DARPA-BAA-13-37_Amendment_No._6_Final_For_Posting_26Mar2014.pdf

Broad Agency Announcement

Living Foundries: 1000 Molecules

MTO

DARPA-BAA-13-37

July 12, 2013 (Amendment No. 06: As amended through 26 March 2014)

Table of Contents

I. FUNDING OPPORTUNITY DESCRIPTION

A. Rapid Design and Prototyping Infrastructure

B. DARPA 1000

C. Advanced Studies for Novel Component Technologies for Improved Engineering of Biology

D. Teaming and Partnerships

E. Program Plan and Technical Milestones

F. Table 1: Living Foundries: 1000 Molecules program milestones and deliverables

G. Bio-Safety and Security

II. AWARD INFORMATION

III. ELIGIBILITY INFORMATION

A. Eligible Applicants

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

H. Cost Sharing/Matching

I. Other Eligibility Criteria

1. Collaborative Efforts

IV. APPLICATION AND SUBMISSION INFORMATION

A. Address to Request Application Package

B. Content and Form of Application Submission

1. Security and Proprietary Issues

2. Proposal Submission Information

3. Full Proposal Format for Task Area 1

4. Full Proposal Format for Task Area 2

5. Full Proposal Format for Advanced Studies

6. Submission Dates and Times

7. Funding Restrictions

V. APPLICATION REVIEW INFORMATION

A. Evaluation Criteria

B. Review and Selection Process

VI. AWARD ADMINISTRATION INFORMATION

A. Selection Notices

B. Administrative and National Policy Requirements

1. Meeting and Travel Requirements

2. Human Subjects Research

3. Animal Use

4. Export Control

5. Subcontracting

6. Electronic and Information Technology

7. Employment Eligibility Verification

8. System for Award Management (SAM) Registration and Universal Identifier Requirements

9. Reporting Executive Compensation and First-Tier Subcontract Awards

10. Updates of Information Regarding Responsibility Matters

11. Representations by Corporations Regarding an Unpaid Delinquent Tax Liability or a Felony Conviction under any Federal Law

12. Cost Accounting Standards (CAS) Notices and Certification

13. Controlled Unclassified Information (CUI) on Non-DoD Information Systems

C. Reporting

D. Electronic Systems

1. Representations and Certifications

2. Wide Area Work Flow (WAWF)

3. i-Edison

VII. AGENCY CONTACTS

VIII. OTHER INFORMATION

A. Intellectual Property Procurement Contract Proposers

1. Noncommercial Items (Technical Data and Computer Software)

2. Commercial Items (Technical Data and Computer Software)

B. Non-Procurement Contract Proposers – Noncommercial and Commercial Items (Technical Data and Computer Software)

C. All Proposers – Patents

D. All Proposers – Intellectual Property Representations

Part I: Overview Information

• Federal Agency Name – Defense Advanced Research Projects Agency (DARPA), Microsystems Technology Office (MTO)

• Funding Opportunity Title – Living Foundries: 1000 Molecules

• Announcement Type – Initial Announcement

• Funding Opportunity Number – DARPA-BAA-13-37

• Catalog of Federal Domestic Assistance Numbers (CFDA) – 12.910 Research and

Technology Development

• Dates o Posting Date: 12 July 2013 o Proposal Due Date for Task Area 1 and Advanced Studies: 8 October 2013 o Proposers’ Day: 24 July 2013 (See Special Notice #DARPA-SN-13-38, slides are posted on http://www.darpa.mil/Opportunities/Solicitations/MTO_Solicitations.aspx) o BAA Process and Proposal Preparation/Submission Overview Webinar:

31 July 2013. The purpose of the webinar is to provide additional details regarding the BAA process and to reiterate the proposal preparation and submission instructions/requirements. Slides for this presentation are posted on http://www.darpa.mil/Opportunities/Solicitations/MTO_Solicitations.aspx.

o Estimated Period of Performance Start Date for Task Area 1 and Advanced Studies: 17 March 2014 o BAA Closing Date: 2 February 2015

• Concise description of the funding opportunity - DARPA’s Living Foundries: 1000

Molecules program seeks to build a scalable, integrated, rapid design and prototyping infrastructure for the facile engineering of biology. This infrastructure will enable transformative and currently inaccessible projects to develop advanced chemicals, materials, sensing capabilities, and therapeutics. Furthermore, the infrastructure will provide a flexible, efficient, and continuously improving capability to Department of Defense (DoD) and the engineering biology community. A final proof-of-principle demonstration of capabilities will require rapid design and prototyping centers to generate 1000 novel molecules and chemical building blocks, thus enabling access to radical new materials.

