[Federal Register: September 26, 2000 (Volume 65, Number 187)]
[Rules and Regulations]
[Page 57726-57732]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26se00-4]
=======================================================================
-----------------------------------------------------------------------
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 Sec. 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)).)
[[Page 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
[[Page 57728]]
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.
[[Page 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 post-prostatectomy 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, pre-clinical, 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
[[Page 57730]]
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 Sec. 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 Sec. 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 Sec. 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
[[Page 57731]]
Sec. 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
Sec. 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, ``Self-reported 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:
Sec. 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
[[Page 57732]]
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