DARPA-BAA-16-09.pdf

Broad Agency Announcement Neural Engineering System Design (NESD)

BIOLOGICAL TECHNOLOGIES OFFICE

DARPA-BAA-16-09

January 21, 2016

DARPA-BAA-16-09, NESD

TABLE OF CONTENTS

PART I: OVERVIEW INFORMATION

PART II: FULL TEXT OF ANNOUNCEMENT

1. Funding Opportunity Description

2. Award Information

3. Eligibility Information

3.1. ELIGIBLE APPLICANTS

3.2. COST SHARING/MATCHING

4. Application and Submission Information

4.1. ADDRESS TO REQUEST APPLICATION PACKAGE

4.2. CONTENT AND FORM OF APPLICATION SUBMISSION

4.3. FORMATTING CHARACTERISTICS

4.4. SUBMISSION DATES AND TIMES

4.5. FUNDING RESTRICTIONS

5. Application Review Information

5.1. EVALUATION CRITERIA

5.2. REVIEW AND SELECTION PROCESS

6. Award Administration Information

6.1. SELECTION NOTICES

6.2. ADMINISTRATIVE AND NATIONAL POLICY REQUIREMENTS

6.3. REPORTING

6.4. ELECTRONIC SYSTEMS

7. Agency Contacts

8. Other Information

8.1. INTELLECTUAL PROPERTY

9. APPENDIX 1 – Volume II checklist

PART I: OVERVIEW INFORMATION

Federal Agency Name – Defense Advanced Research Projects Agency (DARPA), Biological Technologies Office

Funding Opportunity Title – Neural Engineering System Design (NESD) Announcement Type – Initial Announcement Funding Opportunity Number – DARPA-BAA-16-09 Catalog of Federal Domestic Assistance Numbers (CFDA) - 12.910 Research and

Technology Development Dates o Posting Date – January 21, 2016 o Proposal Abstract Due Date – February 25, 2016 o Proposal Due Date – April 14, 2016 o BAA Closing Date – April 14, 2016 o Proposers Days – February 2-3, 2016 https://www.fbo.gov/spg/ODA/DARPA/CMO/DARPA-SN-16-16/listing.html

Concise description of the funding opportunity – DARPA seeks proposals to design, build, demonstrate, and validate a neural interface system capable of recording from more than one million neurons and stimulating more than one hundred thousand neurons in proposer-defined regions of the human sensory cortex (e.g., visual cortex or auditory cortex). The complete system must demonstrate high-precision detection, transduction, and encoding of neural activity.

Total amount of money to be awarded – Total funding up to approximately $60M will be awarded. The actual amount of resources available will depend on the quality of proposals received, successful achievement of milestones and availability of funds.

Anticipated individual awards - Multiple awards are anticipated.

Types of instruments that may be awarded - Procurement contract, cooperative agreement, or Other Transaction.

Any cost sharing requirements – None Agency contact

Dr. Phillip Alvelda, Program Manager, DARPA/BTO BAA Coordinator: DARPA-BAA-16-09@darpa.mil

ATTN: DARPA-BAA-16-09

675 North Randolph Street Arlington, VA 22203-2114 https://www.fbo.gov/spg/ODA/DARPA/CMO/DARPA-SN-16-16/listing.html mailto:name@darpa.mil

PART II: FULL TEXT OF ANNOUNCEMENT

1. Funding Opportunity Description

The Defense Advanced Research Projects Agency often selects its research efforts through the Broad Agency Announcement (BAA) process. This BAA is being issued, and any resultant selection will be made, using procedures under Federal Acquisition Regulation (FAR) 35.016 and the Department of Defense Grant and Agreement Regulatory System (DoDGARS) Part 22 for Grants and Cooperative Agreements. Any negotiations and/or awards will use procedures under FAR 15.4, Contract Pricing, as specified in the BAA (including DoDGARS Part 22 for Grants and Cooperative Agreements). Proposals received as a result of this BAA shall be evaluated in accordance with evaluation criteria specified herein through a scientific review process. DARPA BAAs are posted on the Federal Business Opportunities (FedBizOpps) website, https://www.fbo.gov/, and, as applicable, the Grants.gov website at http://www.grants.gov/. The following information is for those wishing to respond to the BAA.

The most advanced neural interfaces approved to date by the Food and Drug Administration (FDA) for use in human clinical studies are based on electrical recording and stimulation through implants with, at most, hundreds of passive wire electrodes substantially larger in size and pitch than the underlying neurons, drastically limiting the amount and quality of information that can be read from, or stimulated, within the brain.

DARPA’s Neural Engineering System Design (NESD) program is seeking innovative research proposals to design, fabricate and demonstrate safe, scalable, high-precision and fully-implantable next-generation neural interface systems. It is anticipated that these systems will leverage significant advances in other disciplines including microelectronics and photonics along with advances in scalable neural encoding and processing algorithms to demonstrate the transformation of high-definition sensory stimuli to and from proposer-specified human sensory-cortex areas, bridging physiological and electronic neural activity representations.

