### AMENDMENT OF NIAID SOLICITATION

### \"Medical Countermeasures Against Radiological Threats: Product Development Support Services\"

+-----------------------------------+-----------------------------------+
| **Solicitation Number:**          | RFP NIH-NIAID-DAIT-05-37          |
+-----------------------------------+-----------------------------------+
| **Amendment Number:**             | One (1)                           |
+-----------------------------------+-----------------------------------+
| **Amendment Issue Date:**         | Friday, May 20, 2005              |
+-----------------------------------+-----------------------------------+
| **Proposal Intent Response Sheet  | Friday, May 27, 2005              |
| Due Date:**                       | **[(UNCHANGED)]{.mark}**          |
|                                   |                                   |
| **Proposal Due Date:**            | Friday, June 10, 2005 at 4:00 PM  |
|                                   | Local Time                        |
|                                   |                                   |
|                                   | **[(UNCHANGED)]{.mark}**          |
+-----------------------------------+-----------------------------------+
| **Issued By:**                    | Carl A. Newman                    |
|                                   |                                   |
|                                   | Contracting Officer               |
|                                   |                                   |
|                                   | NIAID, NIH, DHHS\                 |
|                                   | Contract Management Program, DEA\ |
|                                   | 6700-B Rockledge Drive            |
|                                   |                                   |
|                                   | Room 3152, MSC 7612               |
|                                   |                                   |
|                                   | Bethesda, Maryland 20892-7612     |
+-----------------------------------+-----------------------------------+
| **Point of Contact:**             | E-Mail: <cn109s@nih.gov>          |
+-----------------------------------+-----------------------------------+
| **This amendment is issued to all |                                   |
| potential Offerors.**             |                                   |
+-----------------------------------+-----------------------------------+

The above numbered solicitation is amended as set forth below. The date
specified for receipt of proposals **HAS NOT** been changed. Offerors
must acknowledge receipt of this and all other amendments, by
identifying this amendment number (and any others) 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 solicitation amendment number and is received
prior to the opening hour and date specified. Except as provided herein,
all terms and conditions of the solicitation remain unchanged and in
full force and effect.

**PURPOSE OF AMENDMENT: This amendment I) Answers three questions, II)
Clarifies the work assignment procedures, III) Amends a portion of the
text of the Introduction, and IV) Amends a portion of the text of the
Evaluation Factors for Award.**

> **I.** Question 1: Page 15 of the RFP, first paragraph states that
> "...the Phase I Clinical Safety studies conducted would require
> 300-500 subjects" and the third paragraph requires the contractor to
> "provide services to plan, initiate, conduct, audit and report on
> human clinical Phase I safety and pharmacokinetic studies on candidate
> drug products in normal human subjects in accordance with GCP
> guideline." Please clarify.
>
> Answer:  The approval of medical countermeasures against radiation
> injury will most likely be under the FDA animal rule.  Phase I
> clinical studies will be required to demonstrate safety in human
> volunteers.  Since efficacy will be studied in animal species, Phase
> II and Phase III clinical studies will not be performed.  Therefore,
> it is anticipated that a larger number of subjects will be needed
> for Phase I studies.  The actual requirements will depend on the
> medical countermeasure, the nonclinical toxicology profile, any
> previous clinical experience, and consultation with the FDA.
>
> **AMENDMENT 2 to RFP NIH-NIAID-DAIT-05-37 PAGE 2 of 2**
>
> Question 2: Will NIH require the organization with proprietary rights
> to the compound to provide the liability insurance for Phase I or will
> the contractor be required to provide the insurance coverage?
>
> Answer: Under **SECTION I (CONTRACT CLAUSES, ARTICLE I.1. GENERAL
> CLAUSES**, see HHSAR clause 352.228-7 Insurance-Liability to Third
> Persons (DEC 1991).
>
> Question 3: My organization intends to subcontract this Phase I study
> to a clinical trial Contract Research Organization. Will NIH provide
> the insurance and/or indemnify the Prime Contractor? 
>
> Answer: While NIH does not provide insurance, if the contractor
> obtains insurance, the cost of the policy may be an allowable cost
> under the contract pursuant to FAR part 31.
>
> **II.** Under **DELIVERABLES**, paragraph c. (Other
> Reports/Deliverables), item 21 (Final Report for Each Study/Work
> Assignment) is amended. For clarity and simplicity, a revised
> DELIVERABLES enclosure (RFP pages 17 through 19) is attached to this
> Amendment.
>
> **III.** The first paragraph of the Introduction is amended to
> reference the relationship of this acquisition to the Project
> BioShield Act of 2003. Page 3 of the RFP is provided (with changed
> text highlighted) as an attachment to this Amendment.
>
> **IV.** Section M -- Evaluation Factors for Award, paragraph 1.
> General is amended to reference the relationship of this acquisition
> to the Project BioShield Act of 2003. Page 28 of the RFP is provided
> (with changed text highlighted) as an attachment to this Amendment.
>
> [END OF AMENDMENT 1 TO RFP NIH-NIAID-DAIT-05-37]{.mark}

