Amendment 3.doc

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:

Three (3)

Amendment Posting Date:

April 10, 2009 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 answers a number of inquiries received subsequent to the March 26, 2009 pre-proposal conference:

1. Question: Are the prototypes more like pre-production units, to be delivered at the end of the contract, or are they more like proof-of-concept units to be delivered after one year or so.

Answer: Typically, a project's scope will determine the type, number and projected delivery timeline of pre-production prototypes. Prototypes will be pre-production pilot units and delivered at the end of the base plus option years if exercised. BARDA expects the Offeror to propose milestones for performance demonstration throughout their development and short term/long term plans to delivery.

2. Question: In that the “FISMA risk levels, if applicable, will be assigned during contract negotiations,” will the affected elements of the budget also be negotiable? Depending on the FISMA level assigned (Low, Moderate, or High), there could be several hundred thousand dollars of cost variability between these levels.

Answer: Prepare the business proposal based on a low FISMA level. The security budget will be reviewed and BARDA will follow-up with the Offeror if necessary.

3. Question: What is the margination and font requirements for both the technical and business proposals? (12 pt Roman times is given for the SOW but we were unable to find information for these requirements for the remaining documentation).

Answer: BARDA requests that you submit your TECHNICAL PROPOSAL in the same format as the SOW using letter-size (8 1/2 ( 11 inch) paper. The body of the text should be in 12 pt Times New Roman Font. The page margins should be set at 1 inch top and bottom and 1 inch left/right sides. Page numbering for the paper should be set in the middle of the footer. We appreciate if you use the same format in the business proposal. Please also see G, General information for Offerors on page 27 of the BAA for other instructions and page number limits.

4. Question: For the ANSI testing requirements, if we are providing retrospective (after IR exposure) POC and high throughput biodosimetry assays, are we required to perform testing in the presence of a 137Cs field? For retrospective dosimetry measurements, this applied IR field could alter the measurement and contribute to error in the dose estimate provided by many retrospective biodosimeter assays. Is the purpose for the IR field component in the test method to simulate the presence of a low IR exposure in the field following and IND or detonation of a dispersion device to test assay performance under this condition?

Answer: No, Point-of-care and high throughput assessments of cumulative absorbed dose in a populated contaminated community (137Cs) downwind of a 10 kiloton nuclear ground blast is beyond the scope of this BAA. This methodology which is applicable to populated areas contaminated by radioactive fallout might be appropriate to the Broad Agency Announcement BAA-BARDA-09-34.

5. Question: How is ramp up time defined in Attachment 4? Is it the time required for an instrument or assay from cold start to full calibrated activity? From cold start to readiness to begin sample processing? Cold start to obtaining first assay result?

Answer: Ramp up time describes the period between product cold-start to ready to process samples, characterized by product and process readiness to run the first samples.

6. Question: For clarification, are the ANSI non-ionizing radiation endpoints to be electrostatic discharge, radiofrequency, magnetic fields, and radiated emissions?

Answer: Yes, non-ionizing radiation is a form of electromagnetic radiation with varying effects on the body and testing systems, depending on frequency, wavelength, and power of the type of radiation concerned. Endpoints will be related to the device safety and function a.

magnetic fields

b. ultraviolet (UV) light c.

radio waves; radiofrequency d.

microwaves e.

electrostatic discharge

f. lasers

7. Question: What is the procedure to request a waiver on physical security plan?

Answer: If applicable, BARDA will help you with the waiver process during the negotiations phase.

8. Question: Do you anticipate a need for standards to validate and quantitate proposed measurements?

Answer: BARDA does see a potential need for such a standard; however, development of such a standard alone would not be appropriate under BAA-BARDA-09-36. This technology might be an appropriate submission under BAA-BARDA-09-34.

9. Question: Why is the time from the announcement to submission so short?

Answer: The Federal Acquisition Regulations (FAR) clause 5.203 requires announcements to be open for 45 days. This announcement is open for 48 days.

10. Question: Who will evaluate the proposals?

Answer: A Technical Evaluation Panel comprised of Government and industry representatives.

