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 ioveraº system is not indicated for treatment of central nervous system tissue.

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, N₂O) to a selected area. The Smart Tip is cooled by the Joule-Thomson Effect and/or latent heat of vaporization. The device comprises 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 document K211334 is a 510(k) Premarket Notification for the Iovera System. This type of submission is for demonstrating substantial equivalence to a legally marketed predicate device, not for proving significant clinical efficacy or performing novel clinical trials to establish acceptance criteria for a new device's performance.

Therefore, the document does not contain the detailed information necessary to answer all parts of your request, especially regarding acceptance criteria for a new device's analytical performance, a groundbreaking study proving its independent performance, reader study details (MRMC), or specifics about training and test sets.

Here's an analysis of what can and cannot be extracted from the provided text:

Key Takeaway from the Document:
The Iovera System (subject device) is being cleared as substantially equivalent to a previously cleared Iovera System (predicate device, K161835). This means the focus of the submission is to show that any modifications to the device since its last clearance do not raise new questions of safety or effectiveness and that the core performance remains the same as the already approved predicate. It does not describe a new study to establish performance metrics against a novel set of acceptance criteria for a first-of-its-kind device.

Information Extracted/Deduced from the Document:

A table of acceptance criteria and the reported device performance:
The document states:
"Design Verification testing was performed for the iovera° system to demonstrate that the device meets product specifications."
"The subject ioveraº system device met the design verification and validation inputs, passing all predetermined acceptance criteria."

However, the document does not provide a specific table of acceptance criteria with numerical targets or the reported device performance outcomes for these criteria. It lists the categories of testing performed:
- Functional Testing
- Product Performance (Handpiece and Cartridge)
- Smart Tip Testing
- User Interface Testing
- Electrical /EMC safety Testing
Given this is a 510(k) for substantial equivalence based on modifications, the "acceptance criteria" likely refer to internal engineering and design verification specifications for the modified components to ensure they perform as intended and don't negatively impact the device's established safety and effectiveness. These are typically pass/fail for specific tests rather than statistical performance metrics like sensitivity/specificity for an AI or diagnostic algorithm.
Sample sizes used for the test set and the data provenance:
The document does not provide information on sample sizes for any "test sets" in the context of clinical performance or algorithm evaluation. The testing described is design verification and validation, which often involves engineering tests on a defined number of units, but these are not typically referred to as "test sets" in the context of clinical data for performance evaluation.
Data provenance (country of origin, retrospective/prospective) is also not mentioned as this type of clinical data is not the focus of this submission.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not applicable and not provided. The device is a cryogenic surgical device, not a diagnostic or AI device that relies on expert interpretation to establish ground truth for performance evaluation.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
This information is not applicable and not provided for the same reasons as point 3.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
This information is not applicable and not provided. The Iovera System is a therapeutic device (cryogenic surgical device), not a diagnostic device or AI software that assists human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
This information is not applicable and not provided. The Iovera System is a physical device used by a clinician, not an algorithm.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
As this is a physical therapeutic device, the concept of "ground truth" for performance evaluation in the context of diagnostic accuracy does not apply in the way it would for an AI or diagnostic device. The performance is assessed through meeting engineering specifications and demonstrating safe and effective tissue destruction/lesion creation as intended.
The sample size for the training set:
This information is not applicable and not provided. The device is not an AI model that requires a "training set."
How the ground truth for the training set was established:
This information is not applicable and not provided for the same reasons as point 8.

In summary, the provided document relates to a 510(k) submission for a physical medical device (cryogenic surgical device) that is being cleared based on substantial equivalence to a predicate device after modifications. It does not contain the type of performance evaluation study details (e.g., test sets, ground truth methodology, reader studies) that would be relevant for an AI/diagnostic device.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the symbol of the Department of Health & Human Services on the left and the FDA acronym along with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name written out next to it. The full name reads "U.S. Food & Drug Administration".

September 10, 2021

Pacira Pharmaceuticals Inc. Kent Jones Senior Director QA/RA 46400 Fremont Blvd Fremont, California 94538

Re: K211334

Trade/Device Name: Iovera System Regulation Number: 21 CFR 882.4250 Regulation Name: Cryogenic Surgical Device Regulatory Class: Class II Product Code: GXH Dated: August 10, 2021 Received: August 11, 2021

Dear Kent Jones:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about 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).

