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.

The iTotal PS 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, polyarthritis, or osteonecrosis of the knee
· Post traumatic loss of joint function
· Moderate varus, valgus, or flexion deformity
· 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® Knee Replacement Systems (hereafter referred to as the "iTotal KRS") are patient specific tricompartmental faceted knee replacement systems. The iTotal® KRS are semi-constrained, cemented knee implants which consist of femoral, tibial, and patellar components.
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 single or dual-piece (CR only) polyethylene inserts. The polyethylene inserts may be manufactured from either UHMWPE, or for iTotal CR KRS, 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 KRS, accessory orthopedic manual surgical instruments designed for use with the modified iTotal KRS are provided to assist with implantation. The ancillary instruments may be provided sterile and for single-use only. The purpose of this submission to propose the alternative option to provide these single-use, disposable iTotal iJig instruments non-sterile to be steam sterilized by the end-user. These patient specific instruments are provided to assist in the positioning of total knee replacement components intra-operatively and in guiding the cutting of bone.
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 K142404.

AI/ML Overview

The provided text is a 510(k) summary for the ConforMIS iTotal Cruciate Retaining Knee Replacement System and ConforMIS iTotal Posterior Stabilized Knee Replacement System. This document focuses on demonstrating substantial equivalence to previously cleared predicate devices, specifically regarding a change in how ancillary instruments are supplied (non-sterile for steam sterilization by the end-user).

This is not a study that provides performance metrics like sensitivity, specificity, accuracy, or effect sizes for a diagnostic or AI-driven device. Instead, it details a regulatory submission for a physical medical device (knee implants and surgical instruments) and the testing conducted to support its safety and effectiveness relative to existing devices. Therefore, many of the requested categories for acceptance criteria and study details are not applicable to this type of submission.

Here's a breakdown of what can be extracted from the provided text, and what cannot:

1. A table of acceptance criteria and the reported device performance

The document does not provide acceptance criteria and reported device performance in terms of diagnostic metrics (e.g., sensitivity, specificity). Instead, it refers to equivalence testing of the sterilization process and product integrity after sterilization.

Acceptance Criteria (Implied for sterilization)	Reported Device Performance
Achieve a Sterility Assurance Level (SAL) of 1x10-6	Steam Sterilization Validation to an SAL of 1x10-6 (Passed)
Maintain product integrity post-steam sterilization	Product Integrity Testing Post-Steam Sterilization (Passed)

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Sample Size for test set: Not explicitly stated regarding the number of devices or sterilization cycles. However, regulatory testing for sterilization validation typically involves multiple samples to demonstrate consistency.
Data Provenance: Not specified, but likely laboratory testing conducted by the manufacturer (ConforMIS, Inc.) in the USA, as per the submission details.
Retrospective or prospective: This would be prospective laboratory testing of the sterilization process and material integrity.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Not applicable. This is not a study requiring expert readers to establish ground truth for a diagnostic outcome. The "ground truth" here is the validation of the sterilization process and physical integrity of the instruments, which is typically assessed through standardized laboratory methods and microbial challenges, not expert consensus on medical images or diagnoses.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable, as this is not a study involving human interpretation or adjudication of diagnostic outputs.

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

Not applicable. This is not a study assessing human reader performance or AI assistance.

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

Not applicable. This is a physical medical device (knee implants and instruments), not an algorithm or AI system.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The "ground truth" implicitly used for this type of submission is the successful demonstration of sterilization to a defined SAL (Sterility Assurance Level) and the maintenance of product integrity under validated test conditions. This is established through microbiology testing (for SAL) and mechanical/material testing (for product integrity), rather than medical expert consensus or patient outcomes.

8. The sample size for the training set

Not applicable. This is not a machine learning or AI algorithm.

9. How the ground truth for the training set was established

Not applicable.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol consisting of three stylized human profiles facing to the right, stacked on top of each other.

October 21, 2015

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: K152704

Trade/Device Name: ConforMIS iTotal Cruciate Retaining Knee Replacement System, ConforMIS iTotal Posterior Stabilized 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, OOG, OIY Dated: September 18, 2015 Received: September 21, 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 of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

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Page 2 - Ms. Amita Shah

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 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/Resourcesfor You/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/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)

K152704

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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Indications for Use

510(k) Number (if known)

K152704

Device Name

ConforMIS iTotal Posterior Stabilized Knee Replacement System

Indications for Use (Describe)

· Painful joint disease due to osteoarthritis, traumatoid arthritis, polyarthritis, or osteonecrosis of the knee

· Post traumatic loss of joint function

· Moderate varus, valgus, or flexion deformity

· 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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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8.0 510(K) SUMMARY (PAGE 1 OF 4)

