis.="" a="" meta-analysis="" of="" the="" literature="" 1970-="" 1993,''="" spine,="" 19="" (suppl.):2256s-2265s,="" 1994.="" 120.="" marek,="" m.,="" and="" r.="" w.="" treharne,="" ``an="" in="" vitro="" study="" of="" release="" of="" nickel="" from="" two="" surgical="" implant="" alloys,''="" clinical="" orthopaedics="" and="" related="" research,="" 167:291-295,="" 1982.="" 121.="" mathiesen,="" e.="" b.,="" j.="" u.="" lindgren="" g.="" g.="" a.="" blomgren,="" and="" f.="" p.="" reinholt,="" ``corrosion="" of="" modular="" hip="" prostheses,''="" journal="" of="" bone="" and="" joint="" surgery,="" 73b:569-575,="" 1991.="" 122.="" matsuzaki,="" h.,="" y.="" tokuhashi,="" f.="" matsumoto,="" m.="" hoshino,="" t.="" kiuchi,="" and="" s.="" toriyama,="" ``problems="" and="" solutions="" of="" pedicle="" screw="" plate="" fixation="" of="" lumbar="" spine,''="" spine,="" 15(11):1159-1165,="" 1990.="" 123.="" mcafee,="" p.c.,="" i.="" d.="" farey,="" c.="" e.="" sutterlin,="" k.="" r.="" gurr,="" k.="" e.="" warden,="" b.="" w.="" cunningham,="" ``device-related="" osteoporosis="" with="" spinal="" instrumentation,''="" spine,="" 14="" (9):919-926,="" 1989.="" 124.="" mcafee,="" p.="" c.,="" d.="" j.="" weiland,="" and="" j.="" j.="" carlow,="" ``survivorship="" analysis="" of="" pedicle="" spinal="" instrumentation,''="" spine,="" 16(8,="" suppl.):422-427,="" 1991.="" 125.="" mcguire,="" r.="" a.,="" and="" g.="" m.="" amundson,="" ``the="" use="" of="" primary="" internal="" fixation="" in="" spondylolisthesis,''="" spine,="" 18(12):1662-1672,="" 1993.="" 126.="" mclain,="" r.="" f.,="" m.="" kabins,="" and="" j.="" n.="" weinstein,="" ``vsp="" stabilization="" of="" lumbar="" neoplasms:="" technical="" considerations="" and="" complications,''="" journal="" of="" spinal="" disorders,="" 4(3):359-365,="" 1991.="" 127.="" mclain,="" r.="" f.,="" e.="" sparling,="" and="" d.="" r.="" benson,="" ``early="" failure="" of="" short-segment="" pedicle="" instrumentation="" for="" thoracolumbar="" fractures.="" a="" preliminary="" report,''="" journal="" of="" bone="" and="" joint="" surgery,="" 75a:162-167,="" 1993.="" 128.="" mcnamara,="" m.="" j.,="" g.="" c.="" stephens,="" and="" d.="" m.="" spengler,="" ``transpedicular="" short-segment="" fusions="" for="" treatment="" of="" lumbar="" burst="" fractures,''="" journal="" of="" spinal="" disorders,="" 5="" (2):183-187,="" 1992.="" 129.="" meachim,="" g.,="" and="" d.="" f.="" williams,="" ``changes="" in="" nonosseous="" tissue="" adjacent="" to="" titanium="" implants,''="" journal="" of="" biomedical="" materials="" research,="" 7:555-572,="" 1973.="" 130.="" mick,="" c.="" a.,="" a.="" carl,="" b.="" sachs,="" t.="" hresko,="" and="" b.="" a.="" pfeifer,="" ``burst="" fractures="" of="" the="" fifth="" lumbar="" vertebra,''="" spine,="" 18(13):1878-1884,="" 1993.="" 131.="" mirkovic,="" s.,="" j.="" j.="" abitbol,="" j.="" steinman,="" c.="" c.="" edwards,="" m.="" schaffler,="" j.="" massie,="" and="" s.="" r.="" garfin,="" ``anatomic="" consideration="" for="" sacral="" screw="" placement,''="" spine,="" 16(6="" suppl.):289-294,="" 1991.="" 132.="" misenhimer,="" g.="" r.,="" r.="" d.="" peek,="" l.="" l.="" wiltse,="" s.="" l.="" g.="" rothman,="" and="" e.="" h.="" widell,="" jr.,="" ``anatomic="" analysis="" of="" pedicle="" cortical="" and="" cancellous="" diameter="" as="" related="" to="" screw="" size,''="" spine,="" 14(4):367-="" 372,="" 1989.="" 133.="" moran,="" j.="" m.,="" w.="" s.="" berg,="" j.="" l.="" berry,="" j.="" m.="" geiger,="" and="" a.="" d.