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.

AI/ML Overview

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).
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.

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.

Summary

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Image /page/0/Picture/0 description: The image shows the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.

September 16, 2022

Nextbiomedical Co., Ltd. % Kyungyoon Kang CEO K-Bio Solutions 201 South 4th St, Suite 727 San Jose, California 95112

Re: K202929

Trade/Device Name: Nexpowder Regulation Number: 21 CFR 878.4456 Regulation Name: Hemostatic Device For Intraluminal Gastrointestinal Use Regulatory Class: Class II Product Code: QAU Dated: September 24, 2020 Received: September 29, 2020

Dear Kyungyoon Kang:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

for Deborah Fellhauer, RN, BSN Assistant Director DHT4B: Division of Infection Control and Plastic Surgery Devices OHT4: Office of Surgical and Infection Control Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K202929

Device Name Nexpowder™

Indications for Use (Describe)

Nexpowder™ is used for hemostasis of non-variceal, upper gastrointestinal bleeding.

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: Nexpowder™

l. Applicant/Manufacturer Information

Type of 510(k) Submission: Traditional 510(k) Premarket Notification

Applicant's Information

Name of Sponsor: NEXTBIOMEDICAL CO., LTD. Address: 6, Venture-ro 100beon-gil, Yeounsu-gu, Incheon, Republic of Korea Contact Name: Eunhye Lee Telephone No.: 82-32-880-0820 Email Address: ehlee@nextbiomedical.co.kr

Correspondent's Information

Company Name: K-Bio Solutions Correspondent Name: Mr. Kyungyoon Kang Email Address: kyungyoon.kang@kbiotechsolutions.com

Date Prepared: September 9th, 2022

II. Regulatory Information

Proposed Device:

Trade/Proprietary Name: Nexpowder™ ●
Classification Name: Hemostatic device for intraluminal gastrointestinal use
Regulatory Class: Class II, Regulation Number: 878.4456, ●
Product Code: QAU
510(K) number: K202929

Predicate Device:

Trade/Proprietary Name: Hemospray® Endoscopic Hemostat ●
Classification Name: Hemostatic device for intraluminal gastrointestinal use .
Product Code: QAU ●
De Novo Clearance number: DEN170015 ●
. 510k Submitter: Wilson-Cook Medical, Inc.

Reference Device:

Trade/Proprietary Name: PerClot® Topical ●
Classification Name: Dressing, Wound, Drug
. Product Code: FRO
510(K) number: K132105
. 510k Submitter: CRYOLIFE, INC.

III. Device Description of the Nexpowder™

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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.

IV. Intended Use/ Indications for Use

Nexpowder™ is used for hemostasis of non-variceal, upper gastrointestinal bleeding.

