Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations 40025

Dated: July 17, 1998.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 98–19895 Filed 7–24–98; 8:45 am]

BILLING CODE 4160–01–F

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.

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 § 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
40026 Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations

1The 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.

2MDR 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.

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.

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.

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
Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations 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, concurrentlycontrolled 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, § 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
40028 Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations

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 metaanalysis 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 welldocumented 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 § 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 metaanalysis 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, § 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 metaanalysis 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 metaanalysis 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,

§ 860.7(c)(2) states that valid scientific

evidence may include ‘‘* * * welldocumented 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 § 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 § 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
Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations 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

§ 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 longerterm 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 postoperative 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 lostto-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-tofollowup 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
40030 Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations

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
Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations 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
40032 Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations

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-inChief 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, rewritten, 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

§ 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
Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations 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 conflictof-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 physicianinvestigators 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
40034 Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations

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 longterm 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 rereview the literature before classifying

and reclassifying these devices. FDA

does agree, however, that the longerterm 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
Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations 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

(§ 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

(§ 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

(§ 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 § 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). FDAapproved 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
40036 Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations

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

(§ 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 wellestablished, 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 longerterm 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,
Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations 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 ‘‘offlabel’’ 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

§ 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
40038 Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations

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 (§ 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.’’ (

§ 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 industrysupported 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 industrysupported 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 industrysupported scientific and educational

activities satisfies all four prongs. First,

as previously discussed, industrysupported 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 industrysupported 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
Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations 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 §§ 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

(§ 888.3030) or smooth or threaded

metallic bone fixation fasteners

(§ 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,
40040 Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations

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:

§ 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
Federal Register / Vol. 63, No. 143 / Monday, July 27, 1998 /Rules and Regulations 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 § 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

ENVIRONMENTAL PROTECTION

AGENCY

40 CFR Part 52

[IN75; FRL–6129–7]

Approval and Promulgation of

Implementation Plan; Indiana

AGENCY: Environmental Protection

Agency.

ACTION: Final rule.

SUMMARY: The United States

Environmental Protection Agency

(USEPA) is approving Indiana’s request

to grant an exemption for the northwest

Indiana (Lake and Porter Counties)

severe ozone nonattainment area from

the applicable Oxides of Nitrogen (NOX)

transportation conformity requirements.

The USEPA proposed approval on

January 6, 1998. The proposal was based

on information the Indiana Department

of Environmental Management (IDEM)

submitted to the USEPA as a State

Implementation Plan (SIP) revision

request for an exemption under section

182(b)(1) of the Clean Air Act (Act). The

technical basis for IDEM’s request was

the urban airshed modeling (UAM)

conducted for an attainment

demonstration for the Lake Michigan

Ozone Study (LMOS) modeling domain.

DATES: This rule is effective August 26,

1998.

ADDRESSES: Copies of the SIP revision,

public comments and USEPA’s

responses are available for inspection at

the following address: United States

Environmental Protection Agency,

Region 5, 77 West Jackson Boulevard,

Chicago, Illinois 60604. (It is

recommended that you telephone

Patricia Morris at (312) 353–8656 before

visiting the Region 5 Office.)

FOR FURTHER INFORMATION CONTACT:

Patricia A. Morris, Regulation

Development Section (AR–18J), Air

Programs Branch, Air and Radiation

Division, United States Environmental

Protection Agency, Region 5, 77 West

Jackson Boulevard, Chicago, Illinois

60604, Telephone Number (312) 353–

8656.

SUPPLEMENTARY INFORMATION:

I. Background

Clean Air Act section 176(c)(3)(A)(iii)

requires, in order to demonstrate

conformity with the applicable SIP, that

transportation plans and Transportation

Improvement Programs (TIPs)

contribute to emissions reductions in

ozone and carbon monoxide

nonattainment areas during the period

before control strategy SIPs are

approved by USEPA. This requirement

is implemented in 40 CFR 93.119,

which establishes what is known as the

‘‘build/no-build test.’’ The conformity

requirements of 176(c)(3)(A) are more

fully explained in the notice of

proposed rulemaking (63 FR 456,

January 6, 1998).

On July 13, 1994, the States of Illinois,

Indiana, Michigan, and Wisconsin (the

States) submitted to the USEPA a

petition for an exemption from the

requirements of section 182(f) of the

Clean Air Act (Act). The States, acting

through the Lake Michigan Air Directors

Consortium (LADCo), petitioned for an

exemption from the Reasonably

Available Control Technology (RACT)

and New Source Review (NSR)

requirements for major stationary

sources of NOX. The petition also asked

for an exemption from the

transportation and general conformity

requirements for NOX in all ozone

nonattainment areas in the Lake

Michigan Modeling domain.

On March 6, 1995, the USEPA

published a rulemaking proposing

approval of the NOX exemption petition

for the RACT, NSR and transportation

and general conformity requirements. A

number of comments were received on

the proposal. Several commenters

argued that NOX exemptions are

provided for in two separate parts of the

Act, in sections 182(b)(1) and 182(f), but

that the Act’s transportation conformity

provisions in section 176(c)(3) explicitly

reference section 182(b)(1). In April

1995, the USEPA entered into an

agreement to change the procedural

mechanism through which a NOX

exemption from transportation

conformity would be granted (EDF et al.

v. USEPA, No. 94–1044, U.S. Court of

Appeals, D.C. Circuit). Instead of a

petition under 182(f), transportation

conformity NOX exemptions for ozone

nonattainment areas that are subject to

section 182(b)(1) now need to be

submitted as a SIP revision request. The

northwest Indiana ozone nonattainment

area is classified as severe and, thus, is

subject to section 182(b)(1). Thus, the

NOX waiver for transportation

conformity would have been granted in

January 26, 1996, at the same time as the

waiver for RACT, NSR and general

conformity except for the technical

correction to require a SIP revision

request under 182(b)(1).

The transportation conformity

requirements are found at sections

176(c)(2), (3), and (4) of the Act. The

conformity requirements apply on an

areawide basis in all nonattainment and

maintenance areas. The USEPA’s

transportation conformity rule was

amended on August 29, 1995 (60 FR

44762) to reference section 182(b)(1)

rather than 182(f) as the means for

exempting areas subject to section

182(b)(1) from the transportation

conformity NOX requirements.

The May 24, 1996, SIP revision

request from Indiana was submitted to

meet the requirements in accordance

with 182(b)(1). Public hearings on this

SIP revision request were held on June

11, 1996.

In evaluating the 182(b) SIP revision

request, the USEPA considered whether

additional NOX reductions would

contribute to attainment of the standard

in the northwest Indiana severe ozone

nonattainment area and also in the

downwind areas of the LMOS modeling

domain. The USEPA granted a NOX

waiver for RACT, NSR, and general

conformity based on the submitted

modeling on January 26, 1996, (61 FR

2428). At the same time and using the

same technical support evaluation, the

USEPA would have granted the

transportation conformity waiver but for

the technical correction to grant the

waiver under 182(b)(1) instead of 182(f).

This rulemaking completes the efforts

under this technical correction.

On January 6, 1998, (63 FR 456), the

USEPA proposed approval of Indiana’s

request to grant an exemption for the

northwest Indiana severe ozone

nonattainment area from the applicable

NOX transportation conformity

requirements.

II. Public Comments

The USEPA received two sets of

comments during the public comment