Specifically excluded is research that primarily results in incremental improvements to the existing state of practice. Proposals with external partners should include letters of support, specific tasking, and a cost breakdown for each proposed subcontractor.

Program Overview

The Neural Engineering System Design (NESD) program seeks innovative research proposals to design, build, demonstrate, and validate in animal and human subjects a neural interface system capable of recording from more than one million neurons, stimulating more than one hundred thousand neurons, and performing continuous, simultaneous full-duplex (read and write) interaction with at least one thousand neurons in regions of the human sensory cortex. In addition to achieving substantial advances in scale of interface (independent channel count), proposed systems must also demonstrate simultaneous high-precision in neural activity detection, transduction, and encoding, with single-neuron spike-train precision for each independent channel.

https://www.fbo.gov/ http://www.grants.gov/

While the NESD program will initially focus on proposer-selected areas of the human sensory cortex (e.g., primary visual cortex [V1] or primary auditory cortex [A1]) that are physically accessible and have a solid scientific foundation on which to build, the fundamental objective of the program is to develop a modular and scalable interface system with the capability to serve a multiplicity of applications to monitor and modulate large-scale activity in the central nervous system. NESD hardware components and algorithms must be modular in design with clear, well-defined hardware interconnect and software Application Programming Interfaces (APIs) that can easily accommodate upgrades to componentry, new neural signal transduction modalities, and/or algorithms to enable their use as foundational engineering platforms for future research and development. DARPA expects that subsequent to this program, there will be a variety of uses for the NESD system beyond these initial proposer-defined applications.

In parallel with hardware developments and innovations in neural transduction techniques, the NESD program seeks to advance the state of the art in algorithms to identify neurons, neural circuits, and patterns of population-coded activity that represent and encode specific sensory stimuli and transform this neural-coded information to and from the digital electronic domain.

New mathematical transformation algorithms will need to accommodate the increased scale of neural input/output, and leverage the developed NESD hardware systems to validate simultaneous high-bandwidth and high-precision, bi-directional information transfer between the system and animal/human subjects.

Successful NESD proposals must culminate in the delivery of complete, functional, implantable neural interface systems and the functional demonstration thereof. The final system must read at least one million independent channels of single-neuron information and stimulate at least one hundred thousand channels of independent neural action potentials in real-time. The system must also perform continuous, simultaneous full-duplex interaction with at least one thousand neurons. While DARPA desires a single 1 cm3 device that satisfies all of these capabilities (read, write, and full-duplex), proposers may propose a design wherein each capability is embodied in separate 1 cm3 devices. Proposed implementations must not require tethers or percutaneous connectors for powering or facilitating communication between the implanted and external portions of the system.

Proposals are strongly encouraged to address all NESD program requirements.

Program Structure

Integrated Neural Engineering System Design [NESD] The NESD program is fundamentally an integrated systems design and innovation program that will require scientific and technical advances in two major Technical Areas (TA 1: Neural Transducers and Algorithms, and TA 2: Hardware, Prototyping, and Manufacture) to be fully integrated in a functioning system. The program is scheduled to span four years in three phases with critical milestones and deliverables expected in each phase. Phase 1 is scheduled for 12 months, Phase 2 for 12 months, and Phase 3 for 24 months (See Table 1).

In order to receive an FDA Investigational Device Exemption (IDE) for Early Feasibility Studies in humans, proposals must clearly define a specific target therapeutic neural interface application and its associated target sensory cortical region(s). System requirements must be driven by the proposer-defined application and used to derive, define, and quantify additional specifications, including necessary levels of precision and area of cortical coverage. Proposers are encouraged to focus on cortical sensory pathways where deterministic neural activity encoding and computation models are best understood and can most easily be tested against precise yet complex stimuli. DARPA strongly prefers applications that highlight the benefits and improved functionality enabled by the scale and precision afforded by the proposed NESD systems compared to the state of the art, and would not be possible without the proposed innovations.

NESD systems should leverage leading academic and industrial expertise and fabrication capabilities in key technical areas of the system. In taking a systems-level approach, designs should leverage the strengths of one component technology against the weaknesses of others to produce a fully integrated system that performs better than the sum of its parts. Proposals wherein essential components or algorithms either lag behind, or fail to utilize, state-of-the-art techniques from that discipline may be considered non-conforming.

Proposed system demonstration designs must explain the tradeoffs between component performance, size, maturity, modularity, and energy consumption relative to achievable scale and precision necessary in order to keep the implantable power budget within thermal and emissionsa safety limits for the duration of any proposed trial. Proposing teams must include individuals with expertise managing system design tradeoffs between components and disciplines, and bringing interdisciplinary products from concept through manufacture to market.

All proposals must include a detailed schedule with clear interim milestones and dependencies, as well as a thorough risk analysis in order to prevent delays in the NESD program timeline, particularly those associated with rapid translation into first-in-human trials. Teams must include individuals or groups with demonstrated expertise in bringing highly integrated medical products to market (see the Evaluation Criteria in Section 5.1.1). Proposers that do not include team members with the necessary expertise to address all program requirements must include a plan for dealing with commercial transition and be prepared to enter into Associate Contractor Agreements (ACA) or other contractual vehicles with other DARPA-selected performers in order to contribute to a joint, complete system that meets the NESD program goals.

