Amendment 2-Final-3-26.pdf

AMENDMENT TO BARDA BROAD AGENCY ANNOUNCEMENT

POINT OF CARE OR HIGH-THROUGHPUT BIOLOGICAL ASSAYS FOR

DETERMINING ABSORBED IONIZING RADIATION DOSE (BIODOSIMETRY) AFTER

RADIOLOGIC AND NUCLEAR EVENTS

Broad Agency Announcement Number: BAA-BARDA-09-36

Amendment Number: Two (2)

Amendment Posting Date: March 26, 2009

Proposal Intent Response Sheet Due Date: April 3, 2009 (Unchanged)

Proposal Due Date: April 17, 2009 at 4:30 P.M. (Unchanged)

Issued By: Biomedical Advanced Research and

Development Authority (BARDA) 330 Independence Ave., SW, Room G640 Washington, D.C. 20201

Point of Contact: Carl A. Newman, Contract Specialist carl.newman@hhs.gov

The above numbered Broad Agency Announcement is amended as set forth below. The hour and date specified for receipt of proposals HAS NOT been extended. Offerors must acknowledge receipt of this and all other amendments, by identifying this amendment number (and any others) and its date on each copy of any offer(s) submitted. Failure to receive your acknowledgement may result in the rejection of your offer. If by virtue of this amendment, you wish to change an offer already submitted, such changes may be made by telegram, letter or e-mail, provided each telegram, letter or e-mail makes reference to this Broad Agency Announcement amendment number and date and is received prior to the proposal due date and hour specified. Except as provided herein, all terms and conditions of the Broad Agency Announcement remain unchanged and in full force and effect. This amendment does not materially change this BARDA requirement.

PURPOSE OF THE AMENDMENT: This amendment: I. revises the language in the criteria for award and revises the point structure and II. revises the Proposal Intent Response Sheet and III. answers a number of inquiries.

I. Under Paragraph F (EVALUATION FACTORS FOR AWARD), subparagraph b.

(TECHNICAL EVALUATION CRITERIA), CRITERIA FOR THE AWARD is deleted and replaced as follows with revisions italicized:

CRITERIA FOR THE AWARD

1. CRITERION 1: STATEMENT OF WORK AND STRATEGIC PLAN

1. A. Proposed Statement of Work (SOW) (20 points) The Offerors’ proposed Statement of Work shall be measured as follows with the total score reflecting the aggregate evaluation of the Reviewers:

a) Objectives: The Statement of Work overall content will be measured in terms of clarity of project objectives, level of detail, linking and flow of tasks, and overall achievability with respect to resources, state of the science and time.

b) Deliverables: The itemization of the deliverables, milestones and decision points to achieve a product level of development for Pre-Market Approval (PMA) or other approval for marketing mechanism as called for by the Food and Drug Administration.

c) Clarity: The clarity of the Statement of Work i.e. descriptions of all necessary activities, timelines, services, personnel, materials, equipment and facilities, inclusive of subcontracting activities and other required activities used in the performance of the proposed Statement of Work.

d) Comprehensive Staged Product Development Plan (CSPDP): Within the context of the Statement of Work, the soundness and feasibility of the Comprehensive Staged Product Development Plan (i.e. identity of all standard and unique project-specific actions and processes, including experimental designs, the respective order of operations and precedence, staffing, time management, manufacturing, and non-clinical validation studies in appropriate models, regulatory obligations, etc) for advancing the diagnostic radiation dose assessment tool, device, biomarker, or bioassay through the PMA/510(k) process pathways.

e) Strategic Staged Product Development Plan (SSPDP): Within the context of the

Statement of Work, the soundness and feasibility of the Strategic Staged Product Development Plan (i.e., development strategy to satisfy a market demand, product marketability and optional markets) for advancing the diagnostic tool, device, biomarker, or bioassay through the PMA/510(k) process pathways.

f) PMA/510K Feasibility: The feasibility of completing the path to PMA/510(k) and producing the Final Summary documents for the PMA/510(k) filing within five (5) years for R&D, including completing Animal Rule studies (if requested) and producing the Animal Rule Study Report(s) within five (5) year contract periods (if the Animal Rule studies have not already been completed at the time of review).

g) Go/No Go Decisions: The soundness, feasibility, suitability and completeness of the proposed “Go/No Go” evaluations of the diagnostic tool, including the qualitative and quantitative criteria to be used to reach “Go/No Go” decisions at the various stages of product development and the budget for each stage of product development.