="" steffee,="" ``transpedicular="" screw="" fixation,''="" journal="" of="" orthopaedic="" research,="" 7:107-114,="" 1989.="" 134.="" morita,="" m.,="" t.="" sasada,="" i.="" nomura,="" y.="" q.="" wei,="" and="" y.="" tsukamoto,="" ``influence="" of="" low="" dissolved="" oxygen="" concentration="" in="" body="" fluid="" on="" corrosion="" fatigue="" behaviors="" of="" implant="" metals,''="" annals="" of="" biomedical="" engineering,="" 20:505-516,="" 1992.="" 135.="" moura="" e="" silva,="" t.,="" j.="" m.="" monteiro,="" g.="" s.="" ferreira,="" and="" j.="" m.="" vieira,="" ``corrosion="" behavior="" of="" aisi="" 316l,="" stainless-steel="" alloys="" in="" diabetic="" serum,''="" clinical="" materials,="" 12:103-106,="" 1993.="" 136.="" nachemson,="" a.,="" ``the="" load="" on="" the="" lumbar="" discs="" in="" different="" positions="" of="" the="" body,''="" clinical="" orthopaedics="" and="" related="" research,="" 45:107,="" 1966.="" 137.="" nachemson,="" a.,="" and="" j.="" m.="" morris,="" ``in="" vivo="" measurement="" of="" intradiscal="" pressure,''="" journal="" of="" bone="" and="" joint="" surgery,="" 46(a):1077-1082,="" 1964.="" 138.="" nasca,="" r.="" j.,="" j.="" m.="" hollis,="" j.="" e.="" lemmons,="" and="" t.="" a.="" cool,="" ``cyclic="" axial="" loading="" of="" spinal="" implants,''="" spine,="" 10:792-798,="" 1985.="" 139.="" nasser,="" s.,="" p.="" a.="" campbell,="" d.="" kilgus,="" n.="" kossovsky,="" and="" h.="" c.="" amstutz,="" ``cementless="" total="" joint="" arthroplasty="" prostheses="" with="" titanium-alloy="" articular="" surfaces--a="" human="" retrieval="" analysis,''="" clinical="" orthopaedics="" and="" related="" research,="" 261:171-185,="" 1990.="" 140.="" olerud,="" s.,="" g.="" karlstrom,="" and="" l.="" sjostrom,="" ``transpedicular="" fixation="" of="" thoracolumbar="" vertebral="" fractures,''="" clinical="" orthopaedics="" and="" related="" research,="" 227:44-51,="" 1988.="" 141.="" olsewski,="" j.="" m.,="" e.="" h.="" simmons,="" f.="" c.="" kallen,="" f.="" c.="" mendel,="" c.="" m.="" severin,="" and="" d.="" l.="" berens,="" ``morphometry="" of="" the="" lumbar="" spine:="" anatomical="" perspectives="" related="" to="" transpedicular="" fixation,''="" journal="" of="" bone="" and="" joint="" surgery,="" 72a:541-549,="" 1990.="" 142.="" panjabi,="" m.="" m.,="" ``biomechanical="" evaluation="" of="" spinal="" fixation="" devices.="" i.="" a="" conceptual="" framework,''="" spine,="" 13:1129-1133,="" 1988.="" 143.="" panjabi,="" m.="" m.,="" k.="" abumi,="" j.="" duranceau,="" and="" j.="" j.="" crisco,="" ``biomechanical="" evaluation="" of="" spinal="" fixation="" devices.="" ii.="" stability="" provided="" by="" eight="" internal="" fixation="" devices,''="" spine,="" 13:1135-1140,="" 1988.="" 144.="" panjabi,="" m.,="" m.="" krag,="" d.="" summers,="" and="" t.="" videman,="" ``biomechanical="" time-tolerance="" of="" fresh="" cadaveric="" human="" spine="" specimens,''="" journal="" of="" orthopaedic="" research,="" 3:292-300,="" 1985.="" 145.="" panjabi,="" m.="" m.,="" k.="" takata,="" v.="" goel,="" d.="" fererico,="" t.="" oxland,="" j.="" duranceau,="" and="" m.="" krag,="" ``thoracic="" human="" vertebrae.="" quantitative="" three-dimensional="" anatomy,''="" spine,="" 16(8):888-901,="" 1991.="" 146.="" pinzur,="" m.="" s.,="" p.="" r.="" meyer,="" e.="" p.="" lautenschlager,="" j.="" c.="" keller,="" w.="" dobozi,="" and="" j.="" lewis,="" ``measurements="" of="" internal="" fixation="" device="" support="" in="" experimentally="" produced="" fractures="" of="" the="" dorsolumbar="" spine,''="" orthopaedics,="" 2:28-34,="" 1979.