The iTotal® CR Knee Replacement System (iTotal CR KRS) is intended for use as a total knee replacement in patients with knee joint pain and disability whose conditions cannot be solely addressed by the use of a prosthetic device that treats only one or two of the three knee compartments, such as a unicondylar, patellofemoral or bicompartmental prosthesis.

The Indications for Use include:

Painful joint disease due to osteoarthritis, traumatic arthritis, rheumatoid arthritis or osteonecrosis of the knee.
Post traumatic loss of joint function.
Moderate varus, valgus or flexion deformity in which the ligamentous structures can be returned to adequate function and stability.
Failed osteotomies, hemiarthroplasties, and unicondylar, patellofemoral or bicompartmental implants.
Revision procedures provided that anatomic landmarks necessary for alignment and positioning of the implant are identifiable on patient imaging scans.

This implant is intended for cemented use only.

Device Description

The iTotal CR Knee Replacement System (hereafter referred to as the "iTotal CR KRS") is a patient specific tricompartmental faceted posterior cruciate liqament (PCL) retaining knee replacement system. The iTotal CR KRS is a semi-constrained cemented knee implant which consists of a femoral, tibial and patellar component.

Using patient imaging (either CT or MR scans) and a combination of proprietary and off-the-shelf software a patient specific implant is designed that best meets the geometric and anatomic requirements of the specific patient. The femoral component is manufactured from cobalt chromium molybdenum ("CoCrMo") alloy. The tibial component includes a metal tray manufactured from CoCrMo alloy and either one or two polyethylene inserts. The polyethylene inserts may be manufactured from UHMWPE or from a highly cross-linked Vitamin E infused polyethylene (iPoly XE™). The patellar component is also manufactured from UHMWPE or from a highly cross-linked Vitamin E infused polyethylene (iPoly XE).

For user convenience, and similar to the predicate iTotal CR KRS, accessory orthopedic manual surqical instruments designed for use with the modified iTotal CR KRS are provided to assist with implantation. The ancillary instruments are provided sterile and for single-use only. These patient specific instruments are provided to assist in the positioning of total knee replacement components intraoperatively and quiding the cutting of bone.

The function and general design features of the patient specific ancillary instruments remain similar to those described in the predicate 510ks i.e. K120316 and K122870.

AI/ML Overview

The provided document is a 510(k) summary for the ConforMIS iTotal® CR Knee Replacement System. It describes the device, its intended use, and the testing performed to demonstrate substantial equivalence to a predicate device. However, it does not contain the specific information requested about acceptance criteria for device performance, a study proving the device meets these criteria, or details regarding sample sizes, data provenance, expert ground truth, adjudication methods, MRMC studies, or training set information.

Instead, the document focuses on:

Device Description: The iTotal CR Knee Replacement System is a patient-specific tricompartmental faceted PCL-retaining knee replacement system.
Indications for Use: Detailed conditions for which the device is intended.
Substantial Equivalence: The primary goal of the 510(k) submission, by comparing the modified device to previously cleared predicate devices (K120316 and K122870).
Nonclinical Testing: A list of types of nonclinical laboratory testing performed (Tibial interlock assembly and disassembly testing, Contact area/contact stress testing, Constraint testing, Cadaveric testing) to demonstrate safety and substantial equivalence.

Therefore, many of your requested fields cannot be filled from the provided text. The document explicitly states: "Clinical data is not necessary to demonstrate substantial equivalence." This means a clinical study, as you might expect for many of the questions asked, was not performed and is not detailed here.

Here's a breakdown of what can be extracted and what cannot:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Not specified in the document. The document details types of nonclinical tests performed (e.g., "Tibial interlock assembly and disassembly testing," "Contact area/contact stress testing," "Constraint testing," "Cadaveric testing") but does not provide specific quantitative acceptance criteria or the numerical results of these tests. Instead, it concludes that based on these tests, the modified device is "substantially equivalent" to predicate devices.

