75A50121R00003 RFP.pdf

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

UNDER DPAS (15 CFR 700)

RATING PAGE OF PAGES

2. CONTRACT NUMBER 3. SOLICITATION NUMBER 4. TYPE OF SOLICITATION 5. DATE ISSUED 6. REQUISITION/PURCHASE NUMBER

CODE7. ISSUED BY 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

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 B. TELEPHONE (NO COLLECT CALLS)

AREA CODE NUMBER EXTENSION

C. E-MAIL ADDRESS

11. TABLE OF CONTENTS

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

A B C D E F G H

I

J

K

L

M EVALUATION FACTORS FOR AWARD

INSTRUCTIONS, CONDITIONS, AND NOTICES TO OFFERORS

REPRESENTATIONS, CERTIFICATIONS AND OTHER

STATEMENTS OF OFFERORS

PART IV - REPRESENTATIONS AND INSTRUCTIONS

LIST OF ATTACHMENTS

PART III - LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACH.

CONTRACT CLAUSESSOLICITATION/CONTRACT FORM

SUPPLIES OR SERVICES AND PRICES/COSTS

DESCRIPTION/SPECS./WORK STATEMENT

PACKAGING AND MARKING

INSPECTION AND ACCEPTANCE

DELIVERIES OR PERFORMANCE

CONTRACT ADMINISTRATION DATA

SPECIAL CONTRACT REQUIREMENTS

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

OFFER (Must be fully completed by offeror)

12. In compliance with the above, the undersigned agrees, if this offer is accepted within 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)

14. ACKNOWLEDGMENT OF AMENDMENTS

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

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

DATEAMENDMENT NO.AMENDMENT NO. DATE

15A. NAME AND

ADDRESS

OF OFFEROR

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

OFFER(Type or print)

15B. TELEPHONE NUMBER

AREA CODE NUMBER EXTENSION

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 21. ACCOUNTING AND APPROPRIATION

22. AUTHORITY FOR USING OTHER THAN FULL OPEN COMPETITION:

10 U.S.C. 2304 (c) ( )41 U.S.C. 3304(a)

24. ADMINISTERED BY (If other than Item 7)

26. NAME OF CONTRACTING OFFICER (Type or print)

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

23. SUBMIT INVOICES TO ADDRESS SHOWN IN

(4 copies unless otherwise specified)

25. PAYMENT WILL BE MADE BY

27. UNITED STATES OF AMERICA

(Signature of Contracting Officer)

28. AWARD DATE

CODE

ITEM

STANDARD FORM 33 (REV. 6/2014)

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

SEALED BID (IFB)

NEGOTIATED (RFP)

(Hour) (Date)

PART I - THE SCHEDULE PART II - CONTRACT CLAUSES

1 111

HHS/OS/ASPR/BARDA/CMA

200 C Street SW, Washington, DC 20024

75A50121R00003

See Section L for Instructions 4:00PM

Jill Johnson Jill.Johnson@hhs.gov

26 72

7/19/2021

202 816 1148

6/17/2021

RFP 75A50121R00003

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 June 28, 2021 at 12PM ET. All questions shall be submitted via e-mail to Jill.Johnson@hhs.gov.

mailto:Jill.Johnson@hhs.gov

PART I – THE SCHEDULE

SECTION B – SUPPLIES OR SERVICE AND PRICE / COST

B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES

In 2007, the Public Health Emergency Medical Countermeasure Enterprise (PHEMCE) recommended that an improved anticonvulsant to treat seizures caused by nerve agent exposure be developed and procured. Attributes of this product would include a non-IV route of administration (e.g. IM) that is fast acting, has greater efficacy than existing products, and that is approved by the Food and Drug Administration (FDA) for adult and pediatric indications. The 2007 PHEMCE Implementation Plan for Chemical, Biological, Radiological, and Nuclear (CBRN) Threats called for updating the CHEMPACK formulary with improved medical countermeasures, such as anticonvulsants, as they became available.

