# Summary Of Safety And Effectiveness Data

## General Information

### Device Generic Name

Totally Implanted Spinal Cord Stimulator for Pain Relief

### Device Trade Name

Genesis Neurostimulation (IPG) System

### Applicant's Name and Address

Advanced Neuromodulation Systems (ANS), Inc.

6501 Windcrest Drive, Suite 100

Plano, Texas 75024

### PMA Number

P010032

### Date of Notice of Approval to the Applicant

> November 21, 2001

## Indications for Use

ANS Genesis Neurostimulation (IPG) System is indicated as an aid in the
management of chronic intractable pain of the trunk and/or limbs,
including unilateral or bilateral pain associated with the following:
failed back surgery syndrome, intractable low back and leg pain.

## Device Description

### Genesis Neurostimulation System

> The Genesis Neurostimulation (IPG) System consists of the following
> components: Model 3608 Implanted Pulse Generator (IPG), Model 3850
> Patient Programmer, Model 1232 Programming Wand, and Model 1210
> Patient Magnet.
>
> The Genesis Neurostimulation (IPG) System is intended to be used with
> the following ANS' legally marketed components:

-   percutaneous lead models 3143, 3146, 3153, 3156, 3183 and 3186

-   surgical lead models 3222, 3240, 3244 and 3280

-   extension models 3382, 3383, 3341, 3342 and 3343

-   ANS TS8 test stimulation system.

The IPG is connected to a lead with four or eight electrodes, either
directly or with a lead extension. The electrodes contact the patient
along the spinal cord. The IPG is implanted in a subcutaneous pocket,
and receives radio frequency (RF) programming signals from an external
Patient Programmer. The IPG decodes the RF signals and delivers
stimulation pulses to the patient via a selected combination of output
electrodes. The IPG is powered by a hermetically sealed battery enclosed
within a hermetically sealed titanium case and uses an integrated
circuit to generate electrical stimulation.

#### Implantable Pulse Generator (IPG)

The Model 3608 IPG is designed to produce a monophasic capacitively
coupled rectangular output pulse. The IPG is current regulated and is
capable of producing output stimulus in the following ranges: amplitude
0 to 25.5 mA, pulse width 52 to 507 µs, and frequency 2 to 200 Hz. The
IPG is powered by an internal 3.7 volt lithium thionyl chloride battery.
The IPG has the following specifications:

> Dimensions: 50mm (1.96") X 54mm (2.11") X 14mm (0.54")
>
> Weight: 53 grams (1.8 oz.)
>
> Volume: 29 cm ^3^ (1.75 in ^3^)

#### Patient Programmer and Wand

The Model 3850 IPG Patient Programmer is a battery-operated device that
is connected to the Model 1232 wand, which allows for two-way
communication with the IPG for the purpose of programming the
stimulation output parameters and receiving feedback from the IPG. The
programmer communicates with the IPG by sending RF signals from the
programmer wand to the implanted IPG. The stimulation RF output signals
are programmed using a combination of amplitude, frequency pulse width
and electrode polarity.. The programmer allows clinicians to set the
output stimulation parameters that best provide pain relief for
individual patients. It also allows the user to select individual
pre-set stimulation parameters within clinician prescribed ranges. The
Patient Programmer has the following specifications:

> Dimensions: 6.8 cm (2.7") X 10.77 cm (4.2 ") X 2.6 cm (1.0")
>
> Weight: 128 grams (4.6 oz)
>
> Power: 3 AAA Alkaline Batteries

#### Magnet

The Genesis Model 1210 magnet allows the user to turn the IPG on and off
at any time.

## Contraindications, Warnings, and Precautions

### Contraindications

The system is contraindicated in patients with demand type cardiac
pacemakers.

Patients that are unable to operate the system or fail to receive
effective pain relief during trial stimulation should not be implanted
with a SCS.

### Warnings

Spinal cord stimulation (SCS) should not be used on patients that are
poor surgical risks, those with multiple illnesses or active general
infections.

**Diathermy Therapy** -- Do not use short-wave diathermy, microwave
diathermy or therapeutic ultrasound diathermy (all now referred to as
diathermy) on patients implanted with a neurostimulation system. Energy
from diathermy can be transferred through the implanted system and cause
tissue damage at the location of the implanted electrodes, resulting in
severe injury or death.

Diathermy is further prohibited because it may also damage the
neurostimulation system components resulting in loss of therapy,
requiring additional surgery for system implantation and replacement.
Injury or damage can occur during diathermy treatment whether the
neurostimulation system is turned "On" or "Off". All patients are
advised to inform their health care professional that they should not be
exposed to diathermy treatment.

**Cardioverter Defibrillators** -- Neurostimulation systems may
adversely affect the programming of implanted cardioverter
defibrillators.

