Orthocon MONTAGE Settable, Resorbable Bone Putty is indicated to fill bony voids or gaps in the skeletal system (i.e. extremities and pelvis). These defects may be surgically created, or osseous defects created as the result of traumatic injury to the bone. MONTAGE is indicated only for filling bony voids or gaps that are not intrinsic to the integrity of the bony structure.

When hardened in situ, MONTAGE may be used to augment provisional hardware (e.g., k-wires, plates and screws) and to help support bone fragments during the surgical procedure. The hardened putty acts only as a temporary support medium and is not intended to provide structural support during the healing process.

MONTAGE can be drilled and tapped, and hardware can be placed through it at any time during the setting process.

Device Description

AI/ML Overview

The provided text describes a 510(k) premarket notification for a medical device called MONTAGE Settable, Resorbable Bone Putty. This type of submission is for demonstrating substantial equivalence to a legally marketed predicate device, rather than proving efficacy through clinical trials with defined acceptance criteria for device performance. Therefore, many of the requested points, particularly those related to clinical study design, expert involvement, and ground truth establishment, are not applicable or cannot be extracted from this document.

However, I can extract information related to the animal study and performance testing that was conducted.

1. Table of Acceptance Criteria and Reported Device Performance

As this is a 510(k) submission focused on substantial equivalence rather than explicit performance acceptance criteria for a new clinical indication, formal acceptance criteria in the traditional sense are not explicitly stated for all performance aspects. The studies aim to demonstrate that MONTAGE performs similarly to or better than the predicate device.

Performance Metric	Acceptance Criteria (Implicit from predicate comparison)	Reported Device Performance (MONTAGE)
New Bone Formation (Rabbit Femoral Defect Model at 12 weeks)	Similar to or better than predicate device (HydroSet XT, 12.4%) and negative control (10%)	16.1%
Implant Material Remaining (Rabbit Femoral Defect Model at 52 weeks)	Similar to predicate device (HydroSet XT)	Approximately 70%
Drillability without fragmenting/displacement	Device can be drilled when hardened without fragmenting or displacement	Device performed as expected, allowing for use with provisional hardware
Temporary Support during Complex Repair	Device provides temporary support until permanent hardware fixation	Device performed as expected, providing temporary support
Biocompatibility	Meets ISO 10993 recommendations (cytotoxicity, irritation, systemic toxicity, genotoxicity, local tissue toxicity, hemolysis, endotoxicity, pyrogenicity)	All tests conducted were in accordance with GLP requirements and recommendations, suggesting successful completion. Labeling adjustment regarding Vitamin E acetate based on CDER assessment.
Sterility	SAL of 10^-6 (Standard for medical devices)	SAL of 10^-9 (exceeds standard)
Bacterial Endotoxin	Lot release criteria met	Each lot is tested and meets release criteria

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

Animal Study: The sample size for the rabbit critical sized femoral defect model is not explicitly stated as a number of animals, but refers to "MONTAGE group," "HydroSet predicate group," and "empty defect negative control group." No specific numbers are given per group.
Data Provenance: The animal study was conducted in a laboratory setting, likely in the country of the manufacturer or a contract research organization. The document does not specify the country. It is a prospective animal study. Other performance data are from in vitro studies.

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

Animal Study: The histopathology/histomorphometry assessments would typically be performed by veterinary pathologists or experts in bone histology. The document does not specify the number or qualifications of these experts.
Other Performance Tests: These were likely evaluated against engineering specifications or known material properties, not by human experts establishing ground truth in the clinical sense.

4. Adjudication method for the test set

Animal Study: Not specified. Histopathology and micro-CT assessments would likely involve independent evaluation, but no formal adjudication process like "2+1" or "3+1" is mentioned.
Other Performance Tests: Not applicable, as these are technical performance assessments rather than interpretations requiring adjudication.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, an MRMC comparative effectiveness study was not done. The device is a bone void filler, not an AI or imaging diagnostic device.

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

Not applicable. This is a physical medical device (bone putty), not an algorithm.

7. The type of ground truth used

Animal Study: The "ground truth" for the animal study was based on quantitative measurements from micro-CT and qualitative/quantitative assessments from histopathology/histomorphometry to determine new bone formation and implant resorption.
Other Performance Tests: The "ground truth" for drillability and temporary support was established through engineering performance tests comparing the device's physical behavior against predetermined functional expectations.
Biocompatibility: The "ground truth" was established by adherence to ISO 10993 standards and their associated endpoints.

8. The sample size for the training set

Not applicable. This is a physical medical device, not a machine learning algorithm requiring a "training set." The development of the material involved formulation and testing, but not in the context of a "training set" for AI.

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

Not applicable for the reasons stated above.

