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 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 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.

AI/ML Overview

The provided document is a 510(k) Summary for the HAL for Medical Use (Lower Limb Type) device. It describes the device, its intended use, and substantial equivalence to a predicate device (K171909). The document focuses on demonstrating safety and effectiveness, particularly for new patient populations.

It's important to note that this document is an FDA 510(k) summary, which typically presents summarized findings rather than a detailed breakdown of all study methodologies. Therefore, some specific details for each point requested might not be explicitly stated or might require inference from the provided text.

Here's an analysis of the provided information against your requested points:

Acceptance Criteria and Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets for each performance metric in a single table. Instead, the document demonstrates meeting acceptance criteria through compliance with recognized standards, successful bench testing, and consistent or improved clinical outcomes compared to baseline or control groups across various studies. The "results" sections for non-clinical and clinical data effectively serve as proof of meeting implicit or explicit acceptance criteria related to safety, functionality, and efficacy.

Table of Acceptance Criteria and Reported Device Performance:

Category	Acceptance Criteria (Implicit/Explicit)	Reported Device Performance/Results
Non-Clinical Performance
Safety Standards Compliance	Conformance with AAMI/ANSI ES60601-1, IEC 60601-1-2, IEC 60601-1-6, IEC 62366, IEC 62133, IEC 60335-1, IEC 60335-2-29, ANSI/UL 1012, IEC 62304.	"Subject devices demonstrate conformance with the following recognized standards" (listed above). "Results of all non-clinical testing support the safety and effectiveness of the subject devices."
Stopper Strength Test (Durability)	Mechanical stopper endures mechanical force applied by patient and maintains conformance after 100 cycles.	Conformance was maintained after 100 cycles. "The mechanical stopper is expected to endure the impact in the joints."
Consecutive Landing Test (Durability)	HAL mechanical/electrical systems withstand repeated impacts for 5-years worth of service life (1,000,000 cycles) without missing parts, cracks, loosening, abnormal noises, etc.	All 3 samples withstood 3,000,000 cycles, with no issues. "it is sufficiently durable."
Effective Output Test (Torque/Velocity)	Actuator meets specifications for effective output torque and provides maximum angular velocity within human knee joint tolerance.	Output verified to meet specification and risk management requirements. Angular velocity verified within human tolerance.
Driving Parts Performance Test	Actual torque output falls within performance criteria range compared to control algorithm's intended output.	Test results show actual torque output falls within criteria range, meeting expected performance.
Joint Angle Measurement (Accuracy)	Accuracy of joint angle sensing meets specification.	"Accuracy of joint angle measurement was verified to meet specification."
Body Trunk Absolute Angle Measurement (Accuracy)	Accuracy of body trunk absolute angle sensing allows sufficient detection of stable posture for safety and effectiveness.	Measurement results "can sufficiently detect the stable posture... thus ensuring the safety and effectiveness."
Plantar Load Measurement (Accuracy)	Accuracy of plantar load measurement allows sufficient detection of planting/lifting of sole to determine leg phase for safety and effectiveness.	Measurement results "can sufficiently detect the planting and lifting of the sole... thus ensuring the safety and effectiveness."
Surface Electromyography Bioelectrical Signal Measurement (Accuracy)	Accuracy of sEMG bioelectrical signal measurement performance meets specifications (input impedance, CMRR, frequency characteristics).	"Accuracy for all measurements were verified to meet specifications."
Ankle Durability Test	Ankle parts withstand repeated twisting impacts for 5-years worth of service life (implied ~300,000 impacts for turning movements) without missing parts, cracks, loosening, abnormal noises, etc.	All 3 samples withstood 300,000 impacts, with no issues. "The ankle part of the device is sufficiently durable."
Clinical Performance (Effectiveness)
SCI - Gait Improvement (10MWT speed)	Significant improvement in 10MWT speed. (e.g., from ~0.25-0.28 m/s pre to ~0.50 m/s post)	Reported differences range from +0.22 m/s to +0.25 m/s, or time improvements of 28.99s to 35.23s (faster). "meaningful improvements for SCI patients in terms of walking ability."
SCI - Gait Improvement (6MWT distance)	Significant improvement in 6MWT distance. (e.g., from ~70-90m pre to ~140-160m post)	Reported differences range from +22.75m to +93.2m. "meaningful improvements for SCI patients in terms of walking ability."
Stroke - Gait Improvement (10MWT speed)	Overall improvement in 10MWT speed, especially in control-inclusive studies or where natural recovery is accounted for. MCID (Minimum Clinically Important Difference) as a benchmark.	Chronic stage: Reported differences up to +0.21 m/s (p<0.001). Acute/Subacute: Differences up to +0.4m/s; "significant improvements in the HAL group that were not seen in the control group." "HAL therapy is an effective method for improving ambulatory function in stroke."
Stroke - Gait Improvement (6MWT distance)	Overall improvement in 6MWT distance. MCID as benchmark.	Acute/Subacute: Differences up to +119.07m (p<0.01). "significant improvements in the HAL group that were not seen in the control group."
Progressive Neuromuscular Diseases - Gait Improvement	Temporary improvement or maintenance of physical function despite progressive nature of disease (2MWT distance, 10MWT speed).	2MWT: treatment effect -10.066±11.062 (P=0.0369); "confirmed therapeutic efficacy." PMS data: ~+20% difference from baseline after 1.5 years. "Results support previous findings from the clinical trial that the device can maintain or even improve physical functions..."
Clinical Performance (Safety)	No Serious Adverse Events (SAEs) or minor adverse events (AEs) typical of the disease, and no damage to muscles.	SCI: "no SAEs reported, and all adverse events were minor incidents." Stroke: "no adverse events typical of the disease. No SAEs are reported." Progressive NM: "No device caused SAEs are reported." CK levels showed a "decreasing trend" suggesting "HAL treatment does not damage the muscles through overuse."

