MIST Systems produce a low energy ultrasound generated mist used to promote wound healing through wound cleansing and maintenance debridement by the removal of yellow slough, fibrin, tissue exudates, and bacteria.

Device Description

MIST Systems (e.g., UltraMIST System) are low frequency ultrasound devices, which utilize a fluid (e.g., saline) mist to deliver the ultrasound to the treatment site. The atomized fluid allows the treatment to be performed without direct contact to the patient. MIST Systems are made up of a main generator component, treatment wand, and disposable applicator.

MIST Systems deliver low-frequency ultrasound to the treatment site using an atomized fluid mist. The mist is generated from a small, portable system consisting of a generator, a treatment wand (encasing an ultrasound transducer), and a disposable applicator that has been designed to connect to a user-provided fluid source (e.g., IV saline bag). The system provides a flow of fluid (irrigant) to the tissue surface by the use of low frequency, low intensity ultrasound. Only the mist touches the tissue, not the ultrasound radiation surface (horn tip), thus the term "non-contact" ultrasound. The flow of fluid as an irrigant is controlled by a peristaltic pump on the generator unit. The fluid is dispensed onto the ultrasound radiation surface where the mist is generated. The mist is projected by fundamental atomization or nebulization and acoustic streaming or acoustic radiation force respectively.

AI/ML Overview

The acceptance criteria and device performance evaluation details for the Alliqua Biomedical, Inc. Stimucel System (K162721) are summarized below, based on the provided 510(k) summary.

It's important to note that this submission is a 510(k) for a device with minor modifications (enclosure material change) to an already cleared predicate device (K140782, UltraMIST® System). Therefore, the study presented focuses on demonstrating that these specific modifications do not adversely affect the safety and performance, rather than establishing original effectiveness for the first time. The information provided aligns with a non-clinical testing approach to establish substantial equivalence.

1. Table of Acceptance Criteria and Reported Device Performance

Feature/Test	Acceptance Criteria (Predicate)	Reported Device Performance (Subject Device)
Control of Fluid Flow	Clamp on tubing line to stop and start fluid flow for priming purposes. Peristaltic pump used to provide consistent flow.	Same
Enclosures	Injection molded PC/ABS polymer and compound curvature	Geon HC 8210, Rigid Polyvinyl Chloride, Flammability rated V-0
Supply Voltage and Current	100-240VAC Universal input	Same
Input Frequency	50-60Hz Universal input	Same
Rated Power	100 watts (fuse limited)	Same
Distal Displacement of Radiation Surface	65 ± 10 microns	Same
Acoustic Frequency	40 ± 1 kHz	Same
Radiation Surface Diameter and Material	0.390 in. ± 0.001 in. Titanium alloy (TI-6AL-4V)	Same
Single Patient Use Disposable Applicator	Injection molded PC/ABS polymer and compound curvature	Same
Packaging and Labeling	System: Non-sterile, reusable. Applicator: Sterile per ISO 11607.	Same
Method of Sterilization	Gamma radiation	Same
Shelf Life / Product Life Cycle	System: 5 years. Applicator: 3 years.	Same
Mode of Exudate and Bacterial Removal	Atomized mist. Acoustic and fluid stream delivery / washout.	Same
Microprocessor	Yes	Same
Patient Contact	None - fluid contact only via atomized mist	Same
Treatment Variables	Treatment duration based on area to be treated (algorithm)	Same
Generator (v0.8) Current Range	Current out of range narrower than original MIST System	Modified to be equivalent to that of the original MIST System
General Safety Testing (IEC 60601-1 3rd Ed.)	The system with the prior enclosure materials was safe and effective.	The system with the new enclosure materials was found to be as safe, as effective, and performed as well as the predicate device.
Biocompatibility Testing (Cytotoxicity)	The prior enclosure materials (for non-contact parts) were non-cytotoxic.	The new enclosure materials for the Generator and Treatment wand were determined to be non-cytotoxic, presenting no new or different biocompatibility issue.

2. Sample Size for Test Set and Data Provenance

The submission does not detail a "test set" in the traditional sense of patient data. Instead, the testing described is related to the physical and electrical performance of the device components and biocompatibility of materials.

General Safety Testing (IEC 60601-1 3rd Ed.): Performed on the subject device to verify changes in enclosure material. This would involve specific units of the manufactured device. The exact number of units tested is not specified in the summary but is typically dictated by testing standards.
Biocompatibility Testing (Cytotoxicity): Performed on the new enclosure materials. This involves samples of the material itself. The exact number of samples is not specified.

