Volpara Imaging Software is a software application intended for use with the raw data from digital breast x-ray systems, including tomosynthesis. Volpara Imaging Software calculates and quantifies a density map and from that determines volumetric breast density as a ratio of fibroglandular tissue and total breast volume estimates. Volpara Imaging Software provides these numerical values along with a BI-RADS breast density 4th or 5th Edition category and quality assurance metrics (i.e., dose and pressure) to aid healthcare professionals in the assessment of breast composition. Volpara Imaging Software is not a diagnostic aid and should be used only as adjunctive information when the final assessment of breast density category is made by an MQSA-qualified interpreting physician.

Device Description

Volpara Imaging Software 3.2 analyzes raw ("For Processing") digital mammograms or raw DBT projections in a fully automated, volumetric fashion. It produces a quantitative assessment of breast composition in the form of a Volpara density map, wherein the value at each pixel represents the thickness of fibroglandular tissue between that pixel and the x-ray source.

From the density maps various quantitative density-map based metrics are computed as follows:

volume of fibroglandular tissue in cm3
volume of breast in cm³
the volumetric breast density (the percentage of fibroglandular tissue in breast)
average thickness of dense tissue in cm
maximum thickness of dense tissue in cm
maximum volume of dense tissue above any 1 cm² square region (and location)
image quality assessment metrics

Volpara Imaging Software typically receives four standard views from the digital x-ray system following a mammographic or digital breast tomosynthesis screening examination (i.e., left CC, right CC, left MLO, right MLO). The generated results are then displayed via either of the following:

A Volpara scorecard (a DICOM Secondary Capture Image)
A DICOM Mammography CAD Structured Report

The device outputs those metrics along with the density maps themselves marked with the location of the various maxima. Using the volumetric breast density, a Bl-RADS 4th Edition and 5th Edition breast density category is generated by applying thresholds set by the software.

Volpara Imaging Software operates on a Microsoft Azure-connected, off-the-shelf virtual appliance, which provides a secure, pre-configured virtual host. Volpara Imaging Software does not contact the patient, nor does it control any life-sustaining devices.

AI/ML Overview

The provided text describes a Special 510(k) submission for Volpara Imaging Software 3.2, which is an updated version of a previously cleared device. While it mentions verification and validation, it does not provide specific acceptance criteria or detailed results of a study (such as a clinical performance study with defined endpoints, sample sizes, and ground truth methodologies) that proves the device meets typical acceptance criteria for medical AI/software.

The document focuses on demonstrating substantial equivalence to a predicate device (Volpara Imaging Software 1.5.6) by highlighting minor changes and stating that "complete verification and validation data testing conducted for the predicate was repeated to ensure integration and backwards compatibility." This implies that the performance shown for the predicate device is considered sufficient for the updated device, given the minor nature of the changes.

Therefore, I cannot fulfill your request for a table of acceptance criteria and reported device performance based solely on the provided text, nor can I provide detailed information about a "study that proves the device meets the acceptance criteria" in the way you've outlined for clinical performance. The submission type (Special 510(k)) and the content provided indicate a focus on demonstrating that the changes do not alter the substantial equivalence to the predicate, rather than a de novo clinical performance study for this specific version.

However, I can extract information related to the device and the nature of its submission:

Based on the provided text, a detailed clinical study demonstrating the specific acceptance criteria and performance of Volpara Imaging Software 3.2 (as defined in your prompt) was not described. The submission focuses on demonstrating substantial equivalence to a predicate device through verification and validation of minor software changes.

Here's what can be inferred or stated from the text, addressing your points where possible, and stating "Not provided" where the information is absent:

1. A table of acceptance criteria and the reported device performance

Not provided in this document. The document discusses "verification and validation" and "compliant to the following standards: ISO 14971:2012, ISO 62304:2006, DICOM 2016." These are general standards for medical device software development and risk management, not specific acceptance criteria or performance metrics for breast density assessment.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Not provided. The document states "complete verification and validation data testing conducted for the predicate was repeated," but does not mention specific test set sizes or data provenance.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Not provided. Given that the device calculates volumetric breast density and BI-RADS categories but is "not a diagnostic aid" and "should be used only as adjunctive information when the final assessment... is made by an MQSA-qualified interpreting physician," the ground truth for such a device would typically relate to the accuracy of its calculations against established physical models or potentially expert consensus on BI-RADS categories. However, no details on how "ground truth" for validation was established are given in this document.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not provided.