**Magnetic Resonance Imaging** (MRI) -- Patients with implanted
neurostimulation systems should not be subjected to MRI. The
electromagnetic field generated by a MRI may dislodge implanted
components, damage the device electronics and induce voltage through the
lead that could jolt or shock the patient.

**Explosive or Flammable Gases** -- Do not use the patient programmer in
an environment where explosive or flammable gas fumes or vapors are
present. The operation of the patient programmer could cause them to
ignite, causing severe burns, injury or death.

**Theft Detectors and Metal Screening Devices** -- Certain types of
antitheft devices such as those used at entrances/exits of department
stores, libraries, and other public establishments, and/or airport
security screening devices may interfere with the operation of the
device. It is possible that patients who are implanted with non-adjacent
multiple leads and/or patients that are sensitive to low stimulation
thresholds may experience a momentary increase in their perceived
stimulation, which has been described by some patients as uncomfortable
or jolting. It is recommended that patients use caution when approaching
such a device and request assistance to bypass the device. If they must
proceed through the device the patient should turn off the stimulator
and proceed with caution, ensuring to move through the detector quickly.

**Lead Movement** -- Patients should be instructed to avoid bending,
twisting, stretching, or lifting objects over five pounds, for six to
eight weeks post-implantation. Extension of the upper torso or neck may
cause lead movement and alter the stimulation field (especially with
leads in the cervical area), resulting in overstimulation or ineffective
stimulation.

**Operation of Machinery and Equipment** -- Patients should not operate
potentially dangerous machinery, power tools, vehicles, climb ladders,
etc., when the IPG is operating. Postural changes or abrupt movement
could alter the perception of stimulation intensity and cause patients
to fall or lose control of equipment or vehicles, injure others, or
bring injury upon themselves.

**Postural Changes** -- Changes in posture or abrupt movements may
result in a decrease or increase in the perceived level of stimulation.
Perception of higher levels of stimulation has been described by some
patients as uncomfortable, painful, or jolting. Patients should be
advised to turn down the amplitude or turn off the IPG before making
extreme posture changes or abrupt movements such as stretching, lifting
of arms over head, or exercising. If unpleasant sensations occur, the
IPG should be turned off immediately.

**Pediatric Use** -- Safety and effectiveness of spinal cord stimulation
has not been established for pediatric use.

**Pregnancy** -- Safety for use during pregnancy has not been
established.

**Device Components** -- The use of non-ANS components with this system
may result in damage to the system and increased risk to the patient.

**Case Damage** -- If the IPG case is pierced or ruptured, severe burns
could result from exposure to the battery chemicals.

### Precautions

[GENERAL PRECAUTIONS]{.underline}

**Physician Training** -- Implanting physicians should be experienced in
the diagnosis and treatment of chronic pain syndromes and have undergone
sufficient surgical and device implantation training.

**Patient Selection** -- It is extremely important to appropriately
select patients for spinal cord stimulation. Thorough psychiatric
screening should be performed. Patients should not be dependent on drugs
and should be able to operate the stimulator.

**Infection** -- It is important to follow proper infection control
procedures. Infections related to system implantation might require that
the device be explanted.

**Implantation of Two Systems** -- If two systems are implanted, ensure
that at least 8 in. (20 cm) separates the implanted IPGs to minimize the
possibility of interference during programming.

**Implantation of Multiple Leads** -- If multiple leads are implanted,
the leads should be routed to the IPG in adjacent tunnels. Nonadjacent
leads have the possibility of creating a conduit for stray
electromagnetic energy that could cause unwanted stimulation in the
patient.

**High Stimulation Outputs** -- Stimulation at high outputs may cause
unpleasant sensations or motor disturbances, or render the patient
incapable of controlling the patient programmer. If unpleasant
sensations occur, the device should be turned off immediately.

**Stimulation Parameters** -- Patients should be cautioned that
stimulation parameters must be determined under the supervision of a
physician and that they should not adjust stimulation parameters within
prescribed programs except under direct orders from their physician.

**Cellular Phones** -- The effect of cellular phones on spinal cord
stimulators is unknown and patients should avoid placing cellular phones
directly over the device.

**FCC Statement** -- **FCC ID: PX2001** -- This device (Patient
Programmer) complies with part 15 of the FCC Rules. Operation is subject
to the following conditions: (1) This device may cause interference, and
(2) this device must accept any interference received, including
interference that may cause undesirable operation.

[STERILIZATION AND STORAGE]{.underline}

**Single-Use Device** -- The implanted components of the ANS Genesis IPG
System are intended for a single-use only. Do not resterilize or
reimplant an explanted system for any reason because of risk of
infection and device malfunction.

**Storage Temperature** -- Store system components between ‑10°C (14°F)
and 55°C (131°F) because temperatures outside this range can damage
components.