Study Details:

This device is a gait training device (exoskeleton), not an AI/imaging device, so many of the requested points related to AI model evaluation, ground truth establishment by experts for image data, MRMC studies, or training/test set sample sizes for an AI algorithm are not directly applicable in the typical sense for this device. The clinical "studies" referred to are more clinical trials or observational studies on human subjects, to demonstrate the effectiveness of the physical device in improving ambulation.

However, I will extract relevant information based on the typical interpretation for evaluating a medical device's performance, applying it to the context of a physical intervention device.

A table of acceptance criteria and the reported device performance: refer to the table above.
Sample sizes used for the test set and the data provenance:
- Spinal Cord Injury (SCI) Group (Effectiveness):
  - Sample Sizes: Studies varied from n=8 to n=55. (I-6 studies were assessed for effectiveness). Specific study IDs and their 'n' values:
    - FDA-ID 11 (Aach et al.): n=8
    - FDA-ID 13 (Grasmucke et al.): n=55
    - FDA-ID 17 (Sczesny-Kais): n=11
    - FDA-ID 18 (Jansen et al.): n=21
    - FDA-ID 19 (Jansen et al.): n=8
    - FDA-ID 110 (Puentes et al.): n=12
  - Data Provenance: Not explicitly stated for each study, but the document mentions a "literature search and data held by the manufacturer." The studies are generally chronic SCI patients where spontaneous recovery is not expected, implying these are retrospective analyses of published literature or manufacturer-held data, likely from various international sources (given author names like Aach, Grasmucke, Sczesny-Kais, Jansen, Puentes suggest European/Japanese origins).
- Stroke Group (Effectiveness):
  - Sample Sizes: Studies varied from n=8 to n=53. (I-14 studies were assessed for effectiveness, categorized by post-stroke stages). Specific study IDs and their 'n' values:
    - I9 (Kawamoto et): n=16 (appears to be a pilot study)
    - I15 (Yoshimoto et): n=18 (for chronic stage)
    - I19 (Tanaka et al.): n=11 (for chronic stage)
    - I20 (Tanaka et al.): n=9 (Chronic, follow-up)
    - I18 (Sczesny-Kais): n=18 (Chronic, crossover RCT)
    - I5 (Nilsson et al.): n=8 (Acute/subacute)
    - I12 (Watanabe et al.): n=22 (Acute/subacute, control group CPT)
    - I14 (Fukuda et al.): n=53 (Acute/subacute)
    - I16 (Tan et al.): n=8 (Acute/subacute)
    - I17 (Puentes et al.): n=11 (Acute/subacute)
    - I11 (Watanabe et al.): n=24 (Acute/subacute, control group CPT)
    - I21 (Yokota et al.): n=37 (Acute stroke rehabilitation)
    - I6 (Yoshikawa et al.): n=16 (End of recovery, comparative study)
    - I13 (Mizukami et al.): n=8 (End of recovery)
  - Data Provenance: Same as SCI group, "literature search and data held by the manufacturer." Given the authors and titles, these are likely retrospective analyses of published literature or manufacturer-held data, likely from various international sources (e.g., Kawamoto, Yoshimoto, Tanaka from Japan; Sczesny-Kais from Europe). One study (I22) and Post-Market Surveillance (PMS) data are specifically mentioned as being from Japan.
- Progressive Neuromuscular Diseases Group (Effectiveness):
  - Sample Sizes:
    - Literature: 1 case report (I33) with n=3 patients.
    - Clinical Trial: I22, n=24 subjects (investigator-initiated randomized controlled crossover clinical study).
    - Post-Market Surveillance (PMS): n=207 patients (as of November 2019).
  - Data Provenance:
    - Literature: "one published study was assessed."
    - Clinical Trial (I22): Prospective, conducted in Japan, approved by the Ministry of Health, Labour and Welfare of Japan.
    - Post-Market Surveillance: Prospective/Real-World Data, collected over four years in Japan after device approval.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This question is generally for AI/imaging data. For a physical device, "ground truth" is measured by clinical outcomes (e.g., walking speed, distance).
- The "ground truth" for the clinical performance (gait function) was established through objective functional tests (e.g., 10MWT - 10-meter walk test, 6MWT - 6-minute walk test, 2MWT - 2-minute walk test), performed without the HAL device. These are standard, quantifiable, and objectively measured clinical endpoints.
- The "experts" involved would be the trained medical professionals (physicians, physical therapists, etc.) who conducted these assessments as part of the clinical studies. Their specific number or qualifications beyond being "medical professionals" are not detailed in this summary, but it's implied they adhere to clinical trial standards.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- This is typically for image interpretation by multiple readers in diagnostic studies. For this device, the "test set" is patient cohorts undergoing a physical intervention, and outcomes are objective measurements.
- Not Applicable in the sense of radiological adjudication. The outcome measures are performance-based and objectively quantifiable.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, an MRMC study was not done. This type of study relates to AI assistance for human readers (e.g., radiologists).
- The document presents clinical studies comparing HAL intervention with baseline (pre-post) or with conventional physical therapy (control group). These are human subjects assisted by the physical device performing a task (walking), not human readers assisted by AI in interpreting data.
