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1 1

SOLICITATION, OFFER AND AWARD 1. THIS CONTRACT IS A RATED ORDER RATING

UNDER DPAS (15 CFR 7900)

PAGE OF PAGES

1 115

2. CONTRACT NUMBER 3. SOLICITATION NUMBER

75A50122R00009

4. TYPE OF SOLICITATION

SEALED BID (IFB)

NEGOTIATED (RFP)

5. DATE ISSUED 6. REQUISITION/PURCHASE NUMBER

7. ISSUED BY CODE 75A501 8. ADDRESS OFFER TO (If other than item 7)

NOTE: In sealed bid solicitations "offer" and "offeror" mean "bid" and "bidder".

SOLICITATION

9. Sealed offers in original and copies for furnishings the supplies or services in the Schedule will be received at the place specified in item 8, or if hand carried, in the depository located in until local time

(Hour) (Date) 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

Jill Johnson

B. TELEPHONE (NO COLLECT CALLS) C. E-MAIL ADDRESS

Jill.Johnson@hhs.gov

AREA CODE

NUMBER

EXT.

11. TABLE OF CONTENTS

(X) SEC. DESCRIPTION PAGE(S) (X) SEC. DESCRIPTION PAGE(S)

PART I - THE SCHEDULE PART II - CONTRACT CLAUSES

X A SOLICITATION/CONTRACT FORM 1 X I CONTRACT CLAUSES 45

X B SUPPLIES OR SERVICES AND PRICES/COSTS 3 PART III - LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACH.

X C DESCRIPTION/SPECS./WORK STATEMENT 7 X J LIST OF ATTACHMENTS 51

X D PACKAGING AND MARKING 15 PART IV - REPRESENTATIONS AND INSTRUCTIONS

X E INSPECTION AND ACCEPTANCE 16

X K REPRESENTATIONS, CERTIFICATIONS AND OTHER

STATEMENTS OF OFFERORS 52

X F DELIVERIES OR PERFORMANCE 17

X G CONTRACT ADMINISTRATION DATA 26 X L INSTRS., CONDS., AND NOTICES TO OFFERORS 58

X H SPECIAL CONTRACT REQUIREMENTS 31 X M EVALUATION FACTORS FOR AWARD 69

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 120 calendar days (60 calendar days unless a different period is inserted by the offeror) from the date for receipt of offers specified above, to furnish any or all items upon which prices are offered at the set opposite each item, delivered at the designated point(s), within the time specified in the schedule.

13. DISCOUNT FOR PROMPT PAYMENT

(See Section I, Clause No. 52.232-8)

10 CALENDAR DAYS (%) 20 CALENDAR DAYS (%) 30 CALENDAR DAYS (%) CALENDAR DAYS(%)

14. ACKNOWLEDGMENT OF AMENDMENTS

(The offeror acknowledges receipt of amendments to the SOLICITATION for offerors and related documents numbered and dated):

AMENDMENT NO. DATE AMENDMENT NO. DATE

15A. NAME AND

ADDRESS

OF OFFER-

OR

CODE FACILITY 16. NAME AND THE TITLE OF PERSON AUTHORIZED TO SIGN OFFER

(Type or print)

15B. TELEPHONE NUMBER

15C. CHECK IF REMITTANCE ADDRESS IS

DIFFERENT FROM ABOVE - ENTER SUCH

ADDRESS IN SCHEDULE.

17. SIGNATURE 18. OFFER DATE

AREA CODE NUMBER EXT.

AWARD (To be completed by Government)

19. ACCEPTED AS TO ITEMS 20. AMOUNT 21. ACCOUNTING AND APPROPRIATION

22. AUTHORITY FOR USING OTHER THAN FULL OPEN COMPETITION:

10 U.S.C. 2304 (c) 41 U.S.C. 253 (c)

23. SUBMIT INVOICES TO ADDRESS SHOWN IN ITEM

(4 copies unless otherwise specified)

24. ADMINISTERED BY (If other than Item 7) 25. PAYMENT WILL BE MADE BY CODE

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.

AUTHORIZED FOR LOCAL REPRODUCTION

Previous edition is unusable

STANDARD FORM1 33 (REV,. 9-97)

Prescribed by GSA - Far (48 CFR) 53.214 (c)

HHS / ASPR / DAAPPO / BARDA DCMA

O'NEILL HOUSE OFFICE BLDG, WASHINGTON, DC 20515

mailto:Jill.Johnson@hhs.gov

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.

If your proposal is not received by the Contracting Officer (CO) or his/her designee at the time and place specified, it will be considered late and handled in accordance with the Federal Acquisition Regulation (FAR), FAR 52.215-1 (Instructions to Offerors – Competitive Acquisition), the Health and Human Services Acquisition Regulation (HHSAR), and HHSAR Clause 352.215-70, “Late Proposals and Revisions” located in Section I of this solicitation.