="" 147.="" poussa,="" m.,="" d.="" schlenzka,="" s.="" seitsalo,="" m.="" ylikoski,="" h.="" hurri,="" and="" k.="" osterman,="" ``surgical="" treatment="" of="" severe="" isthmic="" spondylolisthesis="" in="" adolescents.="" reduction="" or="" fusion="" in="" situ,''="" spine,="" 18(7):894-901,="" 1993.="" 148.="" rooker,="" g.="" d.,="" and="" j.="" d.="" wilkenson,="" ``metal="" sensitivity="" in="" patients="" undergoing="" hip="" replacement,''="" journal="" of="" bone="" and="" joint="" surgery,="" 62b:502-505,="" 1980.="" 149.="" rosen,="" c.="" d.,="" ``complications="" of="" pedicle="" screw="" fixation="" [letter],''="" spine,="" 16(5):599,="" 1991.="" 150.="" roy-camille,="" r.,="" j.="" -p.="" benazet,="" j.="" p.="" desauge,="" and="" f.="" kuntz,="" ``lumbosacral="" fusion="" with="" pedicular="" screw="" plating="" instrumentation.="" a="" 10-year="" follow-up,''="" acta="" orthopaedica="" scandinavica,="" 251="" (suppl.):100-104,="" 1993.="" 151.="" roy-camille,="" r.,="" g.="" saillant,="" d.="" berteaux,="" and="" v.="" salgado,="" ``osteosynthesis="" of="" thoraco-lumbar="" spine="" fractures="" with="" metal="" plates="" screwed="" through="" the="" vertebral="" pedicles,''="" reconstruction="" surgery="" and="" traumatology,="" 15:2-16,="" 1976.="" 152.="" roy-camille,="" r.,="" g.="" saillant,="" and="" c.="" mazel,="" ``internal="" fixation="" of="" the="" lumbar="" spine="" with="" pedicle="" screw="" plating,''="" clinical="" orthopaedics="" and="" related="" research,="" 203:7-17,="" 1986.="" 153.="" sasso,="" r.="" c.,="" and="" h.="" b.="" cotler,="" ``posterior="" instrumentation="" and="" fusion="" for="" unstable="" fractures="" and="" fracture-dislocations="" of="" the="" thoracic="" and="" lumbar="" spine.="" a="" comparative="" study="" of="" three="" fixation="" devices="" in="" 70="" patients,''="" spine,="" 18(4):450-460,="" 1993.="" 154.="" sasso,="" r.c.,="" h.="" b.="" cotler,="" and="" j.="" d.="" reuben,="" ``posterior="" fixation="" of="" thoracic="" and="" lumbar="" spine="" fractures="" using="" dc="" plates="" and="" pedicle="" screws,''="" spine,="" 16="" (suppl.):134-139,="" 1991.="" 155.="" scaglietti,="" o.,="" g.="" frontino,="" and="" p.="" bartolozzi,="" ``technique="" of="" anatomical="" reduction="" of="" lumbar="" spondylolisthesis="" and="" its="" surgical="" stabilization,''="" clinical="" orthopaedics="" and="" related="" research,="" 117:164-176,="" 1976.="" 156.="" scoles,="" p.="" v.,="" a.="" e.="" linton,="" b.="" latimer,="" m.="" e.="" levy,="" and="" b.="" f.="" digiovanni,="" ``vertebral="" body="" and="" posterior="" element="" morphology:="" the="" normal="" spine="" in="" middle="" life,''="" spine,="" 13(10):1082-1086,="" 1988.="" 157.="" shetty,="" r.="" h.,="" l.="" n.="" gilbertson,="" and="" c.="" h.="" jacobs,="" ``effect="" of="" surface="" finish="" on="" corrosion="" and="" fatigue="" properties="" of="" 22-13-5="" stainless="" steel,''="" transcripts="" of="" the="" society="" for="" biomaterials,="" p.="" 86,="" san="" antonio,="" tx,="" 1985.="" [[page="" 51961]]="" 158.="" shetty,="" r.="" h.,="" l.="" n.="" gilbertson,="" and="" c.="" h.="" jacobs,="" ``the="" 22-13-="" 5="" stainless="" steel--an="" alternative="" to="" hot="" forged="" 316l="" stainless="" steel="" in="" fracture="" fixation,''="" abstracts="" for="" the="" orthopaedic="" research="" society,="" 31="" annual="" meeting,="" las="" vegas,="" nv,="" 1985.="" 159.="" sijbrandij,="" s.,="" ``reduction="" and="" stabilization="" of="" severe="" spondylolisthesis.