Mineral Collagen Composite Bioactive Moldable is intended for use as a bone void filler for voids or gaps, that are not intrinsic to the stability of the bony structure. The device is to be gently packed into bony voids or gaps of the skeletal system (i.e., the extremities, pelvis, and posterolateral spine). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. The device resorbs and is replaced with bone during the healing process.

For spine applications, Mineral Collagen Composite Bioactive Moldable is combined with either autogenous bone marrow or autograft with saline and can also be used with autograft as a bone graft extender.

Device Description

Mineral Collagen Composite Bioactive Moldable Bone Graft Matrix is composed of anorganic bone mineral, bioactive glass, and type I collagen that can be molded to fit the bone defect. It is an osteoconductive, bioactive, porous implant that allows for bony ingrowth across the graft site. The bone graft matrix is slowly resorbed and replaced by new bone tissue during the natural healing process.

The anorganic bone mineral component of the bone graft matrix is a natural, porous bone graft material produced by removal of all organic components from bovine bone. The composition of the anorganic bone mineral meets ASTM F1581 standard specifications for composition of anorganic bone for surgical implants. The bioactive glass component of the device is made of 45S5 Bioactive Glass and meets ASTM F1538 standard specifications for glass and glass ceramics biomaterials for implantation. The purified type I collagen is derived from bovine Achilles tendon.

The product is available in various sizes and is provided sterile, non-pvrogenic, and for single use only.

AI/ML Overview

The provided text is a 510(k) summary for the Mineral Collagen Composite Bioactive Moldable device. This document describes a medical device seeking regulatory clearance, not an AI/ML device study. Therefore, most of the requested information regarding acceptance criteria, study design for AI/ML performance, ground truth establishment, expert adjudication, MRMC studies, and standalone algorithm performance does not apply to this document.

The document focuses on demonstrating substantial equivalence to legally marketed predicate devices, primarily through non-clinical testing (biocompatibility, sterilization, pyrogen, packaging, shelf life, and animal studies). Clinical studies were explicitly not required for this determination.

Here's an attempt to answer the questions based on the provided document, highlighting where the requested information is not applicable:

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

The document does not specify quantitative acceptance criteria in a table format for performance. Instead, it relies on demonstrating that the device performs substantially equivalently to its predicate and reference devices, particularly for the expanded indications for use.

Acceptance Criteria (Implied)	Reported Device Performance (Summary)
Biocompatibility	Deemed Biocompatible (ISO 10993) - No new testing required, data from K182074 remains valid.
Sterility	Sterile, SAL 10-6 (Gamma irradiation, ISO11137) - No new testing required, data from K182074 remains valid.
Pyrogenicity	Non-pyrogenic - No new testing required, data from K182074 remains valid.
Packaging & Shelf Life	Validated - No new testing required, data from K182074 remains valid.
Bench Testing	Not required for substantial equivalence, as technological characteristics remain the same.
Animal Performance	Performance in a rabbit femoral condyle critical-sized defect model was "substantially equivalent to the reference device" (SIGNAFUSE bioactive bone graft) with regards to the expansion of indications for use.

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

Animal Study: The document mentions "a rabbit femoral condyle critical-sized defect model." It does not specify the number of rabbits or exact sample size used for this study.
Data Provenance: The studies mentioned (biocompatibility, sterilization, pyrogen, packaging, shelf life) were completed under the original submission (K182074). The animal study appears to be part of the current submission, likely conducted for the expanded indications. The country of origin and whether the data was retrospective or prospective is not specified, but animal studies are typically prospective.

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

This information is not applicable as this is not an AI/ML device requiring human expert annotation for ground truth. Ground truth for a bone void filler would typically be established through histological analysis of tissue regeneration in the animal model. The document does not specify who conducted such analyses or their qualifications.

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

Not applicable for this type of device and study.

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 an AI/ML device that assists human readers.

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

Not applicable. This is not an AI/ML algorithm.