Summary

{0}------------------------------------------------

February 3, 2023

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Orthocon, Inc. Howard Schrayer Consultant 8 Lookout Hilton Head Island. South Carolina 29928

Re: K222063

Trade/Device Name: MONTAGE Settable, Resorbable Bone Putty Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: Class II Product Code: MQV, OIS Dated: July 1, 2022 Received: July 13, 2022

Dear Howard Schrayer:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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) for

{1}------------------------------------------------

devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Sara S. Thompson -S

For

Laura C. Rose, Ph.D. Assistant Director DHT6C: Division of Restorative, Repair and Trauma Devices OHT6: Office of Orthopedic Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

INDICATIONS FOR USE

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2023 See PRA Statement below.

510(k) Number (if known) K222063

Device Name MONTAGE Settable, Resorbable Bone Putty

Indications for Use (Describe)

MONTAGE can be drilled and tapped, and hardware can be placed through it at any time during the setting process.

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)

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."

FORM FDA 3881 (6/20)

PSC Publishing Services (301) 443-6740 EF

{3}------------------------------------------------

General Company Information

Name:Contact:	Orthocon, Inc.Howard SchrayerRegulatory Affairs Consultant
Address:	700 Fairfield Avenue – Suite 1Stamford, CT 06902
Telephone:	(609) 273 - 7350
Date Prepared:	February 3, 2023

General Device Information

Product Name:	MONTAGE™ Settable, Resorbable Bone Putty
Common Name:	Resorbable calcium salt bone void filler device
Classification:	Class II

Classification:	Class II
Product code:	MQV, OIS
Regulation:	21 CFR 888.3045

Predicate Devices

Primary Predicate:
Orthovita, Inc.	HydroSet XT™[510(k) Number K161447]

Reference Devices:

Orthocon, Inc. MONTAGE Settable, Resorbable Hemostatic Bone Putty [510(k) Number K152005]

{4}------------------------------------------------

K222063 Description

MONTAGE Settable, Resorbable Bone Putty is a sterile, biocompatible, resorbable material for use in filling bony voids or gaps in skeletal bones of the extremities. The MONTAGE device comprises two separate components of putty-like consistency containing granular calcium phosphate, calcium stearate, vitamin E acetate, a triglyceride, a polyalcohol and a mixture of a lactide-diester and polyester-based polymers. When mixed together, the components of the MONTAGE device form a cohesive putty-like material that adheres to the bone surface and remains in place following application. The resulting hardened material is primarily calcium phosphate. MONTAGE components must be mixed immediately prior to use. MONTAGE can be drilled and tapped, and hardware can be placed through it at any time during the setting process. The performance of MONTAGE was compared to HydroSet in a rabbit critical sized femoral defect model. At the 12-week timepoint, animal study data demonstrated new bone formation averages of 16.1% in the MONTAGE group, 12.4% in the HydroSet predicate group, and 10% in the empty defect negative control group. Animal study data demonstrated that approximately 70% of implant material remained in both the MONTAGE group and the predicate group at 52 weeks following implantation.

Intended Use (Indications)

When hardened in situ. MONTAGE may be used to augment provisional hardware (e.g., kwires, plates and screws) and to help support bone fragments during the surgical procedure. The hardened putty acts only as a temporary support medium and is not intended to provide structural support during the healing process.

MONTAGE can be drilled and tapped, and hardware can be placed through it at any time during the setting process.

Purpose of Submission

Orthocon is proposing to modify the labeling (Instructions for Use) to provide for use of MONTAGE as a bone void filler that can be used to augment provisional hardware (e.g., kwires, plates and screws) and to help support bone fragments during the surgical procedure.

Substantial Equivalence

This submission supports the position that Orthocon MONTAGE Settable, Resorbable Bone Putty is substantially equivalent to the HydroSet XT primary predicate 510(k) - K161447.

The following table shows comparisons of the several characteristics of MONTAGE Settable, Resorbable Bone Putty and the primary predicate device. The differences noted in the table below do not impact substantial equivalence.

{5}------------------------------------------------

SUBSTANTIAL EQUIVALENCE INFORMATION

Orthocon, Inc. MONTAGE Settable, Resorbable Bone Putty

Orthovita, Inc. HydroSet XT™ Bone Void Filler

510(k) K222063

510(k) - K161447

Similarities and Differences

Device is indicated for use as a bone graftsubstitute to fill voids in damaged bone thatare not intrinsic to the stability of the bonystructure.	Device is indicated for use as a bone graftsubstitute to fill voids in damaged bone thatare not intrinsic to the stability of the bonystructure.

Hardened device can be drilled and tappedto provide temporary support for theplacement of provisional hardware during thesurgical procedure.	Hardened device can provide temporarysupport for the placement of provisionalhardware during the surgical procedure.

