Molecular Flow Simulations is designed as a planning system for pre- and intra-operative planning of stereotactic or image-guided surgeries. It is specially designed to display anatomical images of a patient acquired with magnetic resonance (MR) or computed tomography (CT) scanners as well as images derived from diffusion tensor imaging (DTI) data acquired with MR. Molecular Flow Simulations is a dedicated tool for planning trajectories of intracranial catheters. Guidelines for the catheter placement, such as from catheter suppliers, can be visualized and displayed to support the surgeon in improving catheter placement planning. The guidelines, in combination with anatomical information, can be used to suggest areas that are compliant with the guidelines. Molecular Flow Simulations does not generate or create rules for the placement of intracranial catheters by any means. Molecular Flow Simulations uses MR-DTI and T2- weighted MR images to suggest likely volumes of fluid distribution.

The primary mode of action for Molecular Flow Simulations is a device for creating stereotactic or image-guided surgical plans, especially for the creation of plans for the placement of intracranial catheters.

Device Description

Molecular Flow Simulations is a software tool running on a standard, standalone computer (PC or Laptop), or being accessible via the intranet connection, that can be used by surgeons for pre- or intraoperative planning of treatments based on stereotactic systems or image guided surgery systems. The system is a software-only medical device to be installed on common IT hardware.

AI/ML Overview

The provided text does not contain detailed acceptance criteria or a study proving the device meets those criteria. It focuses on the substantial equivalence determination for the "Molecular Flow Simulations" device to a predicate device ("iPlan Flow").

Here's a breakdown of what is available and what is missing based on your request:

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

Missing. The document states that "Verification testing that product meets product performance and functional specifications" was performed, but it does not list those specifications/acceptance criteria or the specific performance results against them.

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

Partially Available. The document mentions "several tests were performed, in concordance with Duke University, using synthetic, animal and human imaging."
- Sample Size: Not specified for any of the synthetic, animal, or human imaging test sets.
- Provenance: Duke University (USA), for synthetic, animal, and human imaging.
- Retrospective/Prospective: Not specified.

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)

Missing. The document does not provide any information about experts used for establishing ground truth or their qualifications.

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

Missing. No adjudication method is described.

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

Missing. The document does not describe an MRMC comparative effectiveness study where human readers' performance with and without AI assistance was evaluated. The device is described as a "planning system" used by surgeons, not one directly assisting image readers in diagnosis.

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

Partially Available. The device, "Molecular Flow Simulations," is a "software-only medical device" designed for "pre- or intraoperative planning." It "uses MR-DTI and T2-weighted MR images to suggest likely volumes of fluid distribution" and "does not generate or create rules for the placement of intracranial catheters by any means." It calculates "likely fluid distribution from the planned catheter positions." This implies that the software performs its simulations and suggestions as an algorithm without direct human input during the simulation process itself, though the output is used by a human (surgeon) for planning. However, no specific "standalone performance study" with metrics like sensitivity, specificity, accuracy, etc., is provided for these "suggestions" or "calculations."

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

Missing. The document states that testing used "synthetic, animal and human imaging" but does not elaborate on how ground truth was established for any of these data types for performance evaluation.

8. The sample size for the training set

Missing. There is no information provided about a training set since the document describes performance testing rather than model development. Given it's a "planning system" that uses "mathematical modeling," it might not have a traditional "training set" in the context of deep learning, but rather relies on established physical/mathematical principles.

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

Missing. As no training set information is available, no ground truth establishment method for it is mentioned.

In summary, the provided FDA 510(k) summary focuses primarily on demonstrating substantial equivalence to a predicate device based on intended use, technological characteristics, and general verification testing, rather than detailed performance study results against specific acceptance criteria for an AI/CAD-type device.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health and 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 blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

December 3, 2021

Therataxis, LLC % Al Memmolo President, Convergent Clinical, Inc. 6648 Surf Crest St. Carlsbad, California 92011

Re: K201435

Trade/Device Name: Molecular Flow Simulations Regulation Number: 21 CFR 882.4560 Regulation Name: Stereotaxic Instrument Regulatory Class: Class II Product Code: HAW, QRI Dated: November 11, 2021 Received: November 15, 2021

Dear Al Memmolo:

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

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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) K201435

Device Name Molecular Flow Simulations

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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A. Device Information:	510(k) Summary
Category	Comments
Sponsor:	Therataxis, LLCJohns Hopkins Eastern Building Suite B3051101 East 33rd Street Baltimore, MD 21208(443) 451-7154
Correspondent ContactInformation:	Al MemmoloConvergent Clinical, Inc.Carlsbad, CA 92011Email: almemmolo@gmail.com
Device Common Name:	Planning System, Stereotaxic Instrument
Device Regulation & Name:	CFR 882.4560 Stereotaxic Instrument
Classification & Product Code:510(k) Number:	Classification: Class II Product Code: HAW, QRIK201435
Device Proprietary Name:	Molecular Flow Simulations

