57726 Federal Register / Vol. 65, No. 187 / Tuesday, September 26, 2000 / Rules and Regulations

1996. If no fastener is installed, seal the

corresponding fastener hole only, in

accordance with the alert service bulletin.

Alternative Methods of Compliance

(b) An alternative method of compliance or

adjustment of the compliance time that

provides an acceptable level of safety may be

used if approved by the Manager, Atlanta

Aircraft Certification Office (ACO), FAA.

Operators shall submit their requests through

an appropriate FAA Principal Maintenance

Inspector, who may add comments and then

send it to the Manager, Atlanta ACO.

Note 2: Information concerning the

existence of approved alternative methods of

compliance with this AD, if any, may be

obtained from the Atlanta ACO.

Special Flight Permits

(c) Special flight permits may be issued in

accordance with sections 21.197 and 21.199

of the Federal Aviation Regulations (14 CFR

21.197 and 21.199) to operate the airplane to

a location where the requirements of this AD

can be accomplished.

Incorporation by Reference

(d) The actions shall be done in accordance

with EMBRAER Alert Service Bulletin 120–

24–A057, dated November 14, 1996. This

incorporation by reference was approved by

the Director of the Federal Register in

accordance with 5 U.S.C. 552(a) and 1 CFR

part 51. Copies may be obtained from

Empresa Brasileira de Aeronautica S.A.

(EMBRAER), P.O. Box 343—CEP 12.225, Sao

Jose dos Campos—SP, Brazil. Copies may be

inspected at the FAA, Transport Airplane

Directorate, 1601 Lind Avenue, SW., Renton,

Washington; or at the FAA, Atlanta Aircraft

Certification Office, One Crown Center, 1895

Phoenix Boulevard, suite 450, Atlanta,

Georgia; or at the Office of the Federal

Register, 800 North Capitol Street, NW., suite

700, Washington, DC.

Note 3: The subject of this AD is addressed

in Brazilian airworthiness directive 96–12–

02, dated December 13, 1996.

Effective Date

(e) This amendment becomes effective on

October 31, 2000.

Issued in Renton, Washington, on

September 14, 2000.

Donald L. Riggin,

Acting Manager, Transport Airplane

Directorate, Aircraft Certification Service.

[FR Doc. 00–24113 Filed 9–25–00; 8:45 am]

BILLING CODE 4910–13–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 876

[Docket No. 94N–0380]

Gastroenterology and Urology

Devices; Effective Date of Requirement

for Premarket Approval of the

Implanted Mechanical/Hydraulic

Urinary Continence Device

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is issuing a final

rule to require the filing of a premarket

approval application (PMA) or a notice

of completion of a product development

protocol (PDP) for the implanted

mechanical/hydraulic urinary

continence device, a generic type of

medical device intended for the

treatment of urinary incontinence. 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 amendments),

the Safe Medical Devices Act of 1990

(the SMDA), and the Food and Drug

Administration Modernization Act of

1997.

EFFECTIVE DATE: This rule is effective

October 26, 2000.

FOR FURTHER INFORMATION CONTACT:

Nicole L. Wolanski, Center for Devices

and Radiological Health (HFZ–470),

Food and Drug Administration, 9200

Corporate Blvd., Rockville, MD 20850,

301–594–2194.

SUPPLEMENTARY INFORMATION:

I. Introduction

SMDA added new section 515(i) to

the act (21 U.S.C. 360e(i)). This section

requires FDA to review the

classification of preamendments class III

devices for which no final rule has been

issued requiring the submission of

PMA’s and to determine whether each

device should be reclassified into class

I or class II or remain in class III. For

devices remaining in class III, SMDA

directed FDA to develop a schedule for

issuing regulations to require premarket

approval.

In the Federal Register of November

23, 1983 (48 FR 53032), FDA published

a final rule classifying into class III

(premarket approval) the implanted

mechanical/hydraulic urinary

continence device, a medical device.

Section 876.5280 (21 CFR 876.5280) of

FDA’s regulations setting forth the

classification of the implanted

mechanical/hydraulic urinary

continence device applies to: (1) Any

implanted mechanical/hydraulic

urinary continence device that was in

commercial distribution before May 28,

1976, and (2) any device that FDA has

found to be substantially equivalent to

an implanted mechanical/hydraulic

urinary continence device in

commercial distribution before May 28,

1976.

In the Federal Register of February

15, 1995 (60 FR 8595), FDA published

a proposed rule, under section 515(b) of

the act (21 U.S.C. 360e(b)), to require the

filing of PMA’s or PDP’s for the

classified implanted mechanical/

hydraulic urinary continence device

and all substantially equivalent devices.

In accordance with section 515(b)(2)(A)

of the act, FDA included in the

preamble, the agency’s proposed

findings regarding: (1) The degree of risk

of illness or injury designed to be

eliminated or reduced by requiring the

device to meet the premarket approval

requirements of the act, and (2) the

benefits to the public from use of the

device.

The preamble also provided an

opportunity for interested persons to

submit comments on the proposed rule

and the agency’s proposed findings.

