75F40126Q00351.pdf

SEE ADDENDUMIS CHECKED

CODE 18a. PAYMENT WILL BE MADE BY

CODE

FACILITYCODE

17b. CHECK IF REMITTANCE IS DIFFERENT AND PUT SUCH ADDRESS IN OFFER

OFFEROR

DAOWO66 CODE 16. ADMINISTERED BYCODE

X

X

541715

SIZE STANDARD:

% FOR:SET ASIDE:UNRESTRICTED ORDAO

REQUEST FOR

PROPOSAL

(RFP)

INVITATION

FOR BID (IFB)

10. THIS ACQUISITION ISCODE

REQUEST FOR

QUOTE (RFQ)

14. METHOD OF SOLICITATION

13b. RATING

NORTH AMERICAN INDUSTRY

CLASSIFICATION STANDARD

(NAICS):

SMALL BUSINESS

08/31/2026 1200 ET

08/14/2026

IAN WEISS

(No collect calls)

INFORMATION CALL:

FOR SOLICITATION 8. OFFER DUE DATE/LOCAL TIMEb. TELEPHONE NUMBER a. NAME

4. ORDER NUMBER3. AWARD/ 6. SOLICITATION

75F40126Q00351

5. SOLICITATION NUMBER

SOLICITATION/CONTRACT/ORDER FOR COMMERCIAL ITEMS 1. REQUISITION NUMBER PAGE OF

1 64 1291350OFFEROR TO COMPLETE BLOCKS 12, 17, 23, 24, & 30

TELEPHONE NO.

17a. CONTRACTOR/

15. DELIVER TO

North Bethesda MD 20852

11601 Landsdown St., 13th Floor

ATTN: Ryan Alexander

9. ISSUED BY

7.

2. CONTRACT NO.

EFFECTIVE DATE

1,000

18b. SUBMIT INVOICES TO ADDRESS SHOWN IN BLOCK 18a UNLESS BLOCK BELOW

ISSUE DATE

DELIVERY FOR FREE ON BOARD

(FOB) DESTINATION UNLESS

BLOCK IS MARKED

11.

SEE SCHEDULE

12. DISCOUNT TERMS THIS CONTRACT IS A RATED

ORDER UNDER THE DEFENSE

PRIORITIES AND ALLOCATIONS

SYSTEM - DPAS (15 CFR 700)

13a.

SERVICE-DISABLED

VETERAN-OWNED

SMALL BUSINESS

(SDVOSB)

HUBZONE SMALL

BUSINESS

8(A)

DHHS/FDA/OAGS/DAO WOMEN-OWNED SMALL

BUSINESS (WOSB)

ECONOMICALLY DISADVANTAGED

WOMEN-OWNED SMALL

BUSINESS (EDWOSB)

Silver Spring MD 20993

Building 66

10903 New Hampshire Avenue

The US Food and Drug Administration

WHITE OAK CAMPUS, BUILDING 66

North Bethesda MD 20852

11601 Landsdown St., 13th Floor

ATTN: Ryan Alexander

DHHS/FDA/OAGS/DAO

24.

AMOUNT

23.

UNIT PRICE

22.

UNIT

21.

QUANTITY

20.

SCHEDULE OF SUPPLIES/SERVICES

19.

ITEM NO.

Regulatory Science Tool for Transcranial Ultrasound Modeling Period of Performance: 09/15/2026 to 09/14/2027

1 Regulatory Science Tool for Transcranial 1 EA Ultrasound Modeling

Continued ...

(Use Reverse and/or Attach Additional Sheets as Necessary)

HEREIN, IS ACCEPTED AS TO ITEMS:

DATED

IAN S. WEISS

. YOUR OFFER ON SOLICITATION (BLOCK 5),

INCLUDING ANY ADDITIONS OR CHANGES WHICH ARE SET FORTH

COPIES TO ISSUING OFFICE. CONTRACTOR AGREES TO FURNISH AND DELIVER

ARE

ARE

31c. DATE SIGNED

27b. CONTRACT/PURCHASE ORDER INCORPORATES BY REFERENCE FAR 52.212-4. FAR 52.212-5 IS ATTACHED. ADDENDA

31a. UNITED STATES OF AMERICA (SIGNATURE OF CONTRACTING OFFICER)

30c. DATE SIGNED 31b. NAME OF CONTRACTING OFFICER (Type or print)

ALL ITEMS SET FORTH OR OTHERWISE IDENTIFIED ABOVE AND ON ANY ADDITIONAL

SHEETS SUBJECT TO THE TERMS AND CONDITIONS SPECIFIED.

27a. SOLICITATION INCORPORATES BY REFERENCE (FEDERAL ACQUISITION REGULATION) FAR 52.212-1, 52.212-4. FAR 52.212-3

AND 52.212-5 ARE ATTACHED. ADDENDA

26. TOTAL AWARD AMOUNT (For Government Use Only)

OFFER

STANDARD FORM 1449 (REV. 11/2021)

Prescribed by GSA - FAR (48 CFR) 53.212

ARE NOT ATTACHED.

ARE NOT ATTACHED.

