The iovera® System is used to destroy tissue during surgical procedures by applying freezing cold. It can also be used to produce lesions in peripheral nervous tissue by the application of cold to the selected site for the blocking of pain. It is also indicated for the relief of pain and symptoms associated with osteoarthritis of the knee for up to 90 days. The iovera System is not indicated for treatment of central nervous system tissue.

When stimulation compatible components are used, the iovera System can also facilitate target nerve location by conducting electrical nerve stimulation from a compatible 3rd party nerve stimulator.

Device Description

The iovera System is a portable cryogenic surgical device used to destroy tissue and/or produce lesions in nervous tissue through application of extreme cold to the selected site. The device is based on introduction of a Smart Tip internally cooled by the cryogenic fluid (nitrous oxide, NoO) to a selected area. The Smart Tip is cooled by the Joule-Thomson Effect and/or latent heat of vaporization. The iovera8 System may be used in conjunction with standard of-the-shelf nerve stimulator device in applications where precise nerve location is desired.

The device is comprised of four main components:

A reusable Handpiece .
A Charging Dock ●
An assortment of single-patient-use Smart Tips ●
A Cartridge containing nitrous oxide ●

AI/ML Overview

The provided text describes the iovera® System, a cryogenic surgical device cleared by the FDA (K243677). The document focuses on demonstrating substantial equivalence to predicate devices (K220656 and K211334) for a new Smart Tip configuration (STT21180STIM) that also facilitates nerve location.

Here's a breakdown of the acceptance criteria and study information, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document primarily relies on adherence to recognized standards and satisfactory completion of design verification testing. Specific quantitative acceptance criteria for each test (e.g., specific thresholds for biocompatibility, precise tolerances for mechanical tests) are not explicitly detailed in this summary, but the general outcome of "meets all ISO10993-1 and USP acceptance criteria" or "complied with standards" is stated.

Acceptance Criterion Category	Reported Device Performance (Summary)
Biocompatibility	Conformed to ISO 10993-1:2022. No signs of acute systemic toxicity and pyrogenic response, sensitization, or skin irritation. All extractables below Analytical Evaluation Threshold (AET), no unexpected contaminants or material degradation. Negligible toxicological risk with a significant margin of safety.
Electrical Safety & EMC	Complied with IEC 60601-1:2005+AMD1:2012+AMD2:2020 Edition 3.2, IEC 60601-1-6:2010+AMD1:2013+AMD2:2020 Edition 3.2, and IEC 60601-1-8:2006+AMD1:2012+AMD2:2020 Edition 2.2 for safety (e.g., electric shock), usability, and alarms. Met all EMC requirements per IEC TS 60601-4-2:2024 (specific clauses listed).
Software V&V	Documentation provided per FDA guidance. Software classified as "Class B" concern. Followed IEC 62304:2006/AMD1:2015 and relevant FDA guidance documents for software development, risk management, software life cycle processes, and cybersecurity. Specific performance metrics are not provided but the implication is that all V&V activities were completed satisfactorily.
Functional & Product Perf.	Testing performed on Handpiece, stim cable, cartridges, and Smart Tip STT21180STIM. Indicated that the device meets product specifications and is safe and effective. Specific performance metrics (e.g., temperature ranges, cooling times) are listed in the comparison table for different Smart Tips, and implied to be met for the new STT21180STIM tip. For example, cooling time for STT21180STIM is 70 seconds. Post-heat time is 15 seconds. Skin Warmer Set Point is 15°C.
Usability Engineering/UI	Conformed to IEC 62366-1 Ed. 1.1. Assessed usability by identifying hazards and hazardous situations associated with the user interface, ensuring safety features are intuitive and support proper usage. Simulated use testing (Human Factors Study) with the Smart Tip and Stim cable assembly attached was performed.
Mechanical & Resistance	Resistance Testing (difficulty in securing connection between needle and PCBA), Flex Introducer and Leak Test (to ensure needle does not break), Heater Block-to-Needle Bond Strength Test. All tests were conducted successfully, indicating mechanical strength and reliability. Specific quantitative acceptance criteria are not mentioned beyond "ensuring mechanical strength and reliability."
Packaging Evaluation	Conformed to ASTM D4332-22 and ASTM D4169. Package Integrity Peel Strength Testing, Inspection, and bubble test performed. Validated packaging integrity and compliance with ISO 11607 requirements for sterile barrier systems. ASTM F1886/F1886M-16 and ASTM F88/F88M-23 are referenced.
Sterility Assurance	Conformed to ASTM F1980-21 and ISO 11135:2014. Sterilization validation performed (EO). Smart Tip individually packaged and sterile with a SAL of 10-6. Ensured compliance. Also referenced EN ISO 10993-7:2008+A1:2022 (Ethylene oxide sterilization residuals) and BS EN ISO 11737-1:2018+A1:2021 (Microbiological methods-Determination of a population of microorganisms on products).