="" a="" report="" of="" three="" cases,''="" journal="" of="" bone="" and="" joint="" surgery,="" 65b:40-42,="" 1983.="" 160.="" silvestro,="" c.,="" n.="" francaviglia,="" r.="" bragazzi,="" and="" g.="" l.="" viale,="" ``near-anatomical="" reduction="" and="" stabilization="" of="" burst="" fractures="" of="" the="" lower="" thoracic="" or="" lumbar="" spine,''="" acta="" neurological="" (wien),="" 116:53-59,="" 1992.="" 161.="" sim,="" e.,="" ``location="" of="" transpedicular="" screws="" for="" fixation="" of="" the="" lower="" thoracic="" and="" lumbar="" spine.="" computed="" tomography="" of="" 45="" fracture="" cases,''="" acta="" orthopaedica="" scandinavica,="" 64(1):28-32,="" 1993.="" 162.="" simmons,="" e.="" h.,="" and="" w.="" n.="" capicotto,="" ``posterior="" transpedicular="" zielke="" instrumentation="" of="" the="" lumbar="" spine,''="" clinical="" orthopaedics="" and="" related="" research,="" 236:180-191,="" 1988.="" 163.="" simmons,="" e.="" d.,="" and="" e.="" h.="" simmons,="" ``spinal="" stenosis="" with="" scoliosis,''="" spine,="" 17(6,="" suppl.):117-120,="" 1992.="" 164.="" simpson,="" j.="" m.,="" n.="" a.="" ebraheim,="" w.="" t.="" jackson,="" and="" s.="" chung,="" ``internal="" fixation="" of="" the="" thoracic="" and="" lumbar="" spine="" using="" roy-="" camille="" plates,''="" orthopedics,="" 16:663-672,="" 1993.="" 165.="" sivakumar,="" m.,="" u.="" k.="" mudali,="" and="" s.="" rajeswari,="" ``compatibility="" of="" ferritic="" and="" duplex="" stainless="" steels="" as="" implant="" materials:="" in="" vitro="" corrosion="" performance,''="" journal="" of="" biomedical="" materials="" research,="" 28:6081-6086,="" 1993.="" 166.="" sjostrom,="" l.,="" o.="" jacobsson,="" g.="" karlstrom,="" p.="" pech,="" and="" w.="" rauschning,="" ``ct="" analysis="" of="" pedicles="" and="" screw="" tracts="" after="" implant="" removal="" in="" thoracolumbar="" fractures,''="" journal="" of="" spinal="" disorders,="" 6(3):225-231,="" 1993.="" 167.="" smethurst,="" e.,="" and="" r.="" b.="" waterhouse,="" ``a="" physical="" examination="" of="" orthopaedic="" implants="" and="" adjacent="" tissue,''="" acta="" orthopaedica="" scandinavica,="" 49:8-18,="" 1978.="" 168.="" snijder,="" j.="" g.="" n.,="" j.="" m.="" seroo,="" c.="" j.="" snijder,="" and="" a.="" w.="" m.="" schijvens,="" ``therapy="" of="" spondylolisthesis="" by="" repositioning="" and="" fixation="" of="" the="" olisthetic="" vertebra,''="" clinical="" orthopaedics="" and="" related="" research,="" 117:149-156,="" 1976.="" 169.="" soini,="" j.,="" t.="" laine,="" t.="" pohjolainen,="" h.="" hurri,="" and="" h.="" alaranta,="" ``spondylodesis="" augmented="" by="" transpedicular="" fixation="" in="" the="" treatment="" of="" olisthetic="" and="" degenerative="" conditions="" of="" the="" lumbar="" spine,''="" clinical="" orthopaedics="" and="" related="" research,="" 297:111-116,="" 1993.="" 170.="" soshi,="" s.,="" r.="" shiba,="" h.="" kondo,="" and="" k.="" murota,="" ``an="" experimental="" study="" on="" transpedicular="" screw="" fixation="" in="" relation="" to="" osteoporosis="" of="" the="" lumbar="" spine,''="" spine,="" 16="" (11):1335-1341,="" 1991.="" 171.="" m.="" h.="" stauber,="" and="" g.="" s.="" bassett,="" ``pedicle="" screw="" placement="" with="" intraosseous="" endoscopy,''="" spine,="" 19(1):57-61,="" 1994.="" 172.="" steffee,="" a.="" d.,="" r.="" s.="" biscup,="" and="" d.="" j.="" sitkowski,="" ``segmental="" spine="" plates="" with="" pedicle="" screw="" fixation.