[Federal Register: April 12, 2000 (Volume 65, Number 71)]
[Rules and Regulations]               
[Page 19650-19658]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr12ap00-5]                         

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 876

[Docket No. 92N-0445]

 
Gastroenterology-Urology Devices; Effective Date of Requirement 
for Premarket Approval of the Penile Inflatable Implant

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 
penile inflatable implant, a generic type of medical device intended 
for the treatment of erectile dysfunction. This regulation reflects 
FDA's exercise of its discretion to require PMA's or PDP's for 
preamendments devices and is consistent with FDA's stated priorities 
and Congress' requirement that class III devices are to be regulated by 
FDA's premarket review. 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, and the Food and Drug Administration Modernization Act of 
1997.

DATES: This rule is effective April 12, 2000.

FOR FURTHER INFORMATION CONTACT: John H. Baxley, 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

    In the Federal Register of November 23, 1983 (48 FR 53023), FDA 
published a final rule classifying into class III (premarket approval) 
the penile inflatable implant, a medical device. Section 876.3350 (21 
CFR 876.3350) of FDA's regulations setting forth the classification of 
the penile inflatable implant applies to: (1) Any penile inflatable 
implant that was in commercial distribution before May 28, 1976, and 
(2) any device that FDA has found to be substantially equivalent to a 
penile inflatable implant in commercial distribution before May 28, 
1976.
    In the Federal Register of April 28, 1993 (58 FR 25902), 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 
penile inflatable implant and all substantially equivalent devices 
(hereinafter referred to as the April 1993 proposed rule). 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 penile inflatable implant was required to be submitted by May 
13, 1993. The comment period initially closed on June 28, 1993. In the 
Federal Register of July 1, 1993 (58 FR 35416), FDA extended the 
comment period for 60 days to August 27, 1993, to ensure that there was 
adequate time for preparation and submission of comments on the 
proposed rule.
    The agency received 32 comments in response to the April 1993 
proposed rule. These comments were from physicians and other health 
care providers, professional organizations, physician groups, 
manufacturers, and consumers and other individuals. Most of the 
comments supported the proposed rule.
    This regulation is final upon publication and requires PMA's or 
notices of completion of a PDP for all penile inflatable implants 
classified under Sec. 876.3350 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)).) This regulation does not include the penile rigidity 
implant (21 CFR 876.3630).

II. Summary and Analysis of Comments and FDA's Response

A. General Comments

    (Comment 1) FDA received 23 comments from individual physicians and 
2 comments from professional medical organizations. Although the 
majority of these comments did not object to the proposed call for 
PMA's or PDP's, they voiced the following common concerns: (1) Erectile 
dysfunction is a serious medical problem affecting tens of millions of 
American men and their partners, (2) removal of this device from the 
U.S. market would be detrimental to public health, and (3) citing the 
25 years of use of the device, sufficient historical data exist to 
evaluate the safety and effectiveness of the penile inflatable implant. 
This last concern was also noted in two comments from penile inflatable 
implant manufacturers, which stated that the decades of medical 
literature regarding the risks and benefits of this device provide 
sufficient evidence of its safety and effectiveness. Several comments 
remarked that FDA has overstated the risks of the inflatable penile 
implant.
    FDA agrees that erectile dysfunction is a significant medical 
problem that negatively affects the lives of more than 10 million men 
in the United States. Furthermore, since penile inflatable implants 
represent an important option in the treatment of erectile dysfunction, 
FDA agrees with these comments that removal of the penile inflatable 
implant 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 penile inflatable implant during the 
call for PMA's or PDP's: (1) FDA issued the guidance document entitled 
``Draft Guidance for Preparation of PMA Applications for Penile 
Inflatable Implants'' in March 1993 (the 1993 guidance document) to 
provide industry with detailed recommendations on the content of PMA's; 
(2) FDA has communicated closely with each penile inflatable implant 
manufacturer to address the concerns identified in the proposed rule 
using least burdensome methods, as well as provided 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

[[Page 19651]]

