Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a cryogenic surgical device and its components, focusing on mechanical, electrical, and biological safety testing. There is no mention of AI, ML, image processing, or data training/testing, which are typical indicators of AI/ML integration.

Therapeutic

Yes
The "Intended Use / Indications for Use" section explicitly states that the device is used to "destroy tissue during surgical procedures," "produce lesions in peripheral nervous tissue... for the blocking of pain," and for "the relief of pain and symptoms associated with osteoarthritis of the knee." These are all therapeutic applications.

Diagnostic

No

The iovera® System is described as a "cryogenic surgical device used to destroy tissue and/or produce lesions in nervous tissue" and for "relief of pain and symptoms". It also mentions facilitating target nerve location by conducting electrical nerve stimulation from a compatible third-party device. These are therapeutic and assistive functions, not diagnostic ones.

SaMD (Software as a Medical Device)

No

The device description explicitly lists multiple hardware components (Handpiece, Charging Dock, Smart Tips, Cartridge) and the performance studies include testing of these hardware components (Functional and Product Performance Testing, Mechanical and Resistance Testing, Electrical safety and electromagnetic compatibility). While software is mentioned and tested, it is part of a larger hardware system.

IVD (In Vitro Diagnostic)

Based on the provided information, this device is not an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use clearly states the device is used to "destroy tissue during surgical procedures by applying freezing cold" and "to produce lesions in peripheral nervous tissue... for the blocking of pain." It also mentions relief of pain associated with osteoarthritis of the knee. These are all therapeutic or surgical interventions performed on the patient's body.
Device Description: The description details a "portable cryogenic surgical device" that applies cold to tissue. It involves a handpiece, smart tips, and a cartridge containing nitrous oxide. This aligns with a surgical or therapeutic device, not a device used to examine specimens in vitro (outside the body).
Lack of IVD Characteristics: There is no mention of analyzing biological samples (blood, urine, tissue samples, etc.) or providing diagnostic information based on such analysis. The device's function is to physically alter tissue through cryoablation.

Therefore, the iovera® System is a therapeutic/surgical device, not an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

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 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.

Product codes

GXH, ETN

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 ●

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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Peripheral nerves

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Qualified medical personnel (doctors, specialists) Hospital or medical environment (professional clinical setting)

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

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). 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.

Key tests performed:

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 ●
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

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.
Results: 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.

Electrical safety and electromagnetic compatibility (EMC):
Results: 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.

Software Verification and Validation Testing:
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 IEC 62304:2006/AMD1:2015 and relevant FDA Guidance Documents.

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 ●

Overall Conclusion: 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.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s)

iovera® System K220656, iovera® System K211334

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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).

Summary

0

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).

1

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).

2

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

3

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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4

Device Trade Name:	ioveraº System
Device Common Name	Cryogenic Surgical Device
Device Class:	II
Classification Name:	Cryosurgical Unit and Accessories Device
Surgical 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., RAC
Director, Regulatory Affairs Clinical Strategy
Tel: 858 220 3761
Email: niloufa.insanally@pacira.com
Date:	December 26, 2024

510(k) SUMMARY - K243677

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.

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 ●

5

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.