1. B. Comprehensive Staged Product Development Plan (CSPDP) (20 Points)

The Offerors’ proposed CSPDP shall be measured as follows with the total score reflecting the aggregate evaluation of the Reviewers:

a) Technology Advanced Development Readiness: Products which are ready for advanced development should already have supportive (but not yet definitive) data to support the characterization and selection of the radiation dose assessment tool, device, biomarker, or bioassay product for further development. Specifically, a summary of data that demonstrates accurate and reproducible radiation dose assessments in appropriate models is required. This includes: a detailed description of the biodosimetry tool, device, biomarker, or bioassay, in vivo and ex vivo animal models with rationale of the models as well as for the outcome/endpoints selected, the radiation exposure (and method of radiation exposure standardization); documentation that the animal experiments were performed under well-controlled experimental conditions, and, data that support whether and how the dose assessment tool specifically addresses the USG need.

b) Communications with FDA: Communications with appropriate review divisions at the FDA (e.g. CDRH, CDER and CBER) if any, that are relevant to development activities for the proposed device.

c) Critical Path Descriptions: A description of all activities that are part of the critical product development path through submission of a PMA (pre-Market Approval) or 510(k) (addition to or superiority to a predicate device) and activities that are required to enable studies, and identifies distinct stages of the product development pathway for Go/No Go decisions for advancing to the next stage of the Comprehensive and Strategic Staged Product Development Plan.

d) Offeror’s Experience: Adequacy of previous experience of the Offeror, and any proposed subcontractors, in conducting studies in compliance with GLP, cGMP and GCP guidelines as documented by the Offeror with audit histories and reports.

e) Facilities & Compliance: Adequacy of the plan to conduct audits of facilities and maintain compliance with GLP, GMP and cGMP, and/or GCP guidelines, where appropriate, and the inclusion of letters allowing pre-award site visits to Offeror and subcontractor facilities.

f) Animal Rule Protocol: The adequacy of the Animal Rule Protocol Synopsis and documented corporate (or subcontracted) non-clinical study experience in performing Animal Rule pivotal studies research in accordance with the Code of Federal Regulations.

1.C. Strategic Staged Product Development Plan (SSPDP) (10 points)

The Offerors’ proposed SSPDP shall be measured as follows with the total score

a) Overall Market Strategy: The Offeror shall define the overall market strategy for the tool, device, biomarker or bioassay including potential for other uses or platform integration.

b) Risk Mitigation Strategies – Plan / Market: Risk mitigation strategies for modification to the CSPDP, or the proposed market position of the product, based upon adverse market events over the course of the performance period.

c) Risk Mitigation Strategies – Technical / Regulatory: Risk mitigation strategies for adverse experimental or prototype results, new scientific findings, FDA communications and reviews, or changes authorized by the Contract Officer.

d) Feasibility of Meeting Plan: The feasibility of performing the proposed activities that require outside resources within the stated timelines for initiation, conduct, completion and analysis of data.

2. CRITERION 2: PRODUCT SPECIFIC AIMS OF THE CONTRACT (30 points)

The Offerors’ product specific aims shall be measured as follows with the total score

2.A. Functional Criteria:

a) Description of the Tool, Device, Biomarker, or Bioassay:

• The intended use, i.e. indication of absorbed ionizing radiation dose assessment, of the proposed tool, device, biomarker, or bioassay and the biodefense/ public health gap the product is intended to fill.

• The intended target product profile (TPP; see Attachment 4) for radiation dose assessment.

• The features of the product for radiation dose assessment for triage and/or patient management and treatment decisions.

• Device sensitivity to gamma radiation, reproducibility, precision, accuracy, sensitivity (dose range), dose rate effect, linearity, display criteria, ramp-up time, and tolerance. Also included are biomarker rise and plateau time, signal stability, target specificity, inter-individual variation, confounder effects, and detection limits1

b) Deployment: device mobility, ability to be packed up, shipped or transported under typical or atypical conditions, durability, use during a public health emergency2 transportability, storability (additional equipment, peripherals, and supplies), consumable requirements, maintenance requirements (preventive, procedural, storage), unit and maintenance costs, and clean-up requirements after use.

c) Operability: training and operator proficiency, ease of use, materials/user manuals and quality assurance testing procedures for instrumentation, data output, software and firmware maintenance and upgrades, platform requirements and integration, and required actions for routine daily use and maintenance.

2. B. Other Criteria

1 See Attachment 3 for statistical terms and definitions as well as an example of a diagnostic test employing statistical methodologies and how to compare one test system versus another using Receiver Operator Characteristic (ROC) curves 2 A public health emergency could include, importantly, an IND event. The response parameters for such an event are described in the Homeland Security Council’s Planning Guidance for Response to a Nuclear Detonation which can be accessed at http://www.afrri.usuhs.mil/outreach/pdf/planning-guidance.pdf .

a) Design and Development Criteria: Design/development encompasses sample collection and processing, patient tracking, device throughput, throughput from sample collection to data output, additional support equipment, device restrictions, limitations, storage requirements, data integration, hardware/ disposable requirements, durability (field ruggedness/resistance, EMP ruggedness/interference during storage, duration of performance period, environmental sensitivities), power requirements, data retention, data output, data interpretation, software engineering, portability (weight and dimensions), feasibility studies, scientific studies, algorithm development, and prototyping.

b) Manufacturing Criteria: The proposal must demonstrate a concept maturity suitable for advanced development, a predictive time to mass production, manufacturability, time to prototype, an understanding of all documentation as related to development, maintenance, manufacturing and test/evaluation of the dose assessment tool, platform technical approach, shelf life, and useful life.

c) Personnel Requirements: Criteria include training and operator proficiency, certification requirements, materials/user/training manuals, class of operators, communications interface, documentation, data storage, and security.

d) Safety/Hazards Criteria: These criteria include leakage/breakage hazards, reagent hazards and disposal requirements.

