> **SUMMARY OF SAFETY AND EFFECTIVENESS DATA:**

# NovaSure Impedance Controlled Endometrial Ablation System

**I. GENERAL INFORMATION**

DEVICE GENERIC NAME: Thermal (Radio-Frequency) Endometrial Ablation
Device

> DEVICE TRADE NAME: NovaSure Impedance Controlled Endometrial Ablation
> System
>
> APPLICANT'S NAME AND ADDRESS: Novacept, Inc.
>
> 1047 Elwell Court
>
> Palo Alto, CA 94303
>
> PREMARKET APPROVAL APPLICATION
>
> (PMA) NUMBER: P010013
>
> DATE OF PANEL RECOMMENDATION: N/A
>
> DATE OF NOTICE OF
>
> APPROVAL TO THE APPLICANT: September 28, 2001

**II. INDICATIONS FOR USE**

> The **NovaSure™ System** is intended to ablate the endometrial lining
> of the uterus in pre-menopausal women with menorrhagia (excessive
> bleeding) due to benign causes for whom childbearing is complete.

**III. CONTRAINDICATIONS**

### Use of the NovaSure™ Impedance Controlled Endometrial Ablation System (hereafter referred to as the NovaSure™ System) is contraindicated for patients with the following conditions:

-   A patient who is pregnant or who wants to become pregnant in the
    future. Pregnancies following ablation can be dangerous for both
    mother and fetus.

-   A patient with known or suspected endometrial carcinoma (uterine
    cancer) or pre-malignant change of the endometrium, such as
    unresolved adenomatous hyperplasia.

-   A patient with any anatomic or pathologic condition in which
    weakness of the myometrium could exist, such as history of previous
    classical cesarean section or transmural myomectomy.

-   A patient with an active genital or urinary tract infection at the
    time of the procedure (*e.g.*, cervicitis, vaginitis, endometritis,
    salpingitis, or cystitis).

-   A patient with an intrauterine device (IUD) currently in place.

-   A patient with a uterine cavity length less than 4 cm. The minimum
    length of the electrode array is 4 cm. Treatment of a uterine cavity
    with a length less than 4 cm will result in thermal injury to the
    endocervical canal.

-   A patient with active pelvic inflammatory disease.

#### WARNINGS AND PRECAUTIONS

> A listing of Warnings and Precautions can be found in the device
> labeling.

#### DEVICE DESCRIPTION

> The NovaSure™ System consists of the Disposable Device, the RF
> (radio-frequency) Controller, the carbon dioxide (CO~2~) canister,
> desiccant, foot switch, and power cord. The Disposable Device is
> inserted transcervically into the uterine cavity and, using the RF
> Controller, delivers radio-frequency energy to treat the interior
> surface of the uterine cavity. The actual radio-frequency treatment
> requires an average of approximately 90 seconds. Neither concomitant
> hysteroscopic visualization nor endometrial pre-treatment is required.
>
> The Disposable Device consists of a single-patient use, bipolar
> electrode array mounted on a frame that expands to a triangle-like
> shape when deployed in the uterus. During the ablation process,
> radio-frequency energy desiccates and coagulates the endometrium and
> the underlying, superficial myometrium. As tissue destruction
> progresses, electrical impedance of the tissue increases. The
> procedure terminates when impedance at the tissue-electrode interface
> reaches 50 ohms or when the total treatment time reaches two minutes,
> whichever comes first.
>
> The bipolar electrode array is formed from a stretchable, porous
> fabric consisting of silver and gold plated on nylon and spandex.
> Suction drawn through the Disposable Device during the ablation
> process serves to maintain good contact between the tissue and the
> electrode array, and to remove liquids, steam, and other gases
> generated during treatment.
>
> The RF Controller is a constant power output generator with a nominal
> maximum power delivery capability of 180 watts. The power provided to
> the Disposable Device by the RF Controller depends on the uterine
> cavity length and width that the user key-enters into the Controller.
> The uterine cavity length is the difference between the sound
> measurement and the length of the endocervical canal. The uterine
> cavity width is measured by the Disposable Device when it is deployed
> in the uterus.
>
> The RF Controller also has a Cavity Integrity Assessment (CIA) system,
> which is designed to determine whether there is a defect or
> perforation through the wall of the uterus. After the Disposable
> Device is inserted in the uterine cavity, carbon dioxide is delivered
> from the Controller through the Disposable Device and into the uterine
> cavity. The uterine cavity is considered to be intact if carbon
> dioxide pressure in the cavity is maintained for 4 seconds; in this
> case, the user can proceed with the treatment phase.
>
> *[Procedure for Use]{.underline}*

-   Anesthetize and perform a bimanual examination of the patient.

-   Sound the uterus.

-   Measure the length of the cervical canal; dilate the canal to 8.0
    mm.

-   Determine the cavity length setting from the uterine sound and the
    cervical canal measurement.

-   Set the Disposable Device electrode array length to match the
    uterine cavity length.

-   Connect the Disposable Device to the RF Controller; CO~2~
    automatically purges air from the Disposable Device. The Disposable
    Device remains outside the body during this purge cycle, which lasts
    roughly 10 seconds.

-   Deploy and retract the electrode array outside the patient; perform
    equipment checks.

-   Insert the closed Disposable Device into the uterus; deploy and seat
    the electrode array.

-   Read the cornua-to-cornua measurement from the WIDTH dial indicator.

-   Key both the cavity length and cavity width measurements into the RF
    Controller.

-   Perform the Cavity Integrity Assessment test to confirm the uterus
    is not perforated.

-   Ablate the uterus.

-   Retract the electrode array into the protective sheath, and withdraw
    the Disposable Device from the patient.

IV. **ALTERNATIVE PRACTICES OR PROCEDURES**

> The following alternative practices and procedures are currently
> available to treat excessive uterine bleeding due to benign causes:

-   **Drug Therapy**

    Drug therapy, using estrogen-progestogen combinations (such as those
    found in oral contraceptives) or progestogens (progesterone) by
    themselves, is frequently employed for the treatment of menorrhagia.
    Other classes of drugs used include androgens such as danocrine,
    gonadotropin-releasing hormone (GnRH) agonists, and non-steroidal
    anti-inflammatory drugs (NSAIDs). Drug therapy is typically the
    first order treatment to alleviate excessive menstrual bleeding.
    Drug therapies usually require long term treatment. They are
    successful for some patients, but for others they are ineffective
    and may introduce unpleasant side effects. This treatment does,
    however, allow the woman to maintain her fertility.