**Storage Humidity** -- Store components between 10% and 90% humidity.

[HANDLING, IMPLEMENTATION, AND EXPLANTATION]{.underline}

**Expiration Date** -- Do not implant a device if the use-before date
has expired.

**Care and Handling of Components** -- Use extreme care when handling
system components prior to implantation. Excessive heat, excessive
traction, excessive bending, excessive twisting or the use of sharp
instruments may damage and cause failure of the component.

**Package and Component Damage** -- Do not implant a device if the
sterile package or components show signs of damage, the sterile seal is
ruptured, or if contamination is suspected for any reason. Return to ANS
for evaluation.

**Exposure to Body Fluids or Saline** -- Exposure of the internal metal
(i.e., contacts on the lead, the IPG or extension) to body fluids or
saline can cause corrosion and affect stimulation. If this occurs, clean
with sterile, de-ionized or distilled water and dry completely prior to
lead connection and subsequent implantation.

**System Testing** -- The operation of the system should always be
tested after implantation and before the patient leaves the surgery
suite to assure correct operation.

**Component Disposal** -- Return all explanted components to ANS for
safe disposal.

[HOSPITAL AND MEDICAL ENVIRONMENTS]{.underline}

**High Output Ultrasonics and Lithotripsy** -- The use of high output
devices such as an electrohydraulic lithotriptor may cause damage to the
electronic circuitry of an implanted IPG. If lithotripsy must be used,
do not focus the energy near the IPG.

**Ultrasonic Scanning Equipment** -- The use of ultrasonic scanning
equipment may cause mechanical damage to an implanted neurostimulation
system if used directly over the implanted device.

**External Defibrillators** -- The safety of discharge of an external
defibrillator on patients with implanted neurostimulation systems has
not been established.

**Therapeutic Radiation** -- Therapeutic radiation may damage the
electronic circuitry of an implanted neurostimulation system, although
no testing has been done and no definite information on radiation
effects is available. Sources of therapeutic radiation include
therapeutic x‑rays, cobalt machines, and linear accelerators. If
radiation therapy is required the area over the implanted IPG should be
shielded with lead.

**Electrosurgery Devices** -- Electrosurgery devices should not be used
in close proximity to an implanted neurostimulation IPG or lead(s).
Contact between an active electrode and an implanted IPG, lead or
extension can cause direct stimulation of the spinal cord and cause
severe injury to the patient. If use of electrocautery is necessary turn
the IPG off.

[HOME AND OCCUPATIONAL ENVIRONMENTS]{.underline}

**Electromagnetic Interference (EMI)** -- Certain commercial electrical
equipment (arc welders, induction furnaces, resistance welders),
communication equipment (microwave transmitters, linear power
amplifiers, high power amateur transmitters), and high voltage power
lines may generate sufficient EMI to interfere with the neurostimulation
system operation if approached too closely.

## Alternative Practices and Procedures

Alternative practices to the use of totally implanted IPG for spinal
cord stimulation to treat chronic pain of trunk and limbs include:

1.  Non-surgical treatment options for chronic pain patients include:

> a\. Oral medication
>
> b\. Rehabilitative therapy
>
> c\. Transcutaneous electrical nerve stimulation (TENS);
>
> d\. Behavior modification
>
> e\. Neurolysis (i.e.,Therapeutic nerve block, Cryoanalgesia
>
> RF Lesioning)
>
> 2\. Surgical treatment options for chronic pain patients include:
>
> a\. Sympathectomy- severing the nerve pathway
>
> b\. Partially Implanted spinal cord stimulation (SCS) Systems -- RF
> implantable spinal cord stimulators (the power source in this system
> is external).
>
> c\. Commercially available fully implanted SCS Systems.

## Marketing History

The Genesis Neurostimulation (IPG) System for the treatment of chronic
pain of trunk and limbs is currently approved for commercial
distribution in Europe. The CE mark was received in 2000. No Genesis
Neurostimulation (IPG) System has been withdrawn from marketing for
reasons related to safety and effectiveness of the device.

## Potential Adverse Effects of the Device on Health

### Adverse Events

The implantation of a neurostimulation system involves risk. In addition
to those risks commonly associated with surgery, the following risks are
also associated with implantation, and/or use of a neurostimulation
system:

-   Undesirable changes in stimulation may occur over time. These
    changes in stimulation are possibly related to cellular changes in
    tissue around the electrodes, changes in the electrode position,
    loose electrical connections and/or lead failure.

-   Placement of a lead in the epidural space is a surgical procedure
    that may expose the patient to risks of epidural hemorrhage,
    hematoma, infection, spinal cord compression, and/or paralysis.

-   Battery failure and/or battery leakage may occur.

-   Radicular chest wall stimulation.

-   CSF leakage.

-   Persistent pain at the electrode or IPG site.

-   Seroma at the implant site.

