[Federal Register Volume 63, Number 143 (Monday, July 27, 1998)]
[Rules and Regulations]
[Pages 40025-40041]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-19944]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 888

[Docket No. 95N-0176]
RIN 0910-ZA12


Orthopedic Devices: Classification and Reclassification of 
Pedicle Screw Spinal Systems

Agency: Food and Drug Administration, HHS.

Action: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is classifying certain 
previously unclassified preamendments pedicle screw spinal systems into 
class II (special controls) and reclassifying certain postamendments 
pedicle screw spinal systems from class III (premarket approval) to 
class II. FDA is taking this action because it believes that special 
controls would provide reasonable assurance of safety and 
effectiveness. This action is being taken under the Federal Food, Drug, 
and Cosmetic Act (the act), as amended by the Medical Device Amendments 
of 1976 (the 1976 amendments), the Safe Medical Devices Act of 1990 
(the SMDA), and the Food and Drug Administration Modernization Act of 
1997 (FDAMA).

EFFECTIVE DATE: August 26, 1998.

FOR FURTHER INFORMATION CONTACT: Aric D. Kaiser, Center for Devices and 
Radiological Health (HFZ-410), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 301-594-2036.

SUPPLEMENTARY INFORMATION:
Table of Contents
I. Background
II. Regulatory History of the Device
III. Summary of the Final Rule
IV. Proposed Rule Clarifications
V. Analysis of Comments and FDA's Response
    A. Issues Relating to the Recommendations of the Panel, FDA's 
Tentative Findings, and Summary of the Data Upon Which FDA's 
Findings Were Based
    B. Issues Relating to Information Published in the 1994 
Supplementary Issue of the Journal Spine (vol. 20S, 1994)
    C. Issues Relating to the January 1995, 510(k) Substantial 
Equivalence Determination for a Pedicle Screw Spinal System Intended 
for Severe Spondylolisthesis
    D. Issues Relating to Misstatements or False Statements 
Appearing in the Proposed Rule
    E. Issues Relating to the FDA's Issuance of Regulations
    F. Responses to Comments Which Contained Clinical Data
    G. Requests for Additional Pedicle Screw Clinical Trials and 
Data Analyses
    H. Issues Relating to Indications for Use
    I. Issues Relating to Special Controls
    J. Other Issues
    K. Labeling of Bone Screws
    L. Review of New Pedicle Screw Spinal System 510(k)'s
    M. Review of New Information Published and Submitted After 
Publication of the Proposed Rule: Pedicle Screw and Related 
Literature and MedWatch and MDR System Reports
VI. References
VII. Environmental Impact
VIII. Analysis of Impacts

I. Background

    The act (21 U.S.C. 331 et seq.), as amended by the 1976 amendments 
(Pub. L. 94-295), the SMDA (Pub. L. 101-629), and FDAMA (Pub. L. 105-
115), established a comprehensive system for the regulation of medical 
devices intended for human use. Section 513 of the act (21 U.S.C. 360c) 
established three categories (classes) of devices, depending on the 
regulatory controls needed to provide reasonable assurance of their 
safety and effectiveness. The three categories of devices are: Class I 
(general controls), class II (special controls), and class III 
(premarket approval).
    Under section 513 of the act, devices that were in commercial 
distribution before May 28, 1976 (the date of enactment of the 1976 
amendments), generally referred to as preamendments devices, are 
classified after FDA has: (1) Received a recommendation from a device 
classification panel (an FDA advisory committee); (2) published the 
panel's recommendation for comment, along with a proposed regulation 
classifying the device; and (3) published a final regulation 
classifying the device. FDA has classified most preamendments devices 
under these procedures.
    Devices that were not in commercial distribution prior to May 28, 
1976, generally referred to as postamendments devices, are classified 
automatically by statute (section 513(f) of the act) into class III 
without any FDA rulemaking process. Those devices remain in class III 
and require premarket approval, unless and until: (1) The device is 
reclassified into class I or II; (2) FDA issues an order classifying 
the device into class I or II in accordance with new section 513(f)(2) 
of the act, as amended by FDAMA; or (3) FDA issues an order finding the 
device to be substantially equivalent, in accordance with section 
513(i) of the act, to a predicate device that does not require 
premarket approval. The agency determines whether new devices are 
substantially equivalent to previously offered devices by means of 
premarket notification procedures in section 510(k) of the act (21 
U.S.C. 360(k)) and part 807 of the regulations (21 CFR part 807).
    A preamendments device that has been classified into class III may 
be marketed, by means of premarket notification procedures, without 
submission of a premarket approval application (PMA) until FDA 
promulgates a final regulation under section 515(b) of the act (21 
U.S.C. 360e(b)) requiring premarket approval.
    Reclassification of classified preamendments devices is governed by 
section 513(e) of the act. This section provides that FDA may, by 
rulemaking, reclassify a device (in a proceeding that parallels the 
initial classification proceeding) based upon ``new information.'' The 
reclassification can be initiated by FDA or by the petition of an 
interested person. The term ``new information,'' as used in section 
513(e) of the act, includes information developed as a result of a 
reevaluation of the data before the agency when the device was 
originally classified, as well as information not presented, not 
available, or not developed at that time. (See, e.g., Holland Rantos v. 
United States Department of Health, Education, and Welfare, 587 F.2d 
1173, 1174 n.1 (D.C. Cir. 1978); Upjohn v. Finch, 422 F.2d 944 (6th 
Cir. 1970); Bell v. Goddard, 366 F.2d 177 (7th Cir. 1966).)
    Reevaluation of the data previously before the agency is an 
appropriate basis for subsequent regulatory action where the 
reevaluation is made in light of newly available regulatory authority 
(see Bell v. Goddard, supra, 366 F.2d at 181; Ethicon, Inc. v. FDA, 762 
F. Supp. 382, 389-91 (D.D.C. 1991)), in light of changes in ``medical 
science.'' (See Upjohn v. Finch, supra, 422 F.2d at 951.) Regardless of 
whether data before the agency are past or new data, the ``new 
information'' on which any reclassification is based is required to 
consist ``valid scientific evidence,'' as defined in section 513(a)(3) 
of the act and Sec. 860.7(c)(2) (21 CFR 860.7(c)(2)). (See, e.g., 
General Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens 
Assoc. v. FDA, 766 F.2d 592 (D.C. Cir.), cert. denied, 474 U.S. 1062 
(1985).) FDA relies upon ``valid scientific evidence'' in the 
classification process to determine the level of

[[Page 40026]]

regulation for devices. For the purpose of reclassification, the valid 
scientific evidence upon which the agency relies must be publicly 
available. Publicly available information excludes trade secret and/or 
confidential commercial information, e.g., the contents of a pending 
PMA. (See section 520(c) of the act (21 U.S.C. 360j(c).)

II. Regulatory History of the Device

    Consistent with the act and the regulation, FDA referred the 
proposed classification and reclassification of pedicle screw spinal 
systems to the Orthopedic and Rehabilitation Devices Panel (the Panel), 
an FDA advisory committee, for its recommendation on the requested 
classification and change in classification.
    The Panel reviewed complication type and rate data present in the 
literature, a meta-analysis of the literature; a nationwide, 
retrospective Cohort study of patients treated with the devices;\1\ and 
a review of publicly released investigational device exemptions (IDE) 
data from patients treated with pedicle screw spinal systems. The Panel 
recommended that the postamendments pedicle screw spinal systems 
intended to treat spinal fracture and degenerative spondylolisthesis of 
the thoracic, lumbar, and sacral spine, be reclassified from class III 
into class II.
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    \1\ The Cohort study was an open, nonblinded, historical Cohort 
study designed to recruit the maximum number of surgeons to provide 
clinical data on patients who had undergone spinal fusion surgery. 
Three hundred fourteen surgeons were recruited through announcements 
at professional society meetings and direct mailings to professional 
society memberships. Only clinical data from spinal fusion surgeries 
intended to treat degenerative spondylolisthesis or spinal trauma 
(fracture) that were performed between January 1, 1990, and December 
31, 1991, were used in the analysis. This was done in an effort to 
maximize the number of patients with a minimum of 24 months 
followup. Data from 3,498 patients were collected.
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    In January, 1995, a manufacturer was able to demonstrate 
preamendments status for pedicle screw spinal systems intended to 
provide immobilization and stabilization of spinal segments as an 
adjunct to spinal fusion in the treatment of grades 3 or 4 severe 
spondylolisthesis at the fifth lumbar-first sacral (L5-
S1) spinal level. In an April 1995, homework assignment, FDA 
requested that the Panel recommend a classification for this 
unclassified preamendments device. The Panel recommended that the 
unclassified preamendments pedicle screw spinal systems intended to 
provide immobilization and stabilization of spinal segments as an 
adjunct to spinal fusion in the treatment of grades 3 or 4 severe 
spondylolisthesis at the L5-S1 spinal level be 
classified into class II.
    In the Federal Register of October 4, 1995 (60 FR 51946), FDA 
published a proposed rule to classify certain unclassified 
preamendments pedicle screw spinal systems (for use in certain types of 
severe spondylolisthesis ) into class II, to reclassify certain 
postamendments pedicle screw spinal systems (for use in fracture and 
other conditions) from class III to class II, and to retain in class 
III other postamendments pedicle screw spinal systems. The proposed 
rule reflected FDA's belief that the clinical outcomes and 
complications described in the literature, clinical data, and MDR and 
MedWatch surveillance data bases,\2\ described patient risks and 
benefits of pedicle screw spinal systems comparable to other class II 
spinal fixation devices and that special controls have been identified 
which would provide a reasonable assurance of safety and effectiveness, 
i.e., compliance with material standards, mechanical testing standards, 
biocompatibility standards, and special labeling requirements. 
Initially, FDA provided for interested persons to submit comments on 
the proposal by January 2, 1996. Subsequently, in the Federal Register 
of December 29, 1995 (60 FR 67345), FDA extended the comment period 
until March 4, 1996, in response to several requests for extension of 
the comment period.
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    \2\ MDR and MedWatch data bases are two reporting systems that 
FDA uses to track adverse events, e.g., injuries, deaths, and device 
malfunctions, related to medical devices. The information consists 
of a combination of mandatory and/or voluntary adverse event reports 
from manufacturers, distributors, user facilities, healthcare 
professionals, as well as consumers.
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    FDA received 4,060 comments in response to the proposed rule. These 
comments were submitted by physicians, patients, lawyers, device 
manufacturers, trade associations, and other interested parties. The 
overwhelming majority of these comments were in favor of the proposed 
rule, although some comments were opposed to the proposed rule, and a 
few were both in favor of some aspects of the proposed rule and opposed 
to others.
    In response to comments received on the proposed rule, FDA 
reanalyzed the meta-analysis of the literature, the Cohort study, and 
the publicly released IDE data for the indications of spinal fractures 
and degenerative spondylolisthesis. The reanalysis of the meta-analysis 
of the literature consisted of a review of the summary data and 
conclusions from the original, published analysis. The review of the 
Cohort study consisted of an audit (Ref. 1) of a structured sample of 
all 377 patients enrolled by 21 of the 314 participating surgeons, a 
reanalysis (Ref. 2) of all of the data from the audit, and a comparison 
to the data from unaudited surgeons. The Division of Bioresearch 
Monitoring (BIMO) in the Office of Compliance performed the data audit, 
while the Office of Device Evaluation and the Office of Surveillance 
and Biometrics performed the reanalyses. This audit found records were 
incomplete and investigators had not followed the protocol. In review 
of the audit, the agency concluded that the disparities and 
irregularities were consistent, with respect to both type and scope, 
with other audits of similar studies. After careful reanalysis of the 
potential impact of the ``problem'' records, the agency concluded that 
they could not account for the favorable results reported in this 
study.
    The review of the Cohort study in the context of the audit findings 
yielded results that supported the safety and effectiveness of these 
devices. For spinal fracture, pedicle screw spinal systems presented 
risks and benefits that were comparable to those presented by 
nonpedicle screw instrumented spinal fusion. The devices used in the 
comparison group are class II medical devices. For spondylolisthesis, 
the review in the context of the audit findings described an advantage 
for pedicle screw spinal systems with regard to the clinical outcome 
parameters of fusion and improvement in neurological status when 
compared to noninstrumented spinal fusions. For the other parameters 
that were analyzed, e.g., pain, function, and reoperation rate, pedicle 
screw spinal systems did not always demonstrate an advantage compared 
to noninstrumented spinal fusion. When compared to instrumented spinal 
fusions, however, results among pedicle screw spinal system patients 
for these parameters were not statistically equivalent and not worse. 
Thus, FDA has concluded that the results from the review of the Cohort 
study are consistent with those reported in the literature and the 
publicly released IDE data.
    The reanalysis of the meta-analysis of the literature describing 
experience with pedicle screw spinal systems in treating spinal 
fracture and degenerative spondylolisthesis found that pedicle screw 
spinal systems present risks and benefits that are comparable to those 
presented by nonpedicle screw spinal systems and noninstrumented spinal 
fusions. For degenerative spondylolisthesis, the reanalysis found