="" a="" new="" internal="" fixation="" device="" for="" disorders="" of="" the="" lumbar="" and="" thoracolumbar="" spine,''="" clinical="" orthopaedics="" and="" related="" research,="" 203:45-53,="" 1986.="" 173.="" steffee,="" a.="" d.,="" and="" j.="" w.="" brantigan,="" ``the="" variable="" screw="" placement="" spinal="" fixation="" system.="" report="" of="" a="" prospective="" study="" of="" 250="" patients="" enrolled="" in="" food="" and="" drug="" administration="" clinical="" trials,''="" spine,="" 18(9):1160-1172,="" 1993.="" 174.="" steffee,="" a.="" d.,="" and="" d.="" j.="" sitkowski,="" ``posterior="" lumbar="" interbody="" fusion="" and="" plates,''="" clinical="" orthopaedics="" and="" related="" research,="" 227:99-102,="" 1988.="" 175.="" steffee,="" a.="" d.,="" and="" d.="" j.="" sitkowski,="" ``reduction="" and="" stabilization="" of="" grade="" iv="" spondylolisthesis,''="" clinical="" orthopaedics="" and="" related="" research,="" 227:82-89,="" 1988.="" 176.="" steinmann,="" j.="" c.,="" h.="" n.="" herkowitz,="" h.="" el-kommos,="" and="" d.="" p.="" wesolowski,="" ``spinal="" pedicle="" fixation.="" confirmation="" of="" an="" image-="" based="" technique="" for="" screw="" placement,''="" spine,="" 18(13):1856-1861,="" 1993.="" 177.="" steinmann,="" j.="" c.,="" s.="" mirkovic,="" j.="" j.="" abitbol,="" j.="" massie,="" p.="" subbaiah,="" and="" s.="" r.="" garfin,="" ``radiographic="" assessment="" of="" sacral="" screw="" placement,''="" journal="" of="" spinal="" disorders,="" 3(3):232-237,="" 1990.="" 178.="" stephens,="" g.="" c.,="" d.="" p.="" devito,="" and="" m.="" j.="" mcnamara,="" ``segmental="" fixation="" of="" lumbar="" burst="" fractures="" with="" cotrel-dubousset="" instrumentation,''="" journal="" of="" spinal="" disorders,="" 5(3):344-348,="" 1992.="" 179.="" sutow,="" e.="" j.="" and="" s.="" r.="" pollack,="" ``the="" biocompatibility="" of="" certain="" stainless="" steels,''="" in="" biocompatibility="" of="" clinical="" implant="" materials--volume="" i,="" crc="" series="" in="" biocompatibility.="" edited="" by="" williams,="" d.="" f.,="" pp.="" 45-98.="" boca="" raton,="" crc="" press,="" inc.,="" 1981.="" 180.="" syrett,="" b.="" c.,="" and="" e.="" e.="" davis,="" ``in="" vivo="" evaluation="" of="" a="" high-="" strength,="" high-="" ductility="" stainless="" steel="" for="" use="" in="" surgical="" implants,''="" journal="" of="" biomedical="" materials="" research,="" 13:543-556,="" 1979.="" 181.="" taira,="" m.,="" and="" e.="" p.="" lautenschlager,="" ``in="" vitro="" corrosion="" fatigue="" of="" 316l="" cold="" worked="" stainless="" steel,''="" journal="" of="" biomedical="" materials="" research,="" 26:1131-1139,="" 1992.="" 182.="" takamura,="" k.,="" k.="" hayashi,="" n.="" ishinishi,="" t.="" yamada,="" and="" y.="" sugioka,="" ``evaluation="" of="" carcinogenicity="" and="" chronic="" toxicity="" associated="" with="" orthopedic="" implants="" in="" mice,''="" journal="" of="" biomedical="" materials="" research,="" 28:583-589,="" 1994.="" 183.="" temple,="" h.="" t.,="" r.="" w.="" kruse,="" and="" b.="" e.="" van="" dam,="" ``lumbar="" and="" lumbosacral="" fusion="" using="" steffee="" instrumentation,''="" spine,="" 19(5):537-541,="" 1994.="" 184.="" tencer,="" a.="" f.="" and="" r.="" l.="" ferguson,="" a="" biomechanical="" study="" of="" posterior="" fixation="" methods="" after="" wedge="" osteotomy="" of="" a="" thoracic="" vertebra,''="" biomedical="" engineering,="" 224-227,="" 1986.="" 185.="" thalgott,="" j.="" s.,="" h.="" larocca,="" m.="" aebi,="" a.="" p.="" dwyer,="" and="" b.="" e.