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 
penile inflatable implant. However, to FDA's knowledge, these studies 
are neither sufficiently detailed nor properly designed to perform a 
statistically valid evaluation of the safety and effectiveness of any 
of the specific device models currently on the market. As recommended 
in the 1993 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 penile inflatable implants 
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 penile inflatable implant 
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 these data in support of a PMA or PDP for that model.
    While FDA agrees that the April 1993 proposed rule may have 
overstated the risks of some of the specific penile inflatable implant 
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 penile inflatable 
implants. As noted in many of these comments, manufacturers have made 
numerous design modifications to improve the reliability of the penile 
inflatable implant and the medical community continues to improve the 
patient selection criteria, patient counseling information, operative 
technique, and postoperative care to reduce the incidence of 
complications. Therefore, FDA expects the rates of complications 
reported in PMA's or PDP's for particular penile inflatable implants 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 penile 
inflatable implants that currently have legally marketed status in the 
United States.
    (Comment 2) FDA received one comment from a penile inflatable 
implant recipient, who is supportive of the proposed call for PMA's or 
PDP's. This consumer has received a total of four devices to date, and 
his most recent device has failed, requiring replacement. He states 
that the penile inflatable implant affects both his quality of life and 
manhood.
    FDA agrees that the potential benefits of a penile inflatable 
implant include improvements in quality of life and self-image, and 
notes that these secondary benefits of penile inflatable implant 
implantation were cited in the proposed call for PMA's or PDP's. 
Furthermore, FDA believes that requiring the submission of PMA's or 
PDP's for the penile inflatable implant will allow FDA to assess the 
risks and benefits of specific devices in order to determine whether 
there is reasonable assurance of their safety and effectiveness.
    (Comment 3) One comment stated that FDA's assessment of the risks 
of penile inflatable implants is inconsistent with FDA's assessment of 
the risks of class II silicone prostheses such as the bone cap (21 CFR 
888.3000), chin prosthesis (21 CFR 878.3550), the ear prosthesis (21 
CFR 878.3590), and the finger joint prosthesis (21 CFR 888.3230).
    FDA is aware of the existence of information on silicone and 
silicone-containing prostheses, and expects that applicants may include 
such information in their submissions to support the safety and 
effectiveness of the penile inflatable implant. However, FDA does not 
believe that the existing information on silicone and silicone-
containing prostheses can be used as the sole basis of establishing the 
safety and effectiveness of the penile inflatable implant, and believes 
that a determination of safety and effectiveness of the penile 
inflatable implant must be made, at least in part, on data collected on 
each particular device for which a PMA or PDP is submitted. FDA will 
consider all information contained in PMA's and PDP's in determining 
whether there is reasonable assurance of safety and effectiveness of 
this device.
    (Comment 4) Many comments noted that FDA was incorrect in stating 
that some penile inflatable implant models contain silicone gel. These 
comments concluded, therefore, that the risks of silicone gel do not 
apply to the penile inflatable implant.
    FDA disagrees with the comments that no penile inflatable implant 
contains silicone gel. Although silicone gel has never been used as a 
penile inflatable implant inflation medium, FDA is aware of at least 
one device model, no longer marketed in the United States, that 
contained silicone gel within its cylinder tip. FDA agrees with the 
comments that the potential risks of silicone gel are not applicable to 
penile inflatable implants that do not contain silicone gel.
    The agency would not expect PMA's or PDP's for those devices to 
address the risks related to silicone gel.
    (Comment 5) One comment objected that Congress never intended 
``old'' preamendments medical devices to undergo the same scrutiny as 
``new'' postamendments medical devices.
    FDA does not believe that Congress intended to differentiate 
between ``old'' preamendments devices and ``new'' postamendments device 
with respect to the requirement that valid scientific evidence is 
needed to support PMA approval. Neither section 513(a)(3) (21 U.S.C. 
360c(a)(3)) nor section 515(d) of the act makes any distinction between 
``old'' and ``new'' devices with regard to any aspect of the 
requirement for PMA approval.
    (Comment 6) One comment stated that FDA should allow an appropriate 
timeframe prior to issuance of the call for PMA's or PDP's for the 
following reasons: (1) FDA needs sufficient time to develop additional 
guidance on the data requirements for PMA's and PDP's; (2) since 
several of the main suppliers of silicone and polyurethane raw 
materials have announced a planned withdrawal of these products from 
the market, penile inflatable implant manufacturers need sufficient 
time to qualify and test new materials; and (3) device manufacturers 
need sufficient time to collect the preclinical and clinical data 
recommended by FDA.
    FDA believes there has been sufficient time for PMA and PDP 
sponsors to develop data and address the issues identified as potential 
risks. Section 515(b) of the act does not require the agency to provide 
guidance on the contents of specific PMA's. However, FDA issued the 
1993 guidance document to provide industry with detailed 
recommendations on the appropriate data to be included in PMA's and 
PDP's for penile inflatable implants. The 1993 guidance document is 
available from the Internet at www.fda.gov/cdrh/ode/oderp810.html. In 
order to receive the 1993 guidance document via your fax machine, call 
the CDRH Facts-On-Demand (FOD) system at 800-899-0381 or 301-827-0111 
from a touch-tone telephone. Press 1 to enter the system and then enter 
the document number (810) followed by the pound sign (#). Follow the 
remaining voice prompts to complete your request. While the 1993 
guidance document continues to remain in effect, FDA plans to revise 
this document in the near future to incorporate many of the comments 
subsequently received from

[[Page 19652]]

