SUMMARY OF SAFETY AND EFFECTIVENESS DATA

I. [GENERAL INFORMATION]{.underline}

Device Generic Name: Testicular Prosthesis

Device Trade Name: Mentor Saline-Filled Testicular Prosthesis

Applicant: Mentor Corporation

201 Mentor Drive

Santa Barbara, California 93111

Date(s) of Panel Recommendation: None

Premarket Approval Application (PMA) Number: P020003

Date of Notice of Approval to Applicant: July 19, 2002

II\. [INDICATIONS FOR USE]{.underline}

The Mentor Saline-Filled Testicular Prosthesis is intended for use when
cosmetic testicular replacement is indicated; i.e., in the case of
agenesis or following the surgical removal of a testicle.

III\. [CONTRAINDICATIONS]{.underline}

The implantation of testicular prostheses is contraindicated in the
presence of infection or untreated neoplasm.

IV\. [WARNINGS AND PRECAUTIONS]{.underline}

The warnings and precautions can be found in the labeling for the Mentor
Saline-Filled Testicular Prosthesis (Attachment 1).

V. [DEVICE DESCRIPTION]{.underline}

The Mentor Saline-Filled Testicular Prosthesis is a silicone elastomer
device that is designed to approximate the weight, shape, and softness
of the normal testicle. This device is implanted in the scrotum in males
who desire cosmetic replacement of a missing testicle, and consists of a
silicone elastomer shell with an injection port and recessed suture tab.
The Mentor Saline-Filled Testicular Prosthesis is manufactured in four
sizes to accommodate juvenile to adult anatomies. The device is packaged
empty, and filled with sterile saline at the time of implantation.

To facilitate the filling process, the Mentor Saline-Filled Testicular
Prosthesis is packaged with the following accessories: a butterfly
needle with infusion tubing, and a needle stop.

The Mentor Saline-Filled Testicular Prosthesis and accessories are sold
as sterile (gamma radiation) and labeled for single use only.

VI\. [ALTERNATIVE PRACTICES OR PROCEDURES]{.underline}

There are no alternative procedures for cosmetic testicular replacement.

VII\. [MARKETING HISTORY]{.underline}

The Mentor Saline-Filled Testicular Prosthesis has been marketed in 33
countries since its development in 1992. This device has not been
withdrawn from marketing for any reason related to the safety and
effectiveness of the device.

VIII\. [POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH]{.underline}

The following adverse events were observed in the PMA clinical studies
of the Mentor Saline-Filled Testicular Prosthesis: pain, discomfort,
edema (implant or incision site), infection, extrusion,
displacement/migration, genital hematoma, keloid formation, implant
deflation/leakage, inadequate position, fluid accumulation,
constipation, hives, fibrosis, granuloma, mobile implant, neuropathy
(leg), numbness (heel), suture abscess, and unnecessary incision.

Additionally, the following potential risks of testicular prostheses or
their materials were not reported in the PMA clinical studies: erosion
and immune-related connective tissue disorders.

IX\. [SUMMARY OF PRECLINICAL STUDIES]{.underline}

[Material Characterization Studies]{.underline}:

A series of *in vitro* tests were conducted to characterize the chemical
constituents of the materials of the Mentor Saline-Filled Testicular
Prosthesis. The objectives of this testing were to identify the chemical
make-up of these materials and to estimate the exposure of each to the
patient. This information was used to determine the biocompatibility
testing scheme. The complete list of material characterization tests
performed is as follows:

-   analysis of total extractables;

-   identification and quantification of volatiles and semivolatile
    extractables;

-   analysis of chemical crosslinking;

-   molecular weight characterization of nonvolatile extractables;

-   heavy metals assessment; and

-   surface analysis.

All material characterization tests were performed on finished,
sterilized devices.

These tests were found to be adequate for characterizing the materials
of the Mentor Saline-Filled Testicular Prosthesis.

[Biocompatibility Studies]{.underline}:

Using the knowledge gained from the material characterization tests,
biocompatibility testing was conducted on the patient-contacting
components of the Mentor Saline-Filled Testicular Prosthesis. The
objective of this testing was to assess whether these materials are safe
for long-term implantation. The following biocompatibility tests were
performed on the individual patient-contacting materials of the device:

-   cytotoxicity;

-   hemolysis;

-   acute systemic toxicity;

-   intracutaneous toxicity;

-   sensitization;

-   Ames mutagenicity; and

-   implantation (30 and 90 days).

