HAL for Medical Use(Lower Limb type)

K201559 · Cyberdyne, Inc. · PHL · Oct 2, 2020 · Physical Medicine

Device Facts

• Record ID: K201559
• Device Name: HAL for Medical Use(Lower Limb type)
• Applicant: Cyberdyne, Inc.
• Product Code: PHL · Physical Medicine
• Decision Date: Oct 2, 2020
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 890.3480
• Device Class: Class 2
• Attributes: Therapeutic

Indications for Use

HAL for Medical Use (Lower Limb Type) orthotically fits to the lower limbs and trunk; HAL is a gait training device intended to temporarily help improve ambulation upon completion of the HAL gait training intervention. HAL must be used with a Body Weight Support system. HAL is not intended for sports or stair climbing. HAL gait training is intended to be used in conjunction with regular physiotherapy. The device is intended for individuals with: - spinal cord injury at levels C4 to L5 (ASIA C, ASIA D) and T11 to L5 (ASIA A with Zones of Partial Preservation, ASIA B); - post stroke paresis - paraplegia due to progressive neuromuscular diseases (spinal muscular atrophy, spinal and bulbar muscular atrophy, amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, distal muscular dystrophy, inclusion body myositis, congenital myopathy, muscular dystrophy) who exhibit sufficient residual motor and movement-related functions of the hip and knee to trigger and control HAL. In preparation for HAL gait training, the controller can be used while the exoskeleton is not donned to provide biofeedback training through the visualization of surface electromyography bioelectrical signals recorded. HAL is intended to be used inside medical facilities while under trained medical supervision in accordance with the user assessment and training certification program

Device Story

Battery-powered lower extremity exoskeleton; provides assistive torque at hip/knee joints for gait training. Inputs: surface electromyography (sEMG) signals from hip/knee muscles (CVC mode), postural cues, sensor shoe measurements. Operation: CVC mode uses proprietary signal processing to detect sEMG for torque assistance; CAC mode uses postural/shoe data for leg trajectories; CIC mode compensates for motor friction. Used in medical facilities under trained professional supervision; requires Body Weight Support (BWS) system. Output: assistive torque; biofeedback visualization of sEMG signals. Clinical impact: improves ambulation; maintains physical function in progressive neuromuscular disease. Benefits: temporary gait improvement; non-damaging to muscles (monitored via creatine kinase levels).

Clinical Evidence

Evidence includes literature reviews, clinical trials, and post-market surveillance. SCI: 6 effectiveness/8 safety studies (n=8-55) showing gait improvement. Stroke: 14 effectiveness/4 safety studies (n=8-53); comparative data shows significant 10MWT/6MWT improvements vs. conventional therapy. Progressive neuromuscular disease: 1 clinical trial (n=24) and post-market survey (n=207) showing maintained physical function and no muscle damage (decreased creatine kinase). Bench testing: durability (3M cycles), effective torque, and sensor accuracy verified.

Technological Characteristics

Battery-powered exoskeleton; 8 size variations; ~14 kg. Materials: mechanical frame, sensor shoes, cutaneous electrodes. Sensing: sEMG, postural sensors, plantar load sensors. Energy: Lithium-ion battery. Connectivity: Standalone. Sterilization: N/A. Software: Proprietary signal processing algorithm. Standards: AAMI/ANSI ES60601-1, IEC 60601-1-2, IEC 60601-1-6, IEC 62366, IEC 62133, IEC 62304.

Indications for Use

Indicated for individuals with spinal cord injury (C4-L5 ASIA C/D; T11-L5 ASIA A/B), post-stroke paresis, or paraplegia due to progressive neuromuscular diseases (e.g., ALS, SMA, muscular dystrophy) who possess sufficient residual hip/knee motor function to trigger/control the device. Contraindicated for patients with severe body deformations, skin conditions preventing electrode placement, severe spasticity (Ashworth 4), unstable spine/fractures, heterotopic ossification, significant contractures, psychiatric/cognitive impairments, pregnancy, or severe concurrent medical diseases (e.g., infections, heart/lung disease, pressure sores).

Regulatory Classification

Identification

A powered lower extremity exoskeleton is a prescription device that is composed of an external, powered, motorized orthosis that is placed over a person's paralyzed or weakened limbs for medical purposes.