="" razza,="" ``reconstruction="" of="" the="" lumbar="" spine="" using="" ao="" dcp="" plate="" internal="" fixation,="" spine,="" 14:91-96,="" 1989.="" 186.="" thalgott,="" j.,="" h.="" larocca,="" v.="" gardner,="" t.="" wetzel,="" g.="" lowery,="" j.="" white,="" and="" a.="" dwyer,="" ``reconstruction="" of="" failed="" lumbar="" surgery="" with="" narrow="" ao="" dcp="" plates="" for="" spinal="" arthrodesis,''="" spine,="" 16(3,="" suppl.):170-175,="" 1991.="" 187.="" trammell,="" t.="" r.,="" g.="" rapp,="" k.="" m.="" maxwell,="" j.="" k.="" miller,="" and="" d.="" b.="" reed,="" ``luque="" interpeduncular="" segmental="" fixation="" of="" the="" lumbar="" spine,''="" orthopaedic="" review,="" 20(1):57-63,="" 1991.="" 188.="" verbiest,="" h.,="" ``the="" treatment="" of="" lumbar="" spondyloptosis="" or="" impending="" lumbar="" spondyloptosis="" accompanied="" by="" neurologic="" deficit="" and/or="" neurogenic="" claudication,''="" spine,="" 4:68-77,="" 1979.="" 189.="" weinstein,="" j.="" n.,="" b.="" l.="" rydevik,="" and="" w.="" rauschning,="" ``anatomic="" and="" technical="" considerations="" of="" pedicle="" screw="" fixation,''="" clinical="" orthopaedics="" and="" related="" research,="" 284:34-46,="" 1992.="" 190.="" weinstein,="" j.="" n.,="" k.="" f.="" spratt,="" d.="" spengler,="" c.="" brick,="" and="" s.="" reid,="" ``spinal="" pedicle="" fixation:="" reliability="" and="" validity="" of="" roentgenogram-based="" assessment="" and="" surgical="" factors="" on="" successful="" screw="" placement.="" 191.="" west,="" iii,="" j.="" l.,="" d.="" s.="" bradford,="" and="" j.="" w.="" ogilvie,="" ``results="" of="" spinal="" arthrodesis="" with="" pedicle="" screw-plate="" fixation,''="" journal="" of="" bone="" and="" joint="" surgery,="" 73a:1179-1184,="" 1991.="" 192.="" west,="" iii,="" j.="" l.,="" j.="" w.="" ogilvie,="" and="" d.="" s.="" bradford,="" ``complications="" of="" the="" variable="" screw="" plate="" pedicle="" screw="" fixation,''="" spine,="" 16(5):576-579,="" 1991.="" 193.="" whitecloud,="" iii,="" t.="" s.,="" j.="" c.="" butler,="" j.="" l.="" cohen,="" and="" p.="" d.="" candelora,="" ``complications="" with="" the="" variable="" spinal="" plating="" system,''="" spine,="" 14:472-476,="" 1989.="" 194.="" whitecloud,="" iii,="" t.="" s.,="" j.="" m.="" davis,="" and="" p.="" m.="" olive,="" ``operative="" treatment="" of="" the="" degenerated="" segment="" adjacent="" to="" a="" lumbar="" fusion,''="" spine,="" 19(5):531-536,="" 1994.="" 195.="" whitecloud,="" t.="" s.,="" t.="" skalley,="" s.="" d.="" cook,="" and="" e.="" l.="" morgan,="" ``roentgenographic="" measurement="" of="" pedicle="" screw="" penetration,''="" clinical="" orthopaedics="" and="" related="" research,="" 245:57-68,="" 1989.="" 196.="" williams,="" d.="" f.,="" and="" g.="" meachim,="" ``a="" combine="" metallurgical="" and="" histological="" study="" of="" tissue--prosthesis="" interaction="" in="" orthopaedic="" patients,''="" journal="" of="" biomedical="" materials="" research,="" 8:1-9,="" 1974.="" 197.="" williams,="" d.="" f.,="" ``titanium="" and="" titanium="" alloys,''="" biocompatibility="" of="" clinical="" implant="" materials--volume="" i,="" crc="" series="" in="" biocompatibility.="" edited="" by="" williams,="" d.="" f.,="" crc="" press,="" inc.,="" pp.="" 9-44,="" boca="" raton,="" 1981.="" 198.="" williams,="" d.="" f.="" ``titanium:="" epitome="" of="" biocompatibility="" or="" cause="" for="" concern,''="" journal="" of="" bone="" and="" joint="" surgery,="" 76b:348-349,="" 1994.="" [[page="" 51962]]="" 199.="" wu,="" s.="" -s.,="" p.="" -l.="" liang,="" w.="" -m.="" pai,="" m.="" -k.