the industry and public. Furthermore, the agency encourages penile 
inflatable implant manufacturers to meet with FDA before submitting a 
PMA or PDP to obtain additional guidance regarding the recommended data 
to submit to demonstrate the safety and effectiveness of each specific 
device model proposed for market approval.
    In addition, the period of time between the classification of the 
device in 1983 and the date by which PMA's must be filed is more than 
16 years. Thus, FDA believes that sufficient time and guidance have 
been provided to allow sponsors to develop the data for a PMA 
submission.
    FDA agrees that dialogue with industry and with the scientific 
community and medical community is important. To elicit early public 
discussion on the 1993 guidance document and the agency's plans to call 
for PMA's or PDP's for the penile inflatable implant, FDA called a 
meeting of the Gastroenterology and Urology Devices Advisory Panel on 
April 15, 1993, to discuss these topics. Following publication of the 
proposed call for PMA's or PDP's, FDA communicated closely with each 
penile inflatable implant manufacturer to address the concerns 
identified by FDA in the April 1993 proposed rule, as well as provide 
recommendations on the design of preclinical and clinical studies for 
their particular device models. Furthermore, FDA staff have been and 
continue to be accessible to discuss PMA and PDP content information 
with industry and the scientific and medical community.
    (Comment 7) One comment stated that FDA was incorrect in its 
determination that the penile inflatable implant has a high priority 
for initiating a proceeding to require premarket approval due to 
inappropriate comparison to potential adverse effects of silicone gel 
breast implants and due to the volume of Medical Device Reports (MDR's) 
received to date for penile inflatable implants. The comment further 
noted that an early call for PMA's or PDP's is unwarranted since the 
penile inflatable implant was not included in the January 6, 1989 (54 
FR 550), list of 31 ``high priority'' preamendments class III devices.
    FDA believes the call for PMA's or PDP's for this device cannot be 
considered an ``early'' call in light of its classification in 1983 and 
the proposed call for PMA's in 1993.
    By adding section 515(i) to the act in the Safe Medical Devices Act 
of 1990 (Public Law 101-629), Congress made it clear that it expected 
FDA to move forward expeditiously to either require premarket approval 
or notices of completion of PDP for all preamendments class III devices 
or to reclassify them into class I or class II. Therefore, FDA believes 
that it is appropriate to issue this final rule at this time.

B. Infection

    (Comment 8) There were 19 comments on the risk of infection. 
Several comments stated that the incidence of infection associated with 
the implantation of penile inflatable implants is not any higher than 
it is for other implantation surgeries. Many of these comments further 
stated that the risk of infection is minimized by proper patient 
selection, meticulous attention to sterile technique during device 
implantation, and adherence to appropriate postoperative precautions. 
Several comments stated that infection, if it occurs, often can be 
successfully controlled without the need for device removal if it is 
recognized early and treated with appropriate aggressive antibiotic 
therapy with or without drainage and wound irrigation. One comment 
added that infections of penile inflatable implants only rarely result 
in an inability to replace the device due to corporeal fibrosis and 
cavernositis.
    FDA agrees that the risk of infection can be minimized by proper 
patient selection, surgical precautions, and postoperative care. 
However, FDA 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 
penile inflatable implant. As noted in the 1993 guidance document, FDA 
is requesting information on the incidence of infection for this 
device.

C. Migration and Extrusion

    (Comment 9) There were 13 comments regarding the risks of migration 
and extrusion. These comments stated that migration and extrusion of 
penile inflatable implants occur infrequently, are directly related to 
infection or excessive pressure of the prosthesis on surrounding 
tissues, and are minimized by properly placing an appropriately sized 
device using appropriate surgical techniques. For these reasons, 
several comments stated that migration and extrusion should not be 
labeled as ``significant risks'' of implantation of the device.
    While FDA agrees that migration and extrusion can be minimized by 
proper device sizing and placement, insufficient information is 
available to determine the frequency of this event or its effects. 
Therefore, FDA believes that it is important for studies submitted in a 
PMA or PDP to provide accurate information on the incidences of 
migration and extrusion associated with the implantation of the penile 
inflatable implant.
    FDA disagrees with the comment that migration and extrusion are not 
significant risks. Migration and extrusion of the penile inflatable 
implant can lead to surgical intervention, making them serious risks to 
health. As noted in the 1993 guidance document, FDA is requesting 
information to address the incidences of migration and extrusion for 
this device.

D. Erosion

    (Comment 10) There were 13 comments regarding the risk of erosion. 
These comments stated that, similar to migration and extrusion, erosion 
of penile inflatable implants occurs infrequently, is directly related 
to infection or excessive pressure of the prosthesis on surrounding 
tissues, and is minimized by properly placing an appropriately sized 
device using appropriate surgical techniques. For these reasons, 
several comments stated that erosion should not be labeled as a 
``significant risk'' of implantation of the device.
    While FDA agrees that the risk of erosion can be minimized by 
proper device sizing and placement, 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 penile inflatable implant.
    FDA disagrees with the comment that erosion is not a significant 
risk. Erosion of the penile inflatable implant can require surgical 
intervention, making it a serious risk to health. As noted in the 1993 
guidance document, FDA is requesting information to address the 
incidence of erosion for this device.