Under section 515(b)(2)(B) of the act, it

also provided an opportunity for

interested persons to request a change in

the classification of the device based on

new information relevant to its

classification. Any petition requesting a

change in the classification of the

implanted mechanical/hydraulic

urinary continence device was required

to be submitted by March 2, 1995. The

comment period closed on June 15,

1995.

The agency received three comments

in response to the February 15, 1995,

proposed rule. These comments were

from physicians and a manufacturer.

These three comments raised numerous

issues. A summary of the comments and

FDA’s responses are set out below.

This regulation is final upon

publication and requires PMA’s or

notices of completion of a PDP for all

implanted mechanical/hydraulic

urinary continence devices classified

under § 876.5280 and all devices that

are substantially equivalent to them.

PMA’s or notices of completion of a PDP

for these devices must be filed with

FDA within 90 days of the effective date

of this regulation. (See section

501(f)(1)(A) of the act (21 U.S.C.

351(f)(1)(A)).)

Federal Register / Vol. 65, No. 187 / Tuesday, September 26, 2000 / Rules and Regulations 57727

II. Summary and Analysis of Comments

and FDA’s Response

A. General Comments

(Comment 1) FDA received two

comments from individual physicians.

Although these comments did not object

to the proposed call for PMA’s or PDP’s,

they voiced the following common

concerns: (1) The implanted

mechanical/hydraulic urinary

continence device is intended for those

with severe urinary incontinence, in

whom other modalities are

unsuccessful, (2) removal of this device

from the U.S. market would be

detrimental to public health, and (3)

citing the 20 years of use of the device,

sufficient historical data exist to

evaluate the safety and effectiveness of

the implanted mechanical/hydraulic

urinary continence device. This last

concern was also noted in a comment

from an implanted mechanical/

hydraulic urinary continence device

manufacturer, which stated that the

decades of medical literature regarding

the risks and benefits of this device

provide sufficient evidence of its safety

and effectiveness. The comments

remarked that FDA has overstated the

risks of the implanted mechanical/

hydraulic urinary continence device,

that the studies are costly and

unnecessary, and that the agency can

rely on MDR reports or use its authority

to ask for post-market surveillance on

510(k) products.

FDA agrees that urinary incontinence

is a significant medical problem that

negatively affects the lives of many men

and women in the United States.

Furthermore, since implanted

mechanical/hydraulic urinary

continence devices represent an

important option in the treatment of

severe urinary incontinence, FDA agrees

with these comments that removal of

the implanted mechanical/hydraulic

urinary continence device from the

market would negatively impact public

health. As a result of this concern, FDA

has taken the following steps to promote

the continued availability of the

implanted mechanical/hydraulic

urinary continence device during the

call for PMA’s or PDP’s: (1) FDA issued

the guidance document entitled ‘‘Draft

Guidance For Preparation Of PMA

Applications For The Implanted

Mechanical/Hydraulic Urinary

Continence Device(Artificial Urinary

Sphincter)’’ in May 1995 (the 1995

guidance document) to provide industry

with detailed recommendations on the

content of PMA’s; (2) FDA has

communicated closely with each

implanted mechanical/hydraulic

urinary continence device manufacturer

to address the concerns identified in the

proposed rule using least burdensome

methods, as well as provide

recommendations on the design of

preclinical and clinical studies; and (3)

FDA intentionally postponed the call for

PMA’s or PDP’s to allow manufacturers

to collect sufficient data to support the

filing of a PMA or PDP.

FDA agrees with the comments that

there is a significant amount of

information in the published and

unpublished literature regarding the

implanted mechanical/hydraulic

urinary continence device. However, to

FDA’s knowledge, these studies are

neither sufficiently detailed nor

properly designed to perform a

statistically valid evaluation of safety

and effectiveness. As recommended in

the 1995 guidance document, PMA’s or

PDP’s should contain safety and

effectiveness information on the specific

device model(s) proposed in the

application.

Although a large body of historical

data exists regarding the clinical

outcomes of models of implanted

mechanical/hydraulic urinary

continence devices that are no longer

marketed, there is less information

available regarding the safety and

effectiveness of currently-marketed

models. However, if sufficient historical

information exists to document the

safety and effectiveness of a particular

implanted mechanical/hydraulic

urinary continence device model that a

manufacturer desires to market, or if

data about earlier models are directly

relevant to a particular device, FDA

encourages the use of this data in

support of a PMA or PDP for that model.

While FDA agrees that the proposed

rule may have overstated the risks of

some of the specific implanted

mechanical/hydraulic urinary

continence device models that are

currently on the market, we believe that

the information in the proposed rule

represents a reasonable estimate of the

risks and benefits of the entire category

of implanted mechanical/hydraulic

urinary continence devices. As noted in

many of these comments, manufacturers

have made numerous design

modifications to improve the reliability

of the implanted mechanical/hydraulic

urinary continence device and the

medical community continues to

improve the patient selection criteria,

patient counseling information,

operative technique, and post-operative

care to reduce the incidence of

complications. Therefore, FDA expects

the rates of complications reported in

PMA’s or PDP’s for particular implanted

mechanical/hydraulic urinary

continence devices to be lower than

estimated from a review of the literature

on the entire device category. However,

in writing the proposed call for PMA’s

or PDP’s, FDA must consider the risks

and benefits of all implanted

mechanical/hydraulic urinary

continence devices that currently have

the status of being legally marketed in

the United States.