V. Substantial Equivalence Comparison with Predicate Device

ComparisonItem	Proposed Device	Predicate Device	Assessment of SubstantialEquivalence
Trade/DeviceName	Nexpowder™	Hemospray®Endoscopic Hemostat	N/A
Common Name	Hemostatic Devicefor intraluminalgastrointestinal use	Hemostatic Devicefor intraluminalgastrointestinal use	Identical to the predicate device
510k Number	K202929	DEN170015	N/A
Manufacturer	NEXTBIOMEDICALCo., Ltd	Wilson-Cook Medical,Inc.	N/A
Application/DeviceOverview	The device is appliedby using catheter,delivery system and agastrointestinalendoscope.The device iscomprised of ahandheld deliverysystem that propelshemostatic powderthrough a catheter tothe GI bleeding site.	The device is appliedby using endoscopiccatheter, deliverysystem and agastrointestinalendoscope.The device iscomprised of ahandheld deliverysystem that propelshemostatic powderthrough a catheter tothe GI bleeding site.	Similar to the predicate device
Intended Use /Indications for Use	The device is intendedto be used forhemostasis ofnon-variceal, uppergastrointestinalbleeding.	The device is intendedto be used forhemostasis ofnon-varicealgastrointestinalbleeding.	The indications for use are asubset of the indications clearedfor the predicate device.
OperationPrinciple	When the devicecomes in contact withan activelybleeding site, thepowder absorbs water,then acts bothcohesively andadhesively, forming amechanical barrierover the bleeding site.	When the devicecomes in contact withan activelybleeding site, thepowder absorbs water,then acts bothcohesively andadhesively, forming amechanical barrierover the bleeding site.	Similar to the predicate device
	Nexpowder is an inertpowder developed forendoscopichemostasis. Thepowder is delivered byuse of a batterypowered deliverysystem and through acatheter insertedthrough the workingchannel of anendoscope whichprovides access to thesite of the bleed. Itcontains no human oranimal proteins orbotanicals	Hemospray is an inertpowder developed forendoscopichemostasis. Thepowder is delivered byuse of a carbondioxide powereddelivery system andthrough a catheterinserted through theworking channel of anendoscope whichprovides access to thesite of the bleed. Itcontains no human oranimal proteins orbotanicals and has noknown allergens.	Similar to the predicate device,as for the difference in thedelivery system thatNexpowderTM is operated basedon the battery powered deliverysystem, while the predicate,Hemospray® is operated basedon the aerosol delivery systemdoes not raise different questionsin terms of safety andeffectiveness, given NexpowderTMdelivery system has been verifiedto meet the electrical safety andperformance requirements per theFDA's recognized standards ofIEC 60601-1, IEC 60601-1-2, andIEC 60601-1-6 and specialcontrols. The same FDA'srecognized IEC standards havebeen applied for the electricalsafety and performanceevaluation of the predicate,Hemospray Endoscopic Hemostat(DEN170015, Wilson-CookMedical, Inc.).
ProductDesign	The device systemconsists of hemostaticpowder agent and adelivery system.	The device systemconsists of hemostaticpowder agent and adelivery system.	The overall device system withhemostatic agent and deliverysystem is substantiallyequivalent/similar to the predicatedevice in terms of the use ofhemostatic agent and a delivery
			system under gastrointestinalendoscopy.
HemostaticAgent	Powder in a vial,including:• ε-poly-L-lysine• Aldehyded dextran• Polyvinylpyrrolidone• Brilliant Blue FCF• Low-substitutedHydroxypropylcelluloseL-HPC• Lactose Monohydrate• Magnesium Stearate	Sodium bentonite	The composition of thehemostatic powder componentsof the subject and predicatedevices is different.
Specifications	Catheter French size:7.5FrCatheter Length:220.0cm	Catheter French size:7Fr, 10FrCatheter Length:220cm,	Similar dimensional specificationsto the predicate device. Thefavorable results of the designverification and validation testingdemonstrate conformance of theproposed Nexpowder™ to theFDA's recognized standards andthe design requirements. Thetesting results furtherdemonstrate the proposedNexpowder™ is substantiallyequivalent to the predicatedevice, Hemospray® EndoscopicHemostat, as the proposedNexpowder™ and predicatedevice are subject to the samerecognized standards of the FDAfor the special controls evaluationof medical device.
SterilizationMethod	Powder: GammaradiationDelivery system(catheter andconnector): EtOSterilizationSpray Body: Non-sterile	Product: Gammaradiation	Similar Gamma radiationsterilization for hemostatic agentas the predicate device
SterilizationValidationTarget	Sterilization AssuranceLevel of10-6	SterilizationAssurance Level of 10-6	Identical to the predicate devices
Shelf Life	15 months	3 Year	Supported by 15 months shelf lifetesting

Assessment Table of Substantial Equivalence

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Similar to the predicate device, Nexpowder™ is an inert powder developed for endoscopic hemostasis. Nexpowder™ contains Aldehyded Dextran and Poly-L-Lysine (Polysaccharide) derived from microbial extraction. The powder is delivered by use of a battery powered delivery system and through a catheter