Acceptance Criteria

Reported Device Performance

Not specified in the document. The document details types of nonclinical tests performed (e.g., "Tibial interlock assembly and disassembly testing," "Contact area/contact stress testing," "Constraint testing," "Cadaveric testing") but does not provide specific quantitative acceptance criteria or the numerical results of these tests. Instead, it concludes that based on these tests, the modified device is "substantially equivalent" to predicate devices.

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

Sample Size for Test Set: Not specified. The document mentions "Cadaveric testing" as one of the nonclinical tests, implying biological samples were used, but no numbers are provided.
Data Provenance: Not specified for the nonclinical tests. As it's nonclinical (laboratory/cadaveric), geographical provenance is less relevant than for patient data. It is not retrospective or prospective in the sense of a clinical trial.

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

Not applicable/Not specified. The testing described is nonclinical (mechanical/cadaveric), and therefore, the concept of "experts establishing ground truth" in the diagnostic or clinical outcome sense does not apply. The tests likely followed established engineering or biomechanical testing standards.

4. Adjudication Method for the Test Set

Not applicable/Not specified. Adjudication methods (like 2+1 or 3+1) are typically used for clinical interpretation tasks involving expert consensus, which is not described here.

5. 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 MRMC study was done. This device is a knee implant system and associated surgical instrumentation, not an AI-assisted diagnostic tool. The document explicitly states, "Clinical data is not necessary to demonstrate substantial equivalence."

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

While the device uses "a combination of proprietary and off-the-shelf software" for patient-specific implant design based on patient imaging (CT or MR scans), the document does not describe standalone algorithm performance for diagnostic or analytical tasks. The software is part of the design process for the physical implant, not a standalone diagnostic or interpretative algorithm. Therefore, typical standalone performance metrics (e.g., sensitivity, specificity, AUC) are not relevant or provided.

7. The Type of Ground Truth Used

Type of Ground Truth: For the nonclinical tests, the "ground truth" would be based on engineering specifications, biomechanical principles, and established test standards (e.g., for contact area/stress, constraint, interlock functionality). For "cadaveric testing," the ground truth would be the direct observation and measurement of the implant's behavior within the cadaveric model according to predefined experimental protocols. It is not expert consensus, pathology, or outcomes data in the clinical sense.

8. The Sample Size for the Training Set

Not applicable/Not specified. The document does not describe an AI or machine learning model that would require a "training set" in the traditional sense for diagnostic or predictive tasks. The software develops patient-specific designs based on individual patient imaging, not by "training" on a large dataset to learn patterns for diagnosis.

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

Not applicable/Not specified, as no training set for a machine learning model is described. The "ground truth" for the design software would be derived from anatomical principles, biomechanical models, and engineering specifications used to program the design algorithms.

Summary

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K131019 (1/6)

8.0 510(K) SUMMARY

· MAY 2 4 2013

Submitter's Nameand Address	ConforMIS Inc.28 Crosby DriveBedford, MA 01730
EstablishmentRegistrationNumber	3009844603
Date of Summary	April 11, 2013
Contact Person	Amita S. Shah, Vice President, Regulatory and Quality Affairs
Telephone Number	(781) 345-9164
Fax Number	(781) 345-0104
Name of the Device	ConforMIS iTotal® CR Knee Replacement System (iTotal CRKRS)
Common or UsualName	Cruciate Retaining Total Knee Replacement System
Classification Name	Knee joint patellofemorotibial polymer/metal/polymer semi-constrained cemented prosthesis
DeviceClassification	Product Code:JWH, Knee joint patellofemorotibial polymer/metal/polymer semi-constrained cemented prosthesis.
	OOG, Knee Arthroplasty Implantation SystemIntended to be used to assist in the implantation of a specific kneearthroplasty device or a set of specific knee arthroplasty devices.Indicated to include guiding alignment, making or establishing cuts,selecting, sizing, attaching, positioning or orienting implant components.
	OIY, Prosthesis, knee, patellofemorotibial, semi-constrained, cementedpolymer + additive/metal/polymer + additive.This generic type of device includes prosthesis that have a femoralcomponent made of alloys, such as cobalt-chromium-molybdenum, and atibial component(s) and/or a retropatellar resurfacing component made ofultra-high molecular weight polyethylene plus an additive, such as a-tocopherol.

