Vercise Deep Brain Stimulation (DBS) System

P150031S028 · Boston Scientific Corp · NHL · Dec 29, 2020 · Neurology

Device Facts

• Record ID: P150031S028
• Device Name: Vercise Deep Brain Stimulation (DBS) System
• Applicant: Boston Scientific Corp
• Product Code: NHL · Neurology
• Decision Date: Dec 29, 2020
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic, Real-World Evidence

Real-World Evidence

Submission	Device	Sponsor	RWD Sources	RWE Use Summary	Key Tags
P150031S028 · Dec 29, 2020	Vercise Deep Brain Stimulation (DBS) System	Boston Scientific Corp	Medical records of patients from the Medtronic Activa Parkinson's Control Therapy clinical study (P960009/S7)	The FDA utilized clinical data from a previously approved device (Medtronic Activa) to establish reasonable assurance of safety and effectiveness for the Vercise PC/Gevia systems via the FDAMA 'six-year rule'. This included retrospective verification of patient diary and UPDRS motor examination scores against medical records.	FDAMA Section 216; Medical record verification; Retrospective clinical data; Technological comparison

Clinical Evidence

Study Design	Population	Comparator	Key Endpoints
Medtronic Activa Parkinson's Control Therapy Study (P960009/S7); Prospective open label study (with retrospective medical record verification); Follow-up/Duration: 12 months	Subjects with advanced, levodopa-responsive Parkinson's disease not adequately controlled with medication; Sample Size: 160; Number of Sites: 18	Not applicable for this study	UPDRS motor exam scores, patient diaries (ON/OFF time)

Indications for Use

Bilateral stimulation of the globus pallidus internus (GPi) as an adjunctive therapy in reducing some of the symptoms of advanced levodopa responsive PD that are not adequately controlled with medication. Bilateral stimulation of the subthalamic nucleus (STN) as an adjunctive therapy in reducing some of the symptoms of moderate to advanced levodopa responsive PD that are not adequately controlled with medication.

Device Story

Implantable neurostimulation system for Parkinson's disease; consists of IPG (rechargeable or non-rechargeable), leads, and extensions. System delivers electrical pulses to STN or GPi targets. Clinician uses Vercise Neural Navigator software to program stimulation parameters (amplitude, pulse width, frequency, contact configuration). Patient uses handheld remote to turn stimulation on/off and adjust amplitude within clinician-set limits. Rechargeable IPG battery replenished via external RF charger. Current steering technology allows precise stimulation positioning. System provides adjunctive therapy to reduce motor symptoms (dyskinesia, fluctuations) in levodopa-responsive patients. Benefits include improved 'on' time and motor function. Used in clinical settings for programming; patient manages daily therapy at home.

Clinical Evidence

No new clinical data required for this supplement. Safety and effectiveness supported by the INTREPID study (prospective, double-blind, randomized, controlled, n=292) for STN stimulation and historical clinical data from the Medtronic Activa Parkinson's Control Therapy (P960009/S007) for GPi stimulation. Medtronic study showed 6.7-hour improvement in 'on' time and significant UPDRS motor score improvements. Safety profile includes common DBS risks (infection, intracranial hemorrhage, stimulation-related adverse events).

Technological Characteristics

Implantable pulse generator (IPG) with 16-contact capacity; leads (non-directional/directional) with platinum/iridium contacts; polyurethane insulation. Current-regulated, charge-balanced asymmetric biphasic waveform. Connectivity via RF telemetry (remote) and inductive charging (rechargeable model). Sterilization via ethylene oxide (EO). Software-controlled programming via clinician interface.

Indications for Use

Indicated for adults with moderate to advanced levodopa-responsive Parkinson's disease (PD) not adequately controlled with medication, requiring bilateral stimulation of the subthalamic nucleus (STN) or globus pallidus internus (GPi). Contraindicated for patients requiring diathermy, ECT, or TMS; patients with MRI requirements (unless lead-only); patients unable to operate the remote/charger; poor surgical candidates; or patients with unsuccessful test stimulation.

Regulatory Classification

Identification

Bilateral stimulation of the internal globus pallidus (GPi) or the subthalamic nucleus (STN) using Medtronic Activa Parkinson's Control Therapy is indicated for adjunctive therapy in reducing some of the symptoms of advanced, levodopa-responsive Parkinsons disease that are not adequately controlled with medication.

Predicate Devices

• Medtronic Activa Parkinson's Control Therapy (P960009/S007)

Reference Devices

• Medtronic Activa (P960009/S007)
• Medtronic Itrel
• Medtronic Soletra
• Medtronic Kinetra
• St. Jude Medical Infinity Neurostimulation System
• Precision Novi SCS IPG (P150031/S217, S287)
• Precision Montage SCS IPG (P030017/S235)
• Linear 8 Contact Lead (P030017)

Submission Summary (Full Text)

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# SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

## I. GENERAL INFORMATION

Device Generic Name: Stimulator, Electrical, Implanted, for Parkinsonian Tremor

Device Trade Name: Vercise™ PC Deep Brain Stimulation (DBS) System
Vercise Gevia™ Deep Brain Stimulation (DBS) System

Device Procode: NHL

Applicant's Name and Address: Boston Scientific Corporation
25155 Rye Canyon Loop
Valencia, CA 91355

Date(s) of Panel Recommendation: None

Premarket Approval Application (PMA) Number: P150031/S028

Date of FDA Notice of Approval: TBD

The Vercise PC Deep Brain Stimulation (DBS) System and the Vercise Gevia™ Deep Brain Stimulation (DBS) System were approved on January 10, 2019 under P150031/S1 and are indicated for use in bilateral stimulation of the subthalamic nucleus (STN) as an adjunctive therapy in reducing some of the symptoms of moderate to advanced levodopa-responsive Parkinson's disease (PD) that are not adequately controlled with medication.

The current supplement (S028) was submitted to expand the indication for the Vercise PC and Vercise Gevia DBS Systems. The original PMA (P150031) for the Vercise DBS System was approved on December 8, 2017 and the SSED to support the indication is available on the CDRH website (https://www.accessdata.fda.gov/cdrh_docs/pdf15/P150031B.pdf) and is incorporated by reference here. No new clinical data were required to support the approval of the Vercise PC Deep Brain Stimulation (DBS) System and the Vercise Gevia™ Deep Brain Stimulation (DBS) System approved under P150031/S1.

## II. INDICATIONS FOR USE

The Vercise PC and Vercise Gevia Deep Brain Stimulation (DBS) Systems These devices are indicated for the are indicated for use in the following:

- Bilateral stimulation of the globus pallidus internus (GPi) as an adjunctive therapy in reducing some of the symptoms of advanced levodopa responsive PD that are not adequately controlled with medication.

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- Bilateral stimulation of the subthalamic nucleus (STN) as an adjunctive therapy in reducing some of the symptoms of moderate to advanced levodopa responsive PD that are not adequately controlled with medication.

### III. CONTRAINDICATIONS

The Boston Scientific Vercise PC and Vercise Gevia DBS Systems or any of its components, are contraindicated for:

- **Diathermy.** Shortwave, microwave, and/or therapeutic ultrasound diathermy. The energy generated by diathermy can be transferred to the Vercise DBS System, causing tissue damage at the contact site resulting in severe patient injury or death.
- **Electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS)** The safety of these therapies in patients implanted with the DBS System has not been established. It is possible that the energy generated by these therapies can be transferred to the DBS System, causing tissue damage that may result in severe patient injury or death.
- **Magnetic Resonance Imaging (MRI).** Patients implanted with the full Vercise PC DBS System (leads, extensions and stimulator) should not be subjected to an MRI. MRI exposure may result in the following:

- Dislodgement of implanted components
- Heating of the contacts, or other system components, causing permanent tissue lesioning
- Damage to the Stimulator's electronics
- Current induction through the DBS Leads and Vercise PC DBS System causing unpredictable levels of stimulation
- Distortion of the diagnostic image
- Personal injury or death

Note: Vercise DBS lead-only system (before Stimulator is implanted) is MR Conditional. An MRI examination can be conducted safely when all the instructions in the supplemental manual MRI Guidelines for Boston Scientific DBS Systems are followed. MR Conditional labeling for the DBS standard leads (Models DB-2201-30-AC, DB-2201-30-DC, DB-2201-45-BC, DB-2201-45-DC) and DBS Directional Leads (Models DB-2202-30 and DB-2202-45) was approved in PMA Supplements P150031/S5 and P150031/S11. For the latest version of the manual go to www.bostonscientific.com/manuals.

- **Patient Incapability.** Patients who are unable to properly operate the Remote Control and Charging System should not be implanted with the Vercise PC and Vercise Gevia DBS Systems.
- **Poor Surgical Candidates.** The Vercise PC and Vercise Gevia DBS Systems are not recommended for patients who are poor surgical candidates.

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- **Unsuccessful Test Stimulation.** The Vercise PC and Vercise Gevia DBS Systems should not be used in patients who experience unsuccessful test stimulation.

#### IV. **WARNINGS AND PRECAUTIONS**

The warnings and precautions are provided in the Vercise PC and Vercise Gevia DBS System labeling.

