InterGro DBM products (Putty, Paste, Plus) 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, and as an autograft extender in the spine. InterGro Plus may also be used as a bone void filler in the spine (posterolateral spine). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to bone. InterGro DBM 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 is a resorbable, osteoconductive, and osteoinductive bone graft substitute that resorbs and is replaced with bone during the healing process. Its main component, demineralized cortical bone matrix (DBM), is derived from donor human tissue (allograft bone) and contains various growth factors including osteoinductive proteins. The DBM has been granulated, lyophilized and aseptically processed. In some versions of the product, calcium salt granules shall be incorporated to provide additional radiopacity, osteoconduction, and enhanced structural strength. The carrier for InterGro DBM is a resorbable, biocompatible, semi-viscous lipid. InterGro DBM is provided ready-to-use in various physical consistencies. It is packaged in various sizes by volume for single patient use.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study information for the InterGro DBM device:

It is important to note that the provided text is a 510(k) summary for a medical device (bone graft substitute), not an AI/ML medical device. Therefore, the questions related to AI/ML specific criteria (like test set, ground truth, experts, adjudication, MRMC studies, standalone performance, training set) are not applicable in this context. The acceptance criteria and "study" described here pertain to the biological and performance characteristics of a traditional medical device.

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

Acceptance Criteria / Performance Aspect	Reported Device Performance	Comments
Viral Inactivation Potential	The methods for processing the DBM contained in InterGro DBM were evaluated. A select panel of viruses representing various viral 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.	This outlines the evaluation of the manufacturing process's ability to inactivate viruses. The criteria are likely defined by the "suitable viral inactivation potential" against a panel of viruses, implying meeting established benchmarks for viral reduction. No specific log reduction values are provided, but the statement indicates the process was successful.
Osteoinductive Potential (In Vitro)	Each lot of DBM is assayed for its osteoinductive potential using a C2C12 myoblast cell line, measuring alkaline phosphatase production. Resulting osteoinductive index is compared to positive and negative controls.	This describes an in-vitro assay. The implied acceptance criterion is likely to demonstrate osteoinductive activity above a certain threshold and consistent with positive controls. The correlation with in vivo results is discussed below.
Osteoinductive Potential (Correlation to In Vivo)	In-vitro C2C12 assay results correlated with results from implantation of DBM into athymic rat muscle. Demonstrated a correlation coefficient of 0.88 (p<0.0005) and accurately predicted in vivo osteoinductivity in 20 donor lots.	This provides evidence that the in-vitro assay is predictive of in-vivo osteoinductive potential. The acceptance criteria for the correlation would have been set a priori (e.g., correlation coefficient > X and p-value < Y). The reported 0.88 correlation and p<0.0005 suggest strong correlation.
Product Performance Testing (In Vivo)	Performance of InterGro DBM was evaluated in an animal model by radiographic and histological methods.	This indicates that in-vivo performance was assessed. The acceptance criteria would likely involve demonstrating bone formation or integration as observed through radiology and histology, comparable to or better than a control, or meeting pre-defined histological scores. Specific results or quantitative criteria are not provided in this summary.
Substantial Equivalence	InterGro DBM was found to be substantially equivalent to predicate devices based on intended use, base materials, select performance properties, and use of a handling material.	This is an overarching regulatory acceptance criterion for 510(k) clearance. The device must demonstrate it is as safe and effective as a legally marketed predicate device. The specific performance properties evaluated for equivalence are not detailed beyond "select performance properties."
Biocompatibility	The carrier for InterGro DBM is described as "resorbable, biocompatible."	While no specific study is detailed here for biocompatibility, the statement implies previous testing or material history demonstrating biocompatibility, which is a fundamental acceptance criterion for implantable devices.

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

Viral Inactivation Validation: A "select panel of viruses" was used. The specific number of viruses is not stated. Data provenance is not specified but would be from laboratory experiments.
Osteoinductive Potential (In Vitro): "Each lot of DBM" is assayed. This is an ongoing quality control process, not a single test set.
Osteoinductive Potential (Correlation): 20 donor lots were used for the correlation study between the in-vitro C2C12 assay and in-vivo athymic rat muscle testing. The study was prospective in nature, demonstrating the predictive power of the in-vitro assay for future lots. Data provenance is not specified.
Product Performance Testing (Animal Model): An "animal model" was used. The number of animals, their species, and the specific study design (prospective/retrospective) are not specified.

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)

This section is not applicable. This submission is for a traditional medical device (bone graft substitute) and does not involve AI/ML. "Ground truth" in this context refers to the biological and physical properties of the material and its performance in animal models, not expert interpretations of diagnostic images or data. The "ground truth" for the osteoinductive potential correlation was the in-vivo performance in rats.

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

This section is not applicable as it pertains to AI/ML diagnostic or prognostic devices. Adjudication methods are not used for validating the biological properties or in-vivo performance of a bone graft substitute in the manner described for AI.

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 section is not applicable. MRMC studies are specific to evaluating human reader performance with and without AI assistance for diagnostic tasks. This device is a bone graft substitute, not an AI diagnostic tool.

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

This section is not applicable. This device is a physical product (bone graft substitute), not a standalone algorithm.

