rfp neutropenia searchable format.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)

AUTHORIZED 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 99

2. CONTRACT NO.

N/A

3. SOLICITATION NO.

RFP-12-100-SOL-00016

4. TYPE OF SOLICITATION

SEALED BID (IFB)

X NEGOTIATED (RFP)

5. DATE ISSUED

AUGUST 10, 2012

6. REQUISITION/PURCHASE

NO.

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

HHS/OS/ASPR/AMCG

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

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

SOLICITATION

9. Sealed offers in original and 3 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.1. of the RFP until 12:00 PM local time 10/10/2012

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

Vijaya L. Murthy

a. TELEPHONE (NO COLLECT CALLS)

(202) 205-1855

b. E-MAIL ADDRESS

Vijaya.murthy@hhs.gov

11. TABLE OF CONTENTS

((x) DESCRIPTION (x) DESCRIPTION

PART I – THE SCHEDULE PART II – CONTRACT CLAUSES

X A SOLICITATION/CONTRACT FORM 1 X I CONTRACT CLAUSES 58

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

X C DESCRIPTION/SPECS./WORK STATEMENT 9 X J LIST OF ATTACHMENTS 68

X D PACKAGING AND MARKING 22 PART IV – REPRESENTATIONS AND INSTRUCTIONS

X E INSPECTION AND ACCEPTANCE 23 REPRESENTATIONS, CERTIFICATIONS, AND

X F DELIVERIES OR PERFORMANCE 24 X OTHER STATEMENTS OF OFFERORS 69

X G CONTRACT ADMINISTRATION DATA 38 X L INSTRS., CONDS., AND NOTICES TO OFFERORS 75

X H SPECIAL CONTRACT REQUIREMENTS 43 X M EVALUATION FACTORS FOR AWARD 95

OFFER (Must be fully completed by offeror) NOTE: Item 12 does not apply if the solicitation includes the provisions at 52.214-16, Minimum Bid Acceptance Period.

12. In compliance with the above, the undersigned agrees, if this offer is accepted within 180 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 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

NOTE TO OFFERORS

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

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

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

SECTION B – SUPPLIES OR SERVICE AND PRICE / COST

B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES

B.1.1. Background

The Department of Health and Human Services (HHS) has the responsibility of maintaining a definitive supply of medical countermeasures – or the forward deployment of same – for use in national medical emergencies declared by the Secretary of HHS.

HHS has a requirement to acquire, hold, and distribute medical countermeasures that will mitigate injuries caused by exposure to chemical, biological threat agents, and physical radiologic and nuclear exposures. In the case of a physical, chemical or biologic agent that undermines the integrity and homeostasis of neutrophil number and function (i.e., neutropenia), the most common clinical treatment to shorten or reduce time to neutrophil recovery is the use of Colony Stimulating Factor (CSF) as either Granulocyte (G) or Granulocyte-Macrophage (GM).

The primary requirement of this RFP is for the U.S. Government to procure, under a Vendor Managed Inventory contract, one or more types of colony stimulating factors (CSF; either G or GM- CSF) where the products have near identical affinity for the CSF target receptor and exemplify similar mechanisms of action on neutrophil repopulation but may each afford specific advantages in clinical management of neutropenia. The vendor (contractor) shall maintain and provide availability of the products at quantities cited herein 24 hours a day, 7 days a week (24/7). If any, or all, of the specified product under this contract is released at the request of the Government in support of a national emergency, a Notification of Release of Product will be issued in accordance with the contract. An optional requirement of this RFP is for advanced development toward a second licensed indication for treating neutropenia arising from exposure to ionizing radiation. Offerors may submit proposals for acquisition of product only or acquisition of product with advanced development.

B.1.2. Definitions for the purpose of this contract

Contractor Team Arrangement: A potential prime Contractor agrees with one or more other companies to have them act as its subcontractors under a specified Government contract or acquisition program.

Dose: A unit dose for the purpose of this solicitation is an adult daily dose and not a multi-dose vial.

A product that requires less than daily dosing, i.e. a PEGylated cytokine, shall be termed an equivalent to seven daily doses.

Emergency Use Authorization (EUA) – see http://www.fda.gov/oc/guidance/emergencyuse.html

Product: All references to Product mean “a product or product surrogate that is deemed acceptable by the FDA.”

Subcontractor: A subcontractor means any supplier, distributor, vendor, or firm that furnishes supplies or services to or for a prime Offeror or another subcontractor. See FAR 44.101 http://www.fda.gov/oc/guidance/emergencyuse.html

Vendor Managed Inventory/VMI: The vendor shall maintain and provide availability of the products at quantities cited herein, 24 hours a day, 7 days a week (24/7). If any, or all, of the specified product under this contract is released at the request of the Government in support of a national emergency, a Notification of Release of Product will be issued in accordance with the contract.