2. Sample Size Used for the Test Set and Data Provenance:

The document summarizes design verification testing rather than a clinical study with a "test set" of patient data. Therefore, information about sample size for a test set and data provenance (country of origin, retrospective/prospective) is not applicable or provided in this regulatory summary. The testing focuses on engineering verification (e.g., number of units tested for mechanical properties, number of samples for biocompatibility, etc.), not patient data.

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

Again, this pertains to a clinical study with patient data and does not apply to the design verification testing described. The "ground truth" for the engineering tests would be the compliance with recognized standards and specified performance parameters.

4. Adjudication Method for the Test Set:

Not applicable, as this is design verification testing rather than a clinical study requiring consensus from experts on case interpretation.

5. If a Multi-reader Multi-case (MRMC) Comparative Effectiveness Study was Done:

No, an MRMC comparative effectiveness study was not done. The submission focuses on demonstrating substantial equivalence through non-clinical performance testing and comparison to predicate devices, not on evaluating human reader performance with or without AI assistance. The device in question is a physical cryogenic surgical device, not an AI diagnostic tool that assists human readers with interpretations.

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

Not applicable. The iovera® System is a physical medical device, not an algorithm. Performance is assessed through engineering tests of the device itself. While it facilitates nerve location, its primary function is direct tissue destruction via freezing, with a human operator always in the loop.

7. The Type of Ground Truth Used:

For the design verification testing, the "ground truth" used is:

Compliance with recognized international and national standards (e.g., ISO 10993-1, IEC 60601-1, IEC 62366-1, ISO 11135, ASTM standards).
Pre-defined product specifications and design input requirements for physical, electrical, mechanical, software, and biological properties.
Laboratory test results (e.g., chemical analysis for extractables, temperature measurements for cooling performance, force measurements for bond strength).

8. The Sample Size for the Training Set:

Not applicable. This is not a machine learning or AI device that requires a training set of data.

9. How the Ground Truth for the Training Set was Established:

Not applicable, as there is no training set for this type of medical device submission.

Summary

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December 26, 2024

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Pacira Biosciences, Inc. Niloufa Insanally Director, Regulatory Affairs Clinical Strategy 10410 Science Center Drive, Building A San Diego, California 92121

Re: K243677

Trade/Device Name: iovera System Regulation Number: 21 CFR 882.4250 Regulation Name: Cryogenic Surgical Device Regulatory Class: Class II Product Code: GXH, ETN Dated: November 27, 2024 Received: November 27, 2024

Dear Niloufa Insanally:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rue"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 medical devices and radiation-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).

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Sincerely,

Digitally signed by Adam D. Adam D. Pierce -S Pierce -S Date: 2024.12.2 Date: 2024.12.26

Adam D. Pierce, Ph.D. Assistant Director DHT5A: Division of Neurosurgical, Neurointerventional, and Neurodiagnostic Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

Submission Number (if known)

K243677

Device Name

iovera® System

Indications for Use (Describe)

The iovera® System is used to destroy tissue during surgical procedures by applying freezing cold. It can also be used to produce lesions in peripheral nervous tissue by the application of cold to the selected site for the blocking of pain. It is also indicated for the relief of pain and symptoms associated with osteoarthritis of the knee for up to 90 days. The ioveras System is not indicated for treatment of central nervous system tissue.

When stimulation compatible components are used, the ioveras System can also facilitate target nerve location by conducting electrical nerve stimulation from a compatible 3rd party nerve stimulator.

