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A -- Accelerated Manufacturing of Pharmaceuticals (AMP)

Solicitation Number: BAA06-31
Agency: Other Defense Agencies
Office: Defense Advanced Research Projects Agency
Location: Contracts Management Office
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BAA06-31
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Presolicitation
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Added: March 29, 2006
Accelerated Manufacturing of Pharmaceuticals (AMP) BAA06-31, Proposals Due 1600 ET, June 21, 2006, POC: Michael Callahan, M.D., DTM&H, DARPA/DSO; Phone: (571) 218-4596.DESCRIPTION

The Defense Sciences Office (DSO) of the Defense Advanced Research Projects Agency (DARPA) is seeking proposals for new technologies that radically accelerate the manufacturing of protein vaccines and protein-based therapeutics. This program is a key component of an overall DARPA focus to accelerate the insertion of critical therapeutics essential for the military.

The vision of the Accelerated Manufacturing of Pharmaceuticals (AMP) program is to create an extremely rapid, flexible and cost-effective manufacturing system capable of producing three million doses of GMP-quality vaccines or monoclonal antibodies (mAB) within 12 weeks. This revolutionary manufacturing platform will have extraordinary flexibility, allowing for the manufacture of vaccines to protect against a wide range of viral, protozoan, fungal, bacterial and toxin antigens. The monoclonal antibodies produced by the platform will have the same efficacy and solubility profile as current FDA-approved monoclonal antibodies. Strong preference will be given to platforms that are capable of producing both small monomeric proteins (vaccine-like) and monoclonal antibodies.

All proposers to this BAA must provide evidence of a highly integrated, multi-disciplinary team capable of fulfilling the entire vision, meeting all program objectives and milestones for each phase of the program.

An accompanying Proposer Information Pamphlet (PIP) has been developed to aid in the preparation of proposals (www.darpa.mil/dso/solicitations/AMPPIP.pdf). Successful proposals will address the program goals and specifications outlined in this BAA and the associated PIP.

At the conclusion of this program, the proposer will deliver a high capacity, rapid vaccine and monoclonal antibody manufacturing system ready for transition to a commercialization partner and capable of producing protein therapeutics that are eligible for FDA approval.

AMP is a three phase, 42-month program with a goal of revolutionizing protein therapeutics and vaccine manufacture. Unlike previous DARPA programs, the focus of AMP is not to develop new therapeutics or vaccines, but rather to develop new technologies to speed the manufacture of protein based drugs and vaccines to meet the needs of the Warfighter. Each phase requires logarithmic increases in the number of doses of vaccine and/or monoclonal antibody produced in the candidate system.

The AMP program will consider a wide range of novel and non-traditional protein manufacturing platforms provided that they are capable of producing high quality monoclonal antibody and vaccines within the radically-shortened timelines. A key consideration is that protein production must be extremely flexible as the system will need to produce a wide range of proteins after being given the proper DNA construct. All platform systems will need to demonstrate production of a minimum of three proteins, one picked by the proposer and two test cases, where the target protein is selected by DARPA. These tests, known as 'Live Fire Tests,' provide an objective measure of performance. Manufactured proteins may be either a small vaccine antigen or a monoclonal antibody; however, DARPA WILL GIVE PERFERENCE TO TECHNOLOGIES THAT ARE CAPABLE OF PRODUCING THE WIDEST RANGE OF SIMPLE, COMPLEX AND DIMERIZED PROTEINS.



PROGRAM PHASES

The Accelerated Manufacturing of Pharmaceuticals (AMP) program goal of 3 million doses of vaccine or protein therapeutic in 12 weeks is an extremely aggressive effort. This will be conducted in three phases of 12, 15 and 15 months, respectively. A successful proposal will thoroughly cover all details for meeting the milestones set forth for Phase I and Phase II as well as a discussion of the path to accomplish the milestones in Phase III. At the end of each phase, the team’s performance will be evaluated based on its achievement of the Phase’s milestones.



Based on the results of each Phase and the availability of funding, a down-select is possible. SUCCESSFUL COMPLETION OF ANY PHASE DOES NOT GUARANTEE SELECTION IN THE NEXT PHASE. Performers that are selected to continue to Phase III will deliver 3 million doses of a protein therapeutic within 12 weeks in a second DARPA Live Fire Test with additional metrics of increased speed and reduced cost.



Specific program milestones for each of the three Phases are detailed in the accompanying Proposer Information Pamphlet:



In Phase I (12 months), the proposer must demonstrate that the synthesized protein has proper structure and functionality as demonstrated by routine biophysical and biochemical assays such as chromatography and mass spectrometry. Phase I requires that the performer outline a plan to demonstrate protein purity and proper protein folding. As part of the Phase I milestones, the proposer must also demonstrate a clear plan as to how they will achieve the milestones in Phase III, including cost estimates for protein production during manufacture at larger scale.