Molecular Flow Simulations

Predicate Device Information:

Predicate Device:	iPlan Flow
Predicate Device Manufacturer:	Brainlab AG
Predicate Device Common Name:	iPlan Flow
Predicate Device Premarket Notification #	K053164
Predicate Device Classification & Name	Classification: Class IIName: Stereotaxic Instrument
Predicate Device Classification& Product Code:	Classification: Class IIProduct Code: HAW

B. Date Summary Prepared

December 3, 2021

C. Description of Device

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D. Indications for Use

Molecular Flow Simulations is designed as a planning system for pre- and intra-operative planning of stereotactic or image-guided surgeries. It is specially designed to display anatomical images of a patient acquired with magnetic resonance (MR) or computed tomography (CT) scanners as well as images derived from diffusion tensor imaging (DTI)-data acquired with MR. Molecular Flow Simulations is a dedicated tool for planning trajectories of intracranial catheters. Guidelines for the catheter placement, such as from catheter suppliers, can be visualized and displayed to support the surgeon in improving catheter placement planning. The guidelines, in combination with anatomical information, can be used to suggest areas that are compliant with the guidelines. Molecular Flow Simulations does not generate or create rules for the placement of intracranial catheters by any means. Molecular Flow Simulations uses MR-DTI and T2weighted MR images to suggest likely volumes of fluid distribution.

The primary mode of action for Molecular Flow Simulations is a device for creating stereotactic or imageguided surgical plans, especially for the creation of plans for the placement of intracranial catheters.

Characteristic	Application Device:Molecular FlowSimulations(K201435)	Predicate Device:iPlan Flow(K053164)	Impact onSubstantialEquivalence
Company	Therataxis, LLC	Brainlab	-
RegulationNumber	882.4560	882.4560	Identical
Product Code	HAW	HAW	Identical
Intended Use	Molecular Flow Simulationsis designed as a planningsystem for pre- andintraoperative planning ofstereotactic or image guidedsurgery treatments. It isspecially designed to displayanatomical images of apatient acquired with MRand/or CT as well as imagesderived from DTI-dataacquired with MagneticResonance Imaging (MRI).	iPlan Flow is designed as aplanning system for pre-and intraoperative planningof stereotactic or imageguided surgery treatments.It is specially designed todisplay anatomical imagesof a patient acquired withMR and/or CT as well asimages derived from DTI-dataacquired withMagnetic ResonanceImaging (MRI).	Equivalent
Indications for Use	Molecular Flow	iPlan Flow	K201435
	Molecular FlowSimulations is designed asa planning system for pre-and intra-operativeplanning of stereotactic orimage-guided surgeries. Itis specially designed todisplay anatomical imagesof a patient acquired withmagnetic resonance (MR)or computed tomography(CT) scanners as well asimages derived fromdiffusion tensor imaging(DTI)-data acquired withMR. Molecular FlowSimulations is a dedicatedtool for planningtrajectories of intracranialcatheters. Guidelines for thecatheter placement, such asfrom catheter suppliers, canbe visualized and displayedto support the surgeon inimproving catheterplacement planning. Theguidelines, in combinationwith anatomicalinformation, can be used tosuggest areas that arecompliant with theguidelines. Molecular FlowSimulations does notgenerate or create rules forthe placement ofintracranial catheters byany means. Molecular FlowSimulations uses MR-DTIand T2- weighted MRimages to suggest likelyvolumes of fluiddistribution.	iPlan Flow is designed as aplanning system for pre-and intraoperative planningof stereotactic or imageguided surgery treatments.It is specially designed todisplay anatomical imagesof a patient acquired withMR and/or CT as well asimages derived from DTI-data acquired withMagnetic ResonanceImaging (MRI). iPlan Flowis a dedicated tool forplanning trajectories ofintra-cranial catheters.Guidelines for the catheterplacement e.g. fromcatheter suppliers can bevisualized and displayed tosupport the surgeon inimproving catheterplacement planning. Theguidelines, in combinationwith anatomicalinformation, can be used tosuggest areas that arecompliant with theguidelines. iPlan Flow doesnot generate or create rulesfor the placement ofintracranial catheters byany means. iPlan Flow usesMR-DTI and T2- weightedMR images to suggestlikely volumes of fluiddistribution.	Equivalent
	The primary mode of actionfor Molecular FlowSimulations is a device forcreating stereotactic orimage-guided surgical plans,especially for the creation ofplans for the placement ofintracranial catheters.	The Primary mode ofaction for iPlan Flow is adevice for creatingtreatment plans forstereotactic or imageguided surgical treatment,especially for the creationof plans for the placementof intra-cranial catheters.The treatment plans can beused in conjunction withother BrainLAB medicaldevices such asVectorVision for imageguided surgical treatment.
			K201435, Pag
Technology	Molecular FlowSimulations can be usedfor the planning ofintracranial catheters, withimage guided surgery.Guidelines for the exactplacement of intracranialcatheters can bevisualized. Theseguidelines comprise theminimal depth of thecatheter tip in the braintissue, the minimaldistance of the catheter tipfrom intra-cranial surfacesand the minimal distancebetween different cathetertips. The depth guidelinecan be calculated from theflow rate and the catheterdiameter and warningswill be displayed if thetrajectory of a plannedcatheter is likely to crossan intra-cranial surface.Molecular FlowSimulations is able tocalculate a likely fluiddistribution from theplanned catheter positionsto support the physician inhis decision aboutappropriate catheterpositions. These featuresenable the surgeon tobetter plan and place intra-cranial catheters.	iPlan Flow can be used forthe planning ofintracranial catheters, withimage guided surgery.Guidelines for the exactplacement of intracranialcatheters can bevisualized. Theseguidelines comprise theminimal depth of thecatheter tip in the braintissue, the minimaldistance of the catheter tipfrom intra-cranial surfacesand the minimal distancebetween different cathetertips. The depth guidelinecan be calculated from theflow rate and the catheterdiameter and warningswill be displayed if thetrajectory of a plannedcatheter is likely to crossan intra-cranial surface.iPlan Flow is able tocalculate a likely fluiddistribution from theplanned catheter positionsto support the physicianin his decision aboutappropriate catheterpositions. These featuresenable the surgeon tobetter plan and place intra-cranial catheters.	Technology isidentical.
Characteristic	Application Device:Molecular FlowSimulations(K201435)	Predicate Device:iPlan Flow(K053164)	Impact onSubstantialEquivalence
Features	Comprehensive TargetPlanning: Automaticallydefines margins aroundthe tumor.	Comprehensive TargetPlanning: Automaticallydefines margins aroundthe tumor.
Features	Guided Entry PointPlanning: The sulcusdetection featureautomatically segmentscerebrospinal fluid spacesas they are potentialleakage pathways.	Guided Entry PointPlanning: The sulcusdetection featureautomatically segmentscerebrospinal fluid spacesas they are potentialleakage pathways.	Equivalent
	Guided CatheterPlanning: Catheterplanning guidelinesindicate potentialbackflow and other drugleakage pathways aroundthe catheter tip in order tomaximize infusatedistribution.	Guided CatheterPlanning: Catheterplanning guidelinesindicate potentialbackflow and other drugleakage pathways aroundthe catheter tip in order tomaximize infusatedistribution.
	3D DistributionSimulation: The likelydistribution of infusate fora given catheter positionis predicted in 3D basedon patient-specificinformation andmathematical modeling.Flux boundary conditionscan be utilized. This moreaccurately models CEDinfusions, in which theinfusate is delivered at aconstant flow rate ratherthan a constant pressure.	3D DistributionSimulation: The likelydistribution of infusate fora given catheter positionis predicted in 3D basedon patient-specificinformation andmathematical modeling.
	3D capillary loss mapsfrom DCE, poroelasticexpansion of theextracellular space, andflux boundary modeling ofthe infusion sources.