The final NESD deliverables must include a fully implantable device (i.e., no percutaneous leads for data or power), safe for semi-chronic or longer (> 30 days) human use, integrated with components and packing from TA2 and neural transducersb and algorithms developed in TA1, and demonstrate reliable power and data telemetry supporting full-duplex system functionality in animals and humans.

a Proposers are encouraged to read IEC 60601-1, IEC 60601-1-2, and IEC 14708-3.

b “Neural transducer” is the portion of the proposed approach that encompasses the conversion of neural activity between individual neurons and an intermediate form of information. For example, photons, ions, magnetic fields, or ultrasonic vibrations. The neural transducer and intermediate form of information must be developed in conjunction with the manufactured transducers in the implanted portion of the system. For example, voltage-sensitive proteins, the intensity and wavelength of light emitted, and photo-detectors must all be compatible.

Quantitative Metric Requirements

Note: “proposer-defined quantitative metrics” indicates that all proposals must include measurable metrics for the performance of the proposed system that are appropriate to demonstrate significant advances in scale and precision, but are ultimately guided by and defined by the proposer-specified target sensory application and its associated cortical region function.

Non-quantified and/or purely qualitative metrics may be considered non-conforming.

Regulatory Plans and Execution A regulatory plan must be included in all proposals, and must define a credible pathway to human use. Proposers are required to partner with individuals or groups with demonstrated expertise in the regulatory process. Proposers should ensure that the study design has taken into account a power analysis to guarantee an appropriate sample size, describe planned inclusion/exclusion criteria for participants, and provide quantifiable and independently validated minimally clinically important differences (MCID) for each outcome measured. Include study success criteria and patient success criteria. Proposers must satisfy all FDA requirements in characterizing and addressing expected risks to patients (i.e., mitigate or document the severity and likelihood) in a worst-case scenario prior to pre-submission at the beginning of Phase 3.

Human and Animal Validation Proposals must contain a comprehensive test plan encompassing all safety and complete NESD system performance and validation trials. Proposers must justify their choice of animal model(s) and duration of trials for the safety studies. For any human trials within the program timeline, c Surface of the cortex accessible to measurement, with transduction to/from all of the pyramidal layers.

d Proposers are encouraged to read FDA guidance UCM106757:

http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm106757.htm

Table 1. NESD Target System Performance Metrics Phase 1 Phase 2 Phase 3

Bench Demo Integrated Device Final Integrated Systems 12 months 12 months 24 months

System proposer-defined quantitative metrics

< 3 cm3;

< 5 Watt;

< 20 ms latency;

proposer-defined safety metrics

< 1 cm3;

< 1 ˚C rise in tissue;

< 10 ms latency;

proposer-defined safety metrics

Transducer

Read and write to individual neurons within region of interest (ROI) of

> 0.1 cm2 cortexc;

< 100 µm spatial resolution

105 read channels;

> 0.75 cm2 cortex ROI;

< 50 µm resolution

106 read, 105 write, 103 full-duplex;

2 cm2 cortex ROI;

< 25 µm resolution;

60 dB channel isolation

Representation and protocols (proposer-defined quantitative metrics)

Energy budget for representation and compression

Precision of representation reversibility;

energy and link budget Energy and link budget http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm106757.htm proposers must provide compelling arguments defining the specific trials, expected outcomes, and justification regarding the lack of an appropriate animal model.

Proposers are strongly encouraged to include a detailed plan to develop and use quality assurance processes to support later efforts including eventual translation to clinical products.

Security Proposers must use approaches that ensure confidentiality, integrity, and availability (CIA triad) to prevent spoofing, tampering, or denial of service. While the NESD system is intended to be an investigational device, it will be necessary to adequately secure the connection between the NESD system and a subject’s brain. Therefore, proposers must incorporate inherently safe techniques into the wireless and electronic portions of their system and must describe the specific protocols and techniques to be used. A security audit will be performed by an independent third-party security specialist during Phase 3. DARPA will work with performers to identify appropriate security standards based on the platforms that are proposed.

System Transition Proposers must define and publish hardware and software APIs, protocols, and semantics for interoperability between NESD components and systems, making them available to all DARPA-selected performers. Note that this provision is not meant to require disclosure of otherwise proprietary internal component or process IP. DARPA requires distribution of all of the external interface specifications and data necessary for connecting the proposed developed components to other systems to facilitate third-party utilization of the developed technologies.

Proposers should consider how to enable rapid and broad deployment of NESD systems and technologies once an IDE is granted. Proposals should include tasks articulating plans for the wide distribution, use of, and reimbursement for production and distribution expenses, of NESD systems.