In Phase II (15months), the required rate of protein production increases 10-fold and should be demonstrated in standard 30L fermenters or equivalent using alternate protein manufacturing platforms (see Special Case below), over a period of 12 weeks. Requirements for proper structure of the manufactured protein also become more stringent. Phase II includes the first of two DARPA Challenges known as Live Fire Tests in which the proposer has 3-months to manufacture a vaccine or monoclonal antibody against a DARPA-selected target. The Live Fire Test provides an objective measure of the proposer’s technical capability.



Phase III (15 months) will achieve the overall goal of producing 3 million doses of a protein therapeutic within 12 weeks in a second DARPA Live Fire Test. Phase 3 will also require an additional 10-fold increase in the speed of manufacturing compared to Phase II. In Phase III, the estimated costs of manufacture should be less than $1/dose for a vaccine and less than $10/dose for a mAB.



Special Case: Non-fermentative and Alternative Protein Manufacture



Proposers that present alternative protein manufacture such as plant-based, algal, arthropod, transgenic and other non-fermentative based protein manufacturing systems must indicate a metric for assessing equivalent measures to the yield of doses/(liters*week). For example, a proposal based on plant-based monoclonal antibody production, which might be measured in doses per acre, must provide and defend their rate metric for each of the three Phases.



TEAM ORGANIZATION

The aggressive goals of the Accelerated Manufacturing Program require that each proposal include a multi-disciplinary team with demonstrated (or established) capability. The composition of the team might include large pharmaceutical companies, small biotechnology companies, agricultural genetic engineering groups, academic research laboratories, pharmaceutical consultant groups, enzyme and alcohol manufacturers and privately funded research programs. Proposals that center solely on one research sub-component, while neglecting the overall vision and required end capability, will not be considered for funding. At a minimum, teams are expected to possess expertise or demonstrate collaboration with members in the following areas:



a) Molecular Biology- with expertise in protein cloning, purification processes and optimization of growth conditions.

b) Protein Chemistry- with expertise in structure of proteins and post-translational modification (e.g. amidation and glycosylation)

c) Manufacturing- expertise in large scale production of proteins.

d) Expertise in FDA certified Good Manufacturing Processes (c GMP) regulations



Strong, competent team leadership is essential for successful implementation of the elements of this program. For this reason, it is critical that the research team be organized around an integration partner or Systems Integrator (SI) who has the responsibility of overall program management and who will maintain a focus on the AMP objectives.



DARPA will evaluate proposals based on the composite expertise and experience of the teams, their understanding of the challenges, current data, access to facilities to conduct the proposed work, and most importantly, a clear plan to achieve the specific milestones of the program. It is left to the discretion of the proposer to construct their team from the private, academic and commercial parties that will be necessary to carry out the effort.



Since team composition will ultimately determine the success of this program, a teaming website will be set up to facilitate these interactions (http://www.sainc.com/ampteaming/)



EVALUATION AND FUNDING INFORMATION

Proposals will not be evaluated against each other, since they are not submitted in accordance with a common work statement. DARPA's intent is to review proposals as soon as possible after they arrive. For evaluation purposes, a proposal is the document described in Proposal Format. Other supporting or background materials submitted with the proposal will be considered for the reviewer's convenience only and not considered as part of the proposal. DARPA reserves the right to request an oral presentation of proposals. If such a request is made, it is expected that, to the extent possible, all key personnel on the team will be present. The request for an oral presentation, or lack thereof, should not be construed as either a positive or negative assessment of the proposal.

The Government reserves the right to select all, some, or none of the proposals received in response to this solicitation and to make awards without discussions with proposers; however, the Government reserves the right to conduct discussions if the Source Selection Authority later determines them to be necessary. Proposals identified for funding may result in a contract, grant, cooperative agreement, or other transaction depending upon the nature of the work proposed, the required degree of interaction between parties, and other factors. If warranted, portions of resulting awards may be segregated into pre-priced options.

The following evaluation criteria are listed in order of decreasing importance. Proposals that are deemed unsatisfactory in Scientific and Technical merit will not be evaluated further.