• Anticipated individual awards – Multiple awards are anticipated.

• Total amount of money to be awarded – It is anticipated that total funding of approximately $110M will be awarded across Task Areas 1 and 2 and Advanced Studies discussed in this BAA. The actual amount of resources available under this BAA will depend on the quality of proposals received and availability of funds.

• Anticipated funding type – 6.1 (Advanced Studies and Comprehensive Proposals) and

6.2 (Comprehensive Proposals)

• Types of instruments that may be awarded – Procurement contract or other transaction.

http://www.darpa.mil/Opportunities/Solicitations/MTO_Solicitations.aspx http://www.darpa.mil/Opportunities/Solicitations/MTO_Solicitations.aspx

• Any cost sharing requirements – None.

• Agency contact

Dr. Alicia Jackson

DARPA/MTO

ATTN: DARPA-BAA-13-37

675 North Randolph Street Arlington, VA 22203-2114

The BAA Coordinator for this effort can be reached at DARPA-BAA-13- 37@darpa.mil

PROPOSERS ARE CAUTIONED THAT EVALUATION RATINGS MAY BE

LOWERED AND/OR PROPOSALS REJECTED IF PROPOSAL PREPARATION

(PROPOSAL FORMAT, CONTENT, ETC.) AND/OR SUBMITTAL INSTRUCTIONS

ARE NOT FOLLOWED.

mailto:DARPA-BAA-13-37@darpa.mil

Part II: Full Text of Announcement

I. FUNDING OPPORTUNITY DESCRIPTION

The Defense Advanced Research Projects Agency (DARPA) 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. Any negotiations and/or awards will use procedures under FAR 15.4, Contract Pricing, as specified in the BAA. 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, http://www.fbo.gov/. The following information is for those wishing to respond to the BAA.

CONCISE SUMMARY

DARPA’s Living Foundries: 1000 Molecules program seeks to build a scalable, integrated, rapid design and prototyping infrastructure for the facile engineering of biology. This infrastructure will enable transformative and currently inaccessible projects to develop advanced chemicals, materials, sensing capabilities, and therapeutics. Furthermore, the infrastructure will provide a flexible, efficient, and continuously improving capability to Department of Defense (DoD) and the engineering biology community. A final proof-of-principle demonstration of capabilities will require centers to generate 1000 novel molecules and chemical building blocks (DARPA 1000), thus enabling access to radical new materials.

INTRODUCTION

The goal of the DARPA Living Foundries: 1000 Molecules program is to develop and establish the foundational technological infrastructure for engineering biology to provide new materials, capabilities, and manufacturing paradigms for Department of Defense (DoD) and the Nation.

Living Foundries: 1000 Molecules is complementary to and builds upon the Living Foundries:

ATCG program, which is developing new tools and technologies to accelerate the biological design-build-test cycle. (Summary slides highlighting tools and concepts currently under development in Living Foundries: ATCG are included as Attachment 3 for the Living Foundries:

1000 Molecules BAA.) Together, these programs will leverage biology as a technology platform to pursue transformative applications across chemicals, materials, sensing capabilities, and therapeutics.

All of the above transformative applications share an underlying need for large-scale design and rapid prototyping based on a common, integrated platform of technologies and capabilities that span the entirety of the biological design-build-test-learn cycle. Toward this end, DARPA seeks to create a first-of-its-kind infrastructure defined by tools and processes that make possible a scale and sophistication of experimentation and interdisciplinary collaboration that does not exist today. The goal is to establish a technology infrastructure accessible to a broad community of users for the purpose of innovating across multiple application areas, and to create a strategic and economic advantage for the United States by leveraging and driving significant advances in biotechnology.

DARPA is soliciting proposals for Living Foundries: 1000 Molecules that aim to create a fully integrated, rapid design and prototyping infrastructure that spans design tools, scalable, automated, and parallelized design fabrication, and high-throughput design evaluation and validation. To support the infrastructure to be developed, a limited number of proposals for advanced studies that will develop component technologies, including design algorithms, scalable transformation and genetic integration methodologies, and flexible assay systems, may also be considered.

As a demonstration of the functionality and flexibility of the infrastructure being developed, each center will be required to produce a minimum of 350 unique molecules of relevance to DoD by the end of the period of performance. DoD critically needs innovations in chemicals, materials, and therapeutics to advance the Nation’s capabilities, but advances are currently constrained by the limited set of available chemical building blocks and their associated chemistries.