Proposers must complete the attached Specifications Spreadsheet (attachment 3) itemizing the anticipated capabilities and performance metric targets of their final proposed NESD system including clear functional diagrams detailing the expected interrelations of all major components, and the expected dimensions and materials for any implantable packaging.

Technical Area 1 - Neural Transducers and Algorithms TA1 focuses on the scientific and technical advances along with their proofs of principle and function to inform and enable the final design of the NESD system.

Neural Transducer Refinement Strategies to optimize and increase the scalability and precision of the NESD interfaces will depend on the transduction method employed.

Optical interface approaches may require molecular and synthetic biology development to improve efficacy and/or establish safety for human use. Proposed approaches should consider signal detectability with respect to background noise, channel independence, energy efficiency, spectral diversity, methods to improve the safety and control of tissue transfection, and use of infrared wavelengths and/or luminescent complexes to reduce background noise.

In contrast, electronic interface approaches require advances in materials, insertion techniques, scale of hermetic package feed-through, and neural source localization and signal isolation algorithms to achieve NESD program scale and precision targets, without exciting an immune response severe enough to significantly degrade the neural signals over time and/or prevent semi-chronic use.

These two transduction modalities are listed as examples to illustrate the varied distinct technical challenges specific to each method. The list is not exclusive or exhaustive and DARPA is agnostic to the proposed interface modality and technical approach.

Sensory Data Transformation Algorithms Proposers must develop algorithms to identify neurons, neural circuits, patterns of activity, and functional regions of the sensory cortex that represent specific information and transform this information into the digital electronic domain at the new levels of scale and precision enabled by the proposed NESD hardware. This is a brain-to-digital transformation algorithm. Additionally, proposers must develop the inverse algorithms for digital-to-brain transformation. It may be necessary to customize the transformations to each neural transducer mechanism and/or target cortical sensory region.

Proposers must demonstrate that brain-to-digital and digital-to-brain transformation algorithms can be used to convey complex sensory stimuli between the cortical neural population activity domain and the digital domain. The developed algorithms should transform artificial electronic input signals originating as, for example, spatial images and video pixel data, or MP3 audio files, into spatiotemporal patterns of neural activity to be induced in the cortex. Similarly, the inverse brain-to-digital transformation algorithm should convert spatiotemporal patterns of neural population activity into inferred digital stimulus files that, as accurately as possible, reconstruct the original electronic stimuli.

These models should incorporate how those neural population activity patterns change and adapt over time due to variations in stimulus and neural plasticity. While it is not required that these methods are invertible, they should be reversible and deterministic (i.e., passing a stimulus through a brain-to-digital then a digital-to-brain series of transformations should result in a recognizably similar stimulus).

Specifically excluded from the NESD program are transformation algorithms that do not accurately model the naturalistic activity of ensembles of individual neurons as the foundation for higher-level information representation. While general abstractions and higher-level statistical representations describing aggregate grouped neural activity are useful for independent applications, they are not sufficient to interface directly with individual neurons using new NESD system precision. The new algorithms should specify how each individual neuron and ensemble populations thereof should be read or stimulated moment-by-moment in order to encode specific precise and deterministic stimuli.

Neural Activity Representation and Protocols Proposers must develop new methods to significantly reduce the quantity of data necessary to represent neural activity at scale in order to effect energy-efficient wireless telemetry delivery.

These methods must be validated to ensure that there is no functional loss when utilizing the compressed neural information, and the impact on NESD system energy and thermal budgets must be demonstrated. For example, JPEG and MPEG file formats are lossy, but due to accurate psychophysical models they can compress data by two to three orders of magnitude while preserving perceptually important underlying information.

Technical Area 2: Hardware, Prototyping, and Manufacture TA2 will focus on the design, prototyping, integration, fabrication, and test/validation of the NESD components and overall system.

Electronics and Signal Processing Proposers must employ efficient ultra-low-power digital computation methods to sample, process, and telemeter one million channels of neural information. DARPA is agnostic to the technical approach. Proposers are encouraged to incorporate elements of life-cycle requirements for the development of medical software from IEC 62304.

Optical Interface Approaches If constructing a NESD system with a photonic neural transducer, proposers must match optical sensing, emitting, and focusing components to the biological properties of both the neural light-transducing mechanisms in the cortex as well as the materials properties in the implant package where new transparent materials must be proven to meet FDA hermeticity and non-toxicity requirements.

Electronic and Other Interface Approaches If constructing a NESD system with an electrical or other type of neural transducer, proposers must demonstrate scalable high-density package feed-throughs and external interfaces to electronics, as well as assembly and interface manufacture procedures that will satisfy FDA implantable device requirements.

