BIO_NSN_RFP-16-100-SOL-00008.docx

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1. THIS CONTRACT IS A RATED ORDER

UNDER DPAS (15 CFR 700)

RATING

2. CONTRACT NO.

N/A

3. SOLICITATION NO.

RFP-16-100-SOL-00008

05/06/2016

6. REQUISITION/PURCHASE NO.

N/A

8. ADDRESS OFFER TO (If other than Item 7)

HHS/OS/ASPR/AMCG

330 Independence Ave, SW, RM G-640 Washington, DC 20201

NOTE: In sealed bid solicitations “offer” and “Offeror” mean “bid” and “bidder.”

SOLICITATION

(Hour) (Date) (Hour)

CAUTION -- LATE Submissions, Modifications, and Withdrawals: See Section L, Provision No. 52.214-7 or 52.215-1.

All offers are subject to all terms and conditions contained in this solicitation.

10. FOR INFORMATION

CALL:

A. NAME

Elizabeth Steiner

a. TELEPHONE (NO COLLECT CALLS)

(202) 205-8926

b. E-MAIL ADDRESS Elizabeth.Steiner@hhs.gov

11. TABLE OF CONTENTS

((x)PAGE(S)

SEC.

SEC.

PAGE(S)

PAGE(S)

SEC.

SEC.

PAGE(S)

DESCRIPTION

(x)

DESCRIPTION

XK

REPRESENTATIONS, CERTIFICATIONS, AND

OFFER (Must be fully completed by Offeror)

NOTE: Item 12 does not apply if the solicitation includes the provisions at 52.214-16, Minimum Bid Acceptance Period.

12. In compliance with the above, the undersigned agrees, if this offer is accepted within ___150___calendar days (60 calendar days unless a differentCALENDAR DAYS

CALENDAR DAYS

14. ACKNOWLEDGMENT OF AMENDMENTS

(Type or Print)

(Type or Print)

CODE

FACILITY

16. NAME AND ADDRESS OF PERSON AUTHORIZED TO SIGN OFFER

15B. TELEPHONE NO.

AREA CODE NUMBER EXT.

18. OFFER DATE

AWARD (To be completed by Government)

19. ACCEPTED AS TO ITEMS NUMBERED 20. AMOUNT

22. AUTHORITY FOR USING OTHER THAN FULL AND OPEN COMPETITION:

21. ACCOUNTING AND APPROPRIATION

26. NAME OF CONTRACTING OFFICER (Type or print)

27. UNITED STATES OF AMERICA

(Signature of Contracting Officer)

28. AWARD DATE

IMPORTANT -- Award will be made on this form, or on Standard Form 26, or by other authorized official written notice.

FAR (48 CFR) 53.214©

NOTE TO OFFERORS

The information in SECTION A - Solicitation/Contract Form contains important information for any Offeror interested in responding to this solicitation. Any contract resulting from this solicitation will include in its SECTION A - Solicitation/ Contract Form, accounting, appropriation and general information applicable to the contract award.

The contract schedule, set forth in SECTIONS B through H, contains contractual information pertinent to this solicitation. It is not an exact representation of the contract document that will be awarded as a result of this solicitation. The contract cost or price and other contractual provisions unique to the Offeror's proposal may be included in the resultant contract.

The contract schedule is intended to provide the Offeror with information to aid in understanding the likely terms and conditions of any resultant contract.

PART I – THE SCHEDULE

Section B – Supplies or Service and Price / Cost

BARDA Biological Nonclinical Studies Network (NSN)

B.1. Brief Description of Supplies and Services

This Request for Proposal (RFP) solicits proposals for an indefinite delivery, indefinite quantity (IDIQ) contract for the acquisition of biological nonclinical services for animal model studies, analytical services, and toxicology services. It is anticipated that fixed-price and cost reimbursement type task orders under the IDIQ contract will be issued to support the development of biological countermeasures in the BARDA portfolio.

The Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS), seeks to maintain a network of Good Laboratory Practices (GLP) laboratories that will provide capability for animal model development studies, analytical services, and toxicology services in support of the BARDA portfolio. In the animal models, the challenge dose generally should be the same as that which produces the human disease or condition and the pathophysiological mechanism of its toxicity should be reasonably well-understood and mimic the human disease/condition as closely as possible. When these models are used to test the efficacy of potential medical countermeasures (MCMs) against biological threats, the mechanism of action of the countermeasure will need to establish the utility of the animal model as a surrogate for humans. BARDA anticipates that contracts awarded from this RFP will serve to facilitate nonclinical studies in support of development of medical countermeasures and/or supportive reagents and assays for regulatory acceptance in the U.S.

The Pandemic and All Hazards Preparedness Act (PAHPA) of 2006 established the Biomedical Advanced Research and Development Authority (BARDA) to support development and acquisition of MCMs to prevent or treat the medical consequences of chemical, biological, radiological, and nuclear (CBRN) threats, pandemic influenza (PI), and emerging infectious diseases (EID). These MCMs include vaccines, therapeutics, diagnostics, and medical devices. Additionally, BARDA is entrusted to foster innovation of technologies that enable better manufacturing, testing, and utilization of these medical countermeasures.