Potential Offerors must be registered in the System for Award Management (SAM) prior to award of a contract.

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 may 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.

The cutoff date for all questions on this RFP is February 24, 2022 at 12 PM ET. All questions shall be submitted via e-mail to Jill.Johnson@hhs.gov and Kevin.Restrepo@hhs.gov.

mailto:Jill.Johnson@hhs.gov mailto:Kevin.Restrepo@hhs.gov

PART I – THE SCHEDULE

SECTION B – SUPPLIES OR SERVICE AND PRICE / COST

B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES

Antibiotic resistance complicates the treatment of community- and hospital-acquired bacterial infections as well as the response to public health emergencies and natural disasters. Due to the genetic promiscuity of bacteria, the same genetic markers that give rise to antibiotic resistance in community- and hospital-acquired infections can be transferred to biothreat pathogens (e.g. B. anthracis, Y. pestis, F.

tularensis, or B. pseudomallei). Antibiotics available to the Assistant Secretary for Preparedness and Response (ASPR) during a public health emergency or natural disaster may not be sufficient to treat infections caused by antibiotic-resistant secondary bacterial infections and biothreats. In order to address this gap, the current stockpile of antibiotic medical countermeasures (MCMs) must be augmented to include novel and next generation antibiotics. Procurement of antibiotic MCMs that treat biothreat pathogens and overcome known forms of resistance will achieve the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) preparedness goals as indicated in the 2017-2018 PHEMCE Strategy and Implementation Plan. Strategies to mitigate the threat of antibiotic resistance include the development and stockpiling of novel and next generation antibiotics for the general population.

The United States Government (USG) seeks an antibiotic with marketing authorization for a biothreat indication (treatment and, if feasible, post-exposure prophylaxis (PEP)) for one or more of the following pathogen(s): Y. pestis, F. tularensis, or B. pseudomallei. B. anthracis will not be sought for this procurement, as a prior award for this pathogen was made in 2019. Products that expand the USGs existing preparedness posture will be the highest priority. The product must also either have received marketing authorization from the U.S. Food and Drug Administration (FDA) within the last 10 years or be in Phase 3 clinical development.

Under this Request for Proposal (RFP), BARDA intends to use Project BioShield (PBS) funds to support the late-stage development, approval, and potential procurement of an antibiotic. It is anticipated that up to two awards may be made from this RFP solicitation. The anticipated contract award(s) includes completion of the regulatory pathway for a public health pneumonic indication and biothreat indication(s) as well as any efforts related to post-marketing commitments/requirements (PMCR). Offerors must propose a biodefense development plan that has been discussed with FDA for the treatment and, if feasible, PEP of a biothreat indication(s). This development plan must include the conduct of a Phase 3 clinical trial for a pneumonic indication if the product is not already approved for such an indication and it is recommended by the FDA to support the biothreat indication(s). An alternative development/regulatory path may be proposed if a pneumonic indication is not required by the FDA. FDA concurrence with this alternative approach must be provided with the proposal. During the course of the biothreat development program the Offeror will provide necessary data to support an investigational or unapproved use of the USG procured product in the event of a localized outbreak or public health emergency under an appropriate FDA regulatory mechanism. The timing of such submission will depend on the available data.

If milestones are met during development, BARDA may procure the antibiotic using PBS funds for delivery to the ASPR Strategic National Stockpile (SNS) or maintain the antibiotic as vendor managed inventory (VMI).

Note: The Pre-EUA process is a critical step in the preparation for a potential emergency. It allows the FDA to “pre-review” EUA documents before the formal EUA request is made and to expeditiously issue an EUA upon issuance of an Emergency Declaration and requester’s submission of a formal EUA request. Be aware that the sponsorship of the Pre-EUA and EUA application will need to be discussed and determined upon circumstances. Per FDA’s EUA 2017 final guidance: “Based on experience, FDA expects that many requests for an EUA will be submitted by government sponsors (e.g., HHS or the Department of Defense [DoD]), although industry sponsors may also submit such a request.”

B.2. PRICES / COSTS

The final contract will contain the price/cost provisions agreed upon by the Government and the Offeror. It is anticipated that the total contract period of performance (base plus option periods) will be up to 10 years. The base period includes a cost-plus-fixed-fee (CPFF) contract line item number (CLIN) to support late-stage development for a biothreat indication. Supplementary CPFF options will be dedicated to additional late-stage development; post-marketing commitments as established by the FDA; BARDA security requirements; on-shoring commercial manufacturing activities, as feasible; and shelf-life extension program activities, as necessary. Firm-fixed-price (FPP) options will include CLINs to support the procurement of treatment and, if feasible, PEP courses of the antibiotic as final drug product (FDP) for delivery to the ASPR SNS, or as FDP that can be held in VMI until delivery to the ASPR SNS or another site as designated by the USG is required.