-   Lead migration, which can result in changes in stimulation and
    subsequent reduction in pain relief.

-   Allergic or rejection response to implant materials.

-   Implant migration and/or local skin erosion.

-   Paralysis, weakness, clumsiness, numbness or pain below the level of
    implantation.

-   Device Failure

## Summary of Nonclinical Studies

Qualification testing was conducted to provide adequate data to support
the intended use of the device system. Testing was largely based on
commonly recognized test methods and standards, such as International
Standards Organization (ISO), European Standards (EN), American Society
and Materials (ASTM) and military standards.

### IPG

#### Environmental Testing

The following testing was performed to simulate the environmental
conditions the device may encounter during normal usage: operating
pressure, operating temperature, ultrasonic energy, drop testing,
vibration resistance and exposure to defibrillation. IPG function was
verified after exposing the device to the following environmental
conditions: a pressure of 70 and 150 kPa for five minutes respectively
per EN 45502‑1 Section 25.1; operating temperatures of 29°C, 37°C, and
45°C while the IPG is submerged in a 0.9% saline solution; exposure of
the IPG for one hour to ultrasonic energy per EN 45502‑1 Section 22.1;
dropping onto a stainless steel tray resting on a 2 inch thick hard
maple wooden bench top from a distance of 8 inch in each of six axes;
random vibration per EN 45502‑1 Section 23 and exposure to a
defibrillation source per EN 45502‑1 Section 20.2. Testing demonstrated
that the IPG operated according to specification after exposure to the
above environmental conditions. Additionally the device was subjected to
storage temperature extremes (‑20°C to +55°C) and was tested for proper
operation. Testing demonstrated that the device operates as expected and
within specification over the operating temperature range of the device
and after exposure to storage temperature extremes.

Environmental testing for the Genesis IPG was performed to demonstrate
compliance to Environmental Storage, Shipping Sterilization, and Shelf
Life Requirements. Testing was performed in accordance with the
standard: ASTM D 4169 -- 98 -- "Standard Practice for Performance
Testing of Shipping Containers and Systems". The test results met the
standards requirements.

#### Surface Temperature Testing

Testing was performed per EN 45502‑1 to ensure the surface temperature
of the IPG would not be greater than 2°C above normal surrounding body
temperature (37°C) when implanted and functioning under normal
operation, or in any single-fault condition. The test results met the
requirement.

#### Hermeticity

The IPG was tested for hermeticity as defined in MILSTD 883E. Results
demonstrated that the welds for the battery, titanium can and
feedthroughs did not leak when exposed to helium leak testing in
accordance with MILSTD 883E.

#### Electrical Characterization

Characterization of the electrical design of the IPG was performed. The
testing included variations in temperature, supply voltage, load
resistance, output current, pulse width, and frequency. Characterization
of the device's output along the Impedance /Current curve under loads
from 300 to 2000 ohms was performed. Results verified that the IPG
system performed in accordance with design specifications.

#### Header Adhesion Testing

#### Bonding of the IPG header to its titanium can and the bonding of the dip coating material to the titanium case were characterized. The test was designed to ensure the material bonds do not delaminate due to shear stresses between the materials caused by a force applied to one of the two materials. Header bonding was performed using titanium strip samples overlapped with header material strip samples. In addition to the strip samples, three sample IPG devices were assembled and tested to ensure there was no shorting path between the feed through leads and the IPG case. Results of the header bonding test exceeded the anticipated 44.2 PSI shear stress. Results of the dip-coating test demonstrate the shear strength of the dip coating and the titanium is higher than the strength of the header bonding by a factor of 2 to 1. Results of the overall testing for the header demonstrate the method for bonding a header to the IPG can and dip coating the titanium case meet acceptance criteria and are adequate for its intended use.  {#bonding-of-the-ipg-header-to-its-titanium-can-and-the-bonding-of-the-dip-coating-material-to-the-titanium-case-were-characterized.-the-test-was-designed-to-ensure-the-material-bonds-do-not-delaminate-due-to-shear-stresses-between-the-materials-caused-by-a-force-applied-to-one-of-the-two-materials.-header-bonding-was-performed-using-titanium-strip-samples-overlapped-with-header-material-strip-samples.-in-addition-to-the-strip-samples-three-sample-ipg-devices-were-assembled-and-tested-to-ensure-there-was-no-shorting-path-between-the-feed-through-leads-and-the-ipg-case.-results-of-the-header-bonding-test-exceeded-the-anticipated-44.2-psi-shear-stress.-results-of-the-dip-coating-test-demonstrate-the-shear-strength-of-the-dip-coating-and-the-titanium-is-higher-than-the-strength-of-the-header-bonding-by-a-factor-of-2-to-1.-results-of-the-overall-testing-for-the-header-demonstrate-the-method-for-bonding-a-header-to-the-ipg-can-and-dip-coating-the-titanium-case-meet-acceptance-criteria-and-are-adequate-for-its-intended-use. .unnumbered}

### Battery Testing

Design verification testing was divided into segments of non-destructive
and destructive testing and was designed to simulate the conditions of
usage, handling, shipping and storage.