-   **Dilatation and Curettage (D&C)**

    D&C is typically the first surgical step if drug therapy is
    unsuccessful in eliminating excessive bleeding. First the cervix is
    dilated, then the uterine contents are either scraped away by an
    instrument or removed through vacuum aspiration. This may reduce
    bleeding for a few cycles. If a polyp is present and removed, the
    bleeding may stop. In most cases, it does not provide the patient
    with long-term definitive results. It is useful, however, for those
    women who desire to maintain their fertility.

-   **Hysteroscopic Endometrial Ablation**

    Hysteroscopic endometrial ablation is a surgical procedure which
    utilizes a resectoscope or operating hysteroscope, a video monitor,
    a fluid distention medium such as glycine or sorbitol, and a
    surgical ablation device such as an electrode loop, rollerball or
    laser to destroy the inner lining of the uterus, the endometrium.
    The procedure is typically performed under general or epidural
    anesthesia. The cervix must be dilated to accommodate the
    hysteroscopic instrument, and the uterus must be properly distended.
    The most common risks associated with hysteroscopic endometrial
    ablation are hyponatremia from fluid overload, which is a
    life-threatening condition, and uterine perforation. This treatment
    is intended for women who no longer desire to maintain their
    fertility.

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-   **Thermal Endometrial Ablation**

    Thermal endometrial ablation is a surgical procedure in which the
    endometrium is treated with heat for a pre-determined period of
    time. Hot fluid may be injected directly into the uterine cavity or
    into a balloon-like device in the uterine cavity. The procedure may
    be performed under general or local anesthesia with intravenous
    sedation. Dilation of the cervix to 5-8 mm may be required. This
    treatment is intended for women who no longer desire to maintain
    their fertility.

-   **Cryosurgical Ablation**

    In cryosurgical ablation, a surgical device is used to destroy
    tissues of the uterus using extreme cold. A probe is inserted into
    the uterus under ultrasound guidance for pre-determined periods of
    time, and the tip of the probe is cooled to temperature of --100^o^
    to --120^o^C. The procedure may be performed under general or local
    anesthesia with intravenous sedation. Dilation of the cervix to 6-7
    mm may be required. This treatment is intended for women who no
    longer desire to maintain their fertility.

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-   **Hysterectomy**

    Historically, the most common and definitive surgical treatment for
    menorraghia is hysterectomy. It is, however, a major surgical
    procedure performed in the hospital under general anesthesia and is
    associated with the risks and complications of major surgery.
    Depending on the technique, it may require a lengthy recovery
    period.

#### MARKETING HISTORY 

> At the time of approval, the NovaSure System was available in Canada,
> Denmark, Finland, Germany, Holland, Italy, Norway, Sweden, and
> Switzerland, and was approved in Australia. The NovaSure System had
> not been withdrawn from any market due to any reason related to the
> safety or effectiveness of the device.

#### POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

> The NovaSure System was evaluated in a randomized, prospective,
> multi-center clinical study, in which the NovaSure System was
> compared to a control arm of wire loop resection plus rollerball
> endometrial ablation (hysteroscopic endometrial ablation). Tables 1A
> through 1D summarize the adverse events reported during the first year
> of follow-up for all 265 patients entered in this study.
>
> **[Table 1A -- Intra-Operative Adverse Events]{.smallcaps}**

+------------------------+----------------------+---------------------+
| **[Adverse             | **[Nova              | **[Loop             |
| Event]{.smallcaps}**   | Sure]{.smallcaps}** | Resec               |
|                        |                      | tion]{.smallcaps}** |
|                        | **n [(% of           |                     |
|                        | 175)]{.smallcaps}**  | **[Plus             |
|                        |                      | Roller              |
|                        |                      | ball]{.smallcaps}** |
|                        |                      |                     |
|                        |                      | **n (% of 90)**     |
+------------------------+----------------------+---------------------+
| Bradycardia            | > 1 (0.6%)           | 0                   |
+------------------------+----------------------+---------------------+
| Uterine perforation    | > 0                  | 3 (3.3%)            |
+------------------------+----------------------+---------------------+
| Cervical tear          | > 0                  | 2 (2.2%)            |
+------------------------+----------------------+---------------------+
| Cervical stenosis      | > 0                  | 1 (1.1%)            |
+------------------------+----------------------+---------------------+
| *                      | > **[1               | **[6                |
| *[Total]{.smallcaps}** | > (                  | (6                  |
|                        | 0.6%)]{.smallcaps}** | .7%)]{.smallcaps}** |
+------------------------+----------------------+---------------------+

**[Table 1B -- Post-Operative Adverse Events]{.smallcaps}**

**[[\<]{.underline} 24 Hours]{.smallcaps}**

+------------------------+----------------------+---------------------+
| > **[Adverse           | **[Nova              | **[Loop             |
| > Event]{.smallcaps}** | Sure]{.smallcaps}** | Resec               |
|                        |                      | tion]{.smallcaps}** |
|                        | **n [(% of           |                     |
|                        | 175)]{.smallcaps}**  | **[Plus             |
|                        |                      | Roller              |
|                        |                      | ball]{.smallcaps}** |
|                        |                      |                     |
|                        |                      | **n (% of 90)**     |
+------------------------+----------------------+---------------------+
| > Pelvic pain/cramping | 6 (3.4%)             | > 4 (4.4%)          |
+------------------------+----------------------+---------------------+
| > Nausea and/or        | 3 (1.7%)             | > 1 (1.1%)          |
| > vomiting             |                      |                     |
+------------------------+----------------------+---------------------+
| > *                    | **[9                 | > **[5              |
| *[Total]{.smallcaps}** | (5.                  | > (5.6%)            |
|                        | 1%)\*]{.smallcaps}** | \*\*]{.smallcaps}** |
+------------------------+----------------------+---------------------+

> \* 9 events reported in 6 (3.4%) patients
>
> \*\* 5 events reported in 4 (4.4%) patients