Additionally, the following biocompatibility tests were performed on the
finished, sterilized device:

-   cytotoxicity;

-   hemolysis;

-   acute systemic toxicity;

-   intracutaneous toxicity;

-   sensitization;

-   Ames mutagenicity; and

-   pyrogenicity.

Furthermore, the following biocompatibility tests were performed on
other legally marketed implanted devices (manufactured by Mentor) that
are constructed of either identical or similar silicone elastomers as
the Mentor Saline-Filled Testicular Prosthesis:

-   L5178Y TK +/- mouse lymphoma mutagenesis assay;

-   morphological transformation of BALB/3T3 mouse embryo cells;

-   Ames mutagenicity;

-   unscheduled DNA synthesis assay (rat primary hepatocytes);

-   chronic toxicity/carcinogenicity;

-   reproductive toxicity;

-   immunotoxicity; and

-   adjuvancy.

This list of biocompatibility tests is consistent with the tests
suggested in ISO-10993 for permanent implants with bone/tissue contact.
This information demonstrated that the device Mentor Saline-Filled
Testicular Prosthesis does not pose a toxicological concern.

[Mechanical Testing]{.underline}:

Mechanical testing was conducted to assess the safety, effectiveness,
and reliability of the Mentor Saline-Filled Testicular Prosthesis. Bench
tests were conducted to evaluate all device attributes that are critical
to its safety and performance. Furthermore, additional mechanical tests
were performed to measure certain other device attributes for
characterization purposes. The complete list of mechanical tests
performed is as follows:

*Material characteristics*:

-   modulus of elasticity at 200% elongation;

-   tensile strength;

-   ultimate elongation;

-   energy to rupture;

-   tear strength;

-   durometer; and

-   abrasion resistance.

*Subassembly characteristics*:

-   injection site puncture test.

*Finished device characteristics*:

-   injection site puncture test;

-   suture tab strength and elongation;

-   compressive cyclic fatigue test; and

-   fill volume test.

All mechanical tests were performed on sterilized samples using test
conditions that simulated *in vivo* conditions whenever appropriate. The
sample sizes used for each test were justified, and representative
samples of each device size were evaluated when necessary. The results
of this testing demonstrated that the device functions according to the
stated design specifications.

[Shelf Life Testing]{.underline}:

Stability testing was performed on finished, sterilized devices,
accelerated aged to an equivalent of 5 years. This testing justifies a
shelf life claim of 5 years. Testing on real-time aged samples is
ongoing.

X. [SUMMARY OF CLINICAL STUDIES]{.underline}

[Objectives]{.underline}:

Two clinical studies were performed to assess the safety and
effectiveness of the Mentor Saline-Filled Testicular Prosthesis: (i) a
Core Study, and (ii) an Adjunct Study.

The objectives of the Core Study were to assess the safety and
effectiveness of the Mentor Saline-Filled Testicular Prosthesis in males
for whom testicular replacement is indicated. The primary effectiveness
objective of the Core Study was evaluation of the ability of the device
to provide and maintain the intended testicular dimensions. Secondary
effectiveness objectives were evaluation of the effects of the device on
patient quality of life/satisfaction and physician assessment of the
appearance of the implanted device. The primary safety objective was to
determine the occurrence and severity of adverse events, including the
rate of device explantation and the incidence of connective tissue
diseases.

The objective of the Adjunct Study was to collect supplementary
information regarding adverse events following completion of enrollment
of patients into the Core Study.

> [Study Design]{.underline}:
>
> The Core and Adjunct Studies are both baseline-controlled,
> multicenter, prospective clinical studies. The Core Study was
> conducted to evaluate the safety and effectiveness of the Mentor
> Saline-Filled Testicular Prosthesis, with the pre-implant experience
> of patients serving as the comparison for the assessment of device
> outcome. The design of this clinical study is consistent with the
> recommendations contained in the Proposed Rule for Premarket Approval
> of the Testicular Prosthesis (58 FR 4116)^1^, the recommendations of
> the FDA guidance document entitled "Draft Guidance for Preparation of
> PMA Applications for Testicular Prostheses,"^2^ and the subsequent
> recommendations presented to and agreed upon by the Gastroenterology
> and Urology Devices Advisory Panel at the July 29, 1999 open public
> meeting. The Adjunct Study was conducted to collect supplementary data
> on the incidence and severity of adverse events.