AUTHORIZED FOR LOCAL REPRODUCTION

PREVIOUS EDITION IS NOT USABLE

30b. NAME AND TITLE OF SIGNER (Type or print)

30a. SIGNATURE OF OFFEROR/CONTRACTOR

28. CONTRACTOR IS REQUIRED TO SIGN THIS DOCUMENT AND RETURN

25. ACCOUNTING AND APPROPRIATION DATA

29. AWARD OF CONTRACT: REFERENCE

32e. MAILING ADDRESS OF AUTHORIZED GOVERNMENT REPRESENTATIVE

32c. DATE 32b. SIGNATURE OF AUTHORIZED GOVERNMENT REPRESENTATIVE

ACCEPTED, AND CONFORMS TO THE CONTRACT, EXCEPT AS NOTED:

32a. QUANTITY IN COLUMN 21 HAS BEEN

RECEIVED INSPECTED

40. PAID BY39. S/R VOUCHER NUMBER38. S/R ACCOUNT NUMBER

37. CHECK NUMBER

FINALPARTIAL

36. PAYMENT

FINALPARTIAL

35. AMOUNT VERIFIED

CORRECT FOR

34. VOUCHER NUMBER33. SHIP NUMBER

COMPLETE

32g. E-MAIL OF AUTHORIZED GOVERNMENT REPRESENTATIVE

42d. TOTAL CONTAINERS42c. DATE REC'D (YY/MM/DD)

42b. RECEIVED AT (Location)

42a. RECEIVED BY (Print)

41c. DATE41b. SIGNATURE AND TITLE OF CERTIFYING OFFICER

41a. I CERTIFY THIS ACCOUNT IS CORRECT AND PROPER FOR PAYMENT

STANDARD FORM 1449 (REV. 11/2021) BACK

24.

AMOUNT

23.

UNIT PRICE

22.

UNIT

21.

QUANTITY

20.

SCHEDULE OF SUPPLIES/SERVICES

19.

ITEM NO.

2 Regulatory Science Tool for Transcranial 1 EA

Ultrasound Modeling

32f. TELEPHONE NUMBER OF AUTHORIZED GOVERNMENT REPRESENTATIVE

32d. PRINTED NAME AND TITLE OF AUTHORIZED GOVERNMENT REPRESENTATIVE

64 2 of

Solicitation #: 75F40126Q00351 Title: Regulatory Science Tool for Transcranial Ultrasound Modeling

SOLICITATION

SECTION B – SUPPLIES AND PRICES/COSTS

BACKGROUND

The Office of Science and Engineering Laboratories (OSEL), Center for Devices and Radiological Health (CDRH), FDA, is conducting a regulatory science initiative to develop standardized computational tools for transcranial ultrasound (TUS) simulation. As part of this process, OSEL needs to procure contractor services to develop a computational modeling package for simulating TUS sonication protocols as a Regulatory Science Tool (RST) that can be disseminated to device developers, researchers, and regulators.

COMMERCIAL SERVICES PROCUREMENT

This is a solicitation for services in accordance with the procedures of Federal Acquisition Regulation (FAR) Part 12 – Acquisition of Commercial Products and Commercial Services. This is a Simplified acquisition for a single award, Firm Fixed Price (FFP) type contract.

NOTICE OF FAC

The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular (FAC) 2026-01, effective March 13, 2026. All applicable FAR provisions and clauses cited herein are current as of the date of this solicitation. The full text of provisions and clauses may be accessed electronically at www.acquisition.gov. The Department of Health and Human Services (HHS) Acquisition Regulation (HHSAR) provisions and clauses referenced in this solicitation can be found on the following website:

https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/index.html.

NOTICE OF NAICS

The associated North American Industry Classification System (NAICS) code is 541715 Research and Development in the Physical, Engineering, and Life Sciences (except Nanotechnology and Biotechnology).

CONTRACT REQUIREMENTS

See Section C, Description/Specifications/Statement of Work, for a full description of the services to be acquired.

CONTRACT TYPE

The Government anticipates awarding one (1) Firm Fixed Price type contract.

DELIVERY

The period of performance shall be twelve (12) months from the date of contract award.

Deliverables shall be submitted according to the schedule outlined in Section C.

Section C – Description/Specifications/Statement of Work

Statement of Work Regulatory Science Tool for Transcranial Ultrasound Modeling

Background The Food and Drug Administration (FDA) is responsible for protecting public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation's food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing public health by helping to speed innovations that make medical devices more effective, safer, and more affordable.

The Center for Devices and Radiological Health (CDRH) facilitates medical device innovation by advancing regulatory science, providing industry with predictable, consistent, transparent, and efficient regulatory pathways, and assuring consumer confidence in devices marketed in the U.S.

The Office of Science and Engineering Laboratories (OSEL) supports CDRH's mission by undertaking the highest quality science and providing the best methods, tools, and expertise on emerging and innovative medical technologies.

OSEL needs to expand its capabilities in regulatory science tools aligned with FDA needs in the rapidly developing field of transcranial ultrasound (TUS), which can provide noninvasive access deep within the brain to potentially address numerous neurological conditions. Precise delivery of ultrasonic energy through the intact skull presents a challenge due to the skull's high attenuation and distortion of ultrasound waves. TUS treatments therefore rely on computational modeling for pre-operative treatment planning and estimation of ultrasound exposure metrics. There is currently no consensus on the best modeling technique and tissue parameters needed for this modeling, creating a regulatory burden for CDRH and hindering the rapid development of this potentially life-saving technology.

This project is being pursued under FDA/CDRH/OSEL's regulatory science initiative to develop standardized computational tools that can be disseminated to device developers, researchers, and regulators to mitigate uncertainties and support consistent evaluation of medical device safety and performance.

Objectives The objective of this contract is to develop a computational modeling package for simulating transcranial ultrasound (TUS) sonication protocols as a regulatory science tool (RST) that can be disseminated to device developers, researchers, and regulators. The RST is aimed at accomplishing the following regulatory science objectives:

• Mitigate uncertainties arising from modeling variabilities and enable cross-comparisons across different TUS protocols.

• Determine a standard set of acoustic and thermal tissue properties of neuronal tissues relevant to TUS treatment planning.

