Combined_SynSol_HHS-NIH-NIAID-DMID-NIHAI2017088.pdf

COMBINED SYNOPSIS/SOLICITATION

“Therapeutics Testing in Murine Models of Bacterial Thigh & Lung Infections”

HHS-NIH-NIAID-DMID-NIHAI2017088

INTRODUCTION

This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in the Federal Acquisition Regulation (FAR) subpart 12.6, as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested, and a written solicitation document will not be issued.

This solicitation number is HHS-NIH-NIAID-DMID-NIHAI2017088. This solicitation is issued as a request for proposals.

This acquisition is NOT set-aside for small business and is available for full and open competition. The associated North American Industrial Classification System (NAICS) code for this procurement is 541380 with a small business size standard of $15.0 million.

This solicitation is being issued using the simplified acquisition procedures under the authority of FAR 13.5, “Simplified Procedures for Certain Commercial Items.”

Offerors must be registered in the Central Contractor Registry (CCR) prior to award of a contract.

Offerors must access the CCR through The System for Award Management (SAM) at http://www.sam.gov.

The National Institute of Allergy and Infectious Diseases (NIAID) is seeking proposals for the performance of sixty-two (62) assessments of therapeutic candidates in models of thigh and lung infections in neutropenic mice to be performed over twelve (12) months. The Contractor will perform the following types of studies in specified models:

Study Type Number of Studies Number of Option Studies

1. Minimal Inhibitory Concentration (MIC) Determination 25 30

2. Efficacy Assessment 15 10

3. Maximum Tolerated Dose Assessment (MTD) 10 6

4. Bioanalytical Assessment of Drug Concentration 10 6

5. Custom Strain Profiling 2 5

STATEMENT OF WORK

BACKGROUND

The rapid emergence of resistance in both Gram-positive and Gram-negative bacteria has eroded our ability to treat certain kinds of infections, leading to an urgent need for new antimicrobial agents. However, multiple factors have led to a limited interest of the pharmaceutical industry in the development of new antibacterials. Therefore, it is imperative that NIAID support the development of novel antibacterials throughout the product development pipeline.

http://www.sam.gov/ http://www.sam.gov/

An important step in the evaluation of antibacterial therapeutic candidates involves demonstrating in vivo efficacy in rodent models. Access to off-the-shelf, well-validated murine models of thigh and lung infections caused by a variety of drug-susceptible and drug-resistant strains of key bacterial pathogens will allow NIAID to respond to the broad range of requests from external investigators to demonstrate the value of their promising new antibacterial agents through in vivo efficacy testing. Assays commonly used for testing antibacterial therapeutics measure reduction of bacteria (CFU) in infected thigh or lung tissue in mice after treatment for a 24-hour dosing period. MIC (Minimum Inhibitory Concentration) testing and MTD (Maxiumum Tolerated Dose) evaluation will inform the bacterial strain and optimal range of therapeutic doses used in the efficacy study, respectively.

For approved drugs, pharmacokinetic/pharmacodynamic (PK/PD) relationships obtained from rodent models historically have been shown to correlate well with plasma exposures required to treat bacterial infections in the clinic. As a result, these models have become a de facto industry standard for evaluating new therapeutics. The added capability to perform PK measurements in infected mice to correlate with efficacy observations will permit generation of PK/PD relationships that are critical for the understanding of likely efficacy targets in the clinic.

SCOPE

This contract is for the testing of candidate therapeutic products in murine models of bacterial thigh and lung infections, as well as the determination of drug concentration in plasma of infected mice to enable correlation of PK data with efficacy.

STATEMENT OF WORK

The Contractor shall furnish all the necessary services, qualified personnel, material, equipment and facilities as needed to perform the following tasks.

I. Antibacterial therapeutic candidates will be shipped to the Contractor either from the

Government directly or by a third party submitter. The Contractor shall store and maintain the viability of all antibacterial therapeutic candidates shipped to the Contractor with an accompanying executed Service Request Form (SRF). A sample SRF is included as “Attachment 1”. The Contractor shall not begin assessment of any therapeutic for which it does not have an executed SRF signed by the COR.

Upon receipt of an executed SRF, the Contractor shall develop and submit draft and final study protocols in accordance with the Reporting Requirements and Delivery Schedule.

II. Candidate Therapeutics Assessments:

The Contractor shall evaluate candidate therapeutic compounds provided by the Government or by third party submitters (candidate sponsors) using one or more of the five study types described below.

a) Minimal Inhibitory Concentration (MIC) Determination to inform the selection of the most appropriate bacterial strain from among those available in efficacy models. Twenty-five assessments (25) will be required under this study type.

(i) In vitro potency shall be determined for the candidate therapeutic (or combination) against relevant bacterial strains for which efficacy models are available.

(ii) Potency will be measured using standard CLSI methods to determine the MIC for the candidate therapeutic (or combination) against the selected strain.

(iii) The bacterial strain will be selected based on its availability in the desired efficacy model, desired drug-susceptibility profile and preliminary potency data provided by the requestor.

(iv) MIC determination shall be priced on a per strain basis but multiple strains may be tested per candidate therapeutic in order to identify the most suitable efficacy model from those available.

(v) MIC determination using the appropriate control antibiotic shall be included in the per strain price.

b) Efficacy Assessment to determine the inhibitory effect of a candidate therapeutic (or combination) on bacterial growth in the thigh or lungs of infected mice, where the total number of mice in each assessment shall not exceed 70 mice. Fifteen assessments (15) will be required under this study type.