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inserted through the working channel of an endoscope which provides access to the intended hemostasis target site. The overall hemostatic mechanism of Nexpowder™ to form a physical control barrier to achieve hemostasis is similar to the predicate, Hemospray® Endoscopic Hemostatic agent of Nexpowder™ is provided in a form of powder polymer materials, which can be readily sprayed over a bleeding site in the non-variceal upper gastrointestinal tract. The hemostatic agent of powder polymer functions as a physical, mechanical barrier over the bleeding site in the gastrointestinal tract to effectively control bleeding. From the standpoint of forming the mechanical barrier physically, the presence of blood in and of itself is not required. But any type of bodily fluids including digestive fluids excreted in the gastrointestinal tract and blood at the hemostasis target site coming into contact with the Nexpowder™ would lead to the crosslinking gelation effects following the hemostatic agent's rapid absorption of the bodily fluids.

Although the hemostatic agent may differ in chemical composition for each the predicate and subject device, in both of these products, the individual ingredients do not contain human or animal proteins or botanicals and have the same end state, which is a gel that will act as a mechanical barrier and induce hemostasis. In addition, the modified polysaccharide material that comprises the hemostatic agent ingredient of the Nexpowder™ is similar to the polysaccharide material in the reference device, PerClot® Topical (K132105). PerClot® Topical is another class II, hemostat device, intended as a topical wound dressing and used to control bleeding from the skin by rapidly absorbing water and forming a gelled adhesive matrix that provides a mechanical barrier to further bleeding. This demonstrate that polysaccharides used in hemostatic agents are not novel. Moreover, the biocompatibility profile of Nexpowder™ agents has been confirmed with comprehensive biocompatibility testing pursuant to ISO 10993-1.

Utilizing a power source, both the spray body of Nexpowder™ and the predicate provide physical force to push the hemostatic powder agent into the delivery catheter and spray the hemostasis intended site in the gastrointestinal tract. The minor difference in the power source of the delivery system does not raise different questions in terms of safety and effectiveness, since Nexpowder™ delivery system has been verified to meet the electrical safety and performance requirements per the FDA's recognized standards of IEC 60601-1, IEC 60601-1-2, and IEC 60601-1-6.

VI. Biocompatibility Assessment

Nexpowder™ has met the FDA's recognized standards for biocompatibility requirements identified in the FDA Guidance Table A.1, below, Biocompatibility risk assessments have been conducted per FDA Guidance, "Use of ISO 10993-1, Biological Evaluation of Medical Devices-Part 1: Evaluation and Testing within a Risk Management Process (Issued June 16, 2016)". The following biocompatibility testing was performed on Nexpowder™:

BiocompatibilityEndpoint	Method and Purpose	Result
Cytotoxicity	ISO 10993-5: MEM Elution Study used toevaluate device extracts for cytotoxicity risks.	Non-cytotoxic
Sensitization	ISO 10993-10: Guinea Pig MaximizationSensitization Test used to evaluate deviceextracts for dermal sensitization risks.	Non-sensitizer

GLP Biocompatibility Testing Completed for the Hemostatic Agent Powder of Nexpowder™:

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Irritation	ISO 10993-10: Intracutaneous Initiation Testused to evaluate device extracts for irritationrisks.	Non-irritant
Acute Systemic Toxicity	ISO 10993-11: Acute systemic toxicity studyused to evaluate device extracts for systemictoxicity risks.	No acute systemictoxicity
Material MediatedPyrogenicity	ISO 10993-11: Rabbit pyrogen test used toevaluate device extracts for pyrogenicityrisks.	Non-pyrogenic
Hemocompatibility	Hemolytic study (ASTM: F756-17),Complement Activation, PartialThromboplastin Time, Platelet and LeukocyteCounts (ISO10993-4) used to evaluatedevice extracts for hemocompatibility risks.	Hemocompatible
Genotoxicity	ISO 10993-3: Genotoxicity study used toevaluate device extracts for genotoxicity risk.	Non-genotoxic
Implantation	ISO 10993-6: Implantation study used toevaluate device extracts for the local effectsrisk.	Non-irritant
Subchronic Toxicity	ISO 10993-11: Implantation study used toevaluate device extracts for subchronictoxicity risk.	No subchronicsystemic toxicity

