RFP_IV_SPX_Antiviral_FINAL.pdf

PAGES

15A. NAME

AND

ADDRESS

OF

OFFEROR

SEC. PAGE(S) SEC. PAGE(S)

(Date) (Hour)

CALENDAR DAYS

14. ACKNOWLEDGMENT OF AMENDMENTS

(The Offeror acknowledges receipt of amend-ments to the SOLICITATION for Offerors and related documents numbered and dated:

(Type or Print)

PAGES

(Date) (Hour)

SEC. PAGE(S) SEC. PAGE(S)

CALENDAR DAYS

14. ACKNOWLEDGMENT OF AMENDMENTS

(The Offeror acknowledges receipt of amend-ments to the SOLICITATION for Offerors and related documents numbered and dated:

15A. NAME

AND

ADDRESS

OF

OFFEROR

(Type or Print) mAUTHORIZED FOR LOCAL REPRODUCTION STANDARD FORM 33 (REV. 9-97) PREVIOUS EDITION IS UNUSABLE Prescribed by GSA

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

UNDER DPAS (15 CFR 700)

RATING

PAGE OF

1 113

2. CONTRACT NO.

N/A

3. SOLICITATION NO.

18-100-SOL-00011

4. TYPE OF SOLICITATION

SEALED BID (IFB)

X NEGOTIATED(RFP)

5. DATE ISSUED

03/07/2018

6. REQUISITION/PURCHASE

NO.

N/A

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

HHS/OS/ASPR/AMCG

O’Neill House Office Building 200 C Street SW Washington, DC 20024

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

SOLICITATION

9. Sealed offers in original and 0 copies for furnishing the supplies or services in the Schedule will be received at the place specified in Item 8, or if handcarried, in the depository located in See Section L for Instructions until12:00PM ET local time April 23, 2018

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

Christine Park

a. TELEPHONE (NO COLLECT CALLS)

202-805-0382

b. E-MAIL ADDRESS

Christine.Park@hhs.gov

11. TABLE OF CONTENTS

((x) DESCRIPTION (x) DESCRIPTION

PART I – THE SCHEDULE PART II – CONTRACT CLAUSES

X A SOLICITATION/CONTRACT FORM 01 X I CONTRACT CLAUSES 38

X B SUPPLIES OR SERVICES AND PRICES/COSTS 03 PART III - LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACH.

X C DESCRIPTION/SPECS./WORK STATEMENT 07 X J LIST OF ATTACHMENTS 42

X D PACKAGING AND MARKING 13 PART IV – REPRESENTATIONS AND INSTRUCTIONS

X E INSPECTION AND ACCEPTANCE 14 REPRESENTATIONS, CERTIFICATIONS, AND

X F DELIVERIES OR PERFORMANCE 15 X OTHER STATEMENTS OF CONTRACTORS 43

X G CONTRACT ADMINISTRATION DATA 23 X L INSTRS., CONDS., AND NOTICES TO

X H SPECIAL CONTRACT REQUIREMENTS 26 X M EVALUATION FACTORS FOR AWARD 65

OFFER (Must be fully completed by Contractor) 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 Contractor) from the date for receipt of offers specified above, to furnish any or all items upon which prices are offered at the price 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

AMENDMENT NO. DATE AMENDMENT NO. DATE

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

15B. TELEPHONE NO.

AREA CODE NUMBER EXT.

15C. CHECK IF REMITTANCE ADDRESS

IS DIFFERENT FROM ABOVE - ENTER

SUCH ADDRESS IN SCHEDULE.

17. SIGNATURE

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

10 U.S.C. 2304(c)( ) 41 U.S.C. 253(c)( ) 23. SUBMIT INVOICES TO ADDRESS SHOWN IN (4 copies unless otherwise specified)

ITEM

24. ADMINISTERED BY (If other than Item 7) CODE 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.

FAR (48 CFR) 53.214©

K mailto:Brooke.Bernold@hhs.gov

NOTE TO CONTRACTORS

The information in SECTION A - Solicitation/Contract Form, contains important information for any Contractor 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 Contractors – Competitive Acquisition), the Health and Human Services Acquisition Regulation (HHSAR), and HHSAR Clause 352.215-70, “Late Proposals and Revisions” located in section L of this solicitation.

Potential Contractors 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 Contractor's proposal may be included in the resultant contract.

