March 10 Pre-Proposal QA Amendment Final.doc

AMENDMENT TO BARDA BROAD AGENCY ANNOUNCEMENT

ADVANCED DEVELOPMENT OF CHEMICAL, BIOLOGICAL, RADIOLOGICAL, AND NUCLEAR MEDICAL COUNTERMEASURES

Broad Agency Announcement Number:

BAA-BARDA-09-34

Amendment Number:

One (1)

Amendment Posting Date:

March 24, 2009

Issued By:

Biomedical Advanced Research and Development Authority (BARDA)

330 Independence Ave., SW, Room G640

Washington, D.C. 20201

Point of Contact:

Primary: Glynis Fisher, Contract Officer glynis.fisher@hhs.gov

Alternate: Jeannett Jackman, Contract Specialist jeannett.jackman@hhs.gov

SUMMARY OF CHANGES

A. PURPOSE: The purpose of this Amendment is to make minor revisions and post questions received from industry and the government’s responses from the Pre-Proposal Conference conducted March 10, 2009.

(1) Revise: Part I: Research Areas of Interest, Area of Interest #3: Antimicrobials and Antivirals Technical Point of Contact has changed from Dr. Dawn Myscofski to Dr. Edward Niles.

(2) REVISE: Attachment 7: Quad Chart/White Paper Format Template is hereby revised from “Preparation Picture or Graphic that illustrates the research or concept” to “Picture or graphic that demonstrates the technology, research, or concept. Pictures that merely show the threat agent, mock of drug packaging or other marketing graphics are not recommended.”

(3) The date specified for receipt of proposals remains unchanged. Except as provided herein, all terms and conditions of the Broad Agency Announcement remain unchanged.

BAA-BARDA-09-34 - BARDA BROAD AGENCY ANNOUNCEMENT FOR THE ADVANCED DEVELOPMENT OF CHEMICAL, BIOLOGICAL, RADIOLOGICAL, AND NUCLEAR MEDICAL COUNTERMEASURES

QUESTIONS AND ANSWERS FROM PRE-PROPOSAL CONFERENCE #1

TUESDAY,

MARCH 10, 2009

1. What is the timing and process for submitting a proposal under the BAA?

Decision within 90 days

Source Selection Notification (pending availability of funds)

Within 180 days of Full Proposal receipt

Please review Part IV: Proposal Preparation and Submission section on page 19 for further information on review time.

2. How will proposals submitted at different times be evaluated for an award – i.e. is a company disadvantaged by submitting a proposal late in the year, or alternatively will proposals for individual interest areas be evaluated together regardless of when they are submitted?

Proposals (Quad Chart and White Paper) will be accepted until December 31, 2009. The same review time will apply to all proposal submissions regardless of when they are received (Quad Chart and White Paper). See Part IV: Proposal Preparation and Submission for further information.

Note: Our first set of instructions will be issued for anthrax vaccines and therapeutics. Quad Chart and White Papers are due March 24, 2009. See Part VI: Special Instruction for further information.

3. Does BARDA intend to select awardees on a continuous chronological basis, or will awardees be selected on a periodic basis or some target date? (e.g. quarterly/semi-annual or specific date later in the year).

The number for awards will be dependent on the amount of funding available for advanced research and development. BARDA expects to make one award cycle in FY09 due to timing. However, BARDA anticipates at least 2 award cycles per year in FY10 and beyond.

4. What will the mandatory eligibility criteria, in regards to stage of development (technology readiness level), be for products for which an Offeror seeks funding? For example, will products for these two research areas need to have successfully completed a Phase 1 human clinical trial, or will in vivo preclinical efficacy data be adequate to be considered for funding?

The BAA states that product maturity should ideally correlate with TRLs 6 and 7 (pre-IND to Phase 2 clinical study). However, proposals of high technical merit and relevance, outside of the TRLs 6 and 7 may be chosen for award based on USG priorities.