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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Device Trade Name:	ioveraº System
Device Common Name	Cryogenic Surgical Device
Device Class:	II
Classification Name:	Cryosurgical Unit and Accessories DeviceSurgical Nerve Stimulator
Regulation No.:	21 CFR Part 882.4250 and 874.1820
Product Code:	GXH, ETN
Predicate Device:	ioveraº System K220656 and K211334
Owner/Submitter:	Pacira Pharmaceuticals, Inc.10410 Science Center Drive, Building A,San Diego, California 92121
Regulatory Contact:	Niloufa Insanally, Ph.D., RACDirector, Regulatory Affairs Clinical StrategyTel: 858 220 3761Email: niloufa.insanally@pacira.com
Date:	December 26, 2024

510(k) SUMMARY - K243677

DEVICE DESCRIPTION

Device Design

The device is comprised of four main components:

A reusable Handpiece .
A Charging Dock ●
An assortment of single-patient-use Smart Tips ●
A Cartridge containing nitrous oxide ●

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The iovera? System Handpiece is battery powered and provides feedback to the user during device preparation and use. The Handpiece connects to both the Cartridge and to the Smart Tip. The user activates a treatment cycle through a control on the Handpiece, which starts and stops the treatment. The Handpiece contains an LCD display for providing feedback to the user when the device is ready to use. The Charging Dock stores the Handpiece between uses and provides power for charging the battery.

An assortment of Smart Tips is available for the iovera8 system. All Smart Tip needles are made of stainless steel and have a closed-end design that fully contains the cryogen so that it does not enter the target tissue. The Smart Tip is the only patient contacting component of the iovera' System. The user removes the Smart Tip from its sterile packaging and attaches it to the Handpiece immediately before use. Certain Smart Tip designs provide a connection to an external nerve stimulator to facilitate nerve location prior to treatment.

The iovera System uses a commercially available nitrous oxide cylinder. The Cartridge is filled with pure N2O.

Device Functionality/Scientific Concepts:

The device functionality is based on the user introducing the Smart Tip into the selected treatment area or the target nervous tissue. The user then initiates the flow of cryogen by pressing the on/off button. Liquid cryogen flows from the Handpiece into the closed-end Smart Tip. The Smart Tip is cooled by the Joule-Thomson Effect and/or latent heat of vaporization: as the liquid cryogen expands into a gas, the temperature drops around the external surface of the Smart Tip, causing the surrounding tissue to freeze. The treatment is completed after a pre-programmed amount of time, at which time the user can safely remove the Smart Tip from the treatment site.

INTENDED USE/INDICATIONS FOR USE

The iovera? System is used to destroy tissue during surgical procedures by applying freezing cold. It can also be used to produce lesions in peripheral nervous tissue by the application of cold to the selected site for the blocking of pain. It is also indicated for the relief of pain and symptoms associated with osteoarthritis of the knee for up to 90 days. The iovera System is not indicated for treatment of central nervous system tissue.

When stimulation compatible components are used, the iovera System can also facilitate target nerve location by conducting electrical nerve stimulation from a compatible 3rd party nerve stimulator.

Subject Device

The iovera System's "1x180" Smart Tip configuration (indicating one needle which is 180 mm long) can also facilitate target nerve location by conducting electrical nerve stimulation from a separate nerve stimulator.

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SUMMARY/COMPARISON OF IOVERA® SYSTEM DEVICE CHARACTERISTICS

The ioveraº System is substantially equivalent in intended use, technology, design, and materials to the listed legally marketed predicate devices.