Each battery sample was subjected to visual, dimensional, radiographic,
electrical, and hermeticity evaluation before and after environmental
testing to assure the acceptability of the battery. Other
non-destructive tests included high pressure (90 psi), low pressure
(equivalent to atmospheric pressure at 30,000 ft), mechanical shock and
vibration, temperature cycling (‑40 °C to 70 °C twice in 48 hours), high
temperature storage at 60 degrees C, low temperature storage at ‑40 °C,
and short circuit testing for four hours at 37 °C.

Destructive testing included slow dent/puncture, crush and battery
capacity testing. Battery capacity testing included discharging the
batteries at a constant rate to determine any changes due to battery
chemistry and to determine the battery capacity. The batteries showed no
evidence of loss of hermeticity or sudden electrical failure that was
attributable to the design.

Non-destructive and destructive testing for the battery demonstrates
that the battery is suitable and can reliably perform within the IPG.

Electrical characterization for the Elective Replacement Indicator (ERI)
and the End of Service (EOS) was performed. Characterization testing
included ERI voltage, minimum communication voltage and minimum
operating voltage measured under minimum, nominal and maximum operating
conditions as well as for 0, 100, and 200 Ohm source impedances. The
device met acceptance criteria.

Testing demonstrating that the battery source impedance at which a false
ERI could occur was performed. The worst case battery source impedance
at which a false low battery indication occurred was 160 ohms, which is
greater than the typical source impedance expected during normal
operation of a lithium thionyl chloride battery of 10--50 ohms.

### Programmer and Wand Testing 

Software for the Genesis Neurostimulation (IPG) System was developed and
meets the recommendations provided in the Food and Drug Administration
(FDA) guidance document, entitled, "Guidance for the Content of
Premarket Submissions for Software Contained in Medical Devices."
Mechanical verification of the Patient Programmer/Wand design included
size and weight measurements, operational environment testing for
temperature/humidity, pressure, heat generation, vibration, and drop
testing. The devices were tested in accordance with EN 45502‑1 and IEC
60601‑1. Test results demonstrated that the device meets functional
requirements when operated in a worse case fault condition.

In addition to mechanical and software verification tests, testing of
the ability of the packaging to protect the device during shipping and
handling was performed. The packages were tested in accordance with ASTM
shipping test D4169‑98. Results of the testing show that all acceptance
criteria were met. Testing of the programmer's capability to reliably
communicate with the IPG device from specified distances and
orientations was performed. Testing demonstrated the device operates as
expected and exceeds all communication distance/alignment requirements.
Temperature testing for the AAA battery pack and the wand was performed.
The testing demonstrated that the temperature of these devices does not
rise to unsafe levels.

### Electromagnetic Compatibility (EMC) Testing

The Genesis Neurostimulation (IPG) System has been evaluated for effects
on its functioning and /or programming by external sources of
interference in accordance with all applicable sections of IEC 60601‑1‑2
"Medical Electrical Equipment - Part 1: General Requirements for Safety:
Electromagnetic Compatibility- Requirements and Tests". Testing included
radiated emissions, RF immunity, magnetic immunity, and electrostatic
discharge.

The test results met the requirements of the applicable sections of the
standard.

### Hazard Analysis

A risk analysis was performed using the failure modes and effects
analysis (FMEA) on the complete device and the critical components. A
risk assessment was performed in accordance with EN1441. The hazard
analysis was incorporated into the design and development processes to
ensure that critical failure mode or potentially hazard situations have
been identified and adequately eliminated or mitigated. The software
risk assessment was conducted as part of the system risk assessment.

All potential faults were identified in the FMEA/Failure Analysis and in
the Fault/Failure Tree. The full analysis consisting of the Risk
Assessment, the Software Risk Assessment, the Unacceptable Risks
Analysis, and the FMEA all conclude that through the appropriate design,
as well as testing, the hazards or unacceptable risks have been
mitigated to an acceptable level.

### Reliability Testing

The Genesis Neurostimulation (IPG) System was tested and analyzed for
reliability. The testing included accelerated life testing that
estimated the expected real time longevity performance and failure rate
of the device.

Results of the reliability prediction analysis document that the failure
rate for the nominal mode 0.076% per month and the failure rate for
worst case mode was 0.103% per month. The failure rates are lower than
the design goal of 0.15% failures per month.