Biologically produced molecules offer orders-of-magnitude greater diversity in chemical functionality compared to traditional approaches, potentially enabling unexpected and currently unsynthesizable molecules, chemical building blocks, and ultimately materials with novel, superior properties. The rapid design and prototyping infrastructure created by this program should enable rapid exploration and development of this diverse chemical space.

The Government strongly prefers proposals for comprehensive, fully integrated rapid design and prototyping centers and anticipates that these will comprise the majority of awards. The Government expects to fund several types of rapid design and prototyping infrastructure, spanning a range of approaches, foci, and users. In addition to the prototyping centers, the Government anticipates funding a limited number of advanced studies.

A. Rapid Design and Prototyping Infrastructure

The overarching goal of developing an integrated, rapid design and prototyping infrastructure is to build a scalable and accessible technology base to pursue transformative applications and open new frontiers across diverse areas, including new materials and sensing capabilities, and novel therapeutics.

The facilities that comprise the rapid design and prototyping infrastructure should bridge the gap from initial, laboratory-level, proof-of-concept experimentation to industrial pilot production.

Proposed infrastructure should enable a scale (e.g. throughput) and sophistication (e.g. design and analysis) of engineering that is orders of magnitude beyond what is achievable today.

Implementation of this infrastructure should focus on using automated, integrated processes across all stages of design, fabrication, testing, and analysis. Successful proposals will include:

advanced process design utilizing best industrial manufacturing practices, integration and modularization of component technologies, and the identification of driving technical and scientific challenges.

Key technical components to address may include, but are not limited to:

(1) Overarching computational infrastructure to link component technologies, enable end-to-end process monitoring, and accelerate design and engineering troubleshooting;

(2) Design tool innovations to enable forward engineering of novel biosynthetic pathways, gene cluster discovery, and chemical structure prediction;

(3) Methods for automated, scalable, high-throughput construction of genetic designs;

(4) Design evaluation tools to enable massively parallel testing, analysis, validation, and verification of engineered systems, including analysis of intermediates; and

(5) Integrated feedback tools exploiting high-volume data generation to inform future designs and processes, including analysis of failure modes, implementation of learning and data mining algorithms, and generation of design rules for assembling biological systems with predictable behavior.

Ultimately, rapid design and prototyping facilities should consist of fully integrated computational and physical infrastructure supporting design, fabrication, validation/quality control, and analysis, the totality of which should be tightly coupled to algorithms for design and process optimization.

Beyond the technology and process infrastructure comprising the physical plant, each center should also:

• Be applicable to addressing diverse applications in engineering biology beyond the biosynthesis of new molecules (e.g. synthetic biological circuits and networks, creation of libraries of biological ‘parts’, recoding and refactoring of genomes, etc.);

• Readily import, test, and integrate new methods and technologies that are developed externally; and

• Engage and partner with end users (e.g. those that will use engineering design and prototyping processes — academia and industry), technology developers (e.g. to improve and develop new processes), and infrastructure providers (e.g. reagents and equipment) to enable broad access and a broad user base.

As stated previously, DARPA expects to fund multiple, distinct implementations of rapid design and prototyping infrastructure for engineering biology. All proposed infrastructure should be generalizable in that it can address a range of designs, pathways, organisms/systems and/or products.

Figure 1. Schematic for a generalized, example infrastructure, with program focus areas outlined in red.

B. DARPA 1000

To provide a measure of the capabilities of the facilities, over the course of the program each facility will be required to generate at least 350 unique molecules, with at least 1000 unique molecules in total generated across all facilities. This challenge, DARPA 1000, is designed to demonstrate infrastructure capabilities in throughput, rapid product generation, and platform flexibility and generalizability across numerous designs, pathways, and products. During each program phase, performers must identify and justify the molecules they aim to produce, demonstrating a breadth of structural and functional diversity (molecules can be grouped into unique classes as appropriate). DARPA 1000 encompasses three Challenge Areas:

(1) Rapid, improved prototyping of known molecules. These are molecules for which a known biosynthetic pathway exists. This includes, but is not limited to, molecules that have been previously synthesized biologically, as well as natural products that are currently derived through extraction and purification. Facilities should demonstrate improved production (e.g., yield, cost, purity, etc.) relative to state-of-the-art production methods by using a biosynthetic route; and

(2) Prototyping of known, but currently inaccessible, molecules. These are molecules that are not routinely synthesized biologically, but for which a biosynthetic pathway can be constructed. These include, but are not limited to, synthetic pathways constructed from multiple, unique organisms. Of particular interest to DARPA are molecules that are currently very difficult, impossible, or prohibitively expensive to synthesize chemically;

and

(3) Prototyping of novel molecules. These are molecules that are effectively unattainable through synthetic chemistry and cannot be synthesized using existing biological chemistry. Potential examples include creating novel enzymes to enable currently inaccessible pathway reactions that yield new chemicals or specific, incorporation of novel elements from the periodic table, or high-efficiency incorporation of non-natural amino acids into products.