Parameter	Proposed	Predicate 1	Predicate 2
	iovera® System	iovera® System	iovera® System
	STT21180STIM	K220656	K211334
	Subject of this Special 510(k)
Intended Use	Destroy tissue through freezing	Same	Same
Indications forUse	The iovera® System is used todestroy tissue during surgicalprocedures by applying freezingcold. It can also be used toproduce lesions in peripheralnervous tissue by theapplication of cold to theselected site for the blocking ofpain. It is also indicated for therelief of pain and symptomsassociated with osteoarthritis ofthe knee for up to 90 days. Theiovera System is not indicatedfor treatment of central nervoussystem tissue.When stimulation compatiblecomponents are used, the iovera®System can also facilitate targetnerve location by conductingelectrical nerve stimulation from acompatible 3rd party nervestimulator.	The over® System is used todestroy tissue during surgicalprocedures by applying freezingcold. It can also be used toproduce lesions in peripheralnervous tissue by the applicationof cold to the selected site forthe blocking of pain. It is alsoindicated for the relief of painand symptoms associated withosteoarthritis of the knee for upto 90 days. The iovera® system isnot indicated for treatment ofcentral nervous system tissue.When stimulation compatiblecomponents are used, theiovera® System can alsofacilitate target nerve locationby conducting electrical nervestimulation from a compatible3rd party nerve stimulator.	The iovera® System is used todestroy tissue during surgicalprocedures by applying freezingcold. It can also be used toproduce lesions in peripheralnervous tissue by theapplication of cold to theselected site for the blocking ofpain. It is also indicated for therelief of pain and symptomsassociated with osteoarthritisof the knee for up to 90 days.The iovera® system is notindicated for treatment ofcentral nervous system tissue.
Anatomical Sites	Peripheral nerves	Same	Same
Intended Users	Qualified medical personnel(doctors, specialists)	Same	Same
Where used?Clinical Setting	Hospital or medicalenvironment (professionalclinical setting)	Same	Same
Technology	Cryogenic surgical device withneedle which penetrates treatmentarea	Same	Same
Energy used/ordelivered	Cryotherapy removes energyfrom the body.Cryogen used: Nitrous Oxide	Same	Same
Parameter	Proposediovera® SystemSTT21180STIMSubject of this Special 510(k)	Predicate 1iovera® SystemK220656	Predicate 2iovera® SystemK211334
Cryogen cartridge size	21ml (14.3 gram fill) nitrous oxidecartridge	Same	Same
Cryogen cartridgeloading	Cartridge is loaded via a hingeddoor on the side of the device.Closing the door provides the forcenecessary to pierce the cartridge.	Same	Same
Cryogencartridgepiercingpoint/filter	In-line piercing point and filterassembly resides in a replaceableassembly within the device.	Same	Same
Cartridgestatus/detection	Measurement of cryogen pressure;detection switch.	Same	Same
Cartridgeheating	Resistive flex circuit with redundantmonitoring thermistors.	Same	Same
Human Factors	Hand-held device containingcryogen. Detachable cryoprobes(Smart Tips).	Same	Same
Informationdisplay	Color graphic LCD on rear ofdevice. Additional informationregarding failure mode is alsodisplayed.	Same	Same
Charging Dockdisplay	LED light bar indicating ChargingDock is receiving power from AC-DC adapter (Power Supply).Light bar changes color whenCharging Dock is charging currentto Handpiece.	Same	Same
Digital Interfaces	USB Type B Port and SD Card Slot.The SD Card slot is inactive; theUSB Port is not for customer useand is for log retrieval bycompany staff. Cybersecurityaspects of both the SD Card Slotand USP Port are covered andtested in the SoftwareDevelopment Life Cycle activities.	Same	Same
Method of SmartTip attachment	Push-on / pull-off design	Same	Same
Skin-warmerheating	Semiconductor device used asheating element - this element isthermally connected to skinwarmer (heating block) andmonitored with redundantthermistors.	Same	Same