Special Controls

In combination with the general controls of the FD&C Act, the Powered Exoskeleton is subject to the following special controls:

*Classification.* Class II (special controls). The special controls for this device are:(1) Elements of the device materials that may contact the patient must be demonstrated to be biocompatible. (2) Appropriate analysis/testing must validate electromagnetic compatibility/interference (EMC/EMI), electrical safety, thermal safety, mechanical safety, battery performance and safety, and wireless performance, if applicable. (3) Appropriate software verification, validation, and hazard analysis must be performed. (4) Design characteristics must ensure geometry and materials composition are consistent with intended use. (5) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. Performance testing must include: (i) Mechanical bench testing (including durability testing) to demonstrate that the device will withstand forces, conditions, and environments encountered during use; (ii) Simulated use testing ( *i.e.,* cyclic loading testing) to demonstrate performance of device commands and safeguard under worst case conditions and after durability testing;(iii) Verification and validation of manual override controls are necessary, if present; (iv) The accuracy of device features and safeguards; and (v) Device functionality in terms of flame retardant materials, liquid/particle ingress prevention, sensor and actuator performance, and motor performance. (6) Clinical testing must demonstrate a reasonable assurance of safe and effective use and capture any adverse events observed during clinical use when used under the proposed conditions of use, which must include considerations for: (i) Level of supervision necessary, and (ii) Environment of use ( *e.g.,* indoors and/or outdoors) including obstacles and terrain representative of the intended use environment.(7) A training program must be included with sufficient educational elements so that upon completion of training program, the clinician, user, and companion can: (i) Identify the safe environments for device use, (ii) Use all safety features of device, and (iii) Operate the device in simulated or actual use environments representative of indicated environments and use. (8) Labeling for the Physician and User must include the following: (i) Appropriate instructions, warning, cautions, limitations, and information related to the necessary safeguards of the device, including warning against activities and environments that may put the user at greater risk. (ii) Specific instructions and the clinical training needed for the safe use of the device, which includes: (A) Instructions on assembling the device in all available configurations; (B) Instructions on fitting the patient; (C) Instructions and explanations of all available programs and how to program the device; (D) Instructions and explanation of all controls, input, and outputs; (E) Instructions on all available modes or states of the device; (F) Instructions on all safety features of the device; and (G) Instructions for properly maintaining the device. (iii) Information on the patient population for which the device has been demonstrated to have a reasonable assurance of safety and effectiveness. (iv) Pertinent non-clinical testing information ( *e.g.,* EMC, battery longevity).(v) A detailed summary of the clinical testing including: (A) Adverse events encountered under use conditions, (B) Summary of study outcomes and endpoints, and (C) Information pertinent to use of the device including the conditions under which the device was studied ( *e.g.,* level of supervision or assistance, and environment of use (*e.g.,* indoors and/or outdoors) including obstacles and terrain).

Predicate Devices

• HAL for Medical Use (Lower Limb type) (K171909)

Submission Summary (Full Text)

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the FDA name on the right. The symbol on the left is a stylized image of a human figure, while the FDA name on the right is written in blue letters. The words "U.S. FOOD & DRUG ADMINISTRATION" are written in a clear, sans-serif font.

October 2, 2020

Cyberdyne Inc. Yohei Suzuki Head of Production Department 2-2-1 Gakuen-Minami Tsukuba. Ibaraki 305-0818 Japan

Re: K201559

Trade/Device Name: HAL for Medical Use (Lower Limb type) Regulation Number: 21 CFR 890.3480 Regulation Name: Powered Lower Extremity Exoskeleton Regulatory Class: Class II Product Code: PHL, HCC Dated: June 1, 2020 Received: June 10, 2020

Dear Yohei Suzuki:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and probibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part

{1}------------------------------------------------

801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance)and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Heather Dean, PhD Assistant Director, Acute Injury Devices DHT5B: Division of Neuromodulation and Physical Medicine Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

## Indications for Use

510(k) Number (if known) K201559

Device Name HAL for Medical Use (Lower Limb Type)

#### Indications for Use (Describe)

HAL for Medical Use (Lower Limb Type) orthotically fits to the lower limbs and trunk;

HAL is a gait training device intended to temporarily help improve ambulation upon completion of the HAL gait training intervention. HAL must be used with a Body Weight Support system. HAL is not intended for sports or stair climbing. HAL gait training is intended to be used in conjunction with regular physiotherapy.

The device is intended for individuals with:

- spinal cord injury at levels C4 to L5 (ASIA C, ASIA D) and T11 to L5 (ASIA A with Zones of Partial Preservation, ASIA B);

- post stroke paresis

- paraplegia due to progressive neuromuscular diseases (spinal muscular atrophy, spinal and bulbar muscular atrophy, amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, distal muscular dystrophy, inclusion body myositis, congenital myopathy, muscular dystrophy) who exhibit sufficient residual motor and movement-related functions of the hip and knee to trigger and control HAL

In preparation for HAL gait training, the controller can be used while the exoskeleton is not donned to provide biofeedback training through the visualization of surface electromyography bioelectrical signals recorded.