Proposers will be expected to identify and justify classes of molecules proposed for each Challenge Area. While the final list of target molecules may be refined and finalized throughout each program phase, the types of molecules that will be pursued should be clearly described in the proposal. To meet the DARPA 1000 goals, performers will not be expected to demonstrate chemical production at greater than reliably detectable quantities (unless such scale is required to show improvement over state-of-the-art (SOA)).

Note: Proposers will be expected to meet the goals and expectations for both establishing a rapid design and prototyping infrastructure as well as for meeting the goals of DARPA 1000.

The Living Foundries: 1000 Molecules program will consist of two Task Areas — Task Area 1 (TA1) and Task Area 2 (TA2) — with completion of TA1 required for proposing to TA2. TA1 will serve as an initial infrastructure and technical design exploration phase where the infrastructure plan and technical path toward generating molecules for DARPA 1000 are refined and culminates in a technical report detailing the center’s proposed technical approach, physical capabilities, and management structure.

TA2 will build off of and execute the improved technical approach and plan generated during TA1. TA2 will consist of three phases and will require facilities to demonstrate their capabilities to generate genetic designs and platforms with increasing sophistication and scale (see Table 1).

Phase 1 of TA2 will serve as an initial “pressure test” requiring centers to produce at least 10 molecules by the end of Phase 1. Phase 2 will conclude with centers each producing at least 60 molecules, including a minimum of 15 known, but currently inaccessible, molecules (i.e.

Challenge Area 2). During Phase 3, performers must demonstrate production of at least 10 completely novel molecules (i.e. Challenge Area 3) and at least 200 additional molecules from Challenge Areas 1 and 2.

At the program’s end, each facility will have produced at least 350 distinct molecules, including at least 45 known, but currently inaccessible, molecules (Challenge Area 2) and at least 10 completely novel molecules (Challenge Area 3). See Program Plan and Technical Milestones section for further details.

The milestones outlined above are the minimum expected of each rapid design and prototyping center. Critically, all target molecules should be relevant to DoD interests, with particular attention paid to chemicals and materials. Preference will be given to proposals that target molecules with the potential to enable new capabilities, that exceed the minimum established goals, and that show radical improvements to the biological design-build-test-analyze cycle.

DARPA is not interested in incremental improvements to existing infrastructure or funding of bricks and mortar (e.g. building construction). Biological engineering platforms should be generalizable in that they can address a range of designs, pathways, organisms/systems and products. DARPA is not interested in expression platforms that require extensive optimization for each application or focus solely on protein production. Instead, each rapid design and prototyping center should be capable of manufacturing a range of chemical building blocks, small molecules, novel materials, and novel functions that require complex biosynthetic engineered pathways and networks.

C. Advanced Studies for Novel Component Technologies for Improved Engineering of Biology

The rapid design and prototyping infrastructure to be developed through the Living Foundries:

1000 Molecules program will require new, flexible approaches to engineering biology in order to rapidly generate and evaluate new biological designs. A limited number of highly innovative proposals for advanced studies may be considered for radical new technologies that will be directly relevant to and markedly improve the performance of the rapid design and prototyping infrastructure. As such, any advanced study should address one or more of the key technical components outlined above under “RAPID DESIGN AND PROTOTYPING INFRASTRUCTURE.” Example technologies include, but are not limited to: large-scale, high-fidelity DNA assembly tools and processes; automated and scalable genome editing tools applicable to a variety of organisms; methods for the transformation and genetic manipulation of non-traditional production organisms; and generalizable technologies for high-throughput screening and analysis. Proposers should pay consideration to developing component technologies that can be readily automated, parallelized, scaled-up, and/or utilized in reduced reaction volumes as appropriate.

D. Teaming and Partnerships

It is anticipated that successful proposals will be comprised of multi-disciplinary teams, and that successful implementation will require academic and industrial collaborations. Teams may be led by industrial, academic, or non-profit entities, among others. It is expected that the proposed leadership team will include individuals with significant experience and expertise in directing operations and technology development, leading large and diverse teams with both academic and industrial partners, and have significant experience in industrial process design.