- Effect Size (where applicable for human patients with device assistance vs. without):
  - SCI (10MWT Speed): Improvements ranged from +0.22 m/s to +0.25 m/s. For time-based measures, improvements were around 35.23s faster (e.g., 70.45s to 35.22s).
  - SCI (6MWT Distance): Improvements ranged from +22.75m to +93.2m.
  - Stroke (10MWT Speed - Chronic): Improvements up to +0.21 m/s.
  - Stroke (10MWT Speed - Acute/Subacute - HAL vs. CPT): The comparative study in the end of recovery stage shows that patients initially treated with HAL reached 61.4 ± 26.6 m/min vs. 50.1 ± 25.0 m/min for CPT, with a significant difference (p<0.05). Another study (I12) showed HAL group 10MWT speed improving by +0.24 m/s (from 0.61 to 0.85 m/s) with statistical significance (p<0.05), while the CPT group's improvement was not significant. The summary states: "significant improvements in the HAL group that were not seen in the control group."
  - Progressive Neuromuscular Diseases (2MWT Distance - Clinical Trial): Treatment effect was -10.066 ± 11.062 for 2MWT in the crossover study (P=0.0369 for the difference, implying HAL improved performance relative to control).
  - Progressive Neuromuscular Diseases (PMS Data): Participants showed about +20% difference from baseline function after 1.5 years despite the progressive nature of their disease.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Not Applicable in the AI sense. This is a physical device that functions with a human in the loop (the patient wearing it, supervised by medical professionals).
- The "algorithm" mentioned (propriety signal processing algorithm for sEMG) is part of the device's control system, not a standalone diagnostic AI. Its performance is implicitly validated through the overall device's successful operation in non-clinical tests (e.g., torque output, joint angle, sEMG measurement accuracy) and clinical outcomes.
The type of ground truth used (expert concensus, pathology, outcomes data, etc.):
- For clinical effectiveness: Objective Outcomes Data from standardized functional tests (10MWT speed/time, 6MWT distance, 2MWT distance, TUG test) performed by patients without the device. These are widely accepted and quantifiable measures of ambulation.
- For clinical safety: Reported Adverse Events (AEs and SAEs) collection (patient reports, clinician observations).
- For non-clinical performance: Bench test measurements against predefined engineering specifications and standards.
The sample size for the training set:
- This refers to the dataset used to train an AI model. For this physical device, there isn't a "training set" in this sense for a learned AI algorithm that generates the primary output being evaluated.
- However, if we broadly consider "training" as the development and validation data, that would encompass results from various engineering tests, and potentially earlier developmental clinical work that informed the device design and control algorithms. The document does not provide a specific "training set" sample size for the device's functional logic, as it's not a machine learning model in the typical sense presented for FDA clearance. The control algorithms are described as "proprietary signal processing algorithm".
How the ground truth for the training set was established:
- Not applicable in the context of an AI training set.
- The device's control logic (e.g., detecting sEMG to trigger movement) is based on fundamental biomechanical principles and signal processing, validated through the non-clinical tests mentioned (e.g., accuracy of sEMG measurement, joint angle measurement). The "ground truth" for calibrating these systems would involve physical measurements, engineering specifications, and physiological data.

Summary

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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

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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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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

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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;

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

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)

✖ Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) Summary

510(k) Number: K201559

5.1 Applicant Information

Date Prepared:	June 4, 2020
Company Name andAddress:	CYBERDYNE Inc.2-2-1, Gakuen-Minami,Tsukuba, Ibaraki 305-0818 Japan
Contact Person:	Mr. Yohei SuzukiHead of Production DepartmentPhone: +81-29-869-8453FAX: +81-29-869-8443Email: suzuki_yohei@cyberdyne.jp

5.2 Device Information

Device Name:	HAL for Medical Use (Lower Limb Type)
Common or UsualName:	Powered Exoskeleton
Classification Name:	Powered Lower Extremity Exoskeleton (primary)Biofeedback Device (secondary)
Regulation Number:	21 CFR 890.3480 (primary)21 CFR 882.5050 (secondary)
Device Class:	II
Product Code:	PHL
Secondary ProductCode:	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

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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;

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,

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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.