The BAA does not have mandatory eligibility criteria. Proposals will be evaluated based on four criteria (page 31 Part V: Evaluation)

1. Programmatic Relevance

2. The overall scientific and technical merits of the proposal

3. The Offeror’s capabilities, related experience, and past performance, including the qualifications, capabilities, and experiences of the proposed key personnel

4. Cost realism and reasonableness.

Mandatory eligibility criteria may be stated in the special instructions for a particular research area.

Please review Part VI: Special Instructions prior to submission of a Quad Chart and White Paper for research area number 1, 2, 4-5.

5. Can the current requirements or other documents that outline the likely government market size and desired product characteristics for research areas of interest be shared with industry?

Information as to the market size and desired product characteristics of particular products are shared with industry as part of Requests for Proposals, which can be found on the medical countermeasure website (www.medicalcountermeasure.gov), the BARDA website (http://www.hhs.gov/aspr/barda), and FedBizOps. To learn about the overall priorities for medical countermeasure development, please see the 2007 PHEMCE Implementation Plan for Medical Countermeasures for CBRN Threats. See also answer to question #28.

6. Will contracts under this solicitation include an option for procurement? If not, will companies with late stage products -- defined as ready for consistency lot manufacture and conduct of pivotal studies – be expected to go through a separate competition for a procurement contract? If so, how does BARDA intend to reduce the time lag between solicitation and award to minimize delays to ongoing programs?

This BAA is not intended to be used for procurement of products; it is intended to be used to bridge the valley of death between R&D and procurement. Procurement contracts will continue to be issued by BARDA using the Special Reserve Fund under Project BioShield.

The intent of this BAA is to facilitate the development of candidate products through the regulatory approval process towards pre-licensure utilization.

7. What is the anticipated release date for the final BAA and anticipated submission due date? Is it anticipated that BARDA will issue a BAA similar to this once again next year?

This is a “rolling BAA” and proposals can be submitted anytime between March 4, 2009 and December 31, 2009. Submissions after December 31, 2009 will be considered upon renewal of the BAA for 2010 calendar year pending availability of funds.

8. The FY 2008 ASPR Annual Performance Report contemplated FY09 target activities that included "Issue a BAA for evaluation of antibody-based antitoxins currently available in combination therapies (contracts awarded in FY10). Issue BAA for small-molecule antitoxin innovation (contracts awarded in FY10). Fund development of one anthrax vaccine enhancement program." Does BARDA intend to issue these BAAs in FY 2009 or is the BAA issued this month intended to capture these goals?

The current BAA captures these goals.

9. Will there be an EVM requirement? Our understanding is that HHS requires any award over $25M to use EVMS. Please confirm.

Offerors are encouraged to establish and use a project management system with EVMS characteristics in the management of their contract. HHS policy does require EVMS for work at the developmental level for a dollar value exceeding $10M on a cost reimbursement type contract. BARDA will work with the offerors to provide guidance toward development and implementation approach that is appropriate for the specific contract type

10. Assuming that Congress passes the FY 09 budget, which includes $275 million for BARDA, does BARDA anticipate funding any of the selected programs this fiscal year? If so, how will funding determinations across research areas of interest be made?

BARDA anticipates going through one award cycle in FY09. BARDA anticipates two award cycles in FY10.

The number of awards under this BAA for each fiscal year will depend on the amount of funding available to BARDA through the appropriations process. Funding determinations will be made based on the criteria identified in the BAA and alignment with the PHEMCE Implementation Plan for CBRN Threats. http://www.hhs.gov/aspr/barda/phemce/index.html

11. What are BARDA’s plans for spending money from the 2009 proposed omnibus package?

Please see the answer to question 10.

12. What is the intended duration of funding under this BAA?

It is anticipated that contracts awarded under this BAA will be awarded as one-year base contracts with one-year options up to 5 years. Continuation of funding after the initial year is dependent upon availability of funds and achievement of milestones.

