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, 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 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 iPoly XE™ (a highly cross-linked vitamin E infused polyethylene) The patellar component is also manufactured from either UHMWPE or 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 proposed 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), K160025.

AI/ML Overview

The provided document is a 510(k) summary for the ConforMIS iTotal® Cruciate Retaining (CR) Knee Replacement System (iTotal CR KRS). It focuses on establishing substantial equivalence to a predicate device, specifically for an additional sterilization method (Ethylene Oxide) for certain components.

The information requested, which typically relates to the acceptance criteria and study data for device performance in relation to its intended clinical use (e.g., accuracy, sensitivity, specificity, or effects on human readers for AI/diagnostic devices), is not present in this document. This submission primarily deals with changes in manufacturing (sterilization methods) and material properties, rather than clinical efficacy or diagnostic performance. Therefore, the requested information about device performance against acceptance criteria for a "study that proves the device meets the acceptance criteria" in a clinical/diagnostic sense cannot be extracted from this text.

However, I can provide information on the acceptance criteria and supporting "study" (validation testing) related to the sterilization process as outlined in the document:

Here's the information regarding the sterilization validation:

1. Table of Acceptance Criteria and Reported Device Performance (related to sterilization)

Acceptance Criteria	Reported Device Performance
Sterility Assurance Level (SAL) of 1.0 x 10^-6 for all components post-sterilization (VHP or Ethylene Oxide)	Meets Criteria: Sterilization Validation was performed to confirm an SAL of 1.0 x 10^-6 for all components, including those sterilized via Ethylene Oxide. The iPoly XE components, previously cleared for VHP, are now also cleared for EO sterilization to an SAL of 1.0 x 10^-6.
Acceptable Ethylene Oxide (EO) Residuals	Meets Criteria: EO Residual Testing was performed. (Specific residual values are not detailed, but the conclusion of substantial equivalence implies acceptable levels).
Retention of Mechanical, Material, and Chemical Properties Post-EO Sterilization for iPoly XE	Meets Criteria: Testing was performed to demonstrate that the iPoly XE material retains its mechanical, material, and chemical properties after EO sterilization. (Specific tests/results are not detailed, but the conclusion of substantial equivalence implies satisfactory results).
Non-pyrogenic status (<20 EU/Device)	Meets Criteria: Non-pyrogenic status was determined using the LAL test method with an identified acceptable testing limit of <20 EU/Device. Controls are in place to monitor manufacturing processes for endotoxin, and final sterilized devices are routinely tested.

2. Sample size used for the test set and the data provenance

The document does not specify exact sample sizes for the sterilization validation tests (e.g., how many devices or components were tested for SAL, residuals, or material properties).
The data provenance is from ConforMIS, Incorporated, the manufacturer of the device, implying the testing was conducted internally or by a contracted lab as part of their regulatory submission for a premarket notification (510(k)). The studies are retrospective in the sense that they were performed to support a regulatory submission for a device already developed, not as a prospective clinical trial. There is no mention of country of origin for the data beyond the applicant's location (Bedford, Massachusetts).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This question is not applicable to the type of validation described. Sterilization validation and material property testing rely on standardized laboratory protocols and measurements, not expert consensus or ground truth derived from clinical experts.

4. Adjudication method for the test set

This question is not applicable. Adjudication methods (like 2+1, 3+1) are typically used for interpreting ambiguous clinical imaging or data by multiple experts. Such a process is not part of sterilization validation or material property testing.

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

This question is not applicable. The device described (ConforMIS iTotal CR KRS) is a knee replacement system, which is an implantable medical device, not an AI or diagnostic application. Therefore, MRMC studies involving human readers and AI assistance are irrelevant.

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

This question is not applicable, as the device is a physical knee implant, not an algorithm or AI system.

7. The type of ground truth used

For sterilization validation:

Sterility: The "ground truth" for sterility is established by microbiological testing (e.g., bioburden, sterility testing) following international standards, demonstrating the inactivation of microbial populations to the specified SAL.
EO Residuals: Chemical analysis (analytical chemistry methods) to measure residual levels against predefined safety limits.
Material Properties: Standardized mechanical, chemical, and material characterization tests (e.g., tensile strength, wear resistance, chemical composition) to compare pre- and post-sterilization properties against specifications.
Non-pyrogenicity: The LAL (Limulus Amebocyte Lysate) test method, which quantitatively measures endotoxin levels.

8. The sample size for the training set

This question is not applicable, as the device is not an AI/machine learning system that requires a training set.

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

This question is not applicable.