HAL is intended to be used inside medical facilities while under trained medical supervision in accordance with the user assessment and training certification program

Type of Use (Select one or both, as applicable)

| <div> <span style="font-size:16px">✖</span> Prescription Use (Part 21 CFR 801 Subpart D) </div> | <div> Over-The-Counter Use (21 CFR 801 Subpart C) </div> |
|----------------------------------------------------------------------------------------------------|-----------------------------------------------------------------|
|----------------------------------------------------------------------------------------------------|-----------------------------------------------------------------|

#### CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

#### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

# 510(k) Summary

510(k) Number: K201559

## 5.1 Applicant Information

| Date Prepared: | June 4, 2020 |
|------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------|
| Company Name and<br>Address: | CYBERDYNE Inc.<br>2-2-1, Gakuen-Minami,<br>Tsukuba, Ibaraki 305-0818 Japan |
| Contact Person: | Mr. Yohei Suzuki<br>Head of Production Department<br>Phone: [phone]<br>FAX: [phone]<br>Email: [e-mail] |

#### 5.2 Device Information

| Device Name: | HAL for Medical Use (Lower Limb Type) |
|----------------------------|---------------------------------------------------------------------------------|
| Common or Usual<br>Name: | Powered Exoskeleton |
| Classification Name: | Powered Lower Extremity Exoskeleton (primary)<br>Biofeedback Device (secondary) |
| Regulation Number: | 21 CFR 890.3480 (primary)<br>21 CFR 882.5050 (secondary) |
| Device Class: | II |
| Product Code: | PHL |
| Secondary Product<br>Code: | HCC |

#### 5.3 Legally Marketed Predicate Device

| 510(k) Number: | K171909 |
|--------------------|---------------------------------------|
| Primary Predicate | Primary |
| Applicant: | CYBERDYNE Inc. |
| Device Name: | HAL for Medical Use (Lower Limb Type) |
| Regulation Number: | 21 CFR 890.3480 |
| Product Code: | PHL, HCC |
| Device Class: | II |

## 5.4 Device Description

HAL for Medical Use (Lower Limb Type) is a battery powered lower extremity exoskeleton that provides assistive torque at the knee and hip joints for gait training. HAL is comprised of a controller, a main unit, and sensor shoes. The device comes in 8 size variations (4

{4}------------------------------------------------

different leg lengths and 2 different hip widths) for each of the 3 configuration types (doubleleg, right-leg, and left-leg) and weighs ~14 kg (30 lbs). The device uses legally marketed cutaneous electrodes (up to 18 electrodes) to record surface electromyography bioelectrical signals of the hip and knee extensor and flexor muscles when the device is used in Cybernic Voluntary Control (CVC) mode. This mode provides assistive torque at the corresponding ioint (e.g., hip or knee) using surface electromyography bioelectrical signals that are processed using a propriety signal processing algorithm. The propriety processing algorithm allows the device to detect surface electromyography bioelectrical signals to control the HAL device in CVC mode and provide visualization of the surface electromyography bioelectrical signals during biofeedback training. The assistive torque can be adjusted using three parameters: sensitivity level, torque turner, and balance turner. The device can also provide two additional modes: Cybernic Autonomous Control (CAC) mode and Cybernic Impedance Control (CIC) mode. CAC mode provides assistive torque leg trajectories based on postural cues and sensor shoe measurements. CIC mode provides torque to compensate for frictional resistance of the motor based on joint motion. CIC mode does not provide torque assistance for dictating joint trajectories. A trained medical professional (i.e., physician, physical therapist, etc.) can configure, operate, and monitor the device during gait training to make adjustments as needed.

Patients must exhibit sufficient residual motor and movement-related functions of the hip and knee to trigger and control HAL. The patient must be supported by a Body Weight Support (BWS) system before donning the device and during device use. The BWS must not be detached from the patient before doffing this device. HAL is not intended to provide sit-stand or stand-sit movements. HAL is capable of gait speeds up to approximately 2 km/hour on level ground. HAL is not intended for sports or stairclimbing.

In preparation to using HAL, the controller can be used while the exoskeleton is not donned to provide biofeedback training through the visualization of surface electromyography bioelectrical signals recorded.

HAL is intended to be used in conjunction with reqular physiotherapy. HAL is intended to be used inside a medical facility under the supervision of trained medical professionals who have successfully completed the HAL training program.

## 5.5 Indications for Use

HAL for Medical Use (Lower Limb Type) orthotically fits to the lower limbs and trunk;

HAL is a gait training device intended to temporarily help improve ambulation upon completion of the HAL gait training intervention. HAL must be used with a Body Weight Support system. HAL is not intended for sports or stair climbing. HAL gait training is intended to be used in conjunction with reqular physiotherapy.

The device is intended for individuals with:

- spinal cord injury at levels C4 to L5 (ASIA C, ASIA D) and T11 to L5 (ASIA A with Zones of Partial Preservation, ASIA B);

- post stroke paresis

- parapleqia due to progressive neuromuscular diseases (spinal muscular atrophy, spinal and bulbar muscular atrophy, amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease,

{5}------------------------------------------------

distal muscular dystrophy, inclusion body myositis, congenital myopathy, muscular dvstrophy)

who exhibit sufficient residual motor and movement-related functions of the hip and knee to trigger and control HAL.

In preparation for HAL gait training, the controller can be used while the exoskeleton is not donned to provide biofeedback training through the visualization of surface electromyography bioelectrical signals recorded.