Proposers are expected to identify industrial and commercial partners to aid in focusing technology development and identifying target molecules. This expectation allows the rapid design and prototyping infrastructure to benefit from industrial partner knowledge and allows industrial partners to impact design processes based on experience.

Proposed efforts should be fully integrated and demonstrate that all components are necessary and inseparable. Disjointed efforts submitted under a single proposal will be considered non-responsive. DARPA prefers that the core team members and researchers be co-located with the centralized rapid design and prototyping infrastructure (i.e. working side-by-side) to maximize interactions and project focus. Proposers should provide justification for inclusion of any core team members that will not be co-located with the center and provide a clear plan for how they will be fully integrated into the project.

Successful proposals will tightly couple any proposed computational tool development, process optimization, and experimental work. Successful teams will include members with experience in fields such as computer science, engineering, automation, industrial process development, chemistry/chemical engineering, and the biological sciences, among other areas.

E. Program Plan and Technical Milestones

In proposing to the Living Foundries: 1000 Molecules BAA, proposers should focus on 3 aspects:

(1) Designing and demonstrating a rapid design and prototyping infrastructure that will enable a radical improvement in capabilities over state-of-the-art (SOA); and

(2) Outlining the technical approach(es) to be pursued to meet the infrastructure and DARPA 1000 goals; and

(3) Identifying and justifying the molecules and chemical building blocks proposed for each DARPA 1000 Challenge Area.

The Living Foundries: 1000 Molecules program will consist of two sequential Task Areas (i.e.

proposers may not apply to both Task Areas simultaneously)—TA1 and TA2—and should not exceed 60 months in total program length. TA1 may last up to 6 months and is expected to be highly competitive based on the fundamentals of proposed concepts, teaming arrangements, and capabilities. At the completion of TA1, proposers may be encouraged/discouraged to apply to TA2, depending on the quality of TA1 deliverables. TA2 will consist of three phases, and proposals will only be considered from performers that have completed TA1. Phase I and Phase II of TA2 should last no more than 18 months each. Phase III of TA2, the final program phase, should last no more than 24 months.

Task Area 1 (up to 6 months): DARPA requires proposers to submit all initial proposals to TA1. TA1 serves as a design and study phase to allow performers to explore and refine the proposed infrastructure design and technical approach along with the non-physical structures (e.g., management, costing, etc.). As part of TA1, performers should develop metrics and milestones to gauge progress for intended technologies and infrastructure capabilities, as well as quantify the maturity and risk of each technology and capability. In parallel, performers will refine the technical path proposed toward generating target molecules for DARPA 1000 and develop a detailed list, with justification, of molecules targeted in Phase I of TA2, as well as a draft list of molecules and/or molecule classes targeted for Phase II. Additionally, teams will be expected to solidify the infrastructure governance structure, firmly establish academic and industrial partnerships, and finalize project schedules, fee structures, and strategies for intellectual property. Proposers may include a limited number of initial proof-of-concept experiments during TA1 period of performance to further strengthen the project plan and mitigate risk.

Proposers may also include an option period following completion of TA1 for initial work towards early TA2 goals. This option should function to bridge the gap between TA1 and TA2, building on the technology plan developed in the TA1 base period. This option should last no longer than 6 months and should demonstrate progress towards overall program goals. It is anticipated that not all options will be funded, and it should be noted that exercising of the TA1 option does not constitute a guarantee of selection to participate in TA2.

Deliverables from TA1 should include a detailed project plan and a complete description of the proposed rapid prototyping infrastructure and management structure, including addressing all elements described above under “RAPID DESIGN AND PROTOTYPING INFRASTRUCTURE,” that will accomplish the program’s goals and milestones (see Table 1).

Additionally, performers are required to deliver a presentation to the government team summarizing TA1 results, including a refined technical approach and plan for TA2, one month prior to end of the TA1 period of performance to aid in DARPA’s encourage/discourage decision for proposing to TA2. As TA1 consists largely of project plan development, it is anticipated that funding will be limited. Completion of TA1 is mandatory in order to propose to TA2.

Note, there is the potential that not all performers from TA1 will be encouraged to propose to TA2, depending on the quality of the delivered infrastructure plan and presentation. This procedure is intended to minimize unnecessary effort in proposal preparation and review for TA2. Regardless of DARPA’s encourage/discourage decision, proposers who complete TA1 may submit a proposal to TA2. Furthermore, there is the potential that not all of those who propose to TA2 will be selected to perform in TA2, depending on the quality of the proposal and availability of funding.