### Sterilization and Shelf Life

The devices are EtO sterilized with a sterility assurance level (SAL) of
10^‑6^. Validation for the sterilization cycle was performed in
accordance with ISO 11135. Validation of the Shelf Life Study for
sterile package supports a 2 year shelf life for the Genesis
Neurostimulation (IPG) System.

### Biocompatibility

All the tissue contacting raw materials for the implantable components
of the Genesis Neurostimulation (IPG) System have been tested with the
exception of titanium that houses the IPG. Titanium has been
historically used in implanted medical devices. The titanium material
used in the manufacture of the IPG is in compliance with ASTM F67, "
Standard Specification for Unalloyed Titanium for Surgical Implant
Applications". Biocompatibility testing was performed in compliance with
ISO-10993, "Biological Evaluation of Medical Devices, Part 1: Evaluation
and Testing".

The following testing has been conducted on the tissue contacting raw
materials:

-   Cytotoxicity (ISO elution method), Hemolysis (Extraction method)

-   Systemic Toxicity (USP method, rat model), Acute Intracutaneous
    Reactivity (rabbit model)

-   Muscle Implantation (7 day and 90 day)

-   Ames Salmonella/ Mammalian Microsome Mutagenicity Assay

-   Rabbit Pyrogen Study

-   Delayed Contact Sensitization Study (Saline Extract)

The results of these tests showed that the raw materials used in the
Genesis Neurostimulation (IPG) System are biocompatible and therefore,
suitable for the intended use.

ANS performed biocompatibility tests on the finished device in
accordance with ISO 10993 to determine the potential for *in vitro*
cytotoxicity. The results from testing on the sterilized finished IPG
product found the device to be non-toxic.

### Packaging Qualification

Qualification testing for the packaged product consisted of
environmental stress tests including extreme temperature/humidity
conditions, extreme vibration, stacking and drop testing. Visual
inspection and functional testing of sterile package seals, package
materials and contents were performed. Functionality of each device was
verified at the completion of the tests. The packaging met the test
requirements

## Summary of Clinical Studies

The clinical data summarized below consisted of available peer reviewed
published literature for similar implantable spinal cord stimulation
(SCS) systems. The Genesis Neurostimulation (IPG) System device is
similar to the SCS systems reported in the published literature in
intended use, target patient population, technology, device design and
output characteristics. Three key studies which met specific inclusion
and exclusion criteria were included in the effectiveness analysis. A
total of 16 studies which met safety specific inclusion and exclusion
criteria were included in the safety analysis. The effectiveness data
represents a total of 116 patients that were implanted with SCS systems,
while the safety data represents a total of 1253 patients that received
SCS systems.

### Objectives of Studies

Based on nonclinical studies that demonstrated the Genesis
Neurostimulation (IPG) System has comparable output characteristics to
the commercially available SCS systems reported in the literature, the
primary objective was to provide clinical evidence of the effectiveness
of the Genesis Neurostimulation (IPG) System, using literature articles,
for the relief of failed back surgery syndrome, intractable low back,
and limb pain.

Effectiveness was demonstrated by 1) a reduction of pain as demonstrated
by a significant reduction in the Visual Analog Scale (VAS) score, 2) a
50% reduction in pain using either a 3 or 4 point scale in at least 30%
of patients included in that study, 3) a significant difference in pain
reduction as measured by a VAS score when compared to a control group,
and/or 4) a significant reduction in pain medication.

Safety of the Genesis Neurostimulation (IPG) System was established
using literature articles, for the relief of failed back surgery
syndrome, intractable low back, and limb pain. This was accomplished by
examining the incidence of complications of the SCS systems used in the
published literature.

### Effectiveness

Three (3) clinical literature studies were used to assess the
effectiveness of the Genesis Neurostimulation (IPG) System (Ohnmeiss et
al. 1996, Villavicencio et al. 2000 and Hassenbusch SJ et al. 1995). The
studies included a total of 116 patients that were implanted with an SCS
system. A total of approximately 3166 device months of experience was
considered in the retrospective clinical evaluation. All three studies
examined the effectiveness of SCS on patients with chronic pain of the
trunk and/or limbs including unilateral or bilateral pain associated
with the following: failed back surgery syndrome or intractable low back
and leg pain. In all studies, an identified totally implantable spinal
cord stimulator was used in association with a quadripolar percutaneous
epidural lead or a quadripolar lead. These studies provide the same
diagnostic or therapeutic intervention for the same disease/conditions
and patient population as the Genesis Neurostimulation (IPG) System.

-   The prospective study by Ohnmeiss et al. 1996 examined the long-term
    effectiveness of SCS in patients with intractable leg pain. A total
    of 40 patients were implanted with SCS systems and evaluated at 6
    weeks, 12 months, and 24 months follow-up. Outcome measures included
    the VAS, pain drawings, medication use, SIP, isometric lower
    extremity testing, and patient questionnaires. An intent to treat
    analysis was also performed. After patients had SCS for 24 months,
    leg pain, pain when walking, standing pain, pain's effect on overall
    lifestyle, and the total analog scale scores were significantly
    improved from baseline. In this study, SCS was effective in
    improving intractable leg pain.