#### V. **DEVICE DESCRIPTION**

The Vercise PC and Vercise Gevia DBS Systems include non-rechargeable and rechargeable Stimulators respectively, with DBS Leads for stimulation of selected targets (i.e., the subthalamic nucleus and globus pallidus) in the brain. DBS Extensions are used to connect the DBS Leads to the Stimulator implanted near the clavicle.

The Vercise PC and Vercise Gevia DBS Systems utilize current steering across eight contacts per DBS Lead, which is intended to provide precise positioning of stimulation. The Stimulator is controlled by a handheld Remote Control, and can be programmed by a Clinician Programmer using the Vercise Neural Navigator Software. Periodically, the rechargeable Stimulator battery must be replenished with a radiofrequency (RF) charging device provided in the Charging Kit.


**Figure 1. Vercise PC and Vercise Gevia DBS Systems**

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**Figure 2. Typical Implant Location**

# **A. Implanted Components**

Implantable Pulse Generator (IPG, Model # DB-1140-S, DB-1200-S): 16-contact, multi-channel, implantable pulse generator. The Vercise PC IPG (Model# DB- 1140-S has a non-rechargeable power source. The Vercise Gevia IPG (Model# DB-1200-S has a rechargeable power source. The IPGs generate programmable electrical pulses that are conducted to targets in the brain via leads. The IPGs can support up to two 8-contact Leads. A charge density warning appears on the Clinician Programmer when stimulation settings are set to deliver $\geq 30\mu\text{C/cm}^2/\text{phase}$. All contacts have independent current control. Table 1 below provides a summary of the programmable stimulation parameters.

**Table 1: Vercise PC and Vercise Gevia DBS System Stimulation Parameters**

| Parameters | Range |
| --- | --- |
| Waveform | Charge balanced asymmetric biphasic |
| Pulse Shape | Rectangular |
| Current or Voltage Regulated | Current |
| Amplitude Range | 0 - 12.7 mA per contact (up to 20.0 mA per Area) |
| Pulse Width Range | 20µs - 450µs |
| Frequency Range^{1} | 2 - 255Hz |
| Contact Connections (i.e., Channels) | 16 |
| Independent Areas of Stimulation (4 Programs with 4 Areas per Program) | 16 |
| Current Path Options | Unipolar, Bipolar, or Multipolar |

$^{1}$The rate is limited to 255 Hz for a given area. The global rate limit for each Lead is also 255 Hz.

- Leads (Model # DB-2201-xx, DB-2202-xx, xx = 30 or 45, i.e., length of 30cm or 45cm): The DBS leads deliver electrical pulses generated by the IPG to targets in the brain. The DBS Lead model DB-2201 has 8 cylindrical ring contacts at the distal end. The DBS Lead model DB-2202 has 2 ring contacts and two rows of directional contacts that are segmented circumferentially to allow both axial and rotational stimulation selectivity. Each segmented contact covers 90 degrees of the Lead circumference. The lead specifications are provided in Table 2 below.

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**Table 2: DBS Lead Specifications**

| Feature | Description | |
| --- | --- | --- |
| | DB-2201 Lead | DB-2202 Lead |
| Number of Contacts | 8 | 8 |
| Contact Length | 1.5 mm | 1.5 mm |
| Ring Contact Surface Area | 6.0 mm^{2} | 6.0 mm^{2} |
| Segmented Contact Surface Area | N/A | 1.5 mm^{2} |
| Contact Spacing (axial) | 0.5 mm | 0.5 mm |
| Contact Span | 15.5 mm | 7.5 mm |
| Distal Contact to Tip Length | <1.3 mm | N/A |
| Diameter | 1.3 mm | |
| Overall Length | 30 cm, 45 cm | |
| Outer Jacket Tubing (Insulation) | Polyurethane | |
| Contact Material | Platinum/Iridium | |
| Impedance (Ω) | ≤ 90 (measured from each connector to corresponding electrode contact) | |

- Lead Extension (Model # NM-3138-55): The DBS Extension consists of a connector at the distal end and 8 cylindrical contacts at the proximal end. The DBS Lead may be inserted and secured into the connector, which also contains 8 contacts that align with the contacts on the DBS Lead to form electrical connections. The proximal end is inserted into the IPG.
- Implantable Accessories:
- Burr Hole Cover: The Burr Hole Cover is used to permanently secure the DBS lead and to cover the burr hole created in the skull during the surgical implantation of the DBS lead.
- DBS Lead Boot: The DBS Lead Boot protects the proximal end of the DBS Lead prior to the Stimulator implant surgery.
- Suture Sleeve: The Suture Sleeve may be used to anchor the DBS Lead or DBS Extension to the fascia.
- M8 Adaptor: The M8 Adaptor is provided to connect Medtronic Lead models (3387 and 3389) to the Boston Scientific IPG. The M8 Adaptor is compatible with the following Medtronic lead extensions models: 3708640, 3708660, 3708695, 3708540, 3708560, 3708595.

# **B. External Components**

- ETS (Model # DB-5132-S): The External Trial Stimulator (ETS) is a component that may be used for intraoperative testing of stimulation. It provides the identical stimulation capabilities as the IPG.
- Remote Control (Model # DB-5250-S): The Remote Control is a hand-held, battery operated unit that uses telemetry to communicate with the IPG and ETS. It allows the patient to control the stimulation therapy prescribed by the clinician (e.g., turn DBS system on and off).
- Charger (Model # NM-5312): The Charger uses radiofrequency (RF) energy to inductively charge the implanted IPG battery when the Charger is placed externally over the IPG implant site.

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- Base Station (Model # NM-5305): The Base Station connects to a wall-mounted power supply and is utilized to recharge the Charger.
- Clinician Programmer (Model # DB-7161, NM-7161, DB-7161R, NM-7161R): The Clinician Programmer is used by the clinician to program the IPG and ETS, and thus prescribe stimulation therapy for the patient.
- Non-implantable or External Accessories:
- Tunneling Tool: used to create a path for the DBS Lead and DBS Extension in the subcutaneous tissue.
- Lead stop: may be attached to the Lead to prevent the Lead from being advanced beyond a certain depth into the neural tissue during its initial placement.
- Lead Stylet: inserted in the Lead to keep the Lead stiff during placement.
- Charging Collar: used to place the Charger externally over the IPG during charging.
- Charger Spacer: a piece of material placed behind the Charger in the pocket of the Charging Collar.
- Adhesive Kit: for attaching the Charger to the patient's body during charging. Alternative to Charging Collar.
- O.R. Cable and Extension: connects the Lead Extension to the ETS during intraoperative testing.

# VI. ALTERNATIVE PRACTICES AND PROCEDURES

At present there is no cure for PD; treatment is focused on management of symptoms. A patient should fully discuss the below alternatives with his/her physician to select the method that best meets expectations and lifestyle.

# Non-Surgical Treatment Options

Medical therapy for motor symptoms has been primarily focused on restoring dopamine levels through the administration of levodopa, dopamine agonists, or monoamine oxidase B inhibitors. Current standards for patient care recommend levodopa as first line of therapy for the symptomatic control during the early, uncomplicated stages of PD. Unfortunately, chronic treatment with levodopa, and other anti-parkinsonian agents frequently leads to significant side effects, especially dyskinesias and motor fluctuations.

# Surgical Treatment Options

For subjects who have reduced response or complications due to medical therapy, pallidotomy (destruction of a portion of the globus pallidus) and thalamotomy (destruction of a region of the thalamus) are available surgical treatment options. In the 1990s, high-frequency deep brain stimulation (DBS) was introduced as an adjunct to therapy towards reducing the motor complications of subjects with PD. Other DBS devices are also currently marketed in the United States, these include: Medtronic Activa, Itrel, Soletra, and Kinetra DBS Systems and the St. Jude Medical Infinity Neurostimulation System which are approved for bilateral GPi and STN stimulation for PD.

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## **VII. MARKETING HISTORY**

The Vercise PC and Vercise Gevia DBS Systems have been commercially distributed in the EU since September 2015 and June 2017 respectively. They have been commercially distributed in the US since January 2019. They have also been commercially distributed in other European countries, Canada, Australia, Japan, South America, Middle East, Russia, South Korea, and South Africa.

The device has not been withdrawn from marketing for any reason related to its safety or effectiveness.

## **VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH**

The adverse events that may occur with the Vercise PC and Vercise Gevia DBS Systems are among those that may occur in association with surgical complications or DBS specific complications (device-related or stimulation-related complications).

For the specific adverse events that occurred in the clinical studies, please see Section X below. Based on the technical equivalence described in Section IX below, the clinically established safety profile of the Medtronic Activa Parkinson's Control Therapy which was approved under P960009/S007 and the data used to support approval of the Vercise DBS System for stimulation of the STN are directly applicable to the Vercise PC and Vercise Gevia DBS Systems for bilateral GPi DBS as an alternative target for stimulation for PD.