HAL is intended to be used inside medical facilities while under trained medical supervision in accordance with the user assessment and training certification program.

## 5.6 Non-Clinical Performance Data

The subject devices demonstrate conformance with the following recognized standards:

- AAMI/ANSI ES60601-1:2005/(R)2012 and A1:2012 ●
- IEC 60601-1-2:2014
- IEC 60601-1-6:2010 and IEC62366:2014 ●
- IEC 62133:2012, IEC 60335-1:2010, IEC 60335-2-29:2010 and ANSI/UL 1012:2010 ●
- . IEC 62304:2015

The subject device underwent bench testing as part of required performance verification and validation activities. Results show that the subject device has met pre-defined design and performance acceptance criteria. Results of all non-clinical testing support the safety and effectiveness of the subject devices.

| Testing | Objective(s) and Study Design | |
|----------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Stopper Strength<br>Test | <Objective(s)><br>To evaluate the durability of the mechanical stopper of the actuator that<br>limits the maximum angle and verify that it endures the mechanical force<br>that can be applied by the patient | |
| | <Results><br>Conformance with acceptance criteria was maintained after 100 cycles. The<br>mechanical stopper is expected to endure the impact in the joints. | |
| Consecutive<br>Landing Test | <Objective(s)> | |
| | Test the durability of the mechanical and electrical systems of HAL against<br>repeated impacts with the ground that occur while walking. Confirm whether<br>missing parts, cracks/chips of the exterior, loosening of screws, abnormal<br>noises, looseness, operational malfunctions, and<br>loosening/detachment/deformation of the connectors do not occur after 5-<br>years worth (service life of HAL) of consecutive impacts and vibrations. | |
| | <Results> | |
| | | All 3 samples withstood 3,000,000 [cycles] of landing impact, and there<br>were no missing parts, cracks/chips of the exterior, loosening of screws,<br>abnormal noises, looseness, operational malfunctions, and<br>loosening/detachment/deformation of the connectors. The assumed<br>maximum steps of HAL is 1,000,000[cycles] so it is sufficiently durable. |
| | Effective Output<br>Test | <Objective(s)> |
| | | This test consists of two tests, each with different objectives below: |
| | | A. Effective torque test: To verify that the actuator meets specifications for<br>effective output torque by measuring the effective output torque to the input<br>(electrical current). |
| | | B. Maximum angle velocity test: To verify that the maximum angular<br>velocity, generated when maximum torque is output, is within the range of<br>that tolerable by the human knee joint. |
| | | <Results> |
| | | A. Effective torque output test: The output was verified to meet the<br>specification. It was also within the range required by risk management. |
| | | B. Maximum angular velocity test: The angular velocity was verified to be<br>within a range that the human body can tolerate. |
| Driving Parts<br>Performance Test | | <Objective> |
| | | To Measure the actual torque output against the torque output intended by<br>the control algorithm, and confirm that it meets the performance criteria. |
| | <Results> | |
| | | The test results show that the actual torque output compared to the torque<br>output intended by the control algorithm falls within the criteria range, and<br>the performance of the driving parts meets the expected results. |
| | Joint angle<br>measurement | <Objective> |
| | To test the accuracy of joint angle sensing. | |
| | <Results> | |
| | | Accuracy of joint angle measurement was verified to meet specification. |
| Body trunk<br>absolute angle<br>measurement | <Objective> | |
| | To test the accuracy of body trunk absolute angle sensing. | |
| | <Results> | |
| | The measurement results show that the body trunk absolute angle<br>measurement of the device can sufficiently detect the stable posture in the<br>forward/backward directions of the patient, thus ensuring the safety and<br>effectiveness of the device. | |
| | Plantar load<br>measurement | <Objective> |
| | To test the accuracy of plantar load measurement. | |
| | <Results> | |
| | The measurement results show that the plantar force measurement of the device can sufficiently detect the planting and lifting of the sole, to enable the device to determine what phase (swing/support) each leg is in, thus ensuring the safety and effectiveness of the device. | |
| Surface<br>Electromyography<br>Bioelectrical signal<br>measurment<br>performance | <Objective> | |
| | To test the accuracy of surface electromyography bioelectrical signal measurement performance. The tests included an assessment of input impedance, common-mode rejection ratio, and frequency characteristics. | |
| | <Results> | |
| | Accuracy for all measurements were verified to meet specifications. | |
| Ankle Durability<br>Test | <Objective> | |
| | Test the durability of the mechanical systems of the ankle parts against repeated impacts in a twisting direction, simulating impacts applied to the parts during a turning movement. Confirm whether missing parts, cracks/chips of the exterior, loosening of screws, abnormal noises, looseness do not occur after 5-years worth (service life of HAL) of consecutive impacts. | |
| | <Results> | |
| | All 3 samples withstood 300,000 [times] of impact, and there were no missing parts, cracks/chips of the exterior, loosening of screws, abnormal noises, looseness. The ankle part of the device is sufficiently durable. | |

{6}------------------------------------------------

{7}------------------------------------------------

## 5.7 Clinical Performance Data

Clinical performance data were collected for each of the disease groups through literature search and data held by the manufacturer.