The Nonclinical Studies Network (NSN) is a key element in the successful development of medical countermeasures for biological threats, particularly since efficacy of products directed against most of these threats cannot be verified using clinical studies. The United States Government (USG) therefore seeks appropriate GLP facilities that are adequate and available to support establishing new or existing nonclinical tests and/or models for the development of Biological MCMs against biological threats, influenza and emerging infectious diseases.

B.3. Prices / Costs

The final contract will contain the price/cost provisions agreed upon by the Government and the Offeror. It is anticipated that the final contract will contain a base period of five years (60 months).

B.3.1. Base Period

Base Period of Performance: __________ through ___________.

B.3.2. Option Periods

The final contract will not contain Option CLINs.

B.4. ADVANCE UNDERSTANDINGS

The final contract may contain additional advance understandings between the Government and the Offeror.

B.4.1. Minimum Ordering Amount – $50,000

The minimum ordering amount for any task order awarded under this IDIQ is $50,000.

B.4.2. Maximum Ordering Amount – $45,000,000

The Contractor(s) shall not receive payment from the Government in an amount greater than $45,000,000.00 for successful performance under this contract. This contract ceiling is the Government’s most optimistic scenario with respect to the Government’s needs and level of funding.

B.4.3. Minimum Order Guarantee

The total minimum guarantee under this IDIQ contract is $50,000. This one-time amount will be issued upon award on the base contract. This amount can only be claimed at the end of the 60 month period of performance if no task orders are received and if the Contractor takes advantages of fair opportunity, as described in FAR 16.505, by proposing on at least one task order.

B.4.4. Pricing of Task Orders

The Government will issue Requests for Task Order Responses (RTORs) and contractors will compete for task orders for nonclinical research services based on the work described in SECTION C of this contract. Upon delivery and acceptance of the services described in each task order, the Government shall pay to the Contractor the price, costs or fee set forth in the task order.

Individual task orders will be issued as requirements occur, and will specify work to be performed. The Contractor shall perform all services in accordance with each task order’s work statement/specifications. The terms and conditions under the base IDIQ contract are incorporated into all task orders issued pursuant to this contract.

See SECTION G.4. for further ordering information and procedures.

B.4.5. Funding

Funds consisting of the total value of the minimum guarantee will be obligated on the base contract. Funds for the services provided will be obligated, at the task order level, as they become available, unilaterally by the Government.

B.4.6. Cost Unallowable Unless Authorized by the Contracting Officer

This section prohibits or restricts the use of contract funds for the following, unless otherwise approved in advance by the Contracting Officer:

a) Acquisition, by purchase or lease, of any interest in real property;

b) Rearrangement or alteration of facilities;

c) Purchase of lease of any item of general purpose office furniture or office equipment regardless of dollar value;

d) Accountable Government Property;

e) Overtime

f) Travel to attend general scientific meetings/conferences;

g) Foreign Travel Costs;

h) Costs incurred in the performance of any cost-reimbursement type subcontract (including consulting agreements);

i) Costs to be paid for the performance of a fixed-price subcontract that exceeds $150,000.00;

j) Refreshments and Meal Expenditures.

B.4.7. Invoices - Cost and Personnel Reporting, and Variances from the Negotiated Budget

For contract work performed on a cost reimbursement basis, the Contractor agrees to provide a detailed breakdown on invoices of the below cost categories as applicable. A sample invoice form is provided as Attachment #8.

1. Direct Labor - Include salaries and wages paid (or accrued) for direct performance of the contract. List individuals by name, title/position, hourly/annual rate, level of effort (actual hours or % of effort), breakdown by task performed by personnel, and amount claimed.

2. Fringe Benefits - Cite rate and amount

3. Overhead - Cite rate and amount

4. Materials & Supplies - Include detailed breakdown when unit price is over $1,000.

5. Travel - Identify travelers, dates, destination, purpose of trip, and amount. Cite COA, if appropriate. List separately, domestic travel, general scientific meeting travel, and foreign travel.

6. Consultant Fees - Identify individuals and amounts.

7. Subcontracts - Attach subcontractor invoice(s).

8. Equipment - Cite authorization and amount.

9. G&A - Cite rate and amount.

10. Total Cost

11. Fixed Fee

12. Total Cost Plus Fixed Fee (Total CPFF)

For contract work performed on a cost reimbursement basis, monthly invoices must include the cumulative total expenses to date, adjusted (as applicable) to show any amounts suspended by the Government. Also note the Contracting Officer may require the Contractor to submit detailed support for costs claimed on payment requests. Every cost must be determined to be allocable, reasonable, and allowable per FAR Part 31. Invoice submission information is provided in SECTION G.6.