E. Comparison of the Technological Characteristics

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F. Summary of Supporting Data

Several tests were performed, in concordance with Duke University, using synthetic, animal and human imaging. Therefore, Molecular Flow Simulations does not raise any new questions regarding safety and effectiveness.

G. Discussion of Performance Testing

All necessary testing has been performed with Molecular Flow Simulations to assure substantial equivalence to the predicate device.

Summary of non-clinical tests:

Molecular Flow Simulations is a software application; therefore no electrical safety or electromagnetic testing was required.

Testing conducted to demonstrate software validation and substantial equivalence included:

. Verification testing that product meets product performance and functional specifications.
Verification that data submitted is stored properly to maintain data integrity (e.g. no loss of data or corruption).
User performance testing to demonstrate adequate instructional utility of the User Manual. ●

The Requirements Traceability Matrix (RTM) provides a mapping between requirements, risks, test cases, and shows related test results. The RTM confirms that there was a test case authored and executed for all requirements and any applicable risks.

After extensive bench testing to performance requirements and criteria established in accordance with application of ISO 14971, risk analysis standard, no new issues of safety, performance, technology or intended use were identified.

H. Conclusion

Upon reviewing the technical information provided in this submission and comparing intended use, principle of operation, performance data, and overall technological characteristics, Molecular Flow Simulations is determined to be substantially equivalent to the predicate device.

Regulation Number and Section

§ 882.4560 Stereotaxic instrument.

(a)
Identification. A stereotaxic instrument is a device consisting of a rigid frame with a calibrated guide mechanism for precisely positioning probes or other devices within a patient's brain, spinal cord, or other part of the nervous system.(b)
Classification. Class II (performance standards).