5. 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

Not provided. This type of study is not described. The device is a quantitative imaging software, not explicitly an AI-assisted diagnostic tool in the typical sense of MRMC studies (though it uses "automated" analysis). Its primary function is to provide numerical values and BI-RADS categories, which are then used by a physician.

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

Implied, but details not provided. The description of the device's function ("calculates and quantifies a density map and from that determines volumetric breast density... provides these numerical values along with a BI-RADS breast density... category") describes a standalone algorithmic calculation. However, no performance metrics from such a standalone evaluation are presented in this document.

7. The type of ground truth used (expert concensus, pathology, outcomes data, etc)

Not provided. For a volumetric density calculation, ground truth could be established via phantoms, physical measurements, or potentially a highly detailed, independently verified volumetric analysis of breast tissue. No specific method is mentioned.

8. The sample size for the training set

Not provided. This document describes a Special 510(k) for software updates to an already cleared device, implying the original device's training (if any neural networks were involved, though the description sounds more rule-based/analytical) would have occurred for the predicate. Information for this submission focuses on verification/validation of changes, not a new development cycle.

9. How the ground truth for the training set was established

Not provided. (See point 8).

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). On the left is the seal of the Department of Health & Human Services - USA. To the right of the seal is the FDA logo in blue, with the letters "FDA" in a square and the words "U.S. FOOD & DRUG ADMINISTRATION" to the right of the square.

Volpara Health Technologies Limited % Ralph Highnam, Ph.D. CEO Level 14-15, Simpl House, 40 Mercer Street. Wellington Central Wellington, 6011 NEW ZEALAND

Re: K211279

Trade/Device Name: Volpara Imaging Software Regulation Number: 21 CFR 892.2050 Regulation Name: Medical image management and processing system Regulatory Class: Class II Product Code: LLZ Dated: June 25, 2021 Received: July 2, 2021

Dear Dr. Highnam:

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

July 27, 2021

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801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (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 mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

For

Thalia T. Mills, Ph.D. Director Division of Radiological Health OHT7: Office of In Vitro Diagnostics and Radiological Health 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) K211279

Device Name Volpara Imaging Software

Type of Use (Select one or both, as applicable)
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☑ 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/0 description: The image shows the logo for Volpara Health Technologies. The word "volpara" is written in a bold, dark blue font. Above the word is a stylized checkmark in two shades of blue. Below the word "volpara" is the phrase "health technologies" in a smaller, less bold font.

Volpara Imaging Software Special 510(k) Summary

Sponsor:

Volpara Health Technologies Limited

Company Address:

Level 14-15, Simpl House, 40 Mercer Street, Wellington, 6011, New Zealand

Contact Person: Ralph Highnam

Telephone: +64 4 499 6029

Fax: +64 4 499 6029

Email: ralph.highnam@volparahealth.com

Submission Date: 15 April 2021

Device Name: Volpara Imaging Software

Common Name:

Imaging Software

Regulatory Classification: Class II

Review Category:

Class II

Classification Panel:

Radiology; System, Imaging Processing; 21 CFR 892.2050; LLZ

Legally Marketed Predicate Devices:

The modified software, Volpara Imaging Software ("Volpara") 3.2 is substantially equivalent to the Volpara Imaging Software 1.5.6 cleared pursuant to K182310 (Volpara Health Technologies Limited), which serves as the primary predicate.

Predicate Device Description:

The Volpara Imaging Software 1.5.6 software provides volumetric assessment of digital x-ray images of the breast, including in that definition both raw digital mammograms and raw tomosynthesis projections (the central projections of which are just raw digital mammograms). The assessment takes the form of generating and validating density maps wherein the value at each pixel represents the thickness of fibroglandular tissue between that pixel and the x-ray source. From the density maps various quantitative density-map based statistics are computed as follows:

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Image /page/4/Picture/0 description: The image shows the logo for Volpara Health Technologies. The word "volpara" is written in a bold, dark blue font. Above the word "volpara" is a stylized graphic of two curved shapes in light blue and dark blue. Below the word "volpara" is the phrase "health technologies" in a smaller, less bold font.