**[Table 1C -- Post-Operative Adverse Events]{.smallcaps}**

**[\> 24 Hours to 2 Weeks]{.smallcaps}**

+------------------------+----------------------+---------------------+
| **[Adverse             | **[Nova              | **[Loop             |
| Event]{.smallcaps}**   | Sure]{.smallcaps}** | Resec               |
|                        |                      | tion]{.smallcaps}** |
|                        | **n [(% of           |                     |
|                        | 175)]{.smallcaps}**  | **[Plus             |
|                        |                      | Roller              |
|                        |                      | ball]{.smallcaps}** |
|                        |                      |                     |
|                        |                      | **n (% of 90)**     |
+------------------------+----------------------+---------------------+
| Hematometra            | 1 (0.6%)             | > 0                 |
+------------------------+----------------------+---------------------+
| Urinary Tract          | 1 (0.6%)             | > 1 (1.1%)          |
| Infection              |                      |                     |
+------------------------+----------------------+---------------------+
| Vaginal Infection      | 1 (0.6%)             | > 0                 |
+------------------------+----------------------+---------------------+
| Endometritis           | 0                    | > 2 (2.2%)          |
+------------------------+----------------------+---------------------+
| Pelvic Inflammatory    | 0                    | > 1 (1.1%)          |
| Disease                |                      |                     |
+------------------------+----------------------+---------------------+
| Hemorrhage             | 0                    | > 1 (1.1%)          |
+------------------------+----------------------+---------------------+
| Pelvic pain/cramping   | 1 (0.6%)             | > 1 (1.1%)          |
+------------------------+----------------------+---------------------+
| Nausea and/or vomiting | 1 (0.6%)             | > 1 (1.1%)          |
+------------------------+----------------------+---------------------+
| *                      | **[5                 | > **[7              |
| *[Total]{.smallcaps}** | (2.                  | > (7.8%)            |
|                        | 9%)\*]{.smallcaps}** | \*\*]{.smallcaps}** |
+------------------------+----------------------+---------------------+

> \* 5 events reported in 4 (2.3%) patients
>
> \*\* 7 events reported in 6 (6.7%) patients

**[Table 1D -- Post-Operative Adverse Events]{.smallcaps}**

**[\> 2 Weeks -- 1 Year]{.smallcaps}**

+------------------------+----------------------+---------------------+
| > **[Adverse           | **[Nova              | **[Loop             |
| > Event]{.smallcaps}** | Sure]{.smallcaps}** | Resec               |
|                        |                      | tion]{.smallcaps}** |
|                        | **n [(% of           |                     |
|                        | 175)]{.smallcaps}**  | **[Plus             |
|                        |                      | Roller              |
|                        |                      | ball]{.smallcaps}** |
|                        |                      |                     |
|                        |                      | **n (% of 90)**     |
+------------------------+----------------------+---------------------+
| > Hysterectomy         | 3 (1.7%)             | 2 (2.2%)            |
+------------------------+----------------------+---------------------+
| > Hematometra          | 1 (0.6%)             | 2 (2.2%)            |
+------------------------+----------------------+---------------------+
| > Urinary Tract        | 2 (1.1%)             | 2 (2.2%)            |
| > Infection            |                      |                     |
+------------------------+----------------------+---------------------+
| > Vaginal Infection    | 5 (2.9%)             | 2 (2.2%)            |
+------------------------+----------------------+---------------------+
| > Endometritis         | 2 (1.1%)             | 1 (1.1%)            |
+------------------------+----------------------+---------------------+
| > Pelvic Inflammatory  | 2 (1.1%)             | 0                   |
| > Disease              |                      |                     |
+------------------------+----------------------+---------------------+
| > Hemorrhage           | 1 (0.6%)             | 0                   |
+------------------------+----------------------+---------------------+
| > Pelvic pain/cramping | 5 (2.9%)             | 6 (6.7%)            |
+------------------------+----------------------+---------------------+
| > *                    | **[21                | **[15               |
| *[Total]{.smallcaps}** | (12.                 | (16.7%)             |
|                        | 0%)\*]{.smallcaps}** | \*\*]{.smallcaps}** |
+------------------------+----------------------+---------------------+

> \* 21 events in 19 (10.9%) patients
>
> \*\* 15 events in 15 (16.7%) patients
>
> *[Potential Adverse Events]{.underline}*
>
> The following adverse effects might be expected (potential), but were
> not observed in the clinical study of the NovaSure™ System:

-   Thermal injury

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-   Electrical burn

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-   Perforation of the uterine wall

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-   Post-ablation tubal sterilization syndrome

-   Air or gas embolism

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-   Pregnancy and/or complications of pregnancy (Pregnancies following
    endometrial ablation can be dangerous for both mother and fetus.)

> *[Anticipated Post-Procedural Complications]{.underline}*
>
> For any endometrial ablation procedure, commonly reported
> post-operative events include the following:

-   Cramping/pelvic pain. Post-treatment cramping can range from mild to
    severe. This cramping will typically last a few hours and may
    continue beyond the first day following the procedure.

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-   Nausea and vomiting have been reported in patients immediately
    following the procedure and can be managed with medication.

-   Vaginal discharge.

-   Vaginal bleeding/spotting.

IX. **SUMMARY OF PRE-CLINICAL STUDIES**

### PERFORMANCE TESTING -- DESIGN VERIFICATION 

Tests were done to verify the design of the Disposable Device and the RF
Controller. For each test, between 5 and 45 samples were tested. In some
of the tests, failures were observed. These failures were addressed by
minor changes to the manufacturing process and inspection. Additional
samples were re-tested and passed.

#### Disposable Device

1.  [Verification of Dimensions:]{.underline} With the array in the
    closed position, the following dimensions were measured and found to
    be within specifications: working length, external sheath outer
    diameter, overall dimensions, RF cable length, and cervical collar
    length.

2.  [Deployment Tests:]{.underline}

-   The Disposable Device could be smoothly engaged and disengaged 100
    times when set at a length of 4 cm.

-   The maximum length of exposed electrode array was 6.5 cm when the
    device was deployed.

-   The maximum distance between the two distal tips of the array was at
    least 4.5 cm when the device was deployed to length 4.0 or 6.5 cm.

-   The distal tip of the array was 0.1-0.2 cm below the distal tip of
    the external sheath after the array was deployed to length 6.5 cm,
    locked, unlocked and retracted.

3.  [Deployment Mechanism Tests:]{.underline}

-   The deployment mechanism showed no damage after the following
    procedure: (a) set the Disposable Device length to its maximum
    setting and withdraw the sheath to expose the array, (b) restrict
    the array width to the closed position, while squeezing and locking
    the grips together to apply the maximum deployment load to the
    Device, and (c) gradually release the restriction so the array can
    deploy to full width.