="" au,="" and="" l.="" -c.="" lin,="" ``spinal="" transpedicular="" drill="" guide:="" design="" and="" application,''="" j.="" spinal="" dis.,="" 4(1):96-103,="" 1991.="" 200.="" yashiro,="" k.,="" t.="" homma,="" y.="" hokari,="" y.="" katsumi,="" h.="" okumura,="" and="" a.="" hirano,="" ``the="" steffee="" variable="" screw="" placement="" system="" using="" different="" methods="" of="" bone="" grafting,''="" spine,="" 16(11):1329-1334,="" 1991.="" 201.="" yuan,="" h.="" a.,="" s.="" r.="" garfin,="" c.="" a.="" dickman,="" and="" s.="" m.="" mardjetko,="" ``historical="" cohort="" study="" of="" pedicle="" screw="" fixation="" in="" thoracic,="" lumbar,="" and="" sacral="" fusions,''="" spine,="" 19="" (suppl.="" 20):2279s-2296s,="" 1994.="" 202.="" zdeblick,="" t.="" a.,="" ``a="" prospective,="" randomized="" study="" of="" lumbar="" fusion.="" preliminary="" results,''="" spine,="" 18(8):983-991,="" 1993.="" 203.="" zindrick,="" m.="" r.,="" and="" m.="" a.="" lorenz,="" ``the="" use="" of="" intrapedicular="" fixation="" systems="" in="" the="" treatment="" of="" thoracolumbar="" and="" lumbosacral="" fractures,''="" orthopedics,="" 15:337-341,="" 1992.="" 204.="" zindrick,="" m.="" r.,="" l.="" l.="" wiltse,="" a.="" doornik,="" e.="" h.="" widell,="" g.="" w.="" knight,="" a.="" g.="" patwardhan,="" j.="" c.="" thomas,="" s.="" l.="" rothman,="" and="" b.="" t.="" fields,="" ``analysis="" of="" the="" morphometric="" characteristics="" of="" the="" thoracic="" and="" lumbar="" pedicles,''="" spine,="" 12(2):160-166,="" 1987.="" 205.="" zucherman,="" j.,="" k.="" hsu,="" g.="" picetti,="" iii,="" a.="" white,="" g.="" wynne,="" and="" l.="" taylor,="" ``clinical="" efficacy="" of="" spinal="" instrumentation="" in="" lumbar="" degenerative="" disc="" disease,''="" spine,="" 17(7):834-837,="" 1992.="" 206.="" zucherman,="" j.,="" k.="" hsu,="" a.="" white,="" and="" g.="" wynne,="" ``early="" results="" of="" spinal="" fusion="" using="" variable="" spine="" plating="" system,''="" spine,="" 13(5):570-579,="" 1989.="" vii.="" environmental="" impact="" the="" agency="" has="" determined="" under="" 21="" cfr="" 25.24(a)(8)="" and="" (e)(2)="" 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.="" analysis="" of="" impacts="" fda="" has="" examined="" the="" impacts="" of="" the="" proposed="" rule="" under="" executive="" order="" 12866="" and="" the="" regulatory="" flexibility="" act="" (pub.="" l.="" 96-354).="" executive="" order="" 12866="" directs="" agencies="" to="" assess="" all="" costs="" and="" benefits="" of="" available="" regulatory="" alternatives="" and,="" when="" regulation="" is="" necessary,="" to="" select="" regulatory="" approaches="" that="" maximize="" net="" benefits="" (including="" potential="" economic,="" environmental,="" public="" health="" and="" safety,="" and="" other="" advantages;="" distributive="" impacts;="" and="" equity).="" the="" agency="" believes="" that="" this="" proposed="" rule="" is="" consistent="" with="" the="" regulatory="" philosophy="" and="" principles="" identified="" in="" the="" executive="" order.="" in="" addition,="" the="" proposed="" rule="" is="" not="" a="" significant="" regulatory="" action="" as="" defined="" by="" the="" executive="" order="" and="" so="" is="" not="" subject="" to="" review="" under="" the="" executive="" order.="" the="" regulatory="" flexibility="" act="" requires="" agencies="" to="" analyze="" regulatory="" options="" that="" would="" minimize="" any="" significant="" impact="" of="" a="" rule="" on="" small="" entities.