A total of 149 Core Study patients were implanted at 18 institutions in
the United States between September 1998 and September 1999. After Core
Study enrollment was completed, a total of 209 Adjunct Study patients
were implanted at 39 U.S. institutions. The Core and Adjunct Study
reports include all results compiled through March 2002.

Male patients (adult or pediatric) indicated for either unilateral or
bilateral testicular prosthesis implantation were enrolled into the Core
Study. This study included patients with testicular loss due to either
agenesis or surgical removal. All subjects (or parents of pediatric
subjects) provided valid informed consent. Additionally, all subjects
agreed to permit explant analysis of the device (if explanted).
Exclusion criteria for the Core Study included: patient had an active
infection or abscess; patient had uncontrolled or severe diabetes
reducing their wound healing ability; patient had tissue characteristics
that would prevent implantation of the device (e.g., tissue damage from
prior radiation, inadequate tissue coverage, or compromised
vascularity); patient had health or psychological conditions
incompatible with the device implantation or the study requirements;
patient had any prior silicone implant, including a prior testicular
prosthesis; and patient was diagnosed with systemic lupus, discoid
lupus, scleroderma, rheumatoid arthritis, or other connective tissue
disorders.

> After enrollment into the Core Study was completed, patients (adult or
> pediatric) indicated for either unilateral or bilateral testicular
> prosthesis implantation were enrolled into the Adjunct Study. This
> study included patients with testicular loss due to either agenesis or
> surgical removal, as well as patients undergoing gender conversion
> surgery. All subjects (or parents of pediatric subjects) provided
> valid informed consent. Exclusion criteria for the Adjunct Study
> included: patient enrolled in the Core Study; patient had an active
> infection or abscess; patient had uncontrolled or severe diabetes
> reducing their wound healing ability; patient had tissue
> characteristics that would prevent implantation of the device (e.g.,
> tissue damage from prior radiation, inadequate tissue coverage, or
> compromised vascularity); patient had health or psychological
> conditions incompatible with the device implantation or the study
> requirements; and patient was diagnosed with systemic lupus, discoid
> lupus, scleroderma, rheumatoid arthritis, or other connective tissue
> disorders.

[Patient Assessments]{.underline}:

> Evaluation of the safety and effectiveness of the Mentor Saline-Filled
> Testicular Prosthesis is based on 1‑year evaluation of the following
> clinical endpoints:
>
> *Effectiveness Endpoints (Core Study only)*:

-   Physician measurement of the size of the implanted Mentor
    Saline-Filled Testicular Prosthesis, relative to the patient's
    pre-implant scrotal anatomy.

-   Patient assessment of satisfaction and quality of life (Patient
    Assessment Instrument, Rosenberg Self-Esteem Scale, Body Esteem
    Scale, and Body Exposure in Sexual Activities Questionnaire).

-   Physician assessment of cosmetic appearance of the implanted device.

*Safety Endpoints (Core and Adjunct Studies)*:

-   Occurrence and severity of adverse events, including connective
    tissue diseases.

-   Rates of and time to explantation, revision, and other resurgery.

> Prior to enrollment, patients received routine clinical assessments to
> document study eligibility and baseline characteristics. After
> implantation, all Core Study subjects were scheduled for follow-up
> examinations at 1 week, 1 month, 6 months, 1 year, 18 months, 2 years,
> 3 years, 4 years, and 5 years post-implantation. In the Adjunct Study,
> subjects were scheduled for a single follow-up examination 1 year
> post-implantation.