-   The deployment mechanism did not fail when the device length was set
    to its minimum length, and the array was deployed to its maximum
    width.

###### [Deployment Force Tests]{.underline}: 

-   When the electrode array was fully deployed, the nominal deployment
    force developed by the grips and overload spring acting upon the
    mechanism did not exceed the maximum allowable load.

-   When the electrode array width was restricted to 3.5 cm, the maximum
    deployment force did not exceed the maximum allowable load.

-   With the electrode array fully restricted, the maximum deployment
    force did not exceed the maximum allowable load.

4.  [Device Manipulations]{.underline}:

-   When the Disposable Device was deployed in a plastic uterine model,
    it could withstand [+]{.underline} 80° rotation about the
    longitudinal axis.

-   When the device was deployed in a plastic uterine model, it could be
    angled 20° up and down and left and right.

5.  [WIDTH Dial Indicator Accuracy Test]{.underline}: The WIDTH dial
    provided cornu-to-cornu measurements from 2.0 to 4.5 cm with an
    accuracy of [+]{.underline} 0.2 cm.

6.  [Pressure Drop Test]{.underline}: The specified pressure drop was
    achieved in 10 seconds across the system, which included the suction
    tubing, canister, filter, desiccant and monitoring line.

7.  [Vacuum Tests]{.underline}

-   With the electrode array deployed in a uterine cavity test box, a
    specified vacuum level was reached using the RF Controller vacuum
    pump.

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-   The Disposable Device reached specified steady state vacuum levels
    within the specified time limit when deployed in a closed cavity
    containing blood or saline.

-   With the electrode array deployed in a uterine cavity test box, the
    vacuum level remained within specified range of the starting value
    when the device handle was deflected through its range of motion.

8.  [Pressure Tests]{.underline}

-   With the electrode array deployed in a uterine cavity test box, the
    minimum specified pressure was reached within 12 seconds when using
    worst case CO~2~ gas flow rate and pressure.

-   With the electrode array deployed in a uterine cavity test box, the
    minimum specified pressure was held for at least 6 seconds when
    using worst case CO~2~ gas flow rate and pressure.

#### RF Controller

1.  [Cavity Integrity Assessment Procedure]{.underline}

-   CO~2~ flow was within allowable limits.

-   Could not deliver RF energy without first completing the Cavity
    Integrity Assessment.

-   "Cavity Integrity Assessment" LED pulsed green, and an audible tone
    sounded during the assessment test. After 30 seconds without
    building pressure to the required threshold, the LED turned red,
    there was an audible alarm, and the CO~2~ flow stopped.

-   When pressure was gradually increased beyond the minimum threshold
    to pass the test, the LED turned to solid green, the tone turned
    off, and CO~2~ flow stopped.

-   Maximum pressure was within allowable limits.

-   Fresh CO~2~ cylinders provided at least 60 minutes of operation.

2.  [Length/Width Procedure]{.underline}

-   System could not be enabled without entering length and width.

-   Length and width keys functioned properly.

3.  [Vacuum Tests]{.underline}

-   The time required for the Controller to assess the vacuum level was
    within limits.

-   Vacuum levels and flow rates were within limits.

4.  [Power Curve Tests]{.underline}

-   With length 3.5 cm and width 2.5 cm entered, power ramped up to 50
    watts.

-   With length 5.0 cm and width 3.5 cm entered, power ramped up to 100
    watts.

5.  [Impedance Curve Tests]{.underline}

-   In the absence of external resistance, impedance was within limits.

-   With external fixed resistance of 25 ohms, resistance measured 25±3
    ohms.

-   With external fixed resistance of 50 ohms, resistance measured 50±5
    ohms.

6.  [Time Out / High Power Test]{.underline}

-   RF Controller turned off after 120 seconds, and the "procedure
    complete" LED illuminated.

-   "Electrode array position" LED flashed and the RF Controller stopped
    when 2 poles were electrically shorted together during a test
    procedure.

    Additional verification testing is described in Section X. Animal
    Studies.

### ELECTRICAL & MECHANICAL SAFETY; 

### ELECTROMAGNETIC COMPABILITY 

> Underwriters Laboratory tested the RF Controller in accordance with
> IEC 601-1:1988, IEC 60601-1-2, and CISPR 11. It passed all UL testing
> requirements.

### SOFTWARE VALIDATION 

> The NovaSure™ System does not contain software or require software for
> operation.

A.  **MATERIAL SAFETY (TOXICOLOGY)**

    The Disposable Device is the only device component that contacts the
    patient. The materials of the Disposable Device were evaluated for
    their safety and sterility.

#### Biocompatibility/Toxicity Testing

> Biocompatibility testing was conducted on the sterilized Disposable
> Device to provide assurance that the materials were safe for use in a
> medical device. The testing was conducted in accordance with ISO
> 10993-1. All testing was performed in accordance with Good Laboratory
> Practices (GLP).
>
> The Disposable Device passed the intracutaneous reactivity test and
> the sensitization (guinea pig maximization) test. The distal end of
> the device resulted in a positive cytotoxicity finding; this positive
> result was attributed to the silver plating on the nylon/lycra fabric
> of the electrode. Silver is known in the scientific literature to be a
> cytotoxic element, but it has been demonstrated to be clinically safe
> when used as an anti-infective in a variety of pharmaceuticals and as
> a coating on medical devices.

#### Sterility

The Disposable Device is terminally sterilized to a sterility assurance
level of 10^-6^ using ethylene oxide (EtO). The ethylene oxide
sterilization process was validated according to ANSI/AAMI/ISO
guidelines (AAMI/ANSI/ISO 11135). Packaging and pouch seal integrity
were tested to ensure sterility following shipping. Bioburden testing
schedules have been arranged to monitor the manufacturing procedures and
limits have been established to determine when revalidation is performed

B.  **SHELF LIFE**

    An accelerated aging study was used to establish a provisional shelf
    life of 6 months for the Disposable Device. Real-time aging studies
    will be conducted in a post-approval study for periods of 6 and 13
    months.