• Promote the use of consensus acoustic and thermal tissue properties across the TUS research and development community.

• Streamline clinical trial design and promote consistent review of pre-market submissions.

• Enhance patient safety through validated, standardized computational protocols.

Scope The Contractor shall develop a computational modeling package for simulating transcranial ultrasound sonication protocols. The scope includes development of computational forward models of acoustic propagation and thermal spread, validation using shared measurement datasets, determination of a standard reference tissue properties set, sensitivity analysis to identify critical parameters, development of baseline/best-case/worst-case patient models for ultrasound safety, transducer modeling, and comprehensive documentation.

The scope does not require development of entirely new simulation algorithms from scratch; the Contractor shall leverage appropriate algorithms and open-source toolsets such as k-Wave, BabelViscoFDTD, etc. The scope allows for two alternative development approaches:

Single-technique RST Development: The Contractor shall develop one computational modeling package based on a single modeling technique—either Finite Difference Time Domain (FDTD) or Pseudo-Spectral Time Domain (PSTD)—with technical justification for the selected technique.

Dual-technique RST Development: The Contractor shall develop two complementary computational modeling packages (one FDTD-based and one PSTD-based), including cross-validation between the two methods and guidance on appropriate use cases for each.

• Alternative Numerical Techniques: Offerors may propose alternative techniques, including finite element or hybrid methods, in place of or in addition to FDTD and PSTD.

• Any alternative-technique proposal shall provide technical justification demonstrating suitability for TUS applications, including treatment of heterogeneous media, frequency-dependent absorption, and complex geometries.

• The proposal shall include comparative performance analysis versus FDTD/PSTD, relevant biomedical-ultrasound validation evidence, and demonstration that all specified technical performance standards can be achieved.

• The proposal shall identify any necessary scope modifications while maintaining equivalent regulatory-science value and shall include a risk assessment with mitigation strategies.

• All deviations from the baseline FDTD/PSTD approach require Government approval prior to contract award.

• Shared Development Efforts applicable to the selected modeling approach shall include technical evaluation of available toolsets and libraries, development of common user-interface, data-structure, and visualization infrastructure, tissue-property mapping, standard reference tissue properties with uncertainties, benchmark validation datasets, patient reference models, and comprehensive documentation.

• For dual-technique development, the Contractor shall provide comparative analysis of FDTD and PSTD performance and accuracy, cross-validation between methods, and guidance on appropriate use cases for each technique.

• Solver-specific development shall include the three-dimensional TUS acoustic and thermal model, solver-specific verification and validation, and integration of each solver with the shared infrastructure.

• Offerors shall identify allocation of development responsibilities among the prime contractor, subcontractors, or collaborating organizations and shall describe relevant organizational qualifications and the integration plan.

• Offerors shall provide budget and resource justification consistent with the proposed single-technique or dual-technique development approach.

Deliverables / Tasks

Task 1 – Technical Evaluation, Architecture Definition, Prototype Model Development The Contractor shall conduct a comprehensive technical evaluation of available modeling techniques and toolsets, define the complete tool architecture, develop a prototype 3D TUS acoustic and thermal model with single-element transducer capability, establish the initial tissue properties reference set with uncertainty ranges, and create analytical solutions-based test cases for model verification. Specific requirements include:

• 1.1 Technical Evaluation and Consultation: Evaluate state-of-the-art open-source tools including k-Wave, BabelViscoFDTD, and other relevant platforms; assess trade-offs between PSTD, FDTD, and FEM techniques.

• - Document the technical-evaluation methodology, findings, and recommendations.

• - Provide guidance on critical modeling assumptions, including near-field versus far-field transducer approaches, boundary conditions, tissue heterogeneity, nonlinear propagation, implications of excluding shear waves, mesh-refinement strategy, and treatment of frequency-dependent absorption and dispersion.

• 1.2 Tool Architecture and User Interface Definition: Define high-level specifications for tool GUI and/or CLI; develop architecture documentation including class design, user case specifications, module dependencies, and data flow.

• - Architecture documentation shall address extensibility considerations.

• - The Contractor shall specify interoperability requirements with existing treatment-planning platforms.

• 1.3 Prototype 3D Model Development: Develop a prototype 3D TUS acoustic model incorporating single-element transducer geometry and thermal deposition modeling; conduct a verification and sensitivity study comparing the top two modeling techniques.

• - The prototype shall include configurable single-element transducer geometry, three-dimensional device and patient geometry, transducer placement and positioning, phase-aberration modeling in heterogeneous media, and frequency-dependent acoustic properties.

• 1.4 Tissue Properties Reference Set Establishment: Identify all relevant tissue properties for skull, scalp, CSF, white matter, grey matter, and other tissues with baseline values and uncertainty ranges.

• - For each relevant tissue, document density, sound speed, ultrasound attenuation coefficient, ultrasound absorption coefficient, thermal conductivity, specific heat capacity, perfusion rate, and the nonlinearity parameter B/A where applicable, including baseline values and uncertainty ranges.

• - Provide literature sources and technical justification for each parameter value and document uncertainty and variability across patient populations.

• 1.5 Analytical Test Cases Development: Create minimum three (3) analytical solutions-based test cases covering acoustic propagation in homogeneous media, acoustic propagation through layered media, and thermal deposition in simplified geometries.

• - Provide source code and comprehensive documentation for each analytical test case.

• - Establish quantitative acceptance criteria for each analytical test case.