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 StrengthTest	<Objective(s)>To evaluate the durability of the mechanical stopper of the actuator thatlimits the maximum angle and verify that it endures the mechanical forcethat can be applied by the patient
	Conformance with acceptance criteria was maintained after 100 cycles. Themechanical stopper is expected to endure the impact in the joints.
ConsecutiveLanding Test	<Objective(s)>
	Test the durability of the mechanical and electrical systems of HAL againstrepeated impacts with the ground that occur while walking. Confirm whethermissing parts, cracks/chips of the exterior, loosening of screws, abnormalnoises, looseness, operational malfunctions, andloosening/detachment/deformation of the connectors do not occur after 5-years worth (service life of HAL) of consecutive impacts and vibrations.

		All 3 samples withstood 3,000,000 [cycles] of landing impact, and therewere no missing parts, cracks/chips of the exterior, loosening of screws,abnormal noises, looseness, operational malfunctions, andloosening/detachment/deformation of the connectors. The assumedmaximum steps of HAL is 1,000,000[cycles] so it is sufficiently durable.
	Effective OutputTest	<Objective(s)>
		This test consists of two tests, each with different objectives below:
		A. Effective torque test: To verify that the actuator meets specifications foreffective output torque by measuring the effective output torque to the input(electrical current).
		B. Maximum angle velocity test: To verify that the maximum angularvelocity, generated when maximum torque is output, is within the range ofthat tolerable by the human knee joint.

		A. Effective torque output test: The output was verified to meet thespecification. It was also within the range required by risk management.
		B. Maximum angular velocity test: The angular velocity was verified to bewithin a range that the human body can tolerate.
Driving PartsPerformance Test
		To Measure the actual torque output against the torque output intended bythe control algorithm, and confirm that it meets the performance criteria.

		The test results show that the actual torque output compared to the torqueoutput intended by the control algorithm falls within the criteria range, andthe performance of the driving parts meets the expected results.
	Joint anglemeasurement
	To test the accuracy of joint angle sensing.

		Accuracy of joint angle measurement was verified to meet specification.
Body trunkabsolute anglemeasurement
	To test the accuracy of body trunk absolute angle sensing.

	The measurement results show that the body trunk absolute anglemeasurement of the device can sufficiently detect the stable posture in theforward/backward directions of the patient, thus ensuring the safety andeffectiveness of the device.
	Plantar loadmeasurement
	To test the accuracy of plantar load measurement.

	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.
SurfaceElectromyographyBioelectrical signalmeasurmentperformance
	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.

	Accuracy for all measurements were verified to meet specifications.
Ankle DurabilityTest
	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.

	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.

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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.

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 figureGains 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.

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

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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.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/sCPT -> HAL 0.64 +- 0.29 m/s	0.56 +- 0.23 m/s0.80 +- 0.26 m/s	0.60 +- 0.22 m/s0.73 +- 0.3 m/s	not sig. comparingthe two groups	for chronic stage	169.33 +- 81.87 m242.50 +- 132.15 m	190.38 +- 87.98 m243.06 +- 102.62 m	203.25 +- 86.53 m236.78 +- 115.03 m	not sig. comparingthe two groups	Tang 201234.4m

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$0.56 +- 0.43$ m/sCPT group$0.45 +- 0.53$ m/s	HAL group$0.85 +- 0.43$ m/sCPT group$0.61 +- 0.47$ m/s	HAL group$0.84 +- 0.51$ m/sCPT group$0.57 +- 0.41$ m/s	not sig. comparingthe two groups	Perera 2006$0.14$ m/s	$92.4 +- 104.2$ m$106.9 +- 132.6$ m	$156.7 +- 137.8$ m$140.8 +- 127.8$ m	$166.7 +- 143.9$ m$131.0 +- 117.6$ m	not sig. comparingthe two groups	Perera 2006
I21	Acute stroke rehabilitation	Yokota et al.	37	HAL groupFMA, FIM and FAC data onlyCPT groupFMA, FIM and FAC data only	HAL groupFMA, FIM and FAC data onlyCPT groupFMA, FIM and FAC data only			Tilson 2010$0.16$ 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.

