(717 days)
Nexpowder™ is used for hemostasis of non-variceal, upper gastrointestinal bleeding.
The Nexpowder™ is used for hemostasis of non-variceal, upper gastrointestinal bleeding. The Nexpowder™ is a prescription only, single-use device provided with a pre-packaged powder, a vial, and a Delivery System, which consists of a Spray body, a Connector and a Delivery Catheter. The powder vials are provided in a sterile condition with gamma radiation sterilization and the non-sterile external Spray Body delivery system with its sterile Connector and sterile Delivery Catheter. The hemostatic powder agents of the Nexpowder™ are primarily composed of succinic anhydride ({-poly-L-lysine) and oxidized dextran and are endoscopically applied through a catheter channel of the delivery system to control qastrointestinal bleeding in the upper qastrointestinal tract. Utilizing the installed battery power, air pressures are generated from the air pump placed in the spray body of Nexpowder™ delivery system to provide effective physical force to move the hemostatic powder agent into the delivery catheter. The hemostatic agents of the Nexpowder™ ultimately get sprayed onto the hemostasis target site in the gastrointestinal tract. Nexpowder is excreted from the patient's gastrointestinal or digestive system primarily by peristalsis of the human digestive system within the three days.
The device described is Nexpowder™, a hemostatic device for intraluminal gastrointestinal use. The information provided outlines the device's characteristics and the studies performed to demonstrate its safety and effectiveness for FDA 510(k) clearance.
Here's an analysis of the acceptance criteria and the studies that prove the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly derived from the comparison to the predicate device (Hemospray® Endoscopic Hemostat) and the various testing performed to demonstrate substantial equivalence, particularly in terms of hemostatic efficacy and safety. The performance metrics focus on initial hemostasis rates, re-bleeding rates, and the absence of adverse events.
| Acceptance Criteria (Implicit) | Reported Device Performance (Nexpowder™) |
|---|---|
| Hemostatic Efficacy: | |
| - Achieve initial hemostasis | Porcine Study I: Initial hemostasis achieved in all animals (6/6). |
| Porcine Study II: Rate of achieving initial hemostasis was 67% (4/6) in the treatment group. | |
| Clinical Study A: 100% (37/37) initial hemostasis. | |
| Clinical Study B: 96.4% (54/56) initial hemostasis. | |
| Clinical Study C: 94% (16/17) initial hemostasis. | |
| Clinical Study D: 97.5% (40/41) initial hemostasis. | |
| Clinical Study E: 100% (50/50) initial hemostasis. | |
| - Low re-bleeding rates | Porcine Study I & II: None of the animals showed re-bleeding up to the 30-day follow-up. |
| Clinical Study A: 8.11% within 3 days. | |
| Clinical Study B: 3.7% within 30 days. | |
| Clinical Study C: 19% within 30 days. | |
| Clinical Study D: 4.3% within 7 days; 22.5% within 28 days. | |
| Clinical Study E: 2.0% within 3 days; 4.0% within 30 days. | |
| Safety: | |
| - Absence of serious adverse events (e.g., perforation, obstruction, gas embolism) | Porcine Study I & II: No gastrointestinal perforation, obstruction, or gas embolism caused by the device. |
| - Low rate of adverse events/complications in human use | Clinical Study A: 2.7% (1 adverse event - Fever) out of 37 subjects. |
| Clinical Study B, C, D, E: Zero adverse events reported. | |
| - Biocompatibility (Non-cytotoxic, non-sensitizer, non-irritant, no systemic/subchronic toxicity, non-pyrogenic, hemocompatible, non-genotoxic) | All biocompatibility endpoints tested (Cytotoxicity, Sensitization, Irritation, Acute Systemic Toxicity, Material Mediated Pyrogenicity, Hemocompatibility, Genotoxicity, Implantation, Subchronic Toxicity, Endotoxin for delivery system) for both hemostatic powder and delivery system components yielded favorable (passing) results, demonstrating biocompatibility in compliance with ISO 10993 standards and FDA guidance. |
| - Sterility (Sterilization Assurance Level of 10-6) | Achieved for powder (gamma radiation) and catheter/connector (EtO sterilization). Sterility tests of Nexpowder, catheter, and connector at T=0 and T=3 years were favorable. |
| - Physical and Functional Integrity (Design Verification) | All design verification performance tests (Appearance, Weight, Absorption, Water Content, Adhesion, Dimension Verification, Tensile Strength, Air Leak, Spray, Air Pressure, Power Switch Function, Battery Protection Film, Battery Cap) at T=0, T=2 years, and T=3 years accelerated aging showed favorable results, meeting applicable ISO and FDA recognized standards. |
| - Shelf Life (15 months minimally) | Supported by 15 months shelf life testing. |
| - Usability & Transport (Usability Engineering, Packaging, Distribution) | Usability Engineering Evaluation conducted. Packaging validation and verification, including seal peeling, dye penetration for catheter/connector and spray body (T=0 and T=3 years), and distribution transportation tests were performed with favorable results. |
2. Sample Size for the Test Set and Data Provenance
The "test set" for performance evaluation consists of both animal studies and human clinical data.