Section C: Statement of Objectives (SOO)

Introduction and Background

Within the Federal government, the Department of Health and Human Services is tasked with protecting the civilian population by providing leadership in research, development, acquisition, deployment, and use of effective medical countermeasures for the adverse health effects resulting from exposure to pandemics and emerging infectious disease threats. Response and recovery were identified as key elements of national defense in the National Strategy to Combat Weapons of Mass Destruction (http://www.whitehouse.gov/new/releases/2002/12/WMDStrategy.pdf). The lead role of HHS in these endeavors was emphasized in Biodefense for the 21st Century (http://www.whitehouse.gov/homeland/20040430.html) and in the National Strategy for Medical Countermeasures against Weapons of Mass Destruction (http://www.whitehouse.gov/news/releases/2007/02/20070207-2.html). These three documents represent the foundation for addressing the Nation’s CBRN medical countermeasure needs. Additionally, on February 3, 2015, the former BARDA Director, Dr. Robin Robinson, informed Congress that , “HHS has made significant progress improving vaccines and manufacturing technologies. Specifically, BARDA has worked with and engaged with industry to achieve the following: Establishment of a national infrastructure to rapidly develop, manufacture, and test new influenza vaccines and medical countermeasures for emerging infectious diseases, such as Ebola.” This effort includes the, “Nonclinical Studies Network, which is able to perform animal testing.”

HHS, through the interagency Public Health Emergency and Medical Countermeasure Enterprise (PHEMCE) is responsible for the integration of requirements for the advanced development and procurement of medical countermeasures for CBRN threats specified by DHS as material threats. The HHS PHEMCE Strategy for Chemical, Biological, Radiological, and Nuclear Threats (HHS PHEMCE Strategy), published in the Federal Register on March 20, 2007 describes the strategic policy goals and objectives for identifying requirements and establishes the priorities for the development of the medical countermeasures. The HHS PHEMCE Implementation Plan for Chemical, Biological, Radiological, and Nuclear Threats (HHS PHEMCE Implementation Plan), published in the Federal Register on April 2007 and updated December 2012, delineates HHS medical countermeasure priorities for research, development and acquisition to address the highest priority CBRN threats.

The Technical Capabilities required to meet the SOO objectives are the following:

1. Technical Plan and Approach

2. Facilities

3. Scientific and Technical Personnel

4. Quality Systems

5. Program and Risk Management

Please note: Response must be provided for each of the above listed Technical Capabilities (1-5) to be considered for evaluation. Please ensure that your proposal clearly addresses each of the above five technical capabilities in your SOO submission.

A proposal may be submitted for only one, two or all three of the subject areas listed in this RFP. Each proposal must be a standalone submission.

Analytical Services (AS)

BARDA has a requirement for selective, sensitive, qualified, and validated analytical methods for the quantitative evaluation of vaccines, drugs, metabolites (analytes) and biomarkers. These analytical methods are critical for the successful conduct of nonclinical, biopharmaceutics and clinical studies. Successful offerors will be required to perform analytical services such as: assay development, assay validation, and quantitative determinations of biological, chemical, and physical parameters in samples.

C.1.AS Technical Plan & Approach for Analytical Services (AS) C.1.AS.1. The USG seeks appropriate GLP facilities that are adequate and available to provide analytical services to support development of new or existing MCMs.

C.1.AS.2. The USG seeks GLP analytical support (this includes small molecule analysis, large molecules- proteins, biomarkers, and other analytical signals) required by animal studies (toxicology, efficacy, safety) and clinical studies). These laboratories must have the capability to develop assays, validate assays, and provide high through-put analysis of clinical and non-clinical studies.

C.1.AS.3. The USG seeks facilities with the ability to develop methods for quantitative determination of vaccine components, viruses, bacteria, drug and/or metabolites, and biomarkers that are required to support the development of the potential therapeutic or device in accordance with applicable FDA and ICH guidance, and following pharmaceutical/medical device industry best practices.

C.1.AS.4. The USG seeks facilities that can perform for the quantitative determination of drugs and/or metabolites, and proteins in biological matrices, including procedures such as gas chromatograph (GC), high-pressure liquid chromatography (HPLC), combined GC and LC mass spectrometric (MS) procedures, such as LC-MS, LC-MS-MS, GC-MS and GC-MS-MS; ligand binding assays (LBAs), and immunological and microbiological BA procedures.

C.1.AS.5. The USG seeks a description of services such as method development, feasibility, transfer and validation; pharmacokinetic and toxico-kinetic analyses, protein binding determination, antibody drug conjugate and/or other macromolecule analysis, biomarker method development and validation, and/or derivatization assays.

C.1.AS.6. The USG seeks facilities for development or utilization of assays for determination of immune responses in animals and humans for the measurement of T cell responses, ASC, innate immune responses, mucosal immunity among others.

C.1.AS.7. The USG seeks facilities for the development and utilization of virological assays for the qualification or quantification of viruses including, if necessary, those pertaining to select agents with high containment requirements.

C.1.AS.8. The USG seeks a description of the biological matrices in which the offeror has previously conducted method development and validation.

C.1.AS.9 The USG seeks a description of the Offeror’s ability to provide support for the selection and/or synthesis of appropriate internal standards.

C.1.AS.10 The USG seeks a description/listing of analytical methods for both small molecules and therapeutic proteins for which the methods were successfully validated and utilized to support the analysis of study sample in accordance with Good Laboratory Procedures (GLP).