(i) Mice shall be made neutropenic by cyclophosphamide treatment prior to infection using standard methods.

(ii) Mice will be infected with a characterized inoculum of the selected bacterial strain by injection in the thigh or intranasal administration to the lung.

Inoculum size and time to treatment initiation shall be determined based on previous validation studies for the specific bacterial strain used. Typically, treatment will be initiated 1-3 hours post infection at which time infection levels are in the range of 105-107 CFU per thigh/lung.

(iii) Multiple dose groups of mice shall include treatment groups which receive test compound, positive (known drug) and negative (vehicle) control groups, and a control (pretreatment) group to provide a measure of bacterial burden prior to treatment initiation.

i. Group size utilized shall be as needed to achieve statistical significance as demonstrated from prior validation of the model.

ii. Specific parameters (dose, frequency, treatment timing, etc.) can differ across dose groups depending on the specific study design.

iii. Route of administration can vary (po, ip, iv, sc) depending on specific candidate therapeutic but dosing frequency will not exceed four times per day.

(iv) Bacterial (CFU) burden shall be evaluated immediately prior to treatment and after a designated period of time (typically24 hours) using standard methods involving tissue (thigh or lung) homogenization followed by dilution plating to permit accurate colony counts.

(v) Data will be reported as a comparison of CFU values in pre-treatment, treatment, and positive and negative control groups, with statistical analysis of significance.

c) Maximum tolerated dose (MTD) Assessment to determine the optimal range of doses predicted to be tolerated in an efficacy study, where the total number of mice in each assessment shall not exceed 20 mice. Ten assessments (10) will be required under this study type.

(i) Mice shall be made neutropenic by cyclophosphamide treatment and infected with the selected bacterial strain, as in the planned efficacy study

(ii) Multiple groups of mice shall receive different doses of test compound, in addition to a negative (vehicle) control group

i. Route of administration and timing can vary depending on specific candidate therapeutic but should align with that planned for efficacy study

(iii) Mice shall be monitored for adverse clinical signs immediately after dosing and at multiple times during the day.

i. Monitoring should include typical in-life observations for signs of acute toxicity and/or autonomic effects and recorded to inform appropriate dose selection for subsequent efficacy studies.

d) Bioanalytical Assessment of Drug Concentration to determine the drug concentration in plasma (or tissue) samples from infected mice dosed in the same manner as in the efficacy study in order to correlate CFU reduction with drug concentration where the total number of mice in each assessment shall not exceed 100 mice. Ten assessments (10) will be required under this study type.

(i) Mice shall be made neutropenic by cyclophosphamide treatment and infected with the selected bacterial strain, as in the planned efficacy study.

(ii) Multiple groups of mice shall be dosed in the same manner as those used in the efficacy dose groups (excluding the positive and negative control groups). The size of each group shall be sufficient to enable sampling over multiple time points with ≥3 mice per time point. Typically such a satellite PK study would require 36-96 mice, depending on whether 1-2 samples are taken per mouse for analysis.

(iii) Analysis of drug concentration in the samples shall be performed using standard LC-MS/MS methods developed by the contractor or, if applicable, provided by the sponsor.

(iv) Drug concentration data shall be reported for all samples with mean values calculated for each time point, and PK parameters (AUC, Cmax, T>MIC, etc.)

shall be calculated for each dose group to enable correlation with efficacy (CFU) data.

e) Custom Strain Profiling to determine the ability of a new bacterial strain to establish an infection in thighs or lungs of neutropenic mice, where the total number of mice in each assessment shall not exceed 50 mice. Two assessments (2) will be required under this study type.

(i) The external requestor shall provide the custom bacterial strain, including detailed data on source, purity, in vitro growth characterization, and antibiotic susceptibility.

(ii) Mice shall be made neutropenic by cyclophosphamide treatment prior to infection using standard methods.

(iii) A freshly prepared, characterized stock (with known CFU/mL) of the selected bacterial strain shall be used to infect groups of mice with a range of total bacteria by injection in the thigh or intranasal administration to the lung.

Inoculum sizes tested in the different groups typically shall range from 104- 106 CFU per thigh/lung.

(iv) Bacterial (CFU) burden shall be evaluated for each group at 1-3 hours post infection and at 24 hours post infection using standard methods involving tissue (thigh or lung) homogenization followed by dilution plating to permit accurate colony counts.

(v) Data will be reported as a comparison of the change in CFU obtained from the infected tissue over the 2 time points and across the groups with different inoculum sizes and shall include statistical analysis of significance.

III. The Contractor shall prepare and submit the results of each assessment in accordance with the Reporting Requirements and Delivery Schedule.

IV. Ad hoc Teleconferences: The Contractor shall participate in teleconferences involving the COR and third party submitters on an ad hoc basis. Minutes of all teleconferences shall be submitted in accordance with the Reporting Requirements and Delivery Schedule.

OPTIONS

In addition to the services outlined above, to be provided for in the base requirement, options for additional services under this Contract may be exercised at the discretion of the Government and are defined as follows:

Study Type Maximum Number of Quantity Options to Be Exercised

1. Minimal Inhibitory Concentration (MIC) Determination

2. Efficacy Assessment 10

3. Maximum Tolerated Dose Assessment (MTD) 6

4. Bioanalytical Assessment of Drug Concentration 6

5. Custom Strain Profiling 5

[END OF STATEMENT OF WORK]

REPORTING REQUIREMENTS & DELIVERY SCHEDULE

REPORTING REQUIREMENTS

All reports required herein shall be submitted through the NIAID Electronic Reports and Deliverables System (eRDS), found at https://erds.niaid.nih.gov/.