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[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$49.8 \pm 20.1$ m/min	$61.4 \pm 26.6$ m/min	$11.6 \pm 10.6$ m/min	<0.05 comparingthe two groups	Perera et al. 20060.14m/s	* $78.9 \pm 33.3$ m	* $100.1 \pm 40.6$ m	* $21.1 \pm 12.4$ m	not sig. comparingthe two groups	Perera et al. 200650m
				CPT group$47.9 \pm 24.9$ 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. 20100.16m/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:

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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.
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.
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)(K171909)
HAL for Medical Use (Lower Limb Type)orthotically fits to the lower limbs and trunk;HAL is a gait training device intended totemporarily help improve ambulation uponcompletion of the HAL gait trainingintervention. HAL must be used with a BodyWeight Support system. HAL is not intendedfor sports or stair climbing. HAL gait trainingis intended to be used in conjunction withregular physiotherapy.	HAL for Medical Use (Lower Limb Type)orthotically fits to the lower limbs and trunk;the device is intended for individuals withspinal cord injury at levels C4 to L5 (ASIA C,ASIA D) and T11 to L5 (ASIA A with Zones ofPartial Preservation, ASIA B), who exhibitsufficient residual motor and movement-related functions of the hip and knee totrigger and control HAL.
The device is intended for individuals with:- spinal cord injury at levels C4 to L5 (ASIAC, ASIA D) and T11 to L5 (ASIA A withZones of Partial Preservation, ASIA B);- post stroke paresis- paraplegia due to progressiveneuromuscular diseases (spinal muscularatrophy, spinal and bulbar muscularatrophy, amyotrophic lateral sclerosis,Charcot-Marie-Tooth disease, distalmuscular dystrophy, inclusion bodymyositis, congenital myopathy, musculardystrophy)who exhibit sufficient residual motor andmovement-related functions of the hip andknee to trigger and control HAL.	HAL is a gait training device intended totemporarily help improve ambulation uponcompletion of the HAL gait trainingintervention. HAL must be used with a BodyWeight Support system. HAL is not intendedfor sports or stair climbing. HAL gait trainingis intended to be used in conjunction withregular physiotherapy.In preparation for HAL gait training, thecontroller can be used while the exoskeletonis not donned to provide biofeedback trainingthrough the visualization of surfaceelectromyography bioelectrical signalsrecorded.
In preparation for HAL gait training, thecontroller can be used while the exoskeletonis not donned to provide biofeedback training	HAL is intended to be used inside medicalfacilities while under trained medical
through the visualization of surfaceelectromyography bioelectrical signalsrecorded.HAL is intended to be used inside medicalfacilities while under trained medicalsupervision in accordance with the userassessment and training certificationprogram.	supervision in accordance with the userassessment and training certification program

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5.8.2 Similarities and Differences of Intended Use/Indications for Use (IFU)

The subject device expands upon the Indication for Use of the predicate device with the addition of these two patient populations. The stroke population and rare progressive neuromuscular diseases, namely Amyotrophic Lateral Sclerosis, Spinal Muscular Atrophy, Spinal and Bulbar Muscular Atrophy, Charcot-Marie-Tooth Disease, Muscular Dystrophy, Distal Myopathy, Congenital Myopathy and Inclusion Body Myositis.

The inclusion of individuals with post stroke paresis is not uncommon among the devices in the 21 CFR 890.3480 regulation. Individuals with progressive neuromuscular diseases is a new population not found in the indications of any marketed device. Moreover there are not many medical services available for this population, with the exception of several pharmaceuticals.

The new additions to the target patient population raise different questions of safety and effectiveness, but the additional clinical evidence presented show that the device is both safe and effective for these populations.

Device	Subject Device(HAL for Medical Use)	Predicate Device(HAL for Medical Use K171909)
Limitations	• Healthy bone density.• Skeleton does not suffer from anyfractures.• In general good health.• Candidates of the device shouldhave the following characteristics:• i. Hip width and leg segment lengthsare within the range of adjustability• ii. Weight is within the range of 40 -100 kg (89 - 220 lbs)• iii. Height is within the range of 150-190 cm (60 ~ 74 in), with allowancefor exceptions as long as the legsegment length is within the rangeof adjustabilityJudgment of whether this device is	• Healthy bone density.• Skeleton does not suffer from anyfractures.• In general good health.• Candidates of the device shouldhave the following characteristics:• i. Hip width and leg segmentlengths are within the range ofadjustability• ii. Weight is within the range of 40- 100 kg (89 - 220 lbs)• iii. Height is within the range of150- 190 cm (60 ~ 74 in), withallowance for exceptions as longas the leg segment length is withinthe range of adjustabilityJudgment of whether this device is