The contract schedule is intended to provide the Contractor 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 March 21, 2018 until 12PM ET. All questions shall be submitted via e-mail to Brooke.Bernold@hhs.gov and Christine.Park@hhs.gov.

mailto:Brooke.Bernold@hhs.gov mailto:Christopher.Scott@hhs.gov

PART I – THE SCHEDULE

SECTION B – SUPPLIES OR SERVICE AND PRICE / COST

B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES

Medical countermeasures (MCM) against smallpox are urgently needed should a future outbreak of this disease occur; while smallpox was declared eradicated by the WHO in 1980, advances in genetic engineering, the possibility of clandestine stocks in addition to the WHO-sanctioned smallpox repositories in the Russian Federation and in the United States make the possibility of an outbreak or an intentional release of smallpox a present threat. The 2016 Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Strategy and Implementation Plan identifies smallpox virus as a high-priority threat as determined by the Secretary of Homeland Security. Strategies to mitigate the threat of smallpox include the development and stockpiling of vaccines for the general population as well as the development of therapeutic antivirals to treat symptomatic cases of smallpox. BARDA is seeking an antiviral therapeutic(s) that can be safely and effectively used for the U.S. civilian population in individuals with symptomatic orthopoxvirus (e.g. smallpox) infections.

The United States Government (USG) desires an antiviral product which can be available both in a parenteral and nonparenteral (e.g. IV and oral dosing formulations) to be stored in the Centers for Disease Control and Prevention (CDC) Strategic National Stockpile (SNS), or stored as vendor-managed inventory (VMI), that can meet the PHEMCE product requirements for therapeutic MCMs for smallpox.

This notice seeks candidate antivirals which are available both in a parenteral and nonparenteral formulation, which have efficacy data in at least two animal models accepted by the FDA for evaluation of smallpox countermeasures as a result of the Antiviral Drugs Advisory Committee meeting (Dec 14-15, 2011 – e.g. rabbitpox and monkeypox), and data demonstrating the candidate antiviral is safe and well tolerated in human subjects. Under this RFP, BARDA plans to support the procurement of smallpox antiviral(s), which will either be delivered to the SNS or maintained as VMI, using Project BioShield (PBS) funds. PBS fund will also support the necessary late-stage development to complete the regulatory pathway for approval of the product(s) being procured (if applicable) and/or efforts related to post-marketing commitments.

B.2. PRICES / COSTS

The final contract will contain the price/cost provisions agreed upon by the Government and the Contractor. It is anticipated that the final contract will consist of a base period or performance up to five

(5) years and a total contract period of performance (base plus option periods) up to 10 years with the exercise of options. The Base Period includes a Cost Plus Fixed Fee Contract Line Item Number (CLIN) to support late-stage development with the goal of approval for a parenteral or nonparenteral antiviral and a Fixed Price CLIN to support the purchase of antiviral treatment courses. One of the options will be dedicated to post-marketing commitments as established by the FDA for the nonparenteral formulation of the antiviral candidate. The next option will be dedicated to post-marketing commitments as established by the FDA for the parenteral formulation of the antiviral candidate. The other twenty-four (24) options will allow for the procurement of additional treatment courses of both formulations of the antiviral either as Final Drug Product (FDP) for delivery to the SNS, as Bulk Drug Substance (BDS), conversion of BDS into FDP, or as FDP which can be held in vendor managed inventory until delivery to the SNS is required. The options 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 Reimbursement CLIN CLIN Supplies/Services Estimated

Cost Fixed Fee Cost + Fixed

Fee (CPFF) 0001 (Base) Late stage development activities to support approval of an alternative formulation (parenteral or nonparenteral) through FDA approval

Base Period Fixed Price CLIN CLIN Supplies/Services Treatment

Courses (# of Product)

Unit Price

Total ($)

0002 (Base) Initial purchase and delivery of a parental or nonparenteral formulated antiviral as final drug product (FDP) to SNS.

1-50,0001

1 Per Section L.5.1., please propose up to 50,000 treatment courses with a realistic capacity to deliver product in addition to the corresponding price per treatment course.