All electronic reports submitted shall be compliant with Section 508 of the Rehabilitation Act of 1973. Additional information about testing documents for Section 508 compliance, including guidance and specific checklists, by application, can be found at:

http://www.hhs.gov/web/508/index.html under "Making Files Accessible." All paper/hardcopy documents/reports submitted under this contract shall be printed or copied, double-sided, on at least 30 percent post consumer fiber paper, whenever practicable, in accordance with FAR 4.302(b).

The Contracting Officer or the duly authorized representative will perform inspection and acceptance of materials and services to be provide. Acceptance may be presumed unless otherwise indicated in writing by the Contracting Officer or the duly authorized representative within 30 days of receipt. The Contractor shall prepare and submit the following electronic reports in the manner stated below in accordance with the Delivery Schedule:

https://erds.niaid.nih.gov/ http://www.hhs.gov/web/508/index.html

1. Teleconference Meetings and Minutes The Contractor shall prepare and submit minutes for each teleconference to the COR within seven (7) days of the teleconference. The minutes shall capture plans for future study designs, technical progress, issues affecting progress, changes in study designs and cumulative expenditures.

2. Individual Study Protocols

The Contractor shall prepare and submit Draft and Final Individual Study Protocols for each study to be performed under this Contract. Draft Individual Study Protocols shall be submitted to the COR within 7 days of study agreement made by teleconference or email.

Approved Final Individual Study Protocols shall be submitted to the COR within 7 days of receipt of COR’s comments and before work begins on the study.

All Individual Study Protocols shall describe all aspects of the therapeutic evaluation study in the following format:

a. Title page containing

i. Contract Number

ii. Title of study, bacteria strain and tissue infected, internal experiment ID, and test compound identifier

iii. Contractor’s name and address

iv. Date of submission to NIAID COR

v. Name of submitter and submitter email address

vi. Start and end dates for the study

vii. Compound sponsor and organization name

b. Introduction

c. Experimental Methods

i. Test compound and control compound preparation and administration

ii. Bacterial strain and challenge material preparation

iii. Animal care and handling procedures (including scoring criteria for assessing animal health and euthanasia criteria)

iv. Compound dosing and infection plans and procedures

v. Procedures for tissue collection and evaluation of bacterial load (for efficacy assessments only)

vi. Plans for development and use of bioanalytical methods for determining drug concentrations in plasma (for plasma drug concentration assessments only)

d. Procedures for analyzing and reporting study data

3. Individual Study Reports The Contractor shall prepare and submit draft and final Individual Study Reports for each study performed under this Contract. Draft Individual Study Reports shall be submitted to the COR within 7 days of study completion. Final Individual Study Reports shall be submitted to the CO and COR within 7 days of receiving comments from the COR.

All Individual Study Reports shall summarize the procedures and results of the study in the following format:

a. Title page as described in section 2a. above

b. Introduction

c. Materials and Methods

d. Animals (total number of animals, strain, weight)

e. Ethics regulation of Laboratory animals

f. Bacterial strain details and stock preparation

g. Compound(d) and vehicle details

h. Experiment design

i. Statistical analysis

j. Study results and Discussion

k. Conclusions

l. References

m. Pertinent primary and summarized data in tables, graphs and figures as appropriate to present significant results

n. Copy of raw data

4. Unused Test Products

The Contractor shall ship unused test products back to the supplier within 60 days of the COR’s acceptance of the Final Individual Study Report for the study for which the test products were used.

5. Final Report On or before the Completion Date of the Contract, the Contractor shall prepare and submit a Final Report to the COR and CO. The Final Report shall summarize the results of all work completed under the Contract in the following format:

a. Title page as described in section 2a. above

b. Introduction covering purpose and scope of the Contract

c. Description of overall progress including

i. Protocols performed

ii. Contract modifications

iii. Primary and summarized data in tables or graphs to present significant results achieved

iv. Scientific evaluation of data

v. Conclusions from analysis

d. Cumulative list of all studies performed and products tested, including dates for beginning and completion of studies and summary of invoiced expenses

e. Copies of any abstracts, manuscripts, and publications

f. A cumulative listing of all publications including accession numbers

g. Copies of raw data

Invention Reporting Requirement

6. All reports and documentation required by FAR Clause 52.227-11, Patent Rights- Ownership by the Contractor including, but not limited to, the invention disclosure report, the confirmatory license, and the Government support certification, shall be directed to the Division of Extramural Inventions and Technology Resources (DEITR), OPERA, OER, NIH, 6705 Rockledge Drive, Suite 310, MSC 7980, Bethesda, Maryland 20892-7980 (Telephone: 301-435-1986). In addition, one copy of an annual utilization report, and a copy of the final invention statement, shall be submitted to the Contracting Officer. The final invention statement (see FAR 27.303(b)(2)(ii)) shall be submitted to the Contracting Officer on the expiration date of the contract.

