The Robotic Arm Interactive Orthopedic System (RIO®) is intended to assist the surgeon in providing software defined spatial boundaries for orientation and reference information to anatomical structures during orthopedic procedures.

The RIO® is indicated for use in surgical knee procedures in which the use of stereotactic surgery may be appropriate, and where reference to rigid anatomical bony structures can be identified relative to a CT based model of the anatomy. These procedures include:
• Total Knee Arthroplasty (TKA)

The Implants systems with which the system is compatible:
• Kinetis Total Knee System (CR/UC)
• Triathlon Total Knee System (CR/CS/PS cemented Primary)

Device Description

The Robotic Arm Interactive Orthopedic System (RIO) with Total Knee Arthroplasty Application is a stereotactic instrument that includes a robotic arm, an integrated cutting system, an optical detector, a computer, dedicated instrumentation, operating software, a planning laptop, and tools and accessories. RIO uses patient CT data to assist the physician with pre-surgical implant placement planning and intraoperative tracking of the patient's femur and tibia. RIO's robotic arm serves as an "intelligent" tool holder or tool guide used by a surgeon for stereotactic guidance during orthopedic surgical procedures.

The main RIO platform includes an optical detector, computer, dedicated instrumentation, operating software, tools and accessories, cutting system, and a robotic arm. The system's architecture is designed to support total knee procedures. With application specific hardware and software, the system provides stereotactic guidance during orthopedic surgical procedures by using patient CT data to assist a surgeon with pre-surgical planning and interpretive/intraoperative navigation.

RIO's robotic arm, once configured for a specific application, can serve as surgeon's "intelligent" tool holder or tool guide by passively constraining the preparation of an anatomical site for an orthopedic implant with software-defined spatial boundaries.

AI/ML Overview

Here's an analysis of the provided text to extract the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

The document reports primary and secondary endpoints as part of its clinical study.

Acceptance Criteria Category	Specific Criteria	Reported Device Performance
Safety (Primary Endpoint)	No clinically significant increase in the incidence of selected device-related adverse events when using the investigational device relative to manual TKA. This was based on complications identified by the Knee Society TKA Complications Workgroup in 2012, compared against published occurrence rates for manually instrumented TKA.	No subject experienced any of the rare adverse events that comprise the primary composite safety events (0/89). The study met its primary safety study success criterion.
Effectiveness (Secondary Endpoint)	Post-operative radiographic limb alignment of the operative knee assessed at 3 months post-operative. Malalignment was defined as a radiographically determined alignment angular deformity in the coronal plane greater than 10° from the mechanical axis. The goal was to demonstrate non-inferiority to TKA with manual instruments.	Independent surgeon reviewer one measured an estimated mean limb alignment deviation from plan of 1.53° (± 1.05°). Independent surgeon reviewer two measured an estimated mean limb alignment deviation from plan of 1.56° (± 1.04°). No subject reported malalignment (i.e., >10° from mechanical axis).
Functional Outcome (Supporting Endpoint)	Improvement in post-operative subject function at the three-month interval as compared to the subject's pre-operative function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. A reduction in the WOMAC score from pre-op to 3 months was necessary.	Subjects exhibited a mean 29.6 points reduction in the WOMAC score, indicating improvement over the pre-operative score.

Non-Clinical Performance Data (Verification/Validation)

Acceptance Criteria (Purpose)	Reported Device Performance (Results)
Verify integration of RIO, Total Knee Application Software, and instrumentation provides adequate functionality to successfully complete a TKA procedure.	Pass
Verify overall system accuracy by combining bone registration and bone resection accuracy.	Pass
Verify accuracy of bone registration for the TKA 1.0 Application satisfies specified requirements.	Pass
Verify RIO resection accuracy for the Total Knee Arthroplasty Application satisfies specified requirements.	Pass
Verify RIO perimeter retention accuracy for the Total Knee Arthroplasty Application satisfies specified requirements.	Pass
Verify in simulated-use environment integration of RIO with Total Knee Application Software and instrumentation provides adequate functionality and satisfies customer requirements.	Pass

2. Sample Size Used for the Test Set and the Data Provenance

Sample Size for Clinical Study (Test Set): 89 implanted subjects (out of 100 consented and enrolled). Two subjects were excluded from the limb alignment assessment.
Data Provenance: Prospective, non-randomized, multi-center study conducted at three sites in the US.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts

Safety Assessment: Surgeon assessment of complications intra-operatively and at a short-term follow-up. (Number of surgeons/experts not specified, but implied to be the treating surgeons at the three sites.)
Limb Alignment Assessment: Two independent reviewers (implied to be surgeons, given the context of medical devices and clinical studies). Their qualifications are not explicitly stated beyond "independent surgeon reviewer."