Submitter's Name andAddress:	ConforMIS, Inc.28 Crosby DriveBedford, MA 01730
Establishment RegistrationNumber:	3009844603 and 3001153240
Date of Summary:	September 18, 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(s):	ConforMIS iTotal® Cruciate Retaining Knee Replacement System(iTotal CR KRS)ConforMIS iTotal® Posterior Stabilized Knee Replacement System(iTotal PS KRS)
Common Name(s):	Total Cruciate Retaining Knee Replacement SystemTotal Posterior Stabilized Knee Replacement System
Regulatory Status andRegulation Number:	Class II21 CFR 888.3560
Classification Name:	Knee joint patellofemorotibial polymer/metal/polymer semi-constrainedcemented prosthesis
Device Classification:	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 implant components.
	OIY: Prosthesis, knee, patellofemorotibial, semi-constrained, cemented,polymer + additive/metal/polymer + additive. This generic type of deviceincludes prosthesis that have a femoral component made of alloys, suchas cobalt-chromium-molybdenum, and a tibial component(s) and/or aretropatellar resurfacing component made of ultra-high molecular weightpolyethylene plus an additive, such as α-tocopherol.

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510(K) SUMMARY (PAGE 2 OF 4)

Indications for Use:

iTotal CR KRS

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.

iTotal PS KRS

The Indications for Use include:

Painful joint disease due to osteoarthritis, traumatic arthritis, rheumatoid arthritis, polyarthritis or osteonecrosis of the knee.
Post traumatic loss of joint function.
Moderate varus, valgus or flexion deformity.
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.

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510(K) SUMMARY (PAGE 3 OF 4)

Identification of the Legally Marketed Device(s) (Predicate Device(s)):	ConforMIS iTotal CR Knee Replacement System
	Device Class: II
	Product Code: JWH, OOG, OIΥ
	Regulation Number: 21 CFR 888.3560
	510(k) Number: K142161 and K142404
	ConforMIS iTotal PS Knee Replacement System
	Device Class: II
	Product Code: JWH, OOG, OIΥ
	Regulation Number: 21 CFR 888.3560
	510(k) Number: K142161 and K142404
Device Description:	The iTotal® Knee Replacement Systems (hereafter referred to as the "iTotal KRS") are patient specific tricompartmental faceted knee replacement systems. The iTotal® KRS are semi-constrained, cemented knee implants which consist of femoral, tibial, and patellar components.
	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 single or dual-piece (CR only) polyethylene inserts. The polyethylene inserts may be manufactured from either UHMWPE, or for iTotal CR KRS, 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 KRS, accessory orthopedic manual surgical instruments designed for use with the modified iTotal KRS are provided to assist with implantation. The ancillary instruments may be provided sterile and for single-use only. The purpose of this submission to propose the alternative option to provide these single-use, disposable iTotal iJig instruments non-sterile to be steam sterilized by the end-user. These patient specific instruments are provided to assist in the positioning of total knee replacement components intra-operatively and in guiding the cutting of bone.
	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 K142404.

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510(K) SUMMARY (PAGE 4 OF 4)

Comparison Summary of Technological Characteristics and Modifications Proposed:

The modified iTotal KRS and predicate iTotal KRS have the same technological characteristics. There have been no changes to the modified iTotal KRS devices with respect to the intended use and function. The design, materials, and methods of manufacture and packaging remain similar to those cleared via K142161 and K142404.

This submission proposes an alternative option to provide the iTotal iJiq instrumentation as non-sterile to be steam sterilized by the end-user. The implants will continue to be provided sterile as currently cleared (K142161 and K142404).

Devices
How Supplied	iTotal Implants	iTotal iJigInstrumentation
Predicate Devices(K142161 &K142404)	Provided sterile viaVHP (gas glasma) orEO to an SAL of 1x10-6	Provided sterile viaVHP (gas glasma) orEO to an SAL of 1x10-6
This Submission	Provided sterile viaVHP (gas glasma) orEO to an SAL of 1x10-6	Provided sterile viaVHP (gas glasma) orEO to an SAL of 1x10-6ORProvided non-sterile tobe steam sterilized bythe end-user*

Table 8.0-1: Comparison Between the Predicate and Modified

*The following currently marketed systems provide non-sterile, patient-specific instruments:

Signature Patient-Specific Surgical Guides (K140257)
Visionaire (K143226) ●

Substantial Equivalence: The products subject of this premarket notification are substantially equivalent to the iTotal CR and PS KRS (K142161, cleared November 14, 2014 and K142404, cleared December 11, 2014). The following testing was performed to establish substantial equivalence:

. Steam Sterilization Validation to a Sterility Assurance Level (SAL) of 1x10-6
Product Integrity Testing Post-Steam Sterilization ●

Conclusion: The determination of substantial equivalence for these devices was based on detailed device descriptions. Non-clinical laboratory testing was performed demonstrating that the devices can be considered substantially equivalent to the predicate devices for the intended uses. Clinical data is not necessary to demonstrate substantial equivalence.

Based on the testing conducted, it is concluded that the modified iTotal KRS are substantially equivalent to the predicate iTotal KRS (K142161, cleared November 14, 2014 and K142404, cleared December 11, 2014).

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.