Volume of Fibroglandular Tissue in cm3
Volume of Breast in cm3
Volumetric Breast Density (the percentage of fibroglandular tissue in breast)
Average thickness of dense tissue in cm
Maximum thickness of dense tissue in cm
Maximum volume of dense tissue above any 1 cm² square region (and location)
Image quality assurance metrics

From the volumetric breast density, a Bl-RADS 4th Edition breast density category can be attained by applying thresholds set by the software. The device outputs those metrics along with the density maps themselves marked with the location of the various maxima. Volpara Imaging Software 1.5.6 operates on a Windows or Linux server that meets Volpara data input and output requirements and generally is located outside the patient environment. The device does not contact the patient, nor does it control any life-sustaining devices.

Comparison with Predicate Device:

Volpara Imaging Software 3.2 is the same core software as the predicated device Volpara Imaging Software 1.5.6 with the addition of the following software and labeling updates.

The modified device is similar to the predicate, except for:

Modified overall software architecture
Improved combo study logic
Ability to process Giotto Class 2D images
Providing additional quality assurance outputs
Improved density sanity checking
Better support for Hologic Tomosynthesis images
. Updated user manual to include recent updates to accepted manufacturers and Intended Use statement. The minor change to the Intended Use statement is to accommodate the QA metrics (i.e., dose and pressure).

Table 1. Substantial Equivalence Comparison

	Predicate DeviceVolpara Imaging Software 1.5.6(K182310)	Submission DeviceVolpara Imaging Software 3.2
Intended Use	VolparaDensity is a softwareapplication intended for use with theraw data from digital breast x-raysystems, including tomosynthesis.VolparaDensity calculates andquantifies a density map and fromthat determines volumetric breastdensity as a ratio of fibroglandulartissue and total breast volumeestimates. Volpara provides these	Volpara Imaging Software¹ is asoftware application intended for usewith the raw data from digital breastx-ray systems, includingtomosynthesis. Volpara ImagingSoftware calculates and quantifies adensity map and from thatdetermines volumetric breast densityas a ratio of fibroglandular tissue andtotal breast volume estimates.

4 Standardizing on the use of the term Volpara Imaging Software as the name of the cleared medical device. As described in previous 510(k) submissions, Volpara Imaging Software, Volpara and Volpara Density have been used interchangeably.

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Image /page/5/Picture/0 description: The image shows the logo for Volpara Health Technologies. The logo is composed of the word "volpara" in a bold, dark blue font, with the "®" symbol next to it. Above the word "volpara" are two curved shapes in light and dark blue, resembling stylized wings or leaves. Below "volpara" is the phrase "health technologies" in a smaller, lighter font.

DMS #	mtk5970-5
Base Template	mtk2327-1	Rev Date	2021-07-26
Title	Volpara Imaging Software Special 510(k)Summary		Page 3 of 5

	Predicate Device	Submission Device
	Volpara Imaging Software 1.5.6(K182310)	Volpara Imaging Software 3.2
	numerical values along with a BI-RADSbreast density 4th or 5th Editioncategory to aid health careprofessionals in the assessment ofbreast tissue composition.VolparaDensity is not an interpretiveor diagnostic aid and should be usedonly as adjunctive information whenthe final assessment of breast densitycategory is made by an MQSA-qualified interpreting physician.	Volpara Imaging Software providesthese numerical values along with aBI-RADS breast density 4th or 5thEdition category and qualityassurance metrics (i.e., dose andpressure) to aid healthcareprofessionals in the assessment ofbreast composition. Volpara ImagingSoftware is not a diagnostic aid andshould be used only as adjunctiveinformation when the finalassessment of breast density categoryis made by an MQSA-qualifiedinterpreting physician.
Intended Users	Health Care Professionals	Health Care Professionals
Image Source	Digital mammography images	Digital mammography images
Image Sources	Digital mammograms frommammography or tomosynthesissystems, including those obtainedusing with curved paddles.	Digital mammograms frommammography or tomosynthesissystems, including those obtainedusing with curved paddles.
AnatomicalArea	Breast	Breast
AssessmentScope	Volumetric	Volumetric
OperatingEnvironment	Windows/Linux²	Windows/Linux
Image Storageand ReportGeneration	Yes; output to console	Yes; output to console
Numeric Output	Volume of Fibroglandular tissue Volume of Breast Volumetric Breast Density BIRADS 4th or 5th Edition BreastDensity Category, withhighlighting above a certainvolumetric threshold or if focaldensity present Average thickness of dense tissue Maximum thickness of densetissue (and location)	Volume of Fibroglandular tissue Volume of Breast Volumetric Breast Density BIRADS 4th or 5th Edition BreastDensity Category, withhighlighting above a certainvolumetric threshold or if focaldensity present Average thickness of dense tissue Maximum thickness of densetissue (and location)
	Predicate DeviceVolpara Imaging Software 1.5.6(K182310)	Submission DeviceVolpara Imaging Software 3.2
	● Maximum volume of dense tissueabove any 1 cm² square region(and location)● Image quality assessment metrics	● Maximum volume of dense tissueabove any 1 cm² square region(and location)● Image quality assessment metrics
Image Output	Density map in DICOM SCI format, forvisualization as user specifies	Density map in DICOM SCI format, forvisualization as user specifies
Classification	21 CFR 892.2050; LLZ	21 CFR 892.2050; LLZ
Level ofConcern	Moderate	Moderate