The annual utilization report shall be submitted in accordance with the DELIVERY SCHEDULE outlined below. The final invention statement (see FAR 27.303(b)(2)(ii)) shall be submitted on the expiration date of the contract. All reports shall be sent to the following address:

George Kennedy Contracting Officer, Research Contracts Branch-A (MIDRCB-A) Office of Acquisitions, DEA, NIAID, NIH, HHS kennedyg@mail.nih.gov

If no invention is disclosed or no activity has occurred on a previously disclosed invention during the applicable reporting period, a negative report shall be submitted to the Contracting Officer at the address listed above.

To assist contractors in complying with invention reporting requirements of the clause, the NIH has developed "Interagency Edison," an electronic invention reporting system.

Use of Interagency Edison is required as it streamlines the reporting process and greatly reduces paperwork. Access to the system is through a secure interactive Web site to ensure that all information submitted is protected. Interagency Edison and information relating to the capabilities of the system can be obtained from the Web ( http://www.iedison.gov ), or by contacting the Extramural Inventions and Technology Resources Branch, OPERA, NIH.

DELIVERY SCHEDULE

Item Description Reference Delivery Schedule 1 Teleconference Minutes Reporting

Requirements, 1 On or before the 7th day following the teleconference.

2 Individual Study Protocols Reporting Requirements, 2

Draft due within 7 days of receipt of executed SRF.

Final protocol due within 7 days of receiving comments from COR on draft protocol.

3 Individual Study Reports Reporting Requirements, 3

Draft due within 7 days of study completion.

Final report due within 7 days of receiving comments from COR on draft report.

4 Test Products Remaining from Studies

Reporting Requirements, 4

On or before 60 days after the Final Individual Study Report is completed. If subsequent studies are scheduled for the same product, delivery timing refers to the last of the Individual Study Reports

5 Final Report Reporting Requirements, 5

On or before the Contract Completion Date.

6 Invention Reporting Requirement

Reporting Requirements, 6

On the expiration date of the Contract.

mailto:kennedyg@mail.nih.gov http://www.iedison.gov/

The above items shall be addressed and delivered to:

Addressee Deliverable Item(s) No

Contracting Officer (via eRDS) 1-3 & 5-6 Contracting Officer’s Representative (Electronically, email to be provided)

1-3 & 5-6

Contracting Officer’s Representative or Third Party Submitter (Overnight shipping, as agreed with COR)

[END OF REPORTING REQUIREMENTS AND DELIVERY SCHEDULE]

CONTRACT ADMINISTRATION DATA

CONTRACTING OFFICER'S REPRESENTATIVE (COR)

The following Contracting Officer's Representative (COR) will represent the Government for the purpose of this contract:

[To be specified prior to award]

The COR is responsible for: (1) monitoring the Contractor's technical progress, including the surveillance and assessment of performance and recommending to the Contracting Officer changes in requirements; (2) interpreting the statement of work and any other technical performance requirements; (3) performing technical evaluation as required; (4) performing technical inspections and acceptances required by this contract; and (5) assisting in the resolution of technical problems encountered during performance.

The Contracting Officer is the only person with authority to act as agent of the Government under this contract. Only the Contracting Officer has authority to: (1) direct or negotiate any changes in the statement of work; (2) modify or extend the period of performance; (3) change the delivery schedule; (4) authorize reimbursement to the Contractor for any costs incurred during the performance of this contract; (5) otherwise change any terms and conditions of this contract; or

(6) sign written licensing agreements. Any signed agreement shall be incorporated by reference in Representations and Certifications to this the contract.

The Government may unilaterally change its COR designation.

INVOICE SUBMISSION

1. Payment requests shall be submitted to the offices identified below. Do not submit supporting documentation (e.g., receipts, time sheets, vendor invoices, etc.) with your payment request unless specified elsewhere in the contract or requested by the Contracting Officer.

a. The original invoice shall be submitted to the following designated billing office:

National Institutes of Health Office of Financial Management Commercial Accounts 2115 East Jefferson Street, Room 4B-432, MSC 8500 Bethesda, MD 20892-8500

b. One copy of the invoice shall be submitted to the following approving official:

George Kennedy Contracting Officer, Research Contracts Branch-A (MIDRCB-A) Office of Acquisitions, DEA, NIAID, NIH, HHS kennedyg@mail.nih.gov

2. In addition to the requirements specified in FAR 32.905 for a proper invoice, the Contractor shall include the following information on the face page of all payment requests:

a. Name of the Office of Acquisitions. The Office of Acquisitions for this contract is the

National Institute of Allergy and Infectious Diseases.

b. Federal Taxpayer Identification Number (TIN). If the Contractor does not have a valid

TIN, it shall identify the Vendor Identification Number (VIN) on the payment request. The VIN is the number that appears after the Contractor's name on the face page of the contract. [Note: A VIN is assigned to new contracts awarded on or after June 4, 2007, and any existing contract modified to include the VIN number.] If the Contractor has neither a TIN, DUNS, or VIN, contact the Contracting Officer.

c. DUNS or DUNS+4 Number. The DUNS number must identify the Contractor's name and address exactly as stated in the contract and as registered in the Central Contractor Registration (CCR) database. If the Contractor does not have a valid DUNS number, it shall identify the Vendor Identification Number (VIN) on the payment request. The VIN is the number that appears after the Contractor's name on the face page of the contract. [Note: A VIN is assigned to new contracts awarded on or after June 4, 2007, and any existing contract modified to include the VIN number.] If the Contractor has neither a TIN, DUNS, or VIN, contact the Contracting Officer.

d. Invoice Matching Option. This contract requires a two-way match.

e. Unique Invoice Number. Each payment request must be identified by a unique invoice number, which can only be used one time regardless of the number of contracts or orders held by an organization.

f. The Contract Title is: “Therapeutics Testing in Murine Models of Bacterial Thigh & Lung Infections.”