## **IX. SUMMARY OF NONCLINICAL STUDIES**

### **A. Non-clinical Studies**

The Vercise PC and Vercise Gevia DBS Systems are legally marketed. Device systems were tested previously via non-clinical laboratory testing, including bench testing, biocompatibility evaluation, electromagnetic compatibility, sterilization, packaging, and shelf-life testing. Device design and system compatibility involved verification and validation of each system. The test results were found to be acceptable.

#### **Vercise PC and Vercise Gevia Implantable Pulse Generator (IPG)**

The hardware design verification testing was leveraged from the Precision Novi and Precision Montage SCS IPG which have the same hardware as the Vercise PC and Vercise Gevia IPGs respectively.

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**Table 3: IPG Verification Testing**

| Test | Purpose | Acceptance Criteria |
| --- | --- | --- |
| IPG Electronics | Verify the requirements for: • Pulse Generation • Internal IPG circuits • RF Telemetry Interface • Battery Protection Circuitry | • The IPG stimulation output parameters match the programmed parameters within the specified tolerances. • Internal IPG circuits shall function within their specified limits. • The IPG RF receiver shall function as specified. • The battery protection circuits shall function as specified. |
| Environmental and Mechanical Stresses | Verify the integrity and function of the IPG after exposure to environmental and mechanical stress conditions such as: • High and low storage temperature • Temperature changes • Mechanical forces • Random Vibration • High and low atmospheric pressures | The IPG shall pass device level functional tests after exposure to environmental and mechanical stresses. |
| | Verify the integrity of the header after mechanical stresses and suture pull. | Header shall not show visual damage. |
| Hermeticity | Verify that the internal moisture content of the hermetically sealed IPG case is within acceptable limits after environmental stresses. | The internal water vapor content shall be within specifications. |
| Immunity to Medical Procedures /Therapies | Verify that the IPG is functional after exposure to the following medical procedures/therapies: • Diagnostic Ultrasound • Monopolar and bipolar Electrocautery • External Defibrillation X-Ray | The IPG shall pass device level functional tests after exposure. |
| IPG-Lead Interface | • Verify that the Lead to IPG connection meets the requirements for insertion, withdrawal and retention forces. • Verify contact resistance. Verify electrical isolation | • The insertion, extraction and retention forces for the Lead-IPG Connector interface shall meet the specifications after multiple insertion and withdrawal cycles. • The resistance for each contact shall meet the specifications. • The impedance between any two terminations shall be within the specifications. |
| Rechargeable IPG Battery (Vercise Gevia) | • Evaluate battery life. Verify cell performance and integrity. | • The evaluation of battery longevity under typical use conditions shall support the labeled battery life. • After exposure to mechanical and environmental stresses, the battery cells must meet the requirements for hermeticity as well as electrical and mechanical integrity. • The battery cells must meet the requirements for self-discharge and storage loss. • After multiple discharge cycles, battery cells must meet visual, mechanical and hermeticity criteria. • The battery cells shall maintain mechanical integrity during and after application of exposure to short circuits and abnormal discharging. |

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| Test | Purpose | Acceptance Criteria |
| --- | --- | --- |
| Non-rechargeable IPG Battery (Vercise PC) | - Evaluate battery life. - Verify cell performance and integrity. | - The evaluation of battery longevity under typical use conditions shall support the labeled battery life. - After exposure to mechanical and environmental stresses, the battery cells must meet the requirements for hermeticity as well as electrical and mechanical integrity. - The battery cells must meet the requirements for self-discharge. - The battery swelling and capacity must meet specifications after discharge. - The battery cells shall maintain mechanical integrity after exposure to short circuits and forced discharging. |
| Charging (Vercise Gevia) | - Verify that the IPG can be charged at the specified charging distances and operating temperature. - Verify the requirements for heat generated during charging. | - The IPG charging current and charge time shall meet the requirements when the Charger is at a specified distance from the IPG. - The charge rate over the devices operating temperature shall meet the specifications. - The IPG case heating due to heat dissipation during charging shall be within acceptable limits. |

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**Table 4: DBS Leads, Extensions, and Accessories Verification Testing**

| Test | Purpose | Acceptance Criteria |
| --- | --- | --- |
| Physical and Mechanical Characteristics | Verify the physical and mechanical characteristics of : • Lead • Lead Extension • Stylet • Lead Boot • Lead Stop • Burr-Hole Cover | • Lead dimensions, surface finish, Lead straightness shall meet the specifications. • The distal Lead shall experience minimal movement when the proximal Lead is folded at a specified angle. • The Lead shall withstand the specified end-to-end pull force without loss of mechanical or electrical integrity. • The force required to deflect the Lead tip shall meet the requirements. • When exiting the cannula, deflection of the Lead tip shall be within specification. • The Stylet dimensions and deflection force shall meet the specifications. • The Lead Boot shall meet the requirements for fit, smooth profile, seal and retention force when connected to the lead. • The Lead Stop shall meet the dimensional and geometrical requirements and be able to resist translational forces. • The Burr-Hole Cover shall meet the requirements for dimensions, geometric specifications, lead clip placement and assembly. • The Extension shall withstand tunneling and pull forces. • The Lead and Extension shall maintain mechanical and electrical integrity after exposure to flex fatigue. |
| Electrical Tests | Verify that the Lead and Extension meets the requirements for electrical isolation and continuity of conductor paths. | • Current leakage shall be within specifications in dry and soaked states. • The electrical DC resistance of the Lead and Extension shall meet the specifications. |
| Interface Tests | Verify the compatibility and interface between Lead, Extension and other Lead accessories. | • The retention force for the connection between Lead, Extension and other Lead accessories shall meet the specifications. • Components shall maintain mechanical and electrical integrity following multiple connection and disconnection cycles between Lead and Lead accessories. • Lead shall maintain integrity after multiple clamp and unclamp cycles with the Burr-Hole Cover. The Lead is securely held in place by the Burr-Hole Cover. • The locking force for the connection between Extension and IPG connector shall meet the specifications. |
| Storage Conditions | Verify integrity of DBS Leads and Sterile Kit components after exposure to temperature conditions likely to be encountered during shipping and storage. | • Components of DBS System Sterile Kits shall be functional after temperature cycling and after storage in high and low temperatures. |

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## Remote Control

The hardware design verification testing was leveraged from the Freelink SCS Remote Control which has the same hardware as Vercise DBS Remote Control 3.

**Table 5: Remote Control Verification Testing**

| Test | Purpose | Acceptance Criteria |
| --- | --- | --- |
| Environmental and Mechanical Stress | Verify the integrity and function of the Remote Control after exposure to environmental and mechanical stress conditions such as: • High and low storage temperature • Random Vibration • Drop • Humidity • Button presses representing years of use | The Remote Control shall pass device level functional tests after exposure to environmental and mechanical stresses. |
| Remote Control Functions | Verify Remote Control functions. | • Remote Control shall respond to each key press as well as typically used combinations with appropriate action and appropriate display on the LCD screen. • RF communication with stimulators shall meet the specifications at the labeled distance. • Remote Control shall display the proper battery level status. • Internal circuits shall function as specified |

## Charging System

The hardware design verification testing was leveraged from the Precision Charger which is the same device as the Vercise Charger.

**Table 6: Charging System Verification Testing**

| Test | Purpose | Acceptance Criteria |
| --- | --- | --- |
| Environmental and Mechanical Stress | Verify the integrity and function of the Charger and Base Station after exposure to environmental and mechanical stress conditions such as: • High and low storage temperature • Temperature changes • Mechanical forces • Random Vibration • Drop • Humidity | The Charger and Base Station shall pass device level functional tests and visual inspection after exposure to environmental and mechanical stresses. |
| Charger Electronics | Verify functionality of the Charger electronics. | • Protection of charging terminals against over-voltage and over-current conditions shall operate as specified. • The quiescent current, coil voltage and frequency, power dissipation and IPG charge current shall meet the specifications. • The Charger electronics shall function as specified with regards to: – indication of battery status level – charging of the Charger battery – indication of alignment with the IPG – detection of end-of-charge signal when IPG is fully charged – battery protection circuits. |

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| Test | Purpose | Acceptance Criteria |
| --- | --- | --- |
| Heating During Charging | Verify the requirements for heat generated during charging. | - The surface temperature of the Charger shall not exceed the acceptable limit while charging. |
| Base Station | Test for continuity, spring contact fatigue and connector fatigue. | - The resistance between the DC power jack and spring contact shall meet the specifications. - Spring contacts shall remain elastic after repeated deflections. - Power supply plug shall fit and not be loose after repeated insertion/extraction cycles. |

### External Trial Stimulator (ETS)

The hardware design verification testing was leveraged from the Precision Spectra ETS which has the same hardware as Vercise ETS 2.

**Table 7: ETS Verification Testing**

| Test | Purpose | Acceptance Criteria |
| --- | --- | --- |
| ETS Electronics | Verify the requirements for: - Pulse generation - Operation within the operating temperature range and load range - RF Telemetry Interface | - The ETS stimulation output parameters shall be within the specified tolerances across ranges of temperature and load. - The ETS RF transmitter and receiver shall function as specified. |
| Environmental and Mechanical Stress | Verify the integrity and function of the ETS after exposure to environmental and mechanical stress conditions such as: - High and low storage temperature - Random Vibration - Drop - Humidity - Button presses representing years of use | The ETS shall pass device level functional tests after exposure to environmental and mechanical stresses. |
| ETS - O.R. Cable Interface | - Verify that the O.R. Cable to ETS connection meets the requirements for insertion, withdrawal and retention forces. | - The insertion, extraction and retention forces for the ETS-OR Cable Connector interface shall meet the specifications. - Continuity shall be maintained after multiple cycles of insertion and extraction between the OR Cable and ETS |

### Software

Software testing established that the system meets the software requirements and user needs for the intended uses.

