(151 days)
The Thirona LungQ software provides reproducible CT values for pulmonary tissue which is essential for providing quantitative support for diagnosis and follow up examination. The LungQ software can be used to support physician in the diagnosis and documentation of pulmonary tissues images (e.g. abnormalities) from CT thoracic datasets. Three-D segmentation and isolation of sub-compartments, volumetric analysis, density evaluation, and reporting tools are provided.
The LungQ software is designed to aid in the interpretation of Computed Tomography (CT) scans of the thorax that may contain pulmonary abnormalities. LungQ is stand-alone command-line software which must be run from a command-line interpreter and does not have a graphical user interface.
This document describes the acceptance criteria and the study conducted to prove that the device, LungQ v3.0.0, meets these criteria, as presented in the FDA 510(k) summary.
1. Table of Acceptance Criteria and Reported Device Performance
| Feature/Metric | Acceptance Criteria | Reported Device Performance (LungQ v3.0.0 vs LungQ v1.1.0) | Reported Device Performance (LungQ v3.0.0 vs Human Experts) |
|---|---|---|---|
| Lung and Lobar Volume | Difference ≤ 10% | Difference less than threshold value | N/A (compared to experts for (sub)segments) |
| Density Measurements: | |||
| * LAA-950HU | Agreement limits -1% to 1% | Difference less than threshold value | N/A (compared to experts for (sub)segments) |
| * LAA-910HU | Agreement limits -10% and 10% | Difference less than threshold value | N/A (compared to experts for (sub)segments) |
| * 15th Percentile Density (PD15) | Agreement limits -10 HU to 10 HU | Difference less than threshold value | N/A (compared to experts for (sub)segments) |
| Fissure Completeness | Az value ≥ 0.95 (ROC analysis) | Az value = 0.97 | N/A |
| (Sub)segmental Volumes | Tolerable variability (absolute): 150mL | Mean difference (SD) less than threshold value | Mean difference (SD) less than threshold value |
| Tolerable variability (relative): 5% | Mean difference (SD) less than threshold value | Mean difference (SD) less than threshold value | |
| (Sub)segmental Density Scores | Tolerable variability (absolute): 150mL | Mean difference (SD) less than threshold value | Mean difference (SD) less than threshold value |
| Tolerable variability (relative): 5% | Mean difference (SD) less than threshold value | Mean difference (SD) less than threshold value |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: Not explicitly stated in the provided text. The document mentions "scans were taken with a wide variety of scanner brands and models," and lists various scanner types but does not specify the number of cases.
- Data Provenance:
- Country of Origin: Not specified in the provided text.
- Retrospective or Prospective: Not specified in the provided text, but the nature of comparing to a predicate device and expert corrected segmentations suggests it was likely retrospective given the need for ground truth.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- Number of Experts: Not explicitly stated beyond "human experts."
- Qualifications of Experts: Not specified.
4. Adjudication Method for the Test Set
- Adjudication Method: Not explicitly stated. The document mentions "segmentation which were corrected by human experts," implying that human experts refined or established the ground truth for (sub)segmental volumes and density scores. However, the process for this correction (e.g., consensus among multiple experts or a single expert's adjudication) is not detailed. Comparisons between the two devices were done using Bland-Altman plots and ROC analysis.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Was an MRMC study done? No. The study was a "head-to-head performance testing" between the subject device (LungQ v3.0.0) and the predicate device (LungQ v1.1.0), and a comparison of LungQ v3.0.0 to human experts for (sub)segmental measurements. There is no mention of human readers evaluating cases with and without AI assistance to determine an effect size of AI on human performance.
- Effect Size of Human Readers with AI vs. without AI assistance: Not applicable, as an MRMC comparative effectiveness study was not performed.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Performance
- Was a standalone study done? Yes. The entire head-to-head performance study comparing LungQ v3.0.0 to LungQ v1.1.0, and the comparison of LungQ v3.0.0 outputs for (sub)segmental analysis against human expert corrections, represents standalone performance evaluation of the algorithm. The device itself is described as "stand-alone command-line software which must be run from a command-line interpreter and does not have a graphical user interface," further reinforcing its standalone nature.