2. C. Regulatory Criteria The Offeror’s regulatory activities within the Comprehensive Staged Product Development Plan will be evaluated. Descriptions of patents or published patent applications, cooperative agreements, or licenses that will be used in the performance of the contract are required. The Offerors shall provide the patent number or patent application publication number, a summary of the patent or invention title, and disclose the patent or invention owner.

3. CRITERION 3: Capabilities of Staff, Facilities and Project Management (20 Points)

The Offeror’s capabilities of staff, facilities and project management shall be measured as follows with the total score reflecting the aggregate evaluation of the Reviewers:

3. A. Primary Staffing and Company Organization

a) Principal Investigator(s): Appropriateness of the documented qualifications, knowledge, experience, education, competence, and availability of the Principal Investigator (PI) to carry out the proposed Statement of Work.

b) Project Manager: Appropriateness of the documented qualifications, knowledge, experience, education, competence and availability of the Project Manager (PM) to carry out the proposed Statement of Work.

c) Key Personnel: Appropriateness of the documented qualifications, knowledge, experience, education, competence and availability of the other key personnel, provided by the Offeror or by subcontractors or consultants (e.g. manufacturing, regulatory, human and animal models, assay development, etc.) to carry out the proposed Statement of Work, and the appropriateness of the responsibilities and level of effort of all proposed staff of the Offeror and any proposed subcontractors and consultants.

d) Staff Mix: Adequacy of the proposed mix of staff, expertise, experience, and training (e.g., research, manufacturing, veterinary, regulatory, statistical, management, administrative) to carry out the Statement of Work.

3. B. Facilities, Equipment and Other Resources As required and/or appropriate for the Offerors’ proposed Statement of Work:

a) Facilities & Equipment: Availability and adequacy of facilities, equipment, and other resources, including contracted facilities, to safely and adequately perform all phases of the proposed project including, but not limited to, irradiation, dosimetry, animal care, and assays.

• Laboratory and Animal Facilities: Availability and suitability of facilities, and ability to add or delete facilities if needed, to conduct assays and animal studies in accordance with USDA and FDA regulations and guidelines, including GLP & GCP guidelines and AALAS certifications, if applicable.

• Manufacturing Facilities: Availability and suitability of facilities to manufacture radiation dosimetric products according to cGMP guidelines, if applicable.

b) Safety Programs: Environmental health and safety programs, laboratory and site surveillance, adequacy of containment facilities, and radiologic safety as needed (for guidance refer to, for example, the Department of Energy’s Lawrence Berkeley Laboratory Environmental Health and Safety Publication 3000 (http://www.lbl.gov/ehs/pub3000/CH21.html#_Toc407168416 ).

3. C. Project Management

As required and/or appropriate for the Offerors’ proposed Statement of Work:

a) Project Management Plan: Adequacy of the Project Management Plan in terms of staffing, organization, responsibilities, leadership and lines of authority.

b) Project Management Systems: Suitability of systems proposed for tracking project activities and monitoring progress, timelines, and budgets.

c) USG – Offer Communications: Suitability of the plan for how the key personnel will communicate with the Project Officer and the Contracting Officer, as well as establish lines of communication between all performance sites and activities.

d) Sub-Contractor: Suitability of the plan for soliciting, evaluating, negotiating, awarding and managing any proposed subcontracts in accordance with Federal regulations. Adequacy of the plan for identifying and remedying problems in sub-contractor performance.

e) Agreements Between Parties: Completeness of Letter(s) of Understanding between collaborating parties to address intellectual property, facilitate development of commercialization, and resolve disputes.

f) External Advisory Group Communications: Adequacy of the plan to protect and share confidential information with the External Advisory Group members.

g) Review Meetings: Suitability of the plan to organize the Annual Review Meetings and provide for a thorough assessment of contract status, progress, problems, and approaches to their resolution, and future plans.

TOTAL POSSIBLE POINTS: (100 Points)

II. Under Paragraph H (LIST OF ATTACHMENTS), Attachment 2 (Proposal Intent Response Sheet) is deleted and replaced with Attachment A (Proposal Intent Response Sheet) (See Enclosure).

III. The following answers are provided concerning a number of inquiries received subsequent to the issuing of this broad agency announcement:

1. Question: We are familiar with a group that has an ultra sensitive portable protein detection system and we would like to clarify if there would be an opportunity to submit a proposal for this device on its own or if they would have to partner with another group for biomarker content and submit a joint proposal for an IVD.

Answer: The goal of this BAA is to facilitate development of biodosimetry assessment tools (device, biomarker, or bioassay). To meet this goal, the system must contain a means to detect an individual’s absorbed dose of ionizing radiation. A detection system alone does not meet this goal.

However, coupled with a radiation responsive biomarker, it could meet BARDA’s needs.

2. Question: [We] are working on a contract for DARPA for breath tests for diseases. They’ve gone through Phase I and are now working on Phase II. They are looking at biomarkers and oxidative stress. Is this responsive to your effort?

Answer: If the answer for biomarkers and oxidative stress can be linked to radiation response, the system could meet BARDA’s needs.