Requirements for the desired anticonvulsant were listed in the Improved Anticonvulsant Product Specific Requirements (2011), and the PHEMCE recommended that the CHEMPACK formulary be updated with the improved anticonvulsant midazolam. Midazolam is now approved to treat status epilepticus seizures in adult populations, inclusive of seizures subsequent to nerve agent intoxication. Acquisition of pediatric and adult midazolam autoinjectors and their approval for the treatment of status epilepticus would fulfill this requirement. The goal of this acquisition is to replace all expired diazepam autoinjectors (Convulsant Antidote Nerve Agent, CANA) in the Strategic National Stockpile’s (SNS) CHEMPACK Program with autoinjectors containing the improved anticonvulsant midazolam in an autoinjector for rapid intramuscular administration. Midazolam autoinjectors would be used in the prehospital setting (EMS CHEMPACKs) and in the hospital setting in a mass casualty situation to increase the ease and speed of administration.

Prepositioning antidotes throughout the country addresses the time constraints on effective medical treatment, and thus reduces the time of delivery of life saving nerve agent medical countermeasures.

CHEMPACKs supplement the supply of these antidotes available in local hospitals, Emergency Medical Service (EMS) systems, and other local response organizations. CHEMPACKs account for all the diazepam acquired and maintained by the SNS, specifically for the treatment of nerve agent-induced seizures. Project BioShield (PBS) funds will fund Human Factors evaluations for the new autoinjectors, late-stage clinical development, regulatory approval for midazolam autoinjectors (as a drug/device combination product) to treat status epilepticus in adult and pediatric populations, and procurement of pediatric and adult midazolam autoinjectors for the SNS CHEMPACK Program. The urgent need for an improved anticonvulsant (midazolam) autoinjectors within the Strategic National Stockpile to treat seizures caused by nerve agents requires BARDA to enter into a late stage development and procurement contract. This effort is particularly pressing given that the diazepam autoinjectors in CHEMPACKs are currently expired and nearing the end of viability via the Shelf Life Extension Program

(SLEP).

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 final contract will consist of a base period of 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 (CPFF) Contract Line Item Number (CLIN) to support Advanced Research and Development (ARD) necessary for the completion of remaining regulatory activities to obtain FDA approval for midazolam autoinjectors (as a drug/device combination product) to treat status epilepticus in adult and pediatric populations. Eight optional CLINs include both Firm-Fixed Price (FFP) CLINs to support procurement of midazolam autoinjectors for the

SNS/CHEMPACK Program as well as Supplementary CPFF CLINs dedicated to additional late stage development; post-marketing commitments as established by the FDA; BARDA Security requirements as necessary. Purchase of midazolam autoinjectors may occur once the autoinjectors are FDA approved for status epilepticus indication, or acceptable for use under an EUA. The options may be exercised within the previous period of performance of the contract, if needed. Below are the anticipated CLINs.

B.2.1. BASE PERIOD

Base Period Cost Reimbursement CLIN

Anticipated Period of

Performance CLIN Supplies/Services

2021-2026 0001 (Base)

Program Management: Identification and Selection of Pediatric Dose;

Device design changes to support Pediatric autoinjector; Development, qualification and validation of pediatric device manufacturing; Human factors studies for adult and pediatric devices; Regulatory activities to support FDA approval of drug/device combination for midazolam autoinjectors to treat SE in pediatric and adult populations.

B.2.2. OPTIONS

CLIN Supplies/Services Quantity

2021-2026 0002 (Option 1) Procurement of Adult Autoinjector Devices 306,000

Optional Cost Reimbursement CLINs

CLIN Supplies/Services

2023-2028 0004 (Option 3)

Post Marketing Commitments (PMC) and manufacturing optimizations required for maintaining the approval including any studies to monitor safety and efficacy for status epilepticus or during a nerve agent emergency.

2025-2030

(Option 6)

Post Marketing Commitments (PMC) and manufacturing optimizations required for maintaining the approval including any studies to monitor safety and efficacy for status epilepticus or during a nerve agent emergency.

2021-2026 0003

(Option 2) Procurement of Pediatric Dose Autoinjector Devices 54,000

2023-2028

(Option 4) Procurement of Adult Dose Autoinjector Devices 173,000

2023-2028

(Option 5) Procurement of Pediatric Dose Autoinjector Devices 35,000

(Option 7) Procurement of Adult Dose Autoinjector Devices 173,000

(Option 8) Procurement of Pediatric Dose Autoinjector Devices 35,000

B.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 before incurrence of the cost will be included in this Section if the Contracting Officer has granted his/her approval prior to contract award.

a. Person-in-Plant

With seven (7) days advance notice to the Contractor in writing from the Contracting Officer, the Government may place a man-in-plant in the Contractor’s or Subcontractor’s facility, who shall be subject to the Contractor’s or Subcontractor’s policies and procedures regarding security and facility access at all times while in the Contractor’s or Subcontractor’s facility. The Government’s representative shall be provided reasonable access, during normal business hours, of the production areas being utilized in performance on the Contract. As determined by federal law, no Government representative shall publish, divulge, disclose, or make known in any manner, or to any extent not authorized by law, any information coming to him in the course of employment or official duties, while stationed in a contractor or subcontractor plant.