Task 1 Deliverables (End of 1st Quarter):

• Deliverable 1: Technical Evaluation Report & High-Level User Definition of Tool (Architecture documentation in PDF)

• Deliverable 2: Prototype 3D TUS acoustic + thermal model with single-element transducer and preliminary sensitivity analysis (Source code + technical report in PDF)

• Deliverable 3: Tissue Properties Reference Set with Baseline and Uncertainty Ranges (Database file + documentation in PDF)

• Deliverable 4: Test Cases for Model Verification – analytical solutions based, 3 or more (Source code + documentation)

Task 2 – Multi-Element Array Implementation, Validation Dataset Development, and Property Mapping Enhancement The Contractor shall extend the 3D acoustic model to support multi-element transducer arrays (4– 128 elements) at multiple frequencies, develop tissue property mapping techniques from MRI/CT imaging, and generate comprehensive benchmark validation datasets across multiple ex-vivo skulls and frequencies. Specific requirements include:

• 2.1 Multi-Element Transducer Array Implementation: Extend the 3D acoustic model to include multi-element phased array transducers with support for 4–128 elements, individual element phase and amplitude control, and support for at least two distinct operating frequencies.

• - The multi-element phased-array implementation shall model element-to-element coupling and include time-reversal-based phase-correction algorithms.

• - The array implementation shall support arbitrary element geometries, element apodization and weighting schemes, multi-focus and electronically steered beam patterns, and duty cycle and pulsing protocol modeling for thermal safety assessment.

• - The Contractor shall validate the multi-element array implementation against published benchmark problems or manufacturer specifications.

• 2.2 Tissue Property Mapping Technique Development: Develop a baseline property mapping technique to translate patient-specific medical imaging data (CT/MRI) into acoustic and thermal parameters.

• - For CT imaging, implement mapping from Hounsfield Units (HU) to density, sound speed, and attenuation using established empirical relationships.

• - For MRI imaging, develop or implement virtual-CT generation techniques to enable

MRI-only workflows.

• - The mapping method shall account for imaging-modality dependencies, scanner-specific calibrations, spatial interpolation, and partial-volume effects at tissue boundaries.

• - The Contractor shall document assumptions, limitations, and expected accuracy of the property-mapping technique.

• 2.3 Benchmark Validation Dataset Generation: Generate comprehensive benchmark problem solutions at minimum four (4) frequencies (250 kHz, 500 kHz, 670 kHz, and 1000 kHz) with ex vivo skull datasets for minimum five (5) human skull specimens.

• - Benchmark solutions shall include both single-element and multi-element array configurations.

• - The benchmark set shall span skull geometries representing thin/thick and high-/low-attenuation conditions and shall include complete specifications of boundary conditions, material properties, and source definitions.

• - Each ex vivo skull dataset shall include CT imaging data, measured acoustic properties at multiple frequencies, hydrophone-based focal-pressure measurements, and documentation of specimen preparation and measurement protocols.

Task 2 Deliverables (End of 2nd Quarter):

• Deliverable 5: 3D TUS Model with multi-element transducer array (4–128 elements, 2 frequencies) (Source code + validation report in PDF)

• Deliverable 6: Tissue Property Mapping Technique from MRI/CT – baseline (Technical note in PDF)

• Deliverable 7: Benchmark Validation Datasets, 5 skulls at 4 frequencies (Data files + technical note in PDF)

Task 3 – Prototype RST Development, Comprehensive Sensitivity Analysis, Validation Report, and Reference Database Finalization The Contractor shall develop a prototype RST with comprehensive sensitivity analysis capabilities, complete validation of all acoustic and thermal modeling capabilities using ex vivo skulls with statistical analysis, finalize the reference tissue property database, and create three patient reference models (baseline, best-case, and worst-case). Specific requirements include:

• 3.1 Prototype RST Development with Comprehensive Sensitivity Analysis: Integrate all modeling capabilities from Tasks 1 and 2 into a cohesive prototype RST package; conduct systematic sensitivity analysis using OAT parameter variation, DOE, and/or Monte Carlo approaches.

• - Develop a software module that enables users to define custom ultrasonic transducer or multi-element array geometries through an intuitive easy-to-use interface.

• - The module shall allow specification of single-element transducers, including spherical, planar, cylindrical, and custom shapes, and multi-element arrays with flexible element positioning, dimensions, curvature, spatial arrangement, operating frequency, excitation amplitude, and phase.

• - The module shall support interactive visualization of geometry, import from standard file formats, parametric definition of common transducer types, and validation with error checking.

• - The module shall support standard characterization methods, including pressure-field measurements on user-specified surfaces, acoustic power output calculations, focal characteristics including location, volume, and peak pressure, and beam width and directivity patterns.

• - The module shall provide visualization of pressure-field distributions, beam patterns, and focal characteristics and shall enable export of characterization results in standard formats.

• 3.2 Final Acoustic and Thermal Validation: Validate with hydrophone measurements at multiple spatial locations and temperature measurements; report mean error, standard deviation, and maximum error for all validation metrics with rigorous statistical analysis.

• - Complete and document final validation using ex vivo skull measurements and anatomically representative tissue-mimicking phantoms.

• - Acoustic validation shall use hydrophone measurements at multiple spatial locations and assess focal location accuracy (3D position), focal volume accuracy using -3 dB and -6 dB contours, peak pressure amplitude accuracy, and phase aberration correction accuracy. Acoustic validation shall be performed at a minimum of three (3) frequencies.

• - Thermal validation shall use temperature measurements obtained with thermocouples, fiber-optic sensors, or MR thermometry and shall assess temperature-rise prediction accuracy at the focal region and skull surface, thermal dose calculations such as CEM43 or equivalent, and cooling-phase predictions.

• - Thermal validation shall include multiple exposure conditions, including continuous-wave, pulsed, and varying-duty-cycle conditions.