7. Type of Ground Truth Used
- Ground Truth Type:
- Predicate Device Output: For lung and lobar volumes, LAA-950HU, LAA-910HU, PD15, and fissure completeness, the outputs of the predicate device (LungQ v1.1.0) served as a comparative reference.
- Expert Consensus/Correction: For (sub)segmental volumes and density scores, the ground truth was established by "segmentation which were corrected by human experts." This implies expert-adjudicated or expert-derived ground truth.
8. Sample Size for the Training Set
- The document does not provide information regarding the sample size used for the training set. The descriptions focus solely on the performance evaluation of the device in comparison to a predicate and human experts.
9. How the Ground Truth for the Training Set Was Established
- The document does not provide information on how the ground truth for the training set was established, as details about the training set itself are absent.
{0}------------------------------------------------
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services seal on the left and the FDA acronym and name on the right. The FDA acronym is in a blue square, and the full name "U.S. Food & Drug Administration" is in blue text.
January 8, 2024
Thirona BV % Eva Rikxoort Official Correspondent Toernooiveld 300 Toernooiveld 300, 6525 EC NETHERLANDS
Re: K232412
Trade/Device Name: LungO v3.0.0 Regulation Number: 21 CFR 892.1750 Regulation Name: Computed Tomography X-Ray System Regulatory Class: Class II Product Code: JAK Dated: August 10, 2023 Received: December 6, 2023
Dear Eva Rikxoort:
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}------------------------------------------------
2
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.
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 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,
Lu Jiang
Lu Jiang, Ph.D. Assistant Director Diagnostic X-Ray Systems Team DHT8B: Division of Radiologic Imaging Devices and Electronic Products OHT8: Office of Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
{2}------------------------------------------------
Indications for Use
510(k) Number (if known) K232412
Device Name LungQ V3.0.0
Indications for Use (Describe)
The Thirona LungQ software provides reproducible CT values for pulmonary tissue which is essential for providing quantitative support for diagnosis and follow up examination. The LungQ software can be used to support physician in the diagnosis and documentation of pulmonary tissues images (e.g. abnormalities) from CT thoracic datasets. Three-D segmentation and isolation of sub-compartments, volumetric analysis, density evaluation, and reporting tools are provided.
| 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) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
Section 05
Section 5 510(k) Summary
5.1 SUBMITTER
Submitted by:
Thirona BV
Toernooiveld 300
6525 EC Nijmegen the Netherlands
Contact Person:
Eva van Rikxoort
Telephone Number: +31 6 47 14 28 38
Email: evavanrikxoort@thirona.eu
Date Prepared: 8th August 2023
5.2 DEVICE
| Trade Name | LungQ v3.0.0 |
|---|---|
| Common Use/Usual Name | Computer Tomography X-ray system |
| Product Code | JAK |
| Classification | Class II, 21 CFR 892.1750 |
| Device Panel | Radiology |
5.3 PREDICATE DEVICE
| Predicate Device | LungQ V1.1.0 |
|---|---|
| Predicate Classification | Class II, 21 CFR 892.1750 |
5.4 REFERENCE DEVICE
| Predicate Device | VIDA Vision |
|---|---|
| Predicate Classification | Class II, 21 CFR 892.1750 |
{4}------------------------------------------------
5.5 DEVICE DESCRIPTION
The LungQ software is designed to aid in the interpretation of Computed Tomography (CT) scans of the thorax that may contain pulmonary abnormalities. LungQ is stand-alone command-line software which must be run from a command-line interpreter and does not have a graphical user interface.
5.6 INDICATION FOR USE
The Thirona LungQ software provides reproducible CT values for pulmonary tissue which is essential for providing quantitative support for diagnosis and follow up examination. The LungQ software can be used to support physician in the diagnosis and documentation of pulmonary tissues images (e.g., abnormalities) from CT thoracic datasets. Three-D segmentation and isolation of sub-compartments, volumetric analysis, density evaluations, fissure evaluation, and reporting tools are provided.
