(401 days)
DynaGraft® II is indicated for orthopedic applications as filler for gaps or voids that are not intrinsic to the stability of the bony structure. DynaGraft® II is indicated to be packed gently into bony gaps in the skeletal system as a bone graft extender (extremities, spine, and pelvis) and as bony void filler of the extremities and pelvis. These defects may be surgically created or the result of traumatic injury to the bone.
DynaGraft II is derived from selected donated human bone tissue that has been processed into particles. The demineralized bone matrix (DBM) is combined with a hydrogel carrier and formulated to a gel or putty-like consistency. The carrier is a solution of polyethylene oxide polypropylene oxide block copolymer exhibiting reverse phase characteristics (i.e., an increase in viscosity as temperature increases).
Here's an analysis of the provided text regarding the acceptance criteria and supporting studies for the DynaGraft II device:
Important Note: The provided document is a 510(k) Summary, which is a premarket notification to the FDA demonstrating substantial equivalence to a legally marketed predicate device. This type of document focuses on demonstrating equivalence rather than providing exhaustive details of standalone clinical trials for novel devices. As such, some of the information requested in your prompt (e.g., specific acceptance criteria for performance metrics, detailed statistical findings from a comparative effectiveness study, or precise sample sizes for human readers in an MRMC study) is not explicitly present in this summary.
1. Table of Acceptance Criteria and the Reported Device Performance
| Assessment Area | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Viral Inactivation | Suitable viral inactivation potential of processing methods for a wide range of potential human viruses. (Implied: Demonstrated inactivation of all tested viruses to an acceptable safety margin.) | Methods for processing DBM were evaluated against a select panel of viruses (various types, sizes, shapes, genomes). Testing "demonstrated suitable viral inactivation potential of the processing methods for a wide range of potential human viruses." |
| Osteoinductivity (In Vitro) | The in vitro assay for alkaline phosphatase activity of myoblast cells should correlate with the in vivo athymic rat model and predict in vivo osteoinductivity with at least 95% confidence. (Implied: Each lot of DBM must pass this in vitro assay.) | The in vitro assay (measuring alkaline phosphatase activity of myoblast cells compared to controls) "has been validated against the in vivo athymic rat model and predicts with at least 95% confidence the in vivo osteoinductivity of the test material." "Each lot of DBM incorporated in the DynaGraft II is evaluated for osteoinductive potential using an in vitro assay." 67 out of 67 test lots that passed the in vitro assay also passed the in vivo athymic rat assay. |
| Product Performance (In Vivo) | Demonstration of safe and effective performance when used as a bone void filler in orthopedic applications (e.g., bone graft extender, bony void filler in extremities, spine, and pelvis). (Implied: Radiographic and histological findings consistent with new bone ingrowth and integration.) | "Performance of DynaGraft II DBM has been evaluated in rabbit and sheep models by radiographic and histological methods for the indications specified in the Premarket Notification." "Clinical studies using DynaGraft II DBM Putty and Gel have been performed demonstrating acceptable outcomes." These data "substantiate DynaGraft II Putty and Gel safety and effectiveness for the indications presented." |
| Substantial Equivalence | DynaGraft II must be similar in design, materials of construction, and function to its predicate devices (AlloMatrix® DBM Putty and InterGro® DBM). It must also be osteoconductive and provide an environment for new bone ingrowth, be provided sterile, and for single patient use. The differences between the proposed device and predicates must not raise new questions of safety or effectiveness, or raise them but be adequately supported. | DynaGraft II and its predicate devices are "similar in design, materials of construction and function." Both are osteoconductive and provide an environment for new bone ingrowth. Both are sterile and for single patient use. The "only difference" (the inert carrier) is stated to meet AATB requirements, and safety/effectiveness are supported by product quality, validation, materials data, and test results. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Viral Inactivation (Test Set): A "select panel of viruses" was used, representing "various virus types, sizes, shapes, and genomes." The exact number of viruses is not specified.
- Data Provenance: Not explicitly stated, but implies laboratory testing performed by the manufacturer.
- Osteoinductivity (In Vivo Correlation Test Set): 67 test lots of DBM were assessed.
- Data Provenance: Not explicitly stated, but implies laboratory and animal (athymic rat) testing.
- Product Performance (Animal Models): Conducted in "rabbit and sheep models." The specific number of animals or cases is not provided.
- Data Provenance: Animal studies.
- Product Performance (Clinical Studies): "Clinical studies using DynaGraft II DBM Putty and Gel have been performed." The number of patients/cases is not specified.
- Data Provenance: "Clinical studies" implies human data, but details like country of origin or prospective/retrospective nature are not given.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This information is not provided in the 510(k) summary. Given the nature of the studies (viral inactivation, in vitro osteoinductivity, animal models, and general "clinical studies" for "acceptable outcomes"), it's unlikely that "experts to establish ground truth" (in the sense of independent clinical review of images/data) would be explicitly detailed in this type of submission. The ground truth for the non-clinical studies would typically be based on established biological assays, histological analysis, and radiographic interpretation by trained personnel. For "clinical studies," the "acceptable outcomes" would likely have been determined by primary investigators.