4. Adjudication Method for the Test Set

For post-operative radiographic limb alignment, two independent reviewers assessed the outcome. The document reports their measured mean deviations separately (1.53° and 1.56°), implying their individual assessments were presented, rather than an adjudicated consensus. It does not specify an adjudication method like 2+1 or 3+1 if there were discrepancies.
For adverse events, "Study investigators classified relatedness of all AEs." The number of investigators and their adjudication method are not specified.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described in the provided text.
The clinical study focused on demonstrating the safety and effectiveness of the RIO system primarily by comparing its outcomes against literature-reported rates for manual TKA, not a direct head-to-head MRMC comparison with human readers/surgeons performing manual TKA in the same study.
Therefore, an "effect size" of human readers improving with AI vs. without AI assistance cannot be determined from this document.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was Done

The document describes the RIO system as a "stereotactic instrument that includes a robotic arm... used by a surgeon for stereotactic guidance." The system "assists the surgeon" and serves as an "intelligent tool holder or tool guide." This indicates a human-in-the-loop system, not a standalone (algorithm only) device.
The "System Accuracy Test," "Bone Registration Accuracy Test," "RIO 3.0 System Platform Cutting Accuracy Test," and "TKA Perimeter Retention Accuracy Verification" could be considered components of standalone algorithm/system performance tests, but they are integrated within the context of a surgeon-assisted procedure.

7. The Type of Ground Truth Used

Safety: Surgeon assessment of complications, compared against literature-defined complication rates.
Effectiveness (Limb Alignment): Post-operative radiographic measurements, compared against a pre-operatively derived subject-specific intended limb alignment. This can be considered a form of objective measurement against a planned target.
Functional Outcome: Patient-reported outcome measure (WOMAC score).
Non-Clinical Tests: Pre-defined specified requirements and expected functionalities.

8. The Sample Size for the Training Set

The document does not explicitly state the sample size for a training set. The clinical study described is the test set for evaluating the final device's performance. For an AI/ML device, a separate training set would typically be used to develop the algorithm before this evaluation.
The device uses "patient CT data" for pre-surgical planning and intraoperative navigation, implying previous data (potentially a training set) was used to develop the software models for this functionality, but the size and nature of such a set are not provided.

9. How the Ground Truth for the Training Set Was Established

As the document does not specify a training set, it does not describe how its ground truth was established. For a device like this, which relies on CT data for anatomical modeling and guidance, the "ground truth" for training would likely involve a large dataset of CT images with expert annotations (e.g., bone boundaries, anatomical landmarks) or precise cadaveric/phantom studies to establish known true values for registration and cutting accuracy. The "Performance Data" section describes validation tests that establish accuracy against known targets in a controlled environment, which are analogous to establishing ground truth for individual performance metrics.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

August 6, 2015

MA Surgical Corporation Jonathan Reeves Principal Senior Regulatory Specialist 2555 Davie Road Ft. Lauderdale, Florida 33317

Re: K143752 Trade/Device Name: Total Knee Application (TKA) Regulation Number: 21 CFR 882.4560 Regulation Name: Stereotaxic Instrument Regulatory Class: Class II Product Code: OLO Dated: July 1, 2015 Received: Julv 7, 2015

Dear Jonathan Reeves,

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. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions 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 801); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in

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the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Mark N. Melkerson -S

Mark N. Melkerson Director Division of Orthopedic Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug AdministrationIndications for Use	Form Approved: OMB No. 0910-0120Expiration Date: January 31, 2017See PRA Statement below.
510(k) Number ( if known )	K143572
Device Name	Total Knee Application (TKA)
Indications for Use ( Describe )
Indications for Use:
	The Robotic Arm Interactive Orthopedic System (RIO®) is intended to assist the surgeon in providing software defined spatial boundaries for orientation and reference information to anatomical structures during orthopedic procedures.
	The RIO® is indicated for use in surgical knee procedures in which the use of stereotactic surgery may be appropriate, and where reference to rigid anatomical bony structures can be identified relative to a CT based model of the anatomy. These procedures include:• Total Knee Arthroplasty (TKA)
	The Implants systems with which the system is compatible:• Kinetis Total Knee System (CR/UC)• Triathlon Total Knee System (CR/CS/PS cemented Primary)
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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Image /page/3/Picture/0 description: The image is a logo for MAKO Surgical Corp. The logo features the word "MAKO" in large, bold, black letters. Below "MAKO" is the text "SURGICAL CORP" in smaller, black letters. Above the word "MAKO" is a blue, curved shape that resembles a wave or an abstract mountain range.

