(253 days)
DirectInject is a self-setting, calcium phosphate cement intended to repair neurosurgical burr holes, contiguous craniotomy cuts and other cranial defects not intrinsic to the stability of the bony structure. It is also intended for augmentation or restoration of bony contour in the craniofacial skeleton to include the cranial and zygomatic bones. DirectInject is intended to repair cranial defects with a surface area of 4 cm2 or less.
DirectInject is indicated for patients in whom skeletal growth is complete. It can be used in patients with surgically created bone defects.
Stryker DirectInject consists of a sterile dual paste system, provided pre-filled in a double barrel delivery syringe system, which is calcium phosphate based. Upon injection through the Mixer-Cannula, the two pastes form a cement paste which is injectable, moldable and biocompatible. The injected cement paste will harden under normal body conditions to form hydroxyapatite, which is the principle mineral constituent of bone. The contents are supplied sterile for single patient use in sizes of 3 cc, 5 cc, and 10 cc.
The provided text is a 510(k) summary for the Stryker DirectInject device, which is a calcium phosphate cement for cranioplasty. It focuses on demonstrating substantial equivalence to predicate devices rather than providing a performance study with acceptance criteria in the typical sense of a clinical trial for diagnostic devices. Therefore, much of the requested information regarding diagnostic performance, ground truth, experts, and sample sizes for training/test sets is not applicable to this type of submission.
However, I can extract information related to the performance data provided to support the safety and effectiveness of the device, primarily through biocompatibility and bench testing.
Here's a breakdown of the information that can be extracted from the provided text, addressing the points where applicable:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't present acceptance criteria in a table format with corresponding numerical performance metrics for a diagnostic device. Instead, it describes performance testing conducted to demonstrate safety and effectiveness for a medical device (cranioplasty cement).
The acceptance criteria are implied by the standards the device was tested against. The "reported device performance" is generally stated as the device having passed these tests and performing as intended.
| Characteristic | Test | Standard/Guidance | Implied Acceptance Criteria | Reported Device Performance |
|---|---|---|---|---|
| Biocompatibility | Cytotoxicity | ISO-10993-5 | Material is non-cytotoxic. | Device passed. |
| Irritation | ISO-10993-10 & ISO-10993-2 | Material is non-irritating. | Device passed. | |
| Sensitization | ISO-10993-10 & ISO-10993-2 | Material is non-sensitizing. | Device passed. | |
| Acute systemic toxicity | ISO-10993-11 & ISO-10993-2 | Material does not cause acute systemic toxicity. | Device passed. | |
| Genotoxicity (various) | ISO-10993-3 & ISO-10993-2 | Material is not genotoxic. | Device passed. | |
| Haemocompatibility | ISO-10993-4 & ASTM F756 | Material is haemocompatible. | Device passed. | |
| Sub-Chronic Toxicity | ISO-10993-11 & ISO-10993-2 | Material does not cause sub-chronic toxicity. | Device passed. | |
| Chronic toxicity | ISO-10993-11 & ISO-10993-2 | Material does not cause chronic toxicity. | Device passed. | |
| Neurotoxicity (8 weeks) | ISO-10993-6 & ISO-10993-2 | Material is not neurotoxic. | Device passed. | |
| Physical Properties | X-ray diffraction | International Centre for Diffraction Data (ICDD) | Chemical composition matches expected for hydroxyapatite. | Device passed (implies intended chemical characterization was met). |
| Fourier Transform Infrared | N/A | Spectroscopic profile matches expected for hydroxyapatite. | Device passed (implies intended chemical characterization was met). | |
| X-ray Fluorescence | N/A | Elemental composition matches expected. | Device passed (implies intended chemical characterization was met). | |
| Porosity | ASTM D4404-10, ASTM D4284-12 | Porosity within acceptable limits for a bone void filler intended for osteointegration. | Device passed (implies porosity was within specified ranges). | |
| pH testing | USP <791> | pH is within physiologically acceptable range. | Device passed (implies pH was within specified ranges). | |
| Setting time | N/A | Setting time is appropriate for surgical use. | Device passed (implies setting time was within specified ranges for clinical utility). | |
| Dimensional stability | N/A | Maintains shape and volume over time, without significant degradation or expansion. | Device passed (implies dimensional stability was within acceptable limits). | |
| Setting reaction temperature | N/A | Reaction temperature does not cause tissue damage. | Device passed (implies exotherm was within acceptable limits for safety). | |
| Injectability force | N/A | Injectability force is within ergonomic limits for surgeons. | Device passed (implies injectability force was within specified ranges). | |
| Performance | Compressive Strength | N/A | Compressive strength is sufficient for indicated use (non-load-bearing, temporary support). | Device passed (implies compressive strength was within specified ranges for functional integrity). |
| Max supported defect strength | N/A | Ability to repair defects of specified size (4 cm²) and provide adequate temporary support without structural failure. | Device passed (implies it can support the indicated defect size). | |
| Shelf life Assessment | ICH Q1A(R2) | Device maintains characteristics and sterility over specified shelf life. | Device passed (implies shelf life was adequately determined and justified). | |
| In-Vivo Testing | Local effects in sheep & rabbit model | ISO-10993-2 and ISO-10993-6 and "Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA" | Material is stable, osteoconductive, and integrates with bone without adverse local effects. | "These studies demonstrated that Stryker DirectInject is stable, osteoconductive, and integrates with the bone tissue surrounding the defect site." (This implies all aspects of local effects, stability, and osteoconductivity were met). |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Test Set Sample Size: For the in-vivo animal studies, the document mentions "a sheep and rabbit model." It does not specify the exact number of animals used in these models.