E. Fibrous Capsule Formation

    (Comment 11) FDA received 15 comments regarding the risk of fibrous 
capsule formation. Most of these comments stated that fibrous capsule 
formation is part of the body's normal reaction to an implanted device, 
and is not harmful to the patient. One comment stated that fibrous 
capsule formation does not adversely affect the function of the penile 
inflatable implant, while several others acknowledged that the fibrotic 
capsule can keep the reservoir or other device components from 
completely filling, thus hindering the ability of the device

[[Page 19653]]

to fully inflate or deflate. Many of the comments regarding the effect 
of fibrous capsule formation upon inflation and deflation of the penile 
inflatable implant further stated that this risk can be minimized by 
leaving the device deflated during the healing period so that the 
capsule formed around the reservoir minimally impedes refilling. One 
comment further stated that FDA was wrong to refer to fibrous capsule 
formation as a ``foreign body reaction,'' since fibrotic reactions are 
not only related to the material of the implant but also to other 
factors such as loading forces on the implant and the patient's 
biological tendency to form a scar. Two comments stated that fibrous 
capsule formation is only problematic with static prostheses, such as 
breast implants, and, therefore, is not a concern with penile 
inflatable implants.
    FDA agrees that fibrous capsule formation is part of the body's 
normal reaction to all implanted devices including penile inflatable 
implants, and is usually not life-threatening. Also, FDA recognizes 
that the severity of this risk to health is dependent upon multiple 
factors other than foreign body reaction. Furthermore, FDA agrees that 
the risk of inflation/deflation difficulties secondary to fibrous 
capsule formation around the reservoir can be minimized by proper 
postoperative care. However, FDA believes that fibrous capsule 
formation can affect the function of the penile inflatable implant and 
is potentially serious. Severe fibrous capsule formation has been 
reported to impede the ability of the penile inflatable implant to 
operate as it is designed, which reduces or eliminates the benefit of 
the device. In addition, the recipient may then elect to have his 
implant surgically explanted and have a second device implanted. This 
additional surgery makes fibrous capsule formation a potentially 
serious adverse event. As noted in the 1993 guidance document, FDA is 
requesting information to address the incidence of fibrous capsule 
formation for this device.

F. Mechanical Malfunctions

    (Comment 12) There were 14 comments regarding the risk of 
mechanical malfunction. All of these comments stated that while early 
models of penile inflatable implants were associated with high rates of 
mechanical malfunction, improvements in device design and implantation 
technique have steadily decreased the failure rate. Several of these 
comments added that the mechanical malfunction rate of current device 
designs ranges from ``rare'' to 1 to 3 percent. One comment added that 
FDA's statement that a penile inflatable implant ``should not be 
considered a lifetime implant'' is inaccurate, since prostheses may be 
expected to endure indefinitely with the proviso that there is a risk 
of mechanical failure.
    FDA agrees that the mechanical malfunction rate of the penile 
inflatable implant has significantly decreased as compared to early 
models. Despite this observed trend, however, insufficient information 
is available to determine the frequency of this event for each of the 
particular device models that manufacturers intend to market following 
the effective date of this regulation. Therefore, FDA believes that it 
is important for studies submitted in a PMA or PDP to provide accurate 
information on the incidence of mechanical malfunction associated with 
the implantation of the penile inflatable implant.
    FDA disagrees with the comment that the penile inflatable implant 
can be considered a lifetime implant. As complex mechanical devices, 
penile inflatable implants are subject to wear over time and, 
therefore, have finite lifetimes. The fact that each device carries the 
risk of mechanical failure, as acknowledged in the comment, underscores 
the need to inform patients that the device should not be expected to 
function indefinitely.

G. Iatrogenic Disorders

    (Comment 13) FDA received 11 comments regarding the risk of 
iatrogenic disorders. These comments stated that iatrogenic disorders 
occur infrequently, are minimized with proper operative technique and 
surgeon experience, are not directly related to the device, and are 
medical issues outside the domains of clinical testing and premarket 
review.
    FDA agrees that iatrogenic disorders are infrequent events which 
are reduced through adherence to proper surgical technique. FDA also 
agrees that the medical community has had a major role in defining 
these surgical practices in an effort to minimize the incidence of 
iatrogenic disorders. However, FDA believes that iatrogenic disorders 
are, in part, device related, since issues of sizing, device assembly, 
and implantation technique are influenced by the specific device design 
being implanted. As a result, FDA believes that iatrogenic disorders 
should be evaluated in the clinical testing and premarket review of 
penile inflatable implants so that the product-specific information 
obtained from such testing is appropriately incorporated into the 
labeling of that device model. As noted in the 1993 guidance document, 
FDA is requesting information to address the incidence of iatrogenic 
disorders for this device.

H. Patient Dissatisfaction

    (Comment 14) There were 14 comments regarding the risk of patient 
dissatisfaction. These comments stated that patient dissatisfaction is 
infrequent and is only rarely the primary cause for reoperation. 
Additionally, many comments stated that patient dissatisfaction is the 
result of the patient having unrealistic expectations regarding the 
postimplantation appearance and function of his penis, and that this 
situation can be minimized by requiring thorough preoperative 
counseling regarding the realistic outcomes of device implantation. One 
physician comment stated that none of his patients had ever asked him 
to have a penile inflatable implant removed due to dissatisfaction.
    FDA agrees that the majority of patients who receive penile 
inflatable implants report satisfaction with their device. 
Additionally, FDA concurs with the comments that patient 
dissatisfaction is typically the result of the patient having 
unrealistic expectations regarding the implant, and can be minimized by 
patient educational measures such as patient labeling and physician 
counseling. However, since patient dissatisfaction can ultimately 
require surgical intervention, FDA considers patient dissatisfaction a 
risk that should be addressed by manufacturers. Furthermore, since 
implantation of a penile inflatable implant may destroy any latent 
erectile capability the patient may have had, as well as make other, 
more conservative forms of treatment for erectile dysfunction difficult 
or impossible, dissatisfied patients are left with few recourses. To 
assess and optimize the adequacy of information materials available to 
potential implant recipients, 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 incidence of patient 
dissatisfaction associated with the implantation of the penile 
inflatable implant.