### ANIMAL STUDIES

> Bench testing with *ex vivo* porcine livers was completed to verify
> that a pre-specified depth of ablation would be created. Bench studies
> were also conducted to determine the temperatures along the external
> sheath. During the design of the system, bench studies were used to
> optimize power density, electrode array construction, depth of
> destruction and other functional parameters. Further bench studies
> were performed with excised porcine liver to verify the NovaSure™
> subsystem and system level performance.
>
> *Ex vivo* porcine liver tests were performed using liver with saline
> and/or blood, depending on the study being conducted. For each test, a
> simulated uterine cavity was cut from the lobes of a liver. In some
> studies, the simulated uterine cavity was infused with saline, which
> provided the electrical properties of blood. Porcine or human blood
> was infused when the properties of blood (fluid or coagulation) were
> required for the test.
>
> To verify that a pre-specified ablation profile would be created, 5
> tests were conducted at minimum length and width settings (4.0 cm and
> 2.5 cm, respectively), and another 5 tests were conducted at the
> maximum length and width settings (6.5 cm and 4.5 cm, respectively).
> In all cases, the following acceptance criteria were met: 5-9 mm depth
> of ablation in the upper body of the simulated uterine cavity, 4-8 mm
> depth in mid-body, 4-7 mm depth in lower body, 2-4 mm depth in cornua,
> and depth in mid-body at least 1 mm more than depth in lower body.
>
> To determine the maximum temperature of the external sheath, the
> devices were set to the maximum length (6.5 cm) and tested in the
> liver models. Three thermocouples were placed between 5 and 15 mm from
> the distal tip of the external sheath. The temperatures measured by
> the thermocouple were recorded. In the samples tested, the highest
> temperatures recorded were all within the specification of a 10°C
> increase (which would correspond to 47°C in the human body).

XI. **Extirpated HUMAN Uteri Study**

> *Ex vivo* studies were performed on 10 human uteri to evaluate the
> prototype Novacept ablation system. The uteri were heated to 37^o^C
> prior to treatment. The ablation parameters (impedance levels, power
> density and self-termination) performed as expected during these
> studies. In 6 of the 10 cases there was complete absence of any viable
> endometrial tissue within the uterine cavity. The average procedure
> time was 78 seconds and the histology evaluation showed a deeper
> ablation depth in the main uterine body with a shallower penetration
> in the areas of the cornua and internal cervical *os*. The serosal
> temperatures remained within a safe physiological range with the
> maximum temperature recorded as 37.5^o^C. There were no cases of
> uterine perforation.
>
> During the first few extirpated uteri cases it was noted that methods
> of measuring the cornu-to-cornu distance were not sufficiently
> accurate and the Intrauterine Measurement Device (WIDTH Dial) was
> developed and integrated into the Disposable Device.

XII. **SUMMARY OF CLINICAL STUDIES**

##### PRE-HYSTERECTOMY CLINICAL STUDY

> Novacept conducted an *in vivo* pre-hysterectomy study to demonstrate
> the safety and performance of the ablation system in 12 women already
> scheduled for an abdominal hysterectomy. Three thermocouples on the
> serosal surface and one thermocouple approximately 7 to 10 mm within
> the uterine wall (fundus) measured temperatures during the procedure.
> In four patients a D&C was performed prior to the ablation to observe
> the effect of pre-treating the uterus.
>
> There were no cases of uterine perforation and the highest serosal or
> fundal temperature recorded was 38.5^o^C. There was no evidence of
> perforation or thermal penetration through the uterine wall.
>
> Uteri samples were prepared for histological examination. In 9 of the
> 12 cases (75.0%) there was no evidence of viable endometrium following
> the procedure. There was no observed difference in the depths of
> ablation in the uteri that had been pre-treated with a D&C compared
> with those that received no pre-treatment.

##### FEASIBILITY CLINICAL STUDY

A feasibility study was conducted in which 21 patients with menorrhagia
were treated with the Novacept ablation device. All patients were
administered GnRH medications to pre-treat the endometrium four to six
weeks prior to ablation. Four (4) patients reported pelvic pain/cramping
(19.0%) within the first 2 weeks of treatment, and 1 patient reported
endometritis 9 days after ablation. All of these complications were
resolved. No additional complications or adverse events were reported 6
months post-treatment. At 6 months 3 patients (14.3%) reported slight or
normal menstrual bleeding, and 18 patients (85.7%) reported no bleeding.

##### MULTI-CENTER CLINICAL INVESTIGATION

#### Study Objectives

######## 

######## The primary objective was to evaluate the safety and effectiveness of the NovaSure^TM^ System as compared to the control in reducing menstrual blood loss at 12 months post-treatment. The control in this study was a hysteroscopic endometrial ablation procedure that combined loop endometrial resection with rollerball endometrial ablation. An additional objective was to identify complications or adverse events that may occur in using the NovaSure^TM^ System. The two systems were compared in a group of pre-menopausal women with menorrhagia (excessive uterine bleeding) from benign causes who no longer wished to retain fertility.

#### Study Hypothesis

> The study hypothesis proposed a statistical difference of less than
> 20% in patient success rates between the NovaSure^TM^ System as
> compared to the control procedure that combined loop endometrial
> resection with rollerball endometrial ablation.

#### Study Design

The study was designed as a prospective, randomized (2:1), controlled,
multi-center (9 sites) clinical investigation to evaluate 265
pre-menopausal women with menorrhagia.

The primary effectiveness measure was a validated menstrual diary
scoring system developed by Higham (Higham JM, O'Brien PMS, Shaw RW.
Assessment of menstrual blood loss using a pictorial chart; *Br J Obstet
Gynaecol* 1990; 97:734-9). Patient success was defined as a reduction in
menstrual flow at 1 year to a diary score of [\<]{.underline}75.
Secondary endpoints were comparison of procedure time, patient
satisfaction (as recorded by patient self-report via Quality of Life and
Menstrual Impact scales), and amenorrhea rates between the two groups.
Safety evaluation was based on the adverse events reported during the
study, including device-related complications.

#### Study Procedure Methods

> Patient bleeding, the primary study endpoint, was documented by the
> subject in menstrual diaries and scored by the clinical investigator
> or his/her designee to determine amount of blood loss before and after
> treatment. The blood loss was scored using the validated scoring
> system. All patients were instructed to maintain menstrual diaries for
> 12-months post-procedure. All complications and adverse events were
> documented and reported. Protocol deviations and failures of the
> device to meet minimum performance criteria were also recorded.
> Quality of Life Questionnaires were completed prior to treatment and
> at 3, 6 and 12 months post-treatment. As part of the study approval,
> questionnaires are to be completed at 24 and 36 months post-procedure
> as well.
>
> Following determination of patient eligibility and obtaining Informed
> Consent, each woman was stratified by age ([\<]{.underline} 40 or \>
> 40 years of age) and randomized with a 2:1 ratio into either the
> NovaSure™ treatment group or the control group of loop resection with
> rollerball endometrial ablation. None of the patients received
> hormonal pre-treatment to thin the endometrial lining, and patients
> were treated at any time during their menstrual cycle. Patients were
> subjected to the following inclusion/exclusion criteria:

######### ***Inclusion Criteria***

-   Refractory menorrhagia with no definable organic cause (abnormal
    uterine bleeding).