Parameter	Proposediovera ® SystemSTT21180STIMSubject of this Special 510(k)	Predicate 1iovera® SystemK220656	Predicate 2iovera® SystemK211334
	compliant sealing element.Valve is controlled by stepper-motor-based linear actuator.Switch detects valve openposition.
Power Source	Battery poweredBattery type: Single cell LithiumIon, 3100mAhBattery voltage: 3.6Volts Mainspowered Charging Dock withManufacturer- supplied, medicalgrade power supply (5V DC).	Same	Same
OperatingPrinciple	Joule-Thomson Effect / LatentHeat (enthalpy) of Vaporization	Same	Same
Patientcontactingmaterials	Closed tip stainless steel needle	Same	Same
Biocompatibility	Biocompatible patientcontacting materials, tested to"ISO 10993-1:2018,Biological evaluation ofmedical devices - Part 1: Evaluationand testing within a riskmanagement process."	Same	Same
Needle Sizes	27G (STT2309)20G (STT2190)20G (STT2190STIM)25G (STT21180STIM)	27G (STT2309)20G (STT2190)20G (STT2190STIM)	27G (STT2309)20G (STT2190)
CatalogNumbers	STT2309, STT2190, STT2190STIMand STT21180STIM	STT2309, STT2190, andSTT2190STIM	STT2309 and STT2190
Working Length	8.5 mm (STT2309)90mm (STT2190, and STT2190STIM)180 mm (STT21180STIM)	8.5 mm (STT2309)90mm (STT2190, andSTT2190STIM)	8.5 mm (STT2309)90mm (STT2190)
NerveStimulation	Yes (for STT21180STIM)	Yes (for STT2190STIM)	No
Nu ber ofNeedles/SmartTip	1 x 25G (180mm) (STT21180STIM)1 x 20G (90mm) (STT2190, andSTT2190STIM)3 x 27G (8.5mm) (STT2309)	1 x 20G (90mm) (STT2190, andSTT2190STIM))3 x 27G (8.5mm) (STT2309)	1 x 20G (90mm) (STT2190)3 x 27G (8.5mm) (STT2309)
Parameter	Proposediovera® SystemSTT21180STIMSubject of this Special 510(k)	Predicate 1iovera® SystemK220656	Predicate 2iovera® SystemK211334
Silica ID	32 µm (8.5mm)65µm (STT2190, STT2190STIM, andSTT21180STIM)	Same	Same
Applet	11876	Same	Same
Pre-heat time(min)	12-seconds (STT2309)1-second (STT2190, STT2190STIM,and STT21180STIM)	12-seconds (STT2309)1-second (STT2190, andSTT2190STIM)	12-seconds (STT2309)1-second (STT2190)
Cooling Time(max)	33-seconds (STT2309)60-seconds (STT2190, andSTT2190STIM)70-seconds (STT21180STIM)	33-seconds (STT2309)60-seconds (STT2190, andSTT2190STIM)	33-seconds (STT2309)60-seconds (STT2190)
Post -heat Time	20-seconds (STT2309)45-seconds (STT2190, andSTT2190STIM)15-seconds (STT21180STIM)	20-seconds (STT2309)45-seconds (STT2190, andSTT2190STIM)	20-seconds (STT2309)45-seconds (STT2190)
Skin Warmer SetPoint	30°C (STT2309, STT2190, andSTT2190STIM)15°C (STT21180STIM)	30°C (STT2309, STT2190, andSTT2190STIM)	30°C (STT2309, and STT2190)
Clinical Effect	Cellular death throughcryoneurolysis and Walleriandegeneration.Second degree nerve injury(axonotmesis)	Same	Same
TreatmentTemperature	-55° C to -88°C (-88°C is the boilingpoint of N2O).	Same	Same
Treatment Time	Preprogrammed into the SmartTip.	Same	Same
TreatmentOptions	Multiple Smart Tip options areavailable for producing differentcryozone (ice ball) sizes.	Same	Same
Single-patientUse?	Smart Tips are single-use.Handpiece is reusable.	Same	Same
Sterilization(cryoprobes)	EO (provided sterile bymanufacturer)	Same	Same
Sterility Assurancelevel	Smart Tip individually packages andsterile with a SAL of 10-6	Same	Same
Parameter	Proposediovera o SystemSTT21180STIMSubject of this Special 510(k)	Predicate 1iovera o SystemK220656	Predicate 2iovera o SystemK211334
Shelf Life	37 months	Same	Same
Compatibility with intended environments	Verified for operation in aprofessional clinical setting.	Same	Same
Electrical, Mechanical andThermal safety	Conforms to IEC 60601-1Electrical Safety	Same	Same
EMC	Conforms to IEC 60601-1 Ed. 3.2,Medical electrical equipment - Part1: General requirements for basicsafety and essential performance.	Same	Same
Differences
1.	The needle gauge for the 1 x 180mm STIM SmartTip differs from the devices in K211334 [25G(STT21180STIM)]. It is in between the 20G and 27Ggauge. The gauge size for the STT21180 STIMneedle was changed to provide compatibility withthe off-the-shelf introducer.		27G (STT2309)20G (STT2190)