Task Area 2: Performers that complete TA1 may submit proposals to TA2. It is expected that proposals to TA2 will build off of the initial technical approach and plan proposed for and refined during TA1. Proposals should include three phases throughout which each rapid design and prototyping center is expected to demonstrate competency at optimizing increasingly complex engineering of biological systems and to demonstrate production of at least 350 unique molecules and chemical building blocks. Furthermore, in order to probe the capabilities and flexibility of the Facilities at each phase of development, a Government-specified Pressure Test will be administered no less than one month before the end of each of the three Phases in TA2.

The Pressure Test will assess the ability of each team to successfully demonstrate a range of capabilities, to potentially include biosynthesis of defined target molecules, engineered cellular functions, and logic-based genetic circuits. Each team will receive approximately 5-10 targets at least 1 month prior to the end of each phase and will be challenged to produce as many of these as possible during the remainder of that Phase. Proposers also need to consider in their proposal the appropriate resources needed to accomplish these Pressure Tests.

Phase I (up to 18 months): Performers selected to participate in Phase I will establish a rapid design and prototyping infrastructure and initiate system integration and process optimization.

As part of DARPA 1000, performers must demonstrate improved production relative to current state-of-the-art manufacturing processes for at least 10 target molecules by the end of Phase 1.

These target molecules must meet the criteria defined in DARPA 1000 Challenge Areas 1 and 2

(i.e. known molecules for which a known biosynthetic pathway exists and known, but currently inaccessible, molecules). Target molecules should span a wide breadth of structural and functional diversity and may be grouped in distinct performer-defined classes. Because relevant performance metrics vary for production of different target molecules, proposers should include and justify aggressive quantitative metrics relevant to each target. Example metrics may include, but are not limited to, those that relate to product yield, cost, and purity. In addition to the Phase 1 target molecules, performers are also required to deliver a detailed list and justification of the target molecules to be pursued in Phase II, as well as document completion of the first Pressure Test.

Phase II (up to 18 months): During Phase II, performers will continue advancing the infrastructure, and underlying tools with significant emphasis on system integration, throughput, and process optimization. Performers must demonstrate production of at least 60 target molecules from Challenge Areas 1 and 2, with a minimum of 15 known, but currently inaccessible, target molecules from Challenge Area 2 to demonstrate the design capabilities of the infrastructure facilities. Deliverables will include the Phase II target molecules, demonstrated completion of a second Pressure Test, along with a detailed list and justification of the molecules targeted in Phase III.

Phase III (up to 24 months): In Phase III, performers will finalize integration of the rapid design and prototyping infrastructure. Facilities should demonstrate quantifiable improvements in the biological design-build-test cycle, in throughput, and expand the complexity and breadth of products. To pressure test the flexibility and functionality of each facility, performers must generate at least 200 additional target molecules from Challenge Areas 1 and 2, with at least 30 of these molecules from Challenge Area 2 (known, but currently inaccessible, target molecules).

As in previous phases, target molecules should span a large breadth of structural and functional diversity and performers should develop appropriate quantitative production metrics for each target. Finally, each facility will be required to demonstrate the production of at least 10 completely novel molecules (Challenge Area 3), in addition to the unknown Pressure Test targets that will be provided one month before the end of the Phase.

Advanced Studies: Advanced studies for novel component technologies should last a maximum of 24 months and should consist of 2 phases, each no longer than 12 months. Advanced studies should address one or more technical components targeted as part of infrastructure development.

Proposals for advanced studies should be clearly identified as such on the title page of the proposal and explain the relevance of the work to the overall program goals, as well as propose detailed objectives and quantitative metrics. Groups proposing advanced studies are encouraged to identify teams proposing rapid design and prototyping facilities that may be able to leverage the tools and technologies resulting from such a study.

Metrics and Milestones: Proposers shall identify appropriate technical milestones as outlined above. To facilitate evaluation of technical progress and feasibility proposers are required to propose a minimum of one set of intermediate milestones (and corresponding quantitative metrics) relating to infrastructure development, improving the biological design-build-test-analyze cycle, and molecule production at least every 6 months. In addition, proposers should identify and justify the molecules and chemical building blocks proposed for each Challenge Area (note these may be grouped into distinct classes of molecules as appropriate). Performance will be continually evaluated on the likelihood of achieving the final goals of the program, including performance during the Pressure Test. Should it be determined that substantial progress is unlikely, DARPA does not guarantee continued funding (whether that be incremental funding or exercise of an option).