Medical Materials and Device Packaging Proposals will be considered non-conforming if they do not include provisions to package the final NESD deliverable entirely in a self-contained, biocompatible, sterilizable, hermetic package suitable for semi-chronic implantation in humanse. Careful attention must be paid to all aspects of semi-chronic bio-compatibility including tissue response and power dissipation into tissue and related thermal limits. Electromagnetic compatibility and electrical safety will be required. The NESD system is not required to meet MRI compatibility standards. Proposers are strongly encouraged to partner with individuals or groups having demonstrated expertise with implantable medical device design, fabrication, and testing.

e Proposers are encouraged to read ISO 10993, which provides guidance for selecting the tests to evaluate the biological response to medical devices, and FDA guidance UCM348890:

http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm348890.pdf http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm348890.pdf

Prototyping and Design for Manufacturing [DFM] Future manufacturability at ever-increasing scales of production must shape design choices throughout the program, beginning with the initial stages and proposed system designs. The aggressive schedule of NESD will require fast design, optimization, and product development cycles. Proposers are strongly encouraged to include a detailed strategy to develop manufacturing, testing, and quality assurance processes applicable to eventual volume commercialization.

To facilitate and support the use of state-of-the-art capabilities across all technical disciplines, DARPA expects to announce the organization of a NESD Industry Group to facilitate participants’ pre-competitive access to intellectual property, services, and facilities that can accelerate the prototyping and manufacture of advanced neuro-engineering components and services. Supported areas will include: state-of-the-art electronics, photonics, computing, fabrication, assembly, medical materials and packaging, clinical procedures, testing, and regulatory support. If Industry Group member services and capabilities are required to complete the proposed NESD system, proposers are strongly encouraged to independently establish contractual relationships with and among their collaborating team members. Proposals must clearly articulate relevant role, tasks and budget responsibility information, i.e., each participating Industry Group member must be clearly identified as a prime contractor, subcontractor, or vendor.

Proposals must include letter(s) of support from key partners and subcontractors if these capabilities are critical for the completion of the proposed work.

Program Milestones and Schedule

DARPA anticipates down-selecting and/or condensing teams at the end of Phases 1 and 2.

Performers that do not pass preliminary (three months after contract) and critical (12 months after contract) design reviews conducted by DARPA and demonstrate convincing technical achievement in vitro will not advance to subsequent phases of the program. See Figure 1.

Proposers are encouraged to expand upon these required milestones and to add new milestones and deliverables specific to the approaches being proposed. For example, if it is expected that the proposed effort will require an Investigational New Drug (IND) exemption, relevant tasks should have a clearly delineated set of milestones associated with that objective. Proposals must also include application-specific milestones.

Note: intermediate milestones may use a limited number of percutaneous leads to demonstrate portions of the system.

In vitro component demo

In vivo neural-transducer demo

System design

Plan of action

Phase 1 12 months

FDA

pre-submission

In vivo component performance demo

Phase 2 12 months

Phase 3 24 months

FDA IDE

submission

In vivo read and write demo

System development and manufacture

In vivo system demo

Security audit

DARPA

Independent evaluation

PDR

Regulatory plan

CDR

Figure 1 - NESD Program Plan and Milestones

Abstracts and Proposals Proposers are encouraged to submit an abstract that clearly identifies a target sensory cortical area and the demonstration application that will drive complete system requirements and outlines including overall architectural descriptions and diagrams that clearly articulate fundamental system tradeoffs, expected scalability, precision and performance metric targets.

Proposers are strongly encouraged to submit abstracts and proposals that meet all NESD program requirements.

Smaller proposals for individual technical area explorations and developments that offer critical technology leverage and support for the entire NESD performer community will be considered but are a lower priority to DARPA.

Milestones

Performers are expected to achieve the technical objectives in Table 1, and these results must be integrated into the system prototyping and timeline in Figure 1.

Phase 1: 1-12 months after contract (MAC)

1. Plan of Action and Milestones (POAM) (3 MAC)

Milestone: Document the POAM, setting forth specific measurable milestones that DARPA can use to evaluate progress towards a fully compliant Preliminary Design Review (PDR).

Deliverable: POAM to DARPA Program Manager (PM), to include:

a. Detailed execution plan for integration of prime contractor, subcontractors, collaborators, and vendors

b. Detailed technology-to-market plan including transition strategy, IP strategy, manufacturing plan and initial business plan

c. Measurable weekly milestones

2. Preliminary Design Review (6 MAC) Milestone: Design review demonstrating that the proposed system design will credibly meet the NESD program objectives. All system requirements, specifications, regulatory plans, test and validation plans, and manufacturing plans must be reported.

Deliverable: Briefing to DARPA PM, to include

a. Design verification

b. Plan to fabricate the required prototypes

c. Plans to validate prototypes in animal and human subjects

d. Risk analysis – identify all risks, their severity, likelihood, and the approach to mitigate

e. Anticipated performance specifications based on in vitro experiments

3. Critical Design Review (12 MAC) Milestone: Design review demonstrating that the proposed system design will meet the NESD program objectives on time and on budget. All system requirements, specifications, regulatory plans, and manufacturing plans must be completed.