> In addition, 3 patients from this study had their stimulators
> repositioned due to pain at the original location. Also, 3 patients
> had reoperations to adjust lead position; 1 patient required 2
> reoperations, 1 had the device removed due to infection and later to
> have a new device implanted. A diabetic patient had skin problems
> which required device removal; a new device was later implanted. Two
> patients had the device removed due to unsatisfactory pain relief.

-   The prospective study by Villavicencio et al. 2000 included 41
    patients with pain of various etiologies. The majority of the
    patients, 24 (59%), had Failed Back Surgery Syndrome (FBSS), 7 (17%)
    had Complex Regional Pain Syndrome) CRPS I and II, 4 (10%) had
    neuropathic pain syndrome, and 6 (15%) were diagnosed as stroke or
    other. Patients underwent an initial trial period for SCS with
    temporary leads. If the trial resulted in greater than 50% reduction
    in the patient's pain, as measured by the VAS, the patient was
    implanted with a SCS system. In the study, 27/41 (66%) patients had
    permanent implants. All patients were examined after 6 weeks. Pain
    measurements were assessed at 3‑6 month intervals for the first year
    and annually thereafter. The median long-term follow-up was 34
    months. A total of 24/27 (89%) patients reported greater than 50%
    reduction in pain. Since the majority of the patients were treated
    for FBSS, this article supports the use of SCS for the treatment of
    FBSS.

> In this study, 1 patient required a revision because of electrode
> fracture. One patient required removal of the system due to local
> infection. One patient required replacement of the IPG due to
> mechanical failure. Overall, 16 of 27 (59%) patients required a total
> of 36 repositioning procedures.

-   A retrospective analysis by Hassenbusch SJ et al. 1995 included
    patients with chronic lower body pain, predominately neuropathic
    pain and pain either midline lower back and/or unilateral or
    bilateral leg pain treated over a 5 year period. The study was a
    comparison of SCS to spinal infusion of opioids. For patients with
    radicular pain involving one leg with or without unilateral buttock
    pain, a trial of SCS was recommended first. For patients with
    midline back pain and /or bilateral leg pain, a trial of long-term
    spinal infusion was recommended first. If the patients failed
    screening with either of these modalities, the other was then
    tested. If the treatment reduced the pain by 50%, the systems were
    internalized. A retrospective analysis of patients with unilateral
    leg and/or buttock pain treated initially with SCS and bilateral leg
    or mainly low back pain treated initially with spinal infusions of
    opioids was then done.

> In this study, 42 patients were screened; 26 (62%) patients received
> spinal stimulation; 16 (38%) received opioids via a spinal infusion
> pump. A total of 5 patients did not receive adequate pain relief with
> SCS; 3 (7%) of these patients underwent trial spinal infusions and had
> effective pain relief. There were of 4 (10%) patients that underwent a
> trial of spinal infusion of opioid but did not receive adequate pain
> relief; these patients were not tested with SCS. Pain severity was
> rated using a verbal digital pain scale: "On a scale of 0 to 10 where
> 0 is no pain and 10 is the worst pain you could ever imagine, what is
> your pain now?" (Hassenbusch SJ et al. 1995) 16/26 patients (62%) had
> greater than 50% pain relief with SCS. A total of 2/16 (13%) patients
> had greater than 50% pain relief with opioids. Mean follow-up was 2.1
> [+]{.underline} 0.3 years. This analysis supports the use of SCS for
> intractable low back and leg pain.
>
> In the Hassenbusch study, 7 (17%) patients suffered complications
> after implantation of the device; 5 (12%) patients required
> repositioning of catheter type electrodes and 2 patients required
> revision of the stimulator generator.

The output of the Genesis Neurostimulation (IPG) System when used with
percutaneous lead models 3143, 3146, 3153, 3156, 3183, and 3186,
surgical lead models 3222, 3240, 3244 and 3280 and extension models
3382, 3383, 3341, 3342 and 3343 is within the range of the output
parameters of the SCSs and associated leads reported in the
retrospective literature evaluation. The Genesis Neurostimulation (IPG)
System and the associated leads may produce a greater output when
compared with the devices reported in the literature. Instructions for
use will ensure that energy output is adeqaute to achieve optimum
effectiveness.

### Safety

Sixteen (16) studies, as listed in the references, were identified based
on the detailed inclusion/exclusion criteria to demonstrate the safety
of the Genesis (IPG) Neurostimulation System. The studies included a
total of 1253 patients. The following complications were seen in the
retrospective clinical evaluation: lead migration, infection, hematoma,
paralysis, cerebral spinal fluid (CSF) leak, over/under stimulation,
pain over the implant, allergic reaction, skin erosion, lead breakage,
hardware malfunction, loose connection, other biologic reaction specific
to an IPG, and battery failure.