B.2.2. OPTIONS

Optional Cost Reimbursement CLINs CLIN Supplies/Services Estimated

Cost Fixed Fee Cost + Fixed Fee

(CPFF)

0003 (Option) Phase IV post marketing commitments

(nonparenteral formulation) including relabeling of approved drug in the SNS (this is an option that may or may not be exercised as required by the FDA)

0004 (Option) Phase IV post marketing commitments (parenteral formulation) including relabeling of approved drug in the SNS or VMI (this is an option that may or may not be exercised as required by the FDA)

Optional Fixed Price CLINs CLIN Supplies/Services Treatment

Courses (# of Product)

Unit Price

Total

0005 (Option) Additional procurement of a nonparenteral formulated antiviral as FDP and delivery to the SNS.

1 – 262,5002

0006 (Option) Surge Capacity – Initial procurement of parenteral formulated antiviral as bulk drug substance (BDS)

1 – 50,0003

0007 (Option) Surge Capacity – Storage of parenteral formulated antiviral as bulk drug substance (BDS) in VMI for 5 years. (Monthly rate per TC: $_________)4 (from bulk drug substance procured under

CLIN0006).

1 – 50,0003

0008 (Option) Surge Capacity –Fill/finish of final drug product (from bulk drug substance procured under CLIN0006).

1 – 50,0003

0009 (Option) Surge Capacity – Storage of final drug product in VMI for 5 years (Monthly rate per TC: $_________)4 (from bulk drug substance procured under

CLIN0006).

1 – 50,0003

0010 (Option) Surge Capacity – Delivery of FDP to the SNS (from bulk drug substance procured under CLIN0006)

1 – 50,0003

0011 (Option) Additional procurement of a nonparenteral formulated antiviral as FDP and delivery to the SNS

1 - 262,5002

0012 (Option) Surge Capacity – Additional procurement of parenteral formulated antiviral as bulk drug substance (BDS)

1 – 50,0003

0013 (Option) Surge Capacity – Storage of parenteral formulated antiviral as bulk drug substance (BDS) in VMI for 5 years. (Monthly rate per TC: $_________)4 (from bulk drug substance procured under

CLIN0012).

1 – 50,0003

0014 (Option) Surge Capacity –Fill/finish of final drug product (from bulk drug substance procured under CLIN0012)

1 – 50,0003

0015 (Option) Surge Capacity – Storage of final drug product in VMI for 5 years. (Monthly rate per TC: $_________)4 (from bulk drug substance procured under

CLIN0012).

1 – 50,0003

0016 (Option) Surge Capacity – Delivery of FDP to the SNS (from bulk drug substance procured under CLIN0012)

1 – 50,0003

0017 (Option) Additional procurement of a nonparenteral formulated antiviral as FDP and delivery to the SNS

1 - 262,5002

0018 (Option) Surge Capacity – Additional procurement of parenteral formulated antiviral as bulk drug substance (BDS)

1 – 50,0003

0019 (Option) Surge Capacity – Storage of parenteral formulated antiviral as bulk drug substance (BDS) in VMI for 5 years. (Monthly rate per TC: $_________)4 (from bulk drug substance procured under

CLIN0018).

1 – 50,0003

0020 (Option) Surge Capacity –Fill/finish of final drug product from bulk drug substance procured under CLIN0018).

1 – 50,0003

0021 (Option) Surge Capacity – Storage of final drug product in VMI for 5 years (Monthly rate per TC: $_________)4 (from bulk drug substance procured under

CLIN0018).

1 – 50,0003

0022 (Option) Surge Capacity – Delivery of FDP to the SNS (from bulk drug substance procured under CLIN0018).

1 – 50,0003

0023 (Option) Additional procurement of a nonparenteral formulated antiviral as FDP and delivery to the SNS

1 - 262,5002

0024 (Option) Surge Capacity – Additional procurement of parenteral formulated antiviral as bulk drug substance (BDS)

1 – 50,0003

0025 (Option) Surge Capacity – Storage of parenteral formulated antiviral as bulk drug substance (BDS) in VMI for 5 years. (Monthly rate per TC: $_________)4 (from bulk drug substance procured under

CLIN0024).

1 – 50,0003

0026 (Option) Surge Capacity –Fill/finish of final drug product (from bulk drug substance procured under CLIN0024).

1 – 50,0003

0027 (Option) Surge Capacity – Storage of final drug product in VMI for 5 years (Monthly rate per TC: $_________)4 (from bulk drug substance procured under

CLIN0024).

1 – 50,0003

0028 (Option) Surge Capacity – Delivery of FDP to the SNS (from bulk drug substance procured under CLIN0024).