Deliverable: Briefing to DARPA PM, to include

a. Design validation

b. Detailed risk analysis – retired risks; the severity and likelihood of remaining risks; approaches to mitigate remaining risks

c. System energy budget

d. System link budget

e. Scalability analysis for every aspect of the NESD system

f. Roadmap for manufacture of the NESD components and integration of the system

g. Device Evaluation Strategy (DES)

h. Test plan for safety, biocompatibility, and emissions

4. Phase 1 Demo (12 MAC) Milestone: Demonstrate bench prototype NESD components in vitro or in vivo.

Demonstrate proofs of principle for the scalability and precision of the neural transducer in vivo and neural representation and compression. Metrics are specified in Table 1.

Deliverable: Briefing to DARPA PM, to include

a. Detailed component and system description

b. Trials performed, metrics tested against

c. Results measured, metrics achieved

Phase 2: 13-24 MAC

5. Regulatory pre-submission (no later than 15 MAC)

Milestone: Finalize DES, safety testing procedures and pre-submission documentation.

Deliverable: Submit DES and pre-submission request to the FDA.

6. Regulatory plan finalized (no later than 24 MAC) Milestone: Complete a draft of the regulatory submission, which incorporates results from Phase 1 and Phase 2 safety studies and pre-submission discussions with the FDA.

Deliverable: Draft submission delivered to DARPA PM for review.

7. Phase 2 Demo (24 MAC) Milestone: Demonstrate in vivo that the proposed biological transducer and algorithms can achieve the required performance specifications, scalability and precision.

Demonstrate in vivo functionality of a first-generation prototype NESD system.

Performance of individual components may be verified independently of the entire system. Metrics are specified in Table 1.

Deliverable: Five prototype NESD systems delivered to DARPA for independent validation and verification (IVV). Briefing to DARPA PM, to include

a. Detailed component and system description

b. Trials performed, metrics tested against

c. Results measured, metrics achieved

Phase 3: 25-48 MAC

8. Regulatory submission (no later than 26 MAC)

Milestone: Finalize documentation to support first-in-human trials.

Deliverable: IDE submitted to the FDA, following Early Feasibility Study guidelines.

9. Phase 3 Interim Demo (36 MAC) Milestone: Demonstrate in vivo reading from one hundred thousand neurons and writing to one hundred thousand neurons using a fully integrated second-generation NESD prototype. Other metrics are performer-specified.

Deliverable: Five prototype NESD systems delivered to DARPA for IVV. Briefing to DARPA PM, to include

a. Detailed component and system description

b. Trials performed, metrics tested against

c. Results measured, metrics achieved

10. Security Audit (42 MAC) Milestone: Analysis of the methods used to protect the confidentiality, integrity and availability of a prototype NESD system.

Deliverable: Two prototype NESD electronic subsystems delivered to independent security evaluators. Briefing to DARPA PM, to include

a. Trials performed, metrics tested against

b. Results measured, metrics achieved

c. Security flaws identified

d. Actions required to rectify security flaws

e. Plan of action to rectify critical flaws before the Phase 3 Final Demo

11. Phase 3 Final Demo (48 MAC) Milestone: Demonstrate in vivo the safety and efficacy of the final human-ready NESD system. Metrics are specified in Table 1. Demonstrate application-specific capabilities.

Deliverable: Five prototype NESD systems delivered to DARPA for IVV. Briefing to DARPA PM, to include

a. Detailed component and system description

b. Trials performed, metrics tested against

c. Results measured, metrics achieved

d. Actions taken to rectify security flaws identified in Milestone 10

12. Regulatory Approval (48 MAC) Milestone: Attain FDA approval to conduct controlled trials in human subjects using the complete NESD system.

Ethical, Legal, and Societal Implications

All proposers are expected to comport themselves in accordance with the highest ethical standards, particularly with regards to animal and human trials. In addition to fulfilling all Institutional Animal Care and Use Committee (IACUC), Institutional Review Board (IRB), and IDE requirements for animal and human studies, all animal testing will require approval from

Animal Care and Use Review Office (ACURO) prior to release of funds related to animal testing and continuous monitoring thereafter as specified by the relevant oversight bodies. Human trials will require approval and continuous monitoring from a secondary DoD agency, to be identified by DARPA, prior to release of funds related to human subjects. NESD efforts involving development of new biologic treatments may be required to attain an IND exemption from the FDA. All NESD efforts will be required to attain an IDE and/or IND from the FDA by the end of the program.

In preparation for IRB and other regulatory reviews, and to facilitate timely consideration of the relevant safety, efficacy and other issues by regulators, proposers are encouraged to engage with independent bioethics experts. It is incumbent upon all NESD performers to consider, establish, and work within ethical boundaries that take into account such foundational principles as fully informed consent, privacy, and personal autonomy. DARPA encourages proposers to explore the Gray Matters project at http://bioethics.gov/studies.

2. Award Information

Multiple awards are possible. The amount of resources made available under this BAA will depend on the quality of the proposals received and the availability of funds.

The Government reserves the right to select for negotiation all, some, one, or none of the proposals received in response to this solicitation, and to make awards without discussions with proposers. The Government also reserves the right to conduct discussions if it is later determined to be necessary. If warranted, portions of resulting awards may be segregated into pre-priced options. Additionally, DARPA reserves the right to accept proposals in their entirety or to select only portions of proposals for award. In the event that DARPA desires to award only portions of a proposal, negotiations may be opened with that proposer. The Government reserves the right to fund proposals in phases with options for continued work at the end of one or more of the phases.