While FDA acknowledges that MDR

reports and post-market surveillance are

valuable tools for obtaining information

on devices, FDA believes that additional

data are necessary to establish the safety

and effectiveness for the implanted

mechanical/hydraulic urinary

continence device and that these data

should be submitted and evaluated

within a PMA or PDP.

B. Erosion

(Comment 2) There was one comment

regarding the risk of erosion. This

comment stated that erosion of the

implanted mechanical/hydraulic

urinary continence device occurs

infrequently, and for reasons that are

not inherent in the device, but instead

may be due to a variety of conditions

that are characteristic of some patients,

e.g., as a result of scar tissue and/or

eradiated tissue. The comment further

stated that erosion is reported to occur

at low rates which are within acceptable

limits.

While FDA agrees that the risk of

erosion may be small, insufficient

information is available to determine

the frequency of this event or its

consequences. Therefore, FDA believes

that it is important for studies submitted

in a PMA or PDP to provide accurate

information on the incidence of erosion

associated with the implantation of the

implanted mechanical/hydraulic

urinary continence device. As noted in

the 1995 guidance document, FDA is

requesting information to address the

incidence of erosion for this device.

C. Infection

(Comment 3) There was one comment

on the risk of infection. This comment

agreed with the proposed rule in

acknowledging that infections are not

necessarily caused by the device, citing

that surgical infections are also

reported.

FDA believes that proper patient

selection, surgical precautions, and

post- operative care can minimize the

risk of infection. FDA also believes that

it is important for studies submitted in

a PMA or PDP to provide accurate

information on the incidence and

consequences of infection associated

with the implantation of the implanted

mechanical/hydraulic urinary

continence device. As noted in the 1995

57728 Federal Register / Vol. 65, No. 187 / Tuesday, September 26, 2000 / Rules and Regulations

guidance document, FDA is requesting

information on the incidence of

infection for this device.

D. Hydronephrosis

(Comment 4) There were three

comments regarding the risk of

hydronephrosis. These comments stated

that the occurrence of hydronephrosis is

rare and generally a risk only to those

with urinary incontinence owing to

neurogenic bladder if they have

decreased bladder compliance before

implantation. Therefore, this risk can be

addressed by contraindicating use of the

device in patients with decreased

bladder compliance and closely

monitoring all implant recipients who

have neurogenic bladders. Also, one

comment indicated that the presence

and normal use of the implanted

mechanical/hydraulic urinary

continence device does not create a

negative obstruction to the neurogenic

bladder any more than a normally

functioning internal sphincter and

therefore, the use of the device does not

create an additional risk for

hydronephrosis that was not already

present in this group of patients.

Another comment stated that new

solutions bring new risks and new

problems, and the benefit of continence

is well worth the risks. Two comments

cited the need for appropriate followup.

FDA agrees that the majority of

patients who experience

hydronephrosis have been diagnosed

with some type of nerve or spinal cord

damage. Additionally, FDA concurs

with the comments that patients with

decreased bladder compliance should

not receive an implanted mechanical/

hydraulic urinary continence device.

However, since hydronephrosis can

ultimately lead to kidney damage and

require surgical intervention, FDA

considers hydronephrosis a serious risk

to health. To assess the risk/benefit ratio

of an implanted mechanical/hydraulic

urinary continence device, FDA believes

it is essential to evaluate the frequency

of this event and its consequences.

Therefore, FDA believes it is important

for studies submitted in a PMA or PDP

to provide accurate information on the

pathogenesis and incidence of

hydronephrosis with the implantation

of the implanted mechanical/hydraulic

urinary continence device.

E. Human Carcinogenicity

(Comment 5) There was one comment

regarding the risk of human

carcinogenicity. This comment stated

that there is no evidence in the medical

literature that the implanted

mechanical/hydraulic urinary

continence device is associated with the

development of cancer. This comment

further stated that silicone causes solid

state tumors in animals, a phenomenon

thought to be restricted to animals and

not applicable to humans. The comment

also stated that epidemiological studies

have not found that women with

silicone breast implants, which contain

silicone elastomers similar or identical

to those used in the implanted

mechanical/hydraulic urinary

continence device, are at an increased

risk for cancer and that human

carcinogenicity should be removed from

the list of significant risks associated

with the implanted mechanical/

hydraulic urinary continence device.

FDA believes that the potential

carcinogenicity for this device remains

unknown. The agency continues to

believe that carcinogenicity is a

potential risk that should be addressed

in a PMA or PDP.

F. Human Reproductive and

Teratogenic Effects

(Comment 6) There was one comment

related to human reproductive and

teratogenic effects. This comment stated

that there is no evidence that the

implanted mechanical/hydraulic

urinary continence device is

antiandrogenic or teratogenic. This

comment also stated that since most

implant patients are male, any effects on

reproduction or development of

offspring must be mediated largely by

effects on the male spermatozoa or on

male libido. This comment further

stated that human reproductive and

teratogenic effects should be removed

from the list of significant risks

associated with the implanted

mechanical/hydraulic urinary

continence device.