C.1.AS.11 The USG seeks a description of the Offeror’s experience with the use of surrogate matrices.

C.1.AS.12 The USG seeks a description of the Offeror’s sample management procedures from receipt through sample disposal, including how an audit trail of the location and conditions of samples are maintained.

C.1AS.13 The USG seeks a description of the offeror’s approach for reanalysis of samples and reporting of samples which have been reanalyzed.

C.1.AS.14 The USG seeks a brief description of the offeror’s procedure for Incurred Sample Reanalysis, particularly in regard to multi-analyte methods. The USG seeks a description of the software used to collect, analyze, and report bioanalytical study sample data.

C.2.AS Facilities for Analytical Services (AS) C.2.AS.1 The USG seeks facilities that comply with USG biocontainment and biosecurity policies and standards, as well as resources that are appropriate for the management of the biological samples associated with the development or conduct of the analytical assay. If necessary, due to the nature of the biological sample or the assay, this facility shall have permits and associated qualifications to enable access to biological high priority threats (e.g. Select agents), as identified in the 2015 PHEMCE Strategy and Implementation Plan where current approved Federal, State and/or local licenses/certifications for animal work and where applicable, ensure that regulations through CDC and/or USDA are followed (42 CFR Part 73, 7 CFR Part 331, and/or 9 CFR Part 121). Conduct work in accordance with all applicable Federal, state and local laws, codes, ordinances and regulations.

C.2.AS.2 The USG seeks laboratories that can provide analytical support to assess samples from the progression of the disease in animal models and demonstrate prospective correlates of protection (i.e., clinical laboratory capabilities and adoption of novel biomarker testing).

C.3.AS Scientific and Technical Personnel for Analytical Services (AS) C.3.AS.1. The offeror(s) shall provide personnel who possess the necessary education, training, and experience to successfully provide analytical services in support of animal model and medical countermeasure development.

C.3.AS.2. A suitable plan for training, certification and recertification of scientific and technical personnel should be provided.

C.4.AS Quality Systems for Analytical Services (AS) C.4.AS.1. The USG seeks laboratories that can develop a quality control (QC)/quality assurance (QA) monitoring plan that shall ensure appropriate storage conditions of select/test biological agent(s) to be tested as well as the appropriate storage conditions and documentation regarding the handling and security for the candidate products (drugs/biologics) being tested for efficacy.

C.4.AS.2. The USG seeks laboratories that can submit evidence of an effective Regulatory and Quality Management System (QMS) (21 CFR Part 58). Offeror(s) shall ensure that the details in the submitted proposal incorporate: 1) QMS in all aspects of the proposal to provide analytical services; 2) a copy of a Quality Plan; 3) a quality reporting structure; 4) an FDA inspection history that provides all observations listed on the FDA Form-483 and associated corrective actions; 5) a regulatory platform that can comply with the evolving regulatory environment regarding requirements for animal research and the FDA regulatory guideline for animal studies in support of approval/ or licensure, such as, 21 CFR Part 58, “Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies,” and 21 CFR Parts 314 and 601 and subparts, “New Drug and Biological Drug Products: Evidence Needed to Demonstrate Effectiveness of medical countermeasures under New Drugs when Human Efficacy Studies Are Not Ethical or Feasible. (i.e., the Animal Rule).

C.5.AS Program & Risk Management for Analytical Services (AS) C.5.AS.1.The USG seeks laboratories that can provide and implement plans for the overall management, integration and coordination of all contract activities, timelines, and task-linked budgets including the management and coordination of activities carried out under subcontracts. The offeror(s) shall develop a risk mitigation plan highlighting potential problems and/or issues that may arise while providing analytical support, the impact on cost, performance and timelines, and appropriate remediation plans.

C.5.AS.2. The offeror(s) shall propose an integrated management plan for analytical support, including key subcontractors. Management of personnel should include, but is not limited to, providing a list of key individuals and their qualifications to carry out the work detailed in the SOO.

Animal Model Testing (AMT)

BARDA intends to retain and expand its capability to develop animal model and MCM testing. This will insure sufficiently characterized reagents and appropriate studies enable BARDA’s development of therapeutics, either through planned Clinical Studies, or through the FDA Animal Rule. Although not every study conducted under this contract will be GLP, offeror(s) should have previous experience conducting GLP studies in small and large animal models at their facilities

C.1.AMT. Technical Plan & Approach for Animal Model Testing (AMT) C.1.AMT.1. The USG seeks organizations capable of developing animal models to determine the efficacy of potential MCMs (e.g. strain screening) according to FDA Guidelines for the Development of Animal Models.

C.1.AMT.2 The USG seeks organizations capable of carrying-out animal model studies where the challenge dose is similar to that which produces the human disease or condition, and the pathophysiological mechanism of its toxicity should be reasonably well-understood and mimic the human disease/condition as closely as possible.

C.1.AMT.3 The USG seeks laboratories with experience conducting nonclinical safety evaluations following exposure of a drug through multiple routes of administration.