- Data Provenance: The biocompatibility and bench testing are laboratory-based. The in-vivo animal studies are conducted in animal models, likely in a research facility accredited with animal welfare standards. Country of origin for the data is not specified, but the submitter is Stryker Leibinger GmbH & Co. KG (Germany) with regulatory contact in Michigan (USA).
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 information is not applicable. The device is a bone cement, not a diagnostic AI device requiring expert consensus for ground truth. The "ground truth" for biocompatibility and material properties is established by adherence to recognized international standards and scientific testing methodologies. For the animal study, macroscopic and histological evaluations would typically be performed by trained veterinary pathologists, but the number and qualifications are not specified.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- This is not applicable as it relates to expert review for diagnostic ground truth, which is not part of this submission type.
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 is not applicable. This is a medical device (bone cement), not a diagnostic AI system.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- This is not applicable. This is a medical device (bone cement), not a diagnostic algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- For biocompatibility: Ground truth is defined by the passing criteria of the specified ISO and ASTM standards.
- For physical properties: Ground truth is defined by the expected material characteristics (e.g., hydroxyapatite composition, mechanical strength, setting time) as measured against the respective standards and internal specifications.
- For in-vivo testing: Ground truth is established by macroscopic and histological evaluation demonstrating stability, osteoconductivity, and integration with bone tissue, as interpreted by qualified personnel (e.g., veterinary pathologists).
8. The sample size for the training set
- This is not applicable for a non-AI medical device submission.
9. How the ground truth for the training set was established
- This is not applicable for a non-AI medical device submission.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
September 2, 2015
Stryker Craniomaxillofacial Mr. Nathan Van Sweden Senior Manager, Regulatory Affairs 750 Trade Centre Wav. Suite 200 Portage, Michigan 49002
Re: K143661 Trade/Device Name: DirectInject® Regulation Number: 21 CFR 882.5300 Regulation Name: Methyl Methacrylate for Cranioplasty Regulatory Class: Class II Product Code: GXP Dated: July 31, 2015 Received: August 3, 2015
Dear Mr. Van Sweden,
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you; however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in
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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.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Michael J.Hoffmann -S
for Carlos L. Peña, PhD, MS Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K143661
Device Name DirectInject
Indications for Use (Describe)
DirectInject is a self-setting, calcium phosphate cement intended to repair neurosurgical burr holes, contiguous craniotomy cuts and other cranial defects not intrinsic to the stability of the bony structure. It is also intended for augmentation or restoration of bony contour in the craniofacial skeleton to include the cranial and zygomatic bones. DirectIniect is intended to repair cranial defects with a surface area of 4 cm2 or less.
DirectInject is indicated for patients in whom skeletal growth is complete. It can be used in patients with surgically created bone defects.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) | |
|---|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
This section provides a summary of 510(k) safety and effectiveness information in accordance with the requirements of 21 CFR 807.92.
- I. SUBMITTER
| 510(k) Owner: | Stryker Leibinger GmbH& Co. KGBoetzinger Strasse 41D-79111 Freiburg, Germany |
|---|---|
| Submitter/ ContactPerson: | Nathan Van SwedenStryker Craniomaxillofacial750 Trade Centre WayPortage, MI 49002Phone: 269-389-3419Fax: 877-648-7114 |
| Date prepared: | August 31, 2015 |
| II. DEVICE | |
| Trade Name: | DirectInject® |
| Common or Usualname: | Methyl methacrylate for cranioplasty |
| Classificationname: | Methyl methacrylate for cranioplasty (882.5300) |
| Regulatory Class: | Class II |
| Product Code: | GXP |
III. PREDICATE DEVICE
Primary Predicate: Stryker Injectable Cement – K060763 This predicate has not been subject to a design-related recall.
Secondary Predicate: BoneSource HAC - K021440 This predicate has not been subject to a design-related recall.