[[Page 40027]]

that patient results with pedicle screw spinal systems were comparable 
to those with noninstrumented spinal fusions; it did not find a 
clinically significant improvement in results at followup obtained with 
instrumented spinal fusions over noninstrumented spinal fusions.
    The reanalysis of the publicly available IDE data supports the 
Panel's recommendation for the classification and reclassification of 
pedicle screw spinal systems intended to treat spinal fractures and 
severe spondylolisthesis. It also supports the use of pedicle screw 
spinal systems when intended to provide immobilization and 
stabilization of spinal segments in skeletally mature patients as an 
adjunct to fusion for the treatment of the following acute and chronic 
instabilities or deformities of the thoracic, lumbar, and sacral spine: 
degenerative spondylolisthesis with objective evidence of neurologic 
impairment, fractures, dislocations, scoliosis, kyphosis, spinal 
tumors, and failed previous fusion (pseudarthrosis).
    When all of these data are viewed in conjunction with the medical 
literature and the MDR and MedWatch surveillance data, no new issues 
relating to the safety or effectiveness of pedicle screw spinal systems 
are raised. Therefore, the agency has concluded that these data provide 
valid scientific evidence that certain special controls in conjunction 
with the general controls applicable to all devices, will provide a 
reasonable assurance of the safety and effectiveness of pedicle screw 
spinal systems for L5-S1 use and for use at other 
levels for the treatment of degenerative spondylolisthesis with 
objective evidence of neurologic impairment.
    The agency also reviewed whether the Panel was properly 
constituted. Investigation of alleged undisclosed and unwaived 
conflicts of interest held by Panel members found either no omissions 
of current interests or omissions of minor interests for all but one of 
the Panel members. The agency has concluded that the minor omissions 
are insignificant and do not constitute a financial conflict of 
interest that would credibly influence the members' actions in forming 
the Panel's recommendations.
    The agency has found that one voting Panel member did have 
significant undisclosed financial conflicts. However, because the 
recommendation of the Panel, both in the July 23, 1994, meeting and on 
the subsequent homework assignment, was unanimous and this individual 
was not controlling, or unduly influential, of the votes of the other 
Panel members and was not necessary to constitute a quorum, after 
expunging the participation of this Panel member, FDA has concluded 
that this Panel, both in the meeting and on the subsequent homework 
assignment, was a valid scientific Panel to make recommendations to the 
agency.
    The agency's reanalysis of these data has confirmed its original 
conclusion, reflected in the proposed rule, that the risks and benefits 
of pedicle screw spinal systems are comparable to those of other class 
II spinal fixation devices. FDA's decision to classify and reclassify 
these devices into class II is based upon valid scientific evidence 
establishing that the special controls described above, along with the 
general controls applicable to all devices under the act, provide a 
reasonable assurance of the safety and effectiveness of pedicle screw 
spinal systems.

III. Summary of the Final Rule

    In this final rule, FDA is classifying into class II the 
unclassified preamendments pedicle screw spinal systems intended for 
treatment of severe spondylolisthesis (grades 3 and 4) of the 
L5-S1 vertebra in skeletally mature patients 
receiving fusion by autogenous bone graft having implants attached to 
the lumbar and sacral spine with removal of the implants after the 
attainment of a solid fusion. In addition, FDA is reclassifying into 
class II the postamendments class III pedicle screw spinal systems 
intended to provide immobilization and stabilization of spinal segments 
in skeletally mature patients as an adjunct to fusion in the treatment 
of the following acute and chronic instabilities or deformities of the 
thoracic, lumbar, and sacral spine: Degenerative spondylolisthesis with 
objective evidence of neurologic impairment, fracture, dislocation, 
scoliosis, kyphosis, spinal tumor, and failed previous fusion 
(pseudarthrosis). Pedicle screw spinal systems intended for any other 
uses are considered postamendments class III devices for which 
premarket approval is required. The following four special controls 
apply to the devices being classified and reclassified into class II: 
(1) Compliance with materials standards, (2) compliance with mechanical 
testing standards of performance, (3) compliance with biocompatibility 
standards, and (4) adherence to labeling requirements.

IV. Proposed Rule Clarifications

    FDA is taking this opportunity to clarify that neither well-
controlled investigations nor valid scientific evidence relating to 
pedicle screw spinal systems intended for use in the cervical spine is 
available and, therefore, the safety and effectiveness of these devices 
for this intended use have not been demonstrated. As a result, pedicle 
screw spinal systems intended for use in the cervical spine are 
excluded from this classification and reclassification and are 
considered postamendments class III devices for which premarket 
approval is required.
    In addition, although not specifically stated in the preamble to 
the proposed rule, all valid scientific evidence reviewed by the Panel 
and FDA were obtained from skeletally mature populations. To date, the 
safety and effectiveness of pedicle screw spinal systems in pediatric 
populations have not been demonstrated. Consequently, pedicle screw 
spinal systems intended for use in pediatric populations are 
postamendments class III devices for which premarket approval is 
required.

V. Analysis of Comments and FDA's Response

A. Issues Relating to the Recommendations of the Panel, FDA's Tentative 
Findings, and Summary of the Data Upon Which FDA's Findings Were Based

    1. Several comments believed that valid scientific evidence was not 
presented to the Panel or used in formulating the proposed rule. These 
comments argued that only prospective, randomized, concurrently-
controlled clinical trials constitute valid scientific evidence and 
that anything else is insufficient to support device reclassification.
    FDA disagrees that only data from prospective, randomized, 
concurrently-controlled clinical trials can constitute valid scientific 
evidence. Although prospective, randomized, concurrently controlled 
clinical trials have the potential to produce the most convincing and 
reliable data, e.g., all sources of bias have been reduced to a 
minimum, such clinical trials are not the only type of study that can 
produce data adequate to support a determination that there is 
reasonable assurance that a device is safe and effective for its 
conditions for use. In fact, Sec. 860.7(c)(2) defines valid scientific 
evidence as
    * * * evidence from well-controlled investigations, partially 
controlled studies, studies and objective trials without matched 
controls, well-documented case histories conducted by qualified 
experts, and reports of significant human experience with a marketed 
device, from which it can fairly and responsibly be concluded by 
qualified experts that there is reasonable assurance of the safety 
and effectiveness of a device under

[[Page 40028]]

its conditions of use. The evidence may vary according to the 
characteristics of the device, the existence and adequacy of 
warnings and other restrictions, and the extent of experience with 
its use * * *.
From this definition, it is clear that there is a hierarchy of data 
that fits the definition of valid scientific and that, while well-
controlled, prospective clinical trials are at the top of the 
hierarchy, they are not the only source of data that may support a 
determination regarding reasonable assurance of safety and 
effectiveness for purposes of classifying and/or reclassifying a 
device.
    FDA also disagrees that valid scientific evidence was not presented 
to the Panel or used in support of the proposed rule. The three sources 
of data presented to the Panel and used in support of the proposed rule 
were: (1) Reformatted IDE data, (2) a meta-analysis of the literature, 
and (3) the Cohort study. The reformatted IDE data represent data from 
well-controlled investigations, while the meta-analysis of the 
literature and the Cohort study represent studies and objective trials 
without matched controls or well-documented case histories or reports 
of significant human experience. All three sources of data used in 
support of the classification and reclassification of pedicle screw 
spinal systems clearly fall within the definition of valid scientific 
evidence in Sec. 860.7(c)(2).
    2. One comment objected that, in addition to not being valid 
scientific evidence, the three sources of data, i.e., the meta-analysis 
of the literature, the reformatted IDE data and the Cohort study, were 
flawed.
    The comment noted the following deficiencies with the meta-
analysis:
      FDA previously determined that the available literature 
on pedicle screw spinal systems could not be used to support device 
reclassification.
    FDA disagrees. FDA made that statement prior to January, 1993, when 
no adequate analysis of pedicle screw literature had been provided to 
the agency. FDA believes that, while individual literature articles 
describing the use of pedicle screw spinal systems would be 
insufficient to support reclassification of a device, group analysis of 
relevant articles may be adequate, especially where, as here, the group 
analysis is considered in conjunction with other supporting data. 
Furthermore, after noting the limitations of the individual studies 
reported in the literature, FDA concluded that the literature, taken as 
a whole and used in conjunction with the other sources of data, 
provided adequate information to support the reclassification of 
pedicle screw spinal systems intended to treat degenerative 
spondylolisthesis with objective evidence of neurologic impairment or 
spinal trauma.
      The meta-analysis is not an appropriate scientific 
technique, as applied to retrospective studies, because different 
studies have different parameters, biases, and strengths and 
weaknesses, all of which invalidate the pooling of data.
    FDA disagrees. Although meta-analysis of literature may be less 
rigorous than other forms of scientific research, it still provides 
useful information. As discussed in section V.A.1 of this document, 
Sec. 860.7(c)(2) defines ``valid scientific evidence'' to include many 
types of evidence of varying degrees of scientific rigor, including 
meta-analysis of literature. FDA participated in the development of the 
meta-analysis because the agency believed that this analysis could 
produce data meeting the definition of valid scientific evidence. 
Finally, the inherent limitations of a literature meta-analysis were 
discussed during the presentation of this analysis at the July 23, 
1994, Panel meeting and in the preamble to the proposed rule (60 FR 
51946).
      The meta-analysis actually lent support to the conclusion 
that pedicle screw fixation is less effective than other methods of 
treating degenerative spondylolisthesis and spinal fracture and that it 
may present the patient with more risks.
    FDA disagrees. With respect to degenerative spondylolisthesis, 
there was no statistically significant difference in fusion rates 
between the control and the pedicle screw spinal system treatment 
groups. This is supportive data that clarifies the relative safety and 
effectiveness of pedicle screw spinal systems for this use. With 
respect to spinal fracture, significantly higher fusion rates were 
achieved in the pedicle screw spinal system treatment group than in the 
nonpedicle screw treatment groups. Thus, the meta-analysis confirmed 
the comparability of pedicle screw spinal systems to other class II 
devices used to treat spinal fracture in terms of safety and 
effectiveness.
      Fifty-five of the 58 studies in the meta-analysis were 
nonexperimental case-series having no validity as scientific evidence.
    FDA disagrees. As discussed in section V.A.1 of this document, 
Sec. 860.7(c)(2) states that valid scientific evidence may include ``* 
* * well-documented case histories conducted by qualified experts * * 
*''. Moreover, these well-documented case studies, which were conducted 
by qualified experts, were not the sole basis for the proposed 
classification/reclassification, but rather were considered in 
conjunction with data from various other sources.
    The comment also noted the following deficiencies with the 
reformatted IDE data:
      The reformatted IDE data are not appropriate for 
classifying and reclassifying pedicle screw spinal systems because FDA 
previously had determined that these data could not support PMA's for 
these devices.
    FDA disagrees in part. Prior to the August 20, 1993, Panel meeting, 
FDA had determined that data from individual IDE's were insufficient to 
support PMA's for those devices. Nevertheless, FDA recognized that the 
IDE data could still be valuable. In 1993, after receiving permission 
from nine IDE sponsors to publicly release and use their combined data, 
FDA determined that the data, reviewed as a whole, corroborated the 
results of other available data sets demonstrating the safety and 
effectiveness of pedicle screw spinal systems.
      The reformatted IDE data are inherently suspect because 
they (1) were reformatted by the sponsors and not by FDA, (2) were not 
provided for public scrutiny during the Panel meeting or at any other 
time, and (3) may have omitted poor results.
    FDA disagrees that the reformatted data were suspect because they 
were reformatted by the sponsors and not by FDA. If IDE data are not 
properly formatted, FDA requests the sponsor to reformat its data for 
proper presentation to the agency. Furthermore, data in all marketing 
applications are formatted by the sponsor. Therefore, the simple fact 
that the IDE data were reformatted by the sponsor, not by FDA, does not 
make these data inherently suspect.
    FDA also disagrees that the data were suspect because they were not 
presented for public scrutiny. For reclassification purposes, the valid 
scientific evidence upon which the agency relies must be publicly 
available Sec. 860.5(e) (21 CFR 860.5(e)). Publicly available 
information excludes trade secret and/or confidential commercial 
information (21 CFR 20.61). IDE data typically contain trade secret 
and/or confidential commercial information and, consequently, 
ordinarily may not be publicly disclosed by the agency to support 
reclassification of a device (49 FR 17523 at 17531 and 17532, April 24, 
1984). In fact, under Sec. 812.38(a) and (b)(3) (21 CFR 812.38 (a) and 
(b)(3)), FDA generally does not acknowledge the existence of an IDE or 
disclose any