C.2.AMT Facilities for Animal Model Testing (AMT) C.2.AMT.1. The USG seeks safe facilities and resources that can access Select Agents, influenza strains and/or emerging infectious disease pathogens to address biological high priority threats as identified in the 2015 PHEMCE Strategy and Implementation Plan where current approved Federal, State and/or local licenses/ certifications for animal work and where applicable, ensure that regulations through CDC and/or USDA are followed (42 CFR Part 73, 7 CFR Part 331, and/or 9 CFR Part 121). Conduct work in accordance with all applicable Federal, state and local laws, codes, ordinances and regulations.

C.2.AMT.2. The USG seeks laboratories that have established protocols for routine care and health surveillance for laboratory animals, including on-call veterinary coverage 24 hours per day.

C.2.AMT.3. The USG seeks laboratories that can conduct studies to establish the pathophysiology/natural history of selected biological threat agents or infectious pathogens in appropriate animal species at different ages in response to government needs.

C.2.AMT.4. The USG seeks laboratories that can design a protocol and perform efficacy evaluations in various species on candidate compounds (i.e., drugs and biologics) as specified in task order Statement of Work to permit further product development including but not limited to the assessment and optimization of the formulation, route of administration, effective dose levels, dose schedule, therapeutic index (i.e. the ratio of the drug/biologic’s adverse event plasma concentration over the plasma concentration sufficient for efficacy), and timing of administration (pre-exposure, post-exposure, delayed administration, as well as the determination of the effective dose levels and the therapeutic index (i.e., the ratio of the highest plasma concentration not associated with adverse effects over the lowest plasma concentration associated with the demonstration of efficacy).

C.2.AMT.5. The USG seeks laboratories that can provide analytical support to monitor the progression of the disease in animal models and demonstrate prospective correlates of protection; (i.e., clinical laboratory capabilities and adoption of novel biomarker testing).

C.2.AMT.6. The USG seeks laboratories that can provide microbiological support for the pathogens(s) specified in the task order Statement of Work, including quality-controlled master and working banks; SOPs for production and characterization challenge material under standardized media and growth conditions, and master and working banks for cell lines where applicable. USG seeks laboratories that can develop and/or provide acceptance criteria for the use of challenge material in animal model studies.

C.2.AMT.7. The USG seeks laboratories that have adequate statistical and pharmacokinetics support to analyze and predict experimental hypotheses for models, including pharmacokinetic modeling (both individual animal and population approaches using compartmental and non-compartmental methods).

C.2.AMT.8. The USG seeks laboratories with the capability of controlled exposure of various animal species to biological, influenza, or emerging infectious disease pathogens in order to develop models to evaluate the efficacy of potential.

C.2.AMT.9. In all cases described above, the USG seeks laboratories with the capability to perform these procedures and studies in animal models of human at-risk and special populations (e.g., juvenile, pediatric, geriatric, pregnancy, etc).

C.2.AMT.10. The USG seeks laboratories capable of submitting study data to BARDA in SEND format.

C.3.AMT Scientific and Technical Personnel for Animal Model Testing (AMT) C.3.AMT.1. The offeror(s) shall provide personnel who possess the necessary education, training, and experience to work with a wide range of animal species and agents identified on the CDC Biothreat and Emerging Infectious Disease list.

C.3.AMT.2. A suitable plan for training, certification and recertification of scientific and technical personnel should be provided. Specifically, BARDA is interested in the train of technical staff for handling agents in containment, GLP training and the handling of animal in accordance with animal welfare guideline.

C.4.AMT Quality Systems for Animal Model Testing (AMT) C.4.AMT.1. The USG seeks laboratories that can develop a quality control (QC)/quality assurance (QA) monitoring plan that shall ensure appropriate storage conditions of select/test biological agent(s) to be tested as well as the appropriate storage conditions and documentation regarding the handling and security for the candidate products (drugs/biologics) being tested for efficacy. Specifically BARDA is looking for organization with a proactive quality program. This can be simple data trending to the more complex effort associated with real time quality monitoring.

C.4.AMT.2. The USG seeks laboratories that can submit evidence of an effective Regulatory and Quality Management System (QMS) (21 CFR Part 58). Offeror(s) shall ensure that the details in the submitted proposal incorporate: 1) QMS in all aspects of the proposal to fulfill the proposal objectives; 2) a copy of a Quality Plan; 3) a quality reporting structure; 4) an FDA inspection history that provides all observations listed on the FDA Form-483 and associated corrective actions; 5) a regulatory platform that can comply with the evolving regulatory environment regarding requirements for animal research and the FDA regulatory guideline for animal studies in support of approval/ or licensure, such as, 21 CFR Part 58, “Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies,” and 21 CFR Parts 314 and 601 and subparts, “New Drug and Biological Drug Products: Evidence Needed to Demonstrate Effectiveness of medical countermeasures under New Drugs when Human Efficacy Studies Are Not Ethical or Feasible. (i.e., the Animal Rule). Offerors must possess the ability to look at the overall BARDA mission which is the licensure of medical countermeasures.