3. Question: Are these specifications ALL required or are they targeted specifications? For example, our point of care (POC) has an assay that can be done from sample to answer in 60 minutes. Your requirement is 15 minutes so would our current technology still be interesting as we will be able to show a path forward to improve kinetics during the next few years? However, we could deliver prototypes and most of the other parameters sooner based on one hour test.

Could you comment?

Answer: The specifications shown in Attachment 4 of the BAA are nominal unit values not required but rather intended as guidance for the Offerors in developing Target Product Profiles (TPP). Offerors are expected to develop and deliver their intended TPPs with their technical proposal as explained in Section F of the BAA, (EVALUATION FACTORS FOR AWARD). Offerors may indicate threshold and objective values in their TPPs.

4. Question: We have developed a novel high throughput, multiplexed nucleic acid-based assay chemistry that uses microsphere arrays as a platform but that is amenable to DNA microarrays or gel based formats. Our method has been developed for detection of microbial pathogens, and screening of genetic susceptibility to disease but has not been applied to the area of radiation biology.

Can the application of our novel method for the development of a bioassay for radiation biodosimetry be considered "advanced development" as is called out in the BAA?

Answer: The application of a novel method for the development of a bioassay for radiation biodosimetry might be considered advanced development under this BAA if the system contains a means to detect an individual’s absorbed dose of ionizing radiation.

5. Question: Regarding deliverables, the BAA clearly calls for Reporting Requirements and Deliverables (Section E). Will any prototypes need to be delivered? In the 'Scope' section, page 5, 16th line from the top, the BAA mentions a 'possibility' of 'obtaining' prototypes. Will this be done through a separate purchase order or are the offerors expected to price it in - perhaps as another option?

Answer: Yes. The Government expects you to include the cost of your prototypes, if applicable to your project, within your cost proposal.

6. Question: Regarding the data and IP, please clarify the requirements to be placed on an offeror (page 10 - 'Prior to award' MOU). Can you please outline in more detail what BARDA would require from the offerors at a minimum? Will the data be owned exclusively by BARDA? What about IP? Being a small business, we would very much appreciate what FAR clauses - especially regarding IP and data ownership - that will be included in a final contract so that we are prepared accordingly.

Answer: Regarding intellectual property, please see the clause regarding intellectual property found on page 12 of the BAA. Regarding ownership of patent and data rights, potential applicable clauses are FAR 52.227-11 and 52.227-14. For more detail please review FAR subpart 27.3 and 27.4.

7. Question: Are there any previously held vendor conferences or public BARDA meeting notes that you could point us to?

Answer: The BARDA Stakeholders Workshop/BARDA Industry Day was held in September 2008. Many of the plenary presentations from this Workshop and the “HHS PHEMCE Implementation Plan for Medical Countermeasures against CBRN Threats,” as well as other information about BARDA, can be found at the following web sites: www.hhs.gov/aspr/barda and www.medicalcountermeasures.gov/barda

8. Question: After reading through the offering, we had a question on whether or not to use the salary cap of $196,700 (current office of extramural research rate cap: http://grants.nih.gov/grants/policy/salcap_summary.htm) in the application budgets.

Answer: Please do not exceed the direct salary ceiling for one full time equivalent ($196,700) which is noted under the Executive Schedule, Level I.

9. Question: Because our procedures are fairly far advanced and already being done in human subjects, we would like to clarify the rules regarding clinical activities. Specifically the types of samples that need to be used are from human subjects. Also, the procedures required for the developments and the verification of efficacy will be best done in human subjects. We already have approved protocols for these procedures and have carried out the developments in human subjects. There are no suitable animal models for the development of the deployable device. The required studies do not constitute a clinical trial.

Answer: Offerors are expected to submit their clinical/regulatory activities and plans in their proposals including development of suitable animal models for qualification/validation if required.

10. Question: Can we include the personnel needed for the management of the project and the preparation of reports (manager, administrative assistant, financial assistant).

Answer: Yes. Proposals should include all required administrative and managerial support for contract activities.

11. Question: I would like to confirm that the primary contractor can be a university.

(e.g. page 31).

Answer: The prime contractor can be any eligible organization including universities.

12. Question: What is the requirement for small business subcontracting plans?

Page 46 provides the guidelines for large businesses but what are the requirements if the primary contractor is a university? Is this affected if one of the subcontractors is a large business?

Answer: Small businesses are not required to submit a Small Business Subcontracting Plan. The determination of a small business is based on the NAICS code which is 541711 which in this case is an organization with 500 employees or less. All clauses applicable to prime contractors flow to the subcontractors.

http://www.hhs.gov/aspr/barda http://www.medicalcountermeasures.gov/barda http://grants.nih.gov/grants/policy/salcap_summary.htm

13. Question: The instructions indicate that there should be an attachment 3 to the technical proposal but it is not clear what is wanted from the responder.

Answer: Attachment 3, “Statistical Terminology and Definitions and Statistical Test Example,” is found at the end of the BAA, page 58. It was provided as a helpful source of information. BARDA does not request input in Offerors’ proposals with respect to Attachment 3.

14. Question: Please clarify the relevance and importance of including plans for the integration of the products into the response system for dealing with a major event. If it is within the aims of the BAA, we would like to include a significant component in which we assess the needs for the device to meet the needs of the people who would likely be organizing and participating in the response to the event and the information system that will be employed.