[[Page 40029]]

of the collected data. However, on August 13, 1993, after receiving 
permission from nine IDE sponsors to publicly release and use their 
combined data, the Commissioner of Food and Drugs (the Commissioner) 
exercised his discretionary authority under Sec. 812.38(b)(2) and 
publicly released the data from nine IDE's, redacted of the 
identification of the IDE sponsors, institutional review boards, 
investigators, and patients. Although FDA did not make publicly 
available the unformatted data from the IDE studies or the 
identification of the IDE sponsors, institutional review boards, 
investigators or patients, the agency did provide the public with a 
detailed report of the combined IDE data (60 FR 51946 at 51961, ref. 
173). This information was publicly available for analysis for more 
than 2 years before the publication of the proposed rule.
    Finally, FDA disagrees that the data were suspect because they may 
have omitted poor results. Nine of fourteen sponsors provided their 
reformatted IDE data for analysis. There is no evidence that the five 
sponsors who did not offer their data did so because the data reflected 
adversely on the performance of their products. They may not have 
provided their data for any number of reasons. For instance, the 
sponsors may have believed that they had an inadequate amount of data 
to contribute to the effort or that the data may not have been in a 
readily accessible format. Regardless of the reason, the publicly 
available reformatted IDE data corroborate the results of other studies 
that demonstrate the safety and effectiveness of pedicle screw spinal 
systems. Specifically, the fusion rates, complication rates, and 
reoperation, revision, and removal rates attained under publicly 
available IDE studies were consistent with what was observed in the 
literature for such devices.
      The 12-month followup time period was inadequate to 
support any conclusions. Specifically, the comment stated that the 
Panel was not supplied with any information on the safety and 
effectiveness of these devices at more than 1 year following surgery. 
The comment continued that, without a minimum followup period of 2 
years, it is impossible to make appropriate conclusions with regard to 
the longer-term safety and efficacy of these devices in accordance with 
accepted scientific convention.
    FDA agrees that a 12-month followup time period would be inadequate 
and, therefore, selected a 24-month followup period for analysis. The 
24-month followup period was also supported by the Panel and the 
literature. Contrary to the comment's statement, the Panel was supplied 
with information on the safety and effectiveness of pedicle screw 
spinal systems at more than one year following surgery. Spinal fusion 
generally occurs within 6 to 18 months after surgery. The majority of 
post-operative complications occur by the 18th month time point. For 
these reasons, FDA concluded that a 24-month followup period was 
adequate. FDA recognizes that not all of the reformatted IDE data were 
from a 24-month followup examination. However, a sufficient amount of 
data from a 24 month followup evaluation was examined for the Panel to 
make a recommendation about the reasonable assurance of safety and 
effectiveness of pedicle screw spinal systems for their class II 
intended uses.
      The comment stated that the lost-to-followup rate was too 
high.
    FDA agrees that the lost-to-followup rate was high. FDA believes 
that patients with poor results tend to either return to their surgeons 
more frequently or go to other caregivers, attempting to receive the 
pain relief and return of function that they were originally seeking. 
It cannot be determined whether the patients who were lost-to-followup 
had acceptable results or went to other caregivers. However, FDA does 
not believe that this theoretical weakness in the data is of such a 
magnitude as to justify rejecting the studies. Thus, both the Panel and 
FDA believe that the lost-to-followup rate was not unacceptably high.
    The comment noted the following deficiencies with the Cohort study:
      The Cohort study did not constitute valid scientific 
evidence.
    FDA disagrees. As described above, valid scientific evidence 
encompasses a wide variety of data. The Cohort study satisfies the 
definition of valid scientific evidence because it consisted of data 
from well-documented case histories conducted by qualified experts and 
reports of significant human experience.
      The sample size and statistical power used in designing 
the Cohort study were inadequate and, therefore, no reliable 
conclusions can be drawn from the study. Another comment attempted to 
rebut this allegation.
    FDA believes that the sample size and statistical power 
calculations that were performed in the Cohort study were accurate and 
appropriate and, consequently, that the conclusions drawn from the 
study had a sound basis.
      The Cohort study was biased and the data were not 
independently audited.
    FDA disagrees. While the potential for bias exists in any study, it 
was of particular concern in the design of the Cohort study due to its 
retrospective nature. As described at the July 22, 1994, Panel meeting 
and in the preamble to the proposed rule (60 FR 51946 at 51954), 
various steps were taken to minimize the potential effects of bias due 
to the study design. In addition, contrary to the comment's assertion, 
there was a review of the data by an independent auditor and a 
subsequent FDA BIMO audit and review. The review by the independent 
auditor was not extensive and no definitive conclusions can be drawn 
from its analysis of the Cohort study data. Although both audits 
uncovered instances of protocol departures, recordkeeping 
inconsistencies, or a lack of clear understanding or unfamiliarity with 
the protocol requirements on the part of a participating surgeon, these 
inconsistencies and protocol departures did not affect the reliability 
of the data. For example, one type of reported protocol recordkeeping 
departure was that some data forms were incomplete. In some instances, 
the data forms simply omitted the patient's weight, but not the 
patient's fusion status. The absence of that piece of information, 
while rendering the form incomplete, clearly did not affect the 
clinical outcome analysis. A more significant protocol departure 
related to the inclusion and analysis of data from patients whose 
diagnosis did not meet patient eligibility criteria. However, no 
obvious pattern that would improve overall patient outcomes was 
identified because these departures included indications for surgery 
both more and less severe than those targeted by the protocol.
    The data retrieved from the BIMO audit were analyzed to determine 
if the major outcomes of the Cohort study were significantly different 
(statistically or clinically) with or without the presence of protocol 
departures, with or without the presence of recordkeeping 
inconsistencies, or at sites where the participating investigator, 
based on the audit, was or was not familiar with the protocol 
requirements. While some differences were noted between sites with and 
without inconsistencies, in most cases, these were not statistically 
significant and no consistent or clinically relevant patterns were 
noted. The analysis of the audited data did not find systemic bias in 
either the conduct of the study or its reported results. None of the 
analyzed audit data contradicted the published results of the Cohort 
study. Finally, the data audit analysis concluded that the audited data 
were consistent with other publicly available

[[Page 40030]]

data and that the Cohort study data could be used as part of a larger 
body of data to support the classification and reclassification of 
pedicle screw spinal systems.
      Documents relating to the Cohort study were destroyed.
    FDA disagrees. All Cohort study data were maintained in a master 
file. Only extra copies of information were destroyed in an effort to 
maintain the confidentiality of the identities of the participating 
surgeons and their patients. In addition, as a matter of course, FDA 
routinely assists Panel members in destroying copies of documents 
containing trade secret and/or confidential commercial information that 
they have received from FDA as preparatory material for a Panel 
meeting.
      Certain FDA employees had inappropriate relationships 
with pedicle screw manufacturers and others involved in the Cohort 
study.
    This allegation, which has two parts, is unfounded. FDA performed 
an internal affairs investigation of the employees about whom 
allegations were made. This investigation showed that their attendance 
at a health professional meeting was properly paid for by the agency, 
not subsidized by the regulated industry. Also in the case of one 
employee, FDA's investigation showed that negotiations regarding 
outside employment with the regulated industry had been properly 
reported to the employee's supervisors and immediate colleagues in all 
instances.
      The Scientific Committee and the Spinal Implant 
Manufacturers Group (SIMG) were not independent.
    FDA disagrees. The preamble to the proposed rule and the subsequent 
correction (60 FR 51946 and 60 FR 66227, December 21, 1995) described 
the makeup of the Scientific Committee and SIMG. SIMG consisted of 
representatives of manufacturers who provided funding to support a 
nationwide analysis of clinical data relating to pedicle screw spinal 
systems. SIMG did not participate in the design of the study. The study 
was designed and implemented by the Scientific Committee with input 
from FDA as to the feasibility of various clinical study design 
parameters. The Scientific Committee was formed by five professional 
medical societies. Although two SIMG representatives were part of the 
Scientific Committee, they were nonvoting members. Furthermore, even if 
there were not independence between the Scientific Committee and SIMG, 
there is no requirement that clinical studies be performed by parties 
independent of device manufacturers. In fact, FDA routinely receives 
and relies upon studies performed by manufacturers.
    3. Several comments contended that financial conflicts of interest 
were present in the three sources of data relied on by FDA to support 
the classification/reclassification of pedicle screw spinal systems. 
The comments claimed that, in the meta-analysis of the literature, the 
authors of the individual articles had financial conflicts of interest 
due to their relationships with device manufacturers. With respect to 
the analysis of the reformatted IDE data and the Cohort study, the 
comment stated that the IDE investigators and Cohort study participants 
had significant financial interests in the companies whose devices they 
were using and, therefore, had a strong financial incentive to report 
only successful results. Similar objections were raised about the 
authors of the 206 articles cited as constituting the body of medical 
literature bearing on pedicle screw fixation. The comments stated that 
almost all of the surgeons who authored these articles failed to 
disclose their financial connections to manufacturers. The comments 
stated that such interests raise serious concerns about researchers' 
motivation to perform the research, the propriety and importance of 
research questions and research designs, the adequacy of protection of 
human subjects, lack of bias, and veracity in collecting and analyzing 
the data and reporting the results.
    FDA recognizes that some of the clinical investigators involved in 
the three sources of data, as well as some of the authors of the 206 
literature articles used to support classification and reclassification 
of pedicle screw spinal systems, had financial interests in the devices 
they were studying. FDA disagrees, however, that these financial 
interests resulted in biased or unreliable data. Regardless of the 
source of the data, the meta-analysis, the reformatted IDE data, the 
Cohort study, or the collection of cited literature, the conclusions 
were similar, i.e., that pedicle screw spinal systems are safe and 
effective for the uses examined. Because of this, even if financial 
conflicts of interest were present, they did not affect the resulting 
data and the conclusions. Moreover, the agency has concluded that, 
despite the failure to disclose the financial interests of clinical 
investigators, the sponsors of these investigations and/or articles 
took reasonable steps to minimize potential bias.
    Furthermore, the fact that some spine surgeons were compensated by 
industry for research or consulting services, or were reimbursed for 
expenses incurred in connection with continuing medical education 
courses, did not affect the validity of any of the data. Moreover, many 
of the grants to support research were made directly to university 
accounts for general research and development, not directly to 
individual investigators. Consequently, the existence of a financial 
relationship between some surgeons and manufacturers did not 
necessarily result in biased case selection or reporting. Finally, FDA 
notes that research used to support a medical device marketing 
application has always been supported by the sponsor of the device and 
there is neither an expectation of nonsupport nor a requirement of 
disclosure of such support.
    4. Several comments stated that pedicle screw spinal systems 
present different safety and effectiveness issues than do either class 
II spinal devices using hooks and/or wires or noninstrumented spinal 
fusions. One comment identified the following areas of concern as 
having the potential of presenting unreasonable danger for patients:
    (1) Difficulty in placing screws completely within the walls of the 
pedicle;
    (2) Inability to determine screw placement postoperatively using 
radiographic techniques;
    (3) Damage to nerve tissue as a result of transient contact with a 
screw during screw placement;
    (4) Nerve root damage (irritation or compression) as a result of 
screw malposition;
    (5) Device failure;
    (6) Loss of bone density as a result of stress shielding;
    (7) Foreign body tissue response;
    (8) Crevice corrosion;
    (9) Fretting corrosion;
    (10) Fibrosis;
    (11) Bone fracture, particularly that of the pedicles;
    (12) Nerve root or spinal cord compression as a result of fibrosis 
or foreign body tissue response;
    (13) Chronic irritation;
    (14) Spine destabilization possibly leading to nonunion;
    (15) Increased venous pressure as a result of blocked venous 
channels within the bone;
    (16) Increased risk of infection;
    (17) Loss or decrease of sensory and/or motor function;
    (18) Loss of bowel or bladder control; and
    (19) Loss of sexual function.
    FDA agrees that pedicle screw spinal systems have some potential 
risks that