### Electromagnetic Compatibility (EMC) and Wireless Technology

EMC testing was performed in accordance with the relevant clauses of the following standards and met specified acceptance criteria:

- IEC 60601-1-2: 2014, “Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral standard: Electromagnetic compatibility - Requirements and tests” (appropriate essential

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performance criteria were used)
- ANSI/AAMI/ISO 14708-3:2008(R2011): Implants for surgery – Active implantable medical devices – Part 3: Implantable neurostimulators”, Part 27

Testing to address compatibility with Radio-frequency Identification (RFID) and Electronic Article Surveillance systems was also provided.

The wireless technology of the system includes RF telemetry between the Remote Control and the Stimulators and wireless inductive charging of the IPG. These connections were verified to meet the range, security, data integrity and overall system functionality requirements through design verification testing.

### Biocompatibility

Biocompatibility of all tissue-contacting components of the Vercise PC and Vercise Gevia Deep Brain Stimulation (DBS) System was evaluated in accordance with ISO 10993-1, Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing within a risk management process. The Vercise DBS Leads are considered permanent (> 30 days) implants in contact with neural tissue/bone, cerebrospinal fluid (CSF), and blood (indirect contact through CSF). The Vercise PC and Vercise Gevia IPGs, Lead Extensions, Suture sleeves, and Burr-Hole Cover are considered permanent (>30 days) implants in contact with tissue/bone. The Lead Boot is considered an implant device with prolonged (24 hours – 30 days) tissue/bone contact, and implanted accessories meet the biocompatibility requirements for tissue/bone contacting permanent implants per EN ISO 10993-1:2009 COR2010. The Charging Collar is considered an intact skin-contacting device with limited (≤ 24 hours) contact.

Biocompatibility of the Vercise DBS non-directional Leads was demonstrated by cytotoxicity and neuroimplantation testing on the final, sterilized Vercise DBS Leads, leveraging testing previously conducted on the Linear 8 Contact Lead (Model # SC-2138 and SC-2208) approved in P030017, and leveraging biocompatibility data on US marketed devices with direct blood contact. An ISO mammalian cell culture media (MEM) elution cytotoxicity test was conducted on the Vercise DBS Lead with passing results. A neuroimplantation study was conducted in a swine model to assess the safety of the Vercise DBS Leads at approximately 30 and 180 days post-implantation. Implantation of the Vercise DBS Leads was not associated with any unexpected adverse effects. Both cytotoxicity and implantation studies on the Vercise DBS Leads were conducted in compliance with Good Laboratory Practices (GLP) regulations (21 CFR Part 58). The sensitization, intracutaneous reactivity, systemic toxicity (acute, subchronic, and chronic toxicity), material-mediated pyrogenicity, genotoxicity, and carcinogenicity endpoints for the Vercise DBS Leads were assessed by leveraging biocompatibility information on the Linear 8 Contact Lead (P030017). This was appropriate because the Vercise DBS Leads and Linear 8 Contact Lead are identical in terms of the tissue- contacting materials and are manufactured and sterilized by the same processes. Hemolysis (indirect contact) endpoint was assessed by leveraging hemocompatibility data on the US marketed devices (approved in P010012/S274 and P050046/S012) with identical tissue-contacting materials as the Vercise DBS Leads. Biocompatibility of the Vercise Cartesia DBS Directional Leads was based on similarity with the Vercise DBS non-Directional Leads. Both Directional and non-

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directional Leads have the same tissue-contacting materials and are manufactured and sterilized by the same processes. ISO MEM Elution cytotoxicity and particulate matter release tests were performed on the Vercise Cartesia DBS Directional Leads with passing results. In addition, a neuroimplantation study was conducted in a swine model to assess the safety of the Vercise Cartesia DBS Directional Leads at approximately 90 days post-implantation. Implantation of the Vercise Cartesia DBS Directional Leads was not associated with any unexpected adverse effects.

Biocompatibility of the Vercise PC and Vercise Gevia IPGs was demonstrated by leveraging testing previously conducted on the Precision Novi and Precision Montage SCS System IPG Models SC-1140-S (P150031/S217, S287) and SC-1200-S (P030017/S235) respectively. Leveraging this testing information was appropriate because the Vercise PC and Vercise Gevia IPGs are identical to the Precision SCS System IPGs in terms of the tissue-contacting materials, manufacturing including sterilization processes, and the nature and duration of tissue contact.

The Vercise Lead Extensions are the same lead extensions used in the Precision SCS System (P030017).

Biocompatibility of the Vercise Suture Sleeves was demonstrated by appropriately leveraging testing previously conducted on Linear 8 Contact Lead (Model # SC-2138 and SC-2208) approved in P030017. The Vercise Suture Sleeves are made of the identical silicone material that is present in the Linear 8 Contact Lead and both devices have permanent (> 30 days) contact with tissue/bone. In addition, an ISO MEM elution cytotoxicity test was conducted on the finished, sterilized 4.0 cm Vercise Suture Sleeve with passing results.

The Burr Hole Cover consists of a Base, Retaining Clip, Cap and two Screws. Biocompatibility of the Base, Retaining Clip, and the Cap was demonstrated by testing conducted on these components in their finished, sterilized forms and by leveraging data in the device master file and in the US marketed devices with identical material. The MEM elution cytotoxicity, guinea pig maximization sensitization, intracutaneous reactivity, intramuscular implantation (13 weeks), acute systemic toxicity, rabbit pyrogenicity, and genotoxicity (Ames, in vitro chromosomal aberration, and mouse micronucleus) tests were conducted on the Base, Retaining Clip, and Cap. All biocompatibility tests were conducted in compliance with GLP regulations (21 CFR Part 58). All pre-specified test acceptance criteria were met for all tests and all tests passed. The data in the device master file and the US marketed devices were leveraged for the assessment of subchronic/chronic toxicity and carcinogenicity endpoints. Biocompatibility of the Screws was demonstrated by appropriately leveraging biocompatibility data on Precision SCS System IPG Model SC-1110 (P030017) with identical material and nature and duration of tissue contact. In addition, the final, sterilized Burr Hole Cover was used in the swine neuroimplantation study (30 and 180 days) and no device material related adverse findings were noted in the study.

Biocompatibility of the Vercise Lead Boot was demonstrated by leveraging testing previously conducted on the Precision SCS System 55cm 8 Contact Lead Extension (Model SC-3138-55) approved under P030017. Leveraging this testing information was

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appropriate since the Vercise Lead Boot is identical to the Precision SCS System 55cm 8 Contact Lead Extension (Model SC-3138-55) in terms of the tissue-contacting materials, manufacturing and sterilization processes. In addition, an ISO MEM elution cytotoxicity assay was conducted on the finished, sterilized Vercise Lead Boot with passing results.

Biocompatibility testing was conducted on the finished DBS Charging collar in accordance with GLP regulations (21 CFR Part 58). The agarose overlay cytotoxicity assay, primary skin irritation, and repeated patch dermal sensitization tests were conducted on the DBS Charging Collar. All pre-specified test acceptance criteria were met for all tests and all tests passed.

### **Sterilization**

The Vercise PC and Vercise Gevia IPGs, DBS Lead, Extension, OR Cable, Burr Hole Cover and other implanted accessories are sterilized using a validated EO sterilization cycle to achieve a minimal sterility assurance level of 10⁻⁶. Validation of the EO sterilization process for these devices was done in accordance with EN ISO 11135:2014 *Sterilization of health-care products — Ethylene oxide — Requirements for the development, validation and routine control of a sterilization process for medical devices*. EO residual levels found on these devices following EO sterilization process are shown to be below the maximum allowable limits of EO and Ethylene chlorhydrin (ECH) residual levels specified in EN ISO 10993-7:2008(Cor) 2009 *Biological evaluation of medical devices — Part 7: Ethylene oxide sterilization residuals*.

The bacterial endotoxin levels on these device, determined using Limulus Amebocyte Lysate (LAL) testing in accordance with the USP Chapter <161> *Transfusion and Infusion Assemblies and Similar Medical Devices*, and ANSI/AAMI ST72:2011 *Bacterial endotoxins - Test methods, routine monitoring and alternatives to batch testing*, comply with the bacterial endotoxin limits specified in the and FDA’s Guidance for Industry - Pyrogen and Endotoxins Testing: Questions and Answers (June 2012).

### **Packaging and Shelf Life**

Packaging performance and stability testing results demonstrated that the packaging system for the sterile components of the BSN Vercise PC and Vercise Gevia DBS Systems can withstand the environmental and mechanical stresses likely to be encountered during transportation and storage and maintain its sterile barrier up to two years of the established shelf-life.

