ALLOMATRIX® C Putty, ALLOMATRIX® Custom Putty and ALLOMATRIX® DR Putty Products are indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putty Products are intended to be gently packed into bony voids or gaps of the skeletal system (i.e., the extremities and pelvis). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone.

Device Description

ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putty Products come in the form of a kit with a premeasured powder and CBM chips, premeasured mixing solution, and the tools necessary to mix the components. After the powder is hydrated using all the mixing solution supplied in the kit, the resultant putty can then be handled and placed in the appropriate bone voids. This product is supplied sterile for single patient use.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and supporting studies for the ALLOMATRIX® Putty products, organized according to your requested information.

It's important to note that this 510(k) summary focuses on demonstrating substantial equivalence to predicate devices, rather than establishing de novo performance criteria against a specific benchmark. Therefore, some of your requested points, particularly those related to quantitative performance metrics for AI/human reader studies, are not directly applicable or available in this type of submission.

Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Acceptance Criteria / Benchmark	Reported Device Performance
Substantial Equivalence	Device is substantially equivalent to predicate devices.	ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putty Products were found to be substantially equivalent to the predicate devices.
Osteoinductivity (DBM component)	DBM component demonstrates osteoinductive potential.	Bioassay measures proliferation of Saos human osteosarcoma cells in presence of DBM (osteoinductivity index). Results from bioassay correlated with athymic rat muscle implantation (correlation coefficient 0.850, p<0.0005) and accurately predicted in vivo osteoinductivity in 99 of 101 donor lots. Clinical results with DBM >0.20 index showed 92% healing vs. 33% for ≤0.20 index. Each lot of DBM is evaluated with this cell-based bioassay to ensure osteoinductive potential.
Viral Inactivation Potential (DBM)	Processing methods provide significant viral inactivation.	DBM processing methods were determined to provide significant viral inactivation potential for a wide range of potential viruses.
Viral Inactivation Potential (CBM)	Processing methods provide some viral inactivation, with low risk.	CBM processing methods were determined to provide some viral inactivation potential for a wide range of viruses. The risk of disease transmission remains low due to multiple safeguards (donor selection, laboratory testing, material processing).
Clinical Performance (Radiographic)	No significant differences in radiographic outcomes compared to predicate devices.	There were no significant differences in the radiographic outcomes of the ALLOMATRIX® Putty Products and the predicate devices.
Clinical Performance (Adverse Events)	No significant differences in adverse event profiles compared to predicate devices.	There were no significant differences in the adverse event profiles of the ALLOMATRIX® Putty Products and the predicate devices.
Animal Model Performance	DBM putty formulations with CBM show acceptable performance (radiographic and histological).	Performance of DBM putty formulations including varying amounts of CBM were evaluated in a canine model by radiographic and histological methods. (Specific quantitative results not provided in this summary, but the implication is that the performance was acceptable for equivalence).

Study Details (Where Applicable and Provided)