="" because="" this="" proposal="" would="" reduce="" a="" regulatory="" burden="" by="" exempting="" manufacturers="" of="" devices="" subject="" to="" the="" rule="" from="" the="" requirements="" of="" premarket="" approval,="" the="" agency="" certifies="" that="" the="" proposed="" rule="" will="" not="" have="" a="" significant="" economic="" impact="" on="" a="" substantial="" number="" of="" small="" entities.="" therefore,="" under="" the="" regulatory="" flexibility="" act,="" no="" further="" analysis="" is="" required.="" ix.="" comments="" interested="" persons="" may,="" on="" or="" before="" january="" 2,="" 1996="" submit="" to="" the="" dockets="" management="" branch="" (address="" above)="" written="" comments="" regarding="" this="" proposal.="" two="" copies="" of="" any="" comments="" are="" to="" be="" submitted,="" except="" that="" individuals="" may="" submit="" one="" copy.="" comments="" are="" to="" be="" identified="" with="" the="" name="" of="" the="" device="" and="" the="" docket="" number="" found="" in="" brackets="" in="" the="" heading="" of="" this="" document.="" received="" comments="" may="" be="" seen="" in="" the="" office="" above="" between="" 9="" a.m.="" and="" 4="" p.m.,="" monday="" through="" friday.="" list="" of="" subject="" 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,="" it="" is="" proposed="" that="" 21="" cfr="" part="" 888="" be="" amended="" as="" follows:="" part="" 888--orthopedic="" devices="" 1.="" the="" authority="" citation="" for="" 21="" cfr="" part="" 888="" continues="" to="" read="" as="" follows:="" authority:="" secs.="" 501,="" 510,="" 513,="" 515,="" 520,="" 701="" of="" the="" federal="" food,="" drug,="" and="" cosmetic="" act="" (21="" u.s.c.="" 351,="" 360,="" 360c,="" 360e,="" 360j,="" 371).="" 2.="" new="" sec.="" 888.3070="" is="" added="" to="" subpart="" d="" to="" read="" as="" follows:="" sec.="" 888.3070="" pedicle="" screw="" spinal="" system.="" (a)="" identification.="" a="" pedicle="" screw="" spinal="" system="" is="" a="" multiple="" component="" device,="" made="" of="" alloys="" such="" as="" 316l="" stainless="" steel,="" 316lvm="" stainless="" steel,="" 22cr-13ni-5mn="" stainless="" steel,="" unalloyed="" titanium,="" and="" ti-6al-4v,="" that="" allows="" the="" surgeon="" to="" build="" an="" implant="" system="" to="" fit="" the="" patient's="" anatomical="" and="" physiological="" requirements.="" such="" a="" spinal="" implant="" assembly="" consists="" of="" anchors="" (e.g.,="" bolts,="" hooks,="" and="" screws);="" interconnection="" mechanisms="" incorporating="" nuts,="" screws,="" sleeves,="" or="" bolts;="" longitudinal="" members="" (e.g.,="" plates,="" rods,="" and="" plate/rod="" combinations);="" and="" transverse="" connectors.="" the="" device="" is="" intended="" to="" provide="" immobilization="" and="" stabilization="" of="" spinal="" segments="" in="" the="" treatment="" of="" significant="" medical="" instability="" or="" deformity="" requiring="" fusion="" with="" instrumentation="" including="" significant="" medical="" instability="" secondary="" to="" spondylolisthesis,="" vertebral="" fractures,="" and="" dislocations,="" scoliosis,="" kyphosis,="" spinal="" tumors,="" and="" pseudarthrosis="" resulting="" from="" unsuccessful="" fusion="" attempts.="" (b)="" classification.="" class="" ii="" (special="" controls).="" dated:="" september="" 29,="" 1995.="" d.b.="" burlington,="" director,="" center="" for="" devices="" and="" radiological="" health.="" [fr="" doc.="" 95-24686="" filed="" 9-29-95;="" 3:31="" pm]="" billing="" code="" 4160-01-p="">