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

For the animal study, the "ground truth" for assessing device performance would primarily be based on pathology/histology of bone regeneration and integration within the rabbit femoral condyle defects, comparing the test device to the reference device. The document states "The results demonstrate performance substantially equivalent to the reference device with regards to the expansion of the indications for use," implying such an assessment was made.

8. The sample size for the training set

Not applicable. This device is not an AI/ML algorithm that requires a training set.

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

Not applicable.

Summary

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December 20, 2022

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which 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.

Collagen Matrix, Inc. Peggy Hansen SVP, Regulatory and Clinical Affairs 15 Thornton Road Oakland. New Jersey 07436

Re: K221735

Trade/Device Name: Mineral Collagen Composite Bioactive Moldable Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable Calcium Salt Bone Void Filler Device Regulatory Class: Class II Product Code: MQV Dated: November 21, 2022 Received: November 22, 2022

Dear Peggy Hansen:

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

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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 medical devices and radiation-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.

Laura C. Rose -S

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 Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K221375

Device Name

Mineral Collagen Composite Bioactive Moldable

Indications for Use (Describe)

For spine application Mineral Collagen Composite Bioactive Moldable is combined with either autogenous bone marrow or autograft with saline and can also be used with autograft as a bone graft extender.

Type of Use (Select one or both, as applicable)
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|× Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) SUMMARY

1.	Applicant Information
	Applicant Name:Address:Telephone:Fax:	Collagen Matrix, Inc.15 Thornton RoadOakland, New Jersey 07436(201) 405-1477(201) 405-1355
	Contact Person:	Peggy HansenSr. Vice President, Regulatory and Clinical Affairsphansen@collagenmatrix.com
	Date Prepared:	July 18, 2022
2.	Name of the Device
	Device Trade Name:	Mineral Collagen Composite Bioactive Moldable
	Device Common Name(s):	Bone Void FillerBone Graft MatrixBone Graft Substitute
	Device Classification Name:	Filler, Bone Void, Calcium Compound888.3045MQVClass II
3.	Legally Marketed Devices to Which Substantial Equivalence is Claimed
	Primary Predicate Device:	Mineral Collagen Composite Bioactive MoldableCollagen Matrix, Inc.K182074
	Reference Device:	SIGNAFUSE PUTTY Bioactive Bone GraftBioventus, Inc.K132071

4. Description of the Device

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anorganic bone for surgical implants. The bioactive glass component of the device is made of 45S5 Bioactive Glass and meets ASTM F1538 standard specifications for glass and glass ceramics biomaterials for implantation. The purified type I collagen is derived from bovine Achilles tendon.

The product is available in various sizes and is provided sterile, non-pvrogenic, and for single use only.

5. Intended Use

Mineral Collagen Composite Bioactive Moldable is intended for use as a bone void filler for voids or qaps, that are not intrinsic to the stability of the bony structure. The device is to be gently packed into bony voids or gaps of the skeletal system (i.e., the extremities, pelvis, and posterolateral spine). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. The device resorbs and is replaced with bone during the healing process.

6. Summary/Comparison of Technical Characteristics

This submission expands the indications for use of Mineral Collagen Composite Bioactive Moldable for use in the extremities and pelvis. The subject device has equivalent technological characteristics as the cited legally marketed predicate Mineral Collagen Composite Bioactive Moldable (K182074) device.