² Volpara Imaging Software has been previously cleared for both Windows and Linux, which was missed off the 2018 submission. We are now correcting this error.

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Image /page/6/Picture/0 description: The image shows the logo for Volpara Health Technologies. The word "volpara" is written in a bold, dark blue font. Above the word "volpara" are three curved shapes in light and dark blue. Below the word "volpara" is the phrase "health technologies" in a smaller, red font.

Intended Use:

Device Description:

From the density maps various quantitative density-map based metrics are computed as follows:

volume of fibroglandular tissue in cm3
volume of breast in cm³
the volumetric breast density (the percentage of fibroglandular tissue in breast)
average thickness of dense tissue in cm
maximum thickness of dense tissue in cm
maximum volume of dense tissue above any 1 cm² square region (and location)
image quality assessment metrics

A Volpara scorecard (a DICOM Secondary Capture Image)
A DICOM Mammography CAD Structured Report

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Image /page/7/Picture/0 description: The image contains the logo for Volpara Health Technologies. The logo features the word "volpara" in a bold, dark blue font, with a stylized graphic of three blue teardrop shapes above the "a". Below "volpara" is the phrase "health technologies" in a smaller, less bold font, also in dark blue. The overall design is clean and professional, reflecting the company's focus on health technology.

Performance Data:

Volpara Imaging Software has been verified and validated according to the company's design control process. All the documents specified in the FDA's various software guidance documents have been submitted in this Special 510(k) Notification. An ISO 14971 compliant risk analysis has been provided and incorporated into the development effort. Software testing included both unit level and integrated system level testing. A report of outstanding anomalies is included in the software information.

The modified device was tested and determined to be compliant to the following standards: ISO 14971:2012 Medical devices – Application of risk management to medical devices; ISO 62304:2006 Software Life Cycle Processes, DICOM 2016.

In addition to the verification and validation testing conducted for the specific modification to the software detailed in this Special 510(k) submission, complete verification and validation data testing conducted for the predicate was repeated to ensure integration and backwards compatibility.

General Safety and Effectiveness Concerns:

The device labeling contains instructions for use and any necessary cautions and warnings to provide for safe and effective use of this device. Risk management is ensured via a risk analysis, which is used to identify potential hazards. These potential hazards are controlled via software development, verification, and validation testing.

Conclusion:

The Special 510(k) Premarket Notification for Volpara Imaging Software 3.2 contains adequate information and data to demonstrate substantial equivalence to the predicate device.

Regulation Number and Section

§ 892.2050 Medical image management and processing system.

(a)
Identification. A medical image management and processing system is a device that provides one or more capabilities relating to the review and digital processing of medical images for the purposes of interpretation by a trained practitioner of disease detection, diagnosis, or patient management. The software components may provide advanced or complex image processing functions for image manipulation, enhancement, or quantification that are intended for use in the interpretation and analysis of medical images. Advanced image manipulation functions may include image segmentation, multimodality image registration, or 3D visualization. Complex quantitative functions may include semi-automated measurements or time-series measurements.(b)
Classification. Class II (special controls; voluntary standards—Digital Imaging and Communications in Medicine (DICOM) Std., Joint Photographic Experts Group (JPEG) Std., Society of Motion Picture and Television Engineers (SMPTE) Test Pattern).