[[Page 40031]]

are different from those of other class II spinal devices. However, the 
majority of the potential risks presented by these devices, e.g., bone 
fracture, foreign body tissue response, loss or decrease in sensory 
and/or motor function, and device failure or corrosion, are also 
associated with class II spinal devices which use hooks and/or wires 
for the same intended uses. Similarly, potential risks such as nonunion 
and instability are also associated with noninstrumented spinal 
fusions. Moreover, as described in the proposed rule, the incidence of 
these adverse outcomes is no greater when a pedicle screw spinal system 
is used than when other types of spinal fusions, instrumented and 
noninstrumented, are performed in appropriately selected patients (60 
FR 51946 at 51957). Finally, FDA believes that the potential risks that 
are unique to pedicle screw spinal systems, e.g., difficulty in placing 
screws completely within the walls of the pedicle, inability to 
determine screw placement postoperatively using radiographic 
techniques, damage to nerve tissue as a result of transient contact 
with a screw during screw placement, and nerve root damage (irritation 
or compression) as a result of screw malposition, can be adequately 
addressed by the identified special controls and proper surgeon 
training and surgical technique.
    5. One comment asserted that the supposed advantages of pedicle 
screw spinal systems are largely theoretical. The comment stated that, 
while some investigators have shown that instrumented fusions increase 
the likelihood of obtaining a solid fusion, others have demonstrated 
that there is no significant increase in fusion rates performed with 
instrumentation as compared with noninstrumented fusions performed with 
bone graft alone.
    FDA agrees that the data do not always support the theoretical 
advantages of using pedicle screw spinal systems compared to alternate 
methods of achieving spinal fusion. However, in forming its 
recommendations, neither FDA nor the Panel is required to analyze the 
theoretical behavior of a given device. It is only required to 
determine whether the data demonstrate that there is a reasonable 
assurance of safety and effectiveness for its intended uses.
    6. The same comment stated that spinal fusion surgery is usually 
performed because of the belief that spinal instability results in 
pain. The clinical indicators used to determine which patients have 
spinal instability and, therefore, are candidates for spinal fusion 
surgery, are not clearly defined and are often not measurable. Because 
the results of spinal fusion surgery are also dependent on measurements 
of instability, a determination of success is difficult, if not 
impossible.
    FDA agrees that the methods used to measure instability are not 
perfect and that several working definitions of instability exist. 
Nevertheless, instability is measurable. In addition, the same 
instability definitions and measurement techniques are used in 
determining how a patient is to be treated, i.e., with pedicle screw 
spinal systems, class II spinal devices using hooks and/or wires, or 
noninstrumented fusions. FDA agrees that the determination of success 
of spinal fusion surgery is often difficult, but disagrees that it is 
impossible to determine. In fact, the success rates from using the 
three treatment methods described above have been determined and found 
to be reasonably equivalent (60 FR 51946 at 51954).
    7. Three comments questioned the most appropriate classification 
for pedicle screw spinal systems. One comment proposed that pedicle 
screw spinal systems be classified into class I and two comments 
suggested placing them in class III.
    FDA disagrees. Based on the available information, both the Panel 
and FDA concluded that general controls alone are not sufficient to 
provide a reasonable assurance of the safety and effectiveness of 
pedicle screw spinal systems intended to provide immobilization and 
stabilization of spinal segments as an adjunct to fusion in the 
treatment of the following acute and chronic instabilities or 
deformities of the thoracic, lumbar, and sacral spine: Degenerative 
spondylolisthesis with objective evidence of neurologic impairment, 
fractures, dislocations, scoliosis, kyphosis, spinal tumors, and failed 
previous fusion attempts (pseudarthrosis). The Panel and FDA also 
concluded that premarket approval was not necessary to provide such 
assurance. Both the Panel and FDA identified the potential risks 
associated with the use of these devices and concluded that sufficient 
information exists to establish special controls to provide reasonable 
assurance of their safety and effectiveness. As a result, FDA is 
classifying and reclassifying these devices in class II.
    8. A comment believed that classification and reclassification of 
pedicle screw spinal systems into class II is inappropriate because FDA 
was correct in its prior determination that basic principles of 
physiology, anatomy, biology, and biomechanical engineering demonstrate 
that pedicle screw spinal systems present a serious risk of injury to 
the spinal nerves, nerve roots, and surrounding vascular structures, 
and increase the risk of pseudarthrosis. According to this comment, 
these risks are not posed by existing spine fusion technology and 
pedicle screw spinal systems are of questionable efficacy in comparison 
to existing methodologies of treatment.
    FDA disagrees. FDA did not determine that basic principles of 
physiology, anatomy, biology, and biomechanical engineering demonstrate 
that pedicle screw spinal systems present a serious risk of injury. 
Rather, in 1984, FDA determined that a multiple component device system 
intended for attachment to the spine via the pedicles was not 
substantially equivalent to any legally marketed predicate device, in 
accordance with section 513(i)(1) of the act. FDA's decision was based 
on the fact that: (1) The sponsor did not identify a legally marketed 
preamendments device incorporating pedicle screw components and (2) the 
device posed potential risks not exhibited by other legally marketed 
predicate 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 (60 FR 51946 at 51947). As stated previously, FDA 
believes that the risks to health presented by pedicle screw spinal 
systems intended to provide immobilization and stabilization of spinal 
segments as an adjunct to fusion in the treatment of the following 
acute and chronic instabilities or deformities of the thoracic, lumbar, 
and sacral spine: Degenerative spondylolisthesis with objective 
evidence of neurologic impairment, fractures, dislocations, scoliosis, 
kyphosis, spinal tumors, and failed previous fusion (pseudarthrosis) 
can be adequately addressed by special controls. Consequently, FDA is 
classifying and reclassifying these devices into class II.
    9. One comment argued that manufacturers of pedicle screw spinal 
systems are seeking to have FDA down classify the device into class II 
because the manufacturers are unable to prove that pedicle screws are 
safe and effective for posterior implantation into the spine.
    FDA disagrees. First, contrary to the comment's statement, this 
classification and reclassification proceeding was

[[Page 40032]]

initiated by FDA; it is not in response to a petition for 
reclassification. Second, under section 513 of the act, devices are 
classified/reclassified into one of three classes based on reasonable 
assurance, not ``absolute proof,'' of their safety and effectiveness. 
Contrary to the comment's statement, it was not pedicle screw spinal 
system manufacturers, but rather the Panel and FDA, that concluded that 
pedicle screw spinal systems should be classified and reclassified into 
class II because they determined that premarket approval is not 
necessary to provide reasonable assurance of the device's safety and 
effectiveness, general controls alone are insufficient to provide such 
assurance, and there is sufficient information to establish special 
controls to provide such assurance.
    10. According to another comment, by classifying and reclassifying 
pedicle screw spinal systems into class II, FDA is acknowledging that 
there is no need for the manufacturers of pedicle screw spinal systems 
to prove that the devices are safe and effective.
    FDA agrees. The agency has determined that sufficient information 
exists to establish special controls to provide reasonable assurance of 
the safety and effectiveness of pedicle screw spinal systems intended 
to provide immobilization and stabilization of spinal segments in 
skeletally mature patients as an adjunct to fusion in the treatment of 
the following acute and chronic instabilities or deformities of the 
thoracic, lumbar, and sacral spine: Degenerative spondylolisthesis with 
objective evidence of neurologic impairment, fracture, dislocation, 
scoliosis, kyphosis, spinal tumor, and failed previous fusion 
(pseudarthrosis). FDA has determined that premarket approval is not 
necessary to provide such assurance.

B. Issues Relating to Information Published in the 1994 Supplementary 
Issue of the Journal Spine (vol. 20S, 1994)

    11. One comment objected that the manner in which the Scientific 
Committee communicated to the public the results of the Cohort study 
and related meta-analyses of the literature lacked scientific 
integrity. According to the comment, the articles were not peer 
reviewed, but rather they were accepted for publication solely by the 
Editor-in-Chief of the peer-reviewed journal Spine. The comment 
contended that publication of the articles without peer review 
prevented the studies from being submitted to the usual critical 
scrutiny of any peer review in the future.
    While the articles describing the Cohort study and related meta-
analysis were not peer-reviewed in the usual manner, they were 
subjected to a review process and published in an October 19, 1994, 
Special Supplement of Spine. The editorial at the beginning of the 
supplement states that,
    The members of the Scientific Committee and editors of Spine 
felt it important that presentations from the (July 1994, Panel) 
meeting be available to the readers of Spine in an expedited manner. 
The articles have been reviewed by the Scientific Committee, but 
have not gone through the normal review process of the Spine 
Editorial Board. However, it has been prepared, written, re-written, 
and critiqued by all members of the Scientific Committee and member 
of the Spine Editorial Board, as well as presented in an open public 
forum to the scientists who comprised the Orthopedic and 
Rehabilitation Devices Advisory Panel to the FDA. Weaknesses and 
strengths of the studies are readily apparent and have been 
addressed by each author, as well as in my summation.
    12. The comment also stated that the articles should not have been 
accepted for publication because the editorial policy of the journal 
requires that the recommended minimum followup period for studies 
should be 24 months.
    FDA disagrees. Under Spine policy, a sufficient length of time for 
followup of articles is necessary for publication. While the 
recommended time period for surgical procedures is 2 years, the policy 
does not state that studies with less than 2-year followup will not be 
published.

C. Issues Relating to the January 1995, 510(k) Substantial Equivalence 
Determination for a Pedicle Screw Spinal System Intended for Severe 
Spondylolisthesis

    13. A comment stated that the circumstances surrounding the first 
510(k) clearance of a pedicle screw spinal system in January 1995, were 
highly suspect because, until that time, FDA consistently had found 
bone screws for use in the pedicles to be not substantially equivalent 
to the identified predicate device, the lag screws used by Dr. 
Harrington. The comment also stated that the lag screws were 
manufactured as a custom device and used under a funded research grant 
and, therefore, were not in commercial distribution prior to 1976.
    FDA disagrees. The 510(k) applicant provided new evidence 
documenting, for the first time, that: (1) A medical device company had 
manufactured and shipped in interstate commerce bone (lag) screws 
intended for use in the pedicles of the spine prior to May 28, 1976; 
(2) the devices were marketed to physicians, including, but not limited 
to, Dr. Harrington; and (3) the devices were not used solely for 
research purposes.
    14. The same comment also argued that the two devices had different 
technological characteristics because the lag screws attach to fixation 
constructs by wires whereas the pedicle screws attach directly to 
plates or rods. The comment concluded that the applicant could not 
demonstrate that its device did not raise different questions of safety 
and effectiveness compared to the predicate device because the lag 
screws were used on an extremely limited basis and were abandoned 
because of a lack of effectiveness.
    FDA disagrees. The presence of technological differences does not 
preclude a finding of substantial equivalence under section 513(i) of 
the act. In accordance with section 513(i)(1)(A)) of the act and 
Sec. 807.100(b)(2)(ii)(B), for purposes of determining substantial 
equivalence, manufacturers have to demonstrate that their device (1) 
Has the same intended use as a predicate device and (2) if it has 
different technological characteristics than the predicate device, that 
the device is as safe and as effective as a legally marketed device, 
and it does not raise different questions of safety and effectiveness. 
The relative extent of use of one device compared to another is not 
relevant.
    In making its decision, FDA analyzed all of the data provided by 
the sponsor. This included reports describing the clinical and 
mechanical behavior of the device, in addition to affidavits. From 
these data, the Panel and FDA determined that the complications were 
similar to those of a predicate device and that the technological 
differences raised no new questions relating to safety or 
effectiveness.
    15. The comment also stated that FDA's reversal of its position 
with regard to the preamendments status of pedicle fixation devices was 
insupportable and a clear violation of its own regulations. 
Specifically, the comment stated that the agency took the unprecedented 
step of determining the existence of commercial distribution based 
solely on the affidavit of a former employee of a pedicle screw 
manufacturer. According to the comment, this was not sufficient 
evidence to demonstrate that the device was in commercial distribution 
prior to 1976.
    The use of affidavits to document the preamendments status of a 
predicate device is not unprecedented. In fact, FDA routinely allows 
affidavits to be used to document the preamendments status of a device. 
FDA recognizes that obtaining labeling, advertising, and

[[Page 40033]]

other records concerning the marketing status of a device dating back 
more than 20 years is often difficult, if not impossible. Therefore, 
FDA allows sponsors to rely on alternative methods to demonstrate 
interstate commerce. Moreover, contrary to the comment's statement, the 
preamendments status of the device was established by much more than a 
single affidavit. In fact, the 510(k) submission contained several 
affidavits from individuals other than the sponsor, correspondence, and 
other documents, e.g., shipping documentation, that demonstrated the 
preamendments status of the Harrington lag screws for use in a limited 
area of the spine, i.e., L5-S1, and for a 
particular indication, i.e., severe spondylolisthesis.
    16. Finally, the comment alleged that FDA changed its regulatory 
position regarding pedicle screw spinal systems after it made a 
``deal'' with the affected industry on or about June 15, 1993. The 
comment stated that, if manufacturers funded a retrospective study, FDA 
provided assurances that it would (1) Refrain from taking criminal, 
regulatory, or other legal actions against them; and (2) reclassify 
pedicle screw spinal systems without requiring prospective studies and 
without regard to the quality of any of the retrospective data.
    FDA disagrees. Prior to its January 1995, 510(k) decision and the 
publication of this classification and reclassification regulation, FDA 
consistently maintained that pedicle screw spinal systems, except when 
intended for a very limited use, were class III devices requiring 
premarket approval. The purpose of FDA's meeting with the affected 
industry and the orthopaedic professional societies was to request that 
these groups submit to the agency all available clinical data on the 
performance of pedicle screw spinal systems. FDA, at no time, agreed to 
change the regulatory status of these devices without regard to the 
quality of the data or to refrain from taking regulatory action if a 
retrospective study were funded.

