Mobius3D software is used for quality assurance, treatment plan verification, and patient alignment and anatomy analysis in radiation therapy. It calculates radiation dose three-dimensionally in a representation of a patient or a phantom. The calculation is based on read-in treatment plans that are initially calculated by a treatment planning system and may additionally be based on external measurements of radiation from other sources such as linac delivery log data. Patient alignment and anatomy analysis is based on read-in treatment planning images (such as computed tomography) and read-in daily treatment images (such as registered cone beam computed tomography).

Mobius3D is not a treatment planning system. It is only to be used by trained radiation oncology personnel as a quality assurance tool.

Device Description

Mobius3D (v4.0) is a software product used within a radiation therapy clinic for quality assurance and treatment plan verification. It is important to note that while Mobius3D operates in the field of radiation therapy, it is neither a radiation delivery device (e.g. a linear accelerator), nor is it a Treatment Planning System (TPS). Mobius3D cannot design or transmit instructions to a delivery device, nor does it control any other medical device. Mobius3D is an analysis tool meant solely for quality assurance (QA) purposes when used by trained medical professionals. Being a softwareonly QA tool, Mobius3D never comes into contact with patients.

Mobius3D performs dose calculation verifications for radiation treatment plans by doing an independent calculation of radiation dose is initially calculated by a Treatment Planning System (TPS), which is a software tool that develops a detailed set of instructions (i.e. a plan) for another system (e.g. a linear accelerator) to deliver radiation to a patient. The dose calculation performed by Mobius3D uses a proprietary collapsed cone convolution superposition (CCCS) algorithm.

Mobius3D also performs dose delivery quality assurance for radiation treatment plans by using the measured data recorded in a linear accelerator's delivery log files to calculate a delivered dose. This is presented to the end user in a software component of Mobius3D called MobiusFX. The MobiusFX component is available to users through licensing as an add-on to the core Mobius3D software features.

Mobius3D performs quality assurance of a patient's alignment and anatomy analysis is based on comparison of Cone Beam Computed Tomography (CBCT) images taken immediately before treatment to the images used for treatment planning, which are typically acquired using standard Computed Tomography (CT). This analysis is presented to the end user in an add-on software module within Mobius3D called CBCT Checks.

AI/ML Overview

The provided text describes the regulatory clearance of Mobius3D v4.0 and its equivalence to the predicate device Mobius3D v3.0 (K192424) for quality assurance in radiation therapy. However, it does not contain the specific acceptance criteria or the details of a study that proves the device meets those criteria, as requested.

The document states:

"No animal studies or clinical tests have been included in this pre-market submission."
"The predicate device was cleared based only on non-clinical testing, and no animal or clinical studies were performed for the subject device."
"The non-clinical verification and validation data demonstrates that the subject device should perform as intended in the specified use conditions."

This indicates that the clearance was based on software verification and validation testing, and compliance with certain standards, rather than a clinical study with acceptance criteria in the manner typically associated with diagnostic or prognostic AI devices.

Therefore, many of the requested details, such as sample size for test sets, data provenance, number of experts for ground truth, adjudication methods, MRMC studies, standalone performance, and training set details, are not present in this document.

Based on the provided text, here is what can be inferred/stated:

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

Acceptance Criteria (Inferred from regulatory filing context for software)	Reported Device Performance (Inferred from submission)
Conformance to applicable software requirements and specifications	Test results demonstrate conformance to applicable requirements and specifications.
Compliance with relevant medical device software standards	Conforms to IEC 62304, IEC 62366-1, IEC 61217
Functionality of new features (Dose Calculation on CBCT)	Dose calculation on CBCT is performed and presented to the user.
Equivalence to predicate device (Mobius3D v3.0)	Substantially equivalent, with non-clinical verification and validation data.

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

Not specified. The document refers to "Software Verification and Validation Testing" and "non-clinical testing," but no details on the size or nature of data used for these tests are provided.

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 applicable/Not specified. The ground truth in software verification and validation would typically be established based on functional requirements, design specifications, and expected outputs, rather than expert interpretation of medical images or outcomes data.

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

Not applicable/Not specified. This is typically relevant for studies involving human interpretation or clinical outcomes, which are not described here.

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:

No. The document explicitly states: "No animal studies or clinical tests have been included in this pre-market submission." An MRMC study would be considered a clinical test.

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

Yes, to the extent of "non-clinical verification and validation data." The device is a "software-only QA tool" and "an analysis tool," suggesting its performance was evaluated in a standalone capacity against its specified functional requirements. However, specific metrics of its standalone performance (e.g., accuracy against a gold standard for dose calculation) are not provided.

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

Software functional requirements and specifications. For "Dose Calculation on CBCT," the "ground truth" for verification would likely involve comparing the software's calculated dose outputs against established physics models, phantom measurements, or validated reference calculation engines for a given input. This is inferred from the "non-clinical testing" description.

8. The sample size for the training set:

Not specified/Not applicable for this type of submission. Mobius3D uses a "proprietary collapsed cone convolution superposition (CCCS) algorithm" for dose calculation. This is a deterministic physics-based algorithm, not typically a machine learning model that would require a "training set" in the conventional sense of AI/ML.

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

Not applicable. As a deterministic physics-based algorithm, there isn't a "training set" with ground truth in the machine learning context. The algorithm's parameters and underlying physics models would be based on theoretical principles and empirical validation.