1 – 50,0003

2 Please propose up to 262,500 treatment courses with a realistic capacity to deliver product in addition to the corresponding price per treatment course. In addition, please provide volume discounts for CLINs 5, 11, 17 and 23.

3 Please propose up to 50,000 treatment courses with a realistic capacity to deliver product in addition to the corresponding price per treatment course. In addition, please provide volume discounts for CLINs 6, 12, 18, and 24.

4 Please propose the monthly rate pro-rated for storage less than 5 years.

B.3. ADVANCE UNDERSTANDINGS

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

Specific elements of cost, which normally require prior written approval of the Contracting Officer 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.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 including 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 $150,000.00;

j) Refreshments and Meal Expenditures;

k) Promotional Items

l) Printing

SECTION C – DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

C.1. STATEMENT OF OBJECTIVES

1. BACKGROUND AND PURPOSE

This Request for Proposal (RFP) covers the purchase and delivery of at least one antiviral against smallpox disease as caused by the smallpox virus. The objective of this RFP will be to procure up to 1.7 million treatment courses of the antiviral(s) against smallpox.

Smallpox (Variola viridae or VARV, the etiological agent responsible for smallpox disease) is responsible for the deaths of hundreds of millions of people throughout history. An effort spearheaded by the World Health Organization (WHO) led to the eradication of smallpox disease in the 1970s, with the last case of smallpox diagnosed in 1977. With an exceptionally high morbidity and communicability, smallpox is still considered one of the most dangerous human pathogens.

Although smallpox is no longer endemic, the biological weapons program in the Soviet Union, the possible existence of clandestine stocks in addition to the WHO-sanctioned repositories in the Russian Federation, and the United States, and the recent advancements in molecular biology demonstrating the feasibility of creating smallpox from nucleic acids underscore the potential danger of smallpox as a biological threat.

Medical countermeasures (MCM) against Smallpox are urgently needed should future outbreaks of Smallpox occur. The 2014 Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Strategy and Implementation Plan identifies Smallpox as a high-priority threat as determined by the Secretary of Homeland Security.

Vaccines are no longer administered to the US population (outside of deployed military recruits) and there are no therapeutic agents available on the market to treat symptomatic smallpox. To counter the threat, the US Government stockpiles both a large quantity of smallpox vaccine intended for pre-exposure prophylaxis (PrEP), and a limited quantity of antiviral therapeutics intended to treat symptomatic patients during the course of a smallpox event. The government has pursued this multi-faceted approach with the goal of being able to rapidly deploy lifesaving therapeutics to an effected population during a smallpox event and to provide sufficient vaccine to protect the population surrounding an effected area or those who are considered at risk of infection.

While there is a licensed vaccine for the pre-exposure prophylaxis against smallpox, there are currently no approved therapeutic antivirals for the treatment of symptomatic smallpox. However, BARDA and other USG agencies (NIAID, DoD) have funded and supported the development of smallpox antiviral candidates with the goal of approval. Furthermore, the USG recognizes that in the event of a smallpox release, certain patient populations will be unable to be dosed with an oral formulation of an antiviral (e.g. too ill to swallow, dysphagic or pediatric populations) and have pursued the development of alternative, parenteral formulations for an antiviral agent. Utilizing Project BioShield, BARDA has established an inventory of smallpox antiviral therapeutics, however the drugs in the stockpile will soon begin expiring and it is necessary that the USG seek to procure additional treatment courses to maintain the preparedness posture already established.

The United States Government (USG) desires an antiviral(s) that can meet the PHEMCE product requirements for MCM against smallpox exposure. This RFP will also support the necessary late-stage development to achieve approval of the alternative formulation of the product(s) being procured.

2. SCOPE

Independently and not as an agent of the USG, the Contractor 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 up to 1.7 million treatment courses of an antiviral(s) therapeutic against smallpox. Under past procurement contracts, the USG has established a stockpile of over 1.7 million treatment courses of a smallpox antiviral therapeutic MCM against smallpox. The USG will utilize this anticipated procurement to maintain the level of preparedness achieved in the stockpile. The antiviral(s) shall either be delivered to the Centers for Disease Control and Prevention Strategic National Stockpile (CDC/SNS), or maintained as vendor-managed inventory (VMI) as determined by BARDA and the Contracting Officer. The treatment course shall be provided as Final Drug Product (FDP) and a mix of FDP and Bulk Drug Substance (BDS) that shall be filled as needed. The USG is seeking a product(s) that may be administered under an Emergency Use Authorization (EUA) held by the CDC/SNS or VMI if an emergency is declared in response to a future outbreak.