D. Issues Relating to Misstatements or False Statements Appearing in 
the Proposed Rule

    17. One comment alleged that the statement in the preamble to the 
proposed rule regarding the conclusion of the August 20, 1993, Panel 
meeting, i.e., that pedicle screw spinal systems appear to be safe and 
effective when used as adjuncts to spinal fusion procedures, was 
inaccurate.
    FDA disagrees. The description of the August 20, 1993, Panel 
meeting contained in the preamble to the proposed rule states that the 
Panel concluded that mechanical testing data demonstrated that pedicle 
screw spinal systems exhibit adequate mechanical strength, rigidity, 
and fatigue resistance (60 FR 51946 at 51948).
    18. The same comment alleged that neither the transcripts from the 
two Panel meetings, nor the summary in the preamble to the proposed 
rule accurately reflected the Panel's conclusions regarding potential 
risks to health associated with the use of the pedicle screw spinal 
system, special controls, development of performance standards, 
mechanical performance of the device, and the Panel members' own 
personal knowledge of, and clinical experience with, the device.
    FDA disagrees that the transcripts of the two Panel meetings did 
not accurately reflect the Panel's conclusions. The proceedings from 
the two meetings were verbatim stenographic transcripts of oral 
testimony prepared by an independent transcriptionist. FDA also 
disagrees that the preamble to the proposed rule did not accurately 
reflect the Panel's conclusions. The preamble to the proposed rule 
mirrors the transcripts of the meetings.
    19. The same comment alleged that the Panel members (voting members 
and voting/nonvoting consultants), who met July 23, 1994, had 
inappropriate relationships, e.g., financial arrangements and ex parte 
communications, with pedicle screw spinal system manufacturers and had 
participated substantially in the design of the Cohort study, thereby 
compromising their impartiality.
    FDA disagrees in part. While it is expected that Panel members, who 
are experts in a given field, will often have some financial interests 
related to that field (e.g., certain arrangements with a manufacturer 
(designing a device sold by a particular manufacturer; serving as a 
consultant to a manufacturer; or receiving funding, directly or 
indirectly, for research), the required FDA conflict-of-interest 
questionnaire (FDA From 2725a) enables FDA to identify conflicts-of-
interest with a device or manufacturer that all substantial and/or 
material to the subject of a particular Panel meeting, and thereby 
facilitates the disclosure and possible waived for the Panel member(s) 
in order to permit their participation in Panel deliberations.
    FDA performed an internal affairs investigation of the Panel 
members regarding conflicts and ex parte communications . The agency 
reviewed whether the Panel was properly constituted. Investigation of 
alleged undisclosed and unwaived conflicts of interest held by Panel 
members found minor disparities and reporting omissions for two voting 
Panel members and one nonvoting consultant. The agency has concluded 
these disparities and omissions were insignificant and did not 
constitute financial conflicts of interest that would credibly 
influence their recommendations.
    The agency has found that one other voting Panel member had 
significant undisclosed financial conflicts. However, because the 
recommendation of the Panel, both in the July 23 meeting and on the 
subsequent homework assignment, was unanimous and this individual was 
not controlling, of or unduly influential of, the votes of the other 
Panel members and was not necessary to constitute a quorum, after 
expunging the participation of this Panel member, FDA has concluded 
that this Panel, both in the meeting and on the subsequent homework 
assignment, was a valid scientific Panel for purposes of making 
recommendations regarding classification and reclassification.

E. Issues Relating to FDA's Issuance of Regulations

    20. One comment argued that, in issuing a classification 
regulation, FDA may not rely on a scientific study unless it makes 
publicly available all study data, as well as the identities of the 
persons who furnished the data. The comment cited 21 CFR 10.20(j), 
20.63, and 860.5 as authority. In addition, the comment objected that 
FDA refused to disclose the identities of the physician-investigators 
who contributed data to the Cohort study, did not disclose the 
reformatted IDE analysis, the IDE data, or internal information bearing 
on the reliability of such data.
    FDA disagrees. Although the agency did not disclose the raw IDE or 
the Cohort study data, or the identities of the clinical investigators 
who furnished such data to the agency, FDA did provide a detailed 
analysis of the Cohort Study, the clinical data released by the IDE 
sponsors, and the meta-analysis (60 FR 51946 at 51960-51962; refs. 51, 
65, 66, 119, and 201). FDA believes these publicly available data not 
only satisfy the requirements under the statute, but provide the public 
with at least the level of detailed information as that usually 
available from published reports regularly relied upon to support 
classification and reclassification.

F. Response to Comments Which Contained Clinical Data

    21. Several comments provided clinical information to support the 
comment's position on the proposed

[[Page 40034]]

rule. The submitted clinical information consisted of literature 
articles describing clinical trials and two questionnaires, a surgeon/
patient questionnaire and a lawyer/client questionnaire. The surgeon/
patient questionnaire provided mixed results, i.e., some patients were 
satisfied with their clinical results and others were not satisfied, 
whereas the lawyer/client questionnaire provided only negative results, 
i.e., all clients were dissatisfied with their results.
    The majority of the articles submitted or referenced in these 
comments were already reviewed by the Panel and used as part of the 
basis for their recommendation to classify and reclassify pedicle screw 
spinal systems into class II. The remainder of these articles were not 
reviewed by the Panel because they were published after the July 1994, 
Panel meeting. As described in section V.M of this document, these 
articles did not raise new issues or concerns relating to the safety or 
effectiveness of pedicle screw spinal systems. Because of the inherent 
bias present in the questionnaires, e.g., the total number of 
questionnaires sent to patients/clients in relation to the number 
returned and the number included as part of the comment are unknown, 
the data cannot be used in analyzing the success rate of pedicle screw 
spinal systems. These data can be used, however, as part of an analysis 
of the complications. As such, the questionnaires did not describe any 
complications or raise any issues that had not already been reviewed by 
the Panel and FDA in making their determinations with respect to the 
classification and reclassification of pedicle screw spinal systems.

G. Requests for Additional Pedicle Screw Clinical Trials and Data 
Analyses

    22. Ten comments requested that FDA require submission of 
additional data before finalizing the classification and 
reclassification of pedicle screw spinal systems. The comments 
recommended that the following types of data be required: Studies to 
analyze the long-term effects of the device, continuing evaluations, 
collections of data using a recommended data report form for obtaining 
data directly from patients rather than from their surgeons, studies 
similar to the Cohort study but with larger sample sizes, comprehensive 
reviews of the literature, and comprehensive reviews of all data. In 
addition, one comment suggested that FDA was reclassifying these 
devices without reviewing clinical trial data documenting their safety 
and effectiveness.
    FDA disagrees. As previously explained, under section 513 of the 
act, devices are classified and reclassified into one of three classes 
based on reasonable assurance, not absolute proof, of their safety and 
effectiveness. The Panel recommended, and FDA concurred, that pedicle 
screw spinal systems intended to provide immobilization and 
stabilization of spinal segments in skeletally mature patients as an 
adjunct to fusion in the treatment of degenerative spondylolisthesis 
and spinal fractures be classified and reclassified into class II 
because they determined that premarket approval is not necessary to 
provide reasonable assurance of safety and effectiveness; general 
controls alone are insufficient to provide reasonable assurance of the 
device's safety and effectiveness; and there is sufficient information 
to establish special controls to provide such assurance. FDA also 
determined that, when intended to provide immobilization and 
stabilization of spinal segments in skeletally mature patients as an 
adjunct to fusion in the treatment of the following acute and chronic 
instabilities or deformities of the thoracic, lumbar, and sacral spine: 
Degenerative spondylolisthesis with objective evidence of neurologic 
impairment, fractures, dislocations, scoliosis, kyphosis, spinal 
tumors, and failed previous fusion attempts (pseudarthrosis), special 
controls would provide a reasonable assurance of safety and 
effectiveness. The Panel and FDA reached these conclusions only after 
considering a substantial amount of valid scientific evidence. As 
described previously, this valid scientific evidence consisted of 
clinical data collected from three sources--data from IDE's (the 
reformatted IDE data), data from the literature (the meta-analysis), 
and data collected directly from surgeons (the Cohort study). The IDE 
data was prospective clinical data collected under the protocols of 
FDA-approved clinical trials. The meta-analysis was retrospective 
clinical data published in peer-reviewed literature. The Cohort study 
consisted of retrospective nationwide clinical data collected from 
surgeons of various experience levels from a patient population that 
was homogeneous in terms of diagnosis, but mixed in terms of severity 
of disease. In addition to these sources of clinical data, MDR and 
MedWatch reports were analyzed for device problems. FDA does not 
believe that it is necessary to require submission of additional data, 
to conduct additional studies, or to re-review the literature before 
classifying and reclassifying these devices. FDA does agree, however, 
that the longer-term performance of these devices is not fully 
characterized. For this reason, postmarket surveillance (PMS) studies 
will be required.