2.	The needle working length for the 1 x 180mmSTIM Smart Tip differs from the devices inK211334 [180 mm (STT21180STIM)]. It is longerthan the 8.5mm and 90 mm Smart Tips.Topological change to STT21180 STIM needle: theneedle is longer to enable ice ball formation atdeeper peripheral nerves, and gauge size changedto provide compatibility with the off-the-shelfintroducer.		8.5 mm (STT2309)90mm (STT2190)
3.	The number of needles differs from one of thedevices in K211334 (i.e., 8.5mm STT2309 has 3needles) while the 1 x 180 mm STT21180STIMhas one needle.		8.5 mm (STT2309) – has 3needles.
4.	The stimulation feature for the 1 x 180mm STIMSmart Tip differs from the devices in K211334which have no stimulation feature.		8.5 mm (STT2309) – no STIMfeature90mm (STT2190) - no STIM feature
5.	No masking or coating is present on the STT21180STIM needle. Parylene coating was removed sinceall Off-the-shelf RF introducers have insulationcoating except around the distal end of needle.This is the same for the predicate devices whichhave no masking		8.5 mm (STT2309) – nomasking/coating90mm (STT2190) – nomasking/coating
	Parameter	Proposediovera® SystemSTT21180STIMSubject of this Special 510(k)Differences	Predicate 1iovera® SystemK220656	Predicate 2iovera® SystemK211334
6.		The needle geometry for the 1 x 180mm STIMSmart Tip differs from the devices in K211334[Blunt tip (STT21180STIM)]. The 8.5 mm (STT2309)& 90 mm (STT2190) Smart Tips are sharp. TheSTT21180 STIM Smart Tip is first placed inside theintroducer and the use of the introducer (cannula)allows the STT21180 STIM Smart Tip to perform inthe same manner as the 8.5mm and 90mm SmartTips, since the introducer has a sharp tip.		8.5 mm (STT2309) – sharp tip90mm (STT2190) – sharp tip
7.		The cycle times (i.e. pre-heat time, cooling time,post-heat time) for each predicate device(STT2309 and STT2190 & STT2190STIM) remainthe same for each device type. TheSTT21180STIM Smart Tip differs in that thecooling time is 70 seconds and the post-heat timeis 15 seconds.		STT2309:Pre-heat: 12 secCooling: 33 secPost-heat: 20 secSTT2190:Pre-heat: 1 secCooling: 60 secPost-heat: 45 sec
		Differences	Predicate 1iovera® SystemK220656	Predicate 2iovera® SystemK211334
1.		The needle gauge for the 1 x 180mm STIM SmartTip differs from the devices in K220656 [25G(STT21180STIM)]	20G (STT2190STIM)
2.		The needle working length for the 1 x 180mmSTIM Smart Tip differs from the devices inK220656 [180 mm (STT21180STIM)]. The 180mmSmart Tip is longer than the 90 mm Smart Tips(as well as the 8.5mm Smart Tip).	90mm (STT2190, andSTT2190STIM)
3.		The stimulation feature for the 1 x 180mm STIMSmart Tip is the same as that for the 90mm STIMSmart Tip described in K220656. No difference instimulation capability of STT2190 STIM andSTT21180 STIM Smart Tips.	90mm (STT2190STIM) – has thestimulation feature
Parameter	Proposediovera® SystemSTT21180STIMSubject of this Special 510(k)Differences	Predicate 1iovera® SystemK220656	Predicate 2iovera® SystemK211334
4.	The needle geometry for the 1 x 180mm STIMSmart Tip differs from the devices in K220656[Blunt tip (STT21180STIM)]. The 90 mm (STT2190)and 90 mm STIM Smart Tip (STT21190 STIM) aresharp. The STT21180 STIM Smart Tip is first placedinside the introducer and the use of the introducer(cannula) allows the STT21180 STIM Smart Tip toperform in exactly the same manner as the 90mmSmart Tips (as well as the STT2309) since theintroducer has a sharp tip.	STT2309, STT2190, andSTT2190STIM – all have sharptips.
5.	No masking or coating is present on the STT21180STIM needle. Parylene coating was removed sinceall Off-the-shelf RF introducers have insulationcoating except around the distal end of needle.This differs for the predicate device STT2190STIMwhich has masking.	90mm (STT2190STIM) – has themasking feature
6.	The cycle times (i.e. pre-heat time, cooling time,post-heat time) for the predicate deviceSTT2190STIM is the same as for the STT2190Smart Tip, but the STT21180STIM Smart Tipdiffers in that the cooling time is 70 seconds andthe post-heat time is 15 seconds.	STT2190STIM:Pre-heat: 1 secCooling: 60 secPost-heat: 45 sec