Data Provenance: The non-clinical testing was performed by Intertek (for general safety) and WuXi AppTec (for biocompatibility), which are accredited testing laboratories. The data is thus derived from laboratory testing of the device and its materials. This is a form of prospective testing for the specific modifications. Country of origin of the data is not explicitly stated but generally follows the location of these testing facilities.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Experts

This type of information is not applicable for the non-clinical testing performed for this 510(k) submission. The "ground truth" for these tests are objective measurements against established engineering and safety standards (e.g., IEC 60601-1, ISO biocompatibility standards). The results are interpreted by qualified engineers and scientific personnel at the testing laboratories (Intertek, WuXi AppTec) who specialize in these types of evaluations.

4. Adjudication Method for the Test Set

Not applicable. The tests performed are objective, quantitative measurements against defined technical and safety specifications, rather than subjective assessments requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This submission focuses on demonstrating substantial equivalence for minor material changes to an existing device through non-clinical performance and safety testing. MRMC studies are typically used to evaluate the diagnostic performance of imaging devices where human interpretation is involved.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

Not applicable. The device, UltraMIST, is a physical medical device (low energy ultrasound wound cleaner) and not a software algorithm evaluating data independently.

7. The Type of Ground Truth Used

For the non-clinical testing, the "ground truth" is based on:

Established international standard performance requirements (e.g., IEC 60601-1 for electrical safety and performance).
Biocompatibility standards for medical device materials (e.g., ISO standards for cytotoxicity).
Comparison to the performance of the legally marketed predicate device (K140782), specifically demonstrating that the modified device's performance is equivalent.

8. The Sample Size for the Training Set

Not applicable. This device is not an AI/ML algorithm that requires a training set. The term "training set" is relevant for machine learning models, which is not what this device is.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as no training set was used.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

December 22, 2016

Alliqua Biomedical, Inc. Kathy Simpson Director. OA/RA 11495 Valley View Road Eden Prairie, Minnesota 55344

Re: K162721

Trade/Device Name: Stimucel System, Stimucel Generator, Stimucel Treatment Wand, Stimucel Applicator Regulation Number: 21 CFR 878.4410 Regulation Name: Low Energy Ultrasound Wound Cleaner Regulatory Class: Class II Product Code: NRB Dated: November 28, 2016 Received: December 2, 2016

Dear Kathy Simpson:

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,

David Krause -S

for Binita S. Ashar, M.D., M.B.A., F.A.C.S. Director Division of Surgical Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K162721

Device Name UltraMIST

Indications for Use (Describe)

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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510k Summary

510(k) Summary (As required by 21 CFR §807.92)
Submitter	Alliqua BioMedical, Inc.11495 Valley View RoadEden Prairie, MN 55344
Contact Person:	Kathy SimpsonDirector QA / RATelephone: 952-224-8738Fax: 952-224-8797Email: ksimpson@alliqua.com
Date Prepared:	August 29, 2016
Trade Name ofDevice:	UltraMIST™
Common /Usual Name:	UltraMIST™
ClassificationName:	Low Energy Ultrasound Wound CleanerClass: IIRegulation: 21 CFR §878.4410
Product Code:	NRB
Manufacturer:	Alliqua BioMedical, Inc.11495 Valley View RoadEden Prairie, MN 55344
EstablishmentRegistration:	3004580659
PredicateDevice(s):	K140782, UltraMIST® SystemManufacturer: Alliqua BioMedical, Inc.
DeviceDescription:	MIST Systems (e.g., UltraMIST System) are low frequency ultrasounddevices, which utilize a fluid (e.g., saline) mist to deliver the ultrasound tothe treatment site. The atomized fluid allows the treatment to be performedwithout direct contact to the patient. MIST Systems are made up of a maingenerator component, treatment wand, and disposable applicator.MIST Systems deliver low-frequency ultrasound to the treatment site usingan atomized fluid mist. The mist is generated from a small, portable systemconsisting of a generator, a treatment wand (encasing an ultrasoundtransducer), and a disposable applicator that has been designed to connectto a user-provided fluid source (e.g., IV saline bag). The system provides aflow of fluid (irrigant) to the tissue surface by the use of low frequency, lowintensity ultrasound. Only the mist touches the tissue, not the ultrasoundradiation surface (horn tip), thus the term "non-contact" ultrasound. The flowof fluid as an irrigant is controlled by a peristaltic pump on the generatorunit. The fluid is dispensed onto the ultrasound radiation surface where themist is generated. The mist is projected by fundamental atomization ornebulization and acoustic streaming or acoustic radiation force respectively.
Intended Use:	The intended use of the MIST Systems is for the delivery of low energyultrasound via a fluid mist for the promotion of wound healing. It is aprescription use only device.
	The overall target market for MIST Systems is the advanced wound care