4. Adjudication Method for the Test Set
This information is not provided. Given the nature of the studies, formal adjudication methods (like 2+1 or 3+1 for imaging studies) are not described. For the osteoinductivity assay, the "correlation" against a positive and negative DBM control suggests a comparative methodology rather than expert adjudication of individual samples.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study is not explicitly mentioned or described. The document refers to "clinical studies" demonstrating "acceptable outcomes," but these are not detailed as MRMC studies comparing human readers with and without AI assistance. The device is a bone void filler, not an AI-powered diagnostic tool, so such a study would not typically be applicable.
- Effect Size: Not applicable, as no such study was described.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Study was Done
Not applicable. DynaGraft II is a medical device (bone void filler), not an algorithm or AI system. Its performance is inherent to the material properties and biological activity, not an algorithmic output.
7. The Type of Ground Truth Used
- Viral Inactivation: Based on standard virological assays to detect viral clearance/inactivation levels.
- Osteoinductivity (In Vitro): Alkaline phosphatase activity in myoblast cells, with positive and negative DBM controls. This assay was then validated against an in vivo athymic rat muscle pouch model (a biological standard for osteoinductivity, where bone formation in the muscle pouch is the ground truth).
- Product Performance (Animal Models): Radiographic and histological methods for assessing new bone formation, integration, and other healing parameters.
- Product Performance (Clinical Studies): "Acceptable outcomes," which can refer to a variety of clinical endpoints such as fusion rates, pain reduction, functional improvement, lack of complications, etc. The specific outcome data is not provided in detail.
- Substantial Equivalence: Comparison to legally marketed predicate devices based on design, materials, function, and regulatory compliance.
8. The Sample Size for the Training Set
Not applicable. DynaGraft II is a manufactured device, not an AI model that requires a training set. The "training" for the device's development involves material science, biological research, process optimization, and manufacturing controls.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of an AI algorithm.
For the development and optimization of the device itself, the "ground truth" during R&D would be established through a variety of methods:
- Material characterization: Chemical and physical tests to confirm composition and properties.
- Biocompatibility testing: In vitro and in vivo tests to ensure the material is not toxic or harmful.
- Process validation: Ensuring manufacturing processes consistently produce DBM with desired properties, including osteoinductivity. This relies on established biological assays (like the in vitro osteoinductivity assay validated against the athymic rat model) as a "ground truth" for material efficacy.
{0}------------------------------------------------
510(k) Summary
lsoTis OrthoBiologics DynaGraft II
Sponsor 1.
IsoTis OrthoBiologics, Inc. 2 Goodyear, Suite B Irvine, CA 92618 U.S.A
| Contact Person: | Paul Doner |
|---|---|
| Telephone: | 949 855-7168 |
| Facsimile: | 949 595-8711 |
March 2005 Date Prepared:
Device Name 2.
| Proprietary Name: | DynaGraft II Gel and Putty |
|---|---|
| Common/Usual Name: | Bone Void Filler |
| Classification Name: | Sec. 888.3045 Resorbable calcium salt bone void filler device. |
Predicate Devices 3.
AlloMatrix ® DBM Putty with inert carrier Sodium Carboxymethylcellulouse (K040980) InterGro® DBM with inert carrier Lecithin (K031399)
Device Description 4.
DynaGraft II is derived from selected donated human bone tissue that has been DynaGrait if is defived from selociosations are subsequently demineralized using a processed into partier. The demineralized bone matrix (DBM) is combined with nydroomono actu prise carrier and formulated to a gel or putty-like consistency.
The carrier is a solution of polyethylene oxide polypropylene oxide block copolymer The ourner to a colutibiting reverse phase characteristics (i.e., an increase in viscosity as temperature increases).
Intended Use 5.
For orthopedic applications as filler for gaps or voids that are not intrinsic to the r of or the bony structure. DynaGraft II is indicated to be packed gently into bony gaps in the skeletal system as a bone graft extender (extremities, spine, and pelvis) gaps in the extremities and pelvis. These defects may belvis. These defects may be surgically created or the result of traumatic injury to the bone.
{1}------------------------------------------------
Technological Characteristics and Substantial Equivalence 6.
DynaGraft II and its predicate devices are similar in design, materials of construction DynaOration. The proposed and predicate devices are osteoconductive and and function. The proposed afta product and its predicate devices provide an Usteomductive. The Dynachat if in the environment for new bone ingrowth and intereofineoted, porode seemed are provided sterile and for single patient use. Stimulate bono growin. We proposed device and its predicates are the inert The only difference betwoon the proposed areaft II product meets the requirements of can for about safety and effectiveness is adequately supported by the the AATD. Troduct outsity and tion, materials data, and test results provided in this Premarket Notification.