Answer: Offerors should be aware that BARDA is seeking tools to address mass casualty events such as those following a 10 KT Improvised Nuclear Device event, and is working closely with event planners in the Federal Response community to model the scenarios and develop concepts of operation. Therefore, in their proposals, Offerors are encouraged to describe only the feasibility of using the candidate device within its intended setting(s), but should not include the development of implementation plans or assessing the need of the device.

15. Question: Is there a specific form of ionizing radiation that the sponsor is interested in?

Answer: BARDA is interested in the biological response to any form of ionizing radiation. This BAA is looking for a means to measure the post-radiation biological response of subjects, not a direct measure of radiation.

For the purposes of validation protocols, Offerors should be aware that BARDA is seeking tools to address mass casualty events such as those following a 10 KT Improvised Nuclear Device event.

16. Question: If animal studies are being conducted by our collaborator, from which IACUC should we be obtaining approval and associated documents? From the collaborating institution or the institution of the primary offeror?

Answer: Please contact the Office of Laboratory Animal Welfare (OLAW) for details. (http://olaw.nih.gov) (Eileen Morgan, 301-451-0384).

17. Question: For the intended target product profile, do we just include the attachment that fits the intended application of our device, biomarker or assay or do we need to modify the attachment to reflect the performance characteristics we expect to see?

Answer: Offerors should include the performance characteristics (TPPs) that they expect to achieve. The values in Attachment 4 are suggested guidance to develop an Offeror’s product TPPs. Please replace these nominal values with your tool’s actual Threshold and Objective Values.

http://olaw.nih.gov/

18. Question: What is the difference between the TPP and the description of performance specifications and features that the product should have?

Answer: The TPP requested from the Offeror is the description of the performance specifications and features the product should have. The sample TPP provided in Attachment 4 is a generalized set of functional criteria that describe plausible performance parameters for an unknown system. These values are intended targets, not necessarily specific product requirements. With their technical proposal, the Offeror should submit a revised TPP that reflects their product’s performance specifications, and the Offeror should also describe any other product features, characteristics, intended use and feasibility of use.

19. Question: Is the $41 million the max cost per contract or for all contracts that will be awarded under this BAA?

Answer: $41.4M is the total funding available for all contracts awarded under this BAA in year one.

20. Question: On pages 31 and 32, the BAA refers to "performance of Animal Rule trials under Good Clinical Practices (GCP) standards. I'm sure they are referring to Good Laboratory Practices standards because animal work isn't conducted under GCP rules.

Answer: The pivotal efficacy animal studies must be conducted under Good Laboratory Practices (GLP) (21 CFR Part 58), not GCP. For further information on Animal Rule regulatory compliance, see the FDA website noted on page 30 in the BAA (www.accessdata.fda.gov).

21. Question: In several places the BAA mentions that "Use of animal facilities with AALAS (American Association of Laboratory Animal Science;

http://www.aalas.org <https://mail.urmc.rochester.edu/exchweb/bin/redir.asp?URL=http://www.aalas.or g>) certifications is encouraged." (page 22) We assume that the BAA means AAALAC certification of the animal facility because they do mention AAALAC certification later in the BAA. Is AALAS certification of the technical staff required?

Answer: Please contact the Office of Laboratory Animal Welfare (OLAW) for details. (http://olaw.nih.gov) (Eileen Morgan, 301-451-0384)

22. Question: Will a device that is proposed to be cleared under the 510k pathway be scored more favorably than a device that will go through the PMA process?

Answer: A device that is proposed under the 510(k) pathway (as determined by the FDA) will not necessarily be scored more favorably than one that would go through the PMA process. A device that can reference an FDA cleared predicate device in its regulatory filings and therefore qualify to use the 510(k) pathway would appear favorable in regulatory cost and time to approval, but these are not the only criteria that will be scored, and therefore http://www.accessdata.fda.gov/ http://www.aalas.org/ https://mail.urmc.rochester.edu/exchweb/bin/redir.asp?URL=http://www.aalas.org https://mail.urmc.rochester.edu/exchweb/bin/redir.asp?URL=http://www.aalas.org http://olaw.nih.gov/

BARDA would consider devices that must follow a PMA process if their product demonstrates significantly improved performance characteristics.

23. Question: If we anticipate our device will be ready for clinical validation studies within the next five years, should we include those studies in this proposal?

Answer: Yes. Offerors should include plans for pre-clinical and clinical validation studies in their proposals. If Offerors have already conducted pre-clinical or clinical studies, the reports should be referenced in their proposals.

BARDA will rate technologies at a higher maturity level if the products have been demonstrated with supportive data. Please bear in mind the page number limits defined in the BAA Instructions to Offerors section.

24. Question: Our institutional information security officer has asked that BARDA assign a FISMA risk level for this Broad Agency Announcement.

Answer: FISMA risk levels, if applicable, will be assigned during contract negotiations.

25. Question: Are we allowed to include contingency funds or a management reserve fund in the budget?

Answer: No. Contingency funds or management reserve funds are not allowable costs. Please submit the budget based on business risk assessment in accordance with your work elements.