555 Davie Road • Ft. Lauderdale, FL 33317 one 954.927.2044 • Fax 954.927.04 ww.makosurgical.com

510(K) SUMMARY

Submitter: Address: Phone number: Fax number: Contact Person: Date Prepared: Device Trade Name: Regulation Name: Regulation Number: Device Classification: Product Code:

MAKO Surgical Corp. 2555 Davie Road, Fort Lauderdale, FL 33317 954-628-0655 954-927-0446 Jonathan Reeves December 30, 2014 Total Knee Application (TKA) Stereotaxic Instrument 21 CFR 882.4560 Class II OLO

Substantial Equivalence Claimed To:

Total Knee Application is substantially equivalent to MAKO Surgical Corp.'s (Robotic Arm Interactive Orthopedic System) RIO® - (Partial Knee Application) PKA cleared via K112507.

Description:

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Summary of Technological Characteristics Compared to Predicate Devices:

The technological characteristics of Total Knee Application compared to the predicate device are listed below:

TechnologicalCharacteristics	Total Knee Application	RIO-PKA(K112507)
MajorComponents	Guidance Module, robotic arm,camera stand, cutting system,preoperative planning laptop.	Guidance Module, robotic arm,camera stand, cutting system,preoperative planning laptop.
Tools/accessories	Various reusable and disposableinstruments	Various reusable and disposableinstruments
Images Use	CT	CT

Intended Use/Indications for Use:

Total Knee Arthroplasty (TKA) ●
The Implant systems with which the system is compatible:
Kinetis Total Knee System ( CR/UC) .
Triathlon Total Knee System ( CR/CS/PS cemented Primary)

Performance Data:

Validation / VerificationMethod	Purpose	Validation / VerificationResults
Full System Run-ThroughTest	Verify that the integrationof the Robotic ArmInteractive OrthopedicSystem (RIO), with theTotal Knee ApplicationSoftware, and supportinginstrumentation providesadequate functionality to beable to successfullycomplete a MAKOplastyTotal Knee Arthroplastyprocedure	Pass
System Accuracy Test	Verify the overall systemaccuracy by combiningbone registration and bone	Pass

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	resection accuracy.
Bone Registration AccuracyTest	Verify the accuracy of boneregistration for the TKA 1.0Application satisfies thespecified requirements.	Pass
RIO 3.0 System PlatformCutting Accuracy Test	Verify the RIO resectionaccuracy for the Total KneeArthroplasty Applicationsatisfies the specifiedrequirements.	Pass
TKA Perimeter RetentionAccuracy Verification	Verify the RIO perimeterretention accuracy for theTotal Knee ArthroplastyApplication satisfies thespecified requirements.	Pass
TKA Validation	Verify in a simulated-useenvironment that theintegration of the RoboticArm Interactive OrthopedicSystem (RIO) with theTotal Knee ApplicationSoftware and supportinginstrumentation providesadequate functionality tosuccessfully complete aMAKOplasty Total KneeArthroplasty procedure andsatisfies the customerrequirements	Pass

Clinical Data:

The Robotic Arm Interactive Orthopedic System (RIO) Total Knee Arthroplasty (TKA) study was a prospective, non-randomized, multi-center study conducted at three sites in the US. The purpose of the RIO TKA IDE study was to demonstrate safety and effectiveness of the RIO system in total knee arthroplasty at 3 months. A total of 100 subjects were consented and enrolled. A total of 89 subjects were implanted using the RIO System and all have successfully completed pre-operative, intra-operative, and 3 month post-operative visits.

