Quantra™ is a software application intended for use with images acquired using digital breast x-ray systems. Quantra calculates volumetric breast density as a ratio of fibroglandular tissue and total breast volume estimates. Quantra also provides area breast density as a ratio of fibroglandular tissue area estimates. Quantra segregates breast density into categories, which may be useful in the reporting of consistent BI-RADS® breast composition categories as mandated by certain state regulations. The Quantra results for each image, breast, and subject, are intended to aid radiologists in the assessment of breast tissue composition. Quantra produces adjunctive information; it is not an interpretive or diagnostic aid.

Device Description

The Quantra 2.1 software provides volumetric and area assessment on digital x-ray images of the breast. The Quantra software calculates estimates of breast tissue volumes, estimates of breast tissue areas and statistical measures. The Quantra software operates on a Windows server (e.g., Hologic Cenova server) that meets Quantra 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.

AI/ML Overview

Here's an analysis of the acceptance criteria and study information for the Quantra 2.1 device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria in the form of numerical thresholds for device performance. Instead, the "Performance/Bench Testing" section describes the types of evaluations performed and the comparisons made. The conclusion states that the information and data presented were "adequate...to determine substantial equivalence to the predicate device." This implies the device's performance was considered acceptable if it was comparable to or improved upon the predicate.

Acceptance Criteria (Implied)	Reported Device Performance
Accuracy of fibroglandular tissue thickness measurements	Assessed using a breast phantom of known composition. (No specific numerical accuracy reported, but implies the measurements were deemed satisfactory for substantial equivalence).
Reproducibility of breast density measurement (Vbd)	Assessed using an image dataset of the same patients imaged within a short period of time on two different acquisition systems. (No specific reproducibility metric reported, but implies acceptable consistency for substantial equivalence).
Consistency of density measures across different views and breasts	Evaluated statistically between CC and MLO views of the same breast and left and right breasts of the same women, using a large database of images from Hologic (Selenia and Selenia Dimensions), GE (Senographe and Senographe Essential), and Siemens (Mammomat Novation) digital breast x-ray systems. (Implies statistical consistency was found, supporting substantial equivalence).
Correlation with expert BI-RADS® category scores	Images in a database including BI-RADS category scores assigned by 15 readers were used to compare the reader BI-RADS scores to the `q abd, O abd. Vbd and Abd measures`. (Implies a correlation or agreement was sufficient to establish substantial equivalence; no specific correlation coefficient or agreement metric is provided).
Equivalence to Predicate Device (Quantra 2.0)	Quantra 2.1 provides the same breast density and statistical assessments as Quantra 2.0. The algorithm is updated for independence from certain acquisition parameters. Includes a new reference population with Hologic Selenia Dimensions images. The method to combine image level results for per-breast and per-patient breast density measures is updated (averaging vs. maximum in Quantra 2.0). Overall deemed substantially equivalent.

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

Test Set Sample Size:
- For the accuracy of fibroglandular tissue thickness, a "breast phantom" was used. This would be a single or a small set of phantoms, not a large patient sample size.
- For reproducibility of Vbd, an "image dataset of the same patients" was used. No specific number of patients is provided, but it implies multiple patients.
- For consistency of density measures across views/breasts, a "large database of images" was used. No specific number is given, but it is explicitly stated to be "large."
- For correlation with BI-RADS® scores, a database of "images including BI-RADS category scores" was used. No specific number of images or patients is detailed.
Data Provenance: The document explicitly mentions images from "Hologic (Selenia and Selenia Dimensions), GE (Senographe and Senographe Essential), and Siemens (Mammomat Novation) digital breast x-ray systems." This indicates data from various manufacturers, suggesting it's likely multi-centric. The origin countries are not specified, but these are internationally recognized manufacturers. The studies appear to be retrospective as they use "image data sets" and "a large database of images."

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

For the study comparing reader BI-RADS® scores to Quantra measures, 15 readers assigned BI-RADS® category scores.
Qualifications of Experts: The term "readers" is used in the context of assigning BI-RADS® scores, strongly implying these are radiologists. Their specific years of experience or sub-specialization are not provided in the document.

4. Adjudication Method for the Test Set

The document states that "BI-RADS category scores assigned by 15 readers were used to compare the reader BI-RADS scores to the q abd, O abd. Vbd and Abd measures." It does not specify an adjudication method like 2+1 or 3+1 for establishing a single consensus ground truth from these 15 readers. It appears the individual reader scores were used directly for comparison against the Quantra output, rather than an adjudicated consensus being formed.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

The document describes comparing the software's performance with BI-RADS® scores from "15 readers." While this involves multiple readers and multiple cases, the study described is a comparison of the device's output against human ratings, not a "comparative effectiveness study" in the form of 'readers with AI vs. readers without AI assistance'.
Effect Size: No effect size of human readers improving with AI vs. without AI assistance is reported. The device is explicitly stated to produce "adjunctive information; it is not an interpretive or diagnostic aid." This reinforces that it's not intended for human-in-the-loop performance measurement for diagnostic improvement.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, standalone performance was assessed. The entire "Performance/Bench Testing" section describes evaluations of the Quantra 2.1 algorithm's output independently.
- Measurement accuracy on phantoms.
- Reproducibility on patient datasets.
- Statistical evaluation of density measures across views/breasts.
- Comparison of Quantra's density measures to expert BI-RADS® category scores.
  The goal was to demonstrate substantial equivalence, focusing on the algorithm's direct output.