Of the 149 patients implanted in the Core Study, 124 (83.2%) received
1-year follow-up. Of the 25 patients for whom 1-year data are not
available, 5 missed the 1-year visit (but are continuing in the study)
and 20 prematurely discontinued the study prior to 1 year. Reasons for
study discontinuation at 1 year are patient lost-to-follow-up (n=10);
patient withdrew consent (n=5); patient had the prosthesis explanted
(n=2); patient moved (n=2); and the investigational site discontinued
from study due to noncompliance (n=1). The use of 1-year follow-up data
for the review of this PMA permits a thorough assessment of device
effectiveness and adverse events, and also provides preliminary
information regarding the rate of revision surgeries. Based on this
information and the concurrence of the Gastroenterology and Urology
Devices Advisory Panel at the July 29, 1999, meeting, reliance on 1-year
follow-up data is clinically justified. In addition to the 1-year
results, 104 Core Study patients have received 18-month follow-up, and
94 have received 2-year follow-up.

> Of the 209 patients implanted in the Adjunct Study, 68 received 1-year
> follow-up, 58 are not yet eligible for 1-year follow-up, and 83 either
> missed the 1-year follow-up visit or prematurely discontinued from the
> study (5 cases of which were the result of device explantation).
>
> [Demographic Data]{.underline}:

Of the 149 Core Study patients, 73 (49.0%) were pediatric (i.e., \< 18
yrs.) at the time of device implantation. Since the clinical results may
be dependent upon patient age (i.e., pediatric vs. adult) and/or
pre-implantation status (i.e., testicle missing vs. present at
baseline), patients were stratified for analysis as follows:

-   Stratum 1P: Pediatric missing his testicle(s) at baseline.

-   Stratum 2P: Pediatric not missing his testicles at baseline (but
    scheduled for surgical removal).

-   Stratum 1A: Adult missing his testicle(s) at baseline.

-   Stratum 2A: Adult not missing his testicles at baseline (but
    scheduled for surgical removal).

> Additional demographic information for the 149 Core Study patients is
> provided below in Table 1:

Table 1: Demographic Data -- Core Study

+-----------------------------------+-----------------------------------+
|                                   | **Core Study (n=149 pts.)**       |
+-----------------------------------+-----------------------------------+
| Mean age (range):                 | 22.3 yrs (0.5 -- 76 yrs)          |
|                                   |                                   |
| Overall                           | 12.8 yrs (0.5 -- 17 yrs)          |
|                                   |                                   |
| Pediatrics                        | 31.1 yrs (18 -- 76 yrs)           |
|                                   |                                   |
| Adults                            |                                   |
+-----------------------------------+-----------------------------------+
| Race:                             | 91.3%                             |
|                                   |                                   |
| Caucasian                         | 5.4%                              |
|                                   |                                   |
| African American                  | 3.3%                              |
|                                   |                                   |
| Other                             |                                   |
+-----------------------------------+-----------------------------------+
| Reason for testicular prosthesis: | 65.3%                             |
|                                   |                                   |
| Orchiectomy                       | 24.4%                             |
|                                   |                                   |
| Agenesis                          | 8.5%                              |
|                                   |                                   |
| Torsion                           | 1.8%                              |
|                                   |                                   |
| Trauma                            |                                   |
+-----------------------------------+-----------------------------------+
| Number (%) bilateral cases:       | 27 pts. (18.1%)                   |
+-----------------------------------+-----------------------------------+
| Strata:                           | 62 pts. (41.6%)                   |
|                                   |                                   |
| 1P                                | 11 pts. (7.4%)                    |
|                                   |                                   |
| 2P                                | 52 pts. (34.9%)                   |
|                                   |                                   |
| 1A                                | 24 pts. (16.1%)                   |
|                                   |                                   |
| 2A                                |                                   |
+-----------------------------------+-----------------------------------+

> Of the 209 Adjunct Study patients, 80 (38.3%) were pediatric.
> Additional information regarding the Adjunct Study is presented below
> in Table 2.