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

For the areas where a "ground truth" equivalent can be interpreted:

Viral Inactivation Validation: Laboratory-defined acceptable reduction levels (derived from industry standards/scientific understanding) for viral load.
Osteoinductive Potential (Correlation): The in-vivo osteoinductivity demonstrated in the athymic rat muscle model. This is essentially a biological/histological "ground truth."
Product Performance Testing (Animal Model): Radiographic and histological findings of bone formation and integration in the animal model. This is a biological/histological "ground truth."

8. The sample size for the training set

This section is not applicable. This device is not an AI/ML product that undergoes training on a data set.

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

This section is not applicable for the same reasons as #8.

Summary

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K082793

APR – 2 2009

510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR § 807.92

Sponsor:	Biomet Spine/Biomet Trauma100 Interpace ParkwayParsippany NJ 07054
Establishment RegistrationNumber:	2242816
Manufacturing Site	Interpore Cross International181 Technology DrIrvine CA 92618
Manufacturing SiteRegistrationNumber:	2029012
Contact:	Kathleen IdeoRegulatory AssociateInterpore Cross International181 Technology DrIrvine CA 92618(949) 453-3200
Date Prepared:	February 17, 2009
Trade/Proprietary Name:	InterGro DBM (Putty, Paste, Plus)
Common/Usual Name:	DBM Bone Graft Substitute
Classification Name:	Bone Grafting Material
Device Classification:	Class II
Regulation Number	21 CFR 888.3045
Product Codes	MQV, MBP, GXP
Predicate Device:	DynaGraft II, DBX, InterGro DBM
Device Formulation:	InterGro DBM (Putty, Paste, Plus)
Performance:	PerformancestandardsapplicableDBM-basedto

¹⁴
pg 1 of 3

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products have not been published by the FDA. Interpore Cross International intends to manufacture and package this device according to the regulations and standards that are appropriate to the risk that Class II devices reasonably present. Voluntary performance standards, such as materials certifications, in-house SOP's, FDA Guidance Documents, AATB Standards and/or ASTM Standards are used as appropriate.

InterGro DBM is a resorbable, osteoconductive, and Device Description: osteoinductive bone graft substitute that resorbs and is replaced with bone during the healing process. Its main component, demineralized cortical bone matrix (DBM), is derived from donor human tissue (allograft bone) and contains various growth factors including osteoinductive proteins. The DBM has been granulated, lyophilized and aseptically processed. In some versions of the product, calcium salt granules shall be incorporated to provide additional radiopacity, osteoconduction, and enhanced structural strength. The carrier for InterGro DBM is a resorbable, biocompatible, semi-viscous lipid. InterGro DBM is provided ready-to-use in various physical consistencies. It is packaged in various sizes by volume for single patient use.

InterGro DBM products (Putty, Paste, Plus) 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, and as an autograft extender in the spine. InterGro Plus may also be used as a bone void filler in the spine (posterolateral spine). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to bone. InterGro DBM 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.

Indications for Use:

$\frac{+5}{pg}$ 2 of 3

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Substantial Equivalence Viral Inactivation Validation: The methods for processing the DBM contained in InterGro DBM were Information evaluated for their viral inactivation potential. A select panel of viruses representing various viral 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 alkaline phosphatase production of a myoblast cell line (C2C12) 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 0.88 (p<0.0005) and accurately predicted the in vivo osteoinductivity in 20 donor lots. '

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 "C2C12" bioassay will correlate with human clinical performance of InterGro DBM products.

1Han B. Tang B. and Nimni M. Quantitative and Sensitive in vitro Assay for Osteoinductive Activity of Demineralized Bone Matrix. J Ortho Res, 2003, 21:648-54.

Product Performance Testing: Performance of InterGro DBM was evaluated in an animal model by radiographic and histological methods.

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.

InterGro DBM was found to be substantially equivalent to the predicate devices based on the intended use, base materials, select performance properties, and use of a handling material.

Conclusion: .

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its wing and body. The eagle faces to the left. Encircling the eagle is the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in a circular arrangement.

Public Health Service

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Biomet Spine/Biomet Trauma % Ms. Kathleen Ideo 100 Interpace Parkway Parsippany, New Jersey 07054

Re: K082793

Trade/Device Name: InterGro® DBM (Putty, Paste, Plus) Regulation Number: 21 CFR 888,3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: II Product Code: MQV, MBP, GXP Product March 25, 2009 Received: March 26, 2009

Dear Ms. Ideo:

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. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

APR - 2 2009

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 comply 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 (OS) 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 -- Ms. Kathleen Ideo

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 marketed predicate 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 Center for Devices and Radiological Health's (CDRH's) Office of Compliance at (240) 276-0120. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (240) 276-3474. For questions regarding of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at (240) 276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at toll-free number (800) 638-2041 or (240) 276-3150 or the Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Mark N. Melkerson

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): K082793

Device Name: InterGro® DBM (Putty, Paste, Plus)

Indications for Use:

InterGro DBM products (Putty, Paste, Plus) 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, and as an autograft extender in the spine. InterGro Plus may also be used as a bone void filler in the spine (posterolateral spine). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to bone. InterGro DBM may also be used for filling craniofacial defects and craniotomies that are no larger than 25cm². The amount of InterCro DBM products to be used should be based on the type of procedure and size of the graft site.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

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

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Page 1 of 1

Hubert Dinhup
(Division Sign-Off) for MXH

Division of Gene Division
and Neurological Devices

510(k) Number K082793

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.