An article substantially similar to this Person-in-Plant article shall be incorporated into any subcontract for experimental or manufacturing work.

b. Security

No security plan is required at this point for this effort. It is anticipated that a security waiver will be approved.

c. Subcontracts

Prior written consent from the Contracting Officer in the form of Contracting Officer Authorization (COA) is required for any subcontract that:

• Is of the cost-reimbursement type and exceeds $250,000; or

• Is of the fixed price type and exceeds $250,000 or 5% of the contract, whichever is less.

The Contracting Officer shall request appropriate supporting documentation in order to review and determine authorization, pursuant with FAR Clause 52.244-2, Subcontracts.

After receiving written consent of the subcontract by the Contracting Officer, the Contractor shall provide a copy of the signed, executed subcontract and consulting agreement to the Contracting Officer within ten (10) calendar days.

Note: Consulting services are treated as subcontracts and subject to the ‘consent to subcontract’ provisions set forth in this Section.

d. Overtime Compensation

No overtime (premium) compensation is authorized under the subject contract.

e. Sharing of contract deliverables within United States Government (USG)

In an effort to build a robust medical countermeasure pipeline through increased collaboration, the Government may share technical deliverables with Government entities responsible for Medical Countermeasure Development. In accordance with recommendations from the Public Health Emergency Medical Countermeasure Enterprise Review, agreements established in the Integrated Portfolio Advisory Committee (PAC) Charter, and agreements between BARDA and the Department of Defense, the National Institutes of Health, the Centers for Disease Control, and the Food and Drug Administration, BARDA may share technical deliverables and test results created in the performance of this Contract with colleagues within the Integrated Portfolio.

This advance understanding does not authorize the Government to share financial information outside of the United States Government. The Contractor is advised to review the terms of FAR 52.227-14, Rights in Data – General, regarding the government’s rights to deliverables submitted during performance as well as the government’s rights to data contained within those deliverables.

f. Approval of Human and Animal Protocols

The Contractor shall submit all human and animal protocols and human informed consent documents as referenced under this Contract to the COR for review and approval prior to seeking other approvals (Institutional Review Board, Human Use Committee, Institutional Animal Care and Use Committee) unless the contractor already had such approvals prior to contract award. The Government requires no fewer than eight (8) business days to perform a review. The Contractor shall take this review time into account and submit protocols as early as possible to avoid delays. The Government’s comments and feedback shall be addressed prior to approval. The COR will review and provide approval of protocols. Human informed consents shall also be submitted and reviewed with any human protocol.

g. Rights in Data

The contract will incorporate the FAR Clause 52.227-14, Rights in Data—General. The Contractor is advised to review the terms of FAR 52.227-14, Rights in Data, regarding the government’s rights to deliverables submitted during performance as well as the government’s rights to data contained within those deliverables.

h. Invoice Submission during end of Fiscal Year

The government will not accept invoices for processing from Sep 6th through Oct 5th because of end of year fiscal requirements. Any invoices received from September 6th through October 5th will be canceled and returned to the Contractor for resubmission beginning on October 6th.

B.4 ORGANIZATIONAL CONFLICT OF INTEREST

a. General: For the purpose of this provision/clause, “consultant” is defined as a company, firm, LLC, sole proprietor, joint venture member, independent contractor, subcontractor, affiliate, or similar entity that is not an employee of the Contractor.

b. Disclosure: The Contractor shall report contacts with consultants who are paid to furnish advice, information, direction, or assistance to the Contractor or any subcontractor in support of the preparation or submission of the Contractor’s business or technical proposal. The report shall include the following information:

a. The name, title, and contact information for the consultant, including the name and contact information for his/her company/firm/etc.

b. The name, title, and contact information for a Contractor point of contact, including the name and contact information for the prime contractor if the consulting services were received by a subcontractor.

c. The nature of the consulting services received.

c. Resolution: The responsible Contracting Officer will review the Contractor’s disclosure to determine whether an actual or appearance of a conflict of interest exists based on the information disclosed by the Contractor and/or from other sources. The framework for the Contracting Officer’s review will be FAR Subpart 9.5, Organizational and Consultant Conflicts of Interest. If an actual or appearance of a conflict of interest exists, the Contracting officer will take action which may include, but is not limited to, requesting a mitigation plan from the Contractor.