13. Will DHHS consider firm fixed contracts for research related work and/or clinical trials? How will the mechanism of funding (cooperative agreement, grant, or contract) be determined for each project that is given an award?

BARDA reserves the right to award the contract type best suited to the nature of the work proposed and may award any appropriate contract type under the Federal Acquisition Regulation. In the future BARDA may elect to make awards in the form of grants, cooperative agreements, or other transactional agreements (OTAs), as appropriate.

14. Can potential offerors submit multiple proposals for differing targets/projects under this funding mechanism?

Yes, offerors can submit multiple proposals (Quad Chart and White Paper) to the different research area of interest.

15. Will BARDA fund development and procurement of more than one product provided the products have comparable safety/efficacy/cost?

BARDA may fund development of more than one candidate product, but will not fund procurement under this BAA.

16. At what point is BARDA considering funding countermeasure candidates in the future—post Phase 1 clinical studies or earlier? If earlier, how early?

Under this BAA, the desired maturity of products should correlate with TRLs 6 to 7 (pre-IND to Phase 2 clinical study). Please also refer to the response to question #4 above.

17. On page 13, letter M, it states that the Product Development Plan should include a “Potential Plan for consideration of an EUA…” Does this mean that all activities leading to submission of an EUA package are covered under this solicitation? FDA’s Current Thinking requires the use of consistency lot material for EUA – so, one could argue that this solicitation should cover consistency manufacture.

On page 11 Part II: Research and Technical Objectives. This section provided a listing of typical developmental activities in the areas of non-clinical research, manufacturing, clinical evaluation, project management, and regulatory strategy contained in a typical drug, biologic or device development effort. This information is provided to assist and guide Offerors in preparing their Statement of Work (SOW). Offerors shall submit a SOW in their proposal that addresses these topics as appropriate. The specific reference is for a Potential Plan for consideration of an EUA. BARDA reserves the right to fund all, some, or none of the proposals submitted; may elect to fund only part of a submitted proposal; and may incrementally fund any or all awards under this BAA.

Offerors should have a clear understanding of the regulatory path to obtain licensure/approval of their candidate products, for the proposed indication at a relatively early stage of development. Additionally, offerors should have a plan to fulfill the required data set for potential use of the product during a declared emergency under an EUA.

18. The BAA states that the proposal can include manufacturing scale-up to lead to consistency lot manufacturing. Can this include up to 3 validation lots?

Details of product development plan will be discussed further only when Offerors have been invited to submit a Full Proposal. Please also refer to the response to question #4 above.

19. Could these validation lots be used for pivotal safety and efficacy studies? Does this BAA cover pivotal studies?

Currently the BAA does not cover pivotal studies. This activity falls under TRL 8. Please also refer to the response to question #4 above. It is BARDA’s current intent to fund pivotal animal studies and Phase III clinical trials under Project BioShield acquisition contracts.

20. Footnote 4 within TRL7 (Attachment 1, page 40) describes GLP animal efficacy studies to support EUA. Are these supportive animal efficacy studies or pivotal efficacy studies?

These are supportive animal efficacy studies. Pivotal efficacy studies are considered a TRL 8 activity.

21. Will antibody therapeutic approaches be considered as medical countermeasures?

Yes. BARDA has not placed restrictions on the types of MCMs that may be developed under this BAA.

22. Will this BAA fund platform development for subunit vaccine/antigen/epitope discovery?

Yes. However, the desired maturity of products should correlate with TRLs 6 to 7 (pre-IND to Phase 2 clinical study).

23. Will this BAA fund pre-clinical production and testing of vaccine candidates?

Yes. However, under this BAA, the desired maturity of products should correlate with TRLs 6 - 7 (pre-IND to Phase 2 clinical study).

24. Is there an interest in combination vaccines e.g. anthrax/smallpox?

Yes. Under this BAA, the desired maturity of products should correlate with TRLs 6 to 7 (pre-IND to Phase 2 clinical study).