6

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 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.	The over® 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.	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.
Anatomical Sites	Peripheral nerves	Same	Same
Intended Users	Qualified medical personnel
(doctors, specialists)	Same	Same
Where used?
Clinical Setting	Hospital or medical
environment (professional
clinical setting)	Same	Same
Technology	Cryogenic surgical device with
needle which penetrates treatment
area	Same	Same
Energy used/or
delivered	Cryotherapy removes energy
from the body.
Cryogen used: Nitrous Oxide	Same	Same
Parameter	Proposed
iovera® System
STT21180STIM
Subject of this Special 510(k)	Predicate 1
iovera® System
K220656	Predicate 2
iovera® System
K211334
Cryogen cartridge size	21ml (14.3 gram fill) nitrous oxide
cartridge	Same	Same
Cryogen cartridge
loading	Cartridge is loaded via a hinged
door on the side of the device.
Closing the door provides the force
necessary to pierce the cartridge.	Same	Same
Cryogen
cartridge
piercing
point/filter	In-line piercing point and filter
assembly resides in a replaceable
assembly within the device.	Same	Same
Cartridge
status/detection	Measurement of cryogen pressure;
detection switch.	Same	Same
Cartridge
heating	Resistive flex circuit with redundant
monitoring thermistors.	Same	Same
Human Factors	Hand-held device containing
cryogen. Detachable cryoprobes
(Smart Tips).	Same	Same
Information
display	Color graphic LCD on rear of
device. Additional information
regarding failure mode is also
displayed.	Same	Same
Charging Dock
display	LED light bar indicating Charging
Dock is receiving power from AC-
DC adapter (Power Supply).
Light bar changes color when
Charging Dock is charging current
to Handpiece.	Same	Same
Digital Interfaces	USB Type B Port and SD Card Slot.
The SD Card slot is inactive; the
USB Port is not for customer use
and is for log retrieval by
company staff. Cybersecurity
aspects of both the SD Card Slot
and USP Port are covered and
tested in the Software
Development Life Cycle activities.	Same	Same
Method of Smart
Tip attachment	Push-on / pull-off design	Same	Same
Skin-warmer
heating	Semiconductor device used as
heating element - this element is
thermally connected to skin
warmer (heating block) and
monitored with redundant
thermistors.	Same	Same
Parameter	Proposed
iovera ® System
STT21180STIM
Subject of this Special 510(k)	Predicate 1
iovera® System
K220656	Predicate 2
iovera® System
K211334
	compliant sealing element.
Valve is controlled by stepper-
motor-based linear actuator.
Switch detects valve open
position.
Power Source	Battery powered
Battery type: Single cell Lithium
Ion, 3100mAh
Battery voltage: 3.6Volts Mains
powered Charging Dock with
Manufacturer- supplied, medical
grade power supply (5V DC).	Same	Same
Operating
Principle	Joule-Thomson Effect / Latent
Heat (enthalpy) of Vaporization	Same	Same
Patient
contacting
materials	Closed tip stainless steel needle	Same	Same
Biocompatibility	Biocompatible patient
contacting materials, tested to
"ISO 10993-1:2018,
Biological evaluation of
medical devices - Part 1: Evaluation
and testing within a risk
management process."	Same	Same
Needle Sizes	27G (STT2309)
20G (STT2190)
20G (STT2190STIM)
25G (STT21180STIM)	27G (STT2309)
20G (STT2190)
20G (STT2190STIM)	27G (STT2309)
20G (STT2190)
Catalog
Numbers	STT2309, STT2190, STT2190STIM
and STT21180STIM	STT2309, STT2190, and
STT2190STIM	STT2309 and STT2190
Working Length	8.5 mm (STT2309)

90mm (STT2190, and STT2190STIM)

180 mm (STT21180STIM) | 8.5 mm (STT2309)

90mm (STT2190, and
STT2190STIM) | 8.5 mm (STT2309)