B.5. 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 or 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 $250,000.00;

j) Refreshments and Meal Expenditures;

k) Promotional Items

l) Printing

SECTION C – DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

C.1. STATEMENT OF OBJECTIVES

BACKGROUND AND PURPOSE

This Request for Proposal (RFP) covers the advanced research and development, procurement, and delivery of adult and pediatric midazolam autoinjectors that have received FDA approval for the treatment of status epilepticus seizures (including seizures caused by nerve agents) in adult and pediatric populations (2+ years of age). Acceptance of the autoinjectors into the SNS/CHEMPACKs requires that the finished product meet all specifications and reliability requirements as determined by the FDA. The goal of this acquisition is to replace all of expired diazepam autoinjectors (Convulsant Antidote Nerve Agent, CANA) in the Strategic National Stockpile’s (SNS) CHEMPACK Program with autoinjectors containing the improved anticonvulsant midazolam in an autoinjector for rapid intramuscular administration. Midazolam autoinjectors would be used in the prehospital setting (EMS CHEMPACKs) and in the hospital setting in a mass casualty situation involving nerve agents to increase the ease and speed of administration. Midazolam autoinjectors will be FDA approved for pediatric and adult populations and will be available separately for both populations (i.e., pediatric and adult autoinjectors). A needle-free autoinjector is preferred for numerous reasons, including the avoidance of cross contamination, prevention of needle-stick injuries, simplification of disposal (no sharps), and improved dispensing of medication (no void volume).

The US government (USG) has a requirement to acquire, hold, and distribute medical countermeasures that will mitigate injuries caused by chemical, biological, physical radiologic and nuclear exposures. The department of Health and Human Services (HHS) has the responsibility of maintaining a definitive supply of medical Countermeasures for use in public health emergencies. In 2003, The Strategic National Stockpile (SNS) created the CHEMPACK Program to acquire nerve agent antidotes and provide them to the 50 states, four cities, and several territories for pre-positioning in locations that are convenient for responders. CHEMPACKs supplement the supply of these antidotes available in local hospitals, EMS systems, and other local response organizations.

CHEMPACKs account for all of the diazepam acquired and maintained by the SNS specifically for the treatment of nerve agent-induced seizures. The 2007 HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Implementation Plan for CBRN Threats called for updating the CHEMPACK formulary with improved medical countermeasures, such as anticonvulsants, as they become available. In 2011, the PHEMCE recommended that the CHEMPACK formulary be updated with the improved anticonvulsant midazolam, which is now approved to treat status epilepticus seizures in adult populations, inclusive of seizures subsequent to nerve agent intoxication. Acquisition of pediatric and adult midazolam autoinjectors and their approval for the treatment of status epilepticus (as a drug/device combination product) would fulfill this requirement. Fulfilling this requirement is of particular importance since diazepam autoinjectors (CANA) in CHEMPACKs are currently expired and maintained under Shelf Life Extension (SLEP).

This acquisition will allow BARDA to invest Project Bioshield funds for late-stage clinical development, regulatory approval for midazolam autoinjectors (as a drug/device combination product) to treat status epilepticus in adult and pediatric populations, and procurement of pediatric and adult midazolam autoinjectors for the SNS/CHEMPACK Program.

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 approximately 652,000 adult midazolam autoinjectors and 124,000 pediatric midazolam autoinjectors for the treatment of status epilepticus seizures (including seizures caused by nerve agents) in adults and pediatric populations (2+ years).

Midazolam autoinjectors shall be delivered to the SNS/CHEMPACK Program. CHEMPACKs account for all stock of diazepam autoinjectors for treatment of nerve agent-induced seizures, acquired and maintained by the SNS under the Shelf Life Extension Program (SLEP). Diazepam autoinjectors will be replaced by midazolam autoinjectors under this planned procurement. The USG will utilize this procurement of midazolam autoinjectors to prepare for a mass casualty event involving nerve agents.

