InterGro DBM products are to be used for filling bony voids or gaps in the extremities, and pelvis that are not intrinsic to the bony stability of the structure. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to bone. The device may also be used for filling craniofacial defects and craniotomies that are no larger than 25cm². The amount of InterGro DBM products to be used should be based on the type of procedure and size of the graft site.

Device Description

InterGro® DBM products contain human tissue (allograft bone) and are intended for transplantation. The allograft bone has been granulated, demineralized and provided in a lipid carrier. Some versions contain porous ceramic granules that are a composite of highly resorbable calcium carbonate with a slower resorbing 2 to 10 um outer layer of calcium phosphate.

InterGro DBM products have been processed aseptically and are ready to use. They do not require rehydration or any special preparation. InterGro DBM is intended for single patient use only.

AI/ML Overview

The provided 510(k) summary for InterGro® DBM describes a bone graft substitute and its assessment for substantial equivalence. It does not contain information about an AI/ML powered medical device, therefore many of the requested categories related to such systems (e.g., AI assistance, MRMC studies, training set details) are not applicable.

Here's an analysis of the provided text based on your request, focusing on the available information:

Acceptance Criteria and Device Performance for InterGro® DBM (K031399)

This 510(k) pertains to a bone graft substitute. The acceptance criteria and "performance" are framed around biological equivalence and safety rather than diagnostic accuracy metrics typically associated with AI/ML devices.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria/Test	Reported Device Performance/Results
Biocompatibility/Safety	Viral Inactivation Potential: Evaluate processing methods for demineralized bone matrix (DBM) to inactivate viruses.	The viral inactivation testing demonstrated suitable viral inactivation potential of the processing methods for a wide range of potential human viruses (representing various virus types, sizes, shapes, and genomes).
Functional Equivalence	Osteoinductive Potential (In Vitro): Assay each lot of DBM for its ability to induce bone formation (measured as proliferation of SAOS human osteosarcoma cells).	Results of the SAOS assay have been correlated with results from implantation of DBM into athymic rat muscle, demonstrating a correlation coefficient of 0.850 (p<0.0005) and accurately predicting in vivo osteoinductivity in 25 donor lots. Clinical results using DBM with an osteoinductive index (OII) >0.20 showed 92% healing by radiography, while DBM with OII ≤0.20 showed 33% healing, indicating a significant difference. Note: The osteoinductivity of the combined formulation (DBM + carrier +/- ceramic granules) was not evaluated, and correlation with human clinical performance of the full product is unknown.
Product Performance	In Vivo Performance: Evaluate InterGro® DBM in animal models (rabbit and sheep).	Performance was evaluated using radiographic and histological methods in rabbit and sheep models. (Specific quantitative results or detailed criteria not provided in this summary for this section).

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

Viral Inactivation Validation: "A select panel of viruses representing various virus types, sizes, shapes, and genomes were evaluated." (Specific number of viruses not provided). Data provenance is not specified but the nature of the test suggests laboratory-based validation.
Osteoinductive Potential (In Vivo Correlation): 25 donor lots of DBM were used for correlation with athymic rat muscle implantation. Data provenance for these donor lots is not specified but implies human tissue.
Osteoinductive Potential (Clinical Results): "Clinical results using DBM..." (Number of patients or specific studies not provided explicitly for this summary). The context implies human clinical data, but provenance (e.g., country, retrospective/prospective) is not given.
Product Performance Testing (Animal Models): "evaluated in rabbit and sheep models." (Specific number of animals or studies not provided). This is prospective animal study data.

3. Number of Experts and Qualifications for Ground Truth

Not Applicable. This device is a material (bone graft substitute) not an AI diagnostic device. Ground truth is established through laboratory assays, animal studies, and clinical observations of healing, not expert interpretation of outputs.

4. Adjudication Method for the Test Set

Not Applicable. See point 3.

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

Not Applicable. This is not an AI-powered diagnostic device, so MRMC studies comparing human readers with and without AI assistance are irrelevant.

6. Standalone (Algorithm Only) Performance Study

Not Applicable. This is not an algorithm. The in-vitro SAOS assay and in-vivo athymic rat model can be considered "standalone" in vitro/in vivo tests of the DBM's osteoinductivity, independent of human clinical application, but they are not algorithm performances.

7. Type of Ground Truth Used

Viral Inactivation: Laboratory assay results demonstrating a reduction in viral titre.
Osteoinductive Potential:
- In-vitro: Proliferation of SAOS human osteosarcoma cells (a cellular assay).
- In-vivo correlation: Histological evidence of bone formation in athymic rat muscle following DBM implantation.
- Clinical: Radiographic evaluation of healing in human patients following DBM implantation.
Product Performance Testing: Radiographic and histological methods in animal models.