3. Inquiries regarding payment of invoices shall be directed to the designated billing office,

(301) 496-6088.

SPECIAL CONTRACT REQUIREMENTS

RESEARCH INVOLVING RECOMBINANT

OR SYNTHETIC NUCLEIC ACID MOLECULES

All research projects (both NIH-funded and non-NIH-funded) involving recombinant or synthetic nucleic acid molecules that are conducted at or sponsored by an entity in the U.S. that receives any support for recombinant or synthetic nucleic acid research from NIH shall be conducted in accordance with the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules ( NIH Guidelines ) available at: http://osp.od.nih.gov/office-biotechnology-activities/biosafety/nih-guidelines ). All NIH-funded projects abroad that include recombinant or synthetic nucleic acid molecules must also comply with the NIH Guidelines.

The NIH Guidelines stipulate biosafety and containment measures for recombinant or synthetic nucleic acid research, which is defined in the NIH Guidelines as research with (1) molecules that

a) are constructed by joining nucleic acid molecules and b) can replicate in a living cell, i.e.

recombinant nucleic acids, or (2) nucleic acid molecules that are chemically or by other means synthesized or amplified, including those that are chemically or otherwise modified but can base pair with naturally occurring nucleic acid molecules, i.e. synthetic nucleic acids, or (3) molecules that result from the replication of those described in (1) or (2). The NIH Guidelines apply to both basic and clinical research. Specific guidance for the conduct of human gene transfer studies appears in Appendix M of the NIH Guidelines.

Failure to comply with the NIH Guidelines may result in suspension, limitation, or termination of the contract for any work related to recombinant or synthetic nucleic acid research or a requirement for the Contracting Officer to approve any or all recombinant or synthetic nucleic acid molecule projects under this contract. This includes the requirement for the institution to have an Institutional Biosafety Committee (IBC) registered with the NIH Office of Science Policy that complies with the requirements of the NIH Guidelines . Further information about compliance with the NIH Guidelines can be found on the NIH Office of Science Policy website available at: http://osp.od.nih.gov.

ANIMAL WELFARE

All research involving live, vertebrate animals shall be conducted in accordance with the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy). The PHS Policy can be accessed at: http://grants1.nih.gov/grants/olaw/references/phspol.htm

In addition, the research involving live vertebrate animals shall be conducted in accordance with the description set forth in the Vertebrate Animal Section (VAS) of the contractor's technical proposal, as modified in the Final Proposal Revision (FPR), dated , which is incorporated by reference.

RESTRICTION ON PORNOGRAPHY ON COMPUTER NETWORKS

The Contractor shall not use contract funds to maintain or establish a computer network unless such network blocks the viewing, downloading, and exchanging of pornography.

http://osp.od.nih.gov/

GUN CONTROL

The Contractor shall not use contract funds in whole or in part, to advocate or promote gun control.

OPTION PROVISION

Unless the Government exercises its option pursuant to the Option Clause set forth under the Statement of Work, the contract will consist only of the Base Period of the Statement of Work as defined in within the Statement of Work above. Pursuant to FAR Clause 52.217-7, Option for Increased Quantity, the Government may, by unilateral contract modification, require the Contractor to perform additional options set forth in the Statement of Work. If the Government exercises this option, notice must be given prior to the expiration date of this contract.

[END OF SPECIAL CONTRACT REQUIREMENTS]

EVALUATION CRITERIA

1. GENERAL

Selection of an Offeror for contract award will be based on an evaluation of proposals against the criteria below. Although cost/price is a significant factor, technical factors are more important than cost/price. All evaluation factors other than cost/price, when combined, are significantly more important than cost/price. The Government intends to make award to the Offeror(s) whose proposal provides the best overall value to the Government. The Government reserves the right to make award without discussions.

2. MANDATORY QUALIFICATION CRITERIA

The following mandatory qualification criteria establish conditions that must be met at the time of award. It is the obligation of the Offeror to notify NIAID of current status and any changes in status regarding mandatory qualification criteria prior to award, and at any time during the period of performance:

The Offeror must document access to facilities at the appropriate level of biocontainment as required to fulfill the Statement of Work.

3. TECHNICAL EVALUATION FACTORS

The following evaluation factors will be used when reviewing the technical proposals.

The criteria are listed in order of relative importance.

• Technical Approach: The soundness, adequacy and strength of the Offeror’s proposed methodologies and technical approaches to successfully complete the tasks in the Statement of Work.

• Experience and Past Performance: Documented personnel experience and successful performance of testing of candidate therapeutic products in murine models of bacterial thigh and lung infections and the determination of drug concentration in plasma from infected mice. Documented availability of sufficient personnel time, lab space, capacity and resources to conduct the required studies as described in the

SOW.