Adult and pediatric midazolam autoinjectors shall be delivered to the SNS/CHEMPACK Program and shall be FDA approved as a drug/device combination product for the treatment of status epilepticus in both populations, or acceptable for use under an EUA.

The scope of the base period will include late-stage development activities necessary to support FDA approval of midazolam autoinjectors for the SE indication. Optional CLINs will include procurement of autoinjectors as well as additional late-stage development activities, fulfillment of additional USG security requirements as necessary, Post-Marketing Commitments Procurement options represent a series of incremental purchases of midazolam autoinjectors until the entire requirement for the manufacturing and procurement of approximately 652,000 adult midazolam autoinjectors and 124,000 pediatric midazolam autoinjectors is met.

The statement of objectives is outlined in the following sections that the Offeror(s) shall address in their proposed statement of work:

Section 1: Program Management and Risk Mitigation Objectives

Section 2 Late Stage Product Development Objectives

Section 3: Supply and Delivery of Product Objectives

Section 4: Post-Marketing Commitments and/or Requirements (Option)

Section 5: Additional Procurements (Option)

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 COR. This shall include a risk matrix per Attachment 13. The Offeror shall provide a security plan which is associated with all aspects of manufacture of product, process, storage, and inventory of the midazolam autoinjectors. 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 OPTIONS (CLINs 0004 and 0007)

2.1 GENERAL PRODUCT DEVELOPMENT OBJECTIVES

2.1.2. The Offeror shall demonstrate that they can manufacture midazolam autoinjectors that are considered approvable according to FDA guidance and regulation for the treatment of status epilepticus in adult and pediatric populations.

2.1.3. If no midazolam autoinjector is FDA approved, the Offeror must conduct development activities and seek pre-EUA authorization from the FDA for the treatment of status epileptics in adult and pediatric populations. Examples of such development activities could include human factor and bioequivalence studies.

2.1.4. Midazolam autoinjectors must demonstrate compliance with FDA reliability standards outlined in the Draft Guidance for Technical Considerations for Demonstrating Reliability of Emergency-Use Injectors Submitted under a BLA, NDA or ANDA. For more information, visit https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-demonstrating-reliability-emergency-use-injectors-submitted-under-bla-nda.

2.1.5. The product shall have a status epilepticus indication for use in adults and pediatric populations (2+ years).

2.1.6. The product shall be FDA approved or have an authorized EUA with a minimum of three years stability at the intended storage temperature.

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

2.2. REGULATORY OBJECTIVES

2.2.1. The Offeror shall maintain and update, as required by the FDA, all regulatory documentation (Design History File (DHF), clinical documentation, regulatory binder, etc.) that will be used to support use under EUA and/or FDA approval.

2.2.2. The Offeror shall obtain FDA concurrence on the appropriate path for regulatory evaluation and FDA approval of midazolam autoinjectors, as a drug/device combination product, for the treatment of status epilepticus in adult and pediatric populations.

2.2.3. The Offeror shall prepare all documentation for and conduct all necessary meetings with the FDA to support submission of a New Drug Application (NDA).

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-demonstrating-reliability-emergency-use-injectors-submitted-under-bla-nda https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-demonstrating-reliability-emergency-use-injectors-submitted-under-bla-nda https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-demonstrating-reliability-emergency-use-injectors-submitted-under-bla-nda

2.2.4. If investigational product is distributed under EUA authorization, upon FDA approval, the Offeror shall re-label such product to be consistent with the approved product, in accordance with regulatory requirements from the FDA.

2.2.5. The Offeror shall satisfy any Post Marketing Commitments (PMC) required for maintaining the approval including any studies to monitor safety and efficacy during a nerve agent emergency.

2.3. CLINICAL OBJECTIVES

2.3.1. The Offeror shall conduct all necessary clinical studies to support regulatory approval of midazolam autoinjectors for the treatment of status epilepticus in adult and pediatric populations.

2.3.2. The Offeror shall prepare and submit to BARDA a Final Study Report containing 100% quality controlled data and the completion of the clinical study. This report should be prepared in accordance with FDA and ICH Guidelines.