<Group a: spinal cord injury>

6 items were assessed for effectiveness and 8 were assessed for safety. Results related to effectiveness of the treatment is summarized in the table below in the form of a pre-post comparison of gait function. Measurements were conducting without wearing HAL.

| FDA-ID | Title | Authors | n | 10MWT speed | | | 6MWT distance | | |
|--------|------------------------------|------------------|----|------------------------------------------------------------------------------------|--------------------|------------|---------------------|----------------------|------------|
| | | | | Pre | Post | Difference | Pre | Post | Difference |
| 11 | Voluntary driven exoskeleton | Aach et al. | 8 | $0.28 +- 0.28 m/s$ | $0.50 +- 0.34 m/s$ | $0.22 m/s$ | $70.1 +- 130 m$ | $163.3 +- 160.6 m$ | $93.2 m$ |
| 13 | Against the odds: what to | Grasmucke et al. | 55 | $70.45 +- 61.50 s$ | $35.22 +- 30.80 s$ | $35.23 s$ | $97.81 +- 95.80 m$ | $146.34 +- 118.13 m$ | $48.53 m$ |
| 17 | HAL exoskeleton training | Sczesny-Kais | 11 | $0.25 +- 0.05 m/s$ | $0.5 +- 0.07 m/s$ | $0.25 m/s$ | $86 +- 20.86 m$ | $149.73 +- 20.32 m$ | $63.73 m$ |
| 18 | Hybrid Assistive Limb Exos | Jansen et al. | 21 | $61.17 +- 44.27 s$ | $32.18 +- 25.53 s$ | $28.99 s$ | $90.81 +- 110.18 m$ | $149.76 +- 144.28 m$ | $58.95 m$ |
| 19 | Functional Outcome of Neu | Jansen et al. | 8 | $28.61 +- 6.9 s$ | $21.22 +- 6.6 s$ | $7.39 s$ | $126.75 +- 19.25 m$ | $149.5 +- 9.41 m$ | $22.75 m$ |
| | | | | $34.28 +- 18.2 s$ | $34.61 +- 17.3 s$ | $-0.33 s$ | $200 +- 117.42 m$ | $209.5 +- 123.5 m$ | $9.5 m$ |
| 110 | Reshaping of Gait Coordina | Puentes et al. | 12 | Only described as figure<br>Gains in 10MWT speed in all acute and chronic patients | | | - | - | - |

While most of these studies do not have a control, the study populations were mostly chronic SCI where it is widely accepted that spontaneous recovery no longer occurs. The subjects from these studies may be considered their own control, and any changes seen should be attributed to the treatment with the device. From these results we conclude that treatment with the device results in meaningful improvements for SCI patients in terms of walking ability.

#### <Group b: stroke>

14 items were assessed for effectiveness and 4 were assessed for safety. Results related to the effectiveness of the treatment is summarized in the table below in the form of a pre-post comparison of gait function. Measurements were conducting without wearing HAL. The

{8}------------------------------------------------

tables are categorized by post stroke stages of the patient in order to explain the influence of spontaneous recovery.

Overall, the findings from these studies suggest that HAL therapy is an effective method for improving ambulatory function in stroke.

| | FDA-ID Title | Authors | n | 10MWT speed | | | | MCID | 6MWT distance | | | | MCID |
|-----|------------------------------|---------------|----|------------------|------------------|------------|----------|-------------|---------------|------|------------|---------|---------------------|
| | | | | Pre | Post | Difference | P-value | | Pre | Post | Difference | P-value | |
| | | | | 0.41 +- 0.26 m/s | 0.45 +- 0.24 m/s | 0.04 m/s | <0.05 | | - | - | - | - | |
| | Pilot study of locomotion in | Kawamoto et | 16 | 0.24 +- 0.16 m/s | 0.30 +- 0.19 m/s | 0.06 m/s | <0.05 | No MCID | - | - | - | - | Tang et al.<br>2012 |
| | | | | 0.60 +- 0.21 m/s | 0.60 +- 0.19 m/s | 0.00 m/s | not sig. | for chronic | - | - | - | - | |
| 115 | Feasibility and efficacy of | Yoshimoto et | 18 | 0.39 +- 0.18 m/s | 0.60 +- 0.25 m/s | 0.21 m/s | <0.001 | | - | - | - | - | |
| | | | | 0.44 +- 0.16 m/s | 0.42 +- 0.46 m/s | -0.02 m/s | not sig. | stage | - | - | - | - | 34.4m |
| 119 | Spatiotemporal gait charad | Tanaka et al. | 11 | 0.52 +- 0.32 m/s | 0.66 +- 0.42 m/s | 0.14 m/s | <0.05 | | - | - | - | - | |