Scientific and Technical Merit

Proposals will be evaluated as follows: Proposers must demonstrate that their proposal is innovative and unique, that the technical approach is sound, that they have an understanding of critical technical issues and risk and that they have a plan for mitigation of those risks. A significant improvement in capability or understanding above the state of the art in the manufacture of biological pharmaceuticals must be demonstrated. A key consideration is that protein production be extremely flexible as the system will need to produce a wide range of proteins after being given the proper DNA construct. A critical part of the evaluation is to provide details describing a clear pathway to a Phase III transition including plans for transition to a commercialization partner capable of producing protein therapeutics that are eligible for FDA approval. All milestones must be clearly and quantitatively described. Proposers are encouraged to avoid obscure language and indeterminate measures of success as these will not help the application.

Value to Defense

Proposals will be evaluated as follows: Proposers must demonstrate the AMP vision to create technologies that will enable the Department of Defense to have a rapid (within weeks) and highly effective medical therapeutic response to any intentional or naturally emergent pathogen.

Capability of the Personnel and Facilities to Perform the Proposed Effort

Proposals will be evaluated as follows: Proposers must demonstrate that their team has the necessary background and experience to perform this project. Interdisciplinary teams should include expertise or demonstrated collaboration in molecular biology, protein chemistry, and manufacturing expertise in FDA certified cGMP regulation. The Systems Integrator (SI) is responsible for ensuring that the team meets all milestones and metrics and integration of all proposed research. Facilities should be detailed with discussion of any unique capabilities pertinent to the research. Expertise can be acquired from many sources including consultant groups with an active stake in the program.

Cost Realism

The objective of this criterion is to assure that proposed cost is consistent with proposed effort. The proposed cost will be evaluated as follows:

Costs are justified in relation to the scope of the proposed program. Other funding sources and activities are taken into account. A budget for an optional second and third phase is provided and includes justification of all costs.



SUBMISSION REQUIREMENTS

The accompanying Proposer Information Pamphlet (PIP) contains necessary details regarding program planning and objectives as well as guidelines for white paper and proposal preparation, submission and evaluation that are not contained in this BAA (http://www.sainc.com/dso0631/). Other supporting or background materials submitted with the white paper or full proposal will be considered for the reviewer’s convenience only and not considered as part of the white paper or proposal. White papers and proposals received by fax will not be accepted.

All responsible sources capable of satisfying the Government's needs may submit a proposal that shall be considered by DARPA. Small Disadvantaged Businesses (SDB), Historically Black Colleges and Universities (HBCUs) and Minority Institutions (MIs) are encouraged to submit proposals and join others in submitting proposals. However, no portion of this BAA will be set aside for SDB, HBCU and MI participation due to the impracticality of reserving discrete or severable areas of this research for exclusive competition among these entities.

WHITE PAPERS

DARPA encourages the submission of White Papers to allow for comments to the proposer. White papers should be concise and limited to 8 pages in length. The white paper shall consist of: executive summary, scientific and technical challenges, methods to meet milestones, and cost estimations. Details regarding the white paper are included in the PIP.

The white paper should demonstrate that the proposer has a clear understanding of current protein manufacturing systems, including shortcomings in current capability. Milestones must be associated with demonstrable metrics of performance for Phase I and Phase II as well as a clear pathway to advance to Phase III.

White papers may be submitted and received at any time until the white paper deadline.

WHITE PAPERS ARE DUE TO THE ADDRESS SHOWN BELOW NO LATER THAN 1600 ET, May 17, 2006.

Within two weeks of receipt of the white paper, the proposer will receive a confirmation providing a log number. The formal recommendation about whether a full proposal is recommended will be made as soon as possible. However, the exact time for response will depend on a variety of circumstances, including the number of white papers received. Please note: Feedback provided is for the benefit of the proposer and following these recommendations is not a guarantee that the full proposal will be funded.

FULL PROPOSALS

The PIP outlines necessary details for proposal submission. Proposals shall consist of two volumes: Technical and Cost. Specific attention should be paid to technical expertise of the System Integrator and other key research members, and a management plan for multi-organizational teams.

Proposals may be submitted and received at any time until the full proposal deadline.

PROPOSALS ARE DUE TO THE ADDRESS SHOWN BELOW NO LATER THAN 1600 ET, June 21, 2006.

PROPRIETARY INFORMATION



All proprietary information should be clearly marked on the white paper and full proposal. It is the policy of DARPA to treat all white papers and full proposals as competitive information and to disclose their contents only for the purpose of evaluation. Standard proprietary disclaimers notwithstanding, proposals may be reviewed by non-Government technical experts who have signed a nondisclosure agreement with DARPA, unless the specific phrase TO BE REVIEWED BY GOVERNMENT EMPLOYEES ONLY appears on the cover sheet. In any case, personnel under exclusive contract with DARPA who have completed the appropriate nondisclosure agreements will handle the proposals for administrative purposes.