11. Question: As the end products are intended to be used to monitor exposure to ionizing radiation, the potential exists for the equipment to be exposed. Will TPP’s be added for Transient Radiation effects on electronics (Tree) and EMP?

Answer: TPP criteria for air blast induced shock, transient radiation effects on electronics (TREE), nuclear survivability, and conducted EMP can be tailored by the Offeror for all equipment and devices. TPP criteria can include suitable crating and protection from air blast, thermal radiation, and free field EMP, as well as other sources of electromagnetic interference and other environmental effects (eg extreme weather conditions). Offerors should submit TPPs specific to their product (The sample TPPs in Attachment 4 are provided as nominal values).

12. Question: Will proposals that address only the point-of-care (initial triage) problem be competitive or appropriate?

Answer: Yes, these point-of-care devices are appropriate and competitive and called for in this BAA.

13. Question: Will proposals for point-of-care technology be viewed favorably if all they do is indicate a dose of less than or greater than 2Gy?

Answer: Yes. They will be considered for review if they indicate a dose less than or greater than 2 Gy with performance characteristics that are within the scope of this BAA.

14. Question: Year one denumerable is a set of prototypes. Are there any specific denumerable or objectives for years 2,3,4, and 5?

Answer: The goal is for the Offeror to give BARDA a picture of product development towards eventual procurement activity. There are no hard objectives for any base or option years; they will be driven by your product development process. Prototypes can be used to revise design for the purposes of cost reduction through optimization, refinement, and risk mitigation. Building the full design prototype device for production can be time-consuming. The option years will be driven by the contract SOW and meeting milestones and metrics as well as available funding.

15. Question: Is the $40 Million available funding for year 1?

Answer: $40 million, subject to availability of funding, will be the total resources available for all contracts awarded in Year 1.

16. Question: What level of detail in the statement of work (SOW) is expected for the option phases? (Years 2-5) Answer: The proposal statements of work should contain the same level of detail for all years.

17. Question: Would scraping of skin (example: forehead) be considered non invasive?

Answer: Please refer to the FDA guidelines 21 CFR 812.3 (k) which define “noninvasive” when applied to a diagnostic device or procedure. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=812.3

18. Question: What happens after June determination?

Answer: The USG will either respond favorably and negotiations will begin or letters of rejection will be sent.

19. Question: Is there a fast track to determination and award?

Answer: BARDA will proceed with the procurement process at a pace which maintains procurement integrity while adhering to all procurement regulations.

20. Question: Are Co-Principal Investigators allowed on proposals?

Answer: Yes, Co-PIs are allowed.

21. Question: Can the Power Point slides be handed out?

Answer: No, the Power Point presentation used during this conference will not be distributed. However much of the same information can be found on the BARDA web site as referenced in the BAA, specifically see the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Implementation Plan for CBRN Threats, found at http://www.hhs.gov/aspr/barda/phemce/enterprise/strategy/index.html

22. Question: How will BARDA review proposals that need FDA guidance to review?

Answer: The BARDA proposal review team includes members with extensive regulatory background and expertise. BARDA expects Offerors to submit expected FDA meetings and milestone events, including any planned or foreseen meetings/communications with FDA, in their technical proposal statements of work, timelines, Gantt charts, and Strategic Staged Product Development Plans.

23. Question: How does the animal rule bias our proposal? If we use protocols in our animal facility that best approximate GLP, would our proposal still be judged against fully certified GLP laboratories? We have a University Medical Center doing radiation exposures. They have not been GLP certified.

Answer: BARDA recommends that Offerors consult with the Office of Laboratory Animal Welfare to obtain guidance on GLP and animal studies. Technical and business proposals should address how the Offerors plan to achieve GLP compliance (as well as GMP and GCP compliance if applicable) in order to be positioned to make future submissions to the FDA. The “animal rule” will not bias a proposal.