[Chronic stage: 6 months post stroke or longer]

| | | | | 10MWT speed | | | | 6MWT distance (*2MWT distance) | | | | | |
|--------|------------------------------|---------------|----|------------------------------------------------------------|--------------------------------------|-------------------------------------|--------------------------------------|--------------------------------|-----------------------------------------|-----------------------------------------|-----------------------------------------|--------------------------------------|--------------------|
| FDA-ID | Title | Authors | n | Pre | Post | Follow up 3mo. | P-value (Pre-F/U) | MCID | Pre | Post | Follow up 3mo. | P-value (Pre-F/U) | MCID |
| I20 | A follow-up study of the eff | Tanaka et al. | 9 | 0.55 +- 0.30 m/s | 0.72 +- 0.42 m/s | 0.67 +- 0.36 m/s | <0.01 | No MCID | *62.7 +- 36.1 m | *79.8 +- 46.6 m | *72.8 +- 38.2 m | 0.02 | |
| I18 | A Randomized and Control | Sczesny-Kais | 18 | HAL -> CPT 0.49 +- 0.21 m/s<br>CPT -> HAL 0.64 +- 0.29 m/s | 0.56 +- 0.23 m/s<br>0.80 +- 0.26 m/s | 0.60 +- 0.22 m/s<br>0.73 +- 0.3 m/s | not sig. comparing<br>the two groups | for chronic stage | 169.33 +- 81.87 m<br>242.50 +- 132.15 m | 190.38 +- 87.98 m<br>243.06 +- 102.62 m | 203.25 +- 86.53 m<br>236.78 +- 115.03 m | not sig. comparing<br>the two groups | Tang 2012<br>34.4m |

Three studies (14, 119, 120) do not have a legitimate control, but because the study populations are chronic, the subjects were not expected to make any gains from natural recovery based on historical prognoses, making them their own control. The other two studies (115, 118) included a control group, with 115 having a parallel design and 118 having a cross-over design.

Although the overall results from the cross-over study (118) did not show significant differences between the HAL group and control group, when comparing both groups in the first treatment period as in a parallel design, significant treatment effect was seen only in the HAL group. All the other studies show additional improvement effects with HAL treatment.

| | | | | | | 10MWT speed (*6 minute walking test speed) | | | | | 6MWT distance (*2MWT distance) | | | | |
|--------|--------------------------------|-----------------|----|-----------|--|--------------------------------------------|-------------------------|--------------|----------|---------------|--------------------------------|---------------------|------------|----------|---------------|
| FDA-ID | Title | Authors | n | | | Pre | Post | Difference | P-value | MCID | Pre | Post | Difference | P-value | MCID |
| I5 | Gait training early after stro | Nilsson et al. | 8 | | | 111.5 s | 30 s | 81.5 s | N/A | Perera et al. | | | | | |
| I12 | Locomotion improvement | Watanabe et al. | 22 | HAL group | | 0.61 $\pm$ 0.43 m/s | 0.85 $\pm$ 0.43 m/s | 0.24 m/s | <0.05 | 2006 | 97.7 $\pm$ 107.6 m | 156.7 $\pm$ 137.9 m | 59.0 m | <0.05 | |
| | | | | CPT group | | 0.49 $\pm$ 0.55 m/s | 0.63 $\pm$ 0.50 m/s | 0.14 m/s | not sig. | | 111.3 $\pm$ 138.2 m | 134.5 $\pm$ 132.1 m | 23.2 m | not sig. | |
| | | | | Brs I | | - | - | - | - | 0.14m/s | | | | | Perera et al. |
| | | | | Brs II | | - | - | - | - | | | | | | 2006 |
| I14 | Effectiveness of Acute Pha | Fukuda et al. | 53 | Brs III | | 0.2 $\pm$ 0.1 m/s | 0.4 $\pm$ 0.1 m/s | 0.2 m/s | not sig. | | | | | | |
| | | | | Brs IV | | 0.4 $\pm$ 0.2 m/s | 0.4 $\pm$ 0.2 m/s | 0.0 m/s | not sig. | | | | | | 50m |
| | | | | Brs V | | 0.7 $\pm$ 0.3 m/s | 0.8 $\pm$ 0.4 m/s | 0.1 m/s | <0.05 | Tilson et al. | | | | | |
| | | | | Brs VI | | 0.5 $\pm$ 0.3 m/s | 0.9 $\pm$ 0.3 m/s | 0.4 m/s | <0.05 | 2010 | | | | | |
| I16 | Lateral Symmetry of Syner | Tan et al. | 8 | | | 14.36 $\pm$ 12 m/min | 31.47 $\pm$ 12.11 m/min | 17.11 m/min | <0.05 | | | | | | |
| I17 | Reshaping of Bilateral Gait | Puentes et al. | 11 | | | *16.45 $\pm$ 10.1 m/min | *31.4 $\pm$ 13.2 m/min | *14.95 m/min | <0.01 | 0.16m/s | 97.93 $\pm$ 66.1 | 217 $\pm$ 77.9 | 119.07 m | <0.01 | |