Table 1. Substantial Equivalence Comparison Table

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K243677 Page 8 of 12

K243677 Page 8 of 12
Special 510(k) - iovera® System

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SUMMARY OF PERFORMANCE TESTING

Design Verification testing was previously performed for the iovera® System to demonstrate that the device meets product specifications and is safe and effective for its intended clinical use. Design verification testing was performed according to recognized standards which define the test methods and is consistent with the predicate devices (K220656 and K211334) (refer to Table 2, below). The verification methods used and applied have not changed since the previous submission. The verification and validation testing assured the subject device meets design input requirements, product specifications and relevant standards.

Functional and Product Performance Testing, including the Handpiece, stim cable, . cartridges, etc.
Smart Tip STT21180STIM Functional Testing .
Usability Engineering/ User Interface Testing: to IEC 62366-1 Ed. 1.1 ●
Software Development Lifecycle Testing: Conforms to IEC 62304 Ed. 1.1
Basic Safety and Essential Performance/Mechanical and Thermal Safety Testing: Conforms ● to IEC 60601-1 Ed. 3.2
Electromagnetic Compatibility (EMC) Testing: Conforms to IEC 60601-1-2 Ed. 4.1 ●

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Sterility Assurance: Conforms to ASTM F1980-21 and ISO 11135:2014 ●
. Packaging Evaluation Testing: Conforms to ASTM D4332-22
. Biological Evaluation/Biocompatibility Testing: Conforms to ISO 10993-1:2022

Table 2. Reference Standards

Document Number	Description
EN ISO 10993-7:2008+A1:2022	Biological evaluation of medical devices-Ethylene oxide sterilization residuals
EN 60601-1 Edition 3.2	Medical Electrical Equipment Part 1: General Requirements For Basic Safety And EssentialPerformance
EN60601-1-2 Edition 4.1	Medical Electrical Equipment - Part 1-2: Collateral Standard: Electromagnetic Disturbances.Requirements and Tests
IEC 62366-1 Ed. 1.1 b:2020	Medical devices — Part 1: Application of Usability Engineering to Medical Devices
AAMI TIR28:2016 (R)2024	Product adoption and process equivalency for ethylene oxide sterilization.
BS EN ISO 11135:2014 +A1:2019	Sterilization of health-care products - Ethylene oxide - Requirements for the development,validation and routine control of a sterilization process for medical devices - Amendment 1
BS EN ISO 11737-1:2018+A1:2021	Sterilization of health care products. Microbiological methods-Determination of apopulation of microorganisms on products
AAMI/IEC 62304:2006 &A1:2016	Medical device software - Software life cycle processes - Consolidated Text
IEC 62304 Ed. 1.1 b:2015	Medical device software - Software life cycle processes CONSOLIDATED EDITION
ISO 11607-1:2019/Amd1:2023	Packaging for terminally sterilized medical devices - Part 1: Requirements for materials,sterile barrier systems and packaging systems
ISO 11607-2:2019/Amd1:2023	Packaging for terminally sterilized medical devices - Part 2: Validation requirements forforming, sealing and assembly processes
BS EN ISO 11607-1:2020+A11:2023	Packaging for terminally sterilized medical devices
BS EN ISO 11607-2:2020+A1:2023	Packaging for terminally sterilized medical devices
ASTM F1886/F1886M-16	Standard Test Method for Determining Integrity of Seals for Flexible Packaging by VisualInspection
ASTM F88/F88M-23	Standard Test Method for Seal Strength of Flexible Barrier Materials
BS EN ISO 10993-1:2022	Biological evaluation of medical devices, Part 1: Evaluation and testing within a riskmanagement process

The iovera System Smart Tip (STT21180STIM) underwent thorough evaluation using standardized test methods to ensure compliance, safety, and usability, including:

ASTM Standards (D4332, D4169, F88/F88M, F1980, F2096): Validated packaging integrity and compliance with ISO 11607 requirements for sterile barrier systems.
IEC 60601-1 and IEC 60601-1-2: Confirmed Ensuring Basic Safety and Essential Performance, and ● Electromagnetic Compatibility (EMC).
. IEC 62366: Assessed usability by identifying hazards and hazardous situations associated with the user interface, ensuring the device's safety features are intuitive and support proper usage.
ISO 10993-1: Verified the biocompatibility of patient-contacting materials, ensuring safety for ● clinical use.