25. What breadth of coverage would a broad spectrum antibiotic need to cover to be of interest? Will this BAA include further development of a broad-spectrum technology platform?

Specific guidance on the product can only be discussed with the Offeror in context of how it aligns with PHEMCE/BARDA program relevance, when invited to submit a Full Proposal

26. What classes of therapeutics are BARDA interested in (i.e. small molecule, polyclonal antibody, etc.)?

All classes of therapeutics would be considered if they are relevant to PHEMCE/BARD’s program. However, BARDA’s preference would be for MCMs that are less expensive and have a broad spectrum of activities.

27. What is BARDA’s interest in polyclonal antibodies for therapeutics?

See response to Question 26 above

28. Can you tell us anything about the product characteristics you are interested in?

Products should have the typical desirable characteristics for any biologic or drug, including but not limited to, safety and efficacy. BARDA is also interested in developing products that are easy to administer, have a relatively long shelf-life and can be stored and deployed under conditions that minimize the risk to the cold chain, if needed. . Specific guidance on the product can only be discussed with the Offeror in context of how it aligns with PHEMCE/BARDA program relevance and preference, when invited to submit a Full Proposal.

29. Will this BAA fund clinical studies involving pandemic and/or seasonal influenza vaccines?

Seasonal and Pandemic Influenza will not be covered by this BAA. BARDA does support pandemic influenza medical countermeasure programs. Information related to those programs can be found on our website at:

http://www.hhs.gov/aspr/barda/mcm/panflu/activities.html

30. Is there a specific list of targets that this BAA is intended for? Will all pathogens listed in the List of NIAID Emerging and Re-emerging Diseases, Category III – Agents with Bioterrorism Potential be considered? Will any pathogens be given special consideration?

BARDA’s CBRN priorities are aligned with the preparedness mission of the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE), as articulated in the PHEMCE Implementation Plan for CBRN Threats:

http://www.hhs.gov/aspr/barda/phemce/index.html

31. Will this funding mechanism support clinical trials for an anti-nerve gas therapeutic candidate?

Yes, this BAA is in alignment with the PHEMCE Implementation Plan for CBRN Threats, which calls for the development of MCMs against volatile nerve agents.

32. This Offeror believes that the TRL 6 to 7 requirements for proposals concerning drugs and biologics may be so restrictive that valuable opportunities to fund development of technologies aligned with BARDA’s priorities will be missed. Several of the specific Areas of Interest listed in the BAA appear incompatible with the requirement that “for drug and biologic medical countermeasure development efforts, Offerors shall propose a Statement Of Work (SOW) consistent with activities between Integrated Technology Readiness Levels (TRLs) 6 to 7”. The screening and characterization research described in Areas of Interest 2.1 and 3.1 appears to be TRL 3 or even lower; it is also not clear how an offeror would reconcile the concept of a general platform technology (area 1.2) with the very specific TRL 6/7 requirements for GLP animal studies, IND submission and GMP pilot lots. Furthermore, a proposal for the repurposing of a commercially licensed drug against a biodefense threat agent (Area of Interest 3.3) would already exceed TRL6/7 by virtue of having completed GLP pre-clinical work, Phase I trials, and manufacturing, yet the necessary animal models for demonstrating efficacy against the biodefense threat agent may only be at TRL 4. Will BARDA confirm that proposals for drug or biological MCM development that are not at TRL 6/7, or that don’t neatly fit into this category, will not necessarily be considered non-responsive solely on the basis of the TRL of the work proposed?

The BAA guidelines are drawn generally for multiple Areas of Interests, and it is conceivable that specific activities in areas indicated such as Screening and Characterization or Platform technology may belong at a an earlier TRL. The Offeror is expected to have completed these activities and shown by a proof of concept as part of ‘development and characterization’. Offerors are encouraged to make their case in the proposals if they have a compelling reason to be outside of the desired TRL 6/7. Specific guidance on the product can only be discussed with the Offeror in context of how it aligns with BARDA program relevance, when invited to submit a Full Proposal.