[Acute/subacute stages (during recovery)]

| | | | 10MWT speed | | | | 6MWT distance (*2MWT distance) | | | | | | |
|-----|-------------------------------|-----------------|-------------|------------------------------------------------------------------------------------|------------------------------------------------------------------------------------|--------------------------------------------------------------------|--------------------------------------|---------------------------|-----------------------------------------|------------------------------------------|------------------------------------------|--------------------------------------|-------------|
| | Title | Authors | n | Pre | Post | Follow up 12wk | P-value | MCID | Pre | Post | Follow up 12wk. | P-value (Pre-F/U) | MCID |
| I11 | Effects of gait training usin | Watanabe et al. | 24 | HAL group<br>$0.56 +- 0.43$ m/s<br>CPT group<br>$0.45 +- 0.53$ m/s | HAL group<br>$0.85 +- 0.43$ m/s<br>CPT group<br>$0.61 +- 0.47$ m/s | HAL group<br>$0.84 +- 0.51$ m/s<br>CPT group<br>$0.57 +- 0.41$ m/s | not sig. comparing<br>the two groups | Perera 2006<br>$0.14$ m/s | $92.4 +- 104.2$ m<br>$106.9 +- 132.6$ m | $156.7 +- 137.8$ m<br>$140.8 +- 127.8$ m | $166.7 +- 143.9$ m<br>$131.0 +- 117.6$ m | not sig. comparing<br>the two groups | Perera 2006 |
| I21 | Acute stroke rehabilitation | Yokota et al. | 37 | HAL group<br>FMA, FIM and FAC data only<br>CPT group<br>FMA, FIM and FAC data only | HAL group<br>FMA, FIM and FAC data only<br>CPT group<br>FMA, FIM and FAC data only | | | Tilson 2010<br>$0.16$ m/s | FMA, FIM and FAC data only | FMA, FIM and FAC data only | | | 50m |

The literature on the acute/subacute population also can be grouped by studies that have a control group or not. Four studies (15, 114, 116, 117) did not have a control group, and though ambulatory function trended upward, these studies are highly limited by the fact that Stroke patients are known to make significant gains naturally in the acute/subacute phase of recovery.

Three studies (11, 112, 121) had a control and although neither the 10MWT nor 6MWT were measured in one study (121), the findings from the other two studies (11, I12) show significant improvements in the HAL group that were not seen in the control group.

{9}------------------------------------------------

[End of recovery stage (iust after improvement ceases)]

| FDA-ID | Title | Authors | n | 10MWT speed (*6 minute walking test speed) | | | | 6MWT distance (*2MWT distance) | | | | | |
|--------|------------------------------|------------------|----|--------------------------------------------|------------------------|-----------------------|-----------------------------------|--------------------------------|----------------------|-----------------------|---------------------|--------------------------------------|---------------------------|
| | | | | Pre | Post | Difference | P-value | MCID | Pre | Post | Difference | P-value | MCID |
| I6 | Gait training with Hybrid As | Yoshikawa et al. | 16 | HAL group<br>$49.8 \pm 20.1$ m/min | $61.4 \pm 26.6$ m/min | $11.6 \pm 10.6$ m/min | <0.05 comparing<br>the two groups | Perera et al. 2006<br>0.14m/s | * $78.9 \pm 33.3$ m | * $100.1 \pm 40.6$ m | * $21.1 \pm 12.4$ m | not sig. comparing<br>the two groups | Perera et al. 2006<br>50m |
| | | | | CPT group<br>$47.9 \pm 24.9$ m/min | $50.1 \pm 25.0$ m/min | $2.2 \pm 4.1$ m/min | | | * $69.7 \pm 33.9$ m | * $80.1 \pm 38.3$ m | * $10.4 \pm 8.9$ m | | |
| I13 | Gait training of subacute st | Mizukami et al. | 8 | $49.8 \pm 20.10$ m/min | $61.4 \pm 26.64$ m/min | $11.6$ m/min | <0.05 | Tilson et al. 2010<br>0.16m/s | * $78.9 \pm 33.26$ m | * $100.1 \pm 40.58$ m | * $22.2$ m | <0.01 | |

Recognizing the challenges of ruling out natural recovery effects, two studies (16 and 113) approached the treatment timing differently. The authors decided to apply HAL therapy only after the patients stopped showing improvements in walking function from regular physical therapy alone. This approach essentially makes these subjects similar to chronic stroke patients. The 16 study is an addendum to the 113 study, adding a non-randomized control group for comparison.

An ANCOVA analysis with group as a factor and baseline as a covariate showed a significant difference between the HAL group and control group for the 10MWT speed. Although the difference was not statistically significant for the 2MWT distance, patients in the HAL group showed greater improvement.

<Group c: progressive neuromuscular disease (see IFU for specific disease names)> 1 item of literature was assessed for both effectiveness and safety. Results from a clinical trial and post market survey were also assessed for both effectiveness and safety.

