DBX® is intended for use as a Demineralized Bone Matrix for voids or gaps that are not intrinsic to the stability of the bony structure. It can be used in the:

Putty	Mix	Paste
Extremities	Extremities	Extremities
Pelvis	Pelvis	Pelvis
Posterolateral Spine	Spine
Cranium

DBX® is indicated for treatment of surgically created osseous defects or osseous defects created from traumatic injury. DBX® Putty can be used as an extender in the spine with autograft. DBX® can be used with bone marrow. DBX® is for single patient use only.

Device Description

DBX® Demineralized Bone Matrix is available in three forms: Paste, Putty and Mix. DBX® products are completely resorbable. DBX® Paste and Putty are composed of donor cortical bone; the DBX® Mix is composed of donor corticocancellous bone. The bone granules are mixed with sodium hyaluronate (Hy) in varying combinations to form the DBX® Putty, Paste, and Mix.

AI/ML Overview

This 510(k) summary describes a change in the osteoinductivity assay for the DBX® Demineralized Bone Matrix Putty, Paste, and Mix. The device itself is a bone void filler containing human demineralized bone matrix (DBM). The primary focus of the provided document is on the validation of the new osteoinductivity assay as a surrogate for the previously accepted in vivo athymic mouse model, not a study of the overall clinical performance of the device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based solely on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (for Osteoinductivity Assay)	Reported Device Performance (for this specific change)
Predicate Assay (In Vivo Athymic Mouse Model): Must prove positive for lot release (K040262)	N/A (this is the old assay, but the new assay aims to correlate with it)
New Assay (In Vitro BMP-2 ELISA): Must prove positive for lot release when used as a surrogate for the athymic mouse model.	Results from the immunoassay were correlated to the athymic mouse model for the DBM alone and the DBX® Putty.

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

The document does not explicitly provide a "test set" sample size in the traditional sense of a clinical study for device performance. Instead, it discusses the validation of an assay.

Athymic Mouse Model (In Vivo): Used for original and ongoing validation.
- Sample Size: Not specified (e.g., number of mice, number of lots tested).
- Data Provenance: Not specified, but likely laboratory-based.
- Retrospective/Prospective: Not specified for individual tests, but implies ongoing lot testing.
BMP-2 ELISA (In Vitro): This is the new assay being validated against the athymic mouse model.
- Sample Size: "Every final lot of DBX® Putty is tested" or "each lot of DBM incorporated into DBX® Putty is assayed." The number of lots used specifically for the correlation study between the ELISA and the athymic mouse model is not specified.
- Data Provenance: Laboratory testing.
- Retrospective/Prospective: The correlation study would have been prospective to establish the link between the new and old methods. Subsequent lot testing would be prospective for quality control.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

This information is not provided. The "ground truth" here is the osteoinductive potential, as measured by either the athymic mouse model or the BMP-2 ELISA. These are laboratory assays, not interpretations by experts in a clinical context.

4. Adjudication Method for the Test Set

Not applicable. This is not a study requiring adjudication of clinical outcomes or image interpretations. The "adjudication" in this context is the comparison between the results of the in vitro ELISA and the in vivo athymic mouse model. The document states that "Results from this immunoassay were correlated to the athymic mouse model." The specific statistical method or criteria for this correlation are not detailed beyond the statement of correlation.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC study was not done. This device is a bone graft substitute, and the submission concerns a change in a laboratory assay for osteoinductivity, not a diagnostic imaging or clinical assessment device that would typically involve an MRMC study.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, in a way. The "standalone" performance here refers to the new BMP-2 ELISA assay. The study establishes its correlation with the athymic mouse model, suggesting it can function as a standalone test for osteoinductivity in lot release.

7. The Type of Ground Truth Used

The ground truth for determining osteoinductive potential is:

Biological Assay: The in vivo athymic mouse model. This model has a history of use for assessing osteoinductivity.
Biochemical Assay: The BMP-2 ELISA, which is being proposed as a surrogate for the biological assay. The "ground truth" for the validation of the ELISA is therefore the athymic mouse model's results.

8. The Sample Size for the Training Set

The document does not explicitly refer to a "training set" in the context of machine learning or algorithm development. The "correlation" between the BMP-2 ELISA and the athymic mouse model implicitly involves a dataset of DBM lots for which both tests were performed. The size of this dataset (i.e., the number of lots used to establish the correlation) is not specified.

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

The "ground truth" for the training/correlation set (the lots used to compare the two assays) was established by:

Athymic Mouse Model: Historically, this in vivo model was used to determine the osteoinductive potential of DBM. "Standard testing performed in an athymic mouse model... must prove positive for lot release."
The BMP-2 ELISA results were then compared to these established athymic mouse model results to show correlation. The document implies that the positive/negative outcome of the athymic mouse model served as the gold standard for validating the ELISA's accuracy in predicting osteoinductivity.