The required technical milestones and deliverables are listed below in Table 1. Proposals should list the required program goals of each phase and also propose the required intermediate milestones. Proposals that do not propose required intermediate and end-of-program-phase milestones will be considered non-conforming to the solicitation. Proposals should provide a clear technical plan with schedule, associated technical approaches, and risk mitigation plan to achieve the program’s milestones and goals.

F. Table 1: Living Foundries: 1000 Molecules program milestones and deliverables

TA/PHASE Timeline Milestones Deliverables

Task Area

Up to 6 months

• Solidified infrastructure project plan

• Initial proofs-of-concept (option)

• Initial infrastructure development (option)

• Finalized, detailed project plan for the center, including physical infrastructure, technical approach and justification, capabilities to be developed, management and governance structure, academic and industrial partnerships, project schedules, framework for external user/collaborator access, strategies for intellectual property, and all elements described above under “RAPID DESIGN AND

PROTOTYPING INFRASTRUCTURE.”

• Identification and justification of TA2 Phase I target molecules

• Established academic and industrial partnerships

• Presentation to government team summarizing

TA1 results and notional plan for TA2 (due 1 month prior to end of Task Area 1 Period of Performance)

Task Area

Up to 18 months

• Demonstrate production of at least 10 target molecules from Area 1 or 2 of DARPA 1000

• At least 2 additional sets

• Production of at least 10 target molecules from DARPA 1000 Challenge Areas 1 or 2, with quantifiable improvement in production for those that have been previously produced biosynthetically

• Identification and justification of Phase II target

Phase I of proposer defined milestones related to demonstrating infrastructure capabilities molecules

• At least 2 additional sets of proposer defined metrics (corresponding to proposed milestones) related to infrastructure capabilities

• Demonstrate ability to successfully produce as many of the Pressure Test targets as possible, issued one month prior to completion of the Phase.

Task Area

Phase II

Up to 18 months

• Demonstrated production of at least 60 target molecules from Areas 1 and 2 of DARPA 1000

• At least 2 additional sets of proposer defined milestones related to demonstrating infrastructure capabilities.

• Production of a total of at least 60 target molecules from DARPA 1000 Challenge Areas 1 and 2, with quantifiable improvement in production for those that have been previously produced biosynthetically

• Production of at least 15 target molecules from DARPA 1000 Challenge Area 2 as part of the 60 total target molecules to be produced

• Identification and justification of Phase III targets

• At least 2 additional sets of proposer defined metrics (corresponding to proposed milestones) related to demonstrating infrastructure capabilities

• Demonstrate ability to successfully produce as many of the Pressure Test targets as possible, issued one month prior to completion of the Phase.

Task Area

Phase III

Up to 24 months

• Demonstrated production of at least 200 target molecules from Areas 1 and 2 of DARPA 1000

• Demonstrate production of at least 10 novel target molecules from Area 2 of

DARPA 1000

• At least 3 additional sets of proposer defined milestones related to demonstrating infrastructure capabilities

• Production of a total of at least 200 target molecules from DARPA 1000 Challenge Areas 1 and 2, with quantifiable improvement in production for those that have been previously produced biosynthetically

• Production of at least 30 target molecules from DARPA 1000 Challenge Area 2 as part of the 200 total target molecules to be produced

• Production of at least 10 molecules from DARPA 1000 Challenge Area 3

• At least 3 additional sets of proposer defined metrics (corresponding to proposed milestones) related to demonstrating infrastructure capabilities

• Demonstrate ability to successfully produce as many of the Pressure Test targets as possible, issued one month prior to completion of the Phase.

Program End

Up to 60 months

• Demonstrate production of at least 350 distinct target molecules

• Target molecules beyond the minimum required may fall under any DARPA 1000 Challenge Area in order to achieve the 350 molecule goal

• Production of 350 distinct target molecules, with quantifiable improvement in production for those that have been previously produced biosynthetically

• Production of at least 45 target molecules from DARPA 1000 Challenge Area 2 as part of the 350 total target molecules to be produces

• Production of at least 10 novel target molecules from DARPA 1000 Challenge Area 3