26. Question: Are there any special considerations for subcontractors based overseas?

Answer: If award is made to a foreign prime or subcontractor, BARDA will follow the process for notifying the embassy in the affected country prior to the intended award. Regarding regulatory compliance, all sub-contractors, including those based overseas, must comply with FDA standards or demonstrate that compliance with their own country’s standards are equivalent.

27. Question: Is GMP compliance required at all sites or only at those sites producing prototypes for FDA clearance?

Answer: Device manufacturing must comply with QSR (Quality System Regulation, 21 CFR part 820) –see the web-site for the FDA Centers for Devices and Radiological Health: www.fda.gov/cdrh/devadvice/. Good Manufacturing Practices (GMP) compliance requirements vary with project phase and other regulatory stipulations.

28. Question: Does BARDA have a cutoff or minimum level of throughput that they would like to see from any given biodosimeter to make it competitive for their interests? Concordant with that, can BARDA provide guidance as to the minimum amount of time for a sample?

http://www.fda.gov/cdrh/devadvice/

Answer: The nominal values in Attachment 4 for sample collection and analysis times/throughput are for guidance purposes to help Offerors understand the type of information we need in their developed TPPs. For POC devices, BARDA would like to see a time of <15 minutes (or up to 8 hours for high-throughput devices) from “sample collection to decision [result],” but proposals for longer throughput times will also be considered.

Offerors should describe their product’s processing time and throughput (number of samples per hour) in their TPPs. Offerors should also explain the feasibility of using their product/tool in, for example, one possible scenario concerning the need for POC diagnostics to test approximately 1,000,000 exposed individuals’ specimens in a 24-hour period in a given geographic region affected by a 10KT IND. This might be achieved by single-use consumable devices or multi-use devices. For high-throughput diagnostics, BARDA is concerned with testing approximately 400,000 samples (given the same scenario) within approximately 5 days.

29. Question: Is it acceptable to propose a development plan that might involve a change in device specifications (i.e. switching from a bench top to battery powered instrument) that is dependent upon in-development research?

Answer: Yes, it is acceptable to begin with a functional prototype that evolves to meet optimal device characteristics. The rationale for starting with a given prototype/model and then changing it should be fully addressed in the Comprehensive Staged Product Development Plan submitted with the Offeror’s proposal. In addition associated costs should be clearly delineated in the cost proposal and the Offeror should address possible impacts on the regulatory pathway.

30. Question: Is it acceptable to budget for early year R&D funds to develop advanced technologies that could significantly increase the throughput or speed of the device?

Answer: Yes, R&D funds may be budgeted for development of advanced technologies that will further optimize the product. The rationale for these efforts should be fully addressed in the Comprehensive Staged Product Development Plan submitted with the Offeror’s technical proposal.

31. Question: Does BARDA anticipate a biomarker-discovery phase for this work?

Answer: No. BARDA does not anticipate proposals for a biomarker discovery phase. Advanced biomarker development is acceptable.

32. Question: Does BARDA have go/no-go metrics, phasing, and timing in mind?

Answer: In their proposals, Offerors should propose Go/No-Go criteria in their Project Gantt charts as well as their Comprehensive Staged Product Development Plans (CSPDP) and Strategic Staged Product Development Plans (SSPDP).

33. Question: Where does BARDA want us to be at the end of one year?

Answer: BARDA anticipates awarding a variety of efforts that all support or lead to the development of biodosimetry tools, devices, techniques and/or biomarkers. Each effort will have its own milestones unique to the project.

34. Question: What selection criteria will BARDA use for approval of option years?

Answer: Selection criteria for exercise of option years cannot be anticipated at this time. They will be determined during contract negotiations for those proposals that receive awards.

35. Question: Which of the criteria in Attachment 4 are parts of the go/no-go criteria for year 1?

Answer: The TPPs in Attachment 4 are a generalized set of functional criteria that describe plausible performance parameters for an unknown system. These values are intended targets, not necessarily specific product requirements. With their technical proposal, the Offeror should submit a revised TPP that reflects their product’s performance specifications and Offerors should also describe any other product features, characteristics, intended use and their feasibility of use. Offerors should propose timelines and go/no-go criteria for their particular product in their CSPDP and Gantt charts.

36. Question: What is the market size for the POC device and consumables?

Answer: One potential scenario informing BARDA planning is the need to evaluate approximately 1,000,000 potentially exposed individuals’ specimens in a 24-hour period in a given geographic region affected by a 10KT IND event. Leveraging systems that are in routine clinical use for other indications and that could have additional tests integrated into their platforms are preferred, and this could also result in an increase in market size for these devices.

37. Question: What is the maximum acceptable cost per test for the point-of-care device? What is the maximum acceptable cost per test for the high-throughput device?

Answer: The maximum acceptable cost per test for the point of care (POC) or high-throughput device will vary depending on the technology being proposed. BARDA is likely to accept higher per-test costs for the high-throughput devices based on current concepts of operation. BARDA expects Offerors to provide an estimate of this cost—and feasibility of using the product in its intended setting—in their cost proposals.