5.7 COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
Table 5-1 below compares the Thirona LungQ software to the predicate device.
| Item | LungQ v3.0.0Thirona(Subject Device) | LungQ v1.1.0Thirona(Predicate Device) | VIDA visionVIDA Diagnostics, Inc(Reference Device) |
|---|---|---|---|
| 510(k) Number | NA | K173821 | K200990 |
| Product Code | JAK | Same | Same |
| Regulation Number | 21 CFR 892.1750 | Same | Same |
| DeviceClassification | Class II | Same | Same |
| Common Name | Software Accessory to aComputed tomography x-raysystem | Same | Same |
| Intended Use | The Thirona LungQ softwareprovides reproducible CTvalues for pulmonary tissuewhich is essential forproviding quantitativesupport for diagnosis andfollow up examination. TheLungQ software can be usedto support physician in thediagnosis anddocumentation ofpulmonary tissues images(e.g., abnormalities) from CTthoracic datasets. Three-D | Same | Equivalent |
| segmentation and isolationof sub-compartments,volumetric analysis, densityevaluations, fissureevaluation, and reportingtools are provided. | |||
| Modality | CT | Same | Same |
| Data Loading | DICOM | Same | Same |
| Application | Command-line interface | Same | Equivalent |
| OS | Linux | Equivalent | Equivalent |
| Segmentation | Provides 3D segmentation | Same | Same |
| Provides Segmentation ofthe:• Left Lung• Right Lung• Left Upper Lobe• Left Lower Lobe• Right Upper Lobe• Right Middle Lobe• Right Lower Lobe• Pulmonary(sub)segments | Equivalent | Equivalent | |
| Provides AirwaysSegmentation | Same | Same | |
| User cannot manually editsegmentation | Same | Equivalent | |
| Lung VolumeAnalysis Support | Ability to measure volumefor:• Both Lungs• Left Lung• Right Lung• Left Upper Lobe• Left Lower Lobe• Right Upper Lobe• Right Middle Lob• Right Lower Lobe• Pulmonary(sub)segments | Equivalent | Equivalent |
| Volume DensityAnalysis | Ability to measure volume atmultiple density ranges for:• Both Lungs | Equivalent | Equivalent |
| Left Lung Right Lung Left Upper Lobe Left Lower Lobe Right Upper Lobe Right Middle Lob Right Lower Lobe Pulmonary (sub)segments Ability to measure the 15th percentile density analysis | Same | Same | |
| Fissure Analysis | Ability to perform fissure evaluations | Same | Same |
| Analyzed Data Output | Provides a report | Same | Same |
Table 5-1: Substantial Equivalence Comparison between Subject, Predicate and Reference Device
{5}------------------------------------------------
{6}------------------------------------------------
5.8 PERFORMANCE DATA
The performance testing for LungQ consists of norm-compliance testing, design verification and validation testing. For norm-compliance and design verification, the testing was performed per subject device, while the validation, such as non-clinical validation and usability validation, were performed at system level representing a logical clinical workflow following the intended use.
Performance testing data of the proposed devices demonstrate that the subject device is substantially equivalent to the predicate device, and that the design output meets the design input requirements.