Option periods may be exercised within the base period of the contract, if needed. Below are the anticipated CLINs.

B.2.1. BASE PERIOD

Base Period Cost-Plus-Fixed-Fee CLIN

CLIN Supplies/Services Estimated Cost Fixed Fee Cost + Fixed

Fee (CPFF)

0001 (Base)

Late-stage development to support Pre- EUA through FDA marketing authorization for biothreat indication(s) (non-clinical, clinical, regulatory)

B.2.2. OPTION PERIODS

1. The Government may exercise an Option Period as set forth in ARTICLE I.3 of the contract.

2. Unless the government exercises its Option pursuant to the Option clause contained in

ARTICLE I.3, the contract consists only of the Base Work segment specified in the Statement of Work, for the price set forth in ARTICLE B.2.1 of the contract.

3. The Government may modify the contract unilaterally and require the contractor to provide supplies and services for Option Periods listed below, in accordance with ARTICLE I.3.

4. If the Government decides to exercise an Option(s), the Government will provide the

Contractor a preliminary written notice of its intent as referenced in the applicable clause.

Specific information regarding the time-frame for this notice is set forth in Article I.3 of this contract. The estimated cost of the contract will be increased as set forth below:

Optional Cost-Plus-Fixed-Fee CLINs

CLIN Supplies/Services Estimated Cost Fixed Fee Cost + Fixed

Fee (CPFF)

0002 (Option)

Ongoing late-stage development to support Pre-EUA through FDA marketing authorization for biothreat indication(s) (non-clinical, clinical, regulatory)

0003 (Option)

Supplemental late-stage development as requested by FDA to support Pre-EUA through FDA marketing authorization for biothreat indication(s) (non-clinical, clinical, regulatory)

0004 (Option)

BARDA security requirements, on-shoring commercial manufacturing activities, and shelf-life extension program activities

0005 (Option)

Post-marketing study commitments/ requirements for the authorized commercial indication including relabeling of approved drug in the ASPR SNS or VMI (this is an option that may or may not be exercised as required by the

FDA)

0006 (Option)

Post-marketing study commitments/ requirements for the authorized biothreat indication including relabeling of approved drug in the ASPR SNS or VMI (this is an option that may or may not be exercised as required by the FDA)

Optional Firm-Fixed-Price CLINs

CLIN Supplies/Services Treatment/PEP Courses (# of Courses)

Unit Price

Total

0007 (Option) Initial purchase, storage, and delivery of antibiotic as FDP to VMI and/or ASPR SNS sites

1-5,000*

0008 (Option) Additional procurement of antibiotic as FDP to VMI and/or ASPR SNS sites 1-5,000*

0009 (Option) Distribution of product from VMI to sites as directed by the USG†

* Per Section L.5.1., Offerors must propose from 1 – 5,000 treatment/PEP courses with a realistic capacity to deliver product in addition to the corresponding price per treatment and PEP course. However, the USG has discretion to determine the amount of product to be procured based on availability of funds and priorities/requirements.

† When budgeting these costs assume the longest route for delivery within the continental United States.

B.2.3. ADVANCE UNDERSTANDINGS

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

Specific elements of cost, which normally require prior written approval of the Contracting Officer (CO) before incurrence of the cost, will be included in this Section if the Contracting Officer has granted his/her approval prior to contract award.

B.2.4. PROVISIONS TO APPLICABLE COSTS

This section prohibits or restricts the use of contract funds, which includes the following items (costs unallowable unless otherwise approved 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) General scientific meetings/conferences;

g) Travel costs that include foreign travel;

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 $250,000.00;

j) Refreshments and Meal Expenditures;

k) Promotional Items

l) Printing

SECTION C – DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

1.1. STATEMENT OF OBJECTIVES

C.1.1. BACKGROUND AND PURPOSE

The prevalence of infections caused by antibiotic-resistant pathogens and the potential transfer, either natural or intentional, of these antibiotic-resistance genes to biothreat pathogens, are threats to the health security of the United States. Community- and hospital-acquired antibiotic-resistant infections can complicate the Department of Health and Human Services’ (HHS) response to public health emergencies, natural disasters, and chemical, biological, radiological, and nuclear (CBRN) threats. The illness and injuries caused by CBRN threats can lead to secondary bacterial infections, many of which can be antibiotic-resistant. Antibiotic-resistance also has the potential to render the current stockpile of antibiotic MCMs for biothreat pathogens ineffective. Development and procurement of antibiotics that overcome known forms of resistance and treat biothreat pathogens will enhance the USG’s emergency preparedness. During the ongoing SARS-CoV-2 pandemic, several publications from China and Europe, observed patients with bacterial infections, many were antibiotic-resistant [1, 2, 3]. Standard-of-care for these patients included broad-spectrum antibiotics, either for treatment of a diagnosed infection, or empirically due to the possibility of such an infection. These events highlight the precarious situation patients and first responders face during a public health emergency.