33. Would a submission from a program in TRL 4 be discouraged?

Submission of a program in a TRL 4 maturity will not be discouraged; however, all proposals will be evaluated on how well the proposals align with the evaluation criteria for example the scientific and technical merit, how well the proposal fit BARDA’s areas of interests.

34. Will demonstration of in vivo efficacy and preliminary non-GLP toxicology data be needed to be eligible for funding under this BAA?

It is expected, based on the preference of funding between TRL 6 and 7, that this type of work be already completed; however, exceptions may be made.

35. We are not aware of a filovirus countermeasure that is a treatment per se; would BARDA consider vaccines if no treatment exist? Are countermeasures, especially vaccines directed against viral hemorrhagic fever agents other than Lassa and Ebola fever, specifically Rift Valley fever, eligible for funding under this BAA?

As described in PHEMCE IP for CBRN threats, VHF-related MTDs have been issued for Ebola, Marburg and Junin. MCMs for Lassa and RVF are not currently considered PHEMCE priorities. MCMs developed and acquired must align with concepts of operation for public health emergencies. Currently, no FDA-approved filovirus-specific medical countermeasures exist. An antiviral is preferred to treat infected patients and to provide pre-exposure prophylaxis to health care workers and personal contacts. A vaccine will be useful for civilian populations in a post-event context if it provides rapid onset of protective immunity. HHS will continue to invest in research and development for filovirus medical countermeasures.

36. In cases where product has already been delivered to the stockpile under an EUA, will BARDA facilitate discussions with FDA to enable companies with similar products to better understand what is required?

It is the offerors responsibility to communicate directly with FDA regarding the FDA’s current thinking on the requirements for EUA.

37. Would BARDA consider (arenavirus family-Junin) development efforts to be within the scope of the Implementation Plan goals and thus worthy of financial support under this BAA?

Junin virus has been identified as a material threat by the Department of Homeland Security and is listed in the PHEMCE Implementation Plan. Based on current funded constraints, MCMs against Junin virus should ideally have broad spectrum applicability.

38. Would BARDA consider funding the development of a smallpox antiviral topical formulation to prevent or treat adverse events following smallpox vaccination?

HHS has a requirement for a smallpox antiviral for the treatment of symptomatic individuals. Please refer to RFP-BARDA-09-35 for additional information on BARDA’s interest in developing and procuring smallpox antiviral for the Strategic National Stockpile. The link is:

https://www.fbo.gov/spg/HHS/OOS/OASPHEP/RFP-BARDA-09-35/listing.html

39. Is a smallpox antiviral oral suspension formulation a product that BARDA would consider supporting as an addition to the anti-smallpox arsenal?

HHS has a requirement for a smallpox antiviral for the treatment of symptomatic individuals. Please refer to RFP-BARDA-09-35 for additional information on BARDA’s interest in developing and procuring smallpox antiviral for the Strategic National Stockpile. The link is:

https://www.fbo.gov/spg/HHS/OOS/OASPHEP/RFP-BARDA-09-35/listing.html

40. Would BARDA consider funding the development of a smallpox antiviral orally delivered product as an adjunct to the smallpox vaccine to prevent or treat adverse events related to the vaccine?

HHS has a requirement for a smallpox antiviral for the treatment of symptomatic individuals. Please refer to RFP-BARDA-09-35 for additional information on BARDA’s interest in developing and procuring smallpox antiviral for the Strategic National Stockpile. The link is:

https://www.fbo.gov/spg/HHS/OOS/OASPHEP/RFP-BARDA-09-35/listing.html

41. What RFPs are coming in the next year and what are the plans for current RFPs?

Two RFPs have recently been released: an RFP (RFP-BARDA-09-100-SOL-00005) for the development MCMs to treat acute radiation syndrome and an RFP (RFP-BARDA-09-35) to develop smallpox therapeutics. Please monitor FedBizOps, medicalcountermeasures.gov, and the BARDA web site for a complete listing of BARDA RFPs.

