The iTotal CR Knee Replacement System (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, traumatoid arthritis, rheumatoid arthritis or osteonecrosis of the knee
· Post traumatic loss of joint function.
· Moderate varus, valgus or flexion deformity in which the ligamentous structurs 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 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.

Using patient imaging 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 either UHMWPE or a highly cross-linked Vitamin E infused polyethylene (iPoly XE™) The patellar component is also manufactured from either UHMWPE or from a highly cross-linked Vitamin E infused polyethylene (iPoly XE™).

For user convenience, and similar to the predicate iTotal CR KRS, patient specific accessory orthopedic manual surgical instruments designed for use with the modified iTotal CR KRS are provided to assist in the positioning of the total knee replacement components intraoperatively and in guiding the cutting of bone. In addition, reusable orthopedic manual surgical instruments are provided separately.

The function and general design features of the patient specific implants and ancillary instruments remain similar to those described in the predicate 510(k)s K142161 and K152704.

AI/ML Overview

The provided text describes a 510(k) premarket notification for a medical device called the ConforMIS iTotal Cruciate Retaining (CR) Knee Replacement System (KRS). The core of this submission is to demonstrate substantial equivalence to previously cleared predicate devices.

Here's an analysis of the acceptance criteria and the "study" that proves the device meets them, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

It's important to note that this document does not present acceptance criteria in the traditional sense of numerical thresholds for a new device's performance against a gold standard. Instead, the "acceptance criteria" are implied by the demonstration of substantial equivalence to predicate devices, focusing on the functionality and safety of the modifications made.

The primary "performance" being evaluated is the proper functioning of the updated CAD software used in the manufacturing process.

Acceptance Criteria (Implied)	Reported Device Performance (as demonstrated by testing)
Software functionality is robust and accurate.	Software verification and validation testing of proprietary software (iFit iTotalTib CR) was performed, demonstrating its intended function.
Manufacturing process changes (automation) do not adversely affect product design, materials, or manufacturing methods.	The non-clinical testing demonstrated that the device can be considered substantially equivalent to the predicate device for the intended use despite the CAD process updates. No changes were made to design, materials, manufacturing, packaging, or sterilization.
The modified device maintains the same technological characteristics as the predicate.	The modified iTotal CR KRS and predicate iTotal CR KRS have the same technological characteristics.
The device remains suitable for its stated Indications for Use.	The device's Indications for Use are identical to the predicate devices and the non-clinical testing supports continued substantial equivalence for these indications.

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

Test Set Sample Size: Not explicitly stated in terms of a number of patient cases or specific outputs. The testing was focused on software verification and validation testing of proprietary software iFit iTotalTib CR, and not on clinical patient data.
Data Provenance: Not applicable in the context of patient data. The "data" being tested would be internal software outputs and comparisons, rather than external patient cases. The software itself is proprietary to ConforMIS.

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

Number of Experts: Not specified.
Qualifications of Experts: Not specified. Given that this is software verification and validation, the ground truth would typically be established based on engineering specifications, mathematical models, and perhaps manual expert review of CAD outputs to confirm their correctness against design requirements.

4. Adjudication Method for the Test Set

Adjudication Method: Not specified. For software verification and validation, adjudication would involve comparing software outputs with expected results (ground truth defined by specifications or manual calculations/reviews).

5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study

Was an MRMC study done? No, an MRMC comparative effectiveness study was not done. The submission explicitly states: "Clinical data is not necessary to demonstrate substantial equivalence." This is a software and device modification submission, not a new clinical efficacy claim requiring human-in-the-loop performance evaluation.
Effect size of human readers improve with AI vs without AI assistance: Not applicable, as no MRMC study was performed and AI assistance for human readers is not the subject of this submission. The "AI" here refers to automated CAD processes, not decision support for human readers.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Was a standalone study done? Yes, in essence. The "software verification and validation testing of proprietary software iFit iTotalTib CR" constitutes a standalone evaluation of the algorithm's performance in generating the customized implant designs. Although not framed as a "study" in a clinical sense, this testing evaluates the algorithm's functional correctness without human intervention in the design generation phase itself (though humans define parameters and review outputs).

7. Type of Ground Truth Used

Type of Ground Truth: The ground truth for the software verification and validation would be based on engineering specifications, design requirements, and potentially known correct outputs from previous versions of the software or manual calculations. It's likely a combination of:
- Specification-based: Does the software produce outputs that meet predefined engineering specifications for implant geometry and fit?
- Comparison-based: Are the outputs from the new automated CAD processes consistent with those generated by the predicate device's CAD processes or manual processes for similar inputs?

8. Sample Size for the Training Set

Training Set Sample Size: Not applicable. This document describes a submission for a medical device (knee replacement system) with updated manufacturing software, not an AI/ML model that requires a training set of data in the common sense. The "training" for the software would be its initial development and programming based on engineering principles and design rules, not data-driven machine learning.

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

How Ground Truth for Training Set Was Established: Not applicable. As noted above, this is about software verification and validation for a manufacturing process, not an AI/ML model for which a "training set" with established ground truth is required. The software's "knowledge" is encoded during its development from established biomechanical, anatomical, and engineering principles used in knee replacement design.