Compliance Testing
Norm-compliance performance tests were performed on the proposed LungQ software according to the following FDA recognized consensus standards and FDA guidance documents (see Table 5-2 and Table 5-3), and were all passed.
| IdentificationNumber | Edition /Year | Title | RecNumber |
|---|---|---|---|
| AAMI TIR57 | 2016 | Principles for medical device security—Risk management | 13-83 |
| ANSI AAMIIEC TIR 80002-1 | 2009 | Medical device software - Part 1: Guidance on theapplication of ISO 14971 to medical device software | 13-34 |
| ANSI NEMAHN 1 | 2019 | Manufacturer Disclosure Statement for Medical DeviceSecurity | 13-123 |
Table 5-2: Standards and Guidance documents
{7}------------------------------------------------
| IEC 62304 | 1.1/2015 | Medical device software - Software life-cycle processes | 13-79 |
|---|---|---|---|
| IEC 62366-1 | 1.1/2020 | Medical devices - Application of usability engineering tomedical devices | 5-129 |
| IEC 82304-1 | 1.0/2016 | Health software - Part 1: General requirements forproduct safety | 13-97 |
| ISO 14971 | 3/2019 | Medical devices - Application of risk management tomedical devices | 5-125 |
| ISO 15223-1 | 4/2021 | Medical devices — Symbols to be used with informationto be supplied by the manufacturer — Part 1: Generalrequirements | 5-117 |
| ISO 20417 | 1/2021 | Medical devices — Information to be supplied by themanufacturer | 5-135 |
| ISO/IEC 21778 | 1/2017 | Information technology — The JSON data interchangesyntax | - |
| ISO/IEC 27001 | 2/2013 | Information technology - Security techniques -Information security management systems -Requirements | - |
| NEMA PS 3.1 -3.20 | 2022d | Digital Imaging and Communications in Medicine(DICOM) Set | 12-349 |
Table 5-3: Guidance documents
| IdentificationNumber | Year | Title |
|---|---|---|
| FDA-1997-D-0029 | 2002 | General Principles of Software Validation |
| FDA-2011-D-0469 | 2016 | Applying Human Factors and Usability Engineering to MedicalDevices |
| FDA-2011-D-0652 | 2014 | The 510(k) Program: Evaluating Substantial Equivalence inPremarket Notifications [510(k)] |
| FDA-2014-D-0456 | 2018 | Appropriate Use of Voluntary Consensus Standards in PremarketSubmissions for Medical Devices |
| FDA-2015-D-4852 | 2017 | Design Considerations and Pre-market SubmissionRecommendations for Interoperable Medical Devices |
| FDA-2016-D-1853 | 2021 | Unique Device Identification System: Form and Content of theUnique Device Identifier (UDI) |
| FDA-2018-D-1329 | 2019 | Recommended Content and Format of Non-Clinical BenchPerformance Testing Information in Premarket Submissions |
| FDA-2019-D-3598 | 2019 | Off-The-Shelf Software Use in Medical Devices |
| FDA-2021-D-0775 | 2023 | Content of Premarket Submissions for Device Software Functions |
| FDA-2021-D-1158 | 2022 | Cybersecurity in Medical Devices: Quality System Considerations andContent of Premarket Submissions |
| FDA-2023-D-1030 | 2023 | Cybersecurity in Medical Devices: Refuse to Accept Policy for CyberDevices and Related Systems Under Section 524B of the FD&C Act |
{8}------------------------------------------------
Performance Testing
Software Verification testing was conducted to ensure that the Lung Q software met its requirements. The verification testing included white box testing to verify implementation and system integration testing. The LungQ software successfully passed the verification testing.
Software Validation was conducted to ensure the software met the user needs (i.e. input requirements). This validation was based on user scenarios. The LungQ software successfully passed the software validation.
Human factors (HF) engineering process was followed in accordance with the usability standard and FDA guidance. The restricted interface of LungQ with the third party end-user-interface is well controlled by the use of standard input and output formats. The usability is determined by the input requirements, which have been identified during risk management. The human factors validation test (summative usability evaluation) of LungQ was performed.
Substantial equivalence Study
A head-to-head performance testing was conducted between the subject and the predicate device.