-   Ages 25 to 50 years of age

-   Uterine sound measurement of 6.0 -- 10.0 cm (external *os* to
    internal fundus).

-   A minimum PBLAC score of ≥ 150 for 3 months prior to study
    enrollment; [OR]{.underline} PBLAC score ≥ 150 for one month for
    women who 1) had at least 3 prior months (documented) failed medical
    therapy; 2) had a contraindication to medical therapy; or 3) refused
    medical therapy.

######### ***Exclusion Criteria***

-   Presence of bacteremia, sepsis, or other active systemic infection

-   Active or recurrent chronic pelvic inflammatory disease

-   Patient with documented coagulopathies

-   Symptomatic endometriosis

-   Prior uterine surgery (except low segment cesarean section) that
    interrupts the integrity of the uterine wall e.g., transmural
    myomectomy or classical cesarean section. Prior endometrial
    ablations.

-   Patient on medications that could thin the myometrial muscle, such
    as long-term steroid use

-   Patient on anticoagulants

-   Patient desire to have children or to preserve fertility

-   Patient currently on hormonal birth control therapy or unwilling to
    use a [non-hormonal]{.underline} birth control post-ablation.

-   Abnormal/Obstructed Cavity as confirmed by hysteroscopy, SIS or HSG.
    Specifically:

-   Septate or bicornuate uterus or other congenital malformation of the
    uterine cavity

-   Pedunculated, submucous leiomyomata or other leiomyomata which
    distort the cavity; polyps (larger than 2cm) which are likely to be
    the cause of the patient's menorrhagia.

-   Patient with an IUD

-   Patient with suspected or confirmed uterine malignancy or confirmed
    uterine malignancy within the last five years as confirmed by
    histology

-   Patient with endometrial hyperplasia as confirmed by histology

-   Patient with cervical dysplasia

-   Patient with elevated FSH levels consistent with ovarian failure
    (\>40 IU/L)

-   Patient who is pregnant

-   Patient with active sexually transmitted disease

#### Study Period and Population

> The first patient was treated in December 1998 and the last patient
> was treated in April 2000. One-year follow-up was completed in April
> 2001. All patients will be followed for an additional two years for
> adverse events and post-treatment bleeding patterns, as discussed in
> Section XV.

A total of 265 patients were enrolled in the study in a 2:1 ratio (175
NovaSure™, 90 control group of loop resection with rollerball
endometrial ablation).

#### Demographic and Gynecological History Data

Tables 2A and 2B below show the patient demographic and obstetrical and
gynecological history parameters. An evaluation of these data showed
there was no statistically significant difference between the two
treatment groups and, therefore, it was valid to compare treatment
outcome. Additionally, the data across sites was not statistically
significantly different, thus justifying the pooling of patient data
across sites.

> **[Table 2a -- Patient Demographics and Obstetrical
> History]{.smallcaps}**

+-----------------------+----------------+------------------+---------+
| **[Demog              | **[NovaSure™]  | **[Loop          | **[p    |
| raphic]{.smallcaps}** | {.smallcaps}** | Resection plus   | -Value] |
|                       |                | Rollerbal        | {.small |
|                       |                | l]{.smallcaps}** | caps}** |
+-----------------------+----------------+------------------+---------+
| **Age (years)**       | 39.7           | 39.9             | 0.69    |
|                       | ([+]{.         | ([+]             |         |
| > Mean                | underline}5.5) | {.underline}5.1) |         |
| > ([+]{.underline}    |                |                  |         |
| > SD)                 | 26.5-49.9      | 26.0-49.8        |         |
| >                     |                |                  |         |
| > Range               |                |                  |         |
+-----------------------+----------------+------------------+---------+
| **Race**              | 134            | 78               | 0.07    |
|                       |                |                  |         |
| > \# Caucasian        | 4              | 0                |         |
| >                     |                |                  |         |
| > \# Black            | 30             | 11               |         |
| >                     |                |                  |         |
| > \# Hispanic         | 1              | 1                |         |
| >                     |                |                  |         |
| > \# Asian            | 6              | 0                |         |
| >                     |                |                  |         |
| > \# Other            |                |                  |         |
+-----------------------+----------------+------------------+---------+
| **Body Mass Index     | 27.6           | 28.4             | 0.35    |
| (kg/m^2^)**           | ([+]{.         | ([+]             |         |
|                       | underline}6.3) | {.underline}7.5) |         |
| > Mean                |                |                  |         |
| > ([+]{.underline}    | 16.6-49.3      | 16.3-52.1        |         |
| > SD)                 |                |                  |         |
| >                     |                |                  |         |
| > Range               |                |                  |         |
+-----------------------+----------------+------------------+---------+
| **Number of           | 2.7            | 2.6              | 0.71    |
| Pregnancies**         | ([+]{.         | ([+]             |         |
|                       | underline}1.3) | {.underline}1.3) |         |
| > Mean                |                |                  |         |
| > ([+]{.underline}    | 0-7            | 0-8              |         |
| > SD)                 |                |                  |         |
| >                     |                |                  |         |
| > Range               |                |                  |         |
+-----------------------+----------------+------------------+---------+
| **Number of Full-Term | 2.  ([         | 2.               | 0.75    |
| Deliveries**          | +]{.underline} | ([+]{.underline} |         |
|                       |     1.1)       |     1.1)         |         |
| > Mean                |                |                  |         |
| > ([+]{.underline}    | 0-7            | 0-5              |         |
| > SD)                 |                |                  |         |
| >                     |                |                  |         |
| > Range               |                |                  |         |
+-----------------------+----------------+------------------+---------+