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DEVICE DESCRIPTION IV.
Stryker DirectInject consists of a sterile dual paste system, provided pre-filled in a double barrel delivery syringe system, which is calcium phosphate based. Upon injection through the Mixer-Cannula, the two pastes form a cement paste which is injectable, moldable and biocompatible. The injected cement paste will harden under normal body conditions to form hydroxyapatite, which is the principle mineral constituent of bone. The contents are supplied sterile for single patient use in sizes of 3 cc, 5 cc, and 10 cc.
V. INTENDED USE/INDICATIONS FOR USE
DirectInject is a self-setting, calcium phosphate cement intended to repair neurosurgical burr holes, contiguous craniotomy cuts and other cranial defects not intrinsic to the stability of the bony structure. It is also intended for augmentation or restoration of bony contour in the craniofacial skeleton to include the cranial and zygomatic bones. DirectInject is intended to repair cranial defects with a surface area of 4 cm2 or less.
DirectInject is indicated for patients in whom skeletal growth is complete. It can be used in patients with surgically created bone defects.
| Subject Device | Primary Predicate –K060763 | Secondary Predicate– K021440 | |
|---|---|---|---|
| IntendedUse/Indicationsfor Use | DirectInject is a self-setting, calciumphosphate cementintended to repairneurosurgical burrholes, contiguouscraniotomy cuts andother cranial defectsnot intrinsic to thestability of the bonystructure. It is alsointended foraugmentation orrestoration of bonycontour in the | Stryker® InjectableCement is a self-settingcalcium phosphatecement indicated to fillbony voids or gaps ofthe skeletal system (i.e.extremities,craniofacial, spine, andpelvic).These defects may besurgically created orosseous defects createdfrom traumatic injury tothe bone. The StrykerInjectable Cement isindicated only for bonyvoids or gaps that are | BoneSource® is a self-setting, calciumphosphate cementintended for use in therepair of neurosurgicalburr holes, contiguouscraniotomy cuts andother cranial defectsas well as in theaugmentation orrestoration of bonycontour in thecraniofacial skeleton |
TABLE 5-1: COMPARISON OF INDICATIONS FOR USE
Traditional 510(k)
Stryker DirectInject
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stryker®
| craniofacial skeleton toinclude the cranial andzygomatic bones.DirectInject isintended to repaircranial defects with asurface area of 4 cm² orless.DirectInject isindicated for patientsin whom skeletalgrowth is complete. Itcan be used in patientswith surgically createdbone defects. | not intrinsic to thestability of the bonystructure.Stryker® InjectableCement cured in situprovides an openvoid/gap filler that canaugment provisionalhardware (e.g., K-Wires, plates, screws)to help support bonefragments during thesurgical procedure. Thecured cement acts onlyas a temporary supportmedia and is notintended to providestructural supportduring the healingprocess.Stryker® InjectableCement is a self-setting,calcium phosphatecement intended for usein the repair ofneurosurgical burrholes, contiguouscraniotomy cuts andother cranial defects aswell as in theaugmentation orrestoration of bonycontour in thecraniofacialskeleton. |
|---|---|
| --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
The Indications for Use statement for the Subject device is not identical to the Primary predicate device Stryker Injectable Cement; the differences do not alter the intended therapeutic use of the device nor do they affect the safety and effectiveness of the device relative to the predicate. Both devices have intended use. The Primary
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predicate is indicated for a wider anatomical range of the skeletal system (i.e. extremities, craniofacial, spine, and pelvic). The Indications for use of the Stryker DirectInject falls within the scope of the broader Indications for Use statement of the Primary predicate device.
The Indications for Use statement for the Subject device is not identical to the Secondary predicate device Bonesource HAC; however, the differences do not alter the intended therapeutic use of the device nor do they affect the safety and effectiveness of the device relative to the predicate. Both devices have the same intended use.
COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE VI. PREDICATE DEVICE
The Stryker DirectInject is compared to its predicate devices for substantial equivalence based on the following criteria:
- A. Principle of Operation
- B. Technological Characteristics
A. Principle of Operation
The operating principle of the Stryker DirectIniect is to repair neurosurgical burr holes, contiguous craniotomy cuts and other cranial defects. It is also intended for the augmentation or restoration of bony contour in the craniofacial skeleton. The Subject device and Predicate devices have the same principle of operation.
B. Technological and Operational Characteristics
At a high level, the Subject device and Predicate devices are based on the following technological elements:
- Same operating principle: repair neurosurgical burr holes, contiguous craniotomy cuts and other cranial defects.
- -Same area of application: Craniofacial (Cranial and Zygomatic Bones)
- Same duration of implantation: implant is osteointegrated via normal bone physiological conditions.