Table 2: Demographic Data -- Adjunct Study

+-----------------------------------+-----------------------------------+
|                                   | **Adjunct Study (n=209 pts.)**    |
+-----------------------------------+-----------------------------------+
| Number (%) bilateral cases:       | 31 pts. (14.8%)                   |
+-----------------------------------+-----------------------------------+
| Strata:                           | 65 pts. (31.1%)                   |
|                                   |                                   |
| 1P                                | 15 pts. (7.2%)                    |
|                                   |                                   |
| 2P                                | 100 pts. (47.8%)                  |
|                                   |                                   |
| 1A                                | 29 pts. (13.9%)                   |
|                                   |                                   |
| 2A                                |                                   |
+-----------------------------------+-----------------------------------+

> [Data Analysis and Results]{.underline}:
>
> *Device Implantation/Surgical Information*:

Detailed information regarding the implantation of the Mentor
Saline-Filled Testicular Prosthesis was obtained from analysis of the
Core Study. A total of 176 devices were implanted in the Core Study (122
unilateral cases and 27 bilateral cases). The implanted devices included
the large (71.6%), medium (19.3%), and small (9.1%) sizes. No extra
small size devices were implanted during the Core Study, since this
implant size was not introduced until after enrollment was completed.
Although the extra small size was not clinically evaluated, bench
testing of the device demonstrated that the extra small size has
equivalent mechanical and reliability characteristics as the other
sizes. The implantation surgeries were performed using standard
technique. Prophylactic antimicrobials were used prior to and/or during
the implantation procedure in 94.6% of cases, and general anesthesia was
used in 96.0% of cases. For patients with both testes present at
baseline (i.e., strata 2P and 2A), orchiectomy immediately preceded
device implantation. The majority of devices were implanted using either
an inguinal approach (70.0%) or a scrotal approach (22.7%). In
approximately half of the devices implanted, the suture tab was used to
fix the implant in place. For the remaining cases, the investigator
elected not to use the suture tab.

> *Effectiveness Endpoints*:
>
> The evaluation of device effectiveness is based on the results of the
> 149 Core Study patients. The primary effectiveness endpoint for this
> clinical trial was physician measurement of volume of the implanted
> Mentor Saline-Filled Testicular Prosthesis, relative to the volume of
> the patient's pre-implant scrotal anatomy. For patients in Strata 1
> (i.e., testicle(s) missing at baseline), the baseline size was
> recorded as 0 mL. For patients in Strata 2 (i.e., testicles present at
> baseline but scheduled for removal), the actual volume was estimated.
> To standardize data collection among the sites, all estimates of
> testicle/device size were made using a Prader Orchiometer. The
> objectives of this assessment are to demonstrate (i) a significant
> increase in testicular size, compared to baseline, among Stratum 1
> patients, and (ii) stability of post-implantation testicular size
> among Strata 1 and 2 patients. At 1-year post-implantation, the mean
> testicular sizes for Strata 1P and 1A patients were 21.8 mL and 23.0
> mL, respectively. These differences from baseline were highly
> statistically significant (p\<0.001). Similar results were observed at
> the other follow-up exams for which sufficient data are available
> (i.e., 1 month, 6 months, 18 months, and 2 years). The stability of
> testicular size was tested by comparing the mean sizes at the 1-month,
> 6-month, 1-year, 18-month, and 2-year visits. This analysis was
> performed separately for Strata 1 and 2 patients using a repeated
> measures analysis of variance. For patients missing a testicle at
> baseline (i.e., Strata 1), the mean sizes were 22.0, 22.3, 22.7, 23.4,
> and 22.8 mL at the 1‑month through 2-year exams, respectively.
> Although these differences were statistically significant (p=0.007),
> they are clinically insignificant. For patients not missing a testicle
> at baseline (i.e., Strata 2), the mean sizes were 20.3, 21.1, 21.8,
> 21.1, and 21.3 mL at the 1-month through 2-year exams, respectively.
> This variation was not statistically significant. For both strata,
> therefore, stability in testicle size was observed between 1 month and
> 2 years post-implantation.

