(112 days)
For orthopedic applications as filler for gaps or voids that are not intrinsic to the stability of the bony structure. Connexus is indicated to be packed gently into bony gaps in the skeletal system as a bone graft extender and as a bone void filler of the extremities and pelvis. These defects may be surgically created or the result of traumatic injury to the bone.
Connexus is derived from selected donated human bone tissue that has been processed into particles. The bone particles are subsequently demineralized using a hydrochloric acid process. The demineralized bone matrix (DBM) is combined with an inert reverse phase carrier and formulated to a putty-like consistency. The carrier is a solution of polyethylene oxide polypropylene oxide block copolymer dissolved in water exhibiting reverse phase characteristics (i.e., an increase in viscosity as temperature increases).
The provided text describes the 510(k) summary for the Connexus Putty, a bone void filler. It details the device, its intended use, and substantial equivalence to predicate devices, but it does not contain specific acceptance criteria or a dedicated study demonstrating how the device meets such criteria through quantitative performance metrics.
Instead, the document focuses on demonstrating substantial equivalence primarily through:
- Technological Characteristics: Stating similarities in design, materials, and function with predicate devices, and that both are osteoconductive and osteoinductive.
- Viral Inactivation Validation: Describing a study that evaluated the viral inactivation potential of the DBM processing methods.
- Osteoinductivity Potential: Explaining an in vitro assay for osteoinductive potential of the DBM, validated against an in vivo athymic rat model.
- Product Performance Testing: Mentioning evaluations in rabbit and sheep models for safety and effectiveness, but without presenting specific performance data or acceptance criteria.
Therefore, many of the requested details cannot be extracted directly from this document because it is a 510(k) summary focused on substantial equivalence rather than a full study report with detailed acceptance criteria and performance data.
Here's an attempt to answer based on the available information:
1. A table of acceptance criteria and the reported device performance
| Acceptance Criteria Category | Specific Criteria (as inferred or directly stated) | Reported Device Performance |
|---|---|---|
| Viral Inactivation | Suitable viral inactivation potential for a wide range of potential human viruses. | Viral inactivation testing demonstrated "suitable viral inactivation potential of the processing methods for a wide range of potential human viruses." (Specific reduction factors or thresholds are not provided). |
| Osteoinductivity (DBM) | In vitro assay measurement of alkaline phosphatase activity correlated with in vivo athymic rat model. Each lot of DBM must pass the in vitro assay. | 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 Connexus is evaluated for osteoinductive potential using an in vitro assay." |
| Product Performance (Overall) | Safety and effectiveness for indicated uses as evaluated in animal models. | Performance "evaluated in rabbit and sheep models by radiographic and histological methods for the indications specified." "These data substantiate Connexus Putty safety and effectiveness for the indications presented..." (Specific quantitative outcomes, histological scores, or radiographic measures are not provided, nor what specific thresholds constituted "safety and effectiveness"). |
2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Viral Inactivation Validation: No specific sample size mentioned for viruses, just "a select panel of viruses." No data provenance specified.
- Osteoinductivity Potential (Test Set):
- In vivo athymic rat model: 67 test lots were evaluated.
- Data Provenance: Not specified, but likely laboratory-based. The study appears to be prospective in nature for validation, and then individual lots are tested prospectively.
- Product Performance Testing (Animal Models): Samples for "rabbit and sheep models" were used, but specific numbers are not provided. The data is likely prospective experimental data from these animal studies.
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)
Not applicable. The ground truth for viral inactivation is laboratory-based (viral assays). For osteoinductivity, it's based on biochemical markers (alkaline phosphatase) and histological confirmation of bone formation in rats, not expert review of images or clinical outcomes. For the animal performance studies, evaluation by "radiographic and histological methods" likely implies expert interpretation (e.g., veterinary pathologists, radiologists) but the number or qualifications are not stated.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable. This type of adjudication is typically for image-based diagnostic studies or clinical outcomes, which are not the primary focus of the performance data presented here.
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
Not applicable. This device is a bone void filler, not an AI-powered diagnostic tool.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Not applicable. This device is a physical medical device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- Viral Inactivation: Direct viral load measurements and inactivation assays.
- Osteoinductivity:
- In vitro: Alkaline phosphatase activity (biochemical marker).
- In vivo (rat model): Histological confirmation of intramuscular bone formation (pathology/histology).