FDA agrees that there are no

published studies showing that

implanted mechanical/hydraulic

urinary continence devices are

associated with toxic reproductive

effects or teratogenic effects. However,

FDA believes that the reproductive and/

or teratogenic effects of these products

remain potential risks that should be

addressed in a PMA or PDP.

G. Immune Related Connective Tissue

Disorders—Immunological Sensitization

(Comment 7) There was one comment

regarding the risks of immune related

connective tissue disorders and

immunological sensitization. This

comment stated that there is no

evidence that the implanted

mechanical/hydraulic urinary

continence device causes either immune

related connective tissue disorders or

immunological sensitization and that no

definitive link between silicone and

autoimmune diseases has been

established. Furthermore, this comment

stated that since the diseases most

frequently associated with autoimmune

responses occur at a lower frequency in

men than women, it may be impossible

to extrapolate the findings from any

study of silicone breast implants to the

implanted mechanical/hydraulic

urinary continence device. This

comment stated that immune related

connective tissue disorders and

immunological sensitization should be

removed from the list of significant risks

associated with the implanted

mechanical/hydraulic urinary

continence device.

FDA agrees that no definitive causal

relationship has been established

between immunological effects and/or

connective tissue disorders and the

implanted mechanical/hydraulic

urinary continence device.

Epidemiological data published within

the last several years (Refs. 3, 4 and 5)

addressing the relationship between

silicone breast prostheses and

autoimmune diseases or connective

tissue diseases indicate that silicone

breast prostheses have not caused a

large increase in the incidence of

connective tissue disease in women

with breast implants. However, the

possibility of a smaller, increased risk of

immunological effects among patients

with implanted mechanical/hydraulic

urinary continence devices, or of an

atypical, as yet undefined, syndrome or

disease, cannot be eliminated based on

these data.

FDA is aware that differences between

the incidence of autoimmune diseases

or connective tissue diseases in men

and women make it difficult to

extrapolate the results of breast implant

studies (in women) to prospective

outcomes of the implanted mechanical/

hydraulic urinary continence device (in

men and women). In the 1995 guidance

document, FDA recommends that a

cohort of implanted mechanical/

hydraulic urinary continence device

recipients be regularly monitored for the

occurrence of such adverse events as

part of an active surveillance program

for a minimum of 5 years

postimplantation. FDA continues to

believe that adverse immune related

connective tissue disorders and

immunological sensitization remain

potential risks that must be assessed in

a PMA or PDP, but FDA does not

believe that 5 years of prospective data

collection on a specific product will be

necessary for PMA approval or PDP

completion.

Federal Register / Vol. 65, No. 187 / Tuesday, September 26, 2000 / Rules and Regulations 57729

H. Biological Effects of Silica

(Comment 8) One comment stated

that fumed amorphous silica is so

tightly bound in the silicone elastomer

components of the implanted

mechanical/hydraulic urinary

continence device that the fumed

amorphous silica is biologically

inactive. For that reason, this comment

believed that the presence of fumed

amorphous silica is not a risk to health

of the implanted mechanical/hydraulic

urinary continence device. This

comment also stated that complications

related to the release of silica from the

implanted mechanical/hydraulic

urinary continence device have not been

observed.

FDA does not believe there is

sufficient information to eliminate

fumed amorphous silica as a potential

risk to health associated with the

implanted mechanical/hydraulic

urinary continence device, particularly

since the amount of fumed amorphous

silica is varied in order to achieve the

desired physical characteristics of the

device’s components. Consequently, the

agency believes that this potential risk

to health should be addressed in a PMA

or PDP.

I. Silicone Particle Shedding, Silicone

Gel Leakage, and Associated Migration

(Comment 9) There was one comment

regarding the risk of silicone particle

shedding. This comment stated that the

potential risk to patients with implanted

mechanical/hydraulic urinary

continence devices is small, and should

be deleted from the list of significant

risks.

Based upon information presented in

the comments, FDA agrees that silicone

particle shedding is not a risk to health

of the implanted mechanical/hydraulic

urinary continence device. Although

silicone particle shedding and

subsequent migration have been

reported with implanted mechanical/

hydraulic urinary continence devices

(Ref. 1), the quantity of such particles

was minimal and no deleterious effects

were associated with this finding.

Furthermore, subsequent research

published after the proposed call for

PMA’s and PDP’s was unable to

document evidence of silicone particle

migration (Ref. 2). FDA, therefore, does

not believe silicone particle shedding is

a risk that needs to be addressed in

PMA’s or PDP’s for these devices.

(Comment 10) One comment stated

that silicone gel leakage and gel bleed

are not risks to the health associated

with this device since there are no

implanted mechanical/hydraulic

urinary continence devices that contain

silicone gel.

FDA disagrees with the comment that

no implanted mechanical/hydraulic

urinary continence device contains

silicone gel. FDA is aware of at least one

device model, no longer marketed in the

United States, that contained silicone

gel within its silicone elastomer

envelope. FDA agrees with the comment

that the potential risks of silicone gel are

not applicable to implanted mechanical/

hydraulic urinary continence devices

that do not contain silicone gel.

