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, patello-femoral or bi-compartmental 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, hemiarthoplasties, and unicondylar, patello-femoral or bi-compartmental implants.

The implant is intended for cemented use only.

Device Description

The iTotal Cruciate Retaining Knee Replacement System (hereafter referred to as the "iTotal CR KRS") is a patient-specific tricompartmental faceted posterior cruciate ligament (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. The product design incorporates a bone preserving approach with minimal bone resection of the tibia and femur for the treatment of severe pain and/or disability of a knee damaged by osteoarthritis or trauma.

Using patient imaging (either CT or MR scans) and a combination of proprietary and off the shelf software, a patient-specific implant and related instrumentation are designed that best meet 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 manufactured from UHMWPE of identical configuration. The patellar component is manufactured from UHMWPE.

For user convenience, and similar to the predicate iTotal CR KRS, accessory orthopedic manual surgical 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 intra-operatively and in quiding the marking of bone before cutting.

The function and general design features of the patient-specific ancillary instruments remain similar to those described in the predicate 510k i.e. K094050, K103117, K112780, K120068, K113378 and K120316.

AI/ML Overview

Here's an analysis of the provided text regarding the ConforMIS iTotal CR Knee Replacement System, focusing on acceptance criteria and supporting studies:

This document is a 510(k) summary for a medical device (ConforMIS iTotal CR Knee Replacement System) seeking clearance from the FDA. In the context of a 510(k) submission, the primary "acceptance criterion" is demonstrating substantial equivalence to a legally marketed predicate device. The "study" proving this is typically a set of non-clinical tests and comparisons.

1. Table of Acceptance Criteria and Reported Device Performance

For a 510(k) submission, the "acceptance criteria" are demonstrating that the new device shares similar indications for use, technological characteristics, and performance (safety and effectiveness) as the predicate device(s). The "reported device performance" is the evidence presented to support this similarity.

Acceptance Criterion (Based on Substantial Equivalence Principles)	Reported Device Performance (Summary from Document)
Indications for Use (Identical to Predicate)	• 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, patello-femoral or bi-compartmental implants.• Intended for cemented use only. (Identical to predicate)
Technological Characteristics (Similar or Equivalent to Predicate)	Materials: Femoral Implant- CoCrMo, Metal-Backed Tibial Components (Tibial tray- CoCrMo, Tibial Insert-UHMWPE), Patellar Component-UHMWPE. (Identical to predicate)Design: Knee joint patellofemorotibial semi-constrained cemented prosthesis, Constant coronal curvature, Patient-specific sagittal J-curves (femoral implant), Metal Backed Tibial Implant (Single or Dual inserts, sizes 6-16mm, curved articulating surface, patient-specific profile, interference fit tray interlock, anterior lip, tray undercut design), Symmetrical patellar implant (sizes 32-44mm, heights 6-12mm). (Identical to predicate)Instrumentation: Patient-specific Nylon jigs. (Identical to predicate)Principle of Operation: Cemented use, Fixed Bearing Design, PCL Sparing, Patient-Matched. (Identical to predicate)
Performance (Safety and Effectiveness comparable to Predicate)	Nonclinical Testing:• Detailed software description and software verification and validation testing of proprietary software (iTotal iView).Conclusion: Non-clinical laboratory testing demonstrated that the device is safe and can be considered substantially equivalent to the predicate device for the intended use. Clinical data was not deemed necessary to demonstrate substantial equivalence. (This indicates no new safety or effectiveness concerns were raised by the modifications).

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

Test Set Sample Size: The document does not specify a "test set" in the traditional sense of a clinical or analytical study with a defined number of patient cases. The primary testing method described is software verification and validation testing of proprietary software (iTotal iView). This usually involves testing the software against a set of predefined requirements, scenarios, and potentially a dataset of patient images, but the exact number of "samples" or cases used for this internal testing is not disclosed in this summary.
Data Provenance: Not specified for the software V&V. It's likely internal data or simulated data used for engineering validation. Given the nature of patient-specific implants, the input for the software would be patient imaging (CT or MR scans), but the origin of these scans for testing purposes is not explicitly stated. The submission is focused on demonstrating equivalence to an existing product, not on new clinical claims.