38. Question: Would BARDA prefer a 1-year base and two 2-year options or a 1-year base and four 1-year options?

Answer: The schedule for the base year and option periods will be determined during contract negotiations. BARDA would prefer four 1-year options after the one-year base contract.

39. Question: On page 7, does BARDA intend "conduct of animal studies under GCP standards" or "conduct of animal studies under GLP standards"?

Answer: The pivotal efficacy animal studies must be conducted under GLP (21 CFR Part 58), not GCP.

40. Question: What is the time window (relative to the radiologic or nuclear event) for measurement?

Answer: One possible scenario concerns the need for POC diagnostics to test approximately 1,000,000 exposed individuals’ specimens in the first 24-hour period in a given geographic region following a 10KT IND. For high-throughput diagnostics, BARDA is concerned with testing approximately 400,000 samples (given the same scenario) within approximately 5 days. In addition, the nominal values in Attachment 4 for sample collection and analysis times/throughput are for guidance purposes to help Offerors understand the type of information we need in their developed TPPs. For POC devices, BARDA would like to see a time of <15 minutes (or up to 8 hours for high-throughput devices) from “sample collection to decision [result],” but proposals for longer throughput times will also be considered.

Offerors should describe their product’s processing time and throughput (number of samples per hour) in their TPPs.

41. Question: Will a self assessing dosimeter that is capable of also being read at Point of Care with a high-throughput reader that can store the results, meet the requirements of the BAA or is the BAA open for biodosimetry using bio-samples only?

Answer: For the purposes of this BAA (BAA-BARDA-09-36), BARDA is interested in the biological responses to an individual’s exposure to ionizing radiation. However, BARDA is also interested in POC self-assessment dosimeters, and has issued a BAA covering the chemical, biological, radiation and nuclear areas-with BAA-BARDA-09-34, under which interested vendors can submit a White Paper on projects concerning physical dosimetry tools.

42. Question: If a technology is currently available commercially, may prior milestones be used to offset the Research and Development requirements of the Comprehensive Staged Product Development Plan?

Answer: Yes. Offerors are encouraged to use commercially available systems/technologies in their proposals; any prior milestones achieved on the R&D pathway should be fully explained in the Comprehensive Staged Product Development Plan and Project Gantt chart.

43. Question: Is a technology that is currently available commercially and has been field tested, but has not been submitted to the FDA for Pre-market Approval or 510(k), acceptable for consideration under this BAA (non R&D)?

Answer: Yes. R&D funding toward the application of an established technology for the development of a bioassay for radiation biodosimetry would be considered advanced development under this BAA. Non-R&D efforts are not applicable under this BAA. The purpose of this BAA is to advance the maturity level of functional systems through a technology development phase to the point of readiness that can be independently assessed/evaluated by the Government for further consideration for procurement.

44. Question: If prototype hardware is developed, does BARDA want to receive the hardware at the completion of the effort? Should this hardware be defined as a deliverable? If not, how should the developed hardware be dispositioned at the end of the program?

Answer: Yes. Prototype hardware should be developed (if applicable to the proposed project) and delivered to BARDA upon completion of the effort. A small number of prototypes (one to three systems) should be defined as deliverables and included in the cost proposal; please price them on a per device or system basis. (The purpose of this BAA is to advance the maturity level of undemonstrated functional systems through a technology development phase to the point of readiness that can be independently assessed/evaluated by the Government for further consideration for a full scale procurement contract.)

45. Question: Page 24, Section G, 1, (b) identifies that proposal must be reproduced on letter-sized paper. Are 11x17 foldouts acceptable? Will the foldouts count as a single page?

Answer: No. 11x17 fold-outs are not acceptable unless they are needed for otherwise illegible text, such as a Gantt chart or TPP. In those cases, foldouts will count as a single page.

46. Question: Page 72, Attachment 4, Item 3.2.0 identifies the time to develop the first prototype in <= 1 year. Is this the time to develop the first prototype within the BAA effort or the time to develop the first prototype after the effort performed within the BAA is complete?

Answer: Attachment 4 provides an example of “Time to develop a prototype <=one year” as a target value but Offerors’ TPP and CSPDP should state specifically what the timelines will be to develop the first prototype within the BAA effort.

47. Question: Page 10, Will BARDA accept agreements between teammates that are titled differently from “Memorandum of Understanding” as stated in the BAA?

Answer: Yes. BARDA will accept agreements other than those titled “Memorandum of Understanding” as long as they meet the intent stated in the BAA. This will be further determined during contract negotiations.

48. Question: What is the degree of partnership between BARDA and the contractor? Will BARDA take the lead role in the interaction between the contractor and the FDA?

Answer: The Contractor will fulfill the role of developer (and eventually Sponsor). The Contractor will lead interactions between themselves and the FDA and BARDA will participate in those interactions.

49. Question: Will BARDA/NIH accept our resident Government audit agency, DCAA/DCMA, as the audit authority for rates and audit(s)?

Answer: Yes. The representative audit agency for a particular offeror is affiliated with the Government department that procures the most contract awards (in dollars) with that offeror.

50. Question: Are the GLP, GCP and GMP required of all the participants in a team, or is it just for the team member responsible for FDA approval? In other words, LBL (without GLP) can still participate in a team, right?