J. Need for Risk/Benefit Information

(Comment 11) One comment stated

that FDA should justify the need for

risk/benefit data for various subgroups

as is done in the literature. The

literature lists the medical conditions at

high risk for surgery (e.g., spinal cord

injured patients, and Type I diabetics

with high levels of glycosylated

hemoglobin), as well as subgroups for

whom less than optimal results may

occur. Two comments were received

regarding the collection of information

on the presurgical workup and prior

failed conservative treatments. Both

comments stated that this information

can be found in the literature, and that

there is no need for additional studies

to evaluate these areas.

Although some information

pertaining to these issues can be found

in the literature, FDA believes that more

comprehensive and complete data are

needed regarding the risk/benefit

analysis for each subgroup for whom the

device will be indicated.

(Comment 12) There was one

comment objecting to the concern that

the device may have effects upon male

sexual function. This comment stated

that a majority of the male patients

receiving these devices are either postprostatectomy or post-pelvic trauma

patients who, independent of the

device, would be at high risk for

developing erectile function problems.

Because not all patients would be at

risk of developing erectile dysfunction

independent of the device, FDA believes

that all potential risks should be

identified and that the frequency of

these risks should be reported to allow

the patient to make an informed choice

regarding options for treatment.

K. PMA Contents

(Comment 13) FDA received one

extensive comment on the types of

manufacturing information, pre-clinical

testing, and clinical data that should be

required in a PMA for an implanted

mechanical/hydraulic urinary

continence device, as well as two

general comments on the appropriate

contents of a PMA.

FDA agrees with many of the points

raised in these comments. Although the

1995 guidance document describes the

general types of manufacturing, preclinical, and clinical data that FDA

believes can support approval of a PMA

for an implanted mechanical/hydraulic

urinary continence device, the agency

realizes that other, scientifically sound

methods exist for addressing the

identified risks and benefits of the

device and encourages manufacturers to

document the safety and effectiveness of

their device using least burdensome

approaches. In fact, FDA has agreed to

the use of many of these alternative

approaches for the collection and

analysis of data in its past interactions

with manufacturers of implanted

mechanical/hydraulic urinary

continence devices. Furthermore, FDA

intends to revise the 1995 guidance

document to incorporate many of these

comments.

III. Findings With Respect to Risks and

Benefits

A. Degree of Risk

1. Erosion

Erosion is the breakdown of tissue

adjacent to the device. Types of erosion,

which have been reported, include: cuff

erosion into the urethra or bladder neck

and pump erosion through the labia,

vagina, scrotum and the perineum.

Factors contributing to erosion include

infection of the prosthesis, previous

surgery, poor vascularization, prior

pelvic irradiation, improper cuff size,

improper reservoir volume, surgical

injury, excessive urethral compression,

and premature activation. Erosion may

lead to device extrusion, and can

require surgical intervention.

2. Infection

Infection is a risk associated with any

surgical implant procedure, including

the implanted mechanical/hydraulic

urinary continence device.

Compromised device sterility and

surgical techniques may be a major

contributing factor to this risk. Infection

may result in the removal of the implant

and may result in an inability to replace

the device.

3. Mechanical Malfunctions

As with other prosthetic devices

intended to restore a physiologic

function, implanted mechanical/

hydraulic urinary continence devices

may mechanically malfunction.

Reported types of mechanical

malfunctions include leakage, tubing

kinks, disconnection of tube, pump

57730 Federal Register / Vol. 65, No. 187 / Tuesday, September 26, 2000 / Rules and Regulations

assembly failure, and balloon

herniation. Mechanical malfunctions

may be caused by improper device

handling or improper surgical

technique, or problems with the

device’s design or manufacturing

process. Surgical intervention to remove

or replace the device is required if the

patient desires a functional prosthesis or

if the device malfunction results in total

urinary retention.

4. Iatrogenic Disorders

Improper device handling, inadequate

pressure within the system, and device

missizing are among the preventable

complications caused as a result of

surgical technique. Iatrogenic disorders

may be responsible for various adverse

conditions necessitating device removal

and/or replacement.

5. Hydronephrosis

This complication has mostly

occurred when the device is implanted

in patients with nerve or spinal cord

damage. The pathogenesis and

incidence of this risk is unknown.

6. Human Carcinogenicity

The potential for developing cancer as

a result of the long-term implantation of

the implanted mechanical/hydraulic

urinary continence device cannot be

eliminated as a potential risk associated

with this device.

7. Human Reproductive and Teratogenic

Effects

Although FDA is not aware of data

indicating that the implanted

mechanical/hydraulic urinary

continence device is associated with

reproductive and teratogenic effects, the

potential for teratogenicity and other

reproductive adverse effects as a result

of long-term implantation of the device

cannot be eliminated as a possible risk

to health.

8. Immune Related Connective Tissue

Disorders—Immunological Sensitization

The potential for developing

immunological effects and/or

connective tissue disorders as a result of

long-term exposure to the implanted

mechanical/hydraulic urinary

continence device remains uncertain.