90mm (STT2190) | |
| Nerve
Stimulation | Yes (for STT21180STIM) | Yes (for STT2190STIM) | No | |
| Nu ber of
Needles/Smart
Tip | 1 x 25G (180mm) (STT21180STIM)
1 x 20G (90mm) (STT2190, and
STT2190STIM)
3 x 27G (8.5mm) (STT2309) | 1 x 20G (90mm) (STT2190, and
STT2190STIM))
3 x 27G (8.5mm) (STT2309) | 1 x 20G (90mm) (STT2190)
3 x 27G (8.5mm) (STT2309) | |
| Parameter | Proposed
iovera® System
STT21180STIM
Subject of this Special 510(k) | Predicate 1
iovera® System
K220656 | Predicate 2
iovera® System
K211334 | |
| Silica ID | 32 µm (8.5mm)
65µm (STT2190, STT2190STIM, and
STT21180STIM) | 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, and
STT2190STIM) | 12-seconds (STT2309)
1-second (STT2190) | |
| Cooling Time
(max) | 33-seconds (STT2309)
60-seconds (STT2190, and
STT2190STIM)
70-seconds (STT21180STIM) | 33-seconds (STT2309)
60-seconds (STT2190, and
STT2190STIM) | 33-seconds (STT2309)
60-seconds (STT2190) | |
| Post -heat Time | 20-seconds (STT2309)
45-seconds (STT2190, and
STT2190STIM)
15-seconds (STT21180STIM) | 20-seconds (STT2309)
45-seconds (STT2190, and
STT2190STIM) | 20-seconds (STT2309)
45-seconds (STT2190) | |
| Skin Warmer Set
Point | 30°C (STT2309, STT2190, and
STT2190STIM)
15°C (STT21180STIM) | 30°C (STT2309, STT2190, and
STT2190STIM) | 30°C (STT2309, and STT2190) | |
| Clinical Effect | Cellular death through
cryoneurolysis and Wallerian
degeneration.
Second degree nerve injury
(axonotmesis) | Same | Same | |
| Treatment
Temperature | -55° C to -88°C (-88°C is the boiling
point of N2O). | Same | Same | |
| Treatment Time | Preprogrammed into the Smart
Tip. | Same | Same | |
| Treatment
Options | Multiple Smart Tip options are
available for producing different
cryozone (ice ball) sizes. | Same | Same | |
| Single-patient
Use? | Smart Tips are single-use.
Handpiece is reusable. | Same | Same | |
| Sterilization
(cryoprobes) | EO (provided sterile by
manufacturer) | Same | Same | |
| Sterility Assurance
level | Smart Tip individually packages and
sterile with a SAL of 10-6 | Same | Same | |
| Parameter | Proposed
iovera o System
STT21180STIM
Subject of this Special 510(k) | Predicate 1
iovera o System
K220656 | Predicate 2
iovera o System
K211334 | |
| Shelf Life | 37 months | Same | Same | |
| Compatibility with intended environments | Verified for operation in a
professional clinical setting. | Same | Same | |
| Electrical, Mechanical and
Thermal safety | Conforms to IEC 60601-1
Electrical Safety | Same | Same | |
| EMC | Conforms to IEC 60601-1 Ed. 3.2,
Medical electrical equipment - Part
1: General requirements for basic
safety and essential performance. | Same | Same | |
| Differences | | | | |
| 1. | The needle gauge for the 1 x 180mm STIM Smart
Tip differs from the devices in K211334 [25G
(STT21180STIM)]. It is in between the 20G and 27G
gauge. The gauge size for the STT21180 STIM
needle was changed to provide compatibility with
the off-the-shelf introducer. | | 27G (STT2309)
20G (STT2190) | |
| 2. | The needle working length for the 1 x 180mm
STIM Smart Tip differs from the devices in
K211334 [180 mm (STT21180STIM)]. It is longer
than the 8.5mm and 90 mm Smart Tips.
Topological change to STT21180 STIM needle: the
needle is longer to enable ice ball formation at
deeper peripheral nerves, and gauge size changed
to provide compatibility with the off-the-shelf
introducer. | | 8.5 mm (STT2309)
90mm (STT2190) | |
| 3. | The number of needles differs from one of the
devices in K211334 (i.e., 8.5mm STT2309 has 3
needles) while the 1 x 180 mm STT21180STIM
has one needle. | | 8.5 mm (STT2309) – has 3
needles. | |
| 4. | The stimulation feature for the 1 x 180mm STIM
Smart Tip differs from the devices in K211334
which have no stimulation feature. | | 8.5 mm (STT2309) – no STIM
feature
90mm (STT2190) - no STIM feature | |
| 5. | No masking or coating is present on the STT21180
STIM needle. Parylene coating was removed since
all Off-the-shelf RF introducers have insulation
coating except around the distal end of needle.
This is the same for the predicate devices which
have no masking | | 8.5 mm (STT2309) – no
masking/coating
90mm (STT2190) – no
masking/coating | |
| | Parameter | Proposed
iovera® System
STT21180STIM
Subject of this Special 510(k)
Differences | Predicate 1
iovera® System
K220656 | Predicate 2
iovera® System
K211334 |
| 6. | | The needle geometry for the 1 x 180mm STIM
Smart Tip differs from the devices in K211334
[Blunt tip (STT21180STIM)]. The 8.5 mm (STT2309)
& 90 mm (STT2190) Smart Tips are sharp. The
STT21180 STIM Smart Tip is first placed inside the
introducer and the use of the introducer (cannula)
allows the STT21180 STIM Smart Tip to perform in
the same manner as the 8.5mm and 90mm Smart
Tips, since the introducer has a sharp tip. | | 8.5 mm (STT2309) – sharp tip
90mm (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) remain
the same for each device type. The
STT21180STIM Smart Tip differs in that the
cooling time is 70 seconds and the post-heat time
is 15 seconds. | | STT2309:
Pre-heat: 12 sec
Cooling: 33 sec
Post-heat: 20 sec