**DELIVERABLES**

The Contractor shall provide the following information to the NIAID
Program Officer and Contracting Officer:

Reporting Requirements

a\. [Technical Progress Reports]{.underline}

In addition to the required reports set forth elsewhere in this
Schedule, the preparation and submission of regularly recurring
Technical Progress Reports will be required in any contract resulting
from this solicitation. These reports will require descriptive
information about the activities undertaken during the reporting period
and will require information about planned activities for future
reporting periods. The frequency and specific content of these reports
are set forth in the **[REPORTING REQUIREMENTS]{.underline}** Section of
the specific RFP.

1\) Quarterly Progress Report every 90 days that provides a summary of
activities for the period and budgets/ expenditures to date and
projected future work on work assignments due 15 calendar days after the
close of the quarter.

2\) Annual Report - in lieu of the fourth progress report (Due on
contract anniversary).

3\) Final Report will be submitted to the NIAID Project Officer and the
Contract Officer (due 30 days after the close of the contract). The
following components will be included in the final report:

-   Face page to include contract number, contract title, performance
    period covered, Contractor's name and address, telephone, telefax
    and E-mail address and submission date.

-   Introduction covering the purpose and scope of the contract effort
    including a summary of salient results. The Contractor shall submit
    a summary, not to exceed 200 words, of salient results achieved
    during performance of the contract.

-   Executive summary, to include fulfillment of production goals and of
    the specific aims set forth in the proposal.

-   A detailed description of the work performed. Full reporting of
    inventions (including name(s) of inventor(s), title(s) of
    invention(s) and date each invention was reported to NIH) first
    conceived or actually reduced to practice, as well as any copyrights
    produced, under the contract.

b\. [Summary of Salient Results]{.underline}

The contractor will be required to prepare and submit, with the final
report, a summary (not to exceed 200 words) of salient results achieved
during the performance of the contract. This report will be required on
or before the expiration date of the contract.

c\. [Other Reports/Deliverables]{.underline}

1\) Annual Report for Clinical Research (Due 45 days from the end of the
annual performance period.)

2\) Final Study Reports to include protocol, results, and data analysis
in a form for submission to the FDA in support of an IND and licensure
(Due within 30 days of final study analysis or conclusion of experiment
if no study analysis is being performed).

3\) Candidate Product Development Strategy and Plan to include candidate
product development strategy for preclinical, non-clinical and clinical
studies to obtain FDA licensure.

4\) Copies of all raw data.

5\) Copies of validation protocols, testing protocols, and validation
reports.

17

6\) Copies of all regulatory documentation and associated correspondence
required by FDA.