Special 510(k) – Modified iTotal® CR Knee Replacement System

・・

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510(K) SUMMARY CONTINUED

Indications for Use

The Indications for Use include:

. Painful joint disease due to osteoarthritis, traumatic arthritis, rheumatoid arthritis or osteonecrosis of the knee.
. Post traumatic loss of joint function.
. Moderate varus, valgus or flexion deformity in which the ligamentous structures can be returned to adequate function and stability.
Failed osteotomies, hemiarthroplasties, and unicondylar, . patellofemoral or bicompartmental implants.
. Revision procedures provided that anatomic landmarks necessary for alignment and positioning of the implant are identifiable on patient imaging scans.

This implant is intended for cemented use only.

ldentification of the Legally Marketed Device (Predicate Device)

ConforMIS iTotal CR Knee Replacement System (iTotal CR KRS) Device Class: Product Code: JWH, OOG, OIY Regulation Number: 21 CFR 888.3560 510(k) number: K120316 and K122870

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510(K) SUMMARY CONTINUED

Device Description

The function and general design features of the patient specific ancillary instruments remain similar to those described in the predicate 510ks i.e. K120316 and K122870.

The product subject of this premarket notification is substantially equivalent to the iTotal Cruciate Retaining Knee Replacement System (K120316 cleared April 19, 2012 and K122870 cleared January 14, 2013) and other currently marketed, cemented total knee replacement systems. The following testing was performed to establish substantial equivalence:

Tibial interlock assembly and disassembly testing -
-Contact area/contact stress testing
Constraint testing -
Design validation via cadaveric testing -

Substantial Equivalence

Special 510(k) - Modified iTotal® CR Knee Replacement System

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510(K) SUMMARY CONTINUED

Device Comparison

Attribute	PredicateiTotal CR Knee Replacement System(K120316 and K122870)	Modified DeviceiTotal CR Knee Replacement System(This submission)
Components	Femoral Component Tibial Implant Metal Backed Tibial Component Patellar component	Femoral Component Tibial Implant Metal Backed Tibial Component Patellar component
Materials	Femoral Implant: CoCrMo Metal Backed Tibial Components: Tibial tray: CoCrMo Single or dual Tibial Inserts:UHMWPE or iPoly XE(highly cross-linked VitaminE infused polyethylene) All Polymer Patellar Component:UHMWPE or iPoly XE (highly cross-linked Vitamin E infusedpolyethylene)	Femoral Implant: CoCrMo Metal Backed Tibial Components: Tibial tray: CoCrMo Single or dual Tibial Inserts:UHMWPE or iPoly XE(highly cross-linked VitaminE infused polyethylene) All Polymer Patellar Component:UHMWPE or iPoly XE (highlycross-linked Vitamin E infusedpolyethylene)
Design	Knee joint patellofemorotibial semi-constrained cemented prosthesis	Knee joint patellofemorotibial semi-constrained cemented prosthesis
Principle ofOperation	Cemented Use Fixed Bearing Design	Cemented Use Fixed Bearing Design
PatientMatched	Yes	Yes
Patellar Design/Dimensions	Symmetrical, offered in various sizes	Symmetrical, offered in various sizes
Tibial Implantinterlockdesign	Interference fit Anterior lip Undercuts on medial and lateralsides with Central Spine Full Posterior Scallops on Tray,Step-Up on Inserts Insert Snap Features	Interference fit Anterior lip Increased undercuts on medial andlateral sides with Central Spine Reduced Posterior Scallops onTray, Step-Up Removed on Inserts Increased Insert Snap WidthFeatures
Tibial Slope	Fixed at 5 degrees	Fixed at 5 degrees or cut option ofpatient specific tibial slope
MinimumThickness ofTibial Insert(UHMWPE)	6 mm	6 mm
Attribute	PredicateiTotal CR Knee Replacement System(K120316 and K122870)	Modified DeviceiTotal CR Knee Replacement System(This submission)
PosteriorCruciateLigament (PCL)Sparing	Yes	Yes
Instrumentation	Patient specific Nylon jigs	Patient specific Nylon jigs