## **B. Technological Comparison**

In lieu of providing a clinical data set for GPi stimulation with the Vercise PC and Vercise Gevia DBS Systems, the sponsor provided a technological comparison (including a comparison of the technology, surgical procedures, and instructions for use) of the Vercise PC and Vercise Gevia DBS Systems to the Medtronic Activa Parkinson’s Control Therapy which was approved under P960009/S007 for the requested indications for use. The purpose of the technological comparison was to establish sufficient similarity of the Boston Scientific and Medtronic DBS devices such that FDA could apply Section 216 of the Food and Drug Modernization Act (FDAMA), i.e., the “six-year rule,” to assess the effectiveness profile of Infinity DBS.

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According to FDA’s “Guidance on Section 216 of the Food and Drug Modernization Act of 1997” available at:

https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm073709.pdf, FDA may choose to utilize the publicly available detailed SSED of a previously approved device to support approval of a PMA for a new device if the applicant provides “a detailed justification of how the information in the earlier SSED applies to the applicant’s device” and if the applicant is able “to describe how the devices are similar enough to allow for the data from the earlier device to apply to the new device.”

For the purposes of establishing sufficient similarity of the Vercise PC/Vercise Gevia DBS Systems and the Medtronic Activa Parkinson’s Control Therapy, the sponsor provided a technical comparison of the two devices. The comparisons are summarized as follows:

# 1. Volume of Tissue Activation (VTA)

Deep brain stimulation (DBS) systems work by sending electrical stimulation from an implanted neurostimulator to leads in the brain where the current is dispersed through electrodes into the brain tissue in order to activate neurons in specific brain regions. The clinical response of stimulation varies depending on the brain target and the orientation of the DBS lead within the target. As part of DBS programming, the clinician can adjust the combination of parameters, including amplitude, pulse width, frequency and electrode configuration, to tailor the stimulation field to the needs of each patient. By comparing the VTA of the Vercise PC and Vercise Gevia DBS Systems to the Medtronic Activa Parkinson’s Control Therapy it was determined that the Vercise PC and Vercise Gevia DBS Systems stimulate, and thus activate, neurons with volume of brain tissue equivalent to that which was shown to be safe and effective for the Medtronic Activa Parkinson’s Control Therapy approved in P960009/S007.

VTA modeling has been used to estimate the degree of neuronal activation and by extension the degree of stimulation efficacy [1]. Thus, the sponsor provided comparative modeling of the VTA between the stimulation produced by Vercise PC/Vercise Gevia DBS System IPGs and the associated non-directional (DB-2201) and directional (DB-2202) leads and the Medtronic Activa Parkinson’s Control Therapy using the Soletra Neurostimulator and the Medtronic leads (Models 3387 and 3389) that were approved in P960009/S007.

The electric fields generated during stimulation by the DBS electrodes were calculated from the Poisson equation with a finite element model (FEM) solver to determine space-dependent voltage within the tissue medium [1, 2]. Finite element models were constructed to calculate the electric fields produced by DBS leads in a homogenous tissue medium, and the calculated voltages in space were applied to non-linear axon models in accordance with methods described in the literature for evaluation of DBS electrode design and characterization of field shape [1,2]. There are no differences in assumptions and boundary conditions between the previous

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modeling papers and the modeling data presented by the sponsor.

The Boston Scientific Vercise PC and Vercise Gevia IPG waveform includes a current regulated stimulation phase and is passively charged balanced, while the Medtronic Soletra IPG waveform is voltage regulated. The waveform was accounted for in this modeling. Both waveforms were measured from their respective IPGs [2] and the components of the waveform were fed into the model, in addition to appropriate electrode geometry, including edge-to-edge spacing, array length, electrode surface area, and electrode configuration. The following output stimulation parameters were used as the basis for the input parameters for the model: amplitude, pulse width, frequency, and stimulation mode (monopolar or bipolar). Since the maximum clinically relevant output stimulation parameter range used to support approval of P960009/S007 do not appear to be publicly available the sponsor used the values put forth by the Limousin-Dowsey and Tisch (2009) book chapter as typically used parameters for GPi stimulation in Parkinson's disease (i.e., 1.5 – 5.0 V, 30 – 120 μs, and 130–185 Hz). The following scenarios were modeled for the Medtronic leads and the Boston 8 channel non-segmented (2201) and segmented (2202) leads, where current was titrated to achieve a comparable VTA:

Table 8: Parameters Used in Models of the Medtronic Soletra VTAs

| Lead | Configuration | Voltage | Pulse Width^{§} | Frequency |
| --- | --- | --- | --- | --- |
| Medtronic 3387 | Monopolar | 1.5 V | 60 μs | 130 Hz |
| Medtronic 3387 | Monopolar | 5 V | 120 μs | 185 Hz |
| Medtronic 3387 | Bipolar | 1.5 V | 60 μs | 130 Hz |
| Medtronic 3387 | Bipolar | 5 V | 120 μs | 185 Hz |
| Medtronic 3389 | Monopolar | 1.5 V | 60 μs | 130 Hz |
| Medtronic 3389 | Monopolar | 5 V | 120 μs | 185 Hz |
| Medtronic 3389 | Bipolar | 1.5 V | 60 μs | 130 Hz |
| Medtronic 3389 | Bipolar | 5 V | 120 μs | 185 Hz |

§ 60 μs is the minimum programmable pulse width available for the Medtronic Soletra

A total of 16 modeling scenarios were modeled for the Medtronic (8 scenarios, Table 8) and Boston Scientific leads (8 scenarios, corresponding to Table 8 settings but with BSN leads). These scenarios represented relevant output parameters, configurations, and lead types (non-directional (non-segmented) and directional (segmented)). The scenarios were created to demonstrate the capability of both the Boston Scientific Vercise 8-contact non-directional lead (DB-2201) and the Boston Scientific Vercise Cartesia 8-contact directional lead (DB-2202) to produce a VTA comparable to that produced by the Medtronic 4 contact leads. Then for each Medtronic VTA, amplitude was titrated with the

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Boston Scientific DB-2201 and DB-2202 leads to achieve a VTA comparable to that achieved by the Medtronic lead.

# **Results:**

The modeled Boston Scientific leads were able to achieve a comparable VTA volume and shape when compared the Medtronic leads.

In all the scenarios above the percent deviation of the VTAs of the Boston Scientific leads from the VTA of the Medtronic lead ranged between **4.34%** (meaning greater coverage for Boston Scientific leads) and **-3.26%**.

# **Conclusions:**

The results show that parameters of the Vercise PC and Vercise Gevia DBS Systems can be varied to achieve a VTA comparable to that achieved by the Medtronic Activa Parkinson’s Control Therapy approved in P960009/S007; the range of deviation is acceptable. These results also demonstrate that a desired VTA can be achieved by adjusting stimulation parameters on any of the lead models (Boston Scientific lead models DB-2201 and DB-2202, Medtronic lead models 3387 and 3389).

The clinical response to stimulation varies depending on the brain target and the position and orientation of the DBS lead within the target. As part of DBS programming, the clinician can adjust the combination of parameters, including amplitude, pulse width, frequency and electrode configuration, to tailor the stimulation field to the needs of each patient. Parameters can be adjusted to achieve a desired VTA, with shaping customized on a patient by patient basis.

# **2. Output Parameters**

**Table 9: Device Comparison Summary Table of Medtronic Activa Parkinson’s Control Therapy Soletra IPG to Vercise PC and Vercise Gevia DBS System IPG**

| | Vercise PC/ Vercise Gevia | Soletra™ | Safety | Efficacy |
| --- | --- | --- | --- | --- |
| Amplitude (settings) | 0 - 12.7 mA per contact (max 20.0 mA per area) | 1 – 10.5V | Both confined by charge density limit (30 µC/cm²). Parameters verified via Boston Scientific Parkinson’s study to be safe for use in the STN which is also relevant to the GPi. | Can be programmed within clinically relevant parameter ranges, wider ranges that are available through Vercise PC and Vercise Gevia provide additional programming flexibility. |