> 7\) Written minutes for all meetings including any ad hoc advisory or
> other technical advisory groups to the Contract, and meetings with the
> FDA or other regulatory agencies.
>
> 8\) Clinical site monitoring plan, site visit monitoring reports, and
> monitoring SOPs. Provide interim and final statistical analyses
> reports for Phase I human safety trials, data management plans, and
> adverse and serious adverse events listing reports. Provide all
> documents required for clinical studies such as, Investigator
> Brochures, Case Report Forms, subject informed consent forms, and
> materials for Institutional Review Board (IRB) submission.

9\) SOPs to safeguard proprietary and confidential information and data.

10\) Risk Analysis (RA), annual System Security Plan (SSP), and SOP for
compliance with the Privacy Act.

> 11\) Experimental study design and protocols.
>
> 12\) 510(k), PMAs, INDs, NDAs, and BLAs.

13\) Responses to correspondence from regulatory authorities.

> 14\) Interim Statistical Analyses.
>
> 15\) Final Statistical Analyses.

16) Statistical and Analysis Plans.

17) Data Management and Investigator's Brochure

18) Investigational New Drug (IND).

19) New Drug Application (NDA) or Amendment.

20) Biologic License Application (BLA) or Supplement to the Food and
    Drug Administration(FDA).

21) Final Report for Each Study/Work Assignment

> Contractor shall provide responses to Work Assignment (W.A.) requests
> (see Appendix A, Part 8, Work Assignment Procedures on page 36) by
> completing the "Contractors Response to Work Assignment Request (Part
> II). W.A. Responses must be received within 15 days of receiving the
> request or by the W.A. Response Due Date indicated on the W.A.
> request. Contractor shall initiate work on approved work within 7 days
> of receipt of NIAID Project Officer and Contracting Officer approval
> unless otherwise directed by NIAID Project Officer.

22) Records and Reports required for Writing and Submission of an
    Investigational New Drug Application (IND)/New Drug Application
    (NDA) or Biologics License Application (BLA)

23) Non-clinical Strategy and Plan

24) Clinical Development Plan for the Evaluation of the candidate drug
    products

25) Interim Clinical Trial Report that Includes Data Summary, Data
    Analysis and Interpretation and Conclusions for the Phase I Trials.

26) Source Code

27) Object Code

28\) Special Reports or Analyses as required by the SOW

> a\. Tables, Text, Graphs and Diagrams as needed in collaboration with
> investigators and NIAID staff for presentation at meetings or
> professional conferences and other special reports concerning study
> findings
>
> b\. Reports with custom formats summarizing data for monitoring study
> progress or product safety or for use by separate site monitoring
> Contractor, if requested by the Project Officer
>
> c\. Protocol development materials, abstracts/protocol summaries for
> NIH clinical trials database and other databases specified by the
> Project Officer
>
> d\. Quality assurance/quality control plans, training materials used,
> developed or maintained under the contract as specified by the Project
> Officer
>
> e\. All data files, computer programs, computer software, computer
> manuals, and all written documentation of any programs as specified by
> the Project Officer
>
> 18

29\) Interim and final statistical analyses of study data as defined by
the protocol

30\) At the completion of the Phase I safety trial, the Contractor shall
deliver a cleaned and edited public use data set on media to be
determined at the time of delivery, and copies of all data management
tools, including data documentation and data dictionaries, data entry
software and editing programs to allow reading and analysis of the data.
The Contractor shall provide appropriate computer programs capable of:
(1) reading and manipulation all data, and (2) creating SAS compatible
databases. The Contractor shall also deliver an audit trail of all raw
data corrections, hard copies of the original data collected from study
participants from all studies, and all logs and other records related to
data collection, entry, editing, analysis and transfer.

31\) Transition plan (as described in the Statement of Work) - six
months prior to the completion date of the contract.

Note 1: For Other Deliverables, Items 3-30, due dates shall be 45 days
from the end of the specific work assignment.

> Note 2: The items set forth above are likely to become reports or
> deliverables under the contract. As the efforts will be detailed in
> individual work assignments, reports and deliverables will be
> specified herein.