Since the publication of the proposed

rule 5 years ago, new epidemiological

data (Refs. 3, 4 and 5) addressing the

relationship between silicone breast

prostheses and autoimmune diseases or

connective tissue diseases indicate that

silicone breast prostheses have not

caused a large increase in the incidence

of connective tissue disease in women

with breast implants. However, the

possibility of a smaller, increased risk of

immunological effects among people

with implanted mechanical/hydraulic

urinary continence devices, or of an

atypical, as yet undefined, syndrome or

disease, cannot be eliminated based on

these data.

9. Biological Effects of Silica

Amorphous fumed silica is bound to

the silicone in the elastomer of the

implanted mechanical/hydraulic

urinary continence device. Silica

presents a potential risk which should

be addressed in a PMA or PDP.

10. Silicone Gel Leakage and Associated

Migration

Small quantities of silicone gel are

present in at least one model of the

implanted mechanical/hydraulic

urinary continence device. Silicone gel

leakage and associated migration are

potential risks, which should be

addressed in a PMA or PDP for any

device that contains this material.

11. Degradation of Polyurethane

Elastomer

Polyurethane elastomer materials,

which may be present in some

implanted mechanical/hydraulic

urinary continence devices, may

degrade over time and release

degradation products which are

potential carcinogens in animals. When

present, polyurethane elastomer

degradation is a potential risk which

should be addressed in a PMA or PDP.

12. Degradation of Polyurethane Foam

Polyurethane foam materials, which

may be present in some implanted

mechanical/hydraulic urinary

continence devices, are known to

degrade over time. When present,

polyurethane foam degradation is a

potential risk which should be

addressed in a PMA or PDP.

13. Other Reported Complications

Other reported complications

associated with the implantation of the

implanted mechanical/hydraulic

urinary continence device include

perineal discomfort/pain, development

of bladder hyperreflexia, worsening/

persistence of incontinence, urinary

retention, hematoma, inguinal hernia

formation, fibrous capsule formation,

failure of cuff to deflate, broken tubing,

fistula formation from urethral erosion,

urethral scarring, bleeding, urethral

stricture requiring urethrotomy, wound

dehiscence, pelvic abscess, and fistula

to the skin. These complications should

be addressed in a PMA or PDP.

B. Benefits of the Device

The implanted mechanical/hydraulic

urinary continence device is intended to

restore urinary continence. It has the

potential to be an effective treatment for

urinary incontinence. Implant recipients

may also benefit from an improved

quality of life and self-esteem.

IV. Final Rule

Under section 515(b)(3) of the act,

FDA is adopting the findings as

published in the preamble to the

proposed rule and is issuing this final

rule to require premarket approval of

the generic type of device, the

implanted mechanical/hydraulic

urinary continence device, by revising

§ 876.5280(c).

Under the final rule, a PMA or a

notice of completion of a PDP is

required to be filed on or before

December 26, 2000, for any implanted

mechanical/hydraulic urinary

continence device that was in

commercial distribution before May 28,

1976, or that has been found by FDA to

be substantially equivalent to such a

device on or before December 26, 2000.

An approved PMA or a declared

completed PDP is required to be in

effect for any such device on or before

180 days after FDA files the application.

Any other implanted mechanical/

hydraulic urinary continence device

that was not in commercial distribution

before May 28, 1976, or that has not

been found by FDA to be substantially

equivalent to such a device on or before

December 26, 2000, is required to have

an approved PMA or a declared

completed PDP in effect before it may be

marketed.

If a PMA or a notice of completion of

a PDP for an implanted mechanical/

hydraulic urinary continence device is

not filed on or before December 26,

2000, that device will be deemed

adulterated under section 501(f)(1)(A) of

the act, and commercial distribution of

the device will be required to cease

immediately. The device may, however,

be distributed for investigational use, if

the requirements of the investigational

device exemption (IDE) regulations (part

812) (21 CFR part 812) are met.

Under § 812.2(d) of the IDE

regulations, FDA hereby stipulates that,

on the effective date of this rule, the

exemptions from the IDE requirements

in § 812.2(c)(1) and (c)(2) will no longer

apply to clinical investigations of the

implanted mechanical/hydraulic

urinary continence device. Further, FDA

concludes that investigational

implanted mechanical/hydraulic

urinary continence devices are

significant risk devices as defined in

Federal Register / Vol. 65, No. 187 / Tuesday, September 26, 2000 / Rules and Regulations 57731

§ 812.3(m) and advises that, as of the

effective date of this rule, the

requirements of the IDE regulations

regarding significant risk devices will

apply to any clinical investigation of an

implanted mechanical/hydraulic

urinary continence device. For any

implanted mechanical/hydraulic

urinary continence device that is not the

subject of a timely filed PMA or PDP, an

IDE must be in effect under § 812.20 on

or before 90 days after the effective date

of this regulation or distribution of the

device must cease. FDA advises all

persons presently sponsoring a clinical

investigation involving the implanted

mechanical/hydraulic urinary

continence device to submit an IDE

application to FDA no later than 60 days

after the effective date of this final rule

to avoid the interruption of ongoing

investigations.

V. Environmental Impact

The agency has determined under 21

CFR 25.30(h) 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.

VI. Analysis of Impacts

FDA has examined the impacts 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

Enforcement Fairness Act of 1996

(Public Law 104–121), and the

Unfunded Mandates Reform Act of 1995

(Public Law 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 is not

a significant regulatory action as defined

by the Executive Order and so is not

subject to review under the Executive

Order.