A key objective of the 2018 National Biodefense Strategy is to reduce the emergence and spread of antibiotic-resistant pathogens domestically and internationally by accelerating research and development of new antibiotics. BARDA and the PHEMCE recognize the critical need to prepare for an outbreak of antibiotic-resistant secondary bacterial infections as well as infections due to natural or engineered antibiotic-resistant biothreats. Supporting the development and stockpiling of MCMs that have the potential to treat antibiotic-resistant bacteria including biothreats will augment the USG response to any biothreat agent or public health emergency.

This acquisition will allow BARDA to invest in the late-stage development, regulatory biothreat approval, procurement, and stockpile of an antibiotic product that has been developed and received FDA marketing authorization for commercial use but also has utility in preparedness against biothreat pathogens. The acquired product will directly address PHEMCE requirements established in the Product-Specific Requirement (PSR) for Medical Countermeasures to combat antibiotic-resistant bacterial infections, the 2014 National Strategy and Action Plan to Combat Antibiotic Resistant Bacteria, and the 2018 National Biodefense Strategy.

[1] Zhou F, et. al. 2020. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in

Wuhan, China: a retrospective cohort study. The Lancet Respiratory Medicine [2] Yang, X. et. al. 2020. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respiratory Medicine

[3] Clancy, N. COVID-19: Role of superinfections in novel coronavirus deaths highlights urgent need for sustainable development of new antibiotics. IDSA daily newsletter, April 7, 2020.

C.1.2. SCOPE

Independently and not as an agent of the USG, the Offeror shall furnish all the necessary services, qualified personnel, materials, supplies, equipment, and facilities not otherwise provided by the USG as needed to perform the work described below.

The USG is seeking to procure and maintain an antibiotic for the treatment and, if feasible, PEP of a biothreat indication (infection by a biothreat pathogen). However, the USG has discretion to determine the amount of product to be procured based on availability of funds and priorities/requirements.

Developing and stockpiling medical countermeasures that treat antibiotic-resistant bacteria, including biothreats, will augment the USG’s preparedness posture. The USG may procure an initial shipment of product when a Pre-EUA package for the product has been filed for the biothreat indication(s) and reviewed by the FDA, and all identified concerns have been adequately addressed. A second shipment of product may be procured once the antibiotic receives marketing authorization for a biothreat indication.

Security, regulatory, and quality requirements (as determined by BARDA) must also be met. The antibiotic shall be delivered to the ASPR SNS, and/or maintained as VMI as determined by BARDA and the Contracting Officer. The treatment and PEP courses shall be provided as FDP.

The scope of the Base Period will include late-stage development activities necessary to support a pneumonic indication, investigational or unapproved use in the event of a localized outbreak or public health emergency under an appropriate FDA regulatory mechanism, and FDA marketing authorization (nonclinical, clinical, and regulatory) for a biothreat indication. Option Period(s) will include additional late-stage development activities; BARDA security requirements, on-shoring commercial manufacturing activities, and shelf-life extension program activities; post-marketing commitments/requirements; and purchases of antibiotic treatment and PEP courses.

The statement of objectives outlined in the following sections shall be addressed by the Offeror(s) in their proposed statement of work:

Section 1: Program Management and Risk Mitigation Objectives Section 2: Late-stage Product Development Objectives Section 3: Post-Marketing Commitments/Requirements Section 4: Procurement and Delivery of Product Objectives

1. PROGRAM MANAGEMENT AND RISK MITIGATION OBJECTIVES

The Offeror is directed towards details provided in Section F for items below.

1.1. The Offeror shall submit program/risk management documents as described in SECTION F – Deliveries or Performance.

1.2. The Offeror shall develop and maintain a risk mitigation plan that is acceptable to the CO and

Contracting Officer’s Representative (COR). This shall include a risk matrix per Attachment

12. The Offeror shall provide a security plan that is associated with all aspects of manufacture of product, process, storage, and inventory of the FDP. The Security Plan shall include all sites within the supply chain, including proposed shipping carriers. For those sites/carriers that are not defined at the time of award or are added during the period of performance, individualized Security Plans shall be provided to the USG prior to inclusion of sites/carriers into the supply chain. BARDA’s Program Protection Office will be authorized to review and approve Security Plans and will conduct annual audits/site visits to ensure a reliable product is delivered to the USG. Security requirements and a template for a Security Plan are included in Attachments 15 and 16, respectively.

1.3. The Offeror submitting a proposal will be required to provide a copy of their facility security plan with their proposal in response to this solicitation. The Offeror is responsible for ensuring all proposed subcontractors provide a facility security plan to be included in the submission.