**Number of Copies**: 3 (one electronic and two hardcopies)

**Addresses/Distribution**: Contracting Officer, NIAID, 6700-B Rockledge
Drive, Rm. 3214 , Bethesda, MD 20892 and Project Officer, NIAID 6610
Rockledge Drive, Bethesda, MD 20892

19

**BACKGROUND**

World events over the past decade have highlighted the growing threat of
terrorism and its many forms, including the 1995 Oklahoma City bombing,
the 1995 Tokyo sarin gas attack, the terrorist attacks in the U.S. on
September 11, 2001, and the deliberate spread of anthrax and ricin
through the U.S. postal service and Congressional office buildings in
recent years. These incidents provide insight into the range of
approaches used by terrorists, including the potential to use chemical,
biological, and radiological/ nuclear weapons. Threats may include the
use of nuclear weapons or devices, attacks on nuclear power plants or
reactors, detonation of radiological dispersal devices (RDDs) or \"dirty
bombs,\" which combine radioactive material with conventional
explosives) or the placement of radiation sources in public locations or
in food or water.

The effects of radiation on the body may appear within minutes or
develop many years after exposure. Radiation injury is directly
proportional to the dose absorbed by the body. Depending on the dose of
whole-body exposure to external radiation, the effects can range from an
increased risk of cancer years after exposure to more acute effects,
including transient nausea and vomiting; hematopoietic and
gastrointestinal injury, leading to immunosuppression and infection;
metabolic abnormalities; and hemorrhage and anemia. At high exposure
levels, damage to the cardiovascular and central nervous systems may
lead to early mortality.

**Introduction**

Recent meetings convened by the White House Office of Science and
Technology Policy, Homeland Security Council and Radiological/Nuclear
Threat Countermeasures Working Group, and the National Institutes of
Health (NIH) identified serious deficiencies in the available medical
countermeasures to radiological and nuclear threats. Few medical
countermeasures currently exist, and there is no dedicated program
within a Federal research agency to address this problem. The Department
of Health and Human Services (DHHS) has assigned the NIH the
responsibility to identify, characterize, and develop new medical
countermeasures against radiological or nuclear attacks. A robust
research and development program in this area will begin to yield new
diagnostic tools, radio-protectors and mitigators and therapeutic agents
to facilitate an effective response against radiological injury. [The
DHHS has designated this initiative as being subject to the authorities
provided for under the Project BioShield Act of 2003, specifically,
Section 2 Biomedical Countermeasure Research and Development.]{.mark} On
October 14, 2004, the NIH convened an expert panel to review the "NIH
Strategic Plan and Research Agenda for Medical Countermeasures against
Radiological and Nuclear Threats." This strategic plan and research
agenda outline a flexible, collaborative, and comprehensive NIH research
and product development program focused on medical therapies and
diagnostics to counter radiation injury. On behalf of the NIH, the
National Institute of Allergy and Infectious Diseases (NIAID) is charged
with implementing this research agenda.

The "Medical Countermeasures Against Radiological Threats: Product
Development Support Services" contractor will provide: a variety of
assays to screen for and confirm compound activity, safety pharmacology,
and toxicology; use animal models of radiation injury, protection,
therapy, or recovery to provide mechanistic, safety, and animal efficacy
data to support U.S. Food and Drug Administration (FDA) approval for
human use when it is not ethical to perform human efficacy studies;
conduct human safety studies; and formulate and manufacture products
under current Good Manufacturing Practices (cGMP).

It is anticipated that products that prove efficacious and can be
delivered effectively will be deposited in the Strategic National
Stockpile (SNS). The SNS is a national repository of antibiotics,
antitoxins, chemical antidotes and other lifesaving pharmaceuticals and
medical materials. There is an immediate need to move promising medical
countermeasures through development and licensure, and into the SNS,
which, currently, includes a limited number of medications for use
following radiation exposure.