Sample size used for the test set and the data provenance:
- Osteoinductivity Bioassay:
  - Test Set: 101 donor lots for the correlation study with athymic rat model.
  - Provenance: Not explicitly stated, but implied to be human DBM samples. The correlation study references Lindholm TS, Urist MR. A quantitative analysis of new bone formation by induction in compositive 2 grafts of bone marrow and bone matrix, Clin Orthop 1980 Jul-Aug;(150):288-300. for the rat model, and Wilkins, R.M. (1999) Clinical Effectiveness of Demineralized Bone Matrix Assayed in Human Cell l Culture, Advances in Tissue Banking. 3:113-124 for the clinical correlation, suggesting diverse data sources.
  - Retrospective/Prospective: The correlation studies appear to be retrospective analyses of DBM lots. The statement "Each lot of DBM...is evaluated in vitro" implies prospective testing for quality control of the DBM component used in the putties.
- Clinical Performance (Radiographic/Adverse Events):
  - Test Set: Not explicitly stated how many patients or cases were evaluated for the comparison to predicate devices, but described as "a comparison of radiographic outcomes and the adverse event profiles."
  - Provenance: Not specified (e.g., country of origin, retrospective/prospective). This comparison would typically be based on existing clinical data or published literature related to the predicate devices and the new device's preliminary clinical observations.
- Canine Model:
  - Test Set: Not specified how many canines were used.
  - Provenance: Not specified (source of animals, experimental design).
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Osteoinductivity Bioassay: Ground truth for osteoinductivity relies on the definition provided: "The product is considered osteoinductive if one specimen (explant) contains new bone (i.e. bone occupied with lamellae), cartilage, and/or chondrocytes." This implies histological evaluation, which would typically be performed by trained histologists or pathologists. The number is not specified.
- Clinical Performance (Radiographic): For "radiographic outcomes," ground truth would typically be established by radiologists or orthopedic surgeons. The number and qualifications are not specified.
- Canine Model: Histological evaluation would be performed by experts (e.g., veterinary pathologists/histologists). Number and qualifications are not specified.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not specified for any of the studies mentioned.
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 MRMC comparative effectiveness study was done. This product is a bone void filler, not an AI or imaging diagnostic device.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Not applicable. This is not an algorithmic device.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Osteoinductivity: Primarily pathology/histology (for the athymic rat model, defined by the presence of new bone, cartilage, or chondrocytes) and in vitro bioassay results correlated with clinical healing.
- Viral Inactivation: Laboratory testing (measuring viral reduction factors for model viruses).
- Clinical Performance: Radiographic outcomes (interpreted by clinicians) and adverse event profiles (clinical outcomes data).
- Canine Model: Radiography and histology (pathology).
The sample size for the training set:
- Osteoinductivity Bioassay: No specific "training set" in the machine learning sense is described. The bioassay was correlated with clinical results from Wilkins (1999) and Lindholm & Urist (1980), which would represent datasets used to establish the validity and predictive power of the bioassay. The size of these historical datasets is not specified in detail beyond the 101 donor lots used for the correlation study.
- Other studies: Not applicable as these are not machine learning models.
How the ground truth for the training set was established:
- Osteoinductivity Bioassay: The ground truth for the bioassay's predictive capability was established through:
  - Pathology/Histology: For the athymic rat model, where bone formation was histologically confirmed and defined.
  - Clinical Outcomes Data: For the clinical correlation mentioned by Wilkins (1999), where radiographic healing for DBM alone was assessed and linked to the bioassay index. This would involve assessment by qualified medical professionals (e.g., radiologists, orthopedic surgeons) interpreting patient radiographs.

Summary

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K040980

JUL 1 4 2004

510(K) SUMMARY OF SAFETY AND EFFECTIVENESS

In accordance with the Food and Drug Administration Rule to implement provisions of the Safe Medical In wees Act of 1990 and in conformance with 21 CRF 807, this information serves as a Summary of Safety and Effectiveness for the use of ALLOMATRIX® C Putty, ALLOMATRIX® Custom Putty and ALLOMATRIX® DR Putty.

Submitted By:	Wright Medical Technology, Inc.
Date:	April 12, 2004
Contact Person:	Roger D. BrownSr. Director, Clinical, Regulatory & Reimbursement
Proprietary Name:	ALLOMATRIX® C Putty, ALLOMATRIX® CustomPutty and ALLOMATRIX® DR Putty
Common Name:	Bone Void Filler
Classification Name and Reference:	Filler, Calcium Sulfate Preformed Pellets - Class II888.3045
Device Product Code and Panel Code:	Orthopedics/MOV

DEVICE INFORMATION

INTENDED USE A.

ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putty Products are indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putty Products are intended to be gently packed into bony voids or gaps of the skeletal system (i.e., the extremities and pelvis). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone.

DEVICE DESCRIPTION B.

SUBSTANTIAL EQUIVALENCE INFORMATION ﺯ

ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putty Products were found to be substantially equivalent to the predicate devices. The safety and effectiveness of ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putty Products is adequately supported by the substantial equivalence information, materials data, and testing results provided within this Premarket Notification.