• - Statistical analysis shall include regression analysis, correlation coefficients (R-squared), statistical significance, quantification of prediction uncertainty, identification of systematic bias, comparison against applicable established standards, and uncertainty quantification addressing measurement, parameter, and numerical uncertainty.

• 3.3 Final Reference Tissue Property Database Development: Finalize the tissue property database incorporating refinements based on sensitivity analysis, literature review, uncertainty ranges, and population variability where available.

• - The final database shall incorporate reconciliation of conflicting literature values with documented technical rationale and uncertainty ranges derived from literature variability and measurement uncertainty.

• - The database shall include frequency-dependent and temperature-dependent parameters and, where available, population variability for pediatric, adult, and geriatric populations and healthy versus diseased tissue states.

• - The database shall be provided in a machine-readable format such as CSV, JSON, or HDF5 and shall include schema documentation.

• - The database documentation shall include guidance on parameter selection for different modeling scenarios and shall identify known gaps and limitations in available tissue-property data.

• 3.4 Patient Reference Models Development: Create three (3) patient reference models— Baseline (median/typical patient), Best-Case (thin skull, low attenuation, favorable geometry), and Worst-Case (thick skull, high attenuation, unfavorable geometry).

• - For each patient reference model, provide a complete geometric representation of the skull, brain, scalp, and cerebrospinal fluid in standard formats such as STL or VTK.

• - For each model, provide assigned tissue properties with technical justification and

CT/MRI source data, anonymized if based on a real patient.

• - For each model, provide pre-computed simulation results for standard transducer configurations and documentation explaining the model-selection rationale and intended use cases.

• - For each model, provide validation data comparing predictions to measurements when such data are available.

Task 3 Deliverables (End of 3rd Quarter):

• Deliverable 8: Prototype RST with comprehensive Sensitivity Analysis – Alpha/Beta level (Source code + technical report in PDF)

• Deliverable 9: Validation Report – Acoustic and thermal, with Statistical Analysis (Validation Report in PDF)

• Deliverable 10: Final Tissue Property Database with Uncertainty Ranges and Source Documentation (Database file for integration into Technical Reference Manual)

• Deliverable 11: Three Patient Reference Models – Baseline, Best-Case, and Worst-Case for mechanical and thermal risk (Model files + documentation)

Task 4 – Complete RST Package & Documentation, Enhanced Property Mapping, and Dissemination Support The Contractor shall finalize and package the complete RST v1.0 with all source code and test cases for public dissemination, prepare comprehensive documentation, develop an enhanced tissue property mapping technique, prepare a scientific publication draft, and support FDA dissemination activities. Specific requirements include:

• 4.1 Complete RST Package v1.0 Development: Finalize all software components into a production-ready RST package including integrated modeling capabilities, user interface, tissue property database, and automated testing suite; prepare source code for public repository via Git.

• - The production-ready RST shall include all analytical and benchmark test cases for verification and an automated testing suite with regression tests.

• - The Contractor shall perform performance profiling and optimization sufficient to meet the computational-time requirements.

• - The final package shall support Windows, Linux, and macOS and shall be packaged for straightforward installation with dependency management.

• - The public source-code repository shall contain complete version history.

• 4.2 Complete Documentation Package Preparation: Prepare three (3) integrated PDF documents: PDF 1 – User Guide; PDF 2 – Technical Reference Manual; PDF 3 – Verification and Validation Report.

• - The User Guide shall include installation procedures and system requirements, step-by-step operating instructions, tutorial examples demonstrating key capabilities, troubleshooting guidance, and a quick-reference guide.

• - The Technical Reference Manual shall include the underlying acoustic and thermal physics and numerical methods, modeling assumptions and known limitations, best practices, pitfalls and common errors, tissue-property database documentation, guidance on property selection and medical-image property mapping, and API documentation.

• - The Technical Reference Manual shall include function and class references and developer code examples addressing batch processing, parameter sweeps, integration with external tools, and custom transducer geometry definition.

• - The Verification and Validation Report shall document verification against analytical benchmark problems, hydrophone and temperature-measurement validation, statistical analysis, uncertainty quantification, and recommendations for uncertainty reduction and safety evaluation.

• 4.3 Enhanced Tissue Property Mapping Technique Development: Develop enhanced version of tissue property mapping technique building on the baseline version from Task 2, including advanced algorithms and validation against direct acoustic measurements.

• 4.4 Scientific Publication Preparation: Draft scientific publication for submission to peer-reviewed journal, prepared for co-authorship with FDA staff as appropriate.

• 4.5 Dissemination Support: Support FDA dissemination activities including stakeholder meetings and workshops, preparation of dissemination materials, and coordination with FDA on public repository setup.

Task 4 Deliverables (End of 4th Quarter):

• Deliverable 12: Complete RST Package v1.0 with Source Code and All Test Cases (Complete software package via Git repository)

• Deliverable 13: Complete Documentation Package – PDF 1: User Guide; PDF 2: Technical Reference Manual; PDF 3: Validation Report

• Deliverable 14: Tissue Property Mapping Technique from MRI/CT – enhanced version (Source code + Technical note in PDF)

• Deliverable 15: Scientific Publication Draft for Peer-Reviewed Journal (1 electronic copy in Word/LaTeX/OverLeaf)

Chemical Quality Requirements Not applicable to this acquisition.

Performance Standards The final modeling package shall meet the following technical performance standards:

• Focal location prediction error < 2 mm

• Focal volume prediction error < 10 mm³

• Peak pressure prediction error < 25%

• Temperature prediction error < 1°C

• Computation time < 16 hours for a full patient-specific simulation at clinically needed mesh resolutions on typical computational hardware

Code Quality Requirements

• All software developed under this contract shall be well-commented and modular and shall follow software-engineering best practices.