-
Viral Inactivation Validation -
The methods for processing the DBM contained in DynaGraft II 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. -
Osteoinductivety Potential
The osteoinductive potential of the DBM used in DynaGraft II is determined via an in vitro assay The assay measures the alkaline phosphatase activity of myoblast cells. The level of alkaline phosphatese induction is compared to positive and negative DBM controls. Results from the assay were correlated with results from implantation of DBM into an athymic rat muscle pouch. Analysis of these results shows that the in vitro assay has been validated against the in vivo athymic rat model and predicts with at least 95% confidence the in vivo osteoinductivity of the test material. 67 out of 67 test lots that passed the in vitro assay passed the in vivo athymic rat assay via confirmation of intramuscular bone formation.
Each lot of DBM incorporated in the DynaGraft II is evaluated for osteoinductive potential using an in vitro assay. Testing each lot of DBM assures that only DBM with ostoeinductive potential is used in DynaGraft II. Although DBM used in the final product has been shown to be osteoinductive using an in vitro assay, the combination of DBM and inert carrier has not been evaluated for osteoinductivity; therefore, it is unknown to what extent the formulation components may alter the osteoinductivity character of the DBM. Additionally, it is unknown how osteoinductivity of the DBM component, measured via the in vitro assay, will correlate with human clinical performance of DynaGraft II.
Product Performance Testing Performance of DynaGraft II DBM has been evaluated in rabbit and sheep models by radiographic and histological methods for the indications specified in the Premarket Notification.
{2}------------------------------------------------
Clinical studies using DynaGraft II DBM Putty and Gel have been performed Olinioal studios deing of the spintrating acceptable outcomes.
These data substantiate DynaGraft II Putty and Gel safety and effectiveness for the indications presented in this Premarket Notification.
{3}------------------------------------------------
Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird with three stylized wing shapes.
Public Health Service
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
MAR 2 5 2005
Mr. Paul Donor Director of Quality Assurance and Regulatory Affairs IsoTis Orthobiologics, Inc. 2 Goodyear Irvine, CA 92618
Re: K040419
DynaGraft II Gel and DynaGraft II Putty Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler devices Regulatory Class: Class II Product Code: MQV Dated: January 5, 2005 Received: January 7, 2005
Dear Mr. Doner:
We have reviewed your Section 510(k) premarket notification of intent to market the device indication we have reviewed your Section 910(x) premaine is substantially equivalent (for the indications
referenced above and have determined the device is substantial in interests a referenced above and nave determined the actived predicate devices marketed in interstate for use stated in the encrosule) to regally manatise provice Americal Device Ameridments, or to commerce prior to May 28, 1776, the characters and of the Federal Food, Drug, devices that have been reclassified in accordance was a premarket approval application (PMA).
and Cosmetic Act (Act) that do not require approval of a premarket approval appl and Cosment Act (Act) that do not require approvinces of the general controls provisions of the Act. The You may, therefore, market the device, bacyce recurements for annual registration, listing of general controls provisions of the rise labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), in if your device is classifica (see above) into existing major regulations affecting your device can
may be subject to such additional controls. Existing major may be subject to such adultional controlis. Extrong stage of the 21, In addition, FDA may be found in the Code of Pouch oncerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean Prease be advised that FDA s issualled of a budenies with other requirements of the Act that IDA has made a determination in administered by other Federal agencies. You must of any rederal statutes and regulations and limited to: registration and listing (21 comply with an the Act 3 requirements, movements.
CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set
{4}------------------------------------------------
Page 2 - Mr. Paul Donor
forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic form in the quant) of evelsions (Sections 531-542 of the Act); 21 CFR 1000-1050. product radiation control provisions (reting your device as described in your Section 510(k) I mis lotter will and in yours finding of substantial equivalence of your device to a legally premaince notification " Tresults 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 n you desire of Compliance at (240) 276-0120. Also, please note the regulation entitled, Connect the Ories of Course to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small other gotterers, 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,
Stypk Plurke
Mirian C. Provost, Ph.D. Acting Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
{5}------------------------------------------------
K040419 510(k) Number (if known):
Device Name: DynaGraft® II Gel and Putty
Indications for Use:
DynaGraft® II is indicated for orthopedic applications as filler for gaps or voids that are DynaGratt' II is indicated for orthopedically as mar roll gadicated to be packed to be packed to be packed not intrinsic to the stablity of the bony strate. Dyne graft extender (extremities, spine,
gently into bony gaps in the skeletal system as a bone graft extremities, spine, gently into bony gaps in the skeletal System as a some of these defects may be pervis) and as bony vold fillor of the extrainatic injury to the bone.
Prescription Use _____________________________________________________________________________________________________________________________________________________________ (Per 21 CFR 801 Subpart D)
Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________ AND/OR
(Per 21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NECESSARY)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Styke Reurke
Division of General, Restorative, and Neurological Devices
510(k) Number_________________________________________________________________________________________________________________________________________________________________
§ 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.