I. Human Carcinogenicity

    (Comment 15) Sixteen comments were received regarding the risk of 
human carcinogenicity. These comments stated that there is no evidence 
in the medical literature that the penile inflatable implant is 
associated with the development of

[[Page 19654]]

cancer. Furthermore, nine of these comments were from physicians, who 
stated that they had not observed carcinogenicity in their personal 
experiences with these devices. One physician comment added that while 
carcinogenicity has not been proven to occur with the penile inflatable 
implant, further research is necessary to rule out this potential 
complication. Several comments stated that silicone causes solid state 
tumors in rodents, a phenomenon thought to be restricted to rodents and 
not applicable to humans. These comments 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 penile inflatable implant, are at an increased risk 
for cancer. Several comments stated that human carcinogenicity should 
be removed from the list of significant risks associated with the 
penile inflatable implant.
    FDA believes that the potential carcinogenicity for this device 
remains unknown. The agency continues to believe that carcinogenicity 
is a potential risk that must be assessed in a PMA or PDP.

J. Human Reproductive and Teratogenic Effects

    (Comment 16) There were 16 comments related to human reproductive 
and teratogenic effects. These comments stated that there is no 
evidence that the penile inflatable implant is teratogenic. Nine 
comments from physicians stated that they had not observed reproductive 
and teratogenic effects in their personal experiences with these 
devices, one of whom added that further research is necessary to rule 
out this potential complication. Two comments stated that since most 
implant patients are beyond the age of fathering children, the risks of 
reproductive problems and teratogenic effects are not significant 
concerns. Furthermore, the small numbers of patients who do receive a 
device during their reproductive ages would not warrant a prospective 
study. Several comments stated that human reproductive and teratogenic 
effects should be removed from the list of significant risks associated 
with the penile inflatable implant.
    FDA agrees that there are no published studies showing that penile 
inflatable implants 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 assessed in a PMA or PDP.

K. Immune Related Connective Tissue Disorders--Immunological 
Sensitization

    (Comment 17) There were 16 comments regarding the risks of immune 
related connective tissue disorders and immunological sensitization. 
These comments stated that there is no evidence that the penile 
inflatable implant causes either immune related connective tissue 
disorders or immunological sensitization. Nine comments from physicians 
stated that they had not observed connective tissue disorders and other 
immunological effects in their personal experiences with these devices. 
Two comments stated that further research is necessary to rule out this 
potential complication. Several comments stated that no definitive link 
between silicone and autoimmune diseases has been established. 
Furthermore, several comments 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 penile 
inflatable implant. Several comments stated that immune related 
connective tissue disorders and immunological sensitization should be 
removed from the list of significant risks associated with the penile 
inflatable implant.
    FDA agrees that no definitive causal relationship has been 
established between immunological effects and/or connective tissue 
disorders and the penile inflatable implant. 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 
men with penile inflatable implants, or of an atypical, as yet 
undefined, syndrome or disease, cannot be eliminated based on these 
data. FDA is aware that differences in the incidence of such disorders 
between men and women make extrapolation of the results of breast 
implant studies to the outcome of the penile inflatable implant 
difficult. In the 1993 guidance document, FDA recommends that a cohort 
of penile inflatable implant 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 
before PMA approval or PDP completion.

L. Biological Effects of Silica

    (Comment 18) Five comments stated that fumed amorphous silica is so 
tightly bound in the silicone elastomer components of the penile 
inflatable implant that the fumed amorphous silica is biologically 
inactive. For that reason, these comments believed that the presence of 
fumed amorphous silica is not a risk to health of the penile inflatable 
implant. Two other comments stated that complications related to the 
release of silica from the penile inflatable implant have not been 
observed, although one of these comments added that further research is 
necessary to rule out this potential complication.
    FDA does not believe there is sufficient information to eliminate 
fumed amorphous silica as a potential risk to health associated with 
the penile inflatable implant, 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.

M. Silicone Particle Shedding, Silicone Gel Leakage, and Associated 
Migration

    (Comment 19) There were seven comments regarding the risk of 
silicone particle shedding. Four of these comments stated that small, 
but clinically insignificant, quantities of silicone particles have 
been noted in the periprosthetic tissues and inguinal lymph nodes of 
some penile inflatable implant recipients. Two comments stated that 
there is no evidence of silicone particle shedding from the penile 
inflatable implant. One comment stated that minimal, if any, silicone 
particle shedding occurs with this device. Several of these comments 
concluded that silicone particle shedding is not a risk of the penile 
inflatable implant.
    Based upon information presented in the comments, FDA agrees that 
silicone particle shedding is not a risk to health of the penile 
inflatable implant. Although silicone particle shedding and subsequent 
migration have been reported with penile inflatable implants (Ref. 1), 
the quantity of such particles was minimal and no deleterious effects

[[Page 19655]]

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 20) Several comments stated that silicone gel leakage and 
migration are not risks to health of this device since there are no 
penile inflatable implants that contain silicone gel.
    FDA disagrees with the comments that no penile inflatable implant 
contains silicone gel. As stated in response to comment 4 of this 
document, FDA is aware of at least one device model, no longer marketed 
in the United States, that contained silicone gel within its cylinder 
tip. FDA agrees with the comments that the potential risks of silicone 
gel leakage and migration are not applicable to penile inflatable 
implants that do not contain silicone gel.