Feature	Mineral Collagen CompositeBioactive Moldable BoneGraft Matrix(This submission)	Mineral Collagen CompositeBioactive Moldable BoneGraft Matrix(K182074)	Bioactive Bone Graft PuttySIGNAFUSE PUTTYReference Device(K132071)
Indications forUse	Mineral Collagen CompositeBioactive Moldable isintended for use as a bonevoid filler for voids or gaps,that are not intrinsic to thestability of the bony structure.The device is to be gentlypacked into bony voids orgaps of the skeletal system(i.e., the extremities, pelvis,and posterolateral spine).These defects may besurgically created osseousdefects or osseous defectscreated from traumatic injuryto the bone. The deviceresorbs and is replaced withbone during the healingprocess.For spine applications,Mineral Collagen CompositeBioactive Moldable iscombined with eitherautogenous bone marrow orautograft with saline and can	Mineral Collagen CompositeBioactive Moldable combinedwith either autogenous bonemarrow or autograft withsaline is indicated for bonyvoids or gaps, that are notintrinsic to the stability of thebony structure; MineralCollagen Composite BioactiveMoldable can also be usedwith autograft as a bone graftextender.The device is to be gentlypacked into bony voids orgaps of the skeletal system(i.e., posterolateral spine).These defects may besurgically created osseousdefects or osseous defectscreated from traumatic injuryto the bone. The deviceresorbs and is replaced withbone during the healingprocess.	Bioactive Bone Graft Putty isa bone void filler deviceintended for use in bony voidsor gaps that are not intrinsicto the stability of the bonystructure. These defects maybe surgically created osseousdefects or osseous defectscreated from traumatic injuryto the bone. Bioactive BoneGraft Putty is indicated to bepacked gently into bony voidsor gaps of the skeletal system(i.e., extremities, pelvis andposterolateral spine fusionprocedures).Bioactive Bone Graft Puttycan also be used withautograft as a bone graftextender in the posterolateralspine. The device provides abone void filler that isresorbed and replaced withhost bone during the healingprocess.

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Feature	Mineral Collagen CompositeBioactive Moldable BoneGraft Matrix(This submission)	Mineral Collagen CompositeBioactive Moldable BoneGraft Matrix(K182074)	Bioactive Bone Graft PuttySIGNAFUSE PUTTYReference Device(K132071)
	also be used with autograft asa bone graft extender.
Physical Form	Strip or Cylindrical matrix(moldable upon hydration)	Strip or Cylindrical matrix(moldable upon hydration)	Putty preloaded into a syringeapplicator or Strip (moldable)
Color	White to off-white	White to off-white	White to off-white
MaterialComposition	• Calcium phosphate(anorganic bone mineral)• Bioactive glass• Type I bovine collagen	• Calcium phosphate(anorganic bone mineral)• Bioactive glass• Type I bovine collagen	• Calcium phosphate(60%HA:40%TCP)• Bioactive glass• Alkylene oxide polymer
Product Sizes	2.5 cc – 40 cc	2.5 cc – 40 cc	2.5 cc – 10 cc
Biocompatibility	BiocompatibleISO 10993	BiocompatibleISO 10993	BiocompatibleISO 10993
Sterility	Sterile, SAL 10-6	Sterile, SAL 10-6	Sterile, SAL 10-6
	Gamma irradiation, ISO11137	Gamma irradiation, ISO11137	Gamma irradiation, ISO11137
Pyrogenicity	Non-pyrogenic	Non-pyrogenic	Non-pyrogenic
Single Use/Reuse	Single use only	Single use only	Single use only

7. Performance Data

In vivo and in vitro testing of the subject device was conducted to demonstrate substantial equivalence of the subject device to its predicate devices. The following performance data are provided in support of the substantial equivalence determination.

Biocompatibility Testing

Additional biocompatibility data was not required to determine substantial equivalence. There are no changes to the product and the performance data remains the same as that submitted for the original submission (K182074).

Sterilization, Pyrogen, Endotoxin, Packaging and Shelf Life Testing

Sterilization validation, pyrogen testing, packaging validation and shelf life testing were completed under the original submission. K182074, and there have been no changes to the product since the original submission. Each lot of finished devices is tested for bacterial endotoxin for lot release.

Bench Testing

Bench testing was not required to determine substantial equivalence. The technological characteristics remains the same as that submitted for the original submission.

Animal Testing

The performance of the device in a rabbit femoral condyle critical-sized defect model was compared to the performance of the reference device, SIGNAFUSE bioactive bone graft. The results demonstrate performance substantially equivalent to the reference device with regards to the expansion of the indications for use.

Clinical Studies

Clinical performance data was not required to determine substantial equivalence.

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8. Conclusions Drawn from Non-clinical Studies

The conclusions drawn from the nonclinical tests demonstrate that the device is substantially equivalent to its predicate and reference devices.

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.