• All source code shall be version controlled using Git with complete version history.

• The Contractor shall perform performance profiling and optimization needed to meet the computational-time requirements.

• The Contractor shall provide separate modular tests for critical functions.

• The Contractor shall perform regression-type testing to ensure stability across updates.

• Underlying methods shall be unit-tested using analytical solutions where applicable.

Interoperability Requirements

• Open-source toolsets are preferred to maximize accessibility and adoption.

• Standard input formats shall include DICOM for medical images and STL for geometries, as applicable.

• Standard output formats shall include VTK, Nifti, and HDF5 for visualization and data exchange, as applicable.

• The modeling package shall provide command-line and/or GUI interface options.

• The modeling package shall be compatible with Windows, Linux, and macOS.

Documentation Standards

• All documentation shall be written in clear, professional English suitable for FDA reviewers, device developers, and researchers.

• Database files shall include metadata documenting sources, uncertainties, and applicability ranges.

• All documentation provided in PDF format shall contain searchable text and functional hyperlinks where applicable.

• Source code shall contain inline comments explaining complex algorithms.

• Deliverables shall be organized using a logical directory structure and clear naming conventions.

Data Requirements

• All datasets shall be provided in standard formats with comprehensive metadata enabling independent use.

• Metadata shall conform to FAIR principles: Findable, Accessible, Interoperable, and

Reusable.

• Validation datasets shall include uncertainty quantification for all measurements.

Contractor Qualification Requirements The Contractor shall possess the following minimum qualifications at the time of proposal submission:

• Technical Expertise: Principal investigator or co-investigator on a minimum of two (2) completed research projects involving TUS simulation within the past five (5) years, OR development or significant contribution to open-source TUS simulation tools (e.g., k-Wave, BabelViscoFDTD, or equivalent).

• Peer-Reviewed Publications: A minimum of three (3) peer-reviewed journal articles on ultrasound propagation through heterogeneous biological media within the past fifteen (15) years, with at least one (1) addressing transcranial ultrasound applications.

• Software and Compute Access: Immediate access to and demonstrated proficiency with at least one TUS simulation platform and computational infrastructure capable of running full 3D patient-specific TUS simulations within the performance standards specified in this SOW.

Notification of Unavailability

If any required capability, personnel, or resource identified in the proposal becomes unavailable, the Contractor shall notify the Project Officer within 14 days of the award date.

Pricing [See Section J – Pricing]

Delivery All deliverables required under this contract shall be submitted electronically to the Contracting Officer's Representative (COR) via email or secure file transfer as directed. The Government shall have 15 business days to review each deliverable. If revisions are required, the Contractor shall resubmit within 10 business days of receiving feedback.

The Contractor shall guarantee that all required deliverables shall be submitted in accordance with the schedule specified in the Statement of Work. Electronic deliverables shall be submitted to:

US Food and Drug Administration 10903 New Hampshire Ave Silver Spring, MD 20993

Sanjay Yengul Sanjay.Yengul@fda.hhs.gov

Vendor shall contact the Project Officer by phone or email to schedule any required coordination within 14 days of the award date. No deliverables will be accepted without prior authorization from the Project Officer.

Government-Furnished Property, Material, Equipment, or Information (GFP, GFM, GFE, or GFI) The Government will provide the following to the Contractor:

• Access to FDA Technical Expertise: FDA subject matter experts will be available for consultation on regulatory requirements and technical specifications.

• Computational Resources: FDA may provide access to cloud computing resources for model development and validation, subject to availability and security requirements.

• Reference Materials: FDA will provide access to relevant guidance documents, published literature, and regulatory science resources related to TUS devices.

• Collaboration Coordination: FDA will coordinate with collaborating institutions in the U.S.

and/or abroad as needed to support the Contractor's work. The Contractor shall be responsible for all other equipment, software licenses, materials, validation datasets, commercial-tool licenses if used, cloud-computing resources beyond those furnished by FDA, and computational and measurement equipment required to complete the work.

Collaboration and Communication

• The Contractor shall support collaborative development through the ability to exchange and run models at the development site and at FDA.

• The Contractor shall participate in bi-weekly virtual check-in meetings with FDA technical staff to discuss progress, challenges, and technical decisions.

mailto:Sanjay.Yengul@fda.hhs.gov

• The Contractor shall provide quarterly progress reports summarizing work completed with quantitative metrics, challenges and mitigation actions, plans for the next quarter, updated timelines when needed, and current project risks.

• The Contractor shall respond to FDA technical inquiries within five (5) business days.

• The Contractor shall provide at least ten (10) business days advance notice of anticipated delays, including an explanation and proposed recovery plan.

Risk Mitigation

• Throughout contract performance, the Contractor shall proactively identify and communicate risks to project success, including resource availability, validation-data availability or quality, tissue-property uncertainty, generalization across transducers and sonication protocols, numerical implementation, software integration, compatibility, and computational performance.

• For each identified risk, the Contractor shall assess likelihood and potential impact, propose mitigation actions and timelines, monitor risk status, and communicate material changes to

FDA.

Security and Privacy The Contractor shall comply with all FDA security requirements for handling sensitive information. All work products shall be treated as sensitive but unclassified unless otherwise specified. The Contractor shall ensure that all software developed under this contract is free from malicious code and complies with FDA cybersecurity requirements for software tools.

Information Technology Procurements – Security and Privacy Language

This section lists the standards of security and privacy for information and information technology that apply to this contract.

The source of these standards is the FDA policy titled Food and Drug Administration Information Technology Procurements – Security and Privacy Language, Version 3.0 (May 2022), Appendix B, Standards. (Internal link to policy document, this link will not work outside the FDA network).