N. Degradation of Polyurethane Elastomer

    (Comment 21) There were three comments regarding the risk of 
polyurethane elastomer degradation. These comments stated that: (1) 
Currently marketed penile inflatable implants do not use polyurethane 
as a surface material, (2) in vitro testing regarding the degradation 
of polyurethane may not be predictive of degradation in vivo, and (3) 
there is no evidence in the literature of the release of either 
methylene diamine or toluene diamine in vivo from polyurethane.
    FDA is aware of at least two penile inflatable implant models that 
have polyurethane elastomer as one of their surface materials; 
therefore, the agency does not agree with the comment that this 
material is not used. Furthermore, since the available information 
regarding the degradation of polyurethane elastomer is inconclusive, 
FDA does not believe there is sufficient information to eliminate it as 
a potential risk to health associated with the penile inflatable 
implant. Consequently, the agency believes that this potential risk to 
health should be addressed in a PMA or PDP. FDA believes that this 
potential risk is only applicable to penile inflatable implants that 
employ polyurethane elastomer as a surface, patient-contacting 
material.

O. Other Reported Complications

    (Comment 22) Several comments were received regarding the ``other 
reported complications'' of the penile inflatable implant (i.e., 
hematoma, chronic pain, erythema, edema, ulceration, necrosis, 
scarring, and urinary retention). These comments stated that these 
complications either occur infrequently, are transient, or are not 
judged by patients or physicians to be severe.
    FDA believes that insufficient information is available to 
determine the frequency of these events or their consequences. 
Therefore, FDA believes that it is important for studies submitted in a 
PMA or PDP to provide accurate information on the incidence of all 
complications associated with the implantation of the penile inflatable 
implant.

P. Benefits of the Device

    (Comment 23) Many comments were received regarding FDA's 
description of the benefit of the penile inflatable implant. Several 
comments objected to FDA's statement that ``device implantation is a 
discretionary surgical procedure performed for reasons related to 
quality of life, rather than medical reasons.'' One comment stated that 
the benefits of the penile inflatable implant include penile 
reconstruction, in addition to quality of life improvement. This 
comment added that while many patients benefit with an improved quality 
of life, medical necessity and need are important indications for the 
use of penile inflatable implants. Another comment noted that the 
penile inflatable implant is, in fact, used to correct a medical 
problem--erectile dysfunction. A third comment argued that restoration 
of erectile function is analogous to surgical procedures to restore 
vision or hearing, or to salvage a limb, all of which could potentially 
be regarded as discretionary surgical procedures to improve quality of 
life.
    Lastly, several comments stated that the benefits of the penile 
inflatable implant include improvement of quality of life, and the 
psychological benefits of the device should not be underestimated or 
undervalued. Furthermore, a comment from a penile inflatable implant 
recipient stated that the device impacts his ``quality of life and 
manhood.''
    As stated in the proposed call for PMA's or PDP's, FDA believes 
that the penile inflatable implant is designed to provide sufficient 
penile rigidity to permit sexual intercourse. The proposed rule further 
states that this device is intended for the treatment of erectile 
dysfunction resulting from many medical conditions, such as diabetes 
mellitus, spinal cord injury, Peyronie's disease, and pelvic surgery. 
FDA continues to believe that device implantation is usually elective 
in nature, and the agency agrees with the comments that the primary 
benefit of the penile inflatable implant is restoration of erectile 
function. As noted by these comments, however, many implant recipients 
also benefit with an improved quality of life and FDA does not intend 
to underestimate or undervalue this benefit.
    (Comment 24) Three comments objected to FDA's reference to improved 
fertility as being an intended benefit of the penile inflatable 
implant. One comment agreed with the April 1993 proposed rule, noting 
that a benefit of the device is the restoration of the ability for 
young men with erectile dysfunction to father children naturally.
    FDA agrees that restoration of male fertility should not be listed 
as a benefit of the penile inflatable implant. Although this device may 
have provided an opportunity for a small number of patients to father 
children naturally, the agency acknowledges that this consequence of 
the device should not be listed as a benefit of the penile inflatable 
implant for the following reasons: (1) The primary reason for device 
implantation is the treatment of erectile dysfunction; (2) no penile 
inflatable implant manufacturer promotes their device with the claim of 
restoration of fertility; and (3) the majority of penile inflatable 
implant candidates are beyond the age of which they desire to father 
children. The agency's response to these comments is consistent with 
the recommendations provided at an April 15, 1993, meeting of the 
Gastroenterology and Urology Devices Advisory Panel.