• Access to Validated Models: Documented access to and experience with proven neutropenic murine lung and thigh infections validated against bacterial pathogen strains, with emphasis on the following:

Pathogen Antibiotic sensitivity required for individual strains

K. pneumoniae drug susceptible isolate carbapenem-resistant metallo-beta-lactamase (MBL+) isolate carbapenem-resistant (KPC-2+) isolate (not MBL+) E. coli drug-susceptible isolate extended-spectrum beta lactamase (ESBL+) isolate carbapenem-resistant metallo-beta-lactamase (MBL+) isolate P. aeruginosa drug-susceptible isolate carbapenem-resistant, multidrug-resistant (MDR) isolate A. baumannii drug-susceptible isolate multidrug-resistant (MDR) isolate S. aureus USA300 Methicillin-resistant (MRSA) isolate

4. EVALUATION OF OPTIONS

It is anticipated that any contract(s) awarded from this solicitation will contain option provision(s) and period(s).

In accordance with FAR Clause 52.217-5, Evaluation of Options, (July 1990), the Government will evaluate offers for award purposes by adding the total price for all options to the total price for the basic requirement, except when it is determined in accordance with FAR 17.206(b) not to be in the Government's best interests. Evaluation of options will not obligate the Government to exercise the option(s).

5. COST/PRICE EVALUATION

Offeror(s) cost/price proposal will be evaluated for reasonableness. For a price to be reasonable, it must represent a price to the government that a prudent person would pay when consideration is given to prices in the market. Normally, price reasonableness is established through adequate price competition, but may also be determined through cost and price analysis techniques as described in FAR 15.404.

[END OF EVALUATION FACTORS]

PROPOSAL SUBMISSION INSTRUCTIONS

The provision at FAR 52.212-1, Instructions to Offerors – Commercial (Jan. 2017), applies to this acquisition in addition to the following submission instructions.

I. Shipment and marking of the proposal shall be as indicated below:

A. PROPOSAL IDENTIFICATION:

The proposal shall be marked to identify the Solicitation Number and title. It shall also include the following statement:

“TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY”

B. RESPONSE DUE DATE:

The final due date and time for submission of proposals received in response to this Combined Synopsis/Solicitation is Monday, April 17 at 4:30 pm EST. All responses submitted electronically through the Electronic Proposal Submission System (eCPS) by the above due date/time will be evaluated and award decisions will be made based upon the information contained in this Combined Synopsis/Solicitation. Responses received after the above due date/time will not be considered. The Government reserves the right to change the due date/time by amendment to this Combined Synopsis/Solicitation.

Late proposals will be handled in accordance with FAR 52.212-1(f).

Responses must be submitted electronically through the Electronic Proposal Submission System (eCPS) by visiting https://ecps.nih.gov. Follow the “How to Submit an Electronic Proposal” instructions provided on the eCPS website at https://ecps.nih.gov/home/howto.

Facsimile responses will not be accepted.

Questions should be sent electronically to the following individual:

Jason A. Aroz, Contract Specialist Office of Acquisitions National Institute of Allergy and Infectious Diseases, NIH 5601 Fishers Lane, 3rd Floor, MSC 9821 Bethesda, MD 20892 Phone: (301) 761-7468 E-mail: Jason.Aroz@nih.gov

II. PROPOSAL FORMAT

https://ecps.nih.gov/ https://ecps.nih.gov/home/howto

NOTE: Offerors must include a completed copy of the provision at FAR 52.212-3, Offeror Representations and Certifications – Commercial Items (Jan. 2017) with their proposal

a. Cover Letter The Offeror shall submit their proposal with a cover letter signed by an individual authorized to bind the organization. The cover letter shall include the following:

- Date of submission

- Offeror’s DUNs Number

- Total Fixed Price for each study proposed

b. Technical Proposal Prepare a proposal to accomplish the effort described in the Statement of Work.

For each available thigh and lung infection model and strain included in the proposal, provide the following:

• Evidence of the availability of appropriate bacterial strains, including MIC data for a range of known drugs against each strain to demonstrate the desired drug-susceptibility profile. Provide available genetic or other data relevant to known resistance mechanisms for each of the proposed bacterial strains to support the drug susceptibility phenotype data.

• Validation for each bacterial strain in lung and thigh models including documentation of reliable performance with statistical analysis of the reproducibility of infection CFU data cross multiple measurements for the initial challenge material, immediately prior to drug treatment and vehicle control after 24 hours, as well as statistical analysis of the CFU reduction from a range of doses of known drugs that will provide positive controls for the specific models.

A known drug must be available for each strain in each model that can be used as a reliable positive control.

• Data that demonstrates expertise in sampling and liquid chromatography/mass-spectrometry (LC/MS) bioanalytical methods to determine drug concentrations in plasma from satellite groups of infected mice and calculations of standard PK parameters that align with expectations from the for the known, positive control drugs.

c. Business Proposal Complete the pricing sheet below for each study type stating your Fixed Price PER

STUDY.

Price per Study # of Studies Total MIC Determination 25 Efficacy Assessment 15 MTD Studies 10 Bioanalytical Assessment of Drug Concentration 10

Custom Strain Profiling 2

TOTAL PRICE

[END OF PROPOSAL SUBMISSION INSTRUCTIONS]

INCORPORATED TERMS & CLAUSES

The solicitation documents and incorporated provisions and clauses are those in effect through Federal Acquisition Circular 2005-95, effective January 13, 2017.

NOTE: The Contractor selected for award will be subject to the terms of any Non Clinical Evaluation Agreement entered into by the Government with any third party submitters. A Sample Non-Clinical Evaluation Agreement is included as “Attachment 2”.