FDA expects that only one or two

manufacturers will submit a PMA or

PDP for the implanted mechanical/

hydraulic urinary continence device.

FDA estimates that it costs up to $1

million to develop and submit a PMA or

PDP for this type of device. As noted

previously, the implanted mechanical/

hydraulic urinary continence device

was classified into class III on

November 23, 1983, and FDA published

a proposed rule to require a PMA or

PDP for this device on February 15,

1995. Thus, manufacturers have long

been aware of the need to develop

information in support of a PMA or a

PDP. The cost of developing the data,

therefore, has been spread over the past

several years. Moreover, since the

publication of the proposed rule, FDA

has been working closely with the

manufacturers to assist them in

preparing for the submission of a PMA

or a PDP. FDA, therefore, believes that

this final rule will not be an undue

burden on these manufacturers.

Because only one or two companies

will incur costs, the agency therefore

certifies that the final rule will not have

a significant economic impact on a

substantial number of small entities.

Therefore, under the Regulatory

Flexibility Act, no further analysis is

required.

Section 202(a) of the Unfunded

Mandates Reform Act of 1995 (Public

Law 104–4) requires that agencies

prepare a written statement of

anticipated costs and benefits before

proposing any rule that may result in an

expenditure by State, local, and tribal

governments, in the aggregate, or by the

private sector, of $100 million in any

one year (adjusted annually for

inflation). The Unfunded Mandates

Reform Act does not require FDA to

prepare a statement of costs and benefits

for the proposed rule, because the

proposed rule is not expected to result

in any 1-year expenditure that would

exceed $100 million.

VII. Paperwork Reduction Act of 1995

This final rule contains information

collection provisions that are subject to

review by OMB under the Paperwork

Reduction Act of 1995 (44 U.S.C. 3501–

3530). The burden hours required for

’876.5280(c) are reported and approved

under OMB Control No. 0910–0231.

VIII. Federalism

FDA has analyzed this final rule in

accordance with the principles set forth

in Executive Order 13132. FDA has

determined that the rule does not

contain policies that have substantial

direct effects on the States, on the

relationship between the National

Government and the States, or on the

distribution of power and

responsibilities among the various

levels of government. Accordingly, the

agency has concluded that the rule does

not contain policies that have

federalism implications as defined in

the order and, consequently, a

federalism summary impact statement is

not required.

IX. 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 in the

office above between 9 a.m. and 4 p.m.,

Monday through Friday.

1. Barrett, D. M., D. C. O’Sullivan, A.

A. Maliza, H. M. Reiman, and P. C.

Abell-Aleff, ‘‘Particle Shedding and

Migration From Silicone Genitourinary

Prosthetic Devices,’’ The Journal of

Urology, 146:319–322, 1991.

2. Fishman, I. J., and F. N. Flores,

‘‘Retrospective Review of Pelvic Lymph

Nodes in Patients with Previously

Implanted Silicone Penile

Prosthesis,’’The Journal of Urology,

149:355A, 1993.

3. Hennekens, C. H., I. Lee, N. Cook,

P. R. Hebert, E. W. Karlson, F. LaMotte,

J. E. Manson, and J. E. Buring, ‘‘Selfreported Breast Implants and

Connective-Tissue Diseases in Female

Health Professionals,’’Journal of the

American Medical Association,

275:616–621, 1996.

4. Silverman, B. G., S. L. Brown, R. A.

Bright, R. G. Kaczmarek, J. B.

Arrowsmith-Lowe, and D. A. Kessler,

‘‘Reported Complications of Silicone

Gel Breast Implants: An Epidemiologic

Review,’’Annals of Internal Medicine,

124:744–756, 1996.

5. Institute of Medicine, ‘‘Safety of

Silicone Breast Implants,’’ National

Academy Press, Washington, DC, 1999.

List of Subjects in 21 CFR Part 876

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 876 is

amended as follows:

PART 876—GASTROENTEROLOGY

AND UROLOGY DEVICES

1. The authority citation for 21 CFR

part 876 continues to read as follows:

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

360j, 360l, 371.

2. Section 876.5280 is amended by

revising paragraph (c) to read as follows:

§ 876.5280 Implanted mechanical/

hydraulic urinary continence device.

* * * * *

(c) Date PMA or notice of completion

of a PDP is required. A PMA or a notice

of completion of a PDP is required to be

filed with the Food and Drug

Administration on or before December

57732 Federal Register / Vol. 65, No. 187 / Tuesday, September 26, 2000 / Rules and Regulations

26, 2000, for any implanted mechanical/

hydraulic urinary continence device

that was in commercial distribution

before May 28, 1976, or that has, on or

before December 26, 2000, been found

to be substantially equivalent to an

implanted mechanical/hydraulic

urinary continence device that was in

commercial distribution before May 28,

1976. Any other implanted mechanical/

hydraulic urinary continence device

shall have an approved PMA or a

declared completed PDP in effect before

being placed in commercial

distribution.

Dated: September 11, 2000.

Linda S. Kahan,

Deputy Director for Regulations Policy, Center

for Devices and Radiological Health.