2. LATE-STAGE PRODUCT DEVELOPMENT OBJECTIVES (BASE CLIN 0001 and OPTION CLINs 0002 – 0004)

2.1. GENERAL PRODUCT DEVELOPMENT OBJECTIVES

2.1.1. Products that enable the USG to achieve an expanded preparedness posture will be the highest priority.

2.1.2. The product/candidate must be either FDA-approved within the last 10 years or in

Phase 3 clinical development (generic antibiotics will not be considered under this solicitation).

a) Offerors must propose a biodefense development plan including nonclinical, clinical, and chemistry, manufacturing, and control (CMC) activities that have been discussed with FDA that will support an investigational or unapproved use in the event of a localized outbreak or public health emergency and achieve marketing authorization for the treatment of a biothreat indication(s) with the possibility PEP, if feasible.

b) This development plan must include the conduct of a Phase 3 clinical trial for a pneumonic indication if the product is not already approved for such an indication, unless the FDA has provided guidance that such a study will not be required to support the biothreat indication. An alternative development/regulatory path must be proposed if a pneumonic indication is not required by the FDA, and FDA concurrence with this alternative approach must be provided in the proposal.

2.1.3. Under the proposed effort, the Offeror must conduct the necessary studies that will provide phase appropriate data to prepare and sponsor a supplemental New Drug Application (sNDA) package for the treatment of a pneumonic indication (if required), and a sNDA for treatment and PEP of infections due to one or more of the following biothreat pathogens: Y. pestis, F. tularensis, or B. pseudomallei. If targeting more than one biothreat pathogen, the Offeror must propose a development plan that will achieve a sNDA for each pathogen.

2.1.4. The product must have demonstrated efficacy against one or more drug-resistant pathogen(s) identified as Urgent or Serious Threats in the CDC’s 2019 report:

Antibiotic Resistance Threats in the United States.

2.1.5. For pneumonic indications, the product must have demonstrated relevant microbiological profile, target attainment and therapeutic efficacy through pharmacokinetic (PK)/pharmacodynamic (PD) studies, as well as lung infection data model simulating human exposure.

2.1.6. The product minimally must have demonstrated in vitro efficacy against one or more of the following biothreat pathogens: Y. pestis, F. tularensis, or B. pseudomallei.

Preference will be given to products that have in vivo animal model efficacy data at the time of proposal submission. All data supporting activity and efficacy against the biothreat pathogen(s) must be presented in the proposal.

2.1.7. Preference will be given to products formulated for both oral and intravenous administration; products with a single route of administration (either oral only or intravenous only) will be evaluated based on the appropriateness of the route of administration for treatment and PEP of the proposed biothreat indication.

2.1.8. In consideration of inclusion in the SNS, preference will be given to products that are not prone to oxidation, are not prone to thermal and photolytic degradation, and do not require cold-chain storage.

2.1.9. Preference will be given to products that do not have a Black Box Warning; if the product has a Black Box Warning, a risk-benefit assessment must justify its use during a public health emergency.

2.2. REGULATORY OBJECTIVES

2.2.1. During the course of the biothreat development program the Offeror will provide necessary data to support an investigational or unapproved use of the USG procured product in the event of a localized outbreak or public health emergency under appropriate FDA regulatory mechanism. The Offeror and the USG shall submit a pre- EUA package to the FDA. The timing of submitting this data package to regulators will depend on the available data and whether it will support a Pre-EUA with no further comments from FDA (thus supporting an EUA request should an emergency be declared).

Note: The Offeror is strongly encouraged to review the FDA’s guidance to industry on EUAs and hold a Type B meeting with the FDA prior to proposal submission to discuss the proposed biothreat development and regulatory path.

2.2.2. As a potential EUA requestor, the Offeror and the USG shall seek FDA concurrence that the Investigational New Drug (IND)/NDA labeling is acceptable for an EUA, and could be used under EUA without the need to re-label the product. If FDA does not find the existing IND/NDA labeling adequate for safe and effective use of the product under the EUA, the Offeror shall re-label the product in accordance with regulatory requirements from the FDA.

2.2.3. The Offeror shall maintain and update, as required by the FDA, all required regulatory documentation (investigator brochure, regulatory binder, etc.), that will be used to support an investigational or unapproved use in the event of a localized outbreak or public health and marketing authorization packages for review by the FDA.

2.2.4. The Offeror shall obtain FDA concurrence on the appropriate path for regulatory evaluation and marketing authorization (i.e., traditional, accelerated, or Animal Rule).

2.2.5. The Offeror shall conduct all necessary meetings with the FDA to support submission of a NDA or evaluation through amendment to an existing marketed product to the

FDA.

2.2.6. The Offeror shall re-label investigational product (upon marketing authorization) to be consistent with the licensed product, in accordance with regulatory requirements from the FDA.