24. Question: Can samples be generated in a GLP study and then used by a manufacturer for product development under QSR?

Answer: BARDA recommends that Offerors consult with the FDA Center for Devices and Radiological Health as early as possible to understand their current thinking regarding QSR and product development. See their web site at http://www.fda.gov/cdrh/devadvice

25. Question: Can we propose to both Broad Agency Announcements (BAA) 09-34 and 09-36?

Answer: Yes. However, Offerors should note that there are significant differences between the two BAAs in the submission timing and instructions.

26. Question: Do we have to have agreement from FDA on our protocols before we can submit them to BARDA on April 17?

Answer: No, an agreement from the FDA is not required in the proposals that are due on April 17, 2009.

27. Question: What is the Government’s economic commitment post-projects?

Answer: The Government has no economic commitment at the completion of projects awarded under this BAA. At the completion of the projects, BARDA intends to re-assess the state of the technology to determine the potential for transition to a procurement contract.

28. Question: Are there restrictions on commercial use?

Answer: There are no restrictions on commercial use. BARDA encourages Offerors to consider leveraging their proposed product with other commercial applications or using existing systems with a new intended use. By developing a system to meet BARDA’s needs that is based on or lends itself to routine medical practice, it would maintain a warm base of expertise and production capacity.

29. Question: Do we have to have a prototype in Year 1?

Answer: No, a prototype in year 1 is not required.

30. Question: Can the prototype be an assay, not a device?

Answer: Yes. The prototype can be an assay. With this BAA, BARDA is casting a wide net to develop candidate technologies that will meet our future needs.

31. Question: You mentioned the IDE/PMA regulatory pathway most likely the path would be “de novo” Will this be an issue?

Answer: BARDA does not expect this to be an issue, but we recognize we might be breaking new regulatory as well as scientific and engineering ground. The FDA understands this and the importance of our projects. For further guidance please refer to the FDA web site: http://www.fda.gov/cdrh/devadvice

32. Question: What is the basis of initial funding? Is it FY07? FY08?

Answer: It is FY09 funding. It is one-year funding for the base contract. The contracts are to be awarded in mid-September of this year.

33. Question: How many awards are planned?

Answer: BARDA anticipates awarding multiple contracts, the exact number to be determined after receipt and review of proposals.

34. Question: BARDA will be conducting a pre-qualification type audit prior to awarding the contracts. To what standards will you be auditing for compliance?

Answer: The pre-award site visits are not intended to mimic an FDA audit. At the pre-award site visits, BARDA will be looking at your facilities and processes for signs of good clinical / laboratory / manufacturing practices. While compliance with these GxP guidelines is not a requirement at the outset, it is imperative for candidate technologies to be moving toward a path to approval.

35. Question: To what extent is Basic research into the biological basis of biodosimetry a legitimate part of a practical device proposal?

Answer: BARDA does not anticipate funding proposals for discovery phase research efforts. The goal of this BAA is to facilitate development of biodosimetry assessment tools (device, biomarker, or bioassay).

36. Question: Is the salary limitation a notice only?

Answer: The salary rate limitation is a requirement. Please adhere to the salary rate limitation as noted under http://www.opm.gov/oca/09tables/pdf/ex.pdf.

37. Question: Please clarify that the direct salary as mentioned on level one in Salary Table No.2008-EX (and beyond) has the same meaning as a base salary that include either a “cost of living” or “merit increase”.

Answer: Please adhere to the salary ceiling reflected in Executive Level I Salary Table No. 2009-EX ($196,700). Cost of living increases in subsequent years adjust the salary and can be based on CPI projections. Merit increases could be part of the salary or fringe benefits.

38. Question: How does BARDA determine that a person’s direct salary is within the limits of direct salary as mentioned on Executive Schedule Level 1 in Salary Table No. 2008-EX.

Answer: Please provide personnel action forms or similar documentation to verify the budgeted salary.

39. Question: If one institution is doing all the work, will the MOU be required as stated on page 10?

Answer: If the Offeror is the exclusive performer on the contract, the answer is no.

40. Question: Can one MOU be prepared for all the parties or does there have to be one MOU for every pair of collaborating parties?

Answer: There should be an MOU for each pair of collaborating parties.