8. Sample Size for the Training Set

Not Applicable. This device does not involve a "training set" in the context of AI/ML.

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

Not Applicable. See point 8.

Summary

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510(k) SUMMARY

K031399

This summary of 510(k) substantial equivalence information is being submitted in accordance with the requirements of 21 CFR $807.92.

Submitted By:	Interpore Cross International181 Technology DriveIrvine, California 92618
Date:	December 16, 2003
Contact Person:	Mark LoarManager, Regulatory and Clinical Affairs

CLASSIFICATION, COMMON OR USUAL NAME, DEVICE NAME

Classification Name: Human Tissue Common/Usual Name: DBM Bone Graft Substitute Product Classification: Unclassified Proprietary Name: InterGro® DBM

PREDICATE DEVICE

Predicate device information is provided in this premarket notification.

DEVICE DESCRIPTION

InterGro DBM products have been processed aseptically and are ready to use. They do not require rehydration or any special preparation. InterGro DBM is intended for single patient use only.

INDICATIONS-FOR-USE

InterGro DBM products are to be used for filling bony voids or gaps in the extremities, and pelvis that are not intrinsic to the bony stability of the structure. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to bone. The device may also be used for filling craniofacial defects and craniotomies that are no larger than 25cm". The amount of InterGro DBM products to be used should be based on the type of procedure and size of the graft site.

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SUBSTANTIAL EQUIVALENCE INFORMATION

InterGro® DBM was found to be substantially equivalent to the predicate devices. The safety and effectiveness of InterGro DBM is adequately supported by the substantial equivalence information, materials data, and testing results provided within this Premarket Notification.

. Viral Inactivation Validation

The methods for processing the DBM contained in InterGro® DBM were evaluated for their viral inactivation potential. A select panel of viruses representing various virus types, sizes, shapes, and genomes were evaluated. The viral inactivation testing demonstrated suitable viral inactivation potential of the processing methods for a wide range of potential human viruses.

Osteoinductive Potential .
Each lot of DBM incorporated into InterGro® DBM is assayed for its osteoinductive potential. The assay measures the proliferation of SAOS human osteosarcoma cells in the presence of human DBM compared to positive and negative controls (osteoinductive index). Results of the assay have been correlated with results from implantation of DBM into athymic rat muscle, which demonstrated a correlation coefficient of 0.850 (p<0.0005) and accurately predicted the in vivo osteoinductivity in 25 donor lots. Additionally, clinical results using DBM with >0.20 and ≤0.20 (osteoinductive index) demonstrated a significant difference in healing as evaluated by radiography, 92% and 33% healing, respectively.2

The combination of DBM, the carrier and, in some formulations, ceramic granules has not been evaluated for osteoinductivity; therefore it is unknown to what extent the formulation components may alter the osteoinductive character of the DBM. Additionally, it is unknown how osteoinductivity of the DBM component. measured via the in-vitro "SAOS" bioassay will correlate with human clinical performance of InterGro DBM products.

. Product Performance Testing Performance of InterGro® DBM was evaluated in rabbit and sheep models by radiographic and histological methods.
l Adkisson HD, Strauss-Schoenberger J, Gillis M, Wilkins R, Jackson M, and Hruska KA. Rapid Quantitiative Bioassay of Osteoinduction. J Ortho Res, 2000, 18:503-511.

י נ Wilkins RM, Clinical Effectiveness of Demineralized Bone Matrix Assayed in Human Cell Culture, Advances in Tissue Banking. 1999 3:113-124

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the department's name around the perimeter. Inside the circle is an abstract symbol that resembles a stylized caduceus or a representation of human figures.

FEB 1 8 2005

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Mr. Mark Loar Manager, Regulatory and Clinical Affairs INTERPORE CROSS International 181 Technology Drive Irvine, California 92618

Re: K031399

Trade/Device Name: InterGro® DBM Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler Regulatory Class: II Product Code: MQV,GXP Dated: December 16, 2004 Received: December 21, 2004

Dear Mr. Loar:

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 for assession 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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 or any I with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); 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.

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Page 2 -- Mr. Mark Loar

This letter will allow you to begin marketing your device as described in your Section 510(k) Premarket notification. The FDA finding of substantial equivalence of your device to a legally premaince nedicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at (240) 276-0120. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

O. Mark N. Millikan

Celia M. Witten, Ph.D., M.D. Director Division of General, Restorative and

Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K031399

InterGro® DBM Device Name:

Indications-For-Use:

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)
Division of General, Restorative, and Neurological Devices

510(k) Number	K031399
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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.