Summary

{0}------------------------------------------------

January 14, 2021

Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Varian Medical Systems, Inc. % Mr. Peter J. Coronado Senior Director, Regulatory Affairs 3100 Hansen Way PALO ALTO CA 94304

Re: K203669

Trade/Device Name: Mobius3D v4.0 Regulation Number: 21 CFR 892.5050 Regulation Name: Medical charged-particle radiation therapy system Regulatory Class: Class II Product Code: IYE Dated: December 14, 2020 Received: December 16, 2020

Dear Mr. Coronado:

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); 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)

{1}------------------------------------------------

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

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K203669

Device Name Mobius3D v4.0

Indications for Use (Describe)

Mobius3D is not a treatment planning system. It is only to be used by trained radiation oncology personnel as a quality assurance tool.

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}------------------------------------------------

Varian Medical Systems, Inc 3100 Hansen Way Palo Alto, CA 94304-1038 Telephone: 1.650.493.4000 Toll Free: 800.544.4636 www.varian.com

510(k) Summary

The following information is provided as required by 21 CFR 807.92

SUBMITTER
Name and Address:	Varian Medical Systems, Inc.3100 Hansen Way, m/s E110Palo Alto, CA 94304
Contact Person:	Peter J. CoronadoSenior Director, Regulatory AffairsPhone: 650-424-6320 Fax: 650-646-9200submissions.support@varian.com
Date Prepared:	December 21, 2020
DEVICE
Subject Device Name:	Mobius3D v4.0
Common/Usual Name:	Mobius3D
Product Code and Classification:	Medical charged-particle radiation therapy systemIYE 21 CFR 892.5050 Class II
PREDICATE DEVICE
Predicate Device Name:	Mobius3D v3.0 (K192424)
Reference Device(s):	No reference devices were used in this submission

DEVICE DESCRIPTION

{4}------------------------------------------------

Varian Medical Systems, Inc 3100 Hansen Way Palo Alto, CA 94304-1038 Telephone: 1.650.493.4000 Toll Free: 800.544.4636 www.varian.com

INDICATIONS FOR USE

Mobius3D software is used for quality assurance, treatment plan verification, and patient alignment and anatomy analysis in radiation therapy. It calculates radiation dose three-dimensionally in a representation of a patient or a phantom. The calculation is based on read-in treatment plans that are initially calculated by a treatment planning system and may additionally be based on external measurements of radiation fields from other sources such as linac delivery log data. Patient alignment and anatomy analysis is based on read-in treatment planning images (such as computed tomography) and read-in daily treatment images (such as registered cone beam computed tomography).

Mobius3D is not a treatment planning system. It is only to be used by trained radiation oncology personnel as a quality assurance tool.

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

The modified device, referred to as the "subject device" throughout this summary, is release version v4.0 (version 4.0) of the Mobius3D with additional software changes incorporated since the release version of the predicate device, version 3.0 (K192424).

{5}------------------------------------------------

The significant change in the subject device compared with the predicate device is as follows:

1. Dose Calculation on Cone-Beam CT (CBCT)

This is a change to the existing CBCT module. Besides the Gamma Comparison, the CBCT module will (optionally) calculate dose on the CBCT using the applied shifts and TPS (Treatment Planning System) plan and structure set. This allows the user to better understand the impact of a patient's anatomy change or a possible alignment issue because it will show the dose on the patient's 3D image of that day. Dose evaluation can be done in the Slice Viewer by showing calculated isodose lines on CBCT. The dose in the non-deformed targets will be compared with the TPS dose, no deformation of structures is performed. Dose calculation on CBCT is optional and can be configured per Plan Type.

The non-significant changes in the subject device since the predicate device include:

a. Plan type specific calculation and tolerance settings, target objectives and required regions of interests (ROIs)
b. Streamlined processing
Multi-machine support for the MobiusAdapt patient session C.
d. National Language Support (NLS)
e. Active directory support

PERFORMANCE DATA

The following performance data was provided in support of the substantial equivalence determination.

Software Verification and Validation Testing

Software verification and validation 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 "major" level of concern.

Test results demonstrate conformance to applicable requirements and specifications. No animal studies or clinical tests have been included in this pre-market submission.

Standards Conformance

The subject device conforms in whole or in part with the following standards:

IEC 62304:2006+A1:2015 Medical device software - Software lifecycle processes

{6}------------------------------------------------

varian

Varian Medical Systems, Inc 3100 Hansen Way Palo Alto, CA 94304-1038 Telephone: 1.650.493.4000 Toll Free: 800.544.4636 www.varian.com

IEC 62366-1:2015 Medical device Part 1 Application of usability engineering to medical ● devices
IEC 61217:2011 Radiotherapy Equipment Coordinates, Movements and Scales ●

CONCLUSION

The predicate device was cleared based only on non-clinical testing, and no animal or clinical studies were performed for the subject device. The non-clinical verification and validation data demonstrates that the subject device should perform as intended in the specified use conditions.

Therefore, Varian considers the subject device, Mobius3D v4.0, is substantially equivalent to the predicate device Mobius3D v3.0 (K192424).

Regulation Number and Section

§ 892.5050 Medical charged-particle radiation therapy system.

(a)
Identification. A medical charged-particle radiation therapy system is a device that produces by acceleration high energy charged particles (e.g., electrons and protons) intended for use in radiation therapy. This generic type of device may include signal analysis and display equipment, patient and equipment supports, treatment planning computer programs, component parts, and accessories.(b)
Classification. Class II. When intended for use as a quality control system, the film dosimetry system (film scanning system) included as an accessory to the device described in paragraph (a) of this section, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 892.9.