Summary

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

June 14, 2016

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

Re: K161366

Trade/Device Name: ConforMIS iTotal® Cruciate Retaining (CR) 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, OIY Dated: May 13, 2016 Received: May 17, 2016

Dear Ms. Amita 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

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(21 CFR Part 807); labeling Parts 801); medical device reporting (reporting of medical devicerelated 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 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" (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.

Lori A. Wiggins -S

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) K161366

Device Name

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

Indications for Use (Describe)

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.

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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8.0 510(K) SUMMARY (PAGE 1 OF 5)

Submitter's Name andAddress:	ConforMIS, Inc.28 Crosby DriveBedford, MA 01730
Establishment RegistrationNumber:	3009844603 and 3004153240
Date of Summary:	May 13, 2016
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® Cruciate Retaining Knee Replacement System(iTotal CR KRS)
Common Name:	Total 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 Code: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 generic type of device includes prosthesis that have a femoralcomponent made of alloys, such as cobalt-chromium-molybdenum, anda tibial component(s) and/or a retropatellar resurfacing componentmade of ultra-high molecular weight polyethylene plus an additive, suchas α-tocopherol.

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510(K) SUMMARY (PAGE 2 OF 5)

Indications for Use:	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, 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: ll Product Code: JWH, OOG, OIY Regulation Number: 21 CFR 888.3560 510(k) Number: K160025 & K122870

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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 iPoly XE™ (a highly cross-linked vitamin E infused polyethylene) The patellar component is also manufactured from either UHMWPE or 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 proposed 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), K160025.

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510(K) SUMMARY (PAGE 4 OF 5)

Comparison Summary of Technological Characteristics and Modifications Proposed:

The proposed iTotal CR KRS and predicate iTotal CR KRS have the same technological characteristics. There have been no changes to the proposed iTotal CR KRS devices with respect to design, materials, and methods of manufacture, or packaging. The designs of the devices remain similar to those cleared via K160025.

This submission proposes the addition of ethylene oxide sterilization as an alternative sterilization method for the iPoly XE components. The iPoly XE components of the iTotal CR KRS are cleared for sterilization via VHP (Gas Plasma) (K122870). EO Sterilization was cleared as an alternative method of sterilization for the iTotal CR KRS (K133256).

Table 8.0-1: Comparison Between the Proposed and Predicate Implant Components

ComponentMaterial	Predicate iTotal CRKRS(K160025)	Proposed iTotal CRKRS(This submission)
CrCoMo Femoral andTibial Implant	Sterilized via VHP (GasPlasma) or Ethylene Oxideto an SAL of $1.0x10^{-6}$	Sterilized via VHP (GasPlasma) or Ethylene Oxideto an SAL of $1.0x10^{-6}$
UHMWPE TibialInserts and Patella	Sterilized via VHP (GasPlasma) or Ethylene Oxideto an SAL of $1.0x10^{-6}$	Sterilized via VHP (GasPlasma) or Ethylene Oxideto an SAL of $1.0x10^{-6}$
iPoly XE (Vitamin Einfused highly cross-linked UHMWPE) TibialInserts and Patella	Sterilized via VHP (GasPlasma) to an SAL of$1.0x10^{-6}$	Sterilized via VHP (GasPlasma) or Ethylene Oxideto an SAL of $1.0x10^{-6}$

Substantial Equivalence:

The proposed iTotal CR KRS is substantially equivalent to the predicate iTotal CR KRS (K160025 cleared March 7, 2016 and K122870 cleared January 14, 2013). The following non-clinical testing was performed to establish substantial equivalence:

Sterilization Validation to confirm a Sterility Assurance Level . (SAL) of 1.0x10-6
Ethylene Oxide (EO) Residual Testing ●
Mechanical, Material, and Chemical Property Testing Post-. EO Sterilization for iPoly XE
. Non-pyrogenic status for the iTotal CR was determined using the LAL test method with an identified acceptable testing limit of <20 EU/Device. Controls are in place to monitor relevant manufacturing processes for endotoxin. Endotoxin testing of final sterilized devices is performed on a routine basis.

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510(K) SUMMARY (PAGE 5 OF 5)

Conclusion: Based on the testing conducted, it is concluded that the proposed iTotal Cruciate Retaining Knee Replacement System is substantially equivalent to the predicate device, the iTotal Cruciate Retaining Knee Replacement System (K160025 cleared March 7, 2016 and K122870 cleared on January 14, 2013). The components manufactured from the iPoly XE material can be sterilized to an SAL of 1.0x10·6 using Ethylene Oxide sterilization.

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.