GLP Biocompatibility Testing Completed for the Delivery System Catheter and Connector of Nexpowder™:

Biocompatibility Endpoint	Method and Purpose	Result
Cytotoxicity	ISO 10993-5: MEM Elution Study used to evaluate device extracts for cytotoxicity risks.	Non-cytotoxic
Sensitization	ISO 10993-10: Guinea Pig Maximization Sensitization Test used to evaluate device extracts for de1mal sensitization risks.	Non-sensitizer
Irritation	ISO 10993-10: Intracutaneous Initiation Test used to evaluate device extracts for irritation risks.	Non-irritant
Acute Systemic Toxicity	ISO 10993-11: Acute systemic toxicity study used to evaluate device extracts for systemic toxicity risks.	No acute systemic toxicity
Material mediated pyrogenicity	ISO 10993-11: Rabbit pyrogen test used to evaluate device extracts for pyrogenicity risks.	Non-pyrogenic
Endotoxin	USP <85>	Non-pyrogenic
Hemocompatibility	ASTM: F756-17: Hemolytic study used to evaluate device extracts for hemocompatibility risks.	Hemocompatible

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VII. Design Verification and Validation Testing

Design Verification and Validation (DV&V) testing were performed to verify that the proposed Nexpowder™ meets the pre-determined requirements for design verification, validation, and FDA's special control requirements. Testing was also conducted to verify the effectiveness of the implemented risk control measures to mitigate the risks identified within the risk management process per ISO 14971: Medical Devices-Application of Risk Management to Medical Devices. The following design verification or performance testing of Nexpowder have been completed with favorable test results, meeting the applicable ISO standards and FDA's recognized standards pertaining to evaluations of Nexpowder™.

Design Verification Performance Testing

T=0 Baseline Sample Testing, T=2 Years, and T=3 Years Accelerated Aging Testing of Finished Hemostatic Powder Agents of Nexpowder™:

Appearance Test ●
Weight Test .
Absorption Test
Water Content Test ●
Adhesion Test ●

T=0 Baseline Sample Testing, T=3 Years Accelerated Aging Testing of Catheter and Connector of Nexpowder™ Delivery System:

Appearance Test
Dimension Verification Test ●
Tensile Strength Test ●
Air Leak Test
Spray Test

T=0 Baseline Sample Testing, T=3 Years Accelerated Aging Testing of Spray Body of Nexpowder™ Delivery System:

Appearance Test
Dimension Verification Test ●
Air Pressure Test of the Outlet Port
Power Switch Function Test (Battery Function and Vibration operation Test) ●
. Battery Protection Film Test
Battery Cap test ●
. Spray test

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Design Validation Testing

Animal Study ●

Test	Purpose	Method	Results
PorcineStudy I	Assesshemostaticefficacy andsafety of thedevice	Design: Endoscopicsubmucosal dissection(ESD) based bleedingmodelsAnimals: 6 Nexpowder™treated, 6 Hemospray®treated, 3 sham controlsDuration: 30-day follow-up followed by termination	Initial hemostasis was achieved in allanimals (6/6). None of the animals in thetreatment group showed re-bleeding upto the 30-day follow-up time point. Therewas no gastrointestinal perforation,obstruction, or gas embolism caused bythe device. Histopathological evaluationof the device application site did notreveal any important histologicaldifferences between treatment group andcontrol group animals.
PorcineStudy II	Assesshemostaticefficacy andsafety of thedevice	Design: GastroepiploicArtery (Forrest 1a)Bleeding ModelAnimals: 6 Nexpowder™treated, 3 Hemospray®treatedDuration: 30-day follow-up followed by termination	The rate of achieving initial hemostasiswas 67% (4/6) in the treatment group.None of the animals in the treatmentgroup showed re-bleeding up to the 30-day follow-up time point. There were nogastrointestinal perforation, obstruction,and gas embolism which caused bydevice. Histopathological evaluation ofthe device application site did not revealany important histological findings.