2.3. NONCLINICAL OBJECTIVES

2.3.1. The Offeror(s) shall perform the appropriate late-stage nonclinical safety studies needed to establish product safety as a therapeutic against infection by a biothreat agent.

2.3.2. The Offeror shall conduct any FDA required efficacy studies to support FDA marketing authorization of a biothreat indication and a commercial indication, if required.

2.3.3. The Offeror shall conduct any FDA required PK studies to support FDA marketing authorization of a biothreat indication and a commercial indication, if required.

2.3.4. The Offeror shall conduct any PK/PD modeling to establish an appropriate clinical dose and regimen for the biothreat indication.

2.4. CLINICAL OBJECTIVES

2.4.1. The Offeror shall complete any remaining Phase 3 pneumonic clinical studies to support clinical safety under the Animal Rule and biothreat indication as directed by BARDA and the FDA. The Animal Rule neither replaces the need, nor establishes special requirements, for an adequate human safety database for drug development.

The expectation is that drugs will be evaluated for safety under preexisting requirements for establishing the safety of new drug and biological products. FDA anticipates that the nonclinical and clinical safety development programs will proceed in a manner similar to that of drugs developed under traditional regulatory pathways.

2.5. CHEMISTRY, MANUFACTURING, CONTROL OBJECTIVES

2.5.1. Registration/Primary batches must be complete or ongoing with plans for full process validation established or validation complete.

2.5.2. The manufacturing process for active pharmaceutical ingredient (API) and FDP must be developed and established.

2.5.3. U.S.-based manufacturing of the FDP, API, and/or starting materials may be required under the August 6, 2020 Executive Order on “Ensuring Essential Medicines, Medical Countermeasures, and Critical Inputs Are Made in the United States,” unless an exception stated in that Executive Order applies. Priority will be given to Offerors that manufacture their FDP, API, and/or starting materials within the U.S. If manufacturing is not currently conducted in the U.S., on-shoring plans for U.S. manufacturing of the FDP, API, and/or starting materials shall be provided where feasible. If on-shoring is not feasible, the Offeror must explain why.

2.5.4. The Offeror shall deliver product with established acceptable product quality attributes meeting the proposed product safety and efficacy during product shelf life.

2.5.5. The Offeror shall provide a Manufacturing Plan that includes a facility regulatory compliance plan addressing current good manufacturing practice (cGMP) standards, description of the manufacturing facility quality assurance (QA) and regulatory acceptance including quality systems, validation master plan, and regulatory milestones.

2.5.6. The Offeror shall complete any remaining manufacturing and quality control (QC) activities needed to support FDA marketing authorization, and the Offeror shall establish a regulatory strategy and filing processes for successful marketing authorization of the product.

2.5.7. The Offeror shall show extended stability of the product, to include plans for a five-year stability program as agreed upon by FDA for the API and FDP, process validation, registration batches, and annual commercial manufacturing programs.

2.5.8. The Offeror shall demonstrate capability and compliance for all required CMC activities. These include but are not limited to those listed below:

a) Final product manufacturing, process and equipment validation, analytical methods and assays appropriate for product characterization and product release, including tests for the identity, purity, potency, and for demonstrating stability of the intermediate and FDP to support FDA marketing authorization.

b) Identify a stable source and availability of reagents and reference standards for these assays required; execute product stability testing plans as evidenced by available data towards the intended product stability.

c) Develop and maintain documentations such as those describing QC and QA monitoring plan and manufacturing process, facility information, product storage and monitoring inventory systems, and process flow for material and waste disposal.

d) Packaging of FDP to provide for the most cost-effective product life-cycle value and performance and to allow for ease of distribution and use during a declared emergency.

e) Assures selected vendors are GMP compliant.

3. POST-MARKETING COMMITMENTS/REQUIREMENTS (OPTION CLINs 0005 – 0006)

3.1. The Offeror shall satisfy any PMCR required for maintaining the license, including any studies to monitor safety and efficacy during a biothreat emergency.

3.2. The Offeror shall commit to comply with PMCR for the commercial indication as specified by the FDA. Cost estimates for these studies may be based on tentative plans in place prior to direction from the FDA. Based on guidance from the FDA, select items from section 2 of the Statement of Objectives may be moved to the PMCR section.

3.3. The Offeror shall commit to comply with PMCR for the biothreat indication as specified by the FDA. Cost estimates for these studies may be based on tentative plans in place prior to direction from the FDA. Based on guidance from the FDA, select items from section 2 of the Statement of Objectives may be moved to the PMCR section.