Q. Need for Risk/Benefit Information

    (Comment 25) Two comments objected to FDA's proposal that PMA's and 
PDP's analyze the prior treatment history and presurgical workup of 
penile inflatable implant recipients. They stated that it is 
physicians, in consultation with patients, who should decide the choice 
of treatment for erectile dysfunction, and that devices should not be 
treated any differently in this respect than pharmaceuticals where a 
physician has many different drugs available to treat a disorder and 
chooses the appropriate one based on the patient's needs.
    FDA agrees that it should not interfere with the practice of 
medicine. However, the agency believes that manufacturers have a 
responsibility to report the circumstances of use of their device in 
the product's labeling, especially due to the potential for 
irreversible effects following implantation of a penile inflatable 
implant. Consequently, FDA believes that information regarding the

[[Page 19656]]

prior treatment history and presurgical workup of penile inflatable 
implant recipients should be reported in a PMA or PDP to ensure that 
labeling for the product will provide reasonable assurance of safe and 
effective use.
    (Comment 26) Three comments stated that quality of life and 
psychological evaluations are not useful to judge the effectiveness of 
the penile inflatable implant since the primary goal of device 
implantation is restoration of erectile function. Two of these comments 
added that: (1) Manufacturers do not make claims regarding 
psychological benefit, (2) it is inappropriate for FDA to require a 
manufacturer to demonstrate this benefit, (3) there are no accepted 
tests for measuring the psychological impact of the penile inflatable 
implant, and (4) existing tests for psychological well-being and self-
esteem are confounded by multiple life variables, including the 
patient's and partner's general health, sexual functioning, and 
understanding of the potential complications when making the decision 
to have a penile inflatable implant. One comment stated that assessment 
of psychological benefit would likely require large clinical studies.
    FDA agrees that the primary benefit derived from implantation of a 
penile inflatable implant is restoration of erectile function. However, 
FDA continues to believe that the potential quality of life and 
psychological benefits offered by the device are important, albeit 
secondary, components of the device's effectiveness. Although FDA 
agrees that designing studies to assess the psychological benefit of 
implantation with a penile inflatable implant may be difficult, FDA 
believes the psychological impact of the device can and should be 
assessed in a PMA or PDP as a secondary effectiveness measure. The 
agency will accept a variety of types of scientific evidence in support 
of a PMA or PDP, as long as the data constitute valid scientific 
evidence within the meaning of 21 CFR 860.7(c)(2) (e.g., a validated 
quality of life patient questionnaire can provide data to address this 
issue).

R. PMA Contents

    (Comment 27) FDA received two extensive comments on the types of 
manufacturing information, preclinical testing, and clinical data that 
should be required in a PMA for a penile inflatable implant, as well as 
several general comments on the appropriate contents of a PMA. 
Additionally, FDA received one comment proposing detailed modifications 
to the quality of life, satisfaction, and psychological evaluation 
recommendations stated in the proposed call for PMA's and PDP's.
    FDA agrees with many of the points raised in these comments. 
Although the 1993 guidance document describes the general types of 
manufacturing, preclinical, and clinical data that FDA believes can 
support approval of a PMA for a penile inflatable implant, 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 the 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 penile inflatable 
implant manufacturers. Furthermore, FDA intends to revise the 1993 
guidance document to incorporate many of these comments.

III. Findings With Respect to Risks and Benefits

A. Degree of Risk

1. Infection
    Infection is a risk associated with any surgical implant procedure, 
including the penile inflatable implant. 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 due to corporeal fibrosis and 
scarring.
2. Migration and Extrusion
    Migration refers to the movement of the components of the penile 
inflatable implant within the body. In some cases, a portion of the 
implant migrates externally (``extrusion''). The cylinders and pump can 
migrate either proximally or distally, leading to inadequate support of 
the glans penis, difficulty in manipulating the pump, or pressure 
necrosis with subsequent erosion. Extrusion is usually associated with 
wound dehiscence at the site of incision, but can also occur secondary 
to erosion. Factors contributing to migration and extrusion include 
implantation of a device that is too large, iatrogenic injury to the 
surrounding tissues, and infection. Migration and extrusion of the 
penile inflatable implant can lead to surgical intervention.
3. Erosion
    Erosion is the breakdown of tissue adjacent to the device. The 
cylinders can erode through the distal urethra, the pump can erode 
through the scrotal wall, and, rarely, the reservoir can erode through 
the bladder or bowel. Factors contributing to erosion include 
implantation of a device that is too large, iatrogenic injury to the 
surrounding tissues, and infection. Erosion may lead to device 
extrusion, and can require surgical intervention.
4. Fibrous Capsular Formation
    The formation of a fibrous capsule around the components of the 
penile inflatable implant is a risk associated with this device. 
Fibrous capsule formation around the reservoir and/or pump may either 
cause spontaneous inflation of the cylinders or prevent the cylinders 
from completely deflating. Significant fibrous capsular formation may 
be corrected by device manipulation, corrective surgery, or surgical 
removal of the device and adjacent tissues. The effects of fibrous 
capsule formation vary from reduced satisfaction with the implant to 
explantation.
5. Mechanical Malfunctions
    As with other prosthetic devices intended to restore a physiologic 
function, penile inflatable implants may mechanically malfunction. 
Reported types of mechanical malfunctions include leakage, cylinder 
rupture, cylinder aneurysm, spontaneous inflation/deflation, tubing 
kinks, and pump valve failure. 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.
6. Iatrogenic Disorders
    Improper device handling, inadequate or vigorous dilatation, 
aggressive dissection, malpositioning of the device, cylinder suturing, 
and cylinder 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.
7. Patient Dissatisfaction
    If patients are not provided information and counseling regarding 
the risks and benefits of the penile inflatable implant prior to 
implantation, they may not have realistic expectations of the physical, 
psychological, and functional outcomes of the device. Uninformed 
patients may be dissatisfied with the device due to complications such 
as unresolved pain, as well as disappointment in cosmetic appearance,