Device	Subject Device(HAL for Medical Use)	Predicate Device(HAL for Medical Use K171909)
	suitable for a person with an unusualbody shape (such as deformation ofthe leg) shall be made aftercomprehensive consideration of leglength, hip width, positions of cuffsand belts, sizes of sensor shoes, andfit of the joint positions and frame tothe person's body.• Physical and cognitive ability to usea treadmill, walker, or parallelbars. Use does not need to beindependent of clinical support.• Ability to communicate pain andneed to cease session, verbally ornonverbally.• Ability to acknowledgecommunication from the therapist,verbally or nonverbally.	suitable for a person with anunusual body shape (such asdeformation of the leg) shall bemade after comprehensiveconsideration of leg length, hipwidth, positions of cuffs and belts,sizes of sensor shoes, and fit of thejoint positions and frame to theperson's body.
Contraindications	• Persons whose body dimensionssuch as weight, upper leg length,lower leg length and hip width, arenot suitable for this device.• Persons who have severedeformations of their body parts.*• Persons whom physicians havejudged unsuitable for theimplementation of therapeuticexercise such as standing andwalking treatment.• Persons who cannot haveelectrodes affixed to any part oftheir body due to a skin disease orany other reason.• Severe spasticity (Ashworth4)• Unstable spine or unhealed limbs orpelvic fractures.• Heterotopic ossification.• Significant contractures.• Psychiatric or cognitive situationsthat may interfere with properoperation of the device.	• Persons whose body dimensionssuch as weight, upper leg length,lower leg length and hip width, arenot suitable for this device.• Persons who have severedeformations of their body parts.*• Persons whom physicians havejudged unsuitable for theimplementation of therapeuticexercise such as standing andwalking treatment.• Persons who cannot haveelectrodes affixed to any part oftheir body due to a skin disease orany other reason.• Severe spasticity (Ashworth4)• Unstable spine or unhealed limbsor pelvic fractures.• Heterotopic ossification.• Significant contractures.• Psychiatric or cognitive situationsthat may interfere with properoperation of the device.• Pregnant women.
Device	Subject Device(HAL for Medical Use)	Predicate Device(HAL for Medical Use K171909)
	inability to follow directions.• Pregnant women.• History of severe neurologicalinjuries other than SCI, stroke,spinal muscular atrophy, spinal andbulbar muscular atrophy,amyotrophic lateral sclerosis,Charcot-Marie-Tooth disease, distalmuscular dystrophy, inclusion bodymyositis, congenital myopathy ormuscular dystrophy (MS, CP, TBI,subarachnoid hemorrhage, etc.)• Persons with severe concurrentmedical diseases: infections,circulatory, heart or lung, pressuresores• Persons with colostomy• Persons with poor skin integrity inareas in contact with the device• Persons with decreased standingtolerance due to orthostatichypotension• Persons with strict range of motion(ROM) restrictions that cannottolerate the entire ROM of HAL, orthat would prevent a patient fromachieving a normal, reciprocal gaitpattern• Persons with unresolved deep veinthrombosis• Persons with uncontrolledAutonomic Dysreflexia• Persons with uncontrolledhypertension or hypotension• Persons with lower limb prosthesis• Persons who require ventilators• Persons with epilepsy	injuries other than SCI (MS, CP,ALS, TBI, etc.)• Persons with severe concurrentmedical diseases: infections,circulatory, heart or lung, pressuresores• Persons with colostomy• Persons with poor skin integrity inareas in contact with the device• Persons with decreased standingtolerance due to orthostatichypotension• Persons with strict range of motion(ROM) restrictions that cannottolerate the entire ROM of HAL, orthat would prevent a patient fromachieving a normal, reciprocal gaitpattern• Persons with unresolved deepvein thrombosis• Persons with uncontrolledAutonomic Dysreflexia• Persons with uncontrolledhypertension or hypotension• Persons with lower limb prosthesis• Persons who require ventilators• Persons with epilepsy
Patient Height	Same	150-190 cm
Patient Weight	Same	40-100 kg
IntendedEnvironment	Same	• Flat surface oftraining/rehabilitation facility (indooronly)• Must be used in combination with
Device	Subject Device(HAL for Medical Use)	Predicate Device(HAL for Medical Use K171909)
Intended Users	Same	Body Weight Support systemsMedical professionals that havecompleted designated trainingprogram to use the device
Hardware andMainComponents	Same	The system consists of three majorcomponents:• Controller• Main unit• Sensor shoes
Device Variations	• Double leg configuration and Singleleg configurations (right and leftconfigurations)• Same• Same	• Double leg configuration• 8 different size variations: 4different leg lengths, 2 differentwaist widths• Sensor shoes are available indifferent sizes of 23, 24, 25, 26, 27,28, 29, 30 cm
Device Lifetime	Same	5 Years
Power Sources	Same	• Lithium ion battery
Range of Motion	Same	• Hips: 120° flexion to -20° extension• Knee: 120° flexion to -6° extension
Method ofControl	Same	• Surface electromyographyBioelectrical signals at knee andhip extensor and flexor muscles(CVC mode), Attached controllerused by medical professional,Postural and Shoe sensor cues formovement
Modes ofOperation	Same	• CVC (Cybernic Voluntary Control)• CAC (Cybernic AutonomousControl)• CIC (Cybernic Impedance Control)*Can be selected for each joint(right/left hip/knee joints)
Main risk(mitigation)	Same	Drive patient's joints past their ROM(mechanical stoppers)
Safety Features	Same	• Limited joint torque and jointvelocity• Mechanical stoppers to preventexcessive joint flexion or extension• System fault for each componentthroughout operation• Task switching conditions that will
Device	Subject Device(HAL for Medical Use)	Predicate Device(HAL for Medical Use K171909)
Fall PreventionMeasures	Same	not initiate incorrect task changesBWS systems
Bench Testing	Same	• Durability of mechanical stopper: applicant test• Durability of ankle partConsecutive Landing: applicant test• Effective output: applicant test• Software testing: Verification, validation & hazard analysis
OperatingTemperature	Same	• 50° to 86° F (10° to 30° C)
PerformanceStandards	• Same• Electromagnetic Compatibility: IEC 60601-1-2 Edition 4.0, 2014• Same• Same• Same	• Electrical Safety: AAMI/ANSI ES60601-1:2005/(R)2012 and A1:2012• Electromagnetic Compatibility: IEC 60601-1-2: 2007• Usability: IEC 60601-1-6: 2010 and IEC 62366: 2014• Battery Safety: IEC 62133: 2012, IEC 60335-1: 2010, IEC 60335-2-29: 2010 and ANSI/UL 1012: 2010• Software: IEC 62304: 2015