Summary

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K080399 (pg. 1 of 2)

OCT 1 0 2008

510(k) SUMMARY OF SAFETY & EFFECTIVENESS

PROPRIETARY NAME:	DBX® Demineralized Bone Matrix PuttyDBX® Demineralized Bone Matrix PasteDBX® Demineralized Bone Matrix Mix
COMMON NAME:	Bone Void Filler Containing Human DemineralizedBone Matrix (DBM)
PROPOSED REGULATORYCLASS:	Class II
CLASSIFICATIONIDENTIFICATION:	21 C.F.R. §888.3045 Resorable calcium salt bonevoid filler device
PRODUCT CODE:	MBP, MQV, GXP
SPONSOR:	Musculoskeletal Transplant Foundation125 May StreetEdison, NJ 08837732-661-0202

INDICATIONS FOR USE:

DBX® is intended for use as a Demineralized Bone Matrix for voids or gaps that are not intrinsic to the stability of the bony structure. DBX® Putty may be used in the extremities, pelvis, posterolateral spine and cranium. DBX® Mix may be used in the extremities, pelvis and spine. DBX® Paste may be used in the extremities and pelvis. DBX® is indicated for treatment of surgically created osseous defects or osseous defects created from traumatic injury. DBX® Putty can be used as an extender in the spine with autograft. DBX® can be used with bone marrow. DBX® is intended for single patient use only.

DEVICE DESCRIPTION:

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SAFETY AND EFFECTIVENESS INFORMATION:

This 510(k) was submitted for a change in the osteoinductivity assay for DBX® Putty. The fundamental scientific technology of the modified DBX® Putty, using BMP -2 in vitro testing as an alternative for in vivo testing for osteoinductivity, is the same as the technology for the unmodified predicate, DBX® (FDA cleared, K040262).

Biocompatibility of DBX® materials has been established through their long history of safe and effective clinical use, further supported by laboratory testing conducted per ISO 10993. DBX® is single-donor processed using aseptic techniques and is tested for sterility per current USP <71>.

OSTEOINDUCTIVE POTENTIAL

DBX® Demineralized Bone Matrix Putty is osteoconductive and has been shown to have osteoinductive potential in an athymic mouse model. DBX® Putty has been shown to contain the native, i.e., endogenous, Bone Morphogenetic Protein, BMP-2, as detected by an Enzyme-Linked-ImmunoSorbent Assay (ELISA).

Every final lot of DBX® Putty is tested in an in vivo athymic mouse model or, alternatively, each lot of DBM incorporated into DBX® Putty is assayed in vitro using the BMP-2 ELISA as a surrogate test market for osteoinductive potential. Standard testing performed in an athymic mouse model or in the BMP-2 assay must prove positive for lot release. Results from this immunoassay were correlated to the athymic mouse model for the DBM alone and the DBX® Putty. Although only one bone-derived endogenous protein is used as the test marker, i.e., BMP-2, it is the combination of various proteins that is responsible for its osteoinductive potential.

Testing each lot of DBM with this immunoassay assures that only DBM with osteoinductive potential is used in DBX®. The combination of DBM and sodium hyaluronate 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 immunoassay, will correlate with human clinical performance of DBX®.

VIRAL CLEARANCE AND INACTIVATION:

This 510(k) was submitted for a change in the osteoinductivity assay for DBX® Putty. The fundamental scientific technology of the modified DBX® Putty, using in vitro testing as an alternative for in vivo testing for osteoinductivity, is the same as the technology for the unmodified predicate, DBX® (FDA cleared, K040262). The method for processing the DBM contained in DBX® was evaluated for its viral inactivation potential. A panel of model potential human viruses representing various virus types, sizes, shapes and genomes were evaluated. The DBM processing methods were determined to provide significant viral inactivation potential for a wide range of potential viruses.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The logo is black and white.

OCT 1 0 2008

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Musculoskeletal Transplant Foundation % Ms. Nancy Bennewitz Regulatory Affairs Submission Specialist 125 May Street, Suite 300 Edison Corporate Center Edison, New Jersey 08837

Re: K080399

Trade Name: DBX® Demineralized Bone Matrix Putty, Paste and Mix. Regulation Number: 21 CFR § 888.3045 Regulation Name: Resorbable Bone Substitute Regulatory Class: Class II Product Code: MBP Dated: September 25, 2008 Received: September 26, 2008

Dear Ms. Bennewitz:

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. Ilsting 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 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 (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 – Ms. Nancy Bennewitz

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 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

Mark N Wilkerson

Mark N. Melkerson Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

Indications for Use

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IV. INDICATIONS FOR USE

510(k) Number (if known): unknown

Device Name: DBX® Demineralized Bone Matrix Putty, Paste and Mix

Indications for Use:

DBX® is intended for use as a Demineralized Bone Matrix for voids or gaps that are not intrinsic to the stability of the bony structure. It can be used in the:

Putty	Mix	Paste
Extremities	Extremities	Extremities
Pelvis	Pelvis	Pelvis
Posterolateral Spine	Spine
Cranium

OR Prescription Use X (Per 21 CFR 801 Subpart D)

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

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Neil Rk Ogden forman

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

510(k) Number

CONFIDENTIAL

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.