[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]



=======================================================================
-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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 

[[Page 51949]]
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 

[[Page 51950]]
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