4. PROCUREMENT AND DELIVERY OF PRODUCT OBJECTIVES (OPTION CLINs 0007 – 0009)

4.1. To support an interim preparedness posture, the USG may procure an initial shipment of up to 5,000 patient courses of antibiotic under CLIN 0007. This procurement may be triggered prior to marketing authorization when the following development and regulatory milestones have been achieved.

a) In vitro microbiology data (minimum inhibitory concentration data for a panel of 50 biodefense isolates/strains);

b) Data on the activity or efficacy in animals that contributes to understanding the potential treatment and PEP effect in humans (e.g., proof-of-concept in vivo studies in one or more animal species);

c) Completed nonclinical toxicology and safety pharmacology studies that support the conduct of human clinical trials and marketing authorization for pharmaceuticals consistent with ICH M3(R2) taking into consideration the expected drug exposures and treatment duration related to the proposed use as a biothreat MCM;

d) Completed PK study in at least one sufficiently well-characterized animal model to be used for predicting the efficacy/response in humans for the biothreat indication;

e) Completed study demonstrating the exposure/response relationship as well as the fully effective dose in a well-characterized animal model expected to react with a response predictive for humans;

f) Selection of a human dose that is expected to be effective in humans based on the relationship between drug exposure and effectiveness established in animals and available human PK data;

g) Human safety information from clinical trials and individual patient experience at the expected drug exposures related to the proposed use as a biothreat MCM. The expectation is that the drug will be evaluated for safety under preexisting requirements for establishing safety of new drugs and the size and composition of the human safety database should be consistent with the proposed use of the drug;

h) Security, regulatory, and quality requirements (as determined by BARDA) must be met;

i) A Pre-EUA package for the product that includes the data from the development milestones has been filed for the biothreat indication(s) and reviewed by the FDA and all identified concerns have been adequately addressed (as determined by BARDA).

4.2. Under CLIN 0008, the Offeror(s) shall provide additional courses of antibiotic (up to 5,000 patient courses) upon FDA approval of the sNDA for the biothreat indication(s).

4.3. The Offeror shall store FDP, in compliance with cGMP, until release testing has been completed. The FDP will be shipped to and stored at the ASPR SNS or maintained as VMI in a manner consistent with applicable FDA guidance and requirements. The source of transportation used by the Offeror for the delivery of product must meet USG security requirements. Offerors must propose a price per treatment/PEP course for both VMI and

ASPR SNS.

4.4. The Offeror shall maintain cGMP compliance and QC of stored FDP and stability assays to ensure expiry dating for the duration of the contract. As related to VMI, the contractor shall provide a general rotation plan and a rotation plan for the storage and delivery of the product, as applicable. In the plan, logistics for handling expired products should be provided. The plan shall also establish the timeframe for when BARDA is notified of expired product, to include batch numbers, and additional details as relevant, such as location of the batch, shipping destination, replacement of expired product in the inventory, etc. Proposed price rates should include the logistics noted.

4.5. The estimate for the total antibiotic procurement under CLIN 0007 and CLIN 0008 is 10,000 patient courses composed of a combination of treatment and PEP, if feasible. However, the USG has the sole discretion to determine the amount of product to be procured based on availability of funds and priorities/requirements. These efforts include manufacturing, stability testing, and storage. Offerors must propose a price per treatment and PEP course for both VMI and ASPR SNS.

4.6. The Offeror must propose a plan and cost for distribution of product from VMI under CLIN

0009.

C.1.3. REPORTING REQUIREMENTS

See Section F for specific reporting requirements.

Performance of the contract will be monitored by the CO/COR on a regular basis. The CO will be responsible for inspection and acceptance of deliverables and services. Monitoring of the contract will be based on periodic reporting by the Offeror.

C.1.4. MEETINGS/SITE VISITS

The Offeror and BARDA shall participate in regular meetings to coordinate and oversee the contracting effort as requested by the CO/COR. Such meetings may include, but are not limited to, a kickoff meeting to be held at a location determined by the COR, status update meetings or teleconferences, site visits to the Offeror’s and Offeror’s subcontractor facilities, and meetings with individual Offerors and other HHS officials to discuss the technical, regulatory, and ethical aspects of the program. The Offeror shall provide data, reports, and presentations to groups of outside experts and USG personnel and USG-contracted subject matter experts as required by the CO/COR facilitating review of activities. The purpose of the kickoff meeting will be to orient the Offeror to HHS/BARDA and review contract requirements. This meeting usually occurs within a month after contract award. Expect biweekly or monthly status update meetings/teleconferences. The schedule for these meetings will be established by the CO and COR.

Periodic site visits shall occur on an ad hoc basis (at least twice a year).

Within 30 calendar days of an FDA audit of Offeror or Offeror’s subcontractor facilities, the Offeror shall provide copies of the audit findings, final report, and a plan for addressing areas of nonconformance to FDA regulations and guidance for good laboratory practice (GLP), good manufacturing practice (GMP), or good clinical practice (GCP) guidelines as identified in the final audit report.