The secondary endpoints of device effectiveness were assessment of
patient satisfaction, self esteem, body esteem, and body exposure in
sexual activities. Each of these endpoints was evaluated by patient
self-report using standardized surveys at baseline, 6 months, 1 year, 18
months, and 2 years. Additionally, the cosmetic appearance of the
implanted device was rated by the investigator during these
post-treatment examinations. The results of these effectiveness
endpoints are described below:

> [Patient satisfaction]{.underline}, as rated using the Patient
> Assessment Instrument (i.e., a standard set of questions developed by
> Mentor for this study), assessed how the patient feels about his
> genitals before and after implantation of the testicular prosthesis.
> This instrument was completed by all adult patients, and all pediatric
> patients ≥ 13 years old. ([Note]{.underline}: Survey instruments were
> not administered to patients younger than 13 years old due to
> validation/reliability concerns.) Since the baseline satisfaction
> rating would be different depending whether the patient is missing a
> testicle, Strata 1 and 2 patients were analyzed separately. Each
> question was rated by the subject on a scale from 1 (very negative
> rating) to 5 (very positive rating), and the scores of each question
> were averaged to obtain a final score. For Stratum 1 patients
> (testicle missing at baseline), the results of the Patient Assessment
> Instrument were statistically significantly and clinically
> meaningfully improved over baseline for all follow-up periods (i.e.,
> approximately 50.6-601% over baseline). For Stratum 2 (testicles
> present at baseline), for whom meaningful baseline comparisons are not
> possible, the Patient Assessment Instrument results were only
> qualitatively assessed. The mean score at each follow-up time point
> ranged from 4.41-4.31 out of a possible 5 points, indicating a
> positive response toward the implant. Estimates of the correlation
> between the 6-month and 1-year results support the validity of this
> instrument.
>
> [Patient self esteem]{.underline}, as measured by the Rosenberg
> Self-Esteem Scale^3^, was assessed in all adult patients, and all
> pediatric patients ≥ 13 years old. For Stratum 1 patients, small
> levels of improvement (i.e., 1.7-8.1% over baseline) were seen at all
> follow-up periods, some of which were statistically significant. For
> Stratum 2 patients, the post-implantation results were not
> statistically significantly different from the baseline level.
>
> [Body esteem]{.underline}, as measured by the Body Esteem Scale
> (Physical Attractiveness subscale)^4,5^, was assessed in all adult
> patients, and all pediatric patients ≥ 13 years old. For Stratum 1
> patients, small levels of improvement (i.e., 1.6-11.1% over baseline)
> were seen at nearly all follow-up periods, some of which were
> statistically significant. For Stratum 2 patients, the
> post-implantation results were not statistically significantly
> different from the baseline level.
>
> [Body exposure in sexual activities]{.underline} was assessed using
> the Body Exposure in Sexual Activities Questionnaire (BESAQ)^6,\ 7^,
> which rates the subject's response to various statements regarding
> thoughts and behaviors that the individual may experience during
> sexual encounters. Due to the nature of this questionnaire, the BESAQ
> was only assessed in adult patients. For each strata, the results of
> this questionnaire were statistically significantly improved over
> baseline at each follow-up period (i.e., 34.0-43.3% decrease from
> baseline; lower scores indicate improvement).
>
> The [cosmetic appearance]{.underline} and firmness of the device was
> rated by the physician at baseline and at each follow-up period.
> Appearance was rated on a scale ranging from one (very abnormal) to
> five (normal). Overall and for each strata, statistically significant
> improvement from baseline in cosmetic appearance was observed at each
> visit (i.e., 70.0-108.3% improvement in Stratum 1; 28.6-58.1% in
> Stratum 2). Additionally, investigators rated the implanted device as
> "firm" in 94 to 99% of subjects at each visit.

These results demonstrate that the Mentor Saline-Filled Testicular
Prosthesis significantly improved the patient's body exposure in sexual
activity rating, is associated with a high degree of patient
satisfaction, and is cosmetically acceptable as rated by the physician.
As anticipated, patient self esteem and body esteem was maintained or
slightly improved following device implantation.

> *Safety Endpoints*:

The evaluation of device safety is based on the results of the 149 Core
Study patients and 209 Adjunct Study patients. The safety of the Mentor
Saline-Filled Testicular Prosthesis was evaluated through (i) assessment
of adverse events and (ii) the rates of explantation, revision, and
other resurgery. Table 3 summarizes the device and procedure-related
adverse events reported in the Core Study.

> Table 3: Adverse Events -- Core Study (n=149 pts.)