Summary

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March 25, 2016

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

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

Re: K153721

Trade/Device Name: iTotal Cruciate Retaining (CR) Knee Replacement System Regulation Number: 21 CFR 888.3560 Regulation Name: Knee joint patellofemorotibial polymer semi-constrained cemented prosthesis Regulatory Class: Class II Product Code: JWH, OIY, OOG Dated: December 23, 2015 Received: December 28, 2015

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 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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Indications for Use

510(k) Number (if known) K153721

Device Name

ConforMIS iTotal Cruciate Retaining Knee Replacement System

Indications for Use (Describe)

· Painful joint disease due to osteoarthritis, traumatoid arthritis, rheumatoid arthritis or osteonecrosis of the knee
· Post traumatic loss of joint function.
· Moderate varus, valgus or flexion deformity in which the ligamentous structurs 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.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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6.0 510(K) SUMMARY (PAGE 1 OF 5)

Submitter's Nameand Address:	ConforMIS, Inc.28 Crosby DriveBedford, MA 01730
EstablishmentRegistrationNumber:	3009844603 and 3004153240
Date of Summary:	December 21, 2015
Contact Person:Telephone Number:Fax Number:	Amita S. Shah, Sr. Vice President, Regulatory and Quality Affairs(781) 345-9164(781) 345-0147
Name of the Device:	ConforMIS iTotal® CR Knee Replacement System (iTotal CR KRS)
Common Name:	Total Cruciate Retaining Knee Replacement System
Regulatory Statusand RegulationNumber:	Class II21 CFR 888.3560
Classification Name:	Knee joint patellofemorotibial polymer/metal/polymer semi-constrained cemented prosthesis
DeviceClassification:	Product Codes:JWH: Knee joint patellofemorotibial polymer/metal/polymer semi-constrained cemented prosthesis.
	OOG: Knee Arthroplasty Implantation System.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 implantcomponents.
	OIY: Prosthesis, knee, patellofemorotibial, semi-constrained,cemented polymer + additive/metal/polymer + additive. This generictype of device includes prosthesis that have a femoral componentmade of alloys, such as cobalt-chromium-molybdenum, and a tibialcomponent(s) and/or a retropatellar resurfacing component made ofultra-high molecular weight polyethylene plus an additive, such as a-tocopherol.

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510(K) SUMMARY (PAGE 2 OF 5)

Indications for Use: The iTotal® Cruciate Retaining (CR) Knee Replacement System (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.

K142161, K152704

This implant is intended for cemented use only.

ldentification of the ConforMIS iTotal CR Knee Replacement System (ITOTAL CR Legally Marketed KRS) Device (Predicate Device Class: 11 Device): Product Code: JWH, OOG, OIY Regulation Number: 21 CFR 888.3560

510(k) Number:

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510(K) SUMMARY (PAGE 3 OF 5)

Device Description: The iTotal® CR 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.

Using patient imaging 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 either UHMWPE or a highly cross-linked Vitamin E infused polyethylene (iPoly XE™) The patellar component is also manufactured from either UHMWPE or from a highly cross-linked Vitamin E infused polyethylene (iPoly XE™).

For user convenience, and similar to the predicate iTotal CR KRS, patient specific accessory orthopedic manual surgical instruments designed for use with the modified iTotal CR KRS are provided to assist in the positioning of the total knee replacement components intraoperatively and in guiding the cutting of bone. In addition, reusable orthopedic manual surgical instruments are provided separately.

The function and general design features of the patient specific implants and ancillary instruments remain similar to those described in the predicate 510(k)s K142161 and K152704.

The subject of this premarket notification is substantially Substantial Equivalence: equivalent to the iTotal CR KRS (K142161 cleared November 14, 2014 and K152704 cleared October 21, 2015). The following testing was performed to establish substantial equivalence:

Software verification and validation testing of proprietary . software

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510(K) SUMMARY (PAGE 4 OF 5)

Description and Assessment of NonclinicalTesting:

The modified iTotal CR KRS and predicate iTotal CR KRS have the same technological characteristics. There have been no changes to the modified iTotal CR KRS device with respect to design, materials and methods of manufacture, packaging, or sterilization. The design of the device remains similar to that cleared in K142161 and K152704.

The proposed modifications, which represent improving manufacturing efficiencies, are primarily focused on increasing automation of the CAD manufacturing processes via the proprietary software modules as shown in Table 1 below.

Table 1: Comparison between the Modified and Predicate Device

Characteristic	PredicateiTotal CruciateRetaining KneeReplacement System(K142161 and K152704)	iTotal CruciateRetaining KneeReplacementSystem(This submission)
CAD Process forTibial implants	iTotalTib version 3.0 ormanual process	iFit iTotalTib CRversion 4.0 ormanual process
CAD Process forTibial iJigs	iTotal TibJigs version 2.0or manual process	iFit iTotalTib CRversion 4.0 ormanual process
CAD Review oftibial components	Manual Process	iFit iTotalTib CRversion 4.0 ormanual process

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 can be considered substantially equivalent to the predicate device for the intended use:

Detailed software description and software verification . and validation testing of proprietary software iFit iTotalTib CR

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510(K) SUMMARY (PAGE 5 OF 5)

Conclusion 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 can be considered substantially equivalent to the predicate device for the intended use. Clinical data is not necessary to demonstrate substantial equivalence.

Based on the testing conducted, it is concluded that the modified iTotal CR KRS is substantially equivalent to the predicate iTotal CR KRS (K142161 cleared November 14, 2014 and K152704 cleared October 21, 2015).

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.