STT2190:
Pre-heat: 1 sec
Cooling: 60 sec
Post-heat: 45 sec |
| | | Differences | Predicate 1
iovera® System
K220656 | Predicate 2
iovera® System
K211334 |
| 1. | | The needle gauge for the 1 x 180mm STIM Smart
Tip differs from the devices in K220656 [25G
(STT21180STIM)] | 20G (STT2190STIM) | |
| 2. | | The needle working length for the 1 x 180mm
STIM Smart Tip differs from the devices in
K220656 [180 mm (STT21180STIM)]. The 180mm
Smart Tip is longer than the 90 mm Smart Tips
(as well as the 8.5mm Smart Tip). | 90mm (STT2190, and
STT2190STIM) | |
| 3. | | The stimulation feature for the 1 x 180mm STIM
Smart Tip is the same as that for the 90mm STIM
Smart Tip described in K220656. No difference in
stimulation capability of STT2190 STIM and
STT21180 STIM Smart Tips. | 90mm (STT2190STIM) – has the
stimulation feature | |
| Parameter | Proposed
iovera® System
STT21180STIM
Subject of this Special 510(k)
Differences | Predicate 1
iovera® System
K220656 | Predicate 2
iovera® System
K211334 | |
| 4. | The needle geometry for the 1 x 180mm STIM
Smart Tip differs from the devices in K220656
[Blunt tip (STT21180STIM)]. The 90 mm (STT2190)
and 90 mm STIM Smart Tip (STT21190 STIM) are
sharp. The STT21180 STIM Smart Tip is first placed
inside the introducer and the use of the introducer
(cannula) allows the STT21180 STIM Smart Tip to
perform in exactly the same manner as the 90mm
Smart Tips (as well as the STT2309) since the
introducer has a sharp tip. | STT2309, STT2190, and
STT2190STIM – all have sharp
tips. | | |
| 5. | No masking or coating is present on the STT21180
STIM needle. Parylene coating was removed since
all Off-the-shelf RF introducers have insulation
coating except around the distal end of needle.
This differs for the predicate device STT2190STIM
which has masking. | 90mm (STT2190STIM) – has the
masking feature | | |
| 6. | The cycle times (i.e. pre-heat time, cooling time,
post-heat time) for the predicate device
STT2190STIM is the same as for the STT2190
Smart Tip, but the STT21180STIM Smart Tip
differs in that the cooling time is 70 seconds and
the post-heat time is 15 seconds. | STT2190STIM:
Pre-heat: 1 sec
Cooling: 60 sec
Post-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

12

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 ●

13

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 Essential
Performance
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 a
population 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 for
forming, 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 Visual
Inspection
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 risk
management 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.

14

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

15

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.