  -------------------------------------- ------------- ------------------
  **Adverse Event Category**             **Number (%)  **Mean (Range)
                                         of Patients** Onset Time in
                                                       Days**

  Pain                                   8 (5.4%)      127 (1-661)

  Discomfort                             6 (4.0%)      167 (1-668)

  Edema (implant or incision site)       4 (2.7%)      2 (1-4)

  Extrusion                              3 (2.0%)      28 (16-39)

  Displacement/migration                 3 (2.0%)      36 (29-42)

  Genital hematoma                       2 (1.3%)      1\*

  Keloid formation                       2 (1.3%)      112 (39-184)

  Implant deflation\*\*                  1 (0.7%)      35

  Fluid accumulation (inguinal area)     1 (0.7%)      11

  Constipation                           1 (0.7%)      1

  Fibrosis                               1 (0.7%)      207

  Granuloma                              1 (0.7%)      8

  Mobile implant                         1 (0.7%)      42

  Neuropathy (leg)                       1 (0.7%)      1

  Numbness (heel)                        1 (0.7%)      1

  Suture abscess                         1 (0.7%)      33
  -------------------------------------- ------------- ------------------

> \* The onset time was not documented in one case of genital hematoma.
>
> \*\* The case of implant deflation was recorded when an investigator
> felt a small dimple in an implant, believed to be due to incomplete
> filling at the time of implantation rather than fluid loss. Although
> this dimple was palpable, the appearance was cosmetically acceptable
> to both the physician and patient. Therefore, the implant was not
> removed.

The incidence of adverse events was not related to patient strata. With
the exception of the three cases of extrusion and two cases of
displacement/migration (all of which required resurgery), these adverse
events either resolved or were judged by the physician and patient not
to require further treatment.

The device and procedure-related adverse events reported in the Adjunct
Study were similar to those reported in the Core Study. However, these
data are reported separately since the Adjunct Study patients were not
followed as closely as those in the Core Study. These adverse events
are: infection (n=4), displacement/migration (n=2), leakage (n=1),
extrusion (n=1), hives (n=1), inadequate position (n=1), pain (n=1), and
unnecessary incision (n=1).

The following risks of testicular prostheses or their materials have
been reported in the medical literature but did not occur during the
Core or Adjunct Studies: erosion and immune-related connective tissue
disorders. No patients died during the either the Core or Adjunct
Studies.

> The overall resurgery rate for Core Study patients was 3.4% (5/149
> patients). The corresponding 1‑year life table rate for resurgery was
> 2.8% (upper 95% confidence limit = 5.5%). These five resurgeries
> consisted of four device explantations (in the three cases of
> extrusion and one case of displacement/migration) and one surgery to
> relieve dense adhesive bands that formed in the scrotum (which
> occurred in one of the patients listed as experiencing
> displacement/migration). However, the long-term (i.e., 5-year) rates
> of device rupture and revision are currently unknown.

In the Adjunct Study, the overall resurgery rate was 2.9% (6/209). These
six resurgeries consisted of four device explantations (in one case each
of extrusion, leakage, pain, and hives) and two surgeries (both to
reposition the implant in cases of displacement/migration and inadequate
position).

No patient in either the Core or Adjunct Study had his device replaced
with a larger prosthesis as a result of physical maturation of the
subject.

[Device Failures and Replacements]{.underline}:

No device failures/malfunctions occurred during the clinical studies,
and no devices were replaced.

XI\. [CONCLUSIONS DRAWN FROM THE STUDIES]{.underline}

Preclinical testing of the Mentor Saline-Filled Testicular Prosthesis
adequately characterized the device's materials, demonstrated that the
materials of the device are biocompatible, verified that the device is
mechanically reliable, and justified a 5-year shelf-life.

Clinical testing of the device demonstrated that the Mentor
Saline-Filled Testicular Prosthesis is reasonably safe and effective
when used in accordance with the directions for use. However, the
long-term (i.e., 5-year) rates of device rupture and revision are
currently unknown. The results of clinical testing demonstrated that the
device:

-   provided a significant increase in testicular size compared to
    baseline (among Stratum 1 patients), which was maintained through
    the 2-year follow-up examination (among all patients);

-   was associated with a high degree of patient satisfaction, and was
    subjectively rated by the physician as cosmetically acceptable in
    nearly all cases;

-   resulted in an improvement in the patient's perception of his body
    exposure in sexual activities, as compared to baseline;

-   was not associated with a decrease in self esteem or body esteem, as
    compared to baseline;

-   had a 1-year life table rate for resurgery of 2.8% (upper 95%
    confidence limit = 5.5%); and

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-   was associated with relatively few adverse events, which were either
    successfully treated or judged by the physician and patient not to
    require further treatment.