The scope of the base period will include late-stage development activities necessary to support product approval, and initial purchase of antiviral treatment courses. Options will include Phase 4 Post-Marketing Commitments and incremental purchases of therapeutic treatment courses as needed.

The statement of objectives are outlined in the following eight sections that the Contractor(s) shall address in their proposed statement of work:

Section 3: Program Management and Risk Mitigation Objectives Section 4: Late Stage Product Development Objectives Section 5: Procurement, Storage, or Delivery of Product Objectives Section 6: Post-Marketing Commitments and/or Requirements (Option) Section 7: Additional Procurements (Option)

3. PROGRAM MANAGEMENT AND RISK MITIGATION OBJECTIVES

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

3.1. The Contractor shall submit program/risk management documents as described in

Section F.3.2.E and F.3.2.F.

3.2. The Contractor shall develop and maintain a risk mitigation plan that is acceptable to the CO and COR. This shall include a risk matrix per Attachment 13.

3.3. The Contractor shall provide a security plan which 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.

4. LATE STAGE PRODUCT DEVELOPMENT OBJECTIVES (BASE CLIN 0001)

4.1. GENERAL PRODUCT DEVELOPMENT OBJECTIVES

4.1.1. The Contractor shall have more than one formulation available for procurement. At least one of those formulations (parenteral or nonparenteral) must be available for immediate procurement and delivery to the SNS.

4.1.2. The Contractor shall provide a draft Target Product Profile (TPP) which will be further developed through discussion and negotiation with BARDA and/or FDA.

4.1.3. The product shall have an indication for treatment of symptomatic smallpox and/or orthopox disease.

4.1.4. The product shall have an indication for use in healthy adults (Ages 18-55).

4.1.5. The product shall have a minimum of five years stability at the intended storage temperature.

4.1.6. The product shall be able to be manufactured at a scale capable of meeting the USG requirements for stockpiling.

4.2. REGULATORY OBJECTIVES

4.2.1. The Contractor shall maintain and update, as required by the FDA, all required regulatory documentation (investigator brochure, regulatory binder, etc.), that will be used to support use under EUA and/or approval.

4.2.2. The Contractor shall obtain FDA concurrence on the appropriate path for regulatory evaluation and approval (i.e. traditional approval, accelerated approval, or Animal Rule).

4.2.3. The Contractor shall conduct all necessary meetings with the FDA to support submission of a New Drug Application (NDA) or evaluation through amendment to an existing approved product to the FDA.

4.2.4. The Contractor shall re-label investigational product (upon approval) to be consistent with the licensed product, in accordance with regulatory requirements from the FDA.

4.2.5. The Contractor shall satisfy any Post Marketing Commitments (PMC) required for maintaining the license including any studies to monitor safety and efficacy during a smallpox emergency

4.3. NON-CLINICAL OBJECTIVES

4.3.1. The Contractor(s) shall perform the appropriate toxicology studies to demonstrate product safety as a therapeutic against infection by variola. Additionally, non-clinical studies to demonstrate efficacy may be required to generate data to support FDA approval of the product against smallpox.

4.3.2. The Contractor shall conduct any FDA required efficacy studies to support FDA approval.

4.3.3. The Contractor shall conduct any FDA required toxicity studies to support FDA approval.

4.4. CLINICAL OBJECTIVES

4.4.1. The Contractor shall complete any remaining Phase III clinical studies required for product evaluation and determine critical biological markers using validated assays as directed by the BARDA/FDA.

4.5. CHEMISTRY, MANUFACTURING, CONTROL (CMC) OBJECTIVES

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

4.5.2. The Contractor shall provide a Manufacturing Plan that includes a facility regulatory compliance plan addressing cGMP standards; description of the manufacturing facility quality assurance and regulatory acceptance including quality systems, validation master plan and regulatory milestones.

4.5.3. The Contractor shall complete any remaining manufacturing and quality control activities needed to support FDA approval. And/or, the Contractor shall establish regulatory strategy, filing processes for successful product approval

4.5.4. The Contractor shall conduct long term stability studies on Bulk Drug Substance and

FDP to establish an expiry period of at least five years.