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A brief discussion of the nonclinical tests submitted, referenced, or relied on in this premarket notification submission for a determination of substantial equivalence is provided below:

1) Biocompatibility testing

The biocompatibility evaluation for the iovera System device was conducted in accordance with the International Standard ISO 10993-1 "Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing Within a Risk Management Process," as recognized by FDA. The battery of testing included the following tests:

Cytotoxicity
Sensitization ●
Irritation ●
Systemic toxicity ●
. Pyrogen Testing

The comprehensive biocompatibility and chemical characterization studies confirmed the safety of the STT21180STIM Smart Tip. Testing showed no signs of acute systemic toxicity and pyrogenic response, sensitization, skin irritation, , meeting all ISO10993-1 and USP acceptance criteria. Chemical analysis verified that all extractables were below the Analytical Evaluation Threshold (AET), with no unexpected contaminants or material degradation. The toxicological risk assessment reinforced these findings, demonstrating negligible toxicological risk with a significant margin of safety for detected elements and no hazardous compounds identified. These results validate the device's compliance with biocompatibility requirements, ensuring patient safety.

2) Electrical safety and electromagnetic compatibility (EMC)

Electrical safety and EMC testing were conducted on the joyera System device, consisting of the handriece. docking station, cryogen cartridge and Smart Tip needle. The system complies with the IEC 60601-1 and IEC 60601-1-2 standards for safety and the IEC 60601-1-2 standard for EMC. The device complied with IEC 60601-1:2005+AMD1:2012+AMD2:2020 Edition 3.2, IEC 60601-1-6:2010+AMD1:2013 +AMD2:2020 Edition 3.2, and IEC 60601-1-8:2006+AMD1:2012+AMD2:2020 Edition 2.2 standards for safety (e.g. electric shock), usability, and alarms.

Additionally, the iovera System device met all EMC requirements per IEC TS 60601-4-2:2024 specifically the following clauses: 1.3, 4.2.1, 5.1, 5.2.2, 5.2.4, 6, 6.1, 6.2, 8.4, 8.7, 8.9, 8.10, 8.11, 8.12, 8.13 and 8.14.

3) Software Verification and Validation Testing

Software verification and validation testing were conducted and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices." The software for this device was considered as a "Class B" level of concern, since a failure or latent flaw in the software could directly result in non-serious injury to the patient or operator.

The references used for the software development, including the application of risk management (software architecture and dFMEA), the software life cycle processes and the cybersecurity requirements, followed the guidance and conditions set forth in the following references:

IEC 62304:2006/AMD1:2015: Medical Device Software - Software Life Cycle Processes

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1. FDA Guidance Document: Guidance for Industry, FDA Reviewers, and Compliance on Off-the-Shelf Software Use in Medical Devices, issued September 9, 1999.
1. FDA Guidance Document: General Principles for Software Validation; Final Guidance for Industry and FDA Staff, issued January 11, 2002
1. FDA Guidance Document: Content of Premarket Submissions for Device Software Functions, issued June 14, 2023
FDA Guidance Document: Cybersecurity in Medical Devices: Quality System Considerations and న్. Content of Premarket Submissions, issued September 27, 2023

4) Mechanical and Resistance Testing

Additional testing was conducted to ensure mechanical strength and reliability and package integrity (no breach of sterility):

Resistance Testing - test of difficulty in securing connection between needle and PCBA
Flex Introducer and Leak Test - to ensure needle dose not break
Heater Block-to-Needle Bond Strength Test
Simulated use testing Human Factors Study Introducer with the Smart Tip and Stim cable ● assembly attached
Package Integrity Peel Strength Testing Sterilization validation ●
Package Integrity Package Visual Inspection and bubble ●

Verification and validation testing performed on the subject device supports the substantial equivalence of the modified iovera System to the predicate device. The subject ioveras System device met the design verification and validation inputs, passing all predetermined acceptance criteria. No new issues of safety or effectiveness were identified during design verification and validation testing.

CONCLUSION

The subject iovera System, with the same intended use, same indications for use, design, materials, technological features, and principles of operation as the cleared ioveraº Systems (K220656 and K211334), is substantially equivalent to these predicate devices. The new Smart Tip STT21180STIM does not affect the safety and effectiveness of the device as the intended therapeutic use for the creation of lesions with the application of cold in peripheral nerves to block pain has not changed.

In conclusion, the new Smart Tip STT21180STIM described, and the information presented in this special premarket notification demonstrated that the iovera® System is safe and effective, does not introduce or raise new questions of safety and effectiveness, and is substantially equivalent in intended use, technology, design, and materials to the legally marketed predicate devices.

Regulation Number and Section

§ 882.4250 Cryogenic surgical device.

(a)
Identification. A cryogenic surgical device is a device used to destroy nervous tissue or produce lesions in nervous tissue by the application of extreme cold to the selected site.(b)
Classification. Class II (performance standards).