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| | Vercise PC/ Vercise Gevia | Soletra™ | Safety | Efficacy |
| --- | --- | --- | --- | --- |
| Frequency (settings) | 2 - 255 Hz | 2 – 185 Hz | Parameters verified via the Boston Scientific Parkinson’s Study to be safe for use in the STN which is also relevant to the GPi. | Can be programmed within clinically relevant parameter ranges, wider ranges that are available through Vercise PC and Vercise Gevia provide additional programming flexibility. |
| Pulse width (settings) | 20 – 450 µsec | 60 – 450 µsec | Both confined by charge density limit (30 µC/cm²). | Can be programmed within clinically relevant parameter ranges, wider ranges that are available through Vercise PC and Vercise Gevia provide additional programming flexibility. |
| Number of Programs | 4 | 1 | All programs created must be within the available safe parameters. | Can be programmed within clinically relevant parameters, additional parameters provide programming flexibility |
| Independent Frequency/ Hemisphere | Yes | No | All programs created must be within the available safe parameters. | Can be programmed within clinically relevant parameters, additional parameters provide programming flexibility |
| Stim on/off | 1 seconds – 90 minutes | 0.1 seconds – 24 hours | Stimulator ensures charge imbalance condition for all settings. | Can be programmed within clinically relevant parameters. |
| Output waveform | Rectangular | Rectangular | Same | Same |
| Charge balance | Passive discharge | Active discharge | System requirements have been incorporated into the product design to ensure that stimulation pulses are balanced with appropriate discharge. | Waveform shown to be effective in eliciting and inhibiting action potentials as shown in approval for STN stimulation which is also grey matter. |
| Pulse delivery modes | Continuous and Cycle | Continuous and Cycle | System requirements have been incorporated into the product design to ensure that stimulation pulses are balanced with appropriate discharge. | Continuous and cycling effective in eliciting and inhibiting action potentials cycling can help prevent habituation |
| Current distribution to electrodes | Stimulators control the amount of current at each electrode independently during a stimulation pulse | Single voltage source. Impedance dictates the amount of current at each electrode | Stimulation is delivered at clinician prescribed stimulation settings over time. | Impedance changes do not affect stimulation delivery. The prescribed current is maintained at each electrode regardless of impedance changes. |

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The table above demonstrates that the Vercise PC and Vercise Gevia DBS Systems have the capability to replicate at least the same output as the Medtronic Activa Parkinson's Control Therapy system indicating it can provide at least a comparable level of efficacy. Though the waveforms of Vercise PC/Gevia and Soletra differ in their method of charge balancing they both have the capability to inhibit and excite action potentials. The degree of neuronal activation with DBS is proportional to the amount of charge delivered. The intensity of the charge delivered (charge density) also has implications for clinical safety. For parameters that differ between the devices, Table 9 above shows that the Vercise PC and Vercise Gevia DBS Systems ensure safety by providing a charge density limit (30 μC/cm²) and preventing charge imbalance conditions. As the electrode surface area of the Boston Scientific DBS Leads is less than or equal to that of the Medtronic Leads, the maximum charge at the charge density limit is less than or equal to the Medtronic system. The maximum power and power density is limited by the charge density limit.

The Boston Scientific INTREPID Parkinson's study of STN stimulation provides further assurance of the safety of the additional parameters provided by the Vercise PC and Vercise Gevia devices. The study was used to support the safety of DBS at therapeutic levels for Parkinson's disease. Although patients in the study were implanted in the STN, both STN and GPi are grey matter nuclei that can be stimulated to treat some of the symptoms of Parkinson's disease.

# 3. Leads

See VTA analysis in Section IX(B)(1) above. Table 10 below provides an additional comparison of Lead attributes.

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**Table 10: Comparison between Vercise PC and Vercise Gevia DBS System Leads and Medtronic Activa Parkinson’s Control Therapy Leads**

| | Boston Scientific DBS Leads | | Medtronic DBS Leads Models 3387 and 3389 | Clinical Equivalence |
| --- | --- | --- | --- | --- |
| | Standard 8-contact DBS Lead Model DB-2201 | Directional 8-contact DBS Lead Model DB-2202 | | |
| **Electrode configuration** | 1-1-1-1-1-1-1-1 8 electrode configuration, no active tip | 1-3-3-1 8 electrode configuration, active tip | 1-1-1-1 4 electrode configuration, no active tip | See VTA analysis in Section IX(B)(1) above. Additionally, the Directional Lead has the same stimulation output capabilities with additional programming options. 1^{st} and 4^{th} contact rows provide omnidirectional stimulation. 2^{nd} and 3^{rd} rows can use all 3 segments to provide omnidirectional stimulation that is clinically equivalent or use segmented electrodes |
| **Active tip** | No | Yes | No | The presence of Active Tip at the tip of the Directional array (contact 1), results in one contact (tip) with the same larger surface area as the other ring contacts. From a stimulation efficacy perspective, the clinical response of stimulation varies depending on the brain target and the orientation of the DBS lead within the target. See VTA analysis in Section IX(B)(1). |
| **Electrode material** | Platinum/Iridium | Platinum/Iridium | Platinum/Iridium | Same |
| **Conductor Wire** | Nickle based alloy with platinum core | Nickle based alloy with platinum core | Platinum/Iridium | Conductor material facilitates delivery of stimulation current with minimal loss. From a stimulation perspective they are clinically equivalent. |

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| | Boston Scientific DBS Leads | | Medtronic DBS Leads Models 3387 and 3389 | Clinical Equivalence |
| --- | --- | --- | --- | --- |
| | Standard 8-contact DBS Lead Model DB-2201 | Directional 8-contact DBS Lead Model DB-2202 | | |
| **Lead Body** | 55D Polyurethane | 55D Polyurethane | 80A Urethane | All leads are made up of biocompatible materials. The minor differences in materials have no impact on the biological safety or function of these leads. |
| **Electrode Surface area** | 6 mm² | Ring electrodes: 6 mm² Segmented electrodes: 1.5 mm² | 5.98 mm² | See VTA analysis in Section IX(B)(1). |
| **Number of electrodes** | 8 | 8 | 4 | See VTA analysis in Section IX(B)(1). |
| **Contact length (mm)** | 1.5 | 1.5 | 1.5 | Same |
| **Contact spacing (mm)** | 0.5 | 0.5 | 0.5, 1.5 | Same as Medtronic model 3389 |
| **Array length (mm)** | 15.5 | 7.5 | 7.5, 10.5 | See VTA analysis in Section IX(B)(1). |
| **Leads length (cm)** | 30, 45 | 30, 45 | 28, 40 | Lead length does not impact the delivery of stimulation to the targets. |
| **Lead diameter (mm)** | 1.3 | 1.3 | 1.27 | See VTA analysis in Section IX(B)(1). |

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As outlined in Table 10 above, the Vercise PC and Vercise Gevia DBS System and the Medtronic Activa Parkinson’s Control Therapy system Leads are clinically equivalent. Although there are differences in some physical aspects of the Leads, those differences have been demonstrated not to impact the safe and efficacious delivery of the stimulation to the targeted location.

#### 4. Extensions

The table below shows a comparison between attributes of the Boston Scientific DBS Extension and the Soletra Extension.

**Table 11: Comparison between Boston Scientific DBS System Extension and Medtronic Activa Parkinson’s Control Therapy Extension**

| | Boston Scientific DBS 8-contact Extension Model NM-3138 | Medtronic DBS Extension Model 7482 | Clinical Equivalence |
| --- | --- | --- | --- |
| Body diameter (mm) | 1.35 | 2.8 | The diameter does not impact the delivery of electrical stimulation to the target location through the lead contacts. |
| Connector thickness (mm) | 4.52 mm | 3.8 plus boot (total diameter 5.0) | The connector thickness does not impact the delivery of electrical stimulation to the target location through the lead contacts. Physically the connectors are almost identical in size with the inclusion of the boot for the Medtronic extension. |
| Body construction | Continuous | Continuous | The body construction for both extensions is continuous and therefore they are clinically equivalent. |
| Lengths (cm) | 55 | 51 | The additional lengths offered for the Boston Scientific Extensions are available for physicians to use as appropriate for different patient anatomies and do not impact safety and effectiveness of the system as the delivery of effective stimulation is not impacted by the length of the Extension. |
| Number of distal (lead) contacts | 8 | 4 | The variance in the number of contacts is a function of the actual Lead with which the Extension is used. For example, an 8-contact Lead would require 8 distal contacts in order to adequately connect to the Extension and deliver therapy from the IPG to the target location. The difference is the number of contacts does not impact safety and effectiveness because the stimulation can be effectively transmitted along the Extension regardless of the number of contacts. |

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| | Boston Scientific DBS 8-contact Extension Model NM-3138 | Medtronic DBS Extension Model 7482 | Clinical Equivalence |
| --- | --- | --- | --- |
| Wiring | Straight, not coiled | Coiled | Conductor facilitates delivery of stimulation current with minimal loss. From a stimulation perspective they are clinically equivalent. |
| Locking mechanism | 1 setscrew | 4 setscrews | Locking mechanisms are designed and tested to provide adequate retention force of the Lead within the Extension header. Although the Boston Scientific Extension has fewer setscrews, testing establishes that a single setscrew provides sufficient retention force of 14 N or greater for its safe and efficacious use which is a force greater than what would occur clinically. |
| **Patient Contacting Materials** | | | |
| Extension Header | Silicone: Nusil MED 4860 Nusil MED 4870 Nusil MED 1137 Nusil MED1-161 | Siloxane coated silicone rubber (2) | The Extension is made up of biocompatible materials. The minor differences in materials have no impact on the biological safety or function of the Extension. |
| Extension Body | 55D Polyurethane | Silicone Rubber and polyurethane (2) | The Extension is made up of biocompatible materials. The minor differences in materials have no impact on the biological safety or function of the Extension. |

As outlined in Table 11 above, the Vercise PC and Vercise Gevia DBS System and the Medtronic Activa Parkinson's Control Therapy System Extensions are clinically equivalent. Although there are differences in some physical aspects of the Extensions, those differences have been demonstrated not to impact the safe and efficacious delivery of the stimulation to the targeted location.