3

**SECTION M - EVALUATION FACTORS FOR AWARD**

**1. GENERAL**

Selection of an offeror for contract award will be based on an
evaluation of proposals against four factors. The factors in order of
importance are: technical, cost, past performance and Small
Disadvantaged Business (SDB) participation. Although technical factors
are of paramount consideration in the award of the contract, past
performance, cost/price and SDB participation are also important to the
overall contract award decision. All evaluation factors other than cost
or price, when combined, are significantly more important than cost or
price. In any case, the Government reserves the right to make an
award(s) to that offeror whose proposal provides the best overall value
to the Government. [Offerors are hereby notified that this initiative's
designation by the DHHS as being subject to the authorities provided for
under the Project BioShield Act of 2003, allows the NIAID to use
streamlined measures in the evaluation, negotiation and award of the
resultant contract.]{.mark}

The evaluation will be based on the demonstrated capabilities of the
prospective Contractors in relation to the needs of the project as set
forth in the RFP. The merits of each proposal will be evaluated
carefully. Each proposal must document the feasibility of successful
implementation of the requirements of the RFP. Offerors must submit
information sufficient to evaluate their proposals based on the detailed
criteria listed below.

2\. HUMAN SUBJECT EVALUATION

> This research project involves human subjects. NIH Policy requires:

1.  \(a\) **Protection of Human Subjects from Research Risks**

> The offeror's proposal must address the involvement of human subjects
> and protections from research risk relating to their participation, or
> provide sufficient information on the research subjects to allow a
> determination by Institute that a designated exemption is appropriate.
>
> If you claim that this research should be considered exempt from
> coverage by the Federal Regulations at 45 CFR 46, the proposal should
> address why you believe it is exempt, and under which exemption it
> applies.
>
> The reviewers will evaluate the proposal with regard to four issues:
> Risks to Human Subjects, Adequacy of Protection Against Risks,
> Potential Benefits of the Proposed Research to the Subjects and
> Others, and Importance of the Knowledge to be Gained. See Section L
> for a complete discussion of what is required to be addressed for each
> of these issues. Based on the response to this criterion, this section
> of the proposal may be rated "unacceptable" (i.e., concerns are
> identified as to the protections described against risk to human
> subjects or no discussion is found regarding protections against risk
> to human subjects) or "acceptable". If the reviewers find that this
> portion of the proposal is "unacceptable" they will provide a
> narrative supporting their finding.
>
> If the Government includes your proposal in the competitive range (for
> competitive proposals), or if the Government holds discussions with
> the selected source (for sole source acquisitions), you will be
> afforded the opportunity to address the concerns raised by the
> reviewers. You will be able to further discuss and/or clarify your
> position until submission of your Final Proposal Submission (FPR).
> Once discussions are closed with the submission of your FPR, if your
> proposed plan for the protection of human subjects from research risks
> is still found to be unacceptable, then your proposal may not be
> considered further for award.

1.  \(b\) **Data and Safety Monitoring**

> The offeror's proposal must include a general description of the Data
> and Safety Monitoring Plan for all clinical trials. The principles of
> data and safety monitoring require that all biomedical and behavioral
> clinical trails be monitored to ensure the safe and effective conduct
> of human subjects research, and to recommend conclusion of the trial
> when significant benefits or risks are identified or if it is unlikely
> that the trial can be concluded successfully. Risks associated with
> participation in research must be minimized to the extent practical
> and the method and degree of monitoring should be commensurate with
> risk. Additionally, all plans must include procedures for adverse
> event reporting. Finally, generally, for Phase III clinical trials,
> the establishment of a Data and Safety Monitoring Board (DSMB) is
> required, whereas for Phase I and II clinical trials, the
> establishment of a DSMB is optional. The reviewers will rely on the
> Statement of Work and Section L in the solicitation, as well as any
> further technical evaluation criteria in this Section M, as
> applicable, for the solicitations specific requirements for data and
> safety monitoring.
>
> As a part of the evaluation for proposals, the reviewers will consider
> the acceptability of the proposed data and safety monitoring plan with
> respect to the potential risks to human participants, complexity of
> study design, and
>
> 28