42. Is there any consideration for the updating of the PHEMCE plan that was put forth in 2007?

The PHEMCE Implementation Plan is currently undergoing review. It may be revised in 2009 and/or supplanted by the BARDA Strategic Plan.

43. A joint BAA between BARDA and NIAID was released in 2008; is that a separate pot of money from this BAA or is that somehow overlapping?

The National Institute of Allergy and Infectious Diseases and BARDA jointly issued BAA-DMID-NIAID-BARDA-NIHAI20080022 (Platform Technologies) in February 2008. NIAID and BARDA have reviewed the proposals and are currently working out the details of contract awards in FY09. BARDA contracts awarded under the 2008 Platform Technologies BAA and our 2009 BAA will use advanced research and development funds

44. How do programs initiated through this BAA relate to DoD programs?

Through the Integrated National Biodefense Portfolio, HHS and DoD are aligning resources to accelerate the development of medical countermeasures that are in common to both Departments. If applicable, BARDA will share information regarding your proposals with both the NIH and the DoD. Memorandums of Understanding are in place between BARDA, NIAID and the DoD to facilitate the transfer and cross-funding of projects across the government.

45. What are the appropriate communication pathways for developers and BARDA to use during this BAA?

Developers are free to discuss their project plans with BARDA at any point prior to submission of a White Paper. Once a white paper is submitted, Offerors may not contact anyone other than the Contracting Officer with questions related to their proposal. Offerors may discuss their programs with scientific staff at BARDA if their White Papers are not accepted for the second round.

46. Part 1: How does this BAA relate to the RFP recently released for the advanced development of therapeutics for neutropenia from acute exposure to ionizing radiation? Part II: How can BARDA assist Offerors if there is potentially a 90 day window where Offerors cannot speak with scientific staff?

Part 1: The acute radiation syndrome (ARS) RFP specifically requests proposals to develop therapeutics that target the neutropenic component of acute radiation syndrome. The goal of any resulting contract is to bring the therapeutic towards licensure for an ARS indication. Therapeutics that are at an earlier stage of development or that target other aspects of acute radiation syndrome or other effects of radiation would be welcomed under this Broad Agency Announcement.

Part II: Offerors are encouraged to speak with the BARDA contracting officer and scientific points of contract prior to submitting their Quad Charts and White Papers. Offerors are also highly encouraged to seek feedback from BARDA if they are not requested to submit Full Proposals.

47. Would BARDA discourage an Offeror that currently has a candidate at a pre-IND phase?

BARDA encourages proposals with candidates between TRLs 6-7. However, BARDA may consider funding programs that are not currently funded by the USG if the countermeasure has distinct advantages over other USG-funded programs.

48. Part I: How will white papers be processed if there is a subsequent amendment to the BAA? Part II: How will priorities be set among the six categories in terms of funding?

Part I: Amendments to the BAA will largely be in the form of special instructions related to categories of medical countermeasures that BARDA has keen interest in developing. For example, special instructions have been published for the BAA in the fields of anthrax vaccines and anthrax therapeutics development.

Part II: The six categories under this BAA are not given in any order of priority. In 2009, BARDA will prioritize anthrax vaccines and therapeutics. In 2010, BARDA will be prioritizing on the technical merits of proposals as they relate to the Implementation Plan.

49. What will BARDA do with proposals that go through the full proposal review process and are not funded based on funding constraints?

BARDA would provide feedback to the Offeror, at which point the Offeror could submit a revised White Paper to the USG.

50. What is the level of interest in adjuvants?

BARDA is interested in the development of novel adjuvant technologies. If you look at BARDA’s influenza portfolio, for instance, you can see that there's a serious interest in developing adjuvant technologies to mix and match with existing vaccines. Our interest is in developing technologies that enhance our current vaccines by enhancing immunogenicity and reducing reactogenicity.