[FR Doc. 00–24632 Filed 9–25–00; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF THE TREASURY

Internal Revenue Service

26 CFR Part 1

[TD 8903]

RIN 1545–AY01

Qualified Zone Academy Bonds;

Obligations of States and Political

Subdivisions

AGENCY: Internal Revenue Service (IRS),

Treasury.

ACTION: Final regulations.

SUMMARY: This document contains final

regulations relating to the Federal

income tax treatment of qualified zone

academy bonds. These regulations

provide guidance to State and local

governments that issue qualified zone

academy bonds and to banks, insurance

companies and other taxpayers that

hold those bonds. These regulations

make final certain temporary

regulations.

DATES: Effective Date: These regulations

are effective September 26, 2000.

Applicability Date: For dates of

applicability, see § 1.1397E–1(k).

FOR FURTHER INFORMATION CONTACT:

Timothy L. Jones or Allan B. Seller at

202–622–3980 (not a toll-free number).

SUPPLEMENTARY INFORMATION:

Background

Section 226(a) of the Taxpayer Relief

Act of 1997, Public Law 105–34 (111

Stat. 788), amended the Internal

Revenue Code (Code) by redesignating

section 1397E as section 1397F and

adding a new section 1397E. Section

1397E authorizes a type of debt

instrument known as a qualified zone

academy bond.

Explanation of Provisions

In General

A qualified zone academy bond is a

taxable bond issued by a State or local

government, the proceeds of which are

used to enhance certain eligible public

schools. In lieu of receiving periodic

interest payments from the issuer, an

eligible holder of a qualified zone

academy bond is generally allowed

annual federal income tax credits while

the bond is outstanding. These credits

compensate the holder for lending

money to the issuer and function as

payments of interest on the bond.

Temporary regulations (REG–119449–

97) interpreting section 1397E were

published on January 7, 1998 (63 FR

671), and amended on July 1, 1999 (64

FR 35573). The temporary regulations

generally treat the allowance of the

credit as if it were a payment of interest

on the bond.

Code section 1397E(e), as amended by

section 509 of the Ticket to Work and

Work Incentives Improvement Act of

1999, Public Law 106–170 (113 Stat.

1860), imposes a national limitation on

the amount of qualified zone academy

bonds that can be issued. For each

applicable year, the IRS publishes a

revenue procedure allocating the

national limitation among the States and

the possessions.

Bonds Issued by a State or Local

Government

Section 1397E(d)(1)(B) requires that a

qualified zone academy bond be issued

by a State or local government within

the jurisdiction of which a qualified

zone academy (as defined in section

1397E(d)(4)) is located. Commentators

requested clarification that, for these

purposes, a State or local government

means a State or political subdivision as

defined for purposes of section 103(c).

Commentators also requested that the

final regulations include a provision for

the issuance of qualified zone academy

bonds on behalf of a State or local

government in a manner similar to the

issuance of obligations on behalf of a

State or political subdivision under

section 103.

The final regulations provide that, for

purposes of section 1397E(d)(1)(B), the

term State or local government means a

State or political subdivision as defined

for purposes of section 103(c). The final

regulations also specify that a qualified

zone academy bond may be issued on

behalf of a State or local government

under rules similar to those for

determining whether a bond issued on

behalf of a State or political subdivision

constitutes an obligation of that State or

political subdivision for purposes of

section 103.

Private Business Contribution

Requirement

Section 1397E(d)(1)(C)(ii) requires the

issuer of a qualified zone academy bond

to certify that it has written assurances

that the private business contribution

requirement of section 1397E(d)(2) will

be met with respect to the qualified

zone academy. For these purposes, the

private business contribution

requirement is met if the eligible local

education agency (as defined in section

1397E(d)(4)(B)) has written

commitments from private entities to

make qualified contributions having a

present value as of the issue date of 10

percent or more of the proceeds of the

issue.

The Code does not define private

entities for these purposes. Section

1397E(d)(2)(B) defines qualified

contribution as any contribution (of a

type and quality acceptable to the

eligible local education agency) of (i)

equipment for use in the qualified zone

academy, (ii) technical assistance in

developing curriculum or in training

teachers in order to promote appropriate

market driven technology in the

classroom, (iii) services of employees as

volunteer mentors, (iv) internships, field

trips, or other educational opportunities

outside the academy for students, or (v)

any other property or service specified

by the eligible local education agency.

Commentators requested clarification

of the meaning of private entities for

these purposes. For example,

commentators asked whether the term

may include an organization described

in section 501(c)(3) or a private

individual.

The final regulations provide that, for

purposes of section 1397E(d)(2)(A), the

term private entities includes any

person (as defined in section 7701(a))

other than the United States, a State or

local government, or any agency or

instrumentality thereof or related party

with respect thereto.

Commentators also sought

clarification regarding the meaning of

qualified contribution under section

1397E(d)(2)(B). The final regulations

provide that cash received with respect

to a qualified zone academy from a

private entity constitutes a qualified

contribution if it is to be used to

purchase any property or service

described in section 1397E(d)(2)(B)(i),

(ii), (iii), (iv) or (v). The final regulations

also indicate that services of employees

of the eligible local education agency do

not constitute qualified contributions.