(310 days)
NuStat is indicated for temporary control of internal organ space bleeding for patients displaying class III or class IV bleeding. It may also be used for control of severely bleeding wounds such as surgical wounds and traumatic injuries.
The NuStat is a hemostatic wound dressing that is composed of continuous filament silica and bamboo cellulose rayon fiber and is provided with radiopaque thread. The distribution of cellulose and silica fibers in each dressing is 65% silica fiber and 35% bamboo cellulose rayon fiber. The dressings are available in various sizes and provided sterile in either foil, Tyvek, or LDPE pouched configurations. The NuStat hemostatic wound dressings have a number of hemostatic properties that enhance the ability of the dressing to temporarily control bleeding. NuStat Hemostatic Dressing's mode of action is via absorption of fluid, which results in a physical aggregation of blood cells and clotting factors at the site of application. The radiopaque element allows for detection via x-ray.
The document describes a 510(k) premarket notification for a medical device called NuStat®, a non-absorbable, hemostatic gauze for temporary internal use. The submission seeks to expand the prescription (Rx) indication for use for the device. The study proves the device's substantial equivalence to a legally marketed predicate device (Z-Medica, LLC's D2 Dressing, DEN160012) and its identity to a reference device (Beeken Biomedical, LLC's NuStat XR, K160578).
Here's a breakdown of the requested information based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not present specific quantitative acceptance criteria or pass/fail thresholds for each test, but rather describes the performance evaluated against the "special controls for the non-absorbable, hemostatic gauze for temporary internal use as identified in 21 CFR 878.4454" and substantial equivalence to the predicate/reference devices. Therefore, the "acceptance criteria" are implied by the successful testing results and determination of substantial equivalence.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance and Outcome of Study |
|---|---|---|
| Hemostasis | Achieve hemostasis of a moderate to significant bleeding surface, substantially equivalent to predicate device. | Achieved hemostasis of a moderate to significant bleeding surface within 3 minutes in a Pilot study and Pivotal GLP study (liver resection in pig model). Substantially equivalent to the predicate device. |
| Radiographic Detection | Easily visualized radiographically at time of placement and at 48 hours. | The device was rated as being easily visualized radiographically at the time of placement and at 48 hours in a Pilot study and Pivotal GLP study (liver resection in pig model). |
| Vascular Obstruction & Downstream Embolization | No evidence of vascular obstruction or embolization, substantially equivalent to predicate device. | No evidence of vascular obstruction or embolization was observed in either the Pilot study or Pivotal GLP study (liver resection in pig model). In the GLP study, this was substantially equivalent to the predicate device. |
| Sterility | Device is sterile; no evidence of infection. | Validated sterilization testing shows the device is sterile. No evidence of infection was noted in either the Pilot study or Pivotal GLP study (liver resection in pig model). |
| Biocompatibility | Device is biocompatible per ISO 10993-1. | Results show the device is biocompatible based on testing per ISO 10993-1 for prolonged patient contact (>24 hours to 30 days) with blood path and circulating blood. |
| Cytotoxicity | Device is non-cytotoxic per ISO 10993-5. | Device is considered non-cytotoxic per ISO 10993-5 (ISO elution method). |
| Sensitization | Device is non-sensitizing per ISO 10993-10. | Device is considered non-sensitizing per ISO 10993-10 (Magnusson-Kligman method). |
| Irritation | Device is non-irritant per ISO 10993-11. | Device is considered non-irritant per ISO 10993-11 (intracutaneous reactivity testing). |
| Systemic Toxicity (Acute) | Device shows no acute systemic toxicity per ISO 10993-11. | Device showed no acute systemic toxicity based on testing in mice per ISO 10993-11. |
| Pyrogenicity | Device is non-pyrogenic per ISO 10993-11 and USP . | Device is considered non-pyrogenic per ISO 10993-11 and USP (rabbit pyrogen test). |