2.4. CHEMISTRY, MANUFACTURING, CONTROL (CMC) OBJECTIVES

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

2.4.2. The Offeror 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.

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

2.4.4. The Offeror shall conduct long-term stability studies on midazolam autoinjectors to establish an expiry period of at least three years.

2.4.5. 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 according to cGMP standards, process & equipment validation of analytical methods and assays appropriate for product characterization and product release, including tests for the identity, purity, potency, and for demonstrating stability of midazolam autoinjectors to support FDA approval. Assure selected materials and vendors are cGMP compliant.

b) Identify a stable source and availability of reagents and reference standards for these assays as 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, manufacturing process, facility information, product storage and monitoring inventory systems, process flow for personnel, material and waste disposal.

d) Package midazolam autoinjectors 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.

3. SUPPLY AND DELIVERY OF PRODUCT OBJECTIVES (OPTION CLINs 0002 and 0003)

3.1. Delivered Midazolam autoinjectors must be FDA approved or acceptable for use under EUA, in accordance with all federal, state and local regulations, as well as international regulations, if applicable. During the initial option period, the USG estimates procuring 306,000 adult dose autoinjector devices and 54,000 pediatric dose autoinjector devices, and if all options are exercised, the USG estimates procurement of 346,000 autoinjectors for the adult population and 70,000 autoinjectors for the pediatric population. Offerors must propose price per autoinjector, including required labeling/packaging and delivery to SNS/CHEMPACKs. The source of transportation used by the Offeror for the delivery of product must meet USG security requirements. Product will be delivered to the SNS/CHEMPACK Program in a manner consistent with FDA guidance for EUA or FDA 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 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities .

3.2. The Offeror shall store midazolam autoinjectors at their own facility, in compliance with cGMP, until release testing has been completed. The final packaged midazolam autoinjectors will be shipped to and stored at the SNS/CHEMPACKs.

3.3. The Offeror shall maintain cGMP compliance and quality control of stored midazolam autoinjectors and stability assays to ensure expiry dating for the duration of the contract.

4. POST-MARKETING COMMITMENTS AND/OR REQUIREMENTS (OPTION CLINs 0004 and 0007)

4.1. The Offeror shall commit to comply with Post-Marketing Commitments and/or

Requirements (PMCR) 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.

5. ADDITIONAL PROCUREMENT (OPTION CLINS: 0005, 0006, 0008, and 0009)

5.1. During subsequent Option Periods, the USG estimates procuring a total of 346,000 adult dose autoinjector devices and 70,000 pediatric dose autoinjector devices. These efforts include manufacturing, stability testing, and storage. Offerors must propose price per autoinjector, including required labeling/packaging and delivery to SNS/CHEMPACKs.

5.2. To maintain preparedness, the USG shall at its discretion execute optional procurements

(See Section 5 for applicable requirements). These option CLINs (0005, 0006, 0008, and 0009) shall support procurements of midazolam autoinjectors. The procurement will consist of fully packaged midazolam autoinjectors in adult and pediatric configurations shipped to the SNS/CHEMPACK Program.

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 Offeror.

C.3. MEETINGS/SITE VISITS

The Offeror and BARDA/CMA 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 Offeror’s and/or Offeror’s subcontractor facilities, and meetings with individual Offerors and other HHS officials to discuss the technical, regulatory, and contractual aspects of the program. The Offeror shall provide data, reports, and presentations to 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. Bi-weekly or monthly status update meetings/teleconferences will be held. The schedule for these meetings will be established by the CO and COR.

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

Within thirty (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 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 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 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 52.246-3, Inspection of Supplies – Cost-Reimbursement (May 2001)

FAR 52.246-7, Inspection of Research and Development – Fixed Price (August 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) (Apr 1984)

FAR 52.246-16, Responsibility for Supplies (Apr 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 60 months 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), Jill.Johnson@hhs.gov. No hard copies will be accepted.

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 mailto:Jill.Johnson@hhs.gov reporting period. Include progress on administration and management issues (e.g. evaluating and managing subOfferor performance and personnel changes). Offerors must 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 Offeror 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 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.

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 subOfferor performance and personnel changes). Offerors must 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 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.

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 Offeror shall forward the initial draft minutes to the COR. The Offeror shall forward the final minutes when available.

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

c) The Offeror shall forward the dates and times of any meeting with the FDA and other…