# 5. Accessories

Since IPGs, Leads and Extensions play a direct role in the delivery of therapy to patients, detailed equivalence assessments (technical, biological and clinical) are provided. However, the assessment of PMA approved system accessories is focused on how each accessory functions and contributes to the effective delivery of therapy, including how its dimensions, materials and mechanical properties allow it to safely perform that function. Table 12 below provides this comparison and establishes that there are no differences that impact the safety and effectiveness of the respective systems during use for a GPi target location.

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**Table 12: Comparison between Vercise PC and Vercise Gevia DBS System accessories and Medtronic Activa Parkinson’s Control Therapy accessories**

| Accessories Name | Vercise PC/ Vercise Gevia | Soletra | Function | Clinical Equivalence |
| --- | --- | --- | --- | --- |
| **IPG Implant Accessories** | | | | |
| Torque Wrench | Yes | Yes | Secure the Extensions in the IPG | The mechanical properties and dimensions are compatible with the IPG/Lead to safely ensure system performance (e.g. lead connection to IPG) |
| Port Plug | Yes | Yes | Prevent tissue and fluid ingress into unused ports | The mechanical properties and dimensions are compatible with the IPG to safely ensure system performance (e.g. IPG port enclosure). From a material perspective, port plugs are considered biocompatible for their intended use per ISO 10993. |
| Pocket Adapter | Yes | Yes | To adapt Medtronic extensions to the neurostimulator | Boston Scientific provides the M8 Adapter to connect Medtronic Extensions to the Boston Scientific IPG. The mechanical properties and dimensions are compatible with the IPG/extensions to safely ensure system performance (e.g. via electrical connection). From a material perspective the adapters are considered biocompatible for their intended use per ISO 10993. The Boston Scientific Extensions connect directly to the IPG. The absence of a pocket adapter does not impact clinical safety or performance. |
| Patient Magnet | No | Yes | Used to perform magnet enabled functions on the IPG | The Vercise PC and Gevia IPGs do not have any magnet enabled functions. The absence of a patient magnet does not impact clinical safety or performance. |
| Pocket Template | Yes | Yes | Create an IPG implant site that is appropriate for the IPG size | The dimensions match the dimensions of the IPG for use during the implant procedure. From a materials perspective the Pocket Templates are considered biocompatible for their intended use per ISO 10993. |

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| Accessories Name | Vercise PC/ Vercise Gevia | Soletra | Function | Clinical Equivalence |
| --- | --- | --- | --- | --- |
| **External Trial Stimulator Accessories** | | | | |
| OR Cable | Yes | Yes | Connects Lead or Extension to an External Stimulator to evaluate lead placement location and integrity during the procedure | The dimensions and mechanical properties are compatible with the External Stimulator and Leads to safely ensure system performance (e.g. via electrical connection). From a material perspective the O.R. Cables are considered biocompatible for their intended use per ISO 10993. |
| **Lead Surgical Accessories** | | | | |
| Lead Stop | Yes | Yes | To mark the depth of the Lead during implantation. | The mechanical properties and dimensions are compatible with the Leads to safely ensure system performance (e.g. marking a specific position on the Lead). From a material perspective, the Lead Stop is considered biocompatible for its intended use per ISO 10993. |
| Lead Boot | Yes | Yes | To protect the electrodes from damage. | The mechanical properties and dimensions are compatible with the Leads to safely ensure system performance (e.g. isolation and protection of the Lead). From a material perspective, the Lead protection boot is considered biocompatible for its intended use per ISO 10993. |
| Burr Hole Cover | Yes | Yes | To permanently secure the DBS Lead and to cover the burr hole created in the skull during the surgical implantation of the DBS Lead. | The mechanical properties and dimensions are compatible with the Leads to safely ensure system performance (e.g. secure the Lead). From a material perspective, the Burr Hole Cover is considered biocompatible for its intended use per ISO 10993. |
| Suture Sleeves | Yes | No | Used to protect the Lead when using a miniplate. May also be used to anchor the DBS Lead or DBS Extension to the fascia. | The mechanical properties and dimensions are compatible with the Leads to safely ensure system performance (e.g. secure the Lead). From a material perspective, the Suture Sleeves are considered biocompatible for its intended use per ISO 10993 |

#### 6. Remote Control/Therapy Controller capabilities

The patient Remote Control for Both Vercise PC/Vercise Gevia IPGs and the Medtronic Soletra IPG have the following capabilities:

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- Turn Stimulation On/Off
- Check status of Stimulation On/Off

Vercise PC/Gevia Remote Control has the additional ability to:

- Switch between up to 4 programs, as set by the physician in the Clinician Programmer.
- Adjust amplitude within limits set by the physician in the Clinician Programmer.

These additional capabilities do not affect the therapy as prescribed by the physician.

7. Labeling

The instructions for use are equivalent regarding implant procedures, stimulation related device programming (see Table 9 above) and other instructions for use. The devices also have equivalent labeling for contraindications, warnings, precautions, and adverse events.

# X. SUMMARY OF PRIMARY CLINICAL STUDIES

# A. Summary of Study to Support Approval of the Medtronic Activa Parkinson's Control Therapy approved (P960009/S7)

Because of the technological similarity of the Vercise PC and Vercise Gevia DBS Systems to the Medtronic Activa Parkinson's Control Therapy approved under P960009/S7, as described in Section IX above, the clinical studies used to provide evidence of the reasonable assurance of the safety and effectiveness of the Medtronic Activa Parkinson's Control Therapy under P960009/S7 apply equally well to the Vercise PC and Vercise Gevia DBS Systems. A prospective open label study was used to establish reasonable assurance of the safety and effectiveness of the Medtronic Activa Parkinson's Control Therapy and is summarized as follows. Additional details of these studies are provided in the SSED for P960009/S7 that is available on the CDRH website.

The study enrolled subjects with advanced, levodopa-responsive Parkinson's disease that are not adequately controlled with medication. Patients were to have a disability level due to Parkinson's disease based on the following criteria:

- Hoehn and Yahr staging 3 or worse when the patient is in the "off" state;
- Unified Parkinson's Disease Rating Scale (UPDRS) motor exam score of 30 or more in the "off" state; and
- Complications of levodopa therapy motor responses including motor fluctuations and dyskinesias.

Subjects were either implanted in the STN or the GPi. Patients participated in the studies for 12 months; there were 2 pre-implant visits and 4 follow-up visits (1, 3, 6, and 12 months). Each patient's dosage of antiparkinsonian medication was held constant for 1 month prior to surgery. Following surgery, physicians monitored antiparkinsonian medication status throughout the remainder of the study. Data collected at each pre-implant and follow-up visit included the Unified Parkinson's Disease Rating Scale (UPDRS) and 2-day patient diaries recorded prior to the visit. At each visit, patients were evaluated without medication

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(OFF medication) and with medication (ON medication). At follow-up visits, patients were also assessed without stimulation (stimulation OFF) and with stimulation (stimulation ON).

### B. Results Used to Establish Reasonable Assurance of Safety of Vercise PC and Vercise Gevia Systems for GPi Stimulation

#### 1. Safety Results for P150031

INTREPID Study

The INTREPID Study is a multi-center, prospective, double-blind, randomized, controlled study performed by Boston Scientific that was design to evaluate the safety and effectiveness of the Vercise DBS System for bilateral stimulation of the STN as an adjunctive therapy for improving dyskinesia and other symptoms in adults with advanced, levodopa-responsive bilateral Parkinson's disease which is not adequately controlled with medication. This study was used to support approval of the Vercise DBS System under P150031. Additional details of this study is provided in the SSED for P150031 that is available on the CDRH website. The Vercise PC and Vercise Gevia DBS Systems were approved under P150031/S001 based on a similarity of technological characteristics to the Vercise DBS System. Although the data were used to support the safety of DBS at the STN, findings have applicability to the safety of stimulation at the GPi since the STN and GPi are both grey matter nuclei the technological characteristics are similar. Stimulation related adverse effects typically can be resolved at either of the grey matter locations by adjustments to stimulation parameters.

The initial epoch of the study was a period of 12 weeks during which subjects remained blinded to their treatment assignment, and during which a blinded assessor (who was unaware of the subject assignment) completed all study assessments (i.e., double blind study design). Subjects were randomized in a 3:1 ratio to either receive Active or Control settings. Subjects in the Active group received therapeutic settings titrated by the treating neurologist to best clinical effect. Subjects in the Control group received sham stimulation where the stimulation was not set to therapeutic levels. At the Week 12 post-randomization visit, all subjects began an open-label period, with a follow-up period up to 5 years.

The primary safety endpoint of the study included the rates of occurrence of pre-specified adverse device effects at 52 weeks post-randomization. Additional safety parameters evaluated in the study included the rates of occurrence of all serious

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adverse events and all adverse device effects, including serious adverse device effects and unanticipated adverse device effects at 5 years post-randomization.