Therefore, it is reasonable to conclude that the benefits of use of the
device for the target population outweigh the potential risk of illness
or injury when used as indicated in accordance with the directions for
use.

XII\. [PANEL RECOMMENDATION]{.underline}

In accordance with the provisions of section 515(c)(2) of the act as
amended by the Safe Medical Devices Act of 1990, this PMA was not
referred to the Gastroenterology and Urology Devices Advisory Panel, an
FDA advisory committee for review and recommendation based on the
Panel's (i) classification of the testicular prosthesis, (ii) review of
the FDA guidance document entitled "Draft Guidance for Preparation of
PMA Applications for Testicular Prostheses," and (iii) subsequent
recommendations presented to and agreed upon by the Panel at the July
29, 1999 open public meeting.

XIII\. [CDRH DECISION]{.underline}

Based upon the PMA review, CDRH believes that these data provide
reasonable assurance that the device is safe and effective when used in
accordance with the directions for use. Therefore, CDRH believes that
the Mentor Saline-Filled Testicular Prosthesis can be approved with the
following postapproval requirement: continued follow-up of a minimum of
100 patients out to 5 years post-implantation, consistent with the
existing Core Study protocol, for assessment of the rates of device
rupture and resurgery. Following completion of this postapproval study,
the labeling must be revised (via a PMA supplement) to reflect these
long-term results.

The Mentor Saline-Filled Testicular Prosthesis was granted expedited
review status on January 22, 2002 because FDA believes that a testicular
prosthesis for cosmetic testicular replacement is in the best interest
of public health since (i) no legally marketed testicular prosthesis is
available, and (ii) the only treatment option for patients who are
missing a testicle is "no treatment."

The applicant created a Patient Education Guide to inform prospective
recipients of the Mentor Saline-Filled Testicular Prosthesis (or their
parents/guardians) of the risks and benefits of the device (Attachment
1).

The applicant\'s manufacturing facility was inspected on February 26 and
April 19, 2002, and was found to be in compliance with the device Good
Manufacturing Practice regulations.

FDA issued an approval order on July 19, 2002.

XIV\. [APPROVAL SPECIFICATIONS]{.underline}

[Directions for use]{.underline}: See the labeling.

[Hazards to Health from Use of the Device]{.underline}: See Indications,
Contraindications, Warnings, Precautions and Adverse Events in the
labeling.

[Postapproval Requirements and Restrictions]{.underline}: See approval
order.

XV\. [REFERENCES]{.underline}

1.  Federal Register, Vol. 58. No. 8, Wednesday, January 13, 1993, pg.
    4116.

2.  "Draft Guidance for Preparation of PMA Applications for Testicular
    Prostheses," FDA, CDRH, March 1993
    (<http://www.fda.gov/cdrh/ode/oderp809.html>).

3.  Rosenberg, M., [Society and the Adeloscent Self Image]{.underline},
    Princeton University Press, Princeton, New Jersey, 1965.

4.  Franzoi, S. L. and S. A. Shields, "The Body Esteem Scale:
    Multidimensional Structure and Sex Differences in a College
    Population," Journal of Personality Assessment, Vol. 48, pp.
    173-178, 1984.

5.  Franzoi, S. L., "Further Evidence of the Reliability and Validity of
    the Body Esteem Scale," Journal of Clinical Psychology, Vol. 50, pp.
    237-239, 1994.

6.  Faith, M. S. et al., "The Body Exposure in Sexual Activities
    Questionnaire: Psychometric Properties and Sexual Correlates,"
    presented at the 1993 meeting of the Association for Advancement of
    Behavior Therapy (Atlanta, Georgia).

7.  Grant, J. R. and T. F. Cash, "Cognitive-Behavioral Body Image
    Therapy: Comparative Efficacy of Group and Modest-Contact
    Treatments," Behavior Therapy, Vol. 26, pp. 69-84, 1995.