Other U.S. Government Audits The USG reserves the right to conduct an audit of the Offeror with 48 hours advance notice. The USG reserves the right to accompany the Offeror on routine and for-cause site-visits/audits of Offeror subcontractor(s). At the discretion of the USG and independent of testing conducted by the Offeror, BARDA reserves the right to conduct site visits/audits and collect samples of product held by the Offeror and Offeror’s subcontractor(s).

Pre-award site visits may be made with short notice. Offerors are expected to guarantee the availability of key staff or other staff determined by the Government as essential for purposes of this site visit.

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.

All deliverables required under this contract shall be packaged, marked, and shipped in accordance with Government specifications. At a minimum, all deliverables shall be marked with the contract number and Offeror’s name. The Offeror shall guarantee that all required materials shall be delivered in immediate usable and acceptable condition.

D.2. FOB DESTINATION DELIVERIES

The Offeror shall describe the storage conditions for each product, specifically noting the acceptable temperature range required to maintain product quality. The Offeror shall be responsible for maintaining product temperature control until the product(s) arrives at the ASPR/SNS and has completed product acceptance by the USG. The Offeror shall provide the Government with an ambient exposure letter that covers the time the product(s) leaves the Offeror’s validated storage facility until arrival at the ASPR SNS.

Upon Government acceptance of the product(s) to the Government, the responsibility for temperature control shall transfer to the Government as well as the responsibility for logging ambient exposure time (temperatures between 8-25°C). The Offeror will provide and place TempTale(s) on each pallet of product while the product is inside the Offeror’s validated storage facility prior to placing the product(s) onto the truck(s) of the designated carrier. The Government’s acceptance of the aforementioned responsibility applies only to temperature control and does not indicate its acceptance of the lot(s).

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 200 C Street, S.W.

Washington, D.C. 20024

Acceptance may be presumed unless otherwise indicated in writing by the Contracting Officer or the duty authorized representative within 30 days of receipt.

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 52.246-7, Inspection of Research and Development – Fixed-Price (Aug 1996)

FAR 52.246-8, Inspection of Research and Development – Cost-reimbursement (May 2001)

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 period of performance of this contract (base plus option periods) is anticipated for up to 10 years from the date of award. CLINs within the period of performance are set forth in SECTION B.

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 RFP and upon delivery and acceptance of the items described in SECTION F.3 by the Contracting Officer or their duly authorized representative.

F.3. CONTRACT DELIVERABLES AND REPORTING REQUIREMENTS

F.3.1. Submission of Contract Deliverables

Documents shall be delivered electronically via email to the CO and the COR. Additionally, the Contractor shall upload documents to the appropriate Government designated file sharing system. The Government shall provide two contractor representatives authorized log in access to the file share program. Each representative must complete a mandatory training provided by the Government prior to gaining user access. A notification email shall be sent to the CO and COR upon electronic delivery of any documents.

When electronic deliverables are not preferable by the CO, all deliverables and reports furnished to the Government under any potential resultant contract (including invoices) shall be addressed as follows:

UPS/FedEx/Courier USPS Mail Packages Contracting Officer

HHS/ASPR/CMA

200 C St. SW Washington, DC 20024

Contracting Officer

HHS/ASPR/CMA

200 C St. SW Washington, DC 20024

UPS/FedEx/Courier USPS Mail Packages Contracting Officer Representative

HHS/ASPR/BARDA

200 C St. SW Washington, DC 20024

Contracting Officer Representative

HHS/ASPR/BARDA

200 C St. SW Washington, DC 20024

F.3.2. Reporting Requirements

In addition to those reports required by other terms of this RFP, the Offeror shall submit to the CO and the COR technical progress reports as identified in any potential resultant contract. These reports shall be subject to the technical inspection and requests for clarification by the COR, and approval by the CO/COR. These reports shall be brief, factual, and prepared in accordance with the following format:

A. Monthly Progress Report

This report shall include a description of the activities during the reporting period and the activities planned for the ensuing reporting period. The first reporting period consists of the first full month of performance plus any fractional part of the initial month. Thereafter, the reporting period shall consist of each calendar month.

The Offeror shall submit a Monthly Progress Report on or before the 15th calendar day following the last day of each reporting period and shall include the following:

Title Page: The title page for this report shall include the contract number and title; the type of report and period that it covers; the Offeror's name, address, telephone number, fax number, and e-mail address; and the date of submission.

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

Progress:

SECTION I – An introduction covering the purpose and scope of the contract effort.

SECTION II Part A: SUMMARY – A description or table summarizing ongoing activities.

SECTION II Part B: MANAGEMENT AND ADMINISTRATIVE UPDATE – This section shall include a description of all meetings, conference calls, etc. that have taken place during the reporting period. Include progress on administration and management issues (e.g. evaluating and managing subcontractor performance and personnel changes).

Include all Quality Management System, Quality Control, and Quality Assurance Plans as part of this report or as requested by the COR.

SECTION II Part C: TECHNICAL PROGRESS – This section shall document the results…