In vivo animal studies have been conducted to support the substantial equivalence claims of our product as compared to the predicate device Hemospray®. The objective of the study was to validate the efficacy and safety of Nexpowder™ (compared to the predicate device) in a porcine model for upper gastrointestinal bleeding control. The results demonstrated that the proposed is substantially equivalent to the predicate.

Simulation System Test
Usability Engineering Evaluation
Clinical data

Real-world evidence of device safety in nonvariceal upper gastrointestinal bleeding in the OUS market was provided, including data from 315 patients with an additional 50 patients from a Retrospective Aggregated Data Collection survey (see table below). Hemostasis was achieved in 94-100% of patients with a re-bleed rate of <23% at 30 days.

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Clinical Study Title	NumberofPatients	Hemostasis (%)	AdverseEvents/ComplicationRates	Re-Bleedingrate (%)	Bleeding Typesof Enrolled Subjects
A. Prospective, Multicenter, Single-blind (subject)Controlled Clinical Trial toConfirm the Efficacy andSafety of the WoundDressing 'UI-EWD'	76	100%: TestGroup withNexpowder: 37out of 37	2.7%(1 Adverseevent) out of37 Subjects(Fever)	8.11% within3 days	Post-ESD (86.49%,32/37)Forrest Class Ib(75.68%, (28/37)
B. Novel hemostaticadhesive powder fornonvariceal uppergastrointestinal bleeding	56	96.4% (54 outof 56 cases withuse ofNexpowder)	Zero adverseevents	3.7%Within 30days	Post-procedure(97.80%, 45/56)Forrest Class Ib(97.20%, (28/56))
C. Efficacy of a novelhemostatic adhesivepowder in patients withrefractory uppergastrointestinal bleeding: apilot study	17	94% (16 out of17 cases withuse ofNexpowder)	Zero adverseevents	19%Within 30days	Refractory bleedingForrest la (11.8%,2/17)Forrest Ib (88.2%,15/17)
D. Efficacy of a novelhemostatic adhesivepowder in patients withupper gastrointestinaltumor bleeding	41	97.5% (40 outof 41 cases withuse ofNexpowder)	Zero adverseevents	4.3% within 7days22.5% within28 days	Forrest Ib (100.0%)
E. Post Market ClinicalAggregated Data CollectionSurvey on Nexpowder™ forSafety and PerformanceEvaluation	50	100% (50 out of50 cases withuse ofNexpowder)	Zero adverseevents	2.0% within 3days4.0% within30 days	Peptic ulcer (24%,12/50)Tumor bleed (8.0%,4/50)Prevent delayedbleeding (30%, 15/50)

VIII. Sterilization Validation and Verification

The following sterilization and verification testing was performed:

Gamma Sterilization Validation Testing of Hemostatic Powder Agent
. Eto Sterilization Validation Testing of Delivery Catheter/Connector
Sterility Test of Nexpowder, Catheter and Connector both with the baseline time-zero samples and three-year aged samples

IX. Packaging Validation, Verification and Distribution Test

The following packaging validation, verification and distribution testing was performed:

. Packaging Validation Testing of Hemostatic Powder Agent
. Package Seal Peeling Test and Dye Penetration Test of Nexpowder™ Catheter and Connector both with the baseline time-zero samples and three-year aged samples
Package Seal Peeling Test and Dye Penetration Test of Nexpowder™ Spray Body both with the baseline time-zero samples and three-year aged samples

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Distribution Transportation Test of Nexpowder™ .

X. Conclusion

Nexpowder™ functions as intended, and is substantially equivalent to the predicate, Hemospray® Endoscopic Hemostat (DEN170015). Nexpowder™ has the similar intended use and indications for use, and similar key technological and design characteristics and mechanism of action compared to the predicate device. The minor differences between the subject and predicate devices do not raise different questions of safety or effectiveness as the design verification and performance testing data support that the Nexpowder™ is substantially equivalent to the predicate device.

Regulation Number and Section

§ 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.