C.5.AMT Program & Risk Management for Animal Model Testing (AMT)

C.5.AMT.1. The USG seeks laboratories that can provide and implement plans for the overall management, integration and coordination of all contract activities, timelines, and task-linked budgets including the management and coordination of activities carried out under subcontracts. The offeror(s) shall develop a risk mitigation plan highlighting potential problems and/or issues that may arise during animal model development studies, the impact on cost, performance and timelines, and appropriate remediation plans. The USG is interested in how the offerors build team to address the technical efforts (the science), the budget and the coordination of limited facilities.

C.5.AMT.2. The offeror(s) shall propose an integrated management including key subcontractors. Management of personnel should include, but is not limited to, providing a list of key individuals and their qualifications to carry out the work detailed in the SOO. The USG does not expect every offeror to have all of the personnel, equipment and facilities to support all of BARDA’s future task orders. However, the offeror should have a plan to identify other organization with specialized skills to support the BARDA mission.

Toxicology Services (TS)

BARDA has a requirement to evaluate the nonclinical safety and pharmacokinetic/toxicokinetic profile of medical countermeasures under development. These toxicology services are critical for the successful conduct of nonclinical, biopharmaceutics and clinical studies. A successful offeror will be required to carry out necessary toxicology, pharmacokinetics, safety pharmacology, nonclinical absorption, distribution, metabolism and elimination (ADME) studies in accordance with applicable health authority requirements, including, but not limited to the Food and Drug Administration (FDA) and the International Conference on Harmonization the Office of Economic (ICH).

C.1.TS Technical Plan & Approach for Toxicology Services (TS)

C.1.TS.1. The USG seeks organizations capable of providing capability and expertise to execute the nonclinical safety and/or ADME regulatory studies that are required to support the development of potential therapeutics. These studies should be conducted in accordance with the applicable FDA and ICH guidance and follow standard pharmaceutical/medical device industry practices.

C.1.TS.2. The USG seeks organizations capable of conducting Toxicology studies to support the safety of individual phases of clinical development. Studies in at least two animal species (one being a non-rodent) should be used to assess acute, subchronic and chronic toxicity at the proposed site of exposure.

C.1.TS.3. The USG seeks organizations capable of conducting Pharmacokinetic/Toxicokinetic Studies. During the conduct of subchronic and chronic toxicity studies, concurrent pharmacokinetic/toxicokinetic analyses should be performed to evaluate the drug's ADME (absorption, disposition, metabolism and excretion) profile and to determine if the drug is systemically absorbed. Appropriate analytical methodology should be established as early as possible to provide for precise, consistent and reliable pharmacokinetic data.

C.1.TS.4. The USG seeks organizations capable of conducting a standard battery of tests to evaluate all new molecular entities for the potential to induce genotoxic effects. A drug should be evaluated for potential genetic toxicity prior to the submission of the IND.

C.1.TS.5. The USG seeks organizations capable of conducting reproductive toxicology studies, which should be carried out to explore the possible effects of the drug on fertility and reproductive performance. Additional studies should be performed to examine whether the drug is teratogenic or has an effect on perinatal/postnatal development

C.1.TS.6. The USG seeks laboratories with experience conducting nonclinical safety evaluations following exposure of a drug through multiple routes of administration.

C.1.TS.7. The USG seeks laboratories with the ability to carry-out histopathology studies, including slide preparation and evaluation of tissues.

C.1.TS.8. The USG seeks organizations with historical pathology databases that include descriptions regarding route and species.

C.1.TS.9. The USG seeks organizations with the capacity to prepare samples and conduct histological assessment of tissues.

C.1.TS.10. The United States Government (USG) seeks appropriate Good Laboratory Practices (GLP) facilities that are adequate and available to provide nonclinical animal services to support development of new or existing MCMs.

C.2.TS Facilities for Toxicology Services (TS) C.2.TS.1. The USG seeks laboratories that have established protocols for routine care and health surveillance for laboratory animals, including on-call veterinary coverage 24 hours per day.

C.2.TS.2. The USG seeks laboratories that can provide analytical support to monitor the progression of the disease in animal models and demonstrate prospective correlates of protection; (i.e., clinical laboratory capabilities and adoption of novel biomarker testing).

C.2.TS.3. The USG seeks laboratories that have adequate statistical and pharmacokinetics support to analyze and predict experimental hypotheses for models, including pharmacokinetic modeling (both individual animal and population approaches using compartmental and non-compartmental methods).

C.2.TS.4. In all cases described above, the USG seeks laboratories with the capability to perform these procedures and studies in animal models of human at-risk and special populations (e.g., pediatric, geriatric, pregnancy, etc.).

C.2.TS.5. The USG seeks laboratories capable of submitting study data to BARDA in SEND format.

C.3.TS Scientific and Technical Personnel for Toxicology Services (TS)

C.3.TS.1. The offeror(s) shall provide personnel who possess the necessary education, training, and experience to conduct nonclinical safety studies involving common species used in toxicology and safety pharmacology studies. This includes rodents, rabbits, swine, dogs, nonhuman primates and other commonly used species. This training and education should include experience in conducting toxicology, safety pharmacology, and pharmacokinetic studies with pharmaceutical agents and/or devices. The Offeror’s key personnel should also be able to identify and interpret non-clinical safety findings as they relate to clinical drug safety, including special populations such as pediatrics and pregnant women.