GUIDANCE FOR CLASSIFIED INFORMATION AND DATA



The Government anticipates that proposals submitted under a BAA will be unclassified.



In the event that a proposer chooses to submit a classified proposal, the following information is applicable.



Proposals may contain classified information or data (up to the level of Top Secret/SCI). HOWEVER, DO NOT SEND CLASSIFIED FULL PROPOSALS BY EMAIL OR VIA ONLINE SUBMISSION SYSTEMS.



Proposers that intend to include classified information or data in their proposals should contact DARPA security at (571) 218-4842 (or alternatively, the point-of-contact for this BAA) for security guidance and direction in advance of proposal preparation. Proposers must have existing approved capabilities (personnel and facilities) to perform research and development at the classification level they propose.



Security Classification guidance on DD Form 254 will not be provided at this time since DARPA is soliciting ideas only. After reviewing the incoming proposals, if a determination is made that the award instrument may result in access to classified information, a DD Form 254 will be issued and attached as part of the award.



Proposers choosing to submit a classified proposal must first receive permission from the Original Classification Authority to use their information in applying to this BAA. An applicable classification guide should be submitted to ensure that the proposal is protected appropriately.



For instructions on submitting Classified Full Proposals, contact Security & Intelligence Directorate (SID) Classification Management at (571) 218-4842.



RESEARCH INVOLVING HUMAN USE

Proposals selected for funding are required to comply with provisions of the Common Rule (32 CFR 219) on the protection of human subjects in research (http://www.dtic.mil/biosys/downloads/32cfr219.pdf) and the DoD Directive 3216.2 (http://www.dtic.mil/whs/directives/corres/html2/d32162x.htm). All proposals that involve the use of human subjects are required to include documentation of their ability to follow Federal guidelines for the protection of human subjects. This includes, but is not limited to, protocol approval mechanisms, approved Institutional Review Boards (IRB), and Federal Wide Assurances. These requirements are based on expected human use issues sometime during the entire length of the proposed effort.

For proposals involving ‘greater than minimal risk’ to human subjects within the first year of the project, performers must provide evidence of protocol submission to a federally approved IRB at the time of final proposal submission to DARPA. For proposals that are forecasted to involve ‘greater than minimal risk’ after the first year, a discussion on how and when the proposer will comply with submission to a federally approved IRB needs to be provided in the submission. More information on applicable Federal regulations can be found at the Department of Health and Human Services Office of Human Research Protections website (http://www.dhhs.gov/ohrp/).

PATENT INFORMATION

Please include documentation proving your ownership of or possession of appropriate licensing rights to all patented inventions (or inventions for which a patent application has been filed) that will be utilized under your proposal for the DARPA program. If a patent application has been filed for an invention that your proposal utilizes, but the application has not yet been made publicly available and contains proprietary information, you may provide only the patent number, inventor name(s), assignee names (if any), filing date, filing date of any related provisional application, and a summary of the patent title, together with either: 1) a representation that you own the invention, or 2) proof of possession of appropriate licensing rights in the invention. Please also provide a good faith representation that you either own or possess appropriate licensing rights to all other intellectual property that will be utilized under your proposal for the DARPA program. If you are unable to make such a representation concerning non-patent related intellectual property, please provide a listing of the intellectual property to which you do not have needed rights, and provide a detailed explanation concerning how and when you plan to obtain these rights.

ADMINISTRATIVE ADDRESSES

Web address for White Paper Submission: http://www.sainc.com/dso0631/dsowhitepaper/index.asp

Web address for Full Proposal Submission:

http://www.sainc.com/dso0631/dsofullproposal/index.asp



DARPA/DSO, ATTN: BAA06-31

3701 North Fairfax Drive

Arlington, VA 22203-1714



Electronic Mail: BAA06-31@darpa.mil



Related URLs:

BAA 06-31: http://www.darpa.mil/baa/baa06-31.html

PIP 06-31: http://www.darpa.mil/dso/solicitations/AMPPIP.pdf

Teaming Website BAA 06-31: http://www.sainc.com/ampteaming/



Point of Contact:

Michael Callahan, M.D., DTM&H

Program Manager, DSO

Phone (571) 218-4596

Email: Michael.Callahan@darpa.mil

Fax: (703) 807-4945

:
Other Defense Agencies, Defense Advanced Research Projects Agency, Contracts Management Office, 3701 North Fairfax Drive, Arlington, VA, 22203-1714
:
Michael Callahan, DSO Program Manager, Phone (571) 218-4596, Fax (571) 218-4553, Email michael.callahan@darpa.mil