| Endotoxin | Device conforms to FDA and USP requirements for end-product release of medical devices. | Device conforms to FDA and USP requirements for end-product release of medical devices based on LAL Kinetic Turbidimetric Assay. |
| Interaction with Blood | Device performs as expected for a hemostatic device; activated complement. | Device performed as expected for a hemostatic device; activated complement, based on ISO 10993-4 (SC5b-9 Complement Assay). |
| Sub-acute Systemic Toxicity | Device shows no signs of systemic toxicity per ISO 10993-11. | Device showed no signs of systemic toxicity based on implantation in rabbit abdomen per ISO 10993-11. |
| Sub-chronic Systemic Toxicity | Device shows no signs of subchronic toxicity per ISO 10993-11. | Device showed no signs of subchronic toxicity based on the Pivotal Study "Evaluation of the NuStat Trauma Pad XR Dressing When Applied to a Linear Resection Defect, 48 Hours and 28 Day"- FP-SS, per ISO 10993-11. |
| Genotoxicity | Device shows no signs of genotoxicity per ISO 10993-5. | Device showed no signs of genotoxicity based on Ames test and Mouse lymphoma assay per ISO 10993-5. |
| Local Effects after Implantation | Expected irritation for non-absorbable device; no adverse events in pivotal study. | In the rabbit muscle study (ISO 10993-6), the device was considered an irritant, as expected for a non-absorbable device. In the Pivotal GLP Study, the device showed no adverse events. |
| Inflammation, Adhesions, Systemic and Local Toxicity | No signs of systemic/local toxicity; inflammation and adhesions as expected for surgery and substantially equivalent to predicate. | The device showed no signs of systemic or local toxicity. Inflammation and adhesions associated with the device were as expected for this type of surgery (laparotomy and liver resection) and were substantially equivalent to those of the predicate device, per ISO 10993-6, 10993-11 and customized assessments in the Pivotal GLP study. |
| In-vitro Clot Assessment | Device accelerates clotting times from baseline. | Device accelerated clotting times from baseline based on testing PT and aPTT in bench tests. |
| Particulate Release Testing | Substantially equivalent to predicate device, even if numerous. | Tested under worst-case scenario, the device released silica particulates in quantities that were too numerous to count. This was substantially equivalent to the predicate device. Particulate sizes were not enumerated for either device. |
| Swell Percent | Minimal swell. | The swell of the device was minimal, tested as part of absorption capacity. |
| Tensile Strength Testing | Pass according to specifications. | Tested and passed according to specifications. |
| Tear Strength | Pass according to specifications. | Tested and passed according to specifications. |
| Stability | Support a one-year expiration date. | Testing was performed to support a one-year expiration date. |
2. Sample Sizes and Data Provenance
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Sample Size for Test Set (Pre-market Studies):
- Pilot Study: "Pilot study to Develop and Refine a Survival Mode of Severe Hemorrhage for the Evaluation of the NuStat Internal Hemostatic Dressing (NuStat XR)" - ANS 2319 (number of animals not specified)
- Pivotal GLP Study: "Evaluation of the NuStat Trauma Pad XR Dressing When Applied to a Linear Resection Defect, 48 Hours and 28 Day"- FP-SS (number of animals not specified, but GLP implies rigorous standards)
- Biocompatibility/Toxicity Tests: Various ISO 10993 tests (number of animals or in vitro samples not specified, but these are standardized tests).
- In-vitro Clot Assessment: (number of bench tests not specified).
- Particulate Release Testing: (number of tests not specified).
- Swell Percent/Tensile/Tear Strength/Stability: (number of tests not specified).
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Data Provenance:
- The animal studies (Pilot and Pivotal GLP studies) were conducted using a pig model of liver resection.
- Other tests include standardized ISO 10993 biocompatibility and toxicity tests (e.g., mice for acute systemic toxicity, rabbits for pyrogenicity and sub-acute systemic toxicity/implantation).
- The studies were prospective for the purpose of demonstrating safety and effectiveness for a 510(k) submission.
- The country of origin is not explicitly stated, but as a US FDA submission, it's typically expected that these studies conform to international good laboratory practices (GLP) and are conducted in reputable facilities, often in the US or internationally accepted sites.