Answer: All activities that will be filed to FDA to support clearance/approval for medical devices need to be conducted in compliance with the QSR (GMP)—see 21 CFR part 820. All clinical or animal testing that is intended to generate data to support the regulatory submission must also be compliant with appropriate regulatory (Good Laboratory Practices (GLP)/Good Clinical Practices (GCP)) guidance.

51. Question: Please clarify whether submission of a diagnostic biodosimetry test to the FDA for regulatory approval/clearance is expected during the contract period.

Answer: Submission of a biodosimetry test to the FDA for clearance/approval would be supported but is not expected during the contract period.

52. Question: Please clarify the biodosimetry requirement for the POC diagnostic test. The BAA states that the POC device would be used to identify persons exposed to ionizing radiation exceeding 2 Gy (p.5). However, the BAA also states a goal of “accurate determination of an individual’s absorbed dose of ionizing radiation within the boundaries of 0.5 Gray (Gy; a unit of absorbed dose of ionizing radiation) to 10 Gy with a stated statistical certainty” (p.3). Is the POC test expected to provide a threshold determination of exposure to > 2 Gy, or a quantitative assessment of exposure in the range of 0.5-10 Gy?

Answer: The POC result is expected to be a qualitative, not quantitative, result that provides a threshold determination of an individual’s exposure to > 2 Gy. As an example, in the TPP nominal values in Appendix 4, BARDA provided a target dose range of 0.5 to 10 Gy for the POC device in order to obtain a result of > 2 Gy as its target. For a high-throughput system, the device should provide a quantitative assessment of exposure in the range of

0.5 – 10 Gy.

53. Question: How does the FDA Animal Rule mentioned in the BAA apply to the approval of a diagnostic device? Is the rule limited to drug products, or does it apply to devices as well?

Answer: The FDA’s Center for Devices and Radiological Health (the reviewing body on diagnostic device clearance) does not invoke the Animal

Rule per se in approval of a diagnostic device. However, the Offerors should first consult with the FDA.

54. Question: The BAA specifies a requirement for two prototypes within one year.

Could you please provide more details as to what is anticipated for such a prototype?

Answer: Prototype hardware should be developed (if applicable to the proposed project) and delivered to BARDA upon completion of the effort. A small number of prototypes (one to three systems) should be defined as deliverables and included in the cost proposal; please price them on a per device or system basis. (The purpose of this BAA is to advance the maturity level of undemonstrated functional systems through a technology development phase to the point of readiness that can be independently assessed/evaluated by the Government for further consideration for a full scale procurement contract.)

55. Question: The BAA specifies the following capability for the POC devices:”

Large numbers of samples (thousands/day) should be able to be processed, and they should return a result rapidly (i.e. within hours).” (p.67) Can this throughput requirement be addressed through the use of multiple devices, or is this capability expected for a single POC device? Also, the TPP table (p. 69) has a time to result target of less than 15 or 20 minutes, rather than “hours”. Please clarify.

Answer: Multiple devices may be necessary to address this throughput scenario, and they may be single-use consumable devices or multi-use devices. The 15 – 20 minute time to result for the POC, provided in Attachment 4, is a target nominal value that BARDA has provided as an example but is not a minimum required specification. Offerors are expected to provide a TPP in their proposal with values specific to their product.

56. Question: Is the temperature range target given in the TPP for the POC ( –20 °C to 50 °C) meant to be a storage or operational specification?

Answer: The POC devices are intended for use in potentially austere conditions where both operational and storage temperatures could reach extreme levels. The temperature range in Attachment 4 is provided as an example of a nominal target value but is not a minimum required specification. BARDA requests that Offerors submit TPPs in their proposals with values specific to their product.

ATTACHMENT A

PROPOSAL INTENT RESPONSE SHEET

BAA No.: BAA BARDA-09-36 BAA Title: POINT OF CARE OR HIGH-THROUGHPUT BIOLOGICAL ASSAYS

FOR DETERMINING ABSORBED IONIZING RADIATION DOSE

(BIODOSIMETRY) AFTER RADIOLOGIC AND NUCLEAR EVENTS

Please review the attached Broad Agency Announcement and return this page prior to April 3, 2009. Expression of intent is not binding but will greatly assist us in planning for proposal evaluation.

[ ] DO INTEND TO SUBMIT A PROPOSAL

[ ] DO NOT INTEND TO SUBMIT A PROPOSAL FOR THE FOLLOWING

REASONS:

Company/Institution Name (print):

Address (print):

Institutional Representative’s Name (print):

Title (print):

Signature/Date: ________________________________________________ Telephone Number and E-mail Address (print clearly):

Names of Potential Collaborating Institutions and Investigators (include Subcontractors and Consultants) for this initiative (print):

(Continue list on a separate page if necessary)

RETURN VIA FAX OR E-MAIL TO:

Biomedical Advanced Research and Development Authority Assistant Secretary for Preparedness and Response U. S. Department of Health and Human Services 330 Independence Ave. S.W. Room G640 Washington, D.C. 20201 Point of Contact: Carl A. Newman

BAA BARDA-09-36

FAX# (202) 205-4520

Email: carl.newman@hhs.gov mailto:carl.newman@hhs.gov