H. Issues Relating to Indications for Use

    Over 200 comments addressed the various intended uses of pedicle 
screw spinal systems.
    23. Twenty-three comments questioned FDA's authority to regulate 
the indications for use of medical devices. They believed that, 
although restrictions on the use of pedicle screw spinal systems may be 
appropriate, this aspect of medical device regulation is outside the 
scope of FDA's authority and should be decided by professional 
societies, peer review groups, credentialing organizations, and 
hospitals. One comment stated that FDA should regulate the safety of 
medical devices only for certain indications. Several other comments 
stated that there should be no restrictions on the use of pedicle screw 
spinal systems. All of these comments argued that FDA's actions 
interfered with the practice of medicine.
    FDA disagrees. In determining whether or not a device is safe and 
effective, FDA first considers the intended uses for the device. Spinal 
fusion is not a medical indication but a treatment option which can be 
approached in a variety of ways. It is one of the desired outcomes from 
using pedicle screw spinal systems. FDA recognizes, however, that 
fusion in and of itself is not what patients with spinal disease are 
seeking. They wish to be relieved of their symptoms, have their 
objective impairment alleviated, and avoid more symptomatic or 
functional impairment. Devices that share the same outcome for a given 
condition do not necessarily share the same benefits and risks. One of 
the aspects in determining if a device may be legally marketed is 
deciding, based on the available data, what the appropriate indications 
are. A device may be an appropriate treatment for one indication, but 
not for another. In addition, to understand the evidence supporting a 
device's safety and effectiveness, a distinct medical condition 
requiring treatment must be identified. In reviewing the valid 
scientific evidence, the Panel recommended and FDA found that the use 
of pedicle screw spinal systems were safe and effective only for 
certain indications. The valid scientific evidence did not support 
unrestricted use of the device.
    In determining the safety and effectiveness of a device for the 
purpose

[[Page 40035]]

of classification or reclassification, both the Panel and the agency 
are to consider the persons for whose use the device is represented or 
intended, the conditions of use for the device, and the probable 
benefit to health from the use of the device weighed against any 
probable injury or illness from such use (Sec. 860.7(b)). The device is 
to be considered, not in a vacuum, but rather in the context of the 
patient population for whose use it is intended. Accordingly, there is 
reasonable assurance that a device is safe when it can be determined 
that the probable benefits to health from use of the device for its 
intended uses and conditions of use outweigh any probable risks 
(Sec. 860.7(d)(1)). The benefits and risks to health presented by a 
device depend, in large part, on the specific use for which the device 
is intended. There may be reasonable assurance that a device is safe 
for some, but not other, uses. Similarly, there is reasonable assurance 
that a device is effective when it can be determined that, ``in a 
significant portion of the target population,'' the use of the device 
for its intended uses and conditions of use will provide clinically 
significant results (Sec. 860.7(e)(1) (emphasis added)). It is clear, 
then, that when making determinations regarding the classification or 
reclassification of a device, it is appropriate for the agency to 
consider the specific intended uses of a device, including the specific 
patient populations for which it is intended. Consequently, the agency 
disagrees that it does not have authority to regulate the indications 
for use for pedicle screws and that it is interfering with the practice 
of medicine.
    24. One comment objected that FDA's proposed reclassification 
improperly exceeded the recommendations of the Panel.
    The Panel determined that the evidence demonstrated a reasonable 
assurance of safety and effectiveness of pedicle screw spinal systems 
intended for two severe and diagnostically distinct indications--
fracture and degenerative spondylolisthesis. Accordingly, the Panel 
recommended that the device be classified and reclassified into class 
II only when intended for these uses. FDA proposed that the device also 
be classified and reclassified into class II when intended for the 
following acute and chronic mechanical instabilities or deformities of 
the thoracic, lumbar, and sacral spine: degenerative spondylolisthesis 
with objective evidence of neurologic impairment, fractures, 
dislocations, scoliosis, kyphosis, spinal tumors, and failed previous 
fusion (pseudarthrosis). FDA disagrees that it exceeded its authority. 
21 CFR 860.3(h) defines a classification panel as an advisory committee 
established by the Commissioner for the purpose of making 
``recommendations'' (emphasis added) to the Commissioner on the 
classification/reclassification of devices. These recommendations are 
designed to assist the Commissioner in the proper classification and/or 
reclassification of a device. While FDA usually follows a Panel's 
recommendations, it is not required to do so.
    As stated in the preamble to the proposed rule, FDA believes that 
sufficient clinical data exist to classify and reclassify into class II 
pedicle screw spinal systems intended for degenerative 
spondylolisthesis with objective evidence of neurologic impairment, 
fractures, dislocations, scoliosis, kyphosis, spinal tumors, and failed 
previous fusion (pseudarthrosis). The medical literature and data from 
IDE clinical investigations provide adequate evidence that the device 
can safely and effectively stabilize the spine and maintain spinal 
alignment while fusion takes place. 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 or deformities of 
the thoracic, lumbar, and sacral spine are similar to those associated 
with other class II spinal implant devices, such as those classified in 
Sec. 888.3050 (21 CFR 888.3050) (60 FR 51946 at 51956).
    25. Several comments advocated classifying and reclassifying into 
class II pedicle screw spinal systems intended for additional uses, 
including degenerative disc disease, degenerative deformities, 
stenosis, iatrogenic instability and previous multiple laminectomies, 
facet joint disease, pseudospondylolisthesis, low back pain, disc 
herniation, arthritis, and osteomyelitis.
    FDA believes that valid scientific evidence does not currently 
exist to support classifying and reclassifying into class II pedicle 
screw spinal systems when intended for the indications listed above. 
Neither the literature nor the clinical data establish the safe and 
effective use of pedicle screw spinal systems for degenerative disc 
disease, degenerative deformities, stenosis, iatrogenic instability and 
previous multiple laminectomies, facet joint disease, 
pseudospondylolisthesis, low back pain, disc herniation, arthritis, or 
osteomyelitis. As stated in the preamble to the proposed rule, FDA has 
determined that, when intended for use in conditions not categorized as 
acute or chronic instabilities or deformities of the thoracic, lumbar, 
and sacral spine, premarket approval is necessary to ensure the safety 
and effectiveness of the device (60 FR 51946 at 51957). FDA-approved 
clinical trials for some of these indications are ongoing. When data 
from these or other studies become available for any of the indications 
described above, they may be submitted in either an application for 
premarket approval or reclassification petition.
    26. Eight comments advocated adding specific pediatric indications 
and one comment advocated adding general pediatric use to the list of 
indications. The specific indications included myelodysplasia, spina 
bifida, cerebral palsy, muscular dystrophy, myelomeningocele, and 
congenital subluxation.
    FDA disagrees. As stated previously, all valid scientific evidence 
reviewed by the Panel and FDA were obtained from skeletally mature 
populations. To date, the safety and effectiveness of pedicle screw 
spinal systems in pediatric populations have not been demonstrated. 
Therefore, this patient population is excluded from this classification 
and reclassification. When intended for use in pediatric populations, 
pedicle screw spinal systems are considered postamendments class III 
devices for which premarket approval is required.
    27. Several comments addressed ways in which FDA should further 
limit the indications for use of pedicle screw spinal systems, such as 
by including specific patient evaluation criteria or by specifying the 
severity of the condition.
    FDA disagrees that these actions are necessary. FDA classifies 
devices based upon, among other things, patient selection, not 
individual patient management. FDA notes that it is the responsibility 
of individual surgeons to determine the appropriateness of using a 
specific medical device for a given patient.
    28. Four comments stated that pedicle screw spinal systems should 
not be allowed on the market for any use. Another comment requested 
that an additional Panel meeting be convened to discuss further 
restricting the intended uses of pedicle screw spinal systems.
    FDA disagrees. After reviewing all available data and information, 
FDA believes that there is reasonable assurance that pedicle screw 
spinal systems are safe and effective for certain intended uses. FDA 
does not believe that pedicle screw spinal systems present a 
substantial deception or an

[[Page 40036]]

unreasonable and substantial risk of illness or injury. Consequently, 
FDA does not believe it would be appropriate to ban them under section 
516 of the act (21 U.S.C. 360f).
    FDA also disagrees that an additional Panel meeting is necessary 
because the relevant available data have been reviewed.

I. Issues Relating to Special Controls

    29. One comment asserted that PMS studies cannot legally be 
required for pedicle screw spinal systems because the devices are not 
intended for use in supporting or sustaining life and pose risks no 
different from those associated with the use of other preamendments 
class II spinal fixation devices.
    FDA disagrees. Under section 522 of the act (21 U.S.C. 360l), 
postmarket surveillance is required for certain devices and may be 
required for any device for which FDA determines that it is necessary 
to protect the public health or to provide safety or effectiveness data 
for the device. FDA has determined that PMS studies are necessary to 
provide longer-term data on the safety and effectiveness of pedicle 
screw spinal systems.
    Although originally proposed as a special control, FDA has 
determined that PMS studies are best imposed by order in the 
substantial equivalence determination letter for each device. This will 
preserve the discretionary nature of the PMS studies and will allow the 
agency to more easily remove the requirement once it determines that 
these studies are no longer necessary to assure the safety and 
effectiveness of pedicle screw spinal systems. The final regulation has 
been modified to reflect that PMS studies are no longer one of the 
special controls for these devices.
    30. One comment stated that PMS studies are appropriate only for 
devices cleared for marketing with limited clinical performance data. 
The comment noted that there now exists a vast amount of clinical 
information gained from use of pedicle screw spinal systems in several 
thousand patients. The comment also noted that, based on these data, 
the Panel concluded that, with respect to safety and effectiveness, 
these devices are comparable to, or better than, currently available 
spinal systems. The comment concluded that this clinical information 
and the conclusions drawn from this information provide sufficient 
clinical data to adequately identify and characterize the performance 
of pedicle screw spinal systems and the issues pertinent to safety and 
effectiveness, thereby obviating the need to conduct PMS studies.
    FDA disagrees that PMS studies are appropriate only for devices 
cleared for marketing with limited clinical performance data. Section 
522 of the act allows FDA to require PMS studies for any device for 
which it determines such studies would protect the public health or 
provide safety or effectiveness data for the device. As stated in the 
preamble to the proposed rule, FDA will require PMS studies in order to 
address issues related to device specific design differences, surgical 
techniques, and device usage (60 FR 51946 at 51955). Although there is 
ample short-term clinical performance data for these devices, there 
does not now exist sufficient longer-term, i.e., more than 24-month 
followup, safety and/or effectiveness data regarding device specific 
design differences, surgical techniques, and device usage.
    31. A second comment noted that components used to construct 
pedicle screw spinal systems could be identical to those used to 
construct either spinal interlaminal fixation orthoses (Sec. 888.3050) 
or spinal intervertebral body fixation orthoses (21 CFR 888.3060). 
Because PMS studies are not required for these devices, they should not 
be required for pedicle screw spinal systems. A third comment believed 
that PMS studies are inappropriate for well-established, standard of 
care treatments involving medical devices that were in existence prior 
to the 1976 amendments, including pedicle screw spinal systems.
    FDA disagrees that PMS studies are inappropriate for devices that 
were in existence prior to the 1976 amendments. Section 522(a)(2) of 
the act specifically authorizes FDA to require a manufacturer to 
conduct PMS studies for any device, regardless of when it was first 
introduced or delivered for introduction into interstate commerce, for 
which FDA determines that PMS studies are necessary to protect the 
public health or to provide safety or effectiveness data for the 
device. Although, as the comment states, certain devices have been used 
as pedicle screw spinal systems for some time, except for the limited 
severe spondylolisthesis intended use available since January 1995, 
pedicle screw spinal systems have not been legally marketed. Collection 
of the PMS study data will allow FDA to analyze information on the use 
of devices specifically intended, and legally marketed, for use as 
pedicle screw spinal systems.
    32. Five comments believed that PMS studies are unnecessary and 
will not further protect the public health because one or more of the 
following current reporting systems already provides adequate 
information on the performance of pedicle screw spinal systems: (1) The 
MDR System, (2) Voluntary Reporting under MedWatch, (3) User Reporting, 
and (4) Complaint Handling under the current good manufacturing 
practices. One comment supported a requirement that labeling remind 
surgeons they are required to report certain events under MDR. Two 
comments suggested that a statement which encourages health care 
professionals to submit MDR's under the Voluntary MedWatch System be 
placed in the required package insert of the device. Two other comments 
noted that no other class II spinal implant device is subject to PMS 
studies. Three comments also stated that collecting additional 
information will increase health care costs.
    FDA disagrees in part. The purposes of PMS studies and current 
reporting systems are different. PMS studies are active investigations 
of device performance during actual use, whereas other reporting 
systems, i.e., MedWatch, MDR, User Reporting, and Complaint Reporting, 
are passive reporting mechanisms. As such, these current reporting 
systems would not provide the agency with clinical monitoring 
information on pedicle screw spinal systems other than unexpected 
problems in the marketplace. The PMS studies, in contrast, will provide 
longer-term safety and effectiveness data for pedicle screw spinal 
systems once the devices are distributed in the general population 
under actual conditions of use. Finally, FDA is aware that PMS studies 
might have an impact on health care costs. Although this is 
unfortunate, the agency believes that it is necessary to impose this 
requirement and collect this information in order to assure the safety 
and effectiveness of pedicle screw spinal systems.
    33. A comment suggested that, due to the litigious climate 
surrounding these devices, it may be very difficult for manufacturers 
to recruit surgeons to participate in PMS studies.
    FDA recognizes the concern that there may be conditions which would 
make the collection of the data somewhat difficult. However, FDA 
believes that it is important that the data be obtained and that it is 
possible to recruit a sufficient number of surgeons to participate in 
PMS studies.
    34. One comment stated that the proposed identification for pedicle 
screw spinal systems was inaccurate, or at least misleading. The 
comment noted that, as proposed, a pedicle screw spinal system assembly 
must contain all of the components listed as part of the pedicle screw 
spinal system. The comment stated that, for any given assembly,