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

Number of Experts: Not applicable/not specified. The detailed software verification and validation would typically involve software engineers, developers, and potentially expert clinicians (e.g., orthopedic surgeons) in defining requirements and evaluating software output (e.g., implant designs generated by the software), but the document does not outline a formal ground truth adjudication process by external experts with specific qualifications for a test set. The ground truth for the software's performance would be its ability to accurately and precisely process patient imaging data to generate the patient-specific implant and instrumentation designs according to predefined specifications.

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable/not specified. Since there isn't a defined "test set" requiring human interpretation or classification against a ground truth, an adjudication method like 2+1 or 3+1 is not mentioned. Software verification and validation is typically internal and relies on internal quality control processes and predefined acceptance criteria for software functionality and output accuracy.

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

MRMC Study: No, an MRMC comparative effectiveness study was not done. The device (ConforMIS iTotal CR KRS) is a knee replacement system and its associated patient-specific software and instruments used for implantation. It's not an AI diagnostic or assistive tool for image interpretation by human readers. The software assists in designing the implant and instruments based on patient imaging.
Effect Size: Not applicable.

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

Standalone Performance: The core of the new technology described is the "proprietary software iTotal iView" which generates the patient-specific surgical plan and designs the implants/instrumentation. The document states "Software verification and validation testing of proprietary t software iTotal iView" was performed. This implies testing of the algorithm itself, without a human in the loop for the design generation process. However, the outcome (the physical implant and instruments) is intended for human surgical use, and a surgeon is in the loop for the final implantation. The document doesn't explicitly detail "standalone performance" in terms of how the algorithm's output compares to a physician's manual planning, but rather focuses on verifying the software's functionality and accuracy in generating designs.

7. The Type of Ground Truth Used

Type of Ground Truth: For the software verification and validation, the ground truth would likely be established through:
- Engineering specifications and design requirements: The software's output (implant dimensions, bone cut guides) would be compared against the target design parameters derived from the patient's anatomy as interpreted by design engineers and surgeons, often using CAD models or reference anatomical data.
- Clinical expertise and anatomical models: The accuracy of the software's interpretation of patient imaging (CT/MR scans) and its subsequent design generation would be assessed against established anatomical principles and clinical requirements for knee replacement.
- Comparison to predicate device's design principles: Since this is a 510(k) for a modified device, the "ground truth" also heavily relies on demonstrating that the software-generated designs maintain the established safety and effectiveness characteristics of the predicate devices.

8. The Sample Size for the Training Set

Training Set Sample Size: Not applicable/not specified. The document describes "proprietary software" for designing the patient-specific implant and instruments. It does not explicitly state that this software utilizes machine learning or AI models that require a "training set" in the conventional sense. If it's a rule-based or conventional algorithmic software (common for CAD/CAM in medical devices at the time of this filing), a distinct "training set" might not exist. If it incorporates machine learning (which is not explicitly stated but possible even in 2012 for aspects like image segmentation or anatomical landmark identification), the training data details are not provided.

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

Ground Truth Establishment for Training Set: Not applicable/not specified, as a "training set" and its ground truth are not mentioned for this device's software. If machine learning were involved, the ground truth for training data would typically be established by expert annotation of medical images (e.g., outlining anatomical structures) or precise measurements performed by qualified personnel.

Summary

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K122033('/6

2017

5.0 510(K) SUMMARY:

Page 1 of 6

Submitter's Nameand Address	ConforMIS Inc.11 North Ave.Burlington, MA 01803
EstablishmentRegistrationNumber	3004153240 and 3008690421
Date of Summary	June 9, 2012
Contact Person	Amita S. Shah, Vice President, Quality Assurance and RegulatoryAffairs
Telephone Number	(781) 345-9164
Fax Number	(781) 345-0104
Name of the Device	ConforMIS iTotal® CR Knee Replacement System (KRS)
Common or UsualName	Cruciate Retaining Total Knee ReplacementSystem
ClassificationName	Knee joint patellofemorotibial polymer/metal/polymer semi-constrainedcemented prosthesis
Regulation Number	21 CFR 888.3560
DeviceClassification	Product Code:JWH, Knee joint patellofemorotibial polymer/metal/polymer semi-constrained cemented prosthesis.OOG, Knee joint patellofemorotibial polymer/metal/polymer semi-constrained cemented prosthesis.Intended 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.