3. Number of Experts and Qualifications for Ground Truth
The document does not mention the use of human experts to establish ground truth in the context of device performance, as this device (hemostatic gauze) is assessed directly through in-vivo (animal model) and in-vitro laboratory testing for its physical and biological performance characteristics. The "ground truth" is established by direct measurement and observation of the device's hemostatic capabilities, radiographic visibility, biological interactions, and physical properties in these controlled experimental settings.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are typically used in clinical studies involving interpretation of medical images or patient outcomes, often by multiple human readers or experts, to resolve discrepancies and establish a consensus ground truth. This is not applicable here as the device's performance is determined by direct physiological and material science measurements in animal models and laboratory settings, rather than subjective human assessment of ground truth.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not conducted. This type of study is specifically designed for diagnostic devices, particularly those involving medical imaging where human interpretation of AI outputs is a key component. NuStat is a therapeutic hemostatic device, not a diagnostic AI system.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Not applicable. NuStat is a physical medical device (hemostatic gauze), not an algorithm or AI system. Its performance is inherent to its physical properties and biological interactions, not a computational output that would require a "standalone" algorithmic evaluation.
7. Type of Ground Truth Used
The "ground truth" for evaluating NuStat's performance was established through:
- Direct Physiological Measurement/Observation (in-vivo): In the pig model studies, the ability of the device to achieve hemostasis within a specific time (3 minutes), the absence of vascular obstruction/embolization, and the lack of infection were directly observed and measured. Radiographic visibility was visually assessed.
- Pathology/Histology: Likely used in the pivotal GLP study and local effects after implantation study to assess inflammation, adhesions, local toxicity, and the presence or absence of issues like vascular obstruction or embolization. The document mentions "assessments customized to the intended use" in the pivotal GLP study.
- Standardized Laboratory Testing (in-vitro): For biocompatibility, cytotoxicity, sensitization, irritation, systemic toxicity, pyrogenicity, endotoxin, interaction with blood, genotoxicity, in-vitro clot assessment, particulate release, swell percent, tensile strength, tear strength, and stability, the ground truth was established by adherence to recognized international standards (ISO, USP) and the measured outcomes of these tests.
8. Sample Size for the Training Set
Not applicable. NuStat is a physical medical device, not a machine learning model, so there is no "training set" in the context of AI development. The "training" for this device would refer to the research and development phases where the material composition and design were optimized.
9. How Ground Truth for the Training Set Was Established
Not applicable, as explained in point 8.
§ 878.4454 Non-absorbable, hemostatic gauze for temporary internal use.
(a)
Identification. A non-absorbable, hemostatic gauze for temporary internal use is a prescription device intended to be placed temporarily for control of severely bleeding wounds such as surgical wounds and traumatic injuries. The gauze is coated or impregnated with a hemostatic material which may enhance hemostasis by physical means. The device is intended to be removed once the patient is stabilized.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Animal performance testing must demonstrate that the device performs as intended under anticipated conditions of use. Specifically testing must:
(i) Demonstrate that the device is able to achieve hemostasis;
(ii) Demonstrate that the device can be radiographically detected; and
(iii) Assess pertinent safety endpoints including vascular obstruction and adhesion formation.
(2) The device must be demonstrated to be biocompatible.
(3) Non-clinical performance data must demonstrate that the device performs as intended under anticipated conditions of use. The following tests must be performed:
(i) In vitro clot assessment;
(ii) Particulate release testing;
(iii) Physical characterization, including swelling percent and particulate size;
(iv) Chemical characterization;
(v) Radiopacity testing; and
(vi) Mechanical integrity testing, including tensile strength and tear strength.
(4) Performance data must demonstrate the sterility of the device.
(5) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the identified shelf life.
(6) Labeling must include the following:
(i) Instructions for use, including an instruction to remove all visible device components by irrigation;
(ii) The maximum amount of time the device may be left within the body;
(iii) A shelf life;
(iv) A contraindication for intravascular use of the device; and
(v) A warning regarding the potential for adhesion formation.