7. The Type of Ground Truth Used

Mixed types of ground truth were used:
- Known Composition (Phantom): For the measurement accuracy of fibroglandular tissue thickness.
- Expert Consensus/Categorization (Implied): For comparing Quantra's density measures to BI-RADS® scores, the BI-RADS® scores assigned by the 15 readers serve as an expert-driven "ground truth" for categorization.
- Clinical Data (Implied): For reproducibility and consistency evaluations, the actual patient images and their characteristics formed the basis for assessment.

8. The Sample Size for the Training Set

The document states, "Quantra 2.1 includes a new reference population with the more recent Hologic Selenia Dimensions image sets." However, it does not specify the sample size for this new reference population, nor explicitly differentiate it as a "training set." While a "training set" is generally used for machine learning models, the Quantra device performs calculations based on an algorithm, so the term "reference population" might refer to data used for algorithm development, calibration, or internal validation rather than a traditional machine learning training set.

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

The document does not explicitly describe how ground truth was established for any "training set" or "reference population." It describes the use of the reference population (Hologic Selenia Dimensions image sets) but not the process for labeling or establishing ground truth within that set.

Summary

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

October 10, 2014

Hologic, Inc. % Ms. Catherine Williams Sr. Director, Regulatory 2585 Augustine Drive SANTA CLARA CA 95054

Re: K142037 Trade/Device Name: Ouantra Regulation Number: 21 CFR 892.2050 Regulation Name: Picture archiving and communications system Regulatory Class: II Product Code: LLZ Dated: July 25, 2014 Received: July 28, 2014

Dear Ms. Williams:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

FDA

for

Janine M. Morris Director Division of Radiological Health Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K142037

Device Name

Quantra™M

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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Date Prepared: July 25, 2014

Submitted by:

Hologic, Inc. 35 Crosby Drive Bedford, MA 01730 USA

Name, Title and Phone Number of Contact:

Catherine A. Williams Senior Director, Regulatory Affairs Phone: (408) 352-0201 FAX: (866) 300-7860 Email: catherine.williams@hologic.com

Trade Name and Common Name:

Trade Name Quantra™M Software Version 2.1 Common Name Picture Archiving and Communications System

Device Classification:

Regulatory Class II Classification Panel Radiology Image Processing System 21 CFR §892.2050 Product Code 90-LLZ

Predicate Device:

Quantra 2.0 K120472 (Hologic, Inc.) cleared June 22, 2012.

Predicate Device Description:

The Quantra 2.0 software provides volumetric and area assessment on digital x-ray images of the breast. The Quantra software calculates estimates of breast tissue volumes, estimates of breast tissue areas and statistical measures. The Quantra software operates on a Windows server (e.g., Hologic Cenova server) that meets Quantra data input and output requirements and generally is located outside the patient environment.

Comparison with Predicate Device:

The Quantra 2.1 software provides the same breast density and statistical assessments as Ouantra 2.0. The Ouantra 2.1 algorithm is updated to make it independent of certain acquisition parameters related to x-ray spectrum and tube output. Quantra 2.1 includes a new reference population with the more recent Hologic Selenia Dimensions image sets. The method to combine image level results for the per-breast and per-patient breast density measures are updated. Specifically, the results are combined by method of averaging versus maximum (in Quantra 2.0).

Intended Use:

QuantraTM is a software application intended for use with images acquired using digital breast x-ray systems. Quantra calculates volumetric breast density as a ratio of fibroglandular tissue and total breast volume estimates. Quantra also provides area breast

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density as a ratio of fibroglandular tissue area and total breast area estimates. Quantra segregates breast density into categories, which may be useful in the reporting of consistent BI-RADS® breast composition categories as mandated by certain state regulations. The Quantra results for each image, breast, and subject, are intended to aid radiologists in the assessment of breast tissue composition. Quantra produces adjunctive information; it is not an interpretive or diagnostic aid.

Technological Characteristics/Device Description:

Performance/Bench Testing:

Density parameters were evaluated using various image data sets and results were compared against predicate performance, when appropriate.

1. The measurement accuracy for thickness of fibroglandular tissue was assessed using a breast phantom of known composition.
1. The reproducibility of the breast density measurement (Vbd) was assessed using an image dataset of the same patients imaged within a short period of time on two different acquisition systems.
1. All density measures were evaluated statistically between CC and MLO views of the same breast and left and right breasts of the same women, using a large database of images from Hologic (Selenia and Selenia Dimensions), GE (Senographe and Senographe Essential), and Siemens (Mammomat Novation) digital breast x-ray systems).
1. Images in a database including BI-RADS category scores assigned by 15 readers were used to compare the reader BI-RADS scores to the q abd, O abd. Vbd and Abd measures.

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 510(k) Premarket Notification for Quantra contains adequate information and data to enable FDA/CDRH to determine substantial equivalence to the predicate device.

The submission contains the results of a hazard analysis and the "Level of Concern" for potential hazards has been classified as "Moderate".

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).