At the time of application, device is in theform of a putty-like material	At the time of application, device is in theform of a paste-like material

Device is designed to be manually appliedand spread onto voids in bone tissue	Device is designed to be manually applied orinjected with a syringe and spread ontovoids in bone tissue

MONTAGE Settable, Resorbable Bone Puttyis formulated as a two-part putty/putty devicethat forms a "settable" (hardening) materialwhen manually mixed at the time of surgery	HydroSet XT settable, resorbable bone voidfiller device is formulated as a two-partpowder/liquid device that forms a "settable"(hardening) material when manually mixedat the time of surgery

Sterile mixture of two separate componentsof putty-like consistency comprised ofgranular calcium phosphate, (hydroxyapatiteand ß-tricalcium phosphate), calciumstearate, vitamin E acetate, triacetin, 1,4-butanediol and a mixture of a lactide-diesterand polyester-based (lactide andcaprolactone) absorbable polymers.MONTAGE is to be mixed immediately priorto use. Resulting settable material from thetwo putties is primarily comprised of calciumphosphate similar to the mineral phase ofnative bone tissue.	Sterile mixture of two separate components,a powder comprised of dicalcium phosphatedihydrate, tetracalcium phosphate and tri-sodium citrate; and a liquid comprised ofsodium phosphate, polyvinylpyrrolidone andwater. HydroSet XT is to be manually mixedimmediately prior to use. Resulting settablematerial from the two components isprimarily comprised of calcium phosphatesimilar to the mineral phase of native bonetissue.

{6}------------------------------------------------

Implanted device is resorbable in greaterthan 30 days primarily due to presence ofcalcium phosphate.	Implanted device is resorbable in greaterthan 30 days primarily due to presence ofcalcium phosphate.

The non-calcium salt and non-polymericcomponents degrade via dissolution; thepolymer degrades via hydrolysis and calciumsalts degrade via chemical dissolution and/orcellular removal	The non-calcium salt components degradevia dissolution and calcium salts degrade viachemical dissolution and/or cellular removal

Single-patient-use device is provided sterileby gamma irradiation	Single-patient-use device is provided sterileby gamma irradiation and ethylene oxide

The device is available in individual and/ormulti-pack patient use sizes.	The device is available in individual; and/ormulti-pack patient use sizes.

Each putty is placed into a separate inner foil"blister" which are contained within a singleouter foil pouch. The outer foil pouchcontains a desiccant. The inner blister andouter pouch is heat sealed and sterilized.Mixing for homogeneity takes 45 sec.	Each kit contains one liquid-filled glasssyringe and one plastic bowl of powderpackaged within a double pre-formed traywith a Tyvek lid.Mixing for homogeneity takes 45 sec.
Material is settable within 10 minutes ofapplication	Material is settable within 10 minutes ofapplication

Device cures with no appreciable exothermicreaction.	Device cures with no appreciable exothermicreaction

Testing Completed

Performance Animal Testing

The performance of MONTAGE was compared to HydroSet in a rabbit critical sized femoral defect model. Micro-CT and histopathology/histomorphometry assessments were performed on defects treated with each material to quantify device resorption and new bone formation. At the 12-week timepoint, animal study data demonstrated new bone formation averages of 16.1% in the MONTAGE group, 12.4% in the HydroSet predicate group, and 10% in the empty defect negative control group. Animal study data demonstrated approximately 70% of implant material remaining in both the MONTAGE group and the predicate group at 52 weeks following implantation. Clinical performance has not been evaluated.

Performance Data

Testing was conducted to verify that the device may be drilled when hardened without fragmenting or being displaced. This allows use in conjunction with provisional hardware. In addition, an in vitro study was conducted to demonstrate that once placed as indicated,

{7}------------------------------------------------

K222063

the device provides temporary support to a complex repair until permanent hardware fixation is accomplished.

Biocompatibility Testing

Testing was conducted to evaluate the device's biocompatibility in accordance with the recommendations of ISO 10993. The following biocompatibility studies were conducted on the final, finished, gamma-irradiation sterilized device and in accordance with the GLP requirements: cytotoxicity, irritation, systemic toxicity, genotoxicity, local tissue toxicity, hemolysis, endotoxicity and pyrogenicity.

The biocompatibility testing was supplemented by an assessment of the potential impact of the Vitamin E acetate content of MONTAGE. This assessment included an evaluation by CDER and concluded that labeling should include a Caution statement regarding the need to monitor patients taking Vitamin E supplements who may be at risk for bleeding.

Sterilitv

The gamma sterilization process has been validated to provide a SAL of 10-9. Each Jot of finished devices is tested for bacterial endotoxin for lot release.

Conclusions

The information provided establishes that the Orthocon MONTAGE Settable, Resorbable Bone Putty performs substantially equivalent to the predicate device for the same intended use. All results demonstrate that any differences in technology do not impact substantial equivalence.

Regulation Number and Section

§ 888.3045 Resorbable calcium salt bone void filler device.

(a)
Identification. A resorbable calcium salt bone void filler device is a resorbable implant intended to fill bony voids or gaps of the extremities, spine, and pelvis that are caused by trauma or surgery and are not intrinsic to the stability of the bony structure.(b)
Classification. Class II (special controls). The special control for this device is the FDA guidance document entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA.” See § 888.1(e) of this chapter for the availability of this guidance.