41. Question: If the elements of the MOU are part of the offer and/or contract then there is some overlap between all the documents. If covered under the offer and/or contract can the MOU requirement be dropped?

Answer: No

42. Question: Why does BARDA need a MOU and a LOU?

Answer: BARDA must be familiar with the contents of the agreements for the purpose of a smooth transition after contract award and to facilitate the activities and requirements between BARDA and the contractor as well as the contractor and its subcontract(s).

43. Question: There seems to be an overlap between the documents. From BARDA’S perspective what are the distinctions between the MOU and the LOU?

Answer: Please note the difference between the Memorandum of Understanding (MOU) (Page 10) and the Letter of Understanding (Page 33) (Section 8 Project Management). The Memorandum of Understanding provides more detail than the Letter of Understanding.

44. Question: Can the three documents be merged to cover one commitment letter from each individual subcontractor and the prime?

Answer: No

45. Question: Please provide the definitions of “Material” and “Equipment”?

Answer: Equipment and Material are defined under FAR 45.101. Please note that Equipment includes, essentially, ANY equipment that is NOT special tooling, special test equipment or agency peculiar property. It also excludes items that could be considered material because it is to be made part of an end item deliverable to the Government. It includes specialized scientific equipment when that equipment is commercially available and does not need to be specially manufactured for test purposes peculiar to the contract. If the Offeror can purchase the item outright, the item is to be used by itself, and it will not be an end item deliverable to the Government, it is categorized as Equipment. In accordance with the FAR, Material means property that may be consumed or expended during the performance of a contract, component parts of a higher assembly, or items that lose their individual identity through incorporation into an end-item. Material does not include equipment, special tooling and special test equipment

46. Question: Can you elaborate on the Purchase of Equipment? What is meant by equipment and what “support” for the purchase of equipment would be adequate?

Answer: Please see previous question in regards to the definition of Equipment. Financial support for equipment will be determined by Government need. The specific resources to purchase equipment will depend on the marketplace.

47. Question: Can we use our company Comprehensive Small Business Plan in lieu of the individual small Disadvantaged Business Plan?

Answer: Please use the Small Business Subcontracting Plan as noted in Attachment 11.

48. Question: Is there a format and/or specific content for the Intellectual Property Plan?

Answer: No.

49. Question: "The Reps and Certs linked to in section 11 on page 51 is an empty form and part (c ) (2) says "The following certifications are applicable as indicated by the Contracting Officer: [Contracting Officer check as appropriate.]" but there are no checks."

Answer: Please complete the Representations and Certifications located on the Online Representations and Certifications Application (ORCA) website at https://orca.bpn.gov/. See Attachment 12 (Representations, Certifications and Other Statements of Offerors).

50. Question: Does BARDA envision the very significant level of effort required to support compliance with [FDA] regulations or will there be a special dispensation from the FDA for any devices developed under this contract?

Answer: A special dispensation from the FDA is not envisioned under this contract. BARDA recommends that Offerors consult with the FDA Center for Devices and Radiological Health as early as possible to understand their current thinking regarding QSRs and product development. QSR compliance is needed for all developments under this BAA, though these requirements do vary by development phase. It should be noted that contracts under this BAA will not include a procurement phase.

51. Question: Are indirect costs allowed on foreign subcontracts?

Answer: Yes.

52. Question: We have a candidate product in early clinical testing in cancer patients and are nearing clinical trials. How can this product be submitted to address the requirements of this BAA?

Answer: Even though this product is late in the development cycle it would be appropriate to submit a proposal to this BAA. It is not appropriate to use funds from this BAA to fund final clinical trials for development of an FDA submission package. That would be part of a procurement contract, should one be deemed appropriate. Funds from this BAA, for example, can be used to fund preliminary animal studies for whole body radiation effects at the level of 2 Gy or more that typically are not feasible in cancer patients. Development of clinical protocols, refinements in the product, or improvements in an organization’s processes in preparation for final clinical trials are also potential activities that are appropriate to fund under this BAA. We recommend that you consult the FDA Center for Devices and Radiological Health as early as possible to obtain guidance on the appropriate studies and pathways, including the use of animal models.