> **[Table 2b -- Patient Gynecological History]{.smallcaps}**

+--------------------------+------------+----------------+------------+
| **[Gynecological         | **[Nova    | **[Loop        | **[p-      |
| History]{.smallcaps}**   | Sure™]{.sm | Resection plus | Value]{.sm |
|                          | allcaps}** | Rollerball]    | allcaps}** |
|                          |            | {.smallcaps}** |            |
+--------------------------+------------+----------------+------------+
| **Baseline Diary Score** | 562        | 562            | 0.99       |
|                          | ([+]{.unde | ([+]{.         |            |
| > Mean ([+]{.underline}  | rline}381) | underline}487) |            |
| > SD)                    |            |                |            |
| >                        | 152-2358   | 153-3353       |            |
| > Range                  |            |                |            |
+--------------------------+------------+----------------+------------+
| **Number of Days Between | 24.6       | 25.3           | 0.32       |
| Periods**                | ([+]{.     | ([             |            |
|                          | underline} | +]{.underline} |            |
| > Mean ([+]{.underline}  | 6)         | 5.9)           |            |
| > SD)                    |            |                |            |
| >                        | 0-49       | 5-40           |            |
| > Range                  |            |                |            |
+--------------------------+------------+----------------+------------+
| **Menses Frequency**     | 123        | 63             | 0.96       |
|                          |            |                |            |
| > \# Patients Regular    | 52         | 27             |            |
| >                        |            |                |            |
| > \# Patients Irregular  |            |                |            |
+--------------------------+------------+----------------+------------+
| **Uterine Cavity Length  | 8.8        | 8.7            | 0.33       |
| cm**                     | ([+]{.     | ([             |            |
|                          | underline} | +]{.underline} |            |
| > Mean ([+]{.underline}  | 0.8)       | 1.0)           |            |
| > SD)                    |            |                |            |
| >                        | 7.0-12.0\* | 6.0-10.0       |            |
| > Range                  |            |                |            |
+--------------------------+------------+----------------+------------+
| **Uterine Position**     | 126 (73%)  | 62 (69%)       | 0.76       |
|                          |            |                |            |
| > \# Anteverted          | 13 (8%)    | 8 (9%)         |            |
| >                        |            |                |            |
| > \# Mid-position        | 33 (19%)   | 20 (22%)       |            |
| >                        |            |                |            |
| > \# Retroverted         |            |                |            |
+--------------------------+------------+----------------+------------+
| **PMS Present**          | 114 (65%)  | 60 (67%)       | 0.80       |
|                          |            |                |            |
| > Number (%) of Patients |            |                |            |
+--------------------------+------------+----------------+------------+
| **Primary Dysmenorrhea** | 100 (57%)  | 50 (56%)       | 0.80       |
|                          |            |                |            |
| > Number (%) YES         | 75 (43%)   | 40 (44%)       |            |
| >                        |            |                |            |
| > Number (%) NO          |            |                |            |
+--------------------------+------------+----------------+------------+

> \* Patient with 12.0 sound measurement not treated according to
> inclusion/exclusion criteria (aborted procedure).

#### Device Failures and Replacements

> A total of 198 Disposable Device units were used in the clinical
> trial. Of these, the investigators determined that 23 (11.6%) could
> not be used and returned them to Novacept. An additional unit was
> returned after successful use with the complaint that the locking
> mechanism was difficult to adjust. There was no case in which a device
> failure resulted in a patient not being treated.
>
> The reasons for which the Disposable Devices could not be used are
> grouped in the following 3 categories:

-   low vacuum alarms (n=13; 6.6%)

-   high resistance in the electrode array (n=9; 4.5%)

-   inaccuracy of WIDTH dial (n=1; 0.5%)

> These issues were addressed with minor modifications made during the
> incorporation of the Cavity Integrity Assessment system into the
> device.

#### Patient Accountability

A total of 265 subjects were enrolled in the study. Table 2C identifies
the numbers of patients at key points of the study.

**[Table 2c. Patient Accountability]{.smallcaps}**

+---------------------------------------+------------+-----------------+
| **[Number of Patients]{.smallcaps}**  | ###### [No | **[Loop         |
|                                       | vaSure]{. | Resection Plus  |
|                                       | smallcaps} | Rollerball      |
|                                       |            | ]{.smallcaps}** |
+---------------------------------------+------------+-----------------+
| **Entered into Study**                | **175**    | **90**          |
|                                       |            |                 |
| ######### Aborted                     | 4          | 0               |
| procedures---uterine size or shape\*  |            |                 |
|                                       | 0          | 2               |
| ######### Abort                       |            |                 |
| ed procedures---uterine perforation\* |            |                 |
+---------------------------------------+------------+-----------------+
| ## Treated                            | **171**    | **88**          |
|                                       |            |                 |
| > Failed -- required additional       | 4          | 2               |
| > treatment\*                         |            |                 |
| >                                     | 2          | 2               |
| > Hysterectomy performed\*            |            |                 |
| >                                     | 2          | 2               |
| > Lost to follow-up\*                 |            |                 |
| >                                     | 1          | 0               |
| > Hodgkin's disease diagnosed post    |            |                 |
| > treatment\*                         |            |                 |
+---------------------------------------+------------+-----------------+
| **6-Month Follow-up**                 | **162**    | **82**          |
|                                       |            |                 |
| > Hysterectomy performed\*            | 1          | 0               |
| >                                     |            |                 |
| > Pelvic pain -- administered         | 1          | 0               |
| > leuprolide\*                        |            |                 |
| >                                     | 4          | 0               |
| > Lost to follow-up\*                 |            |                 |
+---------------------------------------+------------+-----------------+
| **12-Month Follow-up**                | **156**    | **82**          |
+---------------------------------------+------------+-----------------+

> \* Discontinued patients

#### Efficacy at One Year: Diary Scores

> Patient success was based on a reduction in diary score from
> [\>]{.underline}150 pre-treatment to [\<]{.underline}75 at one year.
> Effectiveness rates were based on the Intent-to-Treat population.

**[Table 3 -- Effectiveness\*: Diary Scores at 1 Year]{.smallcaps}**

+---------------------------------------+------------+----------------+
|                                       | **[Nova    | **[Loop        |
|                                       | Sure]{.sm | Resection]     |
|                                       | allcaps}** | {.smallcaps}** |
|                                       |            |                |
|                                       | **n [(% of | **[Plus        |
|                                       | 175)]{.sm  | Rollerball]    |
|                                       | allcaps}** | {.smallcaps}** |
|                                       |            |                |
|                                       |            | **n (% of      |
|                                       |            | 90)**          |
+---------------------------------------+------------+----------------+
| Number of successful patients (diary  | 136        | 67             |
| score[\<]{.underline}75)              |            |                |
+---------------------------------------+------------+----------------+
| **Study success rate (% patients with | **77.7%**  | **74.4%**      |
| score [\<]{.underline}75)**           |            |                |
+---------------------------------------+------------+----------------+
| Number of patients with amenorrhea    | 63         | 29             |
| (score=0)                             |            |                |
+---------------------------------------+------------+----------------+
| **Amenorrhea rate (% patients with    | **36.0%**  | **32.2%**      |
| score=0)**                            |            |                |
+---------------------------------------+------------+----------------+

> \* Nineteen (19) NovaSure™ patients and 8 control patients were lost
> to follow-up. All of these patients were considered treatment failures
> in calculating the Intent-to-Treat effectiveness rates.