Literature for this group is limited due to the rare nature of the diseases and only one published study was assessed. 133 is a case report of 3 patients with Limb Girdle Muscular Dystrophy. No numerical results were reported, but the figures indicate that the 10MWT speed, Timed Up and Go test, and 6MWT distance showed an improvement in all subjects at the end of the 24 sessions of HAL therapy. The improvements in 10MWT speed and Timed Up and Go test remained at the 6 week follow up as well, though the 6MWT distance did not.

Since the literature is limited, performance needs to be further evaluated for this group using data qenerated or held by the manufacturer.

An investigator-initiated randomized controlled crossover clinical study approved by the Ministry of Health. Labour and Welfare of Japan was conducted for this patient population. and the results were used to gain medical device approval in Japan. The study, ID'd as I22, compared HAL therapy to a conventional gait training program as the control in an AB/BA crossover protocol, where each group received 9 sessions of each treatment in 4 weeks separated by a 1 week washout period. A total of 24 subjects completed the protocol, and inclusion criteria was patients who have ambulatory dysfunction due to one of the 8 rare progressive neuromuscular disorders for this group c.

For the primary endpoint, the 2MWT, the treatment effect was -10.066±11.062 (mean ± SD, hereinafter the same) (P=0.0369), which confirmed the therapeutic efficacy of HAL.

Furthermore, after the device's approval in Japan, data from Post-Market Surveillance have been collected over four years. Though certain aspects of control over adherence to the protocol used by 123 had to be ceded due to the nature of real world data, patients received 9 sessions of HAL therapy for each cycle, and the data was organized accordingly. As of November 2019 a total of 207 patients have participated in the PMS. Results support previous findings from the clinical trial that the device can maintain or even improve physical functions of patients with progressive neuromuscular disease. Overall, there were three main findings related to effectiveness and safety:

{10}------------------------------------------------

1) Participants showed improvement in gait related outcome measures comparing pre-post intervention of the first cycle of treatment (9 sessions). The results are in line with the results obtained in the clinical trial, which the design of the survey was based on.

2) Even after 1.5 years from the measurement of baseline, with intermittent treatment cycles participants showed about +20% difference from the baseline function, despite the progressive nature of their disease.

3) Blood creatine kinase data was collected from a total of 100 participants and results show a decreasing trend when comparing pre-post HAL treatment measurements. The lack of rise in CK levels suggests that HAL treatment does not damage the muscles through overuse.

## 5.8 Comparisons

## 5.8.1 Comparison of Intended Use/Indications for Use

| Indications for Use | |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Subject Device | Predicate Device |
| HAL for Medical Use (Lower Limb Type) | HAL for Medical Use (Lower Limb Type)<br>(K171909) |
| HAL for Medical Use (Lower Limb Type)<br>orthotically fits to the lower limbs and trunk;<br>HAL is a gait training device intended to<br>temporarily help improve ambulation upon<br>completion of the HAL gait training<br>intervention. HAL must be used with a Body<br>Weight Support system. HAL is not intended<br>for sports or stair climbing. HAL gait training<br>is intended to be used in conjunction with<br>regular physiotherapy. | HAL for Medical Use (Lower Limb Type)<br>orthotically fits to the lower limbs and trunk;<br>the device is intended for individuals with<br>spinal cord injury at levels C4 to L5 (ASIA C,<br>ASIA D) and T11 to L5 (ASIA A with Zones of<br>Partial Preservation, ASIA B), who exhibit<br>sufficient residual motor and movement-<br>related functions of the hip and knee to<br>trigger and control HAL. |
| The device is intended for individuals with:<br>- spinal cord injury at levels C4 to L5 (ASIA<br>C, ASIA D) and T11 to L5 (ASIA A with<br>Zones of Partial Preservation, ASIA B);<br>- post stroke paresis<br>- paraplegia due to progressive<br>neuromuscular diseases (spinal muscular<br>atrophy, spinal and bulbar muscular<br>atrophy, amyotrophic lateral sclerosis,<br>Charcot-Marie-Tooth disease, distal<br>muscular dystrophy, inclusion body<br>myositis, congenital myopathy, muscular<br>dystrophy)<br>who exhibit sufficient residual motor and<br>movement-related functions of the hip and<br>knee to trigger and control HAL. | HAL is a gait training device intended to<br>temporarily help improve ambulation upon<br>completion of the HAL gait training<br>intervention. HAL must be used with a Body<br>Weight Support system. HAL is not intended<br>for sports or stair climbing. HAL gait training<br>is intended to be used in conjunction with<br>regular physiotherapy.<br>In preparation for HAL gait training, the<br>controller can be used while the exoskeleton<br>is not donned to provide biofeedback training<br>through the visualization of surface<br>electromyography bioelectrical signals<br>recorded. |
| In preparation for HAL gait training, the<br>controller can be used while the exoskeleton<br>is not donned to provide biofeedback training…