The data used in consideration of PMA P150031 reflected data collected through December 31, 2016, and included 292 patients from 23 investigational sites. A total of 788 adverse events in 143 subjects were reported at the time of the data snapshot. Of these, 74 events were reported as serious adverse events. Of 74 serious adverse events, 19 were related to hardware, 2 related to stimulation, and 31 related to procedure. Infection has been the most commonly reported serious adverse event associated with device-hardware/procedure (8 events, representing 2.7% of subjects). There were three events (each) of device-hardware/procedure- related serious adverse events of peri-operative intracranial hemorrhage (representing 1% of subjects) and seizure (representing 1% of subjects). These events are comparable to published reports

# 2. Safety Results for P960009/S7

For the safety analysis data from both the STN and GPi were combined in the SSED. As stated above, due to the similarity of the technological characteristics, adverse effects are expected to be similar between the STN and GPi, except for some stimulation related adverse effects that may be particular to the location of stimulation. Stimulation related adverse effects typically can be resolved by adjusting the output stimulation.

Of the 160 enrolled patients, 106 patients (106/160, 66.3%) underwent procedures that targeted the STN (bilateral: 96, unilateral: 6, not implanted: 4) and 54 (54/160, 33.8%) underwent procedures that targeted the GPi (bilateral: 38, unilateral: 15, not implanted: 1). All 160 enrolled patients were evaluated for the occurrence of adverse events. One hundred and fifty-four (154/160, 96.3%) of the enrolled patients experienced one or more adverse events. The SSED lists adverse events for all patients reported during the clinical investigation by major category and subcategories.

Over the entire study duration, 12/160 patients (7.5%) had intracranial hemorrhage; 17/160 patients (10.6%) had device-related infection; 16 patients (10.0%) had paresis/asthenia; and 13/160 patients (8.1%) had hemiplegia/hemiparesis. The rate of stimulation-related adverse events was 51.9% (83/160 patients) and the rate of ongoing stimulation-related events was 22.5% (36/160 patients). The rate of serious stimulation-related adverse events was 9.4% (15/160) and the rate of ongoing serious stimulation related adverse events was 3.1% (5/160) patients. Ongoing serious stimulation-related adverse events included: worsening of motor impairment/PD symptoms (dyskinesia), sensory impairment (pain); and speech/language (dysarthria, hypophonia, and speech disorder). Other stimulation related adverse events included: worsening of motor impairment/PD symptoms (worse motor fluctuations, incoordination, abnormal gait, akinesia/bradykinesia, tremor, rigidity, myoclonus and dysphagia); sensory impairment (paresthesia, sensory disturbance, hypesthesia, hearing [tinnitus] and headache); speech/language (voice alteration); eye (visual disturbances [diplopia, abnormal vision and visual field defect] and eye disorders [twitching]); cognitive (thinking abnormal, confusion, alteration of mentation [dizziness]); general (respiratory [laryngismus], musculo-skeletal [abnormal posture], gastrointestinal [vomiting], urogenital [urinary incontinence], metabolic/nutritional [weight loss], skin and appendages [sweating] and

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systemic [accidental injury]; sleep [somnolence and insomnia]; neuropsychological (psychiatric disturbances [manic reaction and neurosis]); general paresis/asthenia; internal system events (shock/jolt, positioning difficulties); cardiovascular (cerebrovascular accident); hemiplegia/hemiparesis (asthenia) and depression.

# **C. Results Used to Establish Reasonable Assurance of Effectiveness of Vercise PC and Vercise Gevia DBS Systems for GPi Stimulation**

# 1. Effectiveness Results for P960009/S7

For effectiveness purposes only the data from subjects implanted in the GPi were used from P960009/S7. Additional details are provided in the SSED for P960009/S7 that is available on the CDRH website. A summary of results follows:

# Patient Diary Results

"On" time improved between pre-implant and 12 months for GPi and STN subjects. "On" time with dyskinesia decreased between pre-implant and 12 months for GPi and STN subjects. For the subset of subjects whose data were verified against medical records:

- The duration of "on" time increased by an average of 6.7 hours in GPi patients and 6.1 hours in STN patients; and
- The duration of "on" time with dyskinesias decreased by an average of 4.2 hours in GPi patients and 2.8 hours in STN patients.

# UPDRS Total Motor Examination (TME) Scores

Data from the STN and GPi were combined in the SSED report of UPDRS TME scores. UPDRS TME scores improved between pre-implant and 12 months for both GPi and STN patients when assessed while ON medication with stimulation ON and when assessed while OFF medication with stimulation ON. For the subset of patients whose data were verified against medical records:

- Symptoms of Parkinson's disease (UPDRS TME scores) improved for 56/117 patients while ON medication;
- Symptoms of Parkinson's disease (UPDRS TME scores) improved for 102/117 patients while OFF medication.

In this premarket application, existing clinical data was not leveraged to support approval of a pediatric patient population.

# **D. Financial Disclosure**

The Financial Disclosure by Clinical Investigators regulation (21 CFR 54) requires applicants who submit a marketing application to include certain information concerning the compensation to, and financial interests and arrangement of, any clinical

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investigator conducting clinical studies covered by the regulation. The pivotal clinical study for the Boston Scientific Vercise DBS System included investigators of which none were full-time or part-time employees of the sponsor and only one had disclosable financial interests/arrangements as defined in 21 CFR 54.2(a), (b), (c) and (f) and described below:

- Compensation to the investigator for conducting the study where the value could be influenced by the outcome of the study: none
- Significant payment of other sorts: one investigator
- Proprietary interest in the product tested held by the investigator: none
- Significant equity interest held by investigator in sponsor of covered study: none

The applicant has adequately disclosed the financial interest/arrangements with clinical investigators. The information provided does not raise any questions about the reliability of the data.

The pivotal clinical studies for Medtronic Activa Parkinson's Control Therapy under P960009/S007 included 18 investigational sites. The SSED does not provide any information with respect to Financial Disclosures since this information was not required to be placed in the SSED at the time of that PMA approval.

## **XI. PANEL MEETING RECOMMENDATION AND FDA'S POST-PANEL ACTION**

In accordance with the provisions of section 515(c)(3) of the act as amended by the Safe Medical Devices Act of 1990, this PMA was not referred to the Neurological Devices Panel, an FDA advisory committee, for review and recommendation because the information in the PMA substantially duplicates information previously reviewed by this panel.

## **XII. CONCLUSIONS DRAWN FROM PRECLINICAL AND CLINICAL STUDIES**

### **A. Conclusions Drawn from Nonclinical Studies**

The Vercise PC and Vercise Gevia DBS Systems were approved for stimulation of the STN in P150031/S001. The pre-clinical studies provided to support approval in P150031/S001 are directly applicable to this PMA because the only requested change is to the indications for use to include stimulation of the GPi, and this change would not affect the non-clinical testing.

### **B. Effectiveness Conclusions**

In this PMA Supplement, the sponsor provided adequate evidence of the sufficient similarity of the Vercise PC and Vercise Gevia DBS Systems with regard to its technological characteristics as described in Section IX(B). Therefore, FDA was able to apply Section 216 of the FDAMA and confirm that the evidence presented in the SSED for the Medtronic Activa Parkinson's Control Therapy approved under

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P960009/S007 in support of the reasonable assurance of its effectiveness is directly applicable towards establishing reasonable assurance of the effectiveness of the Vercise PC and Vercise Gevia DBS Systems for GPi stimulation. As detailed in the SSED for the Medtronic Activa Parkinson's Control Therapy, prospective open label studies of the Medtronic Activa Parkinson's Control Therapy demonstrated that 'On' time improved between pre-implant and 12 months by an average of 6.7 hours for the subset of GPi patients whose data were verified against medical records. Additionally, for the subset of patients whose data were verified against medical records, for the GPi and STN, symptoms of Parkinson's disease (UPDRS TME scores) improved for 56/117 patients while ON medication and symptoms of Parkinson's disease (UPDRS Total Motor Exam (TME) scores) improved for 102/117 patients while OFF medication.

### C. Safety Conclusions

Boston Scientific performed a multi-center, prospective, double-blind, randomized, controlled study (INTREPID Study) that was designed to evaluate the safety and effectiveness of the Vercise DBS System for bilateral stimulation of the STN as an adjunctive therapy for improving dyskinesia and other symptoms in adults with advanced, levodopa-responsive bilateral Parkinson's disease which is not adequately controlled with medication. This study was used to support approval of the Vercise DBS System under P150031. Additional details of this study is provided in the SSED for P150031 that is available on the CDRH website. The Vercise PC and Vercise Gevia DBS Systems were approved under P150031/S001 based on a similarity of technological characteristics to the Vercise DBS System. Although the data were used to support the safety of DBS at the STN, findings have applicability to the safety of stimulation at the GPi of similarity of the technological characteristics. Location of the stimulation is different, but stimulation related adverse effects can be resolved at either of the grey matter locations by adjustments to stimulation parameters.

The INTREPID safety data was based on a total of 292 consented (enrolled) subjects. Of these 292 subjects, 177 subjects received the Vercise System. In the INTREPID Study, a total of 788 adverse events in 143 subjects were reported at the time of the data snapshot. Of these, 74 events were reported as serious adverse events. Infection has been the most commonly reported serious adverse event associated with device-hardware/procedure (8 events, representing 2.7% of subjects). There were three events (each) of device-hardware/procedure-related serio…