- Product Performance: Radiographic and histological findings in animal models (pathology/histology, imaging interpretation).
8. The sample size for the training set
Not applicable. This is a physical medical device, not an AI or machine learning algorithm requiring a "training set" in the conventional sense. The "validation" of the in vitro osteoinductivity assay against the in vivo model could be considered a form of training/validation, where the 67 test lots served to establish the correlation.
9. How the ground truth for the training set was established
Not applicable in the typical AI sense. For the osteoinductivity assay validation, the ground truth for the in-vitro assay was established by correlating its results with the in-vivo osteoinductivity confirmed via histological analysis of intramuscular bone formation in athymic rats.
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JUL 2 - 2005 510(k) Summary
IsoTis OrthoBiologics Connexus
1. Sponsor
IsoTis OrthoBiologics, Inc. 2 Goodvear, 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: | Connexus Putty |
|---|---|
| Common/Usual Name: | Bone Void Filler |
| Classification Name: | Sec. 888.3045 Resorbable calcium salt bone void filler device. |
3. Predicate Devices
DynaGraft II Paste and Putty (K040419) AlloMatrix ® DBM Putty with inert carrier Sodium Carboxymethylcellulouse (K040980) InterGro® DBM with inert carrier Lecithin (K031399) Osteofil Paste DBM with inert carrier Porcine Collagen (K043420)
4. Device Description
Connexus is derived from selected donated human bone tissue that has been processed into particles. The bone particles are subsequently demineralized using a hydrochloric acid process. The demineralized bone matrix (DBM) is combined with an inert reverse phase carrier and formulated to a putty-like consistency.
The carrier is a solution of polyethylene oxide polypropylene oxide block copolymer dissolved in water exhibiting 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 stability of the bony structure. Connexus is indicated to be packed gently into bony gaps in the skeletal system as a bone graft extender and as a bone void filler of the extremities and pelvis. These defects may be surgically created or the result of traumatic injury to the bone.
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6. Technological Characteristics and Substantial Equivalence
Connexus and its predicate devices are similar in design, materials of construction and function. The proposed and predicate devices are osteoconductive and osteoinductive. The Connexus product and its predicate devices provide an interconnected, porous scaffold and an environment for new bone ingrowth and stimulate bone growth. The only differences between the proposed device and its predicates are the percentage of demineralized bone and the inert carriers used. Connexus is provided sterile and for single patient use. The donor bone in the Connexus product meets the requirements of the AATB. Product safety and effectiveness is adequately supported by the substantial equivalence information. materials data, and test results provided in this Premarket Notification.
Viral Inactivation Validation -
The methods for processing the DBM contained in Connexus 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.
Osteoinductivity Potential
The osteoinductive potential of the DBM used in Connexus 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 Connexus 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 Connexus. 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 Connexus.
Product Performance Testing
Performance of Connexus has been evaluated in rabbit and sheep models by radiographic and histological methods for the indications specified in the Premarket Notification.
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These data substantiate Connexus Putty safety and effectiveness for the indications presented in this Premarket Notification.
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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 circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, facing to the left.
JUL 7 - 2005
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
Mr. Paul Doner IsoTis OthoBiologics Incorporated Director of Quality Assurance and Regulatory Affairs 2 Goodyear, Suite B Irvine, California 92618
Re: K050690
Trade Name: Connexus Regulation Number: 21 CFR 888.3045 Regulation Name: Reabsorbable calcium salt bone void filler device Regulatory Class: II Product Code: MQV Dated: June 23, 2005 Received: June 24, 2005
Dear Mr. Doner:
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 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 -Mr. Paul Doner
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 (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
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Sincerely yours
Miriam C. Provost, Ph.D.
Acting Director
Division of General, Restorative
and Neurological Devices
Office of Device Evaluation
Center for Devices and
Radiological Health
Enclosure
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510(k) Number (if known): K050690
Connexus TM Device Name:
Indications for Use:
Connexus is an osteoinductive and osteoconductive bone filling material indicated:
For orthopedic applications as filler for gaps or voids that are not intrinsic to the stability of the bony structure. Connexus is indicated to be packed gently into bony gaps in the skeletal system as a bone graft extender and as bony void filler of the extremities and pelvis. These defects may be surgically created or from the result of traumatic injury to the bone.
Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use _ (Part 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)
Stupt Rurder
(Division 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.