Training	Same(training material has been updated to address new indications and description of additional configurations)	• CYBERDYNE-developed program for medical professionals• The device is intended to be used only in medical facilities for HAL gait training• Must be used under the supervision of a trained medical professional in accordance with the user assessment and training certification program.
Clinical Studies	• There are 6 studies conducted on spinal cord injury subjects, that include the 2 studies listed in K171909, used for assessment of effectiveness. There are 8 studies that were used for assessment of safety.• All studies were non-comparative and non-randomized. One study with an ID of I9 had 2 groups with	• There are 2 studies conducted on spinal cord injury subjects. The studies cover the indications for use of the device. Both effectiveness and safety are measured in the studies and statistical analysis has been performed for results on effectiveness.• The studies were both non-comparative and non-randomized
Device	Subject Device(HAL for Medical Use)	Predicate Device(HAL for Medical Use K171909)
	• different treatment frequencies.• Subjects were mostly chronic SCI patients with the same range of lesion as the studies in K171909.• The sample size range of the studies are the same, 8 ~ 55.• Results on effectiveness of 3 of the newly added studies are consistent with the findings from K171909. The 4th newly added study, I9, showed that gains made from treatment with the HAL device were maintained for a year with continued treatment at the same treatment frequency as during the intervention, as well as with continued treatment at a much lower frequency.• Results on safety is the same, that there were no SAEs reported, and all adverse events were minor incidents. Adverse events that occurred with use of other devices is unlikely to occur with the use of the HAL because falls are mitigated with a mandatory combined use with a BWS system, use on patients with low bone density is labeled as a limitation, and a swollen ankle has never been reported in our global market experience. It is assumed that the sensor shoes, which is an essential component of the HAL, protects the ankle from making physical contact with the rigid parts of the device.• Long term use of the device has been tested, and the result supports long term effects of treatment even with decreased treatment frequency.	• All subjects were chronic (> 1 year since trauma) SCI patients with injuries ranging from C2-L5, ASIA D, C, B and ASIA A with Zones of Partial Preservation• The sample size of the studies are 8 and 55 subjects, respectively• The effectiveness is primarily measured by 10 meter walk tests, 6 minute walk tests, and WISCI-II tests, all measured without wearing the HAL device. The results suggest a statistically significant improvement in gait related outcome measures.• The safety of the device is primarily measured by SAE and AE occurrences. There were no SAE reported. AE's included reports of minor incidents that included: pain due to pressure from device parts that were managed by adjusting a better fit, skin irritation from electrodes and chafed feet due to wrong shoe size.• Long term use of over 12 weeks (60 treatment sessions) has not been clinically tested.
	• There are 14 studies conducted on stroke subjects used for assessment of effectiveness. Of these, 5 were studies for patients of over 6 months
Device	Subject Device(HAL for Medical Use)	Predicate Device(HAL for Medical Use K171909)
	post stroke and 7 were for patientsof less than 6 months post stroke.The remaining 2 studies monitoredweekly 10MWT results duringconventional physicaltherapy/rehabilitation after stroke,and started the intervention with HALwhen the walk speeds stoppedshowing improvements.There are 4 studies that were usedfor assessment of safety.• Some studies were comparative witha control group receivingconventional physical therapy.• The sample size range of the studiesare 8 ~ 53.• The effectiveness is primarilymeasured by the 10MWT and6MWT, all measured withoutwearing the HAL device. Overall, theresults suggest a statisticallysignificant improvement in gaitrelated outcome measures. Resultsfrom studies that could not rule outthe effects of spontaneous recoveryearly after the onset of stroke stilltrended toward improvement of gaitrelated outcome measures, and thestudies that addressed spontaneousrecovery, either through interventiontiming or with a control group,suggest that the treatment with thedevice show statistically andclinically significant improvements ingait related outcome measures whileconventional physical therapy doesnot.• The safety of the device is primarilymeasured by SAE and AEoccurrences. Results on safetysuggest that there are no adverseevents typical of the disease. NoSAEs are reported.• Though limited, there are somestudies that support either lasting orlong term effects.
Device	Subject Device(HAL for Medical Use)	Predicate Device(HAL for Medical Use K171909)
	• There are 3 studies (1 literature, 1clinical trial and 1 post marketsurvey) conducted on patients withdiseases belonging in the group. All3 studies account for both safety andeffectiveness.• The sample size range of the studiesare 3 ~ 207.• The effectiveness is primarilymeasured by the 10MWT and2MWT, all measured withoutwearing the HAL device. Resultssuggest that treatment with the HALdevice shows improvement in gaitrelated outcome measures despitethe progressive nature of thediseases. Since the literature andclinical trial have such small samplesizes, the findings from the postmarket survey bears significantweight and are quickly summarizedbelow:1) Participants showed improvementin gait related outcome measurescomparing pre-post intervention ofthe first cycle of treatment (9sessions).2) Even after 1.5 years from themeasurement of baseline, withintermittent treatment cyclesparticipants showed about +20%difference from the baseline function,despite the progressive nature oftheir disease.3) Blood creatine kinase data wascollected from a total of 100participants and results show adecreasing trend when comparingpre-post HAL treatmentmeasurements. The lack of rise inCK levels suggests that HALtreatment does not damage the
Device	Subject Device(HAL for Medical Use)	Predicate Device(HAL for Medical Use K171909)
	• The safety of the device is primarilymeasured by SAE occurrences. Nodevice caused SAEs are reported.• Long term effects are evident frompost market survey results.
Special Controls	Same	Conforms with special controls per21 CFR 890.3480, as applicable