#### Efficacy at One Year: Quality-of-Life

######### 

Quality of Life questionnaires were completed by patients before
treatment and then at 3, 6, and 12 months post-treatment. Table 4 shows
the results for patients responding to the questionnaire at 12 months.

**Table 4 -- Effectiveness: Quality of Life at 1 Year**

+-----------------------------------+-------------+--------------------+
|                                   | **[No       | **[Loop            |
|                                   | vaSure]{.s | Resect             |
|                                   | mallcaps}** | ion]{.smallcaps}** |
|                                   |             |                    |
|                                   | **n (%)**   | **[Plus            |
|                                   |             | Rollerb            |
|                                   |             | all]{.smallcaps}** |
|                                   |             |                    |
|                                   |             | **n (%)**          |
+-----------------------------------+-------------+--------------------+
| Number of Patients Responding     | 154         | 82                 |
+-----------------------------------+-------------+--------------------+
| PMS pre-treatment                 | 102 (66%)   | 54 (66%)           |
|                                   |             |                    |
| Post-treatment                    | 56 (36%)    | 29 (35%)           |
+-----------------------------------+-------------+--------------------+
| Dysmenorrhea pre-treatment        | 86 (56%)    | 46 (56%)           |
|                                   |             |                    |
| Post-treatment                    | 32 (21%)    | 28 (34%)           |
+-----------------------------------+-------------+--------------------+
| Satisfied or very satisfied with  | 141 (92%)   | 76 (93%)           |
| procedure                         |             |                    |
+-----------------------------------+-------------+--------------------+
| Definitely or probably would      | 146 (95%)   | 78 (95%)           |
| recommend procedure to friend     |             |                    |
+-----------------------------------+-------------+--------------------+

######### **Procedure Time**

> Procedure time, a secondary end-point, was determined for each patient
> by recording the time of device insertion and the time of device
> removal. The mean procedure time for the NovaSure™ patients (4.2
> [+]{.underline} 3.5 minutes) was significantly less than the procedure
> time for the Rollerball Group (24.2 [+]{.underline} 11.4 minutes). The
> mean time for which RF energy was applied was 84.0 [+]{.underline}
> 25.0 seconds, based on monitoring in 48 patients.

######### **Anesthesia**

> The clinical protocol did not specify the type of anesthesia to be
> used for either treatment group. This decision was left to the
> discretion of the physician and anesthesiologist. In the NovaSure™
> group, 73% (127/174) received local and/or IV sedation as compared to
> 18% (16/90) of the control group. General anesthesia or epidural was
> administered to 27% (47/174) of the NovaSure™ patients and 82% (74/90)
> of the control patients.

#### Hysterectomy

> Five women had a hysterectomy within the first year after the ablation
> procedure. Table 5 lists the reasons for hysterectomies.
>
> **Table 5 -- Hysterectomy**

+-----------------------------------+--------------+-------------------+
| **[Reason for                     | **[          | **[Loop           |
| Hysterectomy]{.smallcaps}**       | NovaSure]{. | Resecti           |
|                                   | smallcaps}** | on]{.smallcaps}** |
|                                   |              |                   |
|                                   | **n          | **[Plus           |
|                                   | [(%]         | Rollerba          |
|                                   | {.smallcaps} | ll]{.smallcaps}** |
|                                   | of           |                   |
|                                   | [175)]{.     | **n (% of 90)**   |
|                                   | smallcaps}** |                   |
+-----------------------------------+--------------+-------------------+
| Adenocarcinoma diagnosed at time  | > 1          | 1                 |
| of procedure                      |              |                   |
+-----------------------------------+--------------+-------------------+
| Pain and bleeding                 | > 2          | 0                 |
+-----------------------------------+--------------+-------------------+
| Infection                         | > 0          | 1                 |
+-----------------------------------+--------------+-------------------+
| **Total**                         | > **3        | **2 (2.2%)**      |
|                                   | > (1.7%)**   |                   |
+-----------------------------------+--------------+-------------------+

> The 3 NovaSure™ patient hysterectomies were in women under the age of
> 40 and the 2 Loop Resection plus Rollerball hysterectomies occurred in
> women 40 years of age and older.

XIII. **CONCLUSIONS DRAWN FROM THE STUDIES**

The pre-clinical and clinical data provide reasonable assurance that the
NovaSure™ System is safe and effective when used in accordance with the
directions for use.

XIV. **PANEL RECOMMENDATIONS**

     Pursuant to the provision of Section 515(c)(2) of the Federal,
     Food, Drug and Cosmetic Act (FD&C Act) as amended by the Safe
     Medical Devices Act of 1990, this PMA application was not referred
     to the Obstetrics and Gynecology Devices Panel, an FDA Advisory
     Panel Committee, for review and recommendation. FDA believes that
     previous panel reviews of related endometrial ablation devices
     provided sufficient guidance for the review of this PMA.

#### FDA DECISION 

> CDRH determined that the results of the pre-clinical and clinical
> studies provide reasonable assurance of the safety and effectiveness
> of the NovaSure™ Impedance Controlled Endometrial Ablation System when
> used as indicated in the labeling.

In order to gather long-term safety and effectiveness data, the
applicant must conduct a postapproval study that will continue to follow
all subjects from the multi-center study for a period of three years
from the time of treatment.

> Additionally, CDRH found the applicant's manufacturing facilities to
> be in compliance with the device Quality System Regulation (21 CFR
> 820). CDRH issued an approval order on September 28, 2001.

XV. **APPROVAL SPECIFICATIONS**

> Directions for use: See the Device Labeling.
>
> Hazards to Health from Use of the Device: See Indication,
> Contraindications, Warnings, Precautions and Adverse Events in the
> labeling.
>
> Post-approval Requirements and Restrictions: See approval order.