Table of Contents

I. Procurements Requiring Information Security and/or Physical Access Security

1. Baseline Security Requirements 4

2. Training Requirements 8

3. Rules of Behavior 8

4. Incident Response 8

5. Position Sensitivity Designations 10 https://fda.sharepoint.com/:b:/r/sites/insideFDA-IT-Cybersecurity/OIS%20Document%20Library/Contract-SOW/FDA%20Information%20Technology%20Procurements%20-%20Security%20And%20Privacy%20Language.pdf?csf=1&web=1&e=75ktCh

6. Homeland Security Presidential Directive (HSPD)-12 10

7. Roster 10

8. Contract Initiation and Expiration 10

9. Records Management and Retention 11

II. Privacy Act 12

III. Security Requirements for GOCO and COCO Resources 12

IV. Contracts Involving Cloud Services 17

1. HHS FedRAMP Privacy and Security Requirements. 17

2. Protection of Information in a Cloud Environment 18

3. Assessment and Authorization (A&A) Process 19

4. Reporting and Continuous Monitoring 20

5. Configuration Baseline 21

6. Incident Reporting 21

7. Media Transport 22

8. Boundary Protection: Trusted Internet Connections (TIC) 22

V. Other IT Procurements 22

1. Hardware Procurements 22

2. Non-Commercial and Open-Source Computer Software Procurements 23

3. Information Technology Application Design, Development, or Support 23

4. Physical Access to Government Controlled Facilities 23

VI. Deliverables 24

Procurements Requiring Information Security and/or Physical Access Security

Baseline Security Requirements

Applicability. The requirements herein apply whether the entire contract or modification (hereafter "contract"), or portion thereof, includes either or both of the following:

Access (Physical or Logical) to Government Information: A Contractor (and/or any subcontractor) will have or will be given the ability to have, routine physical (entry) or logical (electronic) access to government information.

Operate a Federal System Containing Information: A Contractor (and/or any subcontractor) will operate a federal system and information technology containing data that supports the FDA mission. In addition to the Federal Acquisition Regulation (FAR) Subpart 2.1 definition of "information technology" (IT), the term as used in this section includes computers, ancillary equipment (including imaging peripherals, input, output, and storage devices necessary for security and surveillance), peripheral equipment designed to be controlled by the central processing unit of a computer, software, firmware and similar procedures, services (including support services), and related resources.

Safeguarding Information and Information Systems. All government information and information systems must be protected in accordance with FDA policies and level of risk. At a minimum, the Contractor (and/or any subcontractor) must

i. Protect the:

• Confidentiality, which means preserving authorized restrictions on access and disclosure, based on the security terms found in this contract, including means for protecting personal privacy and proprietary information;

• Integrity, which means guarding against improper information modification or destruction, and ensuring information non-repudiation and authenticity; and

• Availability, which means ensuring timely and reliable access to and use of information.

ii. Categorize all information owned and/or collected/managed on behalf of FDA and information systems that store, process, and/or transmit FDA information in accordance with FIPS 199 and National Institute of Standards and Technology (NIST) Special Publication (SP) 800-60, Volume II: Appendices to Guide for Mapping Types of Information and Information Systems to Security Categories.

Based on information provided by the System/Data Owner, ISSO, privacy representative, or other POC, the impact level for each Security Objective (Confidentiality, Integrity, and Availability) and the Overall Impact Level, which is the highest watermark of the three factors of the information or information system are the following:

(i) Confidentiality: ☒Low ☐Moderate ☐High

(ii) Integrity: ☒Low ☐Moderate ☐High

(iii) Availability: ☒Low ☐Moderate ☐High

(iv) Overall Impact Level: ☒Low ☐Moderate ☐High

iii. Based on the agreed-upon level of impact, implement the necessary safeguards to protect all information systems and information collected and/or managed on behalf of FDA regardless of location or purpose.

iv. Report any discovered or unanticipated threats or hazards by either the agency or contractor, or if existing safeguards have ceased to function immediately after discovery, within one (1) hour or less, to the government representative(s). This includes notifying the FDA Cybersecurity and Infrastructure Operations Coordination Center (CIOCC) within one (1) hour of discovery/detection in the event of a cybersecurity or privacy incident.

http://csrc.nist.gov/publications/nistpubs/800-60-rev1/SP800-60_Vol2-Rev1.pdf http://csrc.nist.gov/publications/nistpubs/800-60-rev1/SP800-60_Vol2-Rev1.pdf http://csrc.nist.gov/publications/nistpubs/800-60-rev1/SP800-60_Vol2-Rev1.pdf http://csrc.nist.gov/publications/nistpubs/800-60-rev1/SP800-60_Vol2-Rev1.pdf

v. Adopt and implement all applicable policies, procedures, controls, and standards required by the FDA Information Security Program to ensure the confidentiality, integrity, and availability of government information and government information systems for which the Contractor is responsible under this contract or to which the Contractor may otherwise have access under this contract. Obtain the FDA Information Security Program security requirements, outlined in the FDA Information Security and Privacy Protection (IS2P) policy, by contacting the CO/COR or emailing your ISSO.

Privacy Act. Comply with the Privacy Act requirements (when applicable), and tailor FAR and HHSAR clauses as needed.