Awards under this BAA will be made to proposers on the basis of the evaluation criteria listed below (see section labeled “Application Review Information”, Sec. 5.), and program balance to provide overall value to the Government. The Government reserves the right to request any additional, necessary documentation once it makes the award instrument determination. Such additional information may include but is not limited to Representations and Certifications. The Government reserves the right to remove proposers from award consideration should the parties fail to reach agreement on award terms, conditions and cost/price within a reasonable time or the proposer fails to timely provide requested additional information. Proposals identified for negotiation may result in a procurement contract, grant, cooperative agreement, or other transaction depending upon the nature of the work proposed, the required degree of interaction between parties, whether or not the research is classified as Fundamental Research, and other factors.

In all cases, the Government contracting officer shall have sole discretion to select award instrument type and to negotiate all instrument terms and conditions with selectees. Proposers are advised that if they propose cooperative agreements, DARPA may select other award http://bioethics.gov/studies instruments, as it deems appropriate. DARPA will apply publication or other restrictions, as necessary, if it determines that the research resulting from the proposed effort will present a high likelihood of disclosing performance characteristics of military systems or manufacturing technologies that are unique and critical to defense. Any award resulting from such a determination will include a requirement for DARPA permission before publishing any information or results on the program. For more information on publication restrictions, see the section below on Fundamental Research.

Fundamental Research

It is DoD policy that the publication of products of fundamental research will remain unrestricted to the maximum extent possible. National Security Decision Directive (NSDD) 189 established the national policy for controlling the flow of scientific, technical, and engineering information produced in federally funded fundamental research at colleges, universities, and laboratories. The Directive defines fundamental research as follows:

'Fundamental research' means basic and applied research in science and engineering, the results of which ordinarily are published and shared broadly within the scientific community, as distinguished from proprietary research and from industrial development, design, production, and product utilization, the results of which ordinarily are restricted for proprietary or national security reasons.

As of the date of publication of this BAA, the Government expects that program goals as described herein may be met by proposers intending to perform fundamental research. The Government does not anticipate applying publication restrictions of any kind to individual awards for fundamental research that may result from this BAA. Notwithstanding this statement of expectation, the Government is not prohibited from considering and selecting research proposals that, while perhaps not qualifying as fundamental research under the foregoing definition, still meet the BAA criteria for submissions. If proposals are selected for award that offer other than a fundamental research solution, the Government will either work with the proposer to modify the proposed statement of work to bring the research back into line with fundamental research or else the proposer will agree to restrictions in order to receive an award.

Proposers should indicate in their proposal whether they believe the scope of the research included in their proposal is fundamental or not. While proposers should clearly explain the intended results of their research, the Government shall have sole discretion to select award instrument type and to negotiate all instrument terms and conditions with selectees. Appropriate clauses will be included in resultant awards for non-fundamental research to prescribe publication requirements and other restrictions, as appropriate.

For certain research projects, it may be possible that although the research being performed by the prime contractor is restricted research, a subawardee may be conducting fundamental research. In those cases, it is the prime contractor’s responsibility to explain in its proposal why its subawardee’s effort is fundamental research.

The following statement or similar provision will be incorporated into any resultant non-fundamental research procurement contract or other transaction:

There shall be no dissemination or publication, except within and between the contractor and any subawardees, of information developed under this contract or contained in the reports to be furnished pursuant to this contract without prior written approval of DARPA’s Public Release Center (DARPA/PRC). All technical reports will be given proper review by appropriate authority to determine which Distribution Statement is to be applied prior to the initial distribution of these reports by the contractor. With regard to subawardee proposals for Fundamental Research, papers resulting from unclassified fundamental research are exempt from prepublication controls and this review requirement, pursuant to DoD Instruction 5230.27 dated October 6, 1987.

When submitting material for written approval for open publication, the contractor/awardee must submit a request for public release to the DARPA/PRC and include the following information: (1) Document Information: document title, document author, short plain-language description of technology discussed in the material (approx.

30 words), number of pages (or minutes of video) and document type (e.g., briefing, report, abstract, article, or paper); (2) Event Information: event type (conference, principal investigator meeting, article or paper), event date, desired date for DARPA's approval; (3) DARPA Sponsor: DARPA Program Manager, DARPA office, and contract number; and (4) Contractor/Awardee's Information: POC name, email and phone. Allow four weeks for processing; due dates under four weeks require a justification. Unusual electronic file formats may require additional processing time. Requests may be sent either via email to public_release_center@darpa.mil or by mail at 675 North Randolph Street, Arlington VA 22203-2114, telephone (571) 218-4235. Refer to the following for link for information about DARPA’s public release process: http://www.darpa.mil/work-with-us/contract-management/public-release.”