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510(K) SUMMARY CONTINUED

Description and Conclusion of Testing

Nonclinical Testing: The determination of substantial equivalence for this device was based on a detailed device description. The following non-clinical laboratory testing was performed demonstrating that the device is safe and can be considered substantially equivalent to the predicate device for the intended use:

. Tibial interlock assembly and disassembly testing
. Contact area/contact stress testing
Constraint testing .
. Cadaveric testing

The determination of substantial equivalence for this device was based on a detailed device description. Non-clinical laboratory testing was performed demonstrating that the device is safe and can be considered substantially equivalent to the predicate device for the proposed intended use. Clinical data is not necessary to demonstrate substantial equivalence.

Conclusion

Safety and Performance

Based on the testing conducted it is concluded that the modified device is substantially equivalent to the iTotal Cruciate Retaining Knee Replacement System, K120316 cleared April 19, 2012 and K122870 cleared on January 14, 2013.

Special 510(k) - Modified iTotal® CR Knee Replacement System

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Image /page/6/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized human figure with outstretched arms, representing care and protection. The figure is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA", which is arranged in a circular fashion around the figure.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G60 Silver Spring, MD 20993-0002

May 24, 2013

ConforMIS, Incorporated % Ms. Amita Shah Vice President and Quality Affairs 28 Crosby Drive Bedford, Massachusetts 01730

Re: K131019

Trade/Device Name: iTotal CR Knee Replacement System Regulation Number: 21 CFR 888.3560 Regulation Name: Knee joint patellofemorotibial polymer/metal/polymer semi-constrained cemented prosthesis Regulatory Class: Class II Product Code: JWH, OOG, OIY Dated: May 13, 2013 Received: May 14, 2013

Dear Ms. Shah:

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

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Page 2 - Ms. Amita Shah

CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical ' device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) 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 Small Manufacturers, International and Consumer Assistance at its tollfree 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" (21CFR 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/ReportalProblem/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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely vours.

Erin Dkeith

For

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

Enclosure

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Indications for Use

510(k) Number (if known): _K131019

Device Name: iTotal CR Knee Replacement System

Indications for Use:

The iTotal® CR Knee Replacement System is intended for use as a total knee replacement in patients with knee joint pain and disability whose conditions cannot be solely addressed by the use of a prosthetic device that treats only one or two of the three knee compartments, such as a unicondylar, patellofemoral or bicompartmental prosthesis.

The Indications for Use include: .

Painful joint disease due to osteoarthritis, traumatic arthritis, rheumatoid arthritis ● or osteonecrosis of the knee.
Post traumatic loss of joint function. ●
Moderate varus, valgus or flexion deformity in which the ligamentous structures . can be returned to adequate function and stability.
. Failed osteotomies, hemiarthroplasties, and unicondylar, patellofemoral or bicompartmental implants.
Revision procedures provided that anatomic landmarks necessary for alignment . and positioning of the implant are identifiable on patient imaging scans.

The implant is intended for cemented use only.

Prescription Use Over-The-Counter Use AND/OR (Part 21 CFR 801 Subpart D) (21 CFR 801 Subpart C) (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Image /page/8/Picture/14 description: The image shows the words "Casey L. Hanley, Ph.D." on the top line, followed by a horizontal line. The second line says "Division of Orthopedic Devices". The text is in a simple, sans-serif font and appears to be part of a letterhead or official document.

Special 510(k) - Modified iTotal® CR Knee Replacement System

Regulation Number and Section

§ 888.3560 Knee joint patellofemorotibial polymer/metal/polymer semi-constrained cemented prosthesis.

(a)
Identification. A knee joint patellofemorotibial polymer/metal/polymer semi-constrained cemented prosthesis is a device intended to be implanted to replace a knee joint. The device limits translation and rotation in one or more planes via the geometry of its articulating surfaces. It has no linkage across-the-joint. This generic type of device includes prostheses that have a femoral component made of alloys, such as cobalt-chromium-molybdenum, and a tibial component or components and a retropatellar resurfacing component made of ultra-high molecular weight polyethylene. This generic type of device is limited to those prostheses intended for use with bone cement (§ 888.3027).(b)
Classification. Class II.