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Osteoinductivity Potential

Ostomation incorporated into the ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putty Products is assayed in vitro for its osteoinductive potential. The bioassay measures the proliferation of Saos human osteosarcoma cells in the presence of human DBM compared to positive and negative controls (osteoinductivity index). Results from the bioassay were 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 of 99 of 101 donor lots. Additionally, clinical results using DBM with >0.20 and ≤0.20 demonstrated a significant difference in healing as evaluated by radiography, 92% and 33% healing, respectively.3

Each lot of DBM incorporated into ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putties is evaluated in vitro using a surrogate cell-based assay'. The bioassay measures the proliferation of Saos human osteosarcoma cells in the presence of human DBM compared to positive and negative controls (osteoinductivity index)'. Results from this bioassay were correlated to the athymic rat model and to clinical results of assayed DBM alone 3 Testing each lot of DBM with this cell-based bioassay assures that only DBM with osteoinductive potential is used in the ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putties. The combination of DBM, CBM and binding medium 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 bioassay', will correlate with human clinical performance of ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putties.

Wilkins, R.M. (1999) Clinical Effectiveness of Demineralized Bone Matrix Assayed in Human Cell l Culture, Advances in Tissue Banking. 3:113-124
Lindholm TS, Urist MR. A quantitative analysis of new bone formation by induction in compositive 2 grafts of bone marrow and bone matrix, Clin Orthop 1980 Jul-Aug;(150):288-300. Note: The product is considered osteoinductive if one specimen (explant) contains new bone (i.e. bone occupied with lamellae), cartilage, and/or chondrocytes.
Data on file at Wright Medical Technology, Inc. 3

Viral Inactivation Potential

The method for processing the DBM and CBM contained in the ALLOMATRIX® C, ALLOMATRIX® Custom and ALLOMATRIX® DR Putty Products 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. The CBM processing methods were determined to provide some viral inactivation potential for a wide range of viruses. In comparison, the CBM processing methods provided less viral inactivation potential than the DBM processing methods; therefore, the risk for disease transmission from the CBM component is greater than the DBM component. However, the risk of disease transmission for these components remains low due to the multiple safeguards employed, i.e., donor selection, laboratory testing, and material processing.

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Product Performance Testing

I roduct I clinical performance was evaluated by a comparison of radiographic outcomes and the adverse event profiles compared to the predicate devices. There were no significant differences in the radiographic outcomes or adverse event profiles of the ALLOMATRIX® C, attrereless in the radiographic Sul OMATRIX® DR Putty Products and the predicate devices.

Performance of DBM putty formulations that included varying amounts of CBM were evaluated in a canine model by radiographic and histological methods.

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Image /page/3/Picture/1 description: The image is a circular seal for the Department of Health & Human Services - USA. The seal features the department's logo, which consists of a stylized caduceus symbol with three lines representing the human form. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the perimeter of the circle.

Public Health Service

JUL 1 4 2004

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Mr. Roger D. Brown Director, Regulatory Affairs Wright Medical Technology 5677 Airline Road Arlington, Tennessee 38002

Re: K040980

Allomatrix C. Allomatrix Custom and Allomatrix DR Putty Products Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler devices Regulatory Class: Class II Product Code: MQV Dated: April 14, 2004 Received: April 15, 2004

Dear Mr. Brown:

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, 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 vour 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

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applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 (301) 594-4659. 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/dsma/dsmamain.html

Sincerely yours,

Mark A. Millburn

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):_K_040980

ALLOMATRIX® C Putty, ALLOMATRIX® Custom Putty and Device Name: ALLOMATRIX® DR Putty

Indications for Use:

ALLOMATRIX® C Putty, ALLOMATRIX® Custom Putty and ALLOMATRIX® DR Putty are indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. multicated only 10. 8011 10.13 0. gaps TRIX® Custom Putty and ALLOMATRIX® DR Putty are intended to be gently packed into bony voids or gaps of the skeletal system (i.e., the extremities and pelvis). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone.

Prescription Use _ X (Per21 CFR 801.109) OR

Over-The Counter Use (Optional Format 1-2-96)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Mark A. Mulkerson

Division of General, Restorative, and Neurological Devices

510(k) Number K040980

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.