[[Page 40037]]

some or all of the system components could be used.
    FDA agrees in part. As proposed, the identification could be 
interpreted to require that all of the described components were 
necessary to construct a pedicle screw spinal system assembly. FDA has 
amended the identification of the device to clarify that not all of the 
described components are required to be used in a pedicle screw spinal 
system assembly.
    35. In the preamble to the proposed rule, FDA proposed two labeling 
special controls. These controls described the intended uses and 
indications for pedicle screw spinal systems and cautioned the user 
about potential risks to health if the devices were used under certain 
conditions. Three comments stated that the two labeling special 
controls were incorrectly categorized as ``warnings'' according to 
FDA's General Program Memorandum No. G91-1, ``Device Labeling 
Guidance.'' They believed that these labeling requirements are more 
appropriately described as ``precautions'' or ``important notes'' 
because they describe a particular patient population and not specific 
risks or hazards associated with the use of a device. Four comments 
objected that: (1) Use of the phrase ``* * * with significant potential 
risk for serious injury to patients * * *'' in the second labeling 
statement did not accurately reflect the data reviewed by the Panel to 
make its recommendation,(2) references to training and experience 
should not be part of the second labeling special control, and (3) the 
controls containing the language referred to in (1) and (2) should be 
removed or modified.
    FDA agrees with the comments that the two labeling special controls 
should be rewritten, but disagrees with the specific reasons. General 
Program Memorandum No. G91-1 states that ``A warning is appropriate 
when the device is commonly used for a disease or condition for which 
there is a lack of valid scientific evidence of effectiveness for that 
disease or condition and such usage is associated with a serious risk 
to health * * * Include an appropriate warning if there is reasonable 
evidence of an association of a serious hazard with the use of the 
device. A causal relationship need not have been proved.'' This is the 
case when pedicle screw spinal systems are used for indications other 
than significant mechanical instabilities or deformities of the 
thoracic, lumbar, and sacral spine. Because valid scientific evidence 
is not available to support a determination that a reasonable assurance 
exists that pedicle screw spinal systems are safe and effective for 
other indications, categorizing the first labeling special control as a 
``warning'' is the appropriate mechanism to alert users to the 
potential for injury to a patient.
    The second labeling special control does not warrant being 
described as a ``warning'' because it does not meet the definition of 
this term. It does not describe known serious adverse reactions or 
known potential safety hazards; it does not provide specific steps to 
be taken; it does not concern a use for which there is reasonable 
evidence of association with a serious hazard. It does, however, 
provide information on special care to be exercised by a practitioner, 
although the need for special care is implied, not explicitly stated. 
Accordingly, FDA concludes that it is more appropriately categorized as 
a ``precaution''.
    After reviewing the proposed special controls regarding labeling, 
FDA has concluded that the information should be stated more clearly. 
FDA believes that the labeling special controls reflect the data 
reviewed by the Panel. FDA also believes that the labeling special 
controls are necessary to provide reasonable assurance of the safety 
and effectiveness of the devices. Finally, as described in the next 
section, the intent of the second control was not to specify the type 
of training that should be available or to suggest that FDA would 
provide or approve any training. Rather, it was intended to alert 
surgeons to the necessity of receiving appropriate training in the use 
of specific pedicle screw spinal systems. Because of concerns with the 
proposed wording, the labeling special controls have been modified to 
read as follows:
    ``Warning: The safety and effectiveness of pedicle screw spinal 
systems have been established only for spinal conditions with 
significant mechanical instability or deformity requiring fusion 
with instrumentation. These conditions are significant mechanical 
instability secondary to degenerative spondylolisthesis with 
objective evidence of neurologic impairment, fracture, dislocation, 
scoliosis, kyphosis, spinal tumor, and failed previous fusion 
(pseudarthrosis). The safety and effectiveness of these devices for 
any other conditions are unknown.''
    ``Precaution: The implantation of pedicle screw spinal systems 
should be performed only by experienced surgeons with specific 
training in the use of this pedicle screw spinal system because this 
is a technically demanding procedure presenting a risk of serious 
injury to the patient.''
    36. A number of comments stated that appropriate surgeon training 
should be required prior to use of pedicle screw spinal systems and 
that classification/reclassification into class II would make access to 
training and device information easier. In addition, several comments 
believed that professional societies and hospitals, not FDA or the 
manufacturers, should determine what constitutes adequate training for 
surgeons implanting pedicle screw spinal systems.
    FDA agrees that it is important that surgeons who use pedicle screw 
spinal systems have proper training prior to using the device. FDA does 
not believe, however, that it should identify who is most qualified to 
provide such training or determine what constitutes adequate training. 
The precaution statement is intended to inform surgeons (and patients) 
of the possible effect the device could have on the patient if the 
surgeon implanting the device is not trained or experienced in the 
proper use of pedicle screw spinal systems. This includes knowledge of 
the indications, patient selection criteria, and appropriate surgical 
techniques.
    37. A comment questioned the proposed warning label because, in the 
past, FDA has prohibited pedicle screw spinal system manufacturers from 
supporting courses that described surgical techniques of ``off label'' 
uses demonstrating such uses or providing hands-on workshops to learn 
such uses.
    FDA disagrees. Previously, the agency issued several warning 
letters to pedicle screw spinal system manufacturers for participating 
in or supporting the training of practitioners in the use of long bone 
screw, pedicle fixation because, at that time, no long bone screw 
devices had received FDA clearance for use in the pedicles of the 
spine. As a result, FDA considered such use ``off label.'' Because the 
association with these training programs was considered the promotion 
of an ``off-label'' use, the agency stated that the manufacturers had 
misbranded and adulterated the long bone screws in accordance with 
sections 501(f)(1)(B) and 502(o) of the act (21 U.S.C. 351(f)(1)(B) and 
352(o)) and promotion of this use was considered a major modification 
of the intended use, requiring a new premarket notification (510(k)) 
submission under Sec. 807.81(a)(3)(ii). The regulations and the act are 
clear that manufacturers must have clearance for the intended use for 
which their device(s) are promoted, advertised, or held for sale.
    With the issuance of this final regulation, the agency now 
encourages pedicle screw spinal system manufacturers to support 
training for the class II intended uses. Such training, however, should 
not be provided before FDA clearance is received. The above referenced 
warning label will appear

[[Page 40038]]

only on devices that have been cleared for pedicle screw spinal 
fixation.
    38. The comment also claimed that the right to free speech 
guaranteed by the First Amendment to the U.S. Constitution should not 
be restricted by FDA's suppression of training for ``off label'' use.
    FDA disagrees that its limitations on promotional training 
conducted or sponsored by manufacturers for ``off label'' uses for 
pedicle screw spinal systems violate the First Amendment. As described 
above, the act requires that FDA regulate devices based on their 
intended use. The term ``intended use'' is broadly defined and 
encompasses the manner in which a company characterizes its product in 
the marketplace. The intended use of a device refers to the objective 
intent of the persons legally responsible for its labeling (Sec. 801.4 
(21 CFR 801.4)). ``The intent is determined by such persons' 
expressions or may be shown by the circumstances surrounding the 
distribution of the article. This objective intent may, for example, be 
shown by labeling claims, advertising matter, or oral or written 
statements by such persons or their representatives.'' ( Sec. 801.4 
(emphasis added)); (see e.g., Coyne Beahm, Inc. et al. v. United States 
Food and Drug Administration, et al., 958 F. Supp. 1060 (M.D.N.C. 
1997).) Consequently, oral statements and materials presented at 
industry-supported training programs may provide evidence of a device's 
intended use. If these statements or materials promote a use that has 
not been approved by the agency, the device is misbranded under section 
502(f)(1) of the act for failure to bear labeling with adequate 
directions for all intended uses, and under section 502(o) of the act 
because premarket notification was not provided as required under 
section 510(k) of the act. The device is also adulterated under section 
501(f) of the act for failure to have FDA approval. Thus, the various 
means by which manufacturers and their representatives provide 
information about their products to healthcare professionals and 
consumers, including statements and materials presented at industry-
supported scientific and educational activities, directly bear on 
whether a device is improperly promoted and, therefore, adulterated or 
misbranded.
    Because the regulation of devices is an area of extensive Federal 
regulation, the agency may regulate the communications at industry-
supported scientific and educational activities without violating the 
First Amendment. (Cf. SEC v. Wall Street Publishing Institute, Inc., 
851 F.2d 365 (D.C.Cir. 1988), cert. denied, 109 S.Ct. 1342 (1989).) 
Moreover, to the extent that such communications constitute protected 
speech, they are commercial speech and FDA's regulation of such 
activities does not violate the First Amendment. (See Bolger v. Youngs 
Drug Products, 103 S.Ct. 2875 (1983); S.U.N.Y. v. Fox, 109 S.Ct. 3028 
(1989); Cincinnati v. Discovery Network, 113 S.Ct. 1505 (1993).) 
Industry-supported scientific educational activities refer to a 
specific product, are economically motivated, and propose a commercial 
transaction. These programs are intended to convince the audience to 
prescribe, purchase, or otherwise use the particular product.
    The Supreme Court has afforded commercial speech limited 
constitutional protection. (See, e.g., Virginia State Board of Pharmacy 
v. Virginia Citizens Consumer Council, Inc., 96 S.Ct. 1817 (1976); 
Central Hudson Gas & Electric Corp. v. Public Service Commission, 100 
S. Ct. 2343 (1990).) In Central Hudson, the Supreme Court established a 
four-prong test to determine whether limitations on commercial speech 
are constitutional. The four prongs are: (1) Whether the speech 
concerns lawful activity and is not misleading, (2) whether the 
asserted government interest is substantial, (3) whether the limitation 
directly advances the governmental interest asserted, and (4) whether 
the limitation is not more extensive than is necessary to serve that 
interest. The Court has clarified that the fourth prong requires that 
the restriction be ``narrowly tailored'' to serve the asserted 
government interest. Narrow tailoring means a fit that is reasonable. 
(See S.U.N.Y. v. Fox, 109 S.Ct. 3028. 3035 (1989).)
    FDA's regulation of industry-supported scientific and educational 
activities satisfies all four prongs. First, as previously discussed, 
industry-supported scientific and educational activities that promote 
an unapproved device, or promote an approved device for an unapproved 
use, create an unlawful product--a misbranded or adulterated device. 
Accordingly, industry-supported activities that promote unlawful 
products concern illegal activity and may be prohibited. Second, FDA's 
limitations on promotional activities with respect to off label uses 
serve the substantial government interest of protecting the public 
health and safety by helping to ensure the dissemination of truthful 
and nonmisleading information about devices. The Supreme Court has 
repeatedly held that the government's ``interest in the health, safety, 
and welfare of its citizens constitutes a substantial interest.'' 
(Posadas de Puerto Rico Associates v. Tourism Co., 106 S.Ct. 2968, 2977 
(1986); Rubin v. Coors, 115 S.Ct. 1585, 1591 (1995).) The limitations 
also serve the second substantial government interest of protecting the 
public health by preserving the integrity of the premarket approval 
process under which manufacturers are required to establish that their 
devices are safe and effective for each of their intended uses before 
they may be marketed and promoted for those uses. Third, FDA's 
limitations on promotional activities with respect to off-label uses 
directly advance the government's substantial interests in protecting 
the public health and safety by helping to ensure the dissemination of 
truthful and nonmisleading information about devices and by preserving 
the integrity of the premarket approval process by dissuading 
manufacturers from using such activities as a means to promote 
unapproved products and unapproved uses, thereby encouraging scientific 
research and avoiding unnecessary harm to patients. Finally, FDA's 
limitations on industry-sponsored training sessions are narrowly 
tailored and are a reasonable approach to protect the public health and 
safety by discouraging the dissemination of misleading or biased 
information, and by maintaining the integrity of the premarket approval 
process. FDA's limitations apply only to industry-supported activities 
that relate to the supporting company's device or to competing devices. 
They are directed to the regulated sponsors of such activities, and do 
not apply to participating professionals or independent scientists and 
organizations.
    39. Several comments believed that the device should be available 
for use only by neurosurgeons or orthopaedic surgeons supervised by 
neurosurgeons.
    FDA disagrees. According to section 520(e)(1)(B), FDA may not 
restrict access to medical devices based on specialty or board 
certification.