There were 49 female (55.1%) subjects and 40 (44.9%) male subjects. Refer to table below for age, height and weight distribution for this population

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Label	N	Mean	Std Dev	Median	Lower Quartile	Upper Quartile	Minimum	Maximum
Age	89	65.78	8.49	65.00	60.00	72.00	45.00	83.00
Height (in)	89	67.34	3.84	67.00	65.00	70.00	60.00	75.00
Weight (lb)	89	202.61	38.96	197.00	175.00	226.00	122.00	318.00
BMI	89	31.43	5.70	31.07	27.45	33.78	21.61	52.90

The primary study endpoint was to demonstrate the safety of the RIO Total Knee Arthroplasty Application based on surgeon assessment of complications intra-operatively and at a short term follow up. The safety analysis focused on the complications identified by the Knee Society TKA Complications Workgroup in 2012 for total knee arthroplasty. A review of the literature was performed to identify currently published occurrence rates in manually instrumented TKA for each standardized TKA complication. The analysis of the safety profile was designed to provide clinical data necessary to test the hypothesis that there is no clinically significant increase in the incidence of selected device-related adverse events when using the investigational device relative to manual TKA. No subject experienced any of the rare adverse events that comprise the primary composite safety events (0/89). Therefore, the study meets its primary safety study success criterion.

The secondary endpoint was post-operative radiographic limb alignment of the operative knee assessed at the 3 month post-operative by two independent reviewers. The measured post-operative limb alignment was compared to the derived subject-specific value for the intended limb alignment established prior to bone resection. Two subjects were excluded from the assessment due to issues with the methods of collecting the images used to make the assessment. Excluding these two subjects, independent surgeon reviewer one measured an estimated mean limb alignment deviation from plan of 1.53° (± 1.05°) and independent surgeon reviewer two measured an estimated mean limb alignment deviation from plan of 1.56° (± 1.04°).

In addition to reporting accuracy in achieving post-operative limb alignment, malalignment was defined as a radiographically determined alignment angular deformity in the coronal plane greater than 10° from the mechanical axis. Alignment was assessed in descriptive analysis as a categorical variable using the categories appearing in the Knee Society Score, Doctor Portion. These categories are 0-4°, 5-10°, 11-15°, and Other, however, these ranges do not account for the surgeon's subject-specific intended postoperative limb alignment. Forty (40) of 89 subjects (44.9%) reported post-operative KSS limb alignment of 0-4°, which is associated with a 3-point deduction in KSS score per degree, while 49/89 (55.1%) reported KSS limb alignment of 5-10° which received no deduction according to the Knee Society Score. No subject reported malalignment as defined above.

The supporting study endpoint was to demonstrate improvement in post-operative subject function at the three month interval as compared to the subject's pre-operative function as measured by the WOMAC. In order to meet the study success criterion, a reduction in the WOMAC score from pre-op to 3 months was necessary. Subjects exhibited a mean 29.6 points reduction, indicating improvement over pre-operative score.

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There were 33 reported Adverse Events (AEs) occurring in 32 of the study subjects. Study investigators classified relatedness of all AEs as definitely related, possibly related, or not related to the study system or procedure. There was 1 (1/33, 3.0%) AE that was considered related to the system or procedure. The AE was for an Unanticipated Adverse Device Effect (UADE) for retained foreign body (saw tooth). There were 3 (3/33, 9.1%) that were considered possibly related to the device. The SAEs possibly related to the device included: UADEs was for retained foreign body (saw tooth) (1) and swelling and pain (2). There were a total of 9 (9/33, 27.2%) reported serious AEs (SAEs) that were not related to the device or procedure. These included (8) manipulation under anesthesia (MUA) and (1) pulmonary embolism.

A second surgery was required for two subjects to remove a retained foreign body. For one of the subjects, a revision of the tibial insert was required to locate the foreign body and irrigate the joint space.

The safety and effectiveness of the Robot Arm Interactive Orthopaedic System (RIO®) used for Total Knee Replacement (TKR) has been demonstrated. No subject experienced any rare adverse events that comprised the composite safety events. Secondary endpoints of postoperative limb alignment and clinical outcomes scores at three months postoperatively demonstrated non-inferiority to TKR used with manual instruments as reported in the literature.

Conclusions of Clinical and Non-Clinical Data:

The results of the clinical and non-clinical data indicate the device performed within the intended use and did not raise any new safety and efficacy issues. The device was found to be substantially equivalent to the predicate device.

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Regulation Number and Section

§ 882.4560 Stereotaxic instrument.

(a)
Identification. A stereotaxic instrument is a device consisting of a rigid frame with a calibrated guide mechanism for precisely positioning probes or other devices within a patient's brain, spinal cord, or other part of the nervous system.(b)
Classification. Class II (performance standards).