The following clauses regarding the care of animals in the performance of this contract are applicable:

NOTICE TO OFFERORS OF REQUIREMENT FOR COMPLIANCE WITH THE PUBLIC

HEALTH SERVICE POLICY ON HUMANE CARE AND USE OF LABORATORY

ANIMALS, HHSAR 352-270-5A (DECEMBER 18, 2015).

The Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (PHS Policy) establishes a number of requirements for research activities involving animals. Before awarding a contract to an offeror, the organization shall file, with the Office of Laboratory Animal Welfare (OLAW), National Institutes of Health (NIH), a written Animal Welfare Assurance (Assurance) which commits the organization to comply with the provisions of the PHS Policy, the Animal Welfare Act, and the Guide for the Care and Use of Laboratory Animals (National Academy Press, Washington, DC). In accordance with the PHS Policy, offerors must establish an Institutional Animal Care and Use Committee (IACUC), qualified through the experience and expertise of its members, to oversee the institution’s animal program, facilities, and procedures. Offerors must provide verification of IACUC approval prior to receiving an award involving live vertebrate animals. No award involving the use of animals shall be made unless OLAW approves the Assurance and verification of IACUC approval for the proposed animal activities has been provided to the Contracting Officer. Prior to award, the Contracting Officer will notify Contractor(s) selected for projects involving live vertebrate animals of the Assurance and verification of IACUC approval requirement. The Contracting Officer will request that OLAW negotiate an acceptable Assurance with those Contractor(s) and request verification of IACUC approval. For further information, contact OLAW at NIH, 6705 Rockledge Drive, RKL1, Suite 360, MSC 7982 Bethesda, Maryland 20892-7982 (E-mail: olaw@od.nih.gov;

Phone: 301–496–7163).

(End of clause)

CARE OF LIVE VERTEBRATE ANIMALS, 352.270-5B (DECEMBER 18, 2015)

(a) Before undertaking performance of any contract involving animal-related activities where the species is regulated by the United Sates Department of Agriculture (USDA), the Contractor shall register with the Secretary of Agriculture of the United States in accordance with 7

U.S.C. 2136 and 9 CFR sections 2.25 through 2.28. The Contractor shall furnish evidence of the registration to the Contracting Officer.

(b) The Contractor shall acquire vertebrate animals used in research from a dealer licensed by the Secretary of Agriculture under 7 U.S.C. 2133 and 9 CFR sections 2.1-2.11, or from a source that is exempt from licensing under those sections.

(c) The Contractor agrees that the care, use, and intended use of any live vertebrate animals in the performance of this contract shall conform with the Public Health Service (PHS) Policy on Humane Care of Use of Laboratory Animals (PHS Policy), the current Animal Welfare Assurance (Assurance), the Guide for the Care and Use of Laboratory Animals (National Academy Press, Washington, DC) and the pertinent laws and regulations of the United States Department of Agriculture (see 7 U.S.C. 2131 et seq. and 9 CFR subchapter A, Parts 1-4). In case of conflict between standards, the more stringent standard shall govern.

(d) If at any time during performance of this contract, the Contracting Officer determines, in consultation with the Office of Laboratory Animal Welfare (OLAW), National Institutes of Health (NIH), that the Contractor is not in compliance with any of the requirements and standards stated in paragraphs (a) through (c) above, the Contracting Officer may immediately suspend, in whole or in part, work and further payments under this contract until the Contractor corrects the noncompliance. Notice of the suspension may be communicated by telephone and confirmed in writing. If the Contractor fails to complete corrective action within the period of time designated in the Contracting Officer’s written notice of suspension, the Contracting Officer may, in consultation with OLAW, NIH, terminate this contract in whole or in part, and the Contractor’s name may be removed from the list of those contractors with Animal Welfare Assurances.

Note: The Contractor may request registration of its facility and a current listing of licensed dealers from the Regional Office of the Animal and Plant Health Inspection Service (APHIS), USDA, for the region in which its research facility is located. The location of the appropriate APHIS Regional Office, as well as information concerning this program may be obtained by contacting the Animal Care Staff, USDA/APHIS, 4700 River Road, Riverdale, Maryland 20737 (E-mail: ace@aphis.usda.gov; website:

http://www.aphis.usda.gov/wps/portal/aphis/ourfocus/animalwelfare).

The following FAR clauses regarding Safety and Health are applicable:

SAFETY AND HEALTH, 352.223-70 (DECEMBER 18, 2015)

(a) To help ensure the protection of the life and health of all persons, and to help prevent damage to property, the Contractor shall comply with all Federal, State, and local laws and regulations applicable to the work being performed under this contract. These laws are implemented or enforced by the Environmental Protection Agency, Occupational Safety and Health Administration (OSHA) and other regulatory/enforcement agencies at the Federal, State, and local levels.

(1) In addition, the Contractor shall comply with the following regulations when developing and implementing health and safety operating procedures and practices for http://www.aphis.usda.gov/wps/portal/aphis/ourfocus/animalwelfare both personnel and facilities involving the use or handling of hazardous materials and the conduct of research, development, or test projects:

(i) 29 CFR 1910.1030, Bloodborne pathogens; 29 CFR 1910.1450, Occupational exposure to hazardous chemicals in laboratories; and other applicable occupational health and safety standards issued by OSHA and included in 29 CFR part 1910. These regulations are available at https://www.osha.gov/.