J. Other Issues

    40. Several comments objected that publication of the proposed rule 
in the Federal Register was not appropriate because the general public 
is not aware of the Federal Register. The comments noted that another 
vehicle for disseminating the information would have been more 
appropriate.
    FDA disagrees. The act (sec. 513(d)(1) and 513(e)(1)) requires that 
a proposed rule be published in the Federal Register as the formal 
mechanism to provide all interested parties an opportunity to submit 
comments when

[[Page 40039]]

an advisory panel recommends an initial classification or change in 
classification for a medical device. Comments are invited from anyone. 
FDA recognizes that other mechanisms for distribution of this type of 
information is also appropriate. One of the alternate mechanisms 
currently being tested is electronic publication on the World Wide Web.
    41. Several comments objected to FDA's consideration of public 
comments, which may contain only anecdotal information, in determining 
the appropriate class for these devices.
    FDA agrees that comments provided by the public may contain 
anecdotal information that does not meet the definition of valid 
scientific evidence. However, FDA considers this information along with 
the information provided in other comments. These anecdotal comments 
did not raise any issues or comments that were not already addressed by 
the information that the Panel reviewed in making its determination 
that safety and effectiveness of pedicle screw spinal systems could be 
assured by special controls.
    42. Six comments disapproved of the release of the PIN's which 
identified the surgeons participating in the Cohort study.
    FDA regrets any problems that may have been caused by this 
inadvertent release of information. However, release of this 
information did not affect the quality, integrity, or value of the data 
upon which the Panel's recommendation was based.
    43. A comment noted that there is no consensus among spine surgeons 
that pedicle screw fixation has become the standard of care or the gold 
standard for treatment of spinal instability so as to justify the 
conclusion that the devices are safe and effective and to justify 
abandonment of the randomized control trial in making such an 
assessment.
    FDA agrees that there is no consensus among spine surgeons 
regarding pedicle screw spinal systems. However, a medical device does 
not need to be viewed as the ``gold standard'' in order for the agency 
to determine that there is reasonable assurance of its safety and 
effectiveness. Nor is it a requirement for the classification and 
reclassification process that all members of a medical specialty agree 
that a particular device should be used under all conditions. It is 
recognized that certain devices provide their best outcome when used 
for specific indications. This is one of the reasons why degenerative 
disc disease is not included as one of the intended uses in the 
classification and reclassification of pedicle screw spinal systems. 
Finally, as described above, randomized clinical trials are only one of 
the types of valid scientific evidence upon which FDA may rely in 
support of a classification/reclassification determination. Many IDE 
studies from which the reformatted IDE data came are still being 
actively pursued by their sponsors and the patients are being actively 
followed.

K. Labeling of Bone Screws

    44. A comment requested FDA to formally rescind its April 8, 1994, 
and June 15, 1994, letters to manufacturers of bone screws and devices 
classified under Secs. 888.3030 and 888.3040 (21 CFR 888.3030 and 
888.3040), directing them to amend their labeling by including the 
following: ``Warning: This device is not approved for screw attachment 
or fixation to the posterior elements (pedicles) of the cervical, 
thoracic, or lumbar spine.'' According to the comment, this labeling 
requirement will become unnecessary when pedicle screw spinal systems 
are classified into class II.
    FDA disagrees. In this final rule, FDA is classifying and 
reclassifying only pedicle screw spinal systems intended for screw 
attachment or fixation to the pedicles of the thoracic, lumbar, or 
sacral spine for immobilization and stabilization of spinal segments 
for the treatment of significant medical instability or deformity 
requiring fusion with instrumentation. This classification and 
reclassification in no way affects devices classified as single/
multiple component metallic bone fixation appliances and accessories 
(Sec. 888.3030) or smooth or threaded metallic bone fixation fasteners 
(Sec. 888.3040). Those devices are still not approved for screw 
attachment or fixation to the posterior elements (pedicles) of the 
cervical, thoracic, or lumbar spine. Hence, the 1994 amended labeling 
remains appropriate for these devices.
    45. One comment noted that in January 1995, FDA began clearing 
510(k)'s intended to treat grades 3 and 4 spondylolisthesis at the 
L5-S1 junction. The comment concluded that, by 
default, grades 1 and 2 spondylolisthesis, less severe conditions, are 
considered to be postamendments intended uses resulting in the device 
being automatically classified into class III. According to this 
comment, this means that FDA, through required manufacturer labeling, 
is instructing physicians to wait until grades 1 and 2 
spondylolisthesis develop into grades 3 and 4 spondylolisthesis before 
employing treatments utilizing pedicle screw spinal systems, which is 
not in the patient's best interests.
    FDA disagrees. FDA is not limiting physicians, through required 
manufacturer labeling, to wait until grades 1 or 2 spondylolisthesis 
develop into grades 3 or 4 spondylolisthesis. FDA is stating that the 
preamendments documentation in the 510(k) described marketing of the 
device only for the treatment of grades 3 and 4 spondylolisthesis at 
L5-S1. Treatment of grades 1 or 2 
spondylolisthesis does not have to wait until it progresses to grades 3 
or 4. Legally marketed devices which do not utilize pedicle screws are 
available for this purpose.

L. Review of New Pedicle Screw Spinal System 510(k)'s

    46. A comment pointed out that since FDA's January 1995, 
determination regarding the preamendments status of pedicle screw 
spinal systems in the treatment of severe spondylolisthesis, many 
510(k) submissions have been cleared for this use. FDA's proposed rule 
for pedicle screw spinal systems, once final, will essentially 
represent a labeling change for these devices, requiring new 501(k) 
submissions. The comment suggested that the new 510(k)'s should provide 
a draft copy of the revised labeling and a statement that the 
previously-cleared device has not been modified in any way that may 
affect its safety or effectiveness. According to the comment, this 
limited type of review would facilitate and expedite the review process 
and would not unnecessarily burden FDA's device evaluation staff.
    FDA agrees with this approach and intends to apply it in its review 
of 510(k)'s for pedicle screw spinal systems that were cleared 
previously for use in severe spondylolisthesis. Pedicle screw spinal 
systems which have not been previously reviewed, or that represent 
significant modifications compared to the previously cleared device(s), 
will require a complete 510(k) submission, including the device 
labeling.

M. Review of New Information Published and Submitted After Publication 
of the Proposed Rule: Pedicle Screw and Related Literature and MedWatch 
and MDR System Reports

    FDA performed a comprehensive search of the English-language 
medical literature published between 1994 and the present. Thirty-five 
articles pertained to the clinical performance of pedicle screw spinal 
systems. The clinical performance results, e.g., fusion rate and 
complication types and rates,

[[Page 40040]]

from these peer-reviewed articles did not differ from those previously 
reported in the preamble to the proposed rule for either pedicle screw 
spinal systems or the group of class II spinal devices using hooks and/
or wires or noninstrumented fusions.
    FDA also performed a review of the MedWatch and MDR databases from 
1994 to the present. The complications associated with pedicle screw 
spinal systems during this period were comparable to those reported in 
the preamble to the proposed rule for pedicle screw spinal systems and 
the group of class II spinal devices using hooks and/or wires and 
noninstrumented fusions.

VI. References

     The following references have been placed on display in the 
Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. These references may be 
seen by interested persons between 9 a.m. and 4 p.m., Monday through 
Friday.
     1. Rodgers, A. E., ``FDA Pedicle Screw Cohort Study: Audit 
Findings,'' July 30, 1996.
     2. Richter, K. C., ``Assessment of the Impact of BIMO Audit 
Findings for the Pedicle Screw Cohort Study on Study Results,'' August 
29, 1997.

VII. Environmental Impact

    The agency has determined under 21 CFR 25.24(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 impact of the final rule under Executive Order 
12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612) (as amended 
by Subtitle D of the Small Business Regulatory Fairness Enforcement Act 
of 1996 (Pub. L. 104-121), and the Unfunded Mandates Reform Act of 1995 
(Pub. L. 104-4)). 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 final rule is consistent with 
the regulatory philosophy and principles identified in the Executive 
Order. In addition, the final rule has been determined to be 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. Classification and reclassification of the device 
from class III to class II when the device is intended to provide 
immobilization and stabilization of spinal segments as an adjunct to 
fusion in the treatment of the following acute and chronic 
instabilities or deformities of the thoracic, lumbar, and sacral spine: 
Degenerative spondylolisthesis with objective evidence of neurologic 
impairment, fractures, dislocations, scoliosis, kyphosis, spinal 
tumors, and failed previous fusion attempts (pseudarthrosis) will 
relieve all manufacturers of the device of the cost of complying with 
the premarket approval requirements in section 515(b) of the act.
    Because classification and reclassification will reduce regulatory 
costs with respect to this device, it will not impose significant 
economic impact on any small entities, and it may permit small 
potential competitors to enter the marketplace by lowering their costs. 
The Commissioner of Food and Drugs, therefore, certifies that this 
final rule will not have a significant economic impact on a substantial 
number of small entities. In addition, this final rule will not impose 
costs of $100 million or more on either the private sector or State, 
local, and tribal governments in any one year, therefore, a summary 
statement of analysis under section 202(a) of the Unfunded Mandates 
Reform Act of 1995 is not required.

List of Subjects in 21 CFR Part 888

    Medical devices.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
888 is amended as follows:

PART 888--ORTHOPEDIC DEVICES

    1. The authority citation for 21 CFR part 888 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

    2. Section 888.3070 is added to subpart D to read as follows:

Sec. 888.3070  Pedicle screw spinal system.

    (a) Pedicle screw spinal systems--(1) Identification. Pedicle screw 
spinal systems are multiple component devices, made from a variety of 
materials, including alloys such as 316L stainless steel, 316LVM 
stainless steel, 22Cr-13Ni-5Mn stainless steel, Ti-6Al-4V, and 
unalloyed titanium, 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 a combination of anchors (e.g., 
bolts, hooks, and/or screws); interconnection mechanisms incorporating 
nuts, screws, sleeves, or bolts; longitudinal members (e.g., plates, 
rods, and/or plate/rod combinations); and/or transverse connectors. The 
devices are intended to provide immobilization and stabilization of 
spinal segments in skeletally mature patients as an adjunct to fusion 
in the treatment of the following acute and chronic instabilities or 
deformities of the thoracic, lumbar, and sacral spine: degenerative 
spondylolisthesis with objective evidence of neurologic impairment, 
fracture, dislocation, scoliosis, kyphosis, spinal tumor, and failed 
previous fusion (pseudarthrosis).
    (2) Classification. Class II (special controls). Pedicle screw 
spinal systems must comply with the following special controls:
    (i) Compliance with material standards,
    (ii) Compliance with mechanical testing standards,
    (iii) Compliance with biocompatibility standards, and
    (iv) Labeling which contains these two statements in addition to 
other appropriate labeling information:
    ``Warning: The safety and effectiveness of pedicle screw spinal 
systems have been established only for spinal conditions with 
significant mechanical instability or deformity requiring fusion 
with instrumentation. These conditions are significant mechanical 
instability or deformity of the thoracic, lumbar, and sacral spine 
secondary to degenerative spondylolisthesis with objective evidence 
of neurologic impairment, fracture, dislocation, scoliosis, 
kyphosis, spinal tumor, and failed previous fusion (pseudarthrosis). 
The safety and effectiveness of these devices for any other 
conditions are unknown.''
    ``Precaution: The implantation of pedicle screw spinal systems 
should be performed only by experienced spinal surgeons with 
specific training in the use of this pedicle screw spinal system 
because this is a technically demanding procedure presenting a risk 
of serious injury to the patient.''
    (b) Pedicle screw spinal systems for all other uses--(1) 
Identification. Pedicle screw spinal systems for all other uses are 
multiple component devices, made from a variety of materials, including 
alloys such as 316L stainless steel, 316LVM stainless steel, 22Cr-13Ni-
5Mn stainless steel, Ti-6Al-4V, and unalloyed titanium, that allow

[[Page 40041]]

the surgeon to build an implant system to fit the patient's anatomical 
and physiological requirements. Such an spinal implant assembly 
consists of a combination of anchors (e.g., bolts, hooks, and/or 
screws); interconnection mechanisms incorporating nuts, screws, 
sleeves, or bolts; longitudinal members (e.g., plates, rods, and/or 
plate/rod combinations); and/or transverse connectors.
    (2) Classification. Class III (premarket approval).
    (c) Date PMA or notice of completion of a PDP is required. An 
approved PMA or a declared completed PDP must be in effect before 
placing the device in commercial distribution. See Sec. 888.3.

    Dated: April 22, 1998,
Michael A. Friedman,
Lead Deputy Commissioner for the Food and Drug Administration.
Donna E. Shalala,
Secretary of Health and Human Services.
[FR Doc. 98-19944 Filed 7-23-98; 8:45 am]
BILLING CODE 4160-01-F