Table 2 -Summary of Risks Identified In the Literature Review

  -----------------------------------------------------------------------
  **Risks**                     **\# of       **\# of      **% of
                                Patients**    Events**     Patients**
  ----------------------------- ------------- ------------ --------------
  Lead Migration                1059          144          13.6

  Infection                     1253          37           3.0

  Epidural Hemorrhage           1253          0            0

  Seroma                        1253          0            0

  Hematoma                      1253          5            0.4

  Paralysis                     1253          1            0.1

  CSF Leak                      1253          6            0.5

  Over/Under Stim               1059          27           2.6

  Intermittent Stim             1059          0            0

  Pain over Implant             1059          12           1.1

  Allergic Reaction             1059          2            0.2

  Skin Erosion                  1059          1            0.1

  Lead Breakage                 1059          182          17.2

  Hardware Malfunction          1059          32           3.0

  Loose Connection              1059          10           1.0

  Battery Failure               911           17           1.9

  Other                         1059          24           2.3
  -----------------------------------------------------------------------

The above table depicts the number of patients, the number of events
observed, and the percentage of occurrences of each event compared to
the total number of patients. It should be noted that several studies
include both IPG and RF Systems. FDA believes that the clinical
experience reported in the literature on RF systems is relevant to
determining the safety of totally implantable IPG systems.

## Conclusion Drawn from the Studies

The nonclinical laboratory testing performed on the IPG, battery,
programmer and programming wand demonstrate that the individual
components, as well as the combined system, are reliable and that the
probable benefits to health from the use of the device outweigh any
probable injury or illness from such use. Further, the nonclinical
laboratory studies conducted by the applicant, when considered with the
clinical experience reported in the public literature on similar SCS
systems, provides reasonable assurance that the Genesis Neurostimulation
(IPG) System is safe and effective when used to treat chronic
intractable pain of the trunk and/or limbs, including unilateral or
bilateral pain associated with failed back surgery syndrome or
intractable low back and leg pain.

## CDRH Decision 

> Prior to the ANS, Inc. submission of PMA number P010032, the Genesis
> Neurostimulation (IPG) System was the subject of a reclassification
> petition submitted by ANS, Inc. on June 16, 1999. Although the request
> to reclassify this device type from class III (premarket approval) to
> class II (special controls) was subsequently denied by the Agency,
> much of the data and information submitted in this PMA had been
> carefully evaluated by FDA during the review of the reclassification
> petition. In fact, on September 17, 1999, FDA consulted with the
> Neurological Devices Panel (the Panel) during which time the Panel
> reviewed many of the nonclinical studies, as well as the clinical
> literature, that ANS, Inc. included in PMA number P010032 as evidence
> of their device's safety and effectiveness. While FDA disagreed with
> the Panel's recommendation that the device be reclassified from class
> III to class II, FDA acknowledged that considerable valid scientific
> evidence existed in the public domain that the applicant could use to
> streamline the PMA process and support approval of a PMA.

Upon completion of the evaluation of the information submitted in this
PMA, FDA has concluded that the Genesis Neurostimulation (IPG) System is
sufficiently similar to the SCS systems reported in literature in regard
to intended use, targeted patient population, technology, device design,
and electrical output characteristics, that the literature can provide a
basis upon which the performance of the Genesis Neurostimulation (IPG)
System can be judged. FDA has also concluded that the available
published clinical studies constitute valid scientific evidence for the
purposes of determining safety and effectiveness. FDA has determined
that this evidence, when combined with the nonclinical data included in
the PMA, provides reasonable assurance of the safety and effectiveness
of the Genesis Neurostimulation (IPG) System for treating chronic
intractable pain of the trunk and/or limbs, including unilateral or
bilateral pain associated with failed back surgery syndrome or
intractable low back and leg pain. Furthermore, FDA inspections of the
manufacturing facilities demonstrated that all sites involved in the
manufacture of the Genesis Neurostimulation (IPG) System are in
compliance with the Quality System Regulation.

> In arriving at this conclusion, FDA has taken into consideration, as
> required under section 205 of the Food and Drug Administration
> Modernization Act of 1997, the least burdensome means to market, while
> maintaining the statutory threshold for approval of a PMA, i.e.,
> reasonable assurance of safety and effectiveness.

## Approval Specifications (To be completed by FDA)

> Directions for use: See the labeling.

Hazards to Health from Use of the Device: See Indications,
Contraindications, Warnings, precautions and Adverse Events in the
labeling.

Postapproval Requirements and Restrictions: See approval order.

> **[References]{.underline}**
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