G. Bio-Safety and Security

Proposers must ensure and demonstrate throughout the program that all methods, demonstrations of capability, and designs of engineered organisms comply with National guidance for synthetic biology, manipulation of DNA and organisms, and address biological safety, biological security, and concerns associated with Dual Use Research. Proposers should consider and include in the proposal the appropriate measures to manage, monitor, and employ risk mitigation associated with biological safety and security that may need to be instituted with such a Facility. This may not be limited to physical security alone, but should also include cyber security and other intrinsic biologic measures for safeguarding the proper use of production organisms. Note that all work conducted in the Facility associated with biological organisms should be responsive to the United States regulations designed to protect human health, the environment, security, and justice as promulgated by the Environmental Protection Agency, National Institutes of Health, Department of Homeland Security, Department of Health and Human Services, US Department of Agriculture, Federal Bureau of Investigation, Department of Justice, or other relevant agencies of the Federal Government. Proposers must also comply with any state or municipal regulations or ordinances governing biotechnology practices.

Additionally, all proposed prototyping facilities under Living Foundries: 1000 Molecules should be amenable to external review for biosecurity by DARPA- designated groups.

Proposers should be sure to refer to the following documents:

1. Presidential Bioethics Commission Report on Synthetic Biology:

http://bioethics.gov/synthetic-biology-report

2. NIH "Dual Use Research: A Dialogue" (a 7 minute video):

http://oba.od.nih.gov/biosecurity/biosecurity.html

3. NIH Office of Biotechnology Assessment (OBA) "Does Your Research Have Dual Use Potential?" http://oba.od.nih.gov/biosecurity/pdf/EducationalBrochureDualUseResearch.pdf

4. National Science Advisory Board for Biosecurity (NSABB) Reports http://oba.od.nih.gov/biosecurity/biosecurity_documents.html

- Enhancing Responsible Science- Considerations for the Development and Dissemination of Codes of Conduct for Dual Use Research (February 2012)

- Guidance for Enhancing Personnel Reliability and Strengthening the Culture of Responsibility (September 2011)

- Strategies to Educate Amateur Biologists and Scientists in Non-life Science Disciplines about Dual Use Research in the Life Sciences (June 2011)

- Addressing Biosecurity Concerns Related to Synthetic Biology (April 2010) http://bioethics.gov/synthetic-biology-report http://oba.od.nih.gov/biosecurity/biosecurity.html http://oba.od.nih.gov/biosecurity/biosecurity_documents.html

5. United States Department of Health and Human Services Guidance Document on Synthetic Biology and Synthetic dsDNA Research:

http://www.phe.gov/Preparedness/legal/guidance/syndna/Documents/syndna-guidance.pdf

6. NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) http://oba.od.nih.gov/rdna/nih_guidelines_new.htm

7. Biotechnology Program under the Toxic Substances Control Act (TSCA):

http://epa.gov/biotech_rule/pubs/biorule.htm

8. International Treaty and on Prevention of Biological Weapons/ Biological Weapons Convention; http://www.state.gov/www/global/arms/treaties/bwc1.html http://www.unog.ch/80256EE600585943/%28httpPages%29/04FBBDD6315AC720C125718000 4B1B2F?OpenDocument

II. AWARD INFORMATION

Multiple awards are anticipated. 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. V.), 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 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. DARPA will http://www.phe.gov/Preparedness/legal/guidance/syndna/Documents/syndna-guidance.pdf http://oba.od.nih.gov/rdna/nih_guidelines_new.htm http://epa.gov/biotech_rule/pubs/biorule.htm http://www.state.gov/www/global/arms/treaties/bwc1.html http://www.unog.ch/80256EE600585943/%28httpPages%29/04FBBDD6315AC720C1257180004B1B2F?OpenDocument http://www.unog.ch/80256EE600585943/%28httpPages%29/04FBBDD6315AC720C1257180004B1B2F?OpenDocument 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.

A. 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 subcontractor may be conducting contracted fundamental research. In those cases, it is the prime contractor’s responsibility to explain in their proposal why its subcontractor’s effort is contracted 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 subcontractors, 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 subcontractor proposals for Contracted Fundamental Research, papers resulting from unclassified contracted 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 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, e-mail 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 by-mail to prc@darpa.mil or via 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/NewsEvents/Public_Release_Center/Public_Release_Center.aspx.

III. ELIGIBILITY INFORMATION

A. Eligible Applicants

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

1. Historically Black Colleges and Universities (HBCUs), Small Businesses, Small Disadvantaged Businesses and Minority Institutions (MIs) are encouraged to submit proposals and join others in submitting proposals; however, no portion of this announcement will be set aside for these organizations’ participation due to the impracticality of reserving discrete or severable areas of this research for exclusive…