(ii) Nuclear Regulatory Commission Standards and Regulations, pursuant to the Energy Reorganization Act of 1974 (42 U.S.C. 5801 et seq.). The Contractor may obtain copies from the U.S. Nuclear Regulatory Commission, Washington, DC 20555–0001.

(2) The following Government guidelines are recommended for developing and implementing health and safety operating procedures and practices for both personnel and facilities:

(i) Biosafety in Microbiological and Biomedical Laboratories, CDC. This publication is available at http://www.cdc.gov/biosafety/publications/index.htm.

(ii) Prudent Practices for Safety in Laboratories (1995), National Research Council, National Academy Press, 500 Fifth Street, NW., Lockbox 285, Washington, DC 20055 (ISBN 0–309–05229–7). This publication is available at http://www.nap.edu/catalog/4911/prudent-practices-in-the-laboratory-handling-and-disposal-of-chemicals.

(b) Further, the Contractor shall take or cause to be taken additional safety measures as the Contracting Officer, in conjunction with the Contracting Officer’s Representative or other appropriate officials, determines to be reasonably necessary. If compliance with these additional safety measures results in an increase or decrease in the cost or time required for performance of any part of work under this contract, the Contracting Officer will make an equitable adjustment in accordance with the applicable “Changes” clause set forth in this contract.

(c) The Contractor shall maintain an accurate record of, and promptly report to the Contracting Officer, all accidents or incidents resulting in the exposure of persons to toxic substances, hazardous materials or hazardous operations; the injury or death of any person; or damage to property incidental to work performed under the contract resulting from toxic or hazardous materials and resulting in any or all violations for which the Contractor has been cited by any Federal, State or local regulatory/enforcement agency. The report citing all accidents or incidents resulting in the exposure of persons to toxic substances, hazardous materials or hazardous operations; the injury or death of any person; or damage to property incidental to work performed under the contract resulting from toxic or hazardous materials and resulting in any or all violations for which the Contractor has been cited shall include a copy of the notice of violation and the findings of any inquiry or inspection, and an analysis addressing the impact these violations may have on the work remaining to be performed. The report shall also state the required action(s), if any, to be taken to correct any violation(s) noted by the Federal, State, or local regulatory/enforcement agency and the time frame allowed by the agency to accomplish the necessary corrective action.

(d) If the Contractor fails or refuses to comply with the Federal, State or local regulatory/enforcement agency’s directive(s) regarding any violation(s) and prescribed corrective action(s), the Contracting Officer may issue an order stopping all or part of the work until satisfactory corrective action (as approved by the Federal, State, or local regulatory/enforcement agencies) has been taken and documented to the Contracting Officer. No part of the time lost due to any such stop work order shall form the basis for a request for extension or costs or damages by the Contractor.

(e) The Contractor shall insert the substance of this clause in each subcontract involving toxic substances, hazardous materials, or hazardous operations. The Contractor is responsible for the compliance of its subcontractors with the provisions of this clause.

The following FAR clauses regarding patent rights are applicable:

PATENT RIGHTS – OWNERSHIP BY THE CONTRACTOR, 352.227-11

(SEPTEMBER 2014)

352.227-11 Patent Rights – Ownership by the Contractor (September 2014) (Deviation)

This clause deviation applies to all Contractor and subcontractor (at any tier) Subject Inventions.

(a) Definitions.

(1) Agency means the Agency of the U.S. Department of Health and Human Services that is entering into this contract.

(2) “Class 1 Subject Invention” means a Subject Invention described and defined in the DEC that will be assigned to a third party assignee, or assigned as directed by the Agency.

(3) “Class 2 Subject Invention” means a Subject Invention described and defined in the DEC.

(4) “Class 3 Subject Invention” means a Subject Invention that does not fall into Class 1 or Class 2 above.

(5) “DEC” means the Determination of Exceptional Circumstances signed by [insert approving official] ____ on ____ [insert date] ____ and titled “[insert description].”

(6) “Invention” means any invention or discovery which is or may be patentable or otherwise protectable under title 35 of United States Code, or any novel variety of plant that is or may be protectable under the Plant Variety Protection Act (7 U.S.C. 2321, et. seq.)

(7) “Made” means: when used in relation to any invention other than a plant variety, the conception or first actual reduction to practice of such invention; or when used in relation to a plant variety, that the Contractor has at least tentatively determined that the variety has been reproduced with recognized characteristics.

(8) “Material” means any proprietary material, method, product, composition, compound or device, whether patented or unpatented, which is provided to the Contractor under this contract.

(9) “NIAID” means the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH)

(10) “NIH” means the National Institutes of Health, a component of the United States Department of Health and Human Services (HHS).

(11) “Nonprofit organization” means a university or other institution of higher education or an organization of the type described in section 501(c)(3) of the Internal Revenue Code of 1954 (26 U.S.C. 50I(c)) and exempt from taxation under section 501(a) of the Internal Revenue Code (26 U.S.C. 501 (a)) or any nonprofit scientific or educational organization qualified under a state nonprofit organization statute.

(12) “Practical application” means to manufacture, in the case of a composition or product; to practice, in the case of a process or method, or to operate, in the case of a machine or system; and, in each case, under such conditions as to establish that the invention is being utilized and that its benefits are, to the extent permitted by law or Government regulations, available to the public on reasonable terms.

(13) “Provider” means any…