5.8.3 Comparison of Characteristics

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5.8.4 Similarities and Differences of Non-clinical Performance Data

The subject device is an expansion of the predicate device, so the characteristics that they share are many and exactly the same.

The contraindications were adjusted slightly to reflect the addition of stroke and progressive neuromuscular diseases in the indication, as well as to reflect the exclusionary criteria from the studies used to show safety and effectiveness for these new populations.

The subject device adds two single-leg configurations; right and left leg configurations. Each of these additional configurations come with all of the size/shape variations of the double leg device, as well as the different Sensor Shoe sizes. The difference between the single-leg versions and the double-leg version is simple. One of the legs, from the hip joint down has been removed from the main unit, and it is replaced by a long cord that attaches to one of the sensor shoes. The sensor shoe still provides floor reaction force sensor readings, but no assistance is provided for the side with no device leg.

Though different questions about safety may seem like to arise due to the difference in configurations, the non-clinical performance testing also applies to the new single-leg versions. Safety is therefore not compromised.

5.8.5 Similarities and Differences of Clinical Performance Data

In addition to the clinical studies presented for the predicate device that demonstrated safety and efficacy for spinal cord injury, the additional studies presented for the subject device increases the robustness of evidence supporting safety and efficacy.

Stroke is a new indication. Safety and effectiveness for this population is supported by many

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clinical studies, although the significance level of the changes in outcome measures that show effectiveness vary among the studies.

The most representative finding comes from a comparative clinical study for 16 post stroke subjects (8 with HAL and 8 with conventional gait rehabilitation). All subjects were new stroke survivors who underwent conventional rehabilitation until their gait function ceased to improve, showing the end of natural recovery as well as the limits of the effects of conventional rehabilitation. This timing was determined through monitoring of weekly measurements of the 10 meter walk speed. Once gait function ceased to improve from conventional rehabilitation, subjects started the comparative intervention, and results after a 5 week treatment program (5 sessions per week) were compared to show significant differences between the two groups. The group that used the HAL showed great additional improvement (greater than the MCID) whereas the group that continued conventional qait rehabilitation did not show much change. The results of the control group indirectly proves that the criteria used to identify the "end" of natural recovery & rehabilitation was valid, which in turn suggests that the treatment with HAL provides additional improvements for patients in this population.

Patients with progressive neuromuscular disease are not the typical population to use this type of medical device. However a GCP clinical trial and post market survey in Japan shows temporary effects for this population. Although the speed of disease progression greatly depends on the type of disease and the progression phase, as a group, treatment with the HAL helped patients maintain their physical function (distance walked in 2 minutes) above the baseline level before starting treatment for over 1.5 years. Also noteworthy was the finding that CK (Creatine Kinase) levels did not elevate after treatment and instead showed a slight tendency to decrease, which suggests that treatment with HAL does not lead to overuse or excessively burden the muscles when used for patients in this population.

5.9 Conclusions

Based on the information above with comparisons of intended use, indications for use, and technological characteristics, the new differences that raise different questions of safety and effectiveness were addressed, and we believe that the subject device is as safe and effective as, and therefore substantially equivalent to, the identified predicate device.

Regulation Number and Section

§ 890.3480 Powered lower extremity exoskeleton.

(a)
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.(b)
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).