4.5.5. The Contractor 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 & 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 approval.

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 quality control (QC) and quality assurance (QA) monitoring plan, and manufacturing process, facility information, product storage and monitoring inventory systems, process flow for personnel, 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

5. PROCUREMENT AND DELIVERY OF PRODUCT OBJECTIVES (BASE CLIN 0002)

5.1. The Contractor(s) shall provide an initial shipment of product, up to 50,000 treatment courses of smallpox antiviral(s), in accordance with all federal, state and local regulations, as well as international regulations if applicable. The source of transportation used by the Contractor for the delivery of product must meet USG security requirements. Product will be delivered to the CDC/SNS in a manner consistent with FDA guidance for EUA or approved Medical Products, under section 564 of the Federal Food, Drug, and Cosmetic Act, which was amended by the Project BioShield Act of 2004 and the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013. Further guidance can be found at http://www.fda.gov/EmergencyPreparedness/Counterterrorism/ucm182568.htm.

5.2. The Contractor shall store FDP, in compliance with cGMP, until release testing has been completed. The FDP will be shipped to, and stored at, the CDC/SNS or maintained as vendor-managed inventory (Please propose price per treatment course for delivery to the

SNS).

5.3. The Contractor shall maintain cGMP compliance and quality control of stored FDP and stability assays to ensure expiry dating for the duration of the contract.

6. POST-MARKETING COMMITMENTS AND/OR REQUIREMENTS (OPTION CLINs 0003-0004)

6.1. The Contractor shall commit to comply with Post-Marketing Commitments and/or Requirements (PMCR) for the nonparenteral as specified by the FDA. Cost estimates may be http://www.fda.gov/EmergencyPreparedness/Counterterrorism/ucm182568.htm based on tentative plans in place prior to direction from the FDA. Based on guidance from the FDA, select items from section 4 of the Statement of Objectives may be moved to the PMCR section.

6.2. The Contractor shall commit to comply with Post-Marketing Commitments and/or

Requirements (PMCR) for the parenteral as specified by the FDA. Cost estimates may be based on tentative plans in place prior to direction from the FDA. Based on guidance from the FDA, select items from section 4 of the Statement of Objectives may be moved to the PMCR section.

7. ADDITIONAL PROCUREMENT (OPTION CLINs 0005 – 0028)

7.1. The estimate for the total procurement is up to 1,700,000 treatment courses. However, the USG has the sole discretion to determine the amount of product to be procured based on availability of funds. These efforts include manufacturing, stability testing, and storage.

Please propose price per treatment course for both VMI and SNS.

7.2. To maintain preparedness, the USG shall at its discretion execute optional procurements (See Section 5 for applicable requirements). These option CLINs (0005, 0011, 0017, 0023) shall support procurements of a nonparenteral formulation. The procurement will consist of FDP shipped to the CDC/SNS.

7.3. To maintain preparedness, the USG shall at its discretion execute option procurements (See

Section 5 for applicable requirements). Option CLINs (0006, 0012, 0018, and 0028) shall support the additional procurement of a parenteral smallpox antiviral. It is currently estimated that additional procurement under the optional CLINs will not exceed 1.7M treatment courses of FDP or 1.7M FDP treatment courses equivalents of BDS.

C.2. 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 Contracting Officer will be responsible for inspection and acceptance of deliverables and services. Monitoring of the contract will be based on periodic reporting by the Contractor.

C.3. MEETINGS/SITE VISITS

The Contractor and BARDA/AMCG shall participate in regular meetings to coordinate and oversee the contracting effort as requested by the Contracting Officer (CO)/Contracting Officer’s Representative (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 and/or teleconferences, site visits to the Contractor’s and/or subcontractor’s facilities, and meetings with individual Contractors and other HHS officials to discuss the technical, regulatory, and ethical aspects of the program. The Contractor 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 Contractor to HHS/BARDA and review contract requirements. This meeting usually occurs within a month after contract award. Expect Bi-weekly 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 thirty (30) calendar days of an FDA audit of Contractor or subcontractor facilities, the Contractor shall provide copies of the audit findings, final report, and a plan for addressing areas of nonconformance to FDA regulations and guidance for GLP, GMP or 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 Contractor with 48 hours advance notice. The USG reserves the right to accompany the Contractor on routine and for-cause site-visits/audits of subcontractor(s). At the discretion of the USG and independent of testing conducted by the Contractor, BARDA reserves the right to conduct site visits/audits and collect samples of product held by the Contractor and subcontractors.