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510(k) Summary continued Page 2 of 6 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, patello-femoral or bi-compartmental 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, hemiarthoplasties, and unicondylar, patello-. femoral or bi-compartmental implants. The implant is intended for cemented use only ConforMIS iTotal CR Knee Replacement System (KRS) ldentification of the Device Class: Legally Marketed ll JWH, OOG Device Product Code: (Predicate Device) Requlation Number: 21 CFR 888.3560 K094050, K103117, K112780, K113378, 510(k) number: K120068, K120316

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510(k) Summary continued Page 3 of 6

The iTotal Cruciate Retaining Knee Replacement System (hereafter Device Description referred to as the "iTotal CR KRS") is a patient-specific tricompartmental faceted posterior cruciate ligament (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. The product design incorporates a bone preserving approach with minimal bone resection of the tibia and femur for the treatment of severe pain and/or disability of a knee damaged by osteoarthritis or trauma.

Using patient imaging (either CT or MR scans) and a combination of proprietary and off the shelf software, a patient-specific implant and related instrumentation are designed that best meet 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 manufactured from UHMWPE of identical configuration. The patellar component is manufactured from UHMWPE.

For user convenience, and similar to the predicate iTotal CR KRS, accessory orthopedic manual surgical 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 intra-operatively and in quiding the marking of bone before cutting.

The function and general design features of the patient-specific ancillary instruments remain similar to those described in the predicate 510k i.e. K094050, K103117, K112780, K120068, K113378 and K120316.

Substantial Equivalence:

The product subject of this premarket notification is substantially equivalent to the iTotal Cruciate Retaining Knee Replacement System (K094050 cleared September 16, 2010, K103117 cleared January 7, 2011, K112780 cleared December 15, 2011, K120068 cleared February 3, 2012, K113378 cleared February 15, 2012 and K120316 cleared April 19, 2012) The following testing was performed to establish substantial equivalence:

Software verification and validation testing of proprietary t software iTotal iView

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510(k) Summary continued Page 4 of 6

Device Comparison

Characteristic	Modified iTotal CR KRS (This submission)	Predicate iTotal CR KRS (K112780 andK120316)
Indication for Use	The iTotal® CR Knee Replacement System isintended for use as a total knee replacementin patients with knee joint pain and disabilitywhose conditions cannot be solely addressedby the use of a prosthetic device that treatsonly one or two of the three kneecompartments, such as a unicondylar, patello-femoral or bi-compartmental prosthesis. Theindications for use include:• Painful joint disease due toosteoarthritis, traumatic arthritis,rheumatoid arthritis or osteonecrosisof the knee.• Post traumatic loss of joint function.• Moderate varus, valgus or flexiondeformity in which the ligamentousstructures can be returned toadequate function and stability.• Failed osteotomies,hemiarthoplasties, and unicondylar,patello-femoral or bi-compartmentalimplants.	The iTotal® CR Knee Replacement System isintended for use as a total knee replacementin patients with knee joint pain and disabilitywhose conditions cannot be solely addressedby the use of a prosthetic device that treatsonly one or two of the three kneecompartments, such as a unicondylar, patello-femoral or bi-compartmental prosthesis. Theindications for use include:• Painful joint disease due toosteoarthritis, traumatic arthritis,rheumatoid arthritis or osteonecrosisof the knee.• Post traumatic loss of joint function.• Moderate varus, valgus or flexiondeformity in which the ligamentousstructures can be returned toadequate function and stability.• Failed osteotomies,hemiarthoplasties, and unicondylar,patello-femoral or bi-compartmentalimplants.
The implant is intended for cemented use only	The implant is intended for cemented use only	The implant is intended for cemented use only
Intended for CementUse Only	Yes	Yes
ProductClassification	21 CFR 888.3560 (JWH)	21 CFR 888.3560 (JWH)
Components	• Femoral Component• Metal Backed Tibial Component• Patellar Component	• Femoral Component• Metal Backed Tibial Component• Patellar Component
Materials	• Femoral Implant- CoCrMo• Metal-Backed Tibial Components:◦ Tibial tray- CoCrMo◦ Tibial Insert-UHMWPE• Patellar Component: UHMWPE	• Femoral Implant- CoCrMo• Metal-Backed Tibial Components:◦ Tibial tray- CoCrMo◦ Tibial Insert-UHMWPE• Patellar Component: UHMWPE
Characteristic	Modified iTotal CR KRS (This submission)	Predicate iTotal CR KRS (K112780 andK120316)
Design	Knee joint patellofemorotibial semi - constrained cemented prosthesis	Knee joint patellofemorotibial semi - constrained cemented prosthesis
Configuration-Femoral Implant	Constant coronal curvature Patient-specific sagittal J- curves	Constant coronal curvature Patient-specific sagittal J- curves
Tibial Implant	Configuration: Metal Backed TibialImplant Single or Dual inserts Insert sizes:6-16mm Articulating Surface: curved Profile: patient-specific Tray interlock: Interference fit Anterior lip Tray undercut design	Configuration: Metal Backed TibialImplant Single or Dual inserts Insert sizes:6-16mm Articulating Surface: curved Profile: patient-specific Tray interlock: Interference fit Anterior lip Tray undercut design
Patellar Implant	Symmetrical, offered in sizes ranging from 32,35, 38, 41 and 44 mm, with correspondingheights of 6, 7, 8.5, 10 and 12mm.	Symmetrical, offered in sizes ranging from 32,35, 38, 41 and 44 mm, with correspondingheights of 6, 7, 8.5, 10 and 12mm.
Instrumentation	Patient-specific Nylon jigs	Patient-specific Nylon jigs
Principle ofOperation	Cemented useFixed Bearing Design	Cemented useFixed Bearing Design
Posterior CruciateLigament (PCL)Sparing	Yes	Yes
Patient-Matched	Yes	Yes
Packaging	Device components are individually doublepouched using Tyvek® /film pouches whichare sealed and labeled	Device components are individually doublepouched using Tyvek® /film pouches whichare sealed and labeled
Patient-specificsurgical plan	Generated by iTotal iView software ormanually generated	Manually generated
Sterility Method/Assurance Level	VHP Gas Plasma 1x10-6	VHP Gas Plasma 1x10-6
Initial Shelf-Life	6 months	6 months
Labeled Non-pyrogenic	No	No