Privacy Compliance. Comply with the E-Government Act of 2002, NIST SP 800-53, and applicable FDA privacy policies and complete all the requirements below:

i. Per the Office of Management and Budget (OMB) Circular A-130, Personally Identifiable Information (PII), is "information that can be used to distinguish or trace an individual's identity, either alone or when combined with other information that is linked or linkable to a specific individual." Examples of PII include, but are not limited to the following: Social Security number, date and place of birth, mother's maiden name, biometric records, etc.

ii. Based on information provided by the ISSO, System/Data Owner, or other security or privacy representative, it has been determined that this solicitation/contract involves:

☒ No PII ☐ PII

iii. The Contractor must support the agency with conducting a Privacy Threshold Analysis (PTA) for the information system and/or information handled under this contract to determine whether or not a full Privacy Impact Assessment (PIA) needs to be completed.

1. If the results of the PTA show that a full PIA is needed, the Contractor must support the agency with completing a PIA for the system or information after completion of the PTA and in accordance with HHS and FDA policy and OMB M- 03-22, Guidance for Implementing the Privacy Provisions of the E- Government Act of 2002. The PTA/PIA must be completed and approved prior to active use and/or collection or processing of PII and is a prerequisite to agency issuance of an authorization to operate

(ATO).

2. The Contractor must support the agency in reviewing the PIA at least every three years throughout the system development lifecycle (SDLC)/information lifecycle, or when determined by the agency that a review is required based on a major change to the system, or when new types of PII are collected that introduces new or increased privacy risks, whichever comes first.

Controlled Unclassified Information (CUI). Executive Order 13556 defines CUI as "information that laws, regulations, or Government-wide policies require to have safeguarding or dissemination controls, excluding classified information." The Contractor (and/or any subcontractor) must comply with Executive Order 13556, Controlled Unclassified Information, (implemented at 3 CFR, part 2002) when handling CUI. 32 C.F.R. 2002.4(aa) As implemented the term "handling" refers to "…any use of CUI, including but not limited to marking, safeguarding, transporting, disseminating, re-using, and disposing of the information." 81 Fed.

Reg. 63323. The requirements below apply only to nonfederal systems that process, store, or transmit CUI, or that provide security protection for such components. All sensitive information that has been identified as CUI by a regulation or statute, handled by this solicitation/contract, must be:

Marked appropriately;

Disclosed to authorized personnel on a Need-To-Know basis;

Protected in accordance with NIST SP 800-53, Security and Privacy Controls for Information Systems and Organizations applicable baseline if handled by a contractor system operated on behalf of the agency, or NIST SP 800-171, Protecting Controlled Unclassified Information in Nonfederal Information Systems and Organizations if handled by internal Contractor system; and

Returned to FDA control, destroyed when no longer needed, or held until otherwise directed.

Information and/or data must be disposed of in accordance with NIST SP 800- 88, Guidelines for Media Sanitization.

Protection of Sensitive Information. For security purposes, information is or may be sensitive because it requires security to protect its confidentiality, integrity, and/or availability. The Contractor (and/or any subcontractor) must protect all government information that is or may be sensitive by securing it with a solution that is validated with current FIPS 140 validation certificate from the NIST CMVP.

Government Furnished Equipment (GFE) for Foreign Travel. FDA personnel are prohibited from taking GFE when participating in personal, unofficial travel to foreign countries. FDA personnel are strictly prohibited from teleworking using GFE in foreign countries. FDA personnel must also request loaner GFE from the FDA Foreign Travel program for official travel to any foreign country. Please see the FDA IS2P, Appendix T Government Furnished Equipment for Foreign Travel.

Confidentiality and Nondisclosure of Information. Any information provided to the contractor (and/or any subcontractor) by FDA or collected by the contractor on behalf of FDA must be used only for the purpose of carrying out the provisions of this contract and must not be disclosed or made known in any manner to any persons except as may be necessary in the performance of the contract. The Contractor assumes responsibility for protection of the confidentiality of Government records and must ensure that all work performed by its employees and subcontractors must be under the supervision of the Contractor. Each Contractor employee or any of its subcontractors to whom any FDA records may be made available or disclosed must be notified in writing by the Contractor that information disclosed to such employee or subcontractor can be used only for that purpose and to the extent authorized herein. The confidentiality, integrity, and availability of such information must be protected in accordance with HHS and FDA policies. Unauthorized disclosure of information will be subject to the HHS and FDA sanction policies and/or governed by the following laws and regulations:

18 U.S.C. 641 (Criminal Code: Public Money, Property or Records);

18 U.S.C. 1905 (Criminal Code: Disclosure of Confidential Information); and

44 U.S.C. Chapter 35, Subchapter I (Paperwork Reduction Act).

Internet Protocol Version 6 (IPv6). All procurements using Internet Protocol must comply with OMB Memorandum M-05-22, Transition Planning for Internet Protocol Version 6 (IPv6).

Information and Communications Technology (ICT). ICT products and services from prohibited entities/sources must not be used/acquired in compliance with Public Law 115-232, Section 889 Parts A and B, FAR 4.21, FAR 52.204.23, FAR 52.204.24, and FAR 52.204.25. The contractor (and/or any subcontractor) must notify the government if they identify prohibited ICT products and/or services are used during the contract performance.

Government Websites. All new and existing public-facing government websites must be securely configured with Hypertext Transfer Protocol Secure (HTTPS) using the most recent version of Transport Layer Security (TLS). In addition, HTTPS must enable HTTP Strict Transport Security (HSTS) to instruct compliant browsers to assume HTTPS at all times to reduce the number of insecure redirects and protect against attacks that attempt to downgrade connections to plain HTTP. For internal-facing websites, HTTPS is not required, but it is highly recommended. Consult the HHS Policy for Internet and Email Security for additional information.

Contract Documentation. The Contractor must use provided templates, policies, forms, and other agency documents to comply with contract deliverables as appropriate.

Standard for Encryption. The Contractor (and/or any subcontractor) must:

Comply with the…