3. Eligibility Information

All responsible sources capable of satisfying the Government’s needs may submit a proposal that shall be considered by DARPA.

3.1. ELIGIBLE APPLICANTS

3.1.1. Federally Funded Research and Development Centers (FFRDCs) and Government Entities

Federally Funded Research and Development Centers (FFRDCs) and Government entities (e.g., Government/National laboratories, military educational institutions, etc.) are subject to applicable direct competition limitations and cannot propose to this BAA in any capacity unless they meet the following conditions: (1) FFRDCs must clearly demonstrate that the proposed work is not otherwise available from the private sector; and (2) FFRDCs must provide a letter on official letterhead from their sponsoring organization citing the specific authority establishing their eligibility to propose to Government solicitations and compete with industry, and their compliance with the associated FFRDC sponsor agreement’s terms and conditions. This information is required for FFRDCs proposing to be prime contractors or subawardees.

mailto:public_release_center@darpa.mil

Government entities must clearly demonstrate that the work is not otherwise available from the private sector and provide written documentation citing the specific statutory authority and contractual authority, if relevant, establishing their ability to propose to Government solicitations. At the present time, DARPA does not consider 15 U.S.C. § 3710a to be sufficient legal authority to show eligibility. While 10 U.S.C.§ 2539b may be the appropriate statutory starting point for some entities, specific supporting regulatory guidance, together with evidence of agency approval, will still be required to fully establish eligibility. DARPA will consider FFRDC and Government entity eligibility submissions on a case-by-case basis; however, the burden to prove eligibility for all team members rests solely with the proposer.

3.1.2. Non-U.S. Organizations

Non-U.S. organizations are/or individuals may participate to the extent that such participants comply with any necessary nondisclosure agreements, security regulations, export control laws, and other governing statutes applicable under the circumstances. See Section 4.2 “Security and Proprietary Issues” regarding the proposers capabilities to perform research and development at the classification level they propose.

Procurement Integrity, Standards of Conduct, Ethical Considerations, and Organizational Conflicts of Interest

Current federal employees are prohibited from participating in particular matters involving conflicting financial, employment, and representational interests (18 U.S.C. §§ 203, 205, and 208). Once the proposals have been received, and prior to the start of proposal evaluations, the Government will assess potential conflicts of interest and will promptly notify the proposer if any appear to exist. The Government assessment does NOT affect, offset, or mitigate the proposer’s responsibility to give full notice and planned mitigation for all potential organizational conflicts, as discussed below.

Without prior approval or a waiver from the DARPA Director, in accordance with FAR 9.503, a contractor cannot simultaneously provide scientific, engineering, technical assistance (SETA) or similar support and also be a technical performer. As part of the proposal submission, all members of the proposed team (prime proposers, proposed subawardees, and consultants) must affirm whether they (their organizations and individual team members) are providing SETA or similar support to any DARPA technical office(s) through an active contract or subcontract. All affirmations must state which office(s) the proposer, subawardees, consultant, or individual supports and identify the prime contract number(s). All facts relevant to the existence or potential existence of organizational conflicts of interest (FAR 9.5) must be disclosed. The disclosure must include a description of the action the proposer has taken or proposes to take to avoid, neutralize, or mitigate such conflict. If in the sole opinion of the Government after full consideration of the circumstances, a proposal fails to fully disclose potential conflicts of interest and/or any identified conflict situation cannot be effectively mitigated, the proposal will be rejected without technical evaluation and withdrawn from further consideration for award.

If a prospective proposer believes a conflict of interest exists or may exist (whether organizational or otherwise) or has questions on what constitutes a conflict of interest, the proposer should send his/her contact information and a summary of the potential conflict via email to the BAA email address before time and effort are expended in preparing a proposal and mitigation plan.

3.2. COST SHARING/MATCHING

Cost sharing is not required; however, it will be carefully considered where there is an applicable statutory condition relating to the selected funding instrument (e.g., for any Other Transactions under the authority of 10 U.S.C. § 2371). Cost sharing is encouraged where there is a reasonable probability of a potential commercial application related to the proposed research and development effort.

4. Application and Submission Information

4.1. ADDRESS TO REQUEST APPLICATION PACKAGE

This solicitation contains all information required to submit a proposal. No additional forms, kits, or other materials are needed. This notice, with the classified addendum, constitutes the total solicitation. No additional information is available, except as provided at FBO.gov or Grants.gov, nor will a formal Request for Proposal (RFP) or additional solicitation regarding this announcement be issued. Requests for the same will be disregarded.

4.2. CONTENT AND FORM OF APPLICATION SUBMISSION

4.2.1. Proprietary and Security Information

DARPA policy is to treat all submissions as source selection information (see FAR 2.101 and 3.104), and to disclose their contents only for the purpose of evaluation. Restrictive notices notwithstanding, during the evaluation process, submissions may be handled by support contractors for administrative purposes and/or to assist with technical evaluation. All DARPA support contractors performing this role are expressly prohibited from performing DARPA-sponsored technical research and are bound by appropriate nondisclosure agreements.

Submissions…