C.3.TS.2. A suitable plan for training, certification and recertification of scientific and technical personnel should be provided. Specifically, BARDA is interested in staff trained to lead and conduct multisite studies in accordance with GLPs, OECD, current international drug development regulatory guidance and guidelines, as well as standard pharmaceutical industry practices. Personnel should also be trained and certified to support all aspects of a toxicology study, including formulation preparation and analysis, drug supply, bioanalytical analysis, and toxicokinetic evaluation.

C.4.TS Quality Systems for Toxicology Services (TS)

C.4.TS.1. The USG seeks laboratories that can develop a quality control (QC)/quality assurance (QA) monitoring plan that shall ensure appropriate security, handling, and storage conditions of test articles, biological specimens, study records and final reports in accordance with GLP regulations.

C.4.TS.2. The USG seeks laboratories that can submit evidence of an effective Regulatory and Quality Management System (QMS) (21 CFR Part 58). Offeror(s) shall ensure that the details in the submitted proposal incorporate: 1) QMS in all aspects of the proposal to fulfill the proposal objectives; 2) a copy of a Quality Plan; 3) a quality reporting structure; 4) an FDA inspection history that provides all observations listed on the FDA Form-483 and associated corrective actions; 5) a regulatory platform that can comply with the evolving regulatory environment regarding requirements for animal research and the FDA regulatory guideline for animal studies in support of approval/ or licensure, such as, 21 CFR Part 58, “Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies,” OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring, No. 13, and all applicable FDA Pharm/Tox and ICH Safety guidance.

C.5.TS Program & Risk Management for Toxicology Services (TS)

C.5.TS.1. The USG seeks laboratories that can provide and implement plans for the overall management, integration and coordination of all contract activities, timelines, and fixed-price budgets including the coordination of activities carried out by subcontractors as part of an OECD- compliant multidose study. The offeror(s) shall develop a risk mitigation plan highlighting potential problems and/or issues that may arise during each task order, their impact on cost, performance and timelines, and appropriate remediation plans

C.5.TS.2. The offeror(s) shall maintain a historical control database of clinical pathology, anatomical pathology and reproductive toxicity in all toxicology species used for the conduct of nonclinical GLP toxicology and safety pharmacology studies.

Section D – Packaging, Marking and Shipping

D.1. METHOD OF DELIVERY

Unless otherwise specified by the Contracting Officer, all deliverable items to be furnished to the government under this contract (including invoices) shall be made by first class mail, overnight carrier, or email as described in SECTION F.3.1.

Section E – Inspection and Acceptance

E.1. INSPECTION AND ACCEPTANCE

Inspection and acceptance of the product, services, and documentation called for herein shall be accomplished by the Contracting Officer or a duly authorized representative. Technical inspection and acceptance will be take place at:

Biomedical Advanced Research and Development Authority Office of the Assistant Secretary for Preparedness and Response 330 Independence Avenue, S.W.

Room G640 Washington, D.C. 20201

E.2. FEDERAL ACQUISITION REGULATION CLAUSES INCORPORATED BY

REFERENCE

This contract incorporates the following clause by reference, with the same force and effect as if it were given in full text. Upon request, the Contracting Officer will make its full text available.

FAR 52.246-4, Inspection of Services - Fixed Price (August 1996)

FAR 52.246-5, Inspection of Services - Cost-Reimbursement (April 1984)

FAR 52.246-9, Inspection of Research and Development (Short Form) (April 1984)

FAR 52.246-16, Responsibility for Supplies (April 1984)

Section F – deliveries or Performance

F.1. PERIOD OF PERFORMANCE

The base period of performance under this contract will be for sixty (60) months from date of award. There are no options.

F.2. DELIVERIES

Successful performance of the final contract shall be deemed to occur upon performance of the work described in SECTION C of this contract and upon delivery and acceptance of the items described in SECTION F.3 by the Contracting Officer or their duly authorized representative.

Deliverables will be further defined upon the issuance of specific task orders.

F.3. CONTRACT DELIVERABLES AND REPORTING REQUIREMENTS

F.3.1. Submission of Contract Deliverables

Documents will be delivered electronically (via email to the Contracting Officer) and in original hard copy to the Contracting Officer and the Contracting Officer’s Representative. Unless otherwise specified by the Contracting Officer all hard copy deliverables and reports furnished to the Government under the resultant contract (including invoices) shall be addressed as follows:

Contracting Officer

HHS/ASPR/AMCG

200 C St. SW Washington, DC 20024 Email: Elizabeth.Steiner@hhs.gov Contracting Officer

HHS/ASPR/AMCG

330 Independence Ave. SW, Room G640

Contracting Officer Representative

HHS/ASPR/BARDA

200 C St. SW Washington, DC 20024 Email: Elizabeth.Steiner@hhs.gov Contracting Officer Representative

HHS/ASPR/BARDA

330 Independence Ave. SW, Room G640

In addition to those reports required by other terms of this contract, the Contractor(s) shall submit to the CO and the COR technical progress reports as identified in the TO. These reports shall be subject to the technical inspection and requests for clarification by the COR. These reports shall be brief and factual and prepared in accordance with the formats described in the following section.