The aim of this study was to assess and compare the measurement of lung structure parameters, such as lung and lobar volumes, density scores (LAA-950HU and LAA-910HU), 15th percentile lung density (PD15), and fissure completeness between LungQ v3.0.0 (subject device) and LungQ v1.1.0 (primary predicate, K1738210). Firstly, both devices analyzed the lung and lobar volumes, density scores, PD15 and fissure completeness. Subsequently, Bland-Altman plots were used for the pairwise comparison of lung and lobar volumes, density scores, PD15 measurements between the two devices. Moreover, for comparison of the fissure completeness measurements between both devices, receiver operating characteristic (ROC) analysis was performed and the area under de ROC curve (Az value) was calculated. The tolerable variability for absolute and relative threshold values was defined as:
- . Lung and lobar volume: Difference ≤ 10%
- . Lung and lobar density measurements:
- LAA-950HU: Agreements limits -1% to 1%
- LAA-910HU: Agreement limits -10% and 10% o
- 15™ Percentile: Agreement limits -10 HU to 10 HU O
- Fissure completeness classification: Az value ≥ 0.95
The (sub)segmental volumes and density scores were not compared with the primary predicate but with segmentation which were corrected by human experts. The pairwise comparison between LungQ v3.0.0 and the experts was performed using Blant-Altman analysis of (sub)segmental volumes and density scores. The tolerable variability for absolute and relative values are 150mL and 5%, respectively.
The results showed that for the lung and lobar volumes, density scores (LAA-950HU and LAA-910HU), and 15th percentile lung density (PD15), the difference between LungQ v3.0.0 (subject device) and
{9}------------------------------------------------
the primary predicate were less than the threshold value. The area under the AUC curve (Az value) for the comparison of fissure completeness measurements between LungQ v3.0.0 (subject device) and the primary predicate was found to be 0.97, above the minimal threshold value. The mean difference (SD) between LungQ v3.0.0 and the reference of the human experts for the (sub)segmental volumes and density scores were less than the threshold value.
The scans were taken with a wide variety of scanner brands and models used to obtain scans in the datasets used for the equivalence study testing are shown in Table 5-4.
| Table 5-4: Imaging parameters equivalence study. | ||
|---|---|---|
| -------------------------------------------------- | -- | -- |
| Imaging parameters Equivalence study | |
|---|---|
| Scanner manufacture | GE MEDICAL SYSTEMS; SIEMENS; Philips |
| Scanner types | LightSpeed16; LightSpeed VCT; Sensation 64;Definition; Sensation 16; Definition AS+;SOMATOM Definition Flash; Brilliance 64;LightSpeed Pro 16; Discovery CT750 HD;SOMATOM Definition; LightSpeed UltraSOMATOM Definition AS; LightSpeed16 |
The results showed that outputs from Thirona LungQ v3.0.0 are equivalent to the predicate device, LungQ v1.1.0.
Conclusion on performance testing
All compliance, verification and validation tests have been used to support substantial equivalence of the subject device and to demonstrate that the LungQ v3.0.0 device:
- comply with the aforementioned international and FDA recognized consensus standards and FDA guidance documents; and
- meet the acceptance criteria and are adequate for their intended use.
Based on the information provided above, the LungQ v3.0.0 device is considered substantially equivalent to the predicate device in terms of safety and effectiveness.
No clinical testing was required as substantial equivalence was demonstrated by the attributes of intended use, technological characteristics, and non-clinical testing.
5.9 CONCLUSIONS
The proposed device, LungQ v3.0.0, is substantially equivalent to the above-mentioned predicate device, in terms of intended use, technological characteristics and, safety and effectiveness.
Substantial equivalence was demonstrated by non-clinical performance tests provided in this 510(k) premarket notification. These tests demonstrate that the proposed device comply with the user needs specifications and product requirements, as well as the requirements specified in the international and
Thirona
{10}------------------------------------------------
FDA-recognized consensus standards, and are as safe and effective as the predicate device, and do not raise any new safety and/or effectiveness concerns.
§ 892.1750 Computed tomography x-ray system.
(a)
Identification. A computed tomography x-ray system is a diagnostic x-ray system intended to produce cross-sectional images of the body by computer reconstruction of x-ray transmission data from the same axial plane taken at different angles. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories.(b)
Classification. Class II.