- -Similar control mechanism: The Subject device uses a dual syringe with pastes and a Mixer-Cannula, while the predicate devices use powder and liquid bases, a mixing apparatus and syringe (primary predicate).
- -Similar material formulation: Both the Primary and Secondary predicates and the Subject device form Hydroxyapatite cement, however, due to the paste form of the Subject device, a proprietary material formulation is used.
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VII. PERFORMANCE DATA
The following performance data are provided in support of the substantial equivalence determination.
Biocompatibility Testing
The biocompatibility evaluation for the Stryker DirectInject was conducted in accordance with
- The FDA Blue Book Memorandum #G95-1 "Use of International Standard ISO-10993, 'Biological Evaluation of Medical Devices Part 1: Evaluation and Testing,"" May 1, 1995,
- ISO 10993-1 "Biological Evaluation of Medical Devices Part 1: Evaluation and . Testing Within a Risk Management Process," as recognized by FDA.
- FDA draft guidance "Use of International Standard ISO- 10993, "Biological . Evaluation of Medical Devices Part 1: Evaluation and Testing", issued April 23, 2013
Stryker DirectInject is considered a permanent implant, tissue/bone contacting greater than 30 days. The implant is Hydroxyapatite cement, the same as the Predicate devices.
| Test | Standard |
|---|---|
| Cytotoxicity | ISO-10993-5 |
| Irritation | ISO-10993-10 & ISO-10993-2 |
| Sensitization | ISO-10993-10 & ISO-10993-2 |
| Acute systemic toxicity | ISO-10993-11 & ISO-10993-2 |
| Genotoxicity: Bacterial reverse mutation | ISO-10993-3 |
| Genotoxicity: Mouse lymphoma Assay | ISO-10993-3 |
| Genotoxicity: Mouse peripheral blood micronucleusstudy | ISO-10993-3 & ISO-10993-2 |
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Image /page/8/Picture/0 description: The image shows the word "stryker" in a bold, sans-serif font. The word is all lowercase, and the letters are closely spaced together. There is a registered trademark symbol to the right of the letter "r". The overall impression is one of a strong, modern brand.
| Haemocompatibility | ISO-10993-4 & ASTM F756 |
|---|---|
| Sub-Chronic Toxicity | ISO-10993-11 & ISO-10993-2 |
| Chronic toxicity | ISO-10993-11 & ISO-10993-2 |
| Neurotoxicity (8 weeks) | ISO-10993-6 & ISO-10993-2 |
Performance Bench Testing
The following performance bench tests were completed per the requirements of 'Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA '.
| Characteristic | Test | Standard |
|---|---|---|
| Chemical Characterization | X-ray diffraction | International Centre forDiffraction Data (ICDD) |
| Fourier Transform InfraredSpectroscopy | N/A | |
| X-ray Fluorescence | N/A | |
| Physical Properties | Porosity | ASTM D4404-10, ASTMD4284-12 |
| Performance | pH testing | USP <791> |
| Setting time | N/A | |
| Dimensional stability | N/A | |
| Setting reaction temperature | N/A | |
| Injectability force | N/A |
TABLE 5-3 PERFORMANCE TESTING FOR STRYKER DIRECTINJECT
In addition to the test methods identified above, the following tests were performed to address risk identified or design requirements.
| Characteristic | Test | Standard |
|---|---|---|
| Performance | Compressive Strength | N/A |
| Performance | Max supported defect strength | N/A |
| Performance | Shelf life Assessment | ICH Q1A(R2) |
| TABLE 5-4 PERFORMANCE TESTING FOR STRYKER DIRECTINJECT | |
|---|---|
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In-Vivo Testing
The following local effects in-vivo tests were performed as per the requirements of ISO-10993-2 and ISO-10993-6. The in-vivo local effects of Stryker DirectInject were evaluated in a sheep and rabbit model, by macroscopic and histological evaluation of the tissue in the treatment areas. These studies demonstrated that Stryker DirectInject is stable, osteoconductive, and integrates with the bone tissue surrounding the defect site.
Clinical Testing
Clinical testing was not required as a basis for substantial equivalence.
VIII. CONCLUSIONS
The results of the non-clinical data demonstrate the Stryker DirectInject will perform as intended in the specified use conditions. According to the comparison based on the requirements of 21 CFR 807.87 and the information provided herein, it is concluded that the information included in this submission supports substantial equivalence.
§ 882.5300 Methyl methacrylate for cranioplasty.
(a)
Identification. Methyl methacrylate for cranioplasty (skull repair) is a self-curing acrylic that a surgeon uses to repair a skull defect in a patient. At the time of surgery, the surgeon initiates polymerization of the material and forms it into a plate or other appropriate shape to repair the defect.(b)
Classification. Class II (performance standards).