F.3.2 Description and Format of Reports

1. Monthly Technical Progress Reports

During periods in which work is being performed under a TO, Monthly Technical Progress Reports are due on the fifteenth (15th) calendar day of each month for the previous calendar month. The Contractor shall submit a report to the COR and the CO. The Contractor shall submit a separate Monthly Technical Progress Report for each TO under which work is being performed. Monthly Technical Progress Reports are not required for periods with no active task orders.

The format and type of Monthly Technical Progress Report and Executive Summary will be provided by the COR within fifteen (15) calendar days of contract award. Monthly Technical Progress Reports will include project timelines, milestones and summaries. A Monthly Technical Progress Report will not be required for the period when a Quarterly Technical Report or Final Technical Report is due. The Contractor shall submit one copy of the Monthly Technical Progress Report electronically via e-mail to the COR and the CO.

The report shall be submitted in Microsoft Word, Microsoft Excel, Microsoft PowerPoint, Microsoft Project or compatible, editable formats. Technical Progress reports shall, at a minimum, include the following information:

Title Page: The Technical Progress Report title page shall include the contract number and title, the period of performance or milestone being reported, the contractor's name, address, and other contact information, the author(s), and the date of submission.

Distribution List: A list of persons receiving the Technical Progress report.

Introduction/ Background: An introduction covering the purpose and scope of the report.

Summary: A table organized by task order summarizing ongoing activities

Progress: The report shall detail, document and summarize, organized by task order, the results of work performed, test results and milestones achieved during the period covered. Progress should be represented as % of total project plan completed, as well as % completed for the month based on forecasted for the month. Information supporting the summary shall also be provided.

A summary of work planned for the next reporting period shall be included.

Issues: Issues resolved, new issues and outstanding issues shall be enumerated with options and recommendations for resolution. An explanation of any difference between planned progress and actual progress, why the differences have occurred, and, if project activity is delinquent, then what corrective steps are planned. Revised timelines shall be provided.

Invoices: Summary of any invoices submitted during the reporting period.

Action Items: Summary table of activities or tasks to be accomplished by a certain date and by whom.

Attachments: Each report will include an attachment with an up to date contract history including invoice submission/acceptance dates, and modifications. Results on the project are provided as attachments where appropriate.

1. Quarterly Technical Progress Reports

The format and type of the Quarterly Technical Progress Report and Executive Summary will be provided by the COR within fifteen (15) calendar days of contract award. Quarterly Technical Progress Reports will include project summaries as well as performance metrics for the prime contractor. A Quarterly Technical Progress Report will not be required for the period when the Final Technical Report is due. The Contractor shall submit one copy of the Quarterly Technical Progress Report electronically via e-mail to the COR and CO. The report shall be submitted in Microsoft Word, Microsoft Excel, Microsoft PowerPoint, Microsoft Project or compatible, editable formats.

Quarterly Technical Progress Reports are not required for periods with no active task orders. Quarterly Technical Progress reports shall, at a minimum, include the following information:

Title Page: The Quarterly Technical Progress Report title page shall include the contract number and title, the period of performance being reported, the contractor's name, address, and other contact information, the author(s), and the date of submission.

Distribution List: A list of persons receiving the Technical Progress report.

Introduction/ Background: An introduction covering the purpose and scope of the report.

Summary: A table organized by task order summarizing ongoing activities.

Progress: The report shall summarize, organized by Task Order, the results of work performed. Progress should be represented as % of total project plan completed, as well as % completed for the quarter based on forecasted for the quarter. Information supporting the summary shall also be provided. A summary of work and travel planned for the next reporting period shall also be provided.

Issues: Issues resolved, new issues and outstanding issues shall be enumerated with options and recommendations for resolution. An explanation of any difference between planned progress and actual progress, why the differences have occurred, and, if project activity is delinquent, then what corrective steps are planned. Revised timelines shall be provided.

Invoices: Summary of any invoices submitted during the reporting period.

Action Items: Summary table of activities or tasks to be accomplished by a certain date and by whom.

Attachments: Each report will include an attachment with an up to date contract history including invoice submission/acceptance dates, and modifications. Results on the project are provided as attachments where appropriate.

Executive Summary

The Executive Summary shall accompany each Technical Progress Report, be formatted as a Microsoft PowerPoint presentation, and include the following:

Title page: Executive Title, the contract number and title, the period of performance or milestone being reported, the contractor's name and the date of submission.

Project Progress: Presented as milestone events, test results, tasks and other activities achieved during the reporting period as talking point bullets.

Project Issues: Presented headings and each item as a talking point bullet.

Final Technical Report

For each TO, a Final Technical closeout report will be compiled. The Final Technical Closeout Report will include the following:

Title page: containing Executive Title, the contract number and title, TO Title and period of performance reported, the…