-
Animal Studies (Porcine Studies I & II):
- Sample Size:
- Study I: 6 Nexpowder™ treated, 6 Hemospray® treated (predicate), 3 sham controls (total 15 pigs).
- Study II: 6 Nexpowder™ treated, 3 Hemospray® treated (predicate) (total 9 pigs).
- Data Provenance: Prospective animal studies conducted in a controlled environment (porcine model for upper gastrointestinal bleeding).
- Sample Size:
-
Human Clinical Data (Real-world evidence from OUS market):
- Sample Size:
- Clinical Study A: 76 patients (37 Nexpowder™ in test group)
- Clinical Study B: 56 patients
- Clinical Study C: 17 patients
- Clinical Study D: 41 patients
- Clinical Study E: 50 patients (Retrospective Aggregated Data Collection survey)
- Total: 240 patients (excluding the 39 from study A that likely received a comparator or were not Nexpowder treated based on the provided numbers, and noting that the document states "315 patients with an additional 50 patients from a Retrospective Aggregated Data Collection survey" which doesn't perfectly match the sum of individual study patient numbers provided. Assuming the sum of reported patients in the table are the test set.)
- Data Provenance: Real-world evidence (RWE) from the OUS (outside U.S.) market. Clinical Studies A, B, C, D are likely retrospective or prospective observational studies from OUS. Clinical Study E is explicitly stated as a "Retrospective Aggregated Data Collection survey." The specific countries of origin are not detailed in this summary.
- Sample Size:
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
This information is not explicitly provided in the given text.
- For the animal studies, histopathological evaluation was performed, implying expert pathologists. However, the number and qualifications are not mentioned.
- For the human clinical data, clinical outcomes (hemostasis, re-bleeding, adverse events) are reported, which by definition would be assessed by medical professionals. However, the specific number of experts, their role in establishing "ground truth," or their qualifications (e.g., "radiologist with 10 years of experience") are not detailed. It's common in clinical trials for treating physicians to establish these outcomes.
4. Adjudication Method for the Test Set
This information is not explicitly provided in the given text.
- For the prospective clinical study (Study A), it is described as "Prospective, Multicenter, Single-blind (subject) Controlled Clinical Trial." This suggests formal data collection, but it does not specify if an independent adjudication committee was used for outcomes like hemostasis or adverse events, or if a 2+1/3+1 consensus method was employed for ground truth establishment.
- For the other clinical studies and the retrospective survey, the adjudication method for reported outcomes is not mentioned.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of how much human readers improve with AI vs without AI assistance
An MRMC study is typically performed for diagnostic imaging devices where human readers interpret images with and without AI assistance. This device, Nexpowder™, is a hemostatic device, not an imaging or diagnostic device. Therefore, an MRMC comparative effectiveness study as described (human readers with/without AI assistance) would not be applicable and was not performed.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
This question is also not applicable in the context of Nexpowder™ as it is a physical medical device (hemostatic powder and delivery system), not an AI algorithm. The device's performance is inherently "standalone" in how it acts on the tissue, but it still requires a human operator (endoscopist) for delivery. There is no AI component to the device itself that would be evaluated in an "algorithm only" manner.
7. The Type of Ground Truth Used
- Animal Studies:
- Direct observation: Initial hemostasis, re-bleeding episodes.
- Histopathology: Microscopic examination of tissue at the device application site, likely confirmed by expert pathologists.
- Human Clinical Data:
- Clinical Outcomes: Initial hemostasis, re-bleeding events, and adverse events as observed and documented by treating clinicians. This represents clinical consensus based on standard medical practice and diagnostic criteria.
8. The Sample Size for the Training Set
This information is not applicable as Nexpowder™ is a physical medical device, not an AI, algorithm-driven, or machine learning device that requires a "training set." The development of the device involves engineering, chemical formulation, and preclinical testing, rather than data-driven model training.
9. How the Ground Truth for the Training Set was Established
This information is not applicable for the same reasons as point 8.
§ 878.4456 Hemostatic device for intraluminal gastrointestinal use.
(a)
Identification. A hemostatic device for intraluminal gastrointestinal use is a prescription device that is endoscopically applied to the upper and/or lower gastrointestinal tract and is intended to produce hemostasis via absorption of fluid or by other physical means.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device must be demonstrated to be biocompatible.
(2) Performance data must support the sterility and pyrogenicity of the device.
(3) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the identified shelf life.
(4) In vivo performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The testing must evaluate the following:
(i) The ability to deliver the hemostatic material to the bleeding site;
(ii) The ability to achieve hemostasis in a clinically relevant model of gastrointestinal bleeding; and
(iii) Safety endpoints, including thromboembolic events, local and systemic toxicity, tissue trauma, gastrointestinal tract obstruction, and bowel distension and perforation.
(5) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be evaluated:
(i) Materials characterization of all components must demonstrate the device meets established specifications, which must include compositional identity and purity, characterization of impurities, physical characteristics, and reactivity with fluids.
(ii) Performance testing must demonstrate the mechanical integrity and functionality of the system used to deliver the device and demonstrate the device meets established specifications, including output pressure for propellant-based systems.
(6) Labeling must include:
(i) Information identifying and explaining how to use the device and its components; and
(ii) A shelf life.