Sincerely,

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

510(k) Number (if known) K211334

Device Name Iovera System

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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Image /page/3/Picture/1 description: The image shows the logo for Pacira Pharmaceuticals, Inc. The logo is in purple and gray. The words "PACIRA" and "PHARMACEUTICALS, INC." are in large, bold letters. Below that, in smaller letters, it says "A Subsidiary of Pacira BioSciences, Inc."

510(k) Summary

a. Date Summary Prepared:

Date: 09/10/2021

510(k) Type:	Special
Name of Device:	iovera° System
Device Class:	Class II
Product Code:	GXH-Cryogenic Surgical device
Regulation:	21 CFR Part 882.4250
Sponsor/Submitter:	Pacira Pharmaceuticals, Inc.46400 Fremont BlvdFremont, CA 94538Ph: 510-933-1500Fax: 510-933-1501
Establishment Registration:	3009131456
Correspondent ContactInformation:	Kent Jones,Senior Director QA/RAPacira Pharmaceuticals Inc.Email: kent.jones@pacira.comPh: 510-933-1513

b. Predicate Device Information:

The iovera° system is substantially equivalent to the following currently legally marketed device:

510(k) Number	Product	Sponsor
K161835	iovera° system	Pacira Pharmaceuticals

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Image /page/4/Picture/1 description: The image shows the logo for Pacira Pharmaceuticals, Inc. The logo features the company name in a stylized font, with the letters "PACIRA" in a larger, bolder font than the rest of the name. Above the company name is a curved line. Below the company name is the text "A Subsidiary of Pacira BioSciences, Inc."

ioveraº system

Description of Device: ﻥ

Device Design

The device comprises four main components:

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

The iovera® 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 iovera° 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.

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.

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Image /page/5/Picture/1 description: The image shows the logo for Pacira Pharmaceuticals, Inc. The logo is in purple and features the company name in a bold, sans-serif font. Above the company name is a curved line. Below the company name is the text "A Subsidiary of Pacira BioSciences, Inc."

d. 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.

e. Technological Characteristics Comparison to Predicate Device:

The iovera° system is substantially equivalent in intended use, technology, design, and materials to the above listed legally marketed predicate device.

TechnologicalCharacteristics
Predicate Device	Subject Device
Cryogenic device	Same
Nitrous oxide coolant, pressurized cylinder	Same
Reusable handpiece, battery powered	Same
Single use tip for subdermal cooling, EO sterilized	Same
Charging dock	Same
Sensors monitor nitrous oxide delivery	Same

Performance Data: f.

Design Verification testing was performed for the iovera° system to demonstrate that the device meets product specifications. Using a risk-based approach for the modifications, design verification testing was performed according to recognized standards, and is consistent with the predicate device and test methods described in previous 510(k) submissions for the iovera° system. The verification methods used and applied are appropriate for the changes. The verification and validation testing assures the modified subject device meet design input requirements, product specifications and relevant standards.

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Image /page/6/Picture/1 description: The image shows the logo for Pacira Pharmaceuticals, Inc. The logo is in purple and gray. The word "PACIRA" is in large, purple letters, and the words "PHARMACEUTICALS, INC." are in smaller, gray letters below. There is a gray arch above the word "PACIRA". The text "A Subsidiary of Pacira BioSciences, Inc." is below the company name.

ioveraº system

Verification and validation performed on the subject device supports the substantial equivalence of the modified iovera9 system to the predicate device:

Functional Testing ●
Product Performance (Handpiece and Cartridge)
Smart Tip Testing
User Interface Testing
. Electrical /EMC safety Testing

The subject ioveraº 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.

g. Conclusion:

The subject ioveraº system, with the same intended use, indications for use, design, materials, technological features, and principles of operation as the cleared iovera° system (K161835), is substantially equivalent to the predicate device. The modification proposed in this 510(k) 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.

The modifications described, and the data presented, in this special premarket notification demonstrates that 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 device.

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).