Pre-award site visits may be made with short notice. Contractors 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 Contractor’s name. The Contractor shall guarantee that all required materials shall be delivered in immediate usable and acceptable condition.

D.2. FOB DESTINATION DELIVERIES

The Contractor shall describe the storage conditions for each product, specifically noting the acceptable temperature range required to maintain product quality. The Contractor shall be responsible for maintaining product temperature control until the product(s) arrives at the SNS and has completed product acceptance by the USG. The Contractor shall provide the Government with an ambient exposure letter that covers the time the product(s) leaves the Contractor’s validated storage facility until arrival at DSNS. 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 Contractor will provide and place TempTale(s) on each pallet of product while the product is inside the Contractor’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 52.246-2, Inspection of Supplies – Fixed Price (August 1996)

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

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

FAR 52.246-8, 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 base period of performance of this contract is anticipated for sixty (60) months from the date of award. The period of performance may be extended up to 5 years with the exercise of option(s), structured as CLINs, as 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 Contracting Officer (CO) and the Contracting Officer’s Representative (COR). When electronic deliverables are not preferable by the Contracting Officer, 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 Brooke Bernold Contracting Officer

HHS/ASPR/AMCG

200 C St. SW Washington, DC 20024 Email: Brooke.Bernold@hhs.gov

Brooke Bernold Contracting Officer

HHS/ASPR/AMCG

200 C St. SW

UPS/FedEx/Courier USPS Mail Packages Andrew Albright Contracting Officer Representative

HHS/ASPR/BARDA

200 C St. SW Washington, DC 20024 Email: Andrew.Albright@hhs.gov

Andrew Albright Contracting Officer Representative

HHS/ASPR/BARDA

200 C St. SW

F.3.2. Reporting Requirements

In addition to those reports required by other terms of this RFP, the Contractor 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 Contractor 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 Contractor'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). Please 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 of work completed and costs incurred during the period covered in relation to the proposed progress, effort, and budget. The report shall be in sufficient detail to explain comprehensively the results achieved.

SECTION II Part D: ISSUES – This section shall include a description of problems encountered and proposed corrective action; differences between planned and actual progress; why the differences have occurred and what corrective actions are planned; and if a project activity is delinquent, then what corrective action steps are planned. Revised timelines shall be provided.

SECTION II Part E: PROPOSED WORK – This section shall include a summary of work proposed as a rolling three (3) month forecast for the next reporting period, by a certain date, and by whom.

SECTION II Part F: MANUFACTURING AND SUPPLY CHAIN MANAGEMENT – This section shall include a summary of the manufacturing and supply-chain related activities. Also include in this section updates to the production plan, capacity projections, stability results, inventory and shipment/distribution information.

SECTION II Part G: CONTRACTING OFFICER APPROVALS – This section shall include a table indicating each Contracting Officer Approval (COA) request, its current status (e.g. date submitted, date approved, date returned), amount requested, and the vendor for which the COA authorizes subcontracted work to be performed.

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

A Monthly Progress Report will not be required in the same month Annual Progress Reports or a Final Report are due.

B. Annual Progress Report

This report shall include a summation 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 year of performance plus any fractional part of the initial year. Thereafter, the reporting period shall consist of each calendar year.

The Contractor shall submit an Annual Progress Report on or before the 30th 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 Contractor'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.

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). Please 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 of work completed and costs incurred during the period covered in relation to proposed progress, effort, and budget. The report shall be in sufficient detail to explain comprehensively the results achieved.

SECTION II Part D: ISSUES – This section shall include a description of problems encountered and proposed corrective action; differences between planned and actual progress; why the differences have occurred and what corrective actions are planned; and if a project activity is delinquent, then what corrective action steps are planned. Revised timelines shall be provided.

SECTION II Part E: PROPOSED WORK – This section shall include a summary of work proposed as a rolling three (3) month forecast for the next reporting period, by a certain date, and by whom.

SECTION II Part F: MANUFACTURING AND SUPPLY CHAIN MANAGEMENT – This section shall include a summary of the manufacturing and supply-chain related activities. Also include in this section updates to the production plan, capacity projections, stability results, inventory and shipment/distribution information.