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510(k) Summary continued Page 5 of 6

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510(k) Summary continued Page 6 of 6

Description andConclusion ofTesting	Nonclinical Testing: The determination of substantial equivalence forthis device was based on a detailed device description. The followingnon-clinical laboratory testing was performed demonstrating that thedevice is safe and can be considered substantially equivalent to thepredicate device for the intended use:• Detailed software description and software verification andvalidation testing of proprietary software
Safety and
Performance	The determination of substantial equivalence for this device was basedon a detailed device description. Non-clinical laboratory testing wasperformed demonstrating that the device is safe and can be consideredsubstantially equivalent to the predicate device for the intended use.Clinical data is not necessary to demonstrate substantial equivalence.
Conclusion:	Based on the testing conducted, it is concluded that the iTotal CruciateRetaining Knee Replacement System with the use of the iTotal iViewproduction software is substantially equivalent to the iTotal CruciateRetaining Knee Replacement System (K094050 cleared September 16,2010, K103117 cleared January 7, 2011, K112780 cleared Dec 15,2011, K120068 cleared on February 3, 2012 and K113378 cleared onFebruary 15, 2012 and K120316 cleared April 19, 2012.

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Image /page/6/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" written around the perimeter. Inside the circle is an abstract image of an eagle with its wings spread.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

2 7 2012

Conformis, Incorporated
% Ms. Amita S. Shah
Vice President, Quality Assurance and Regulatory Affairs
11 North Ave
Burlington, Massachusetts 01803

Re: K122033

Trade/Device Name: ConforMIS® iTotal Cruciate Knee Replacement System (iTotal CR KRS)

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 Dated: July 9, 2012

Received: July 16, 2012

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 S. 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 go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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/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 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 yours,

Mark N. Melkerson

Director Division of Surgical, Orthopedic and Restorative Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

K122033 510(k) Number (if known):

Device Name:

ConforMIS® iTotal Cruciate Retaining (CR) Knee Replacement System (iTotal CR KRS)

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, hemiatthoplasties, and unicondylar, patello-femoral or bi-. compartmental implants.

The implant is intended for cemented use only.

Adf

(Division Sign-Off) Division of Surgical, Orthopedic, and Restorative Devices

510(k) Number K122033

Over-The-Counter Use Prescription Use _ X 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)

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

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.