[[Page 19657]]

concealability, rigidity/firmness, and penile sensation. Some 
dissatisfied patients have elected to have the device surgically 
removed because the implant did not meet their expectations.
8. Human Carcinogenicity
    The potential for developing cancer as a result of the long-term 
implantation of the penile inflatable implant cannot be eliminated as a 
potential risk associated with this device.
9. Human Reproductive and Teratogenic Effects
    Although FDA is not aware of data indicating that the penile 
inflatable implant 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.
10. 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 
penile inflatable implant remains uncertain. Since the publication of 
the proposed rule 6 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 men with penile inflatable implants, or of an atypical, 
as yet undefined, syndrome or disease, cannot be eliminated based on 
these data.
11. Biological Effects of Silica
    Amorphous fumed silica is bound to the silicone in the elastomer of 
the penile inflatable implant. Silica presents a potential risk which 
should be addressed in a PMA or PDP.
12. Silicone Gel Leakage and Associated Migration
    Small quantities of silicone gel are present in at least one model 
of penile inflatable implant. 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.
13. Degradation of Polyurethane Elastomer
    Polyurethane elastomer materials, which have been used as surface 
materials in some penile inflatable implants, may degrade over time and 
release degradation products which are potential carcinogens in 
animals. When present, polyurethane elastomer degradation is a 
potential risk that should be addressed in a PMA or PDP.
14. Other Reported Complications
    Other reported complications associated with implantation of the 
penile inflatable implant include hematoma, chronic pain, erythema, 
edema, ulceration, necrosis, scarring, and urinary retention, which 
should be addressed in a PMA or PDP.

B. Benefits of the Device

    The penile inflatable implant is intended to restore the ability to 
have an erection in men with erectile dysfunction. It has the potential 
to be an effective treatment for erectile dysfunction. Implant 
recipients may also benefit from an improved quality of life.

IV. Final Rule

    Under section 515(b)(3) of the act, FDA is adopting the findings as 
published in the preamble to the April 1993 proposed rule and is 
issuing this final rule to require premarket approval of the generic 
type of device, the penile inflatable implant, by revising 
Sec. 876.3350(c).
    Under the final rule, a PMA or a notice of completion of a PDP is 
required to be filed on or before July 11, 2000, for any penile 
inflatable implant 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 July 11, 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 penile inflatable implant 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 July 11, 
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 a penile inflatable 
implant is not filed on or before the 90th day past the effective date 
of this regulation, that device will be deemed adulterated under 
section 501(f)(1)(A) of the act (21 U.S.C. 351(f)(1)(A)), 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 penile inflatable implant. Further, FDA 
concludes that investigational penile inflatable implants are 
significant risk devices as defined in 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 a penile inflatable implant. For any penile 
inflatable implant 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 penile inflatable implant 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 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. The Office of Management and Budget (OMB) has 
determined that this final rule is a significant regulatory action 
subject to review under the Executive Order.

[[Page 19658]]

    FDA expects that only two manufacturers will submit a PMA or PDP 
for the penile inflatable implant. FDA does not believe that two 
companies are a significant number of small entities. 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 penile inflatable implant 
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 April 28, 
1993. 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 both manufacturers to assist them in preparing for the 
submission of a PMA or a PDP, and one has successfully completed a PDP 
for two device models. FDA estimates based on such information as is 
publicly available, that these two companies have annual revenues in 
excess of several hundred million dollars. FDA, therefore, believes 
that this final rule will not be an undue burden on these 
manufacturers. 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.

VII. Paperwork Reduction Act of 1995

    This proposed 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 Sec. 876.3350(c) 
are reported and approved under OMB Control No. 0910-0231.

VIII. 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 Dockets Management Branch 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-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 876.3350 is amended by revising paragraph (c) to read as 
follows:

Sec. 876.3350  Penile inflatable implant.

* * * * *
    (c) Date premarket approval application (PMA) or notice of 
completion of a product development protocol (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 July 11, 2000, for any penile 
inflatable implant that was in commercial distribution before May 28, 
1976, or that has, on or before July 11, 2000, been found to be 
substantially equivalent to a penile inflatable implant that was in 
commercial distribution before May 28, 1976. Any other penile 
inflatable implant shall have an approved PMA or a declared completed 
PDP in effect before being placed in commercial distribution.

    Dated: March 24, 2000.
Linda S. Kahan,
Deputy Director for Regulations Policy, Center for Devices and 
Radiological Health.
[FR Doc. 00-9002 Filed 4-11-00; 8:45 am]
BILLING CODE 4160-01-F