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	market. There have been no changes to the intended use of the subject ofthis submission.
Indications forUse	MIST Systems produce a low energy ultrasound generated mist usedto promote wound healing through wound cleansing and maintenancedebridement by the removal of yellow slough, fibrin, tissue exudatesand bacteria.
Summary ofTechnicalComparisons:	A summary of the technical components of the subject device and thepredicate UltraMIST System are presented in the Table below:
	TechnicalComponent	UltraMIST System	SubjectDevice
	Control of Fluid Flow	Clamp on tubing line to stopand start fluid flow for primingpurposes.Peristaltic pump used toprovide consistent flow	Same
	Enclosures	Injection molded PC/ABSpolymer and compoundcurvature	Geon HC8210, RigidPolyvinylCyholride,Flammabilityrated V-0
	Supply Voltage andCurrent	100-240VAC Universal input	Same
	Input Frequency	50-60Hz Universal input	Same
	Rated Power	100 watts (fuse limited)	Same
	Distal Displacement ofRadiation Surface	$65 \pm 10$ microns	Same
	Acoustic Frequency	$40 \pm 1$ kHz	Same
	Radiation SurfaceDiameter and Material	0.390 in. $\pm$ 0.001 in.Titanium alloy (TI-6AL-4V)	Same
	Single patient UseDisposable Applicator	Injection molded PC/ABSpolymer and compoundcurvature	Same
	Packaging andLabeling	System: Non-sterile, reusableApplicator: Sterile per ISO11607	Same
	Method of Sterilization	Gamma radiation	Same
	Shelf Life / Product LifeCycle	System: 5 yearsApplicator: 3 years	Same
	Mode of Exudate andBacterial Removal	Atomized mistAcoustic and fluid streamdelivery / washout	Same
	Microprocessor	Yes	Same
	Patient contact	None - fluid contact only viaatomized mist	Same
	Treatment variables	Treatment duration based onarea to be treated (algorithm)	Same
	- Generator v0.8	current out of range narrowerthan original MIST System	modified tobe equivalentto that of theoriginal MISTSystem
PerformanceData - Non-Clinical Testing:	Testing performed on the subject device to demonstrate SubstantialEquivalence:IEC 60601-1 3rd Ed. General Safety Testing -Testing was performed byIntertek to verify that the change in enclosure material for the Generatorand Treatment Wand did not have an adverse effect on the safety orperformance of the system. The results of the testing demonstrated thatthe system with the new material enclosures was as safe, as effective,and performed as well as the predicate device with the previousenclosure materials. The complete test report is included in thesubmission materials and can be found in VOL_16, Appendix C. Biocompatibility testing, Cytotoxicity – Testing was performed by WuXiAppTec to verify that the change in enclosure material for the Generatorand the Treatment Wand did not have an adverse effect on thebiocompatibility of the system. Since the Generator and TreatmentWand do not come into contact with a breached or compromisedsurface, or potential indirect contact with a breached or compromisedsurface like the Applicator, only Cytotoxicity testing was performed toensure that the new enclosure materials do not present a new ordifferent biocompatibility issue for the user of the device. The results ofthe testing demonstrated that the new enclosure materials for theGenerator and Treatment wand were as safe, as effective, andperformed as well as the previous enclosure material as both weredetermined to be non-cytotoxic. The complete test report is included inthe submission materials and can be found in VOL_15, Appendix B. Consensus standards used in the testing and preparation of thispremarket notification may be found in VOL_005, Standards DataReport Forms.
Clinical Studies:	NA for this submission.
Conclusions:	The modifications made to the subject device are substantially equivalent toits predicate, the UltraMIST System.

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Regulation Number and Section

§ 878.4410 Low energy ultrasound wound cleaner.

(a)
Identification. A low energy ultrasound wound cleaner is a device that uses ultrasound energy to vaporize a solution and generate a mist that is used for the cleaning and maintenance debridement of wounds. Low levels of ultrasound energy may be carried to the wound by the saline mist.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Low Energy Ultrasound Wound Cleaner.” See § 878.1(e) for the availability of this guidance document.