SECTION II Part G: CONTRACTING OFFICER APPROVALS – This section shall include a table indicating each Contracting Officer Approval (COA) request, its current status (e.g. date submitted, date approved, date returned), amount requested, and the vendor for which the COA authorizes subcontracted work to be performed.

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

An Annual Progress Report will not be required for the period when the Final Technical Progress Report is due.

C. Draft Final Report and Final Report

These reports are to include a summation of the work performed and results obtained for execution of various studies or technical work packages during the entire contract period of performance. This report shall be in sufficient detail to describe comprehensively the results achieved. The Draft Final Progress Report shall be due forty-five (45) calendar days prior to the expiration date of the contract and the Final Progress Report is due no later than 30 days following the expiration date of the contract. The report shall conform to the following format:

Title Page: The title for these reports shall include the contract number and title; the type of report and period that it covers; the Contractor'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.

SECTION I: EXECUTIVE SUMMARY - Summarize the purpose and scope of the contract effort including a summary of the major accomplishments relative to the specific activities set forth in the Statement of Work.

SECTION II: RESULTS - A detailed description of the work performed and the results obtained including all expenses for the entire contract period of performance.

D. FDA Regulatory Agency Correspondence, Meeting Summaries, and Submissions.

a) Within five business days of any formal meeting with the FDA or other regulatory agency, the Contractor shall forward the initial draft minutes to the COR. The Contractor shall forward the final minutes when available.

b) Within five business days of any informal meeting with the FDA or other regulatory agency, the Contractor shall forward the initial draft minutes to the COR. The Contractor shall forward the final minutes when available and if applicable.

c) The Contractor shall forward the dates and times of any meeting with the FDA and other regulatory agencies to the COR as soon as the meeting times are known and make arrangements for appropriate BARDA staff to attend the meetings.

d) The Contractor shall provide the COR the opportunity to review and comment upon any documents to be submitted to the FDA or other regulatory agency. The Contractor shall provide the COR with five (5) business days in which to review and provide comments back to the Contractor prior to the Contractor’s submission to the FDA.

e) The Contractor shall forward Standard Operating Procedures (SOPs) upon request from the COR.

f) The Contractor shall provide raw data and/or specific analysis of data generated with

USG funds upon request from the COR.

g) The Contractor shall notify the Contracting Officer’s Representative and Contracting

Officer within 24 hours of all FDA arrivals to conduct site visits/audits by any regulatory agency. The Contractor shall provide the USG with an exact copy (non-redacted) of the FDA Form 483 and the Establishment Inspection Report (EIR). The Contractor shall provide the Contracting Officer’s Representative and Contracting Officer copies of the plan for addressing areas of non-conformance to FDA regulations for GLP guidelines as identified in the audit report, status updates during the plans execution, and a copy of all final responses to the FDA. The Contractor shall also provide redacted copies of any FDA audits received from subcontractors that occur as a result of this contract or for this product. The redactions shall be limited to issues that are unrelated to the subcontractor’s performance on any award made under this RFP. The Contractor shall make arrangements with the COR for the appropriate BARDA representative(s) to be present during the final debrief by the regulatory inspector.

E. Other Requirements/Deliverables

a) Integrated Master Project Plan

The Contractor shall provide an Integrated Master Project Plan (including tabular and Gantt forms) to the COR that clearly indicates the critical path to annual deliverables and Work Breakdown Structure (WBS) elements. Attention shall be placed on providing sufficient turnaround time for the USG (BARDA, FDA, and CDC) for review of critical documentation. The Contractor shall integrate to demonstrate interdependencies among all CLINS. The Integrated Master Project Plan shall be incorporated into any potential contract and will be used to monitor performance of the contract. This report shall be due within 90 days of contract award. Updates shall be due as requested by the COR.

I. Critical Path Milestones

The Integrated Master Project Plan shall outline key, critical path milestones, with “Go/No Go” decision criteria (entrance and exit criteria for each phase of the project). This report shall be due within 90 days of contract award. Updates shall be due as requested by the COR.

II. Work Breakdown Structure

The WBS shall be discernable and consistent. The COR may require the Contractor to furnish WBS data at the work package level or at a lower level if there is significant complexity and risk associated with the task. This report shall be due within 90 days of contract award. Updates shall be due as requested by the COR.

III. Risk Mitigation Plan/Matrix The Contractor shall develop and maintain a risk management plan that highlights potential problems and/or issues that may arise during the life of the contract, their…