B.1.3. Specific Requirements

This RFP solicits proposals for the acquisition of:

1) Product: a recombinant human Colony Stimulating Factor (CSF) as either Granulocyte (G) or Granulocyte-Macrophage (GM), also known as G-CSF or GM-CSF, for use in the treatment of neutropenia arising as a primary pathology from hematopoietic progenitor cell injury caused by a radiation or nuclear incident; and/or

2) Services: a vendor-managed inventory (VMI, or an inventory management plan as otherwise proposed by the offeror) with rotation of stock to control product expiry. The inventory management plan shall also include a plan for rapid “at need” United States Government (USG) access of product at the Contractor’s storage facility(s) should the USG have an immediate need for access to product in an emergency situation.

3) Optional advanced development: It is the requirement of this RFP to obtain licensed products which have the indication of treatment of neutropenia (regardless of cause). No product currently holds a US license for the indication of neutropenia arising from exposure to ionizing radiation alone.

Thus, the USG intends to fund the advanced development of G- and GM-CSF products for this new indication. Prior to the submission of the proposal, the Offeror must have regulatory consult on the appropriate path for approval of their respective therapeutic for use in the treatment of neutropenia arising from exposure to ionizing radiation. It is the requirement of BARDA to acquire one or more Colony Stimulating Factors (G- or GM-CSF) for mitigation of neutropenia arising from exposure to ionizing radiation. The optional advanced development will provide BARDA with a compendium of studies that will support the use of the product in a declared emergency and aid in taking the product to license or approval.

This RFP requires a plan to acquire, hold, control and deploy the product such that the required number of doses is made available upon USG demand. Offerors shall propose a product delivery schedule that may be subject to negotiation. The schedule for USG control of product will be incorporated into the final contract.

Either as a single contractor or as a contractor team arrangement, the Offeror(s) shall provide: 1) the designated product(s), and 2) inventory storage, distribution, and management for avoidance of product expiry, timely product availability and product location(s) upon USG demand, participation in simulation exercises, and product deployment from the Contractor’s holding with formal coordination with HHS/CDC and HHS/OPEO upon the declaration of an emergency by the Secretary of HHS.

One or more awards may be made as a result of this solicitation. The Contractor(s) selected for this acquisition shall be providing either the designated product, the vendor-managed inventory (VMI), or both. The successful Offeror(s) shall provide product and service, or assure coordination with the product contractor (sponsor) or provider of the VMI (as appropriate) in providing product holding with stock rotation. The Government may also provide support toward a second licensed indication for treating neutropenia arising from exposure to ionizing radiation under an optional Contract Line Item Number (CLIN) to qualified offeror(s) in the Advanced Development of their product.

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 contain a base period of five years (60 months).

a. This is a Multiple Award Indefinite Delivery/Indefinite Quantity contract as contemplated by FAR 16.5. The Contractor shall be reimbursed by the Government in an amount not less than a total of $500,000 (minimum) or more than a total of $ TBD (maximum) for successful performance of this contract.

b. The [costs/prices] set forth in this SECTION will cover the contract period through .

c. The Government will issue [Task/Delivery] Orders based on the work described in SECTION C of this contract and the following schedule. Upon delivery and acceptance of the item(s) described in each Task/Delivery Order, the Government shall pay to the Contractor the [unit price(s)/costs] set forth below:

Example:

CLIN# Cost Type Supply or Service Qty* Unit

Price/dose Extended

Price 0001 FFP Acquire and USG access to G or GM-CSF products as described in SECTION C **

TBD TBD TBD

* The USG may order up to a maximum of up to 2.79 million unit doses as a part of the base period.

** Offeror shall propose a delivery schedule that may be subject to negotiation. The schedule for delivery of the product shall be set forth in SECTION F of this contract.

d. Payments will be made from the following Line Items as follows:

Line Item No. Line Item

Description Line Item

Period of Performance Funded Amount

e. Ordering procedures are described in SECTION G.4. of this contract.

B.3. OPTION PRICES

The final contract will contain the price/cost provisions for Options agreed upon by the Government and the Offeror.

Below is a list of possible Optional CLINs; the final contract will contain Optional CLINs agreed upon by the Government and the Offeror:

Optional

CLIN #

Cost Type

Description of Option Item(s) -or- Option Service(s)

Quantity (Units)

Unit Price

Total Price of Option

0002 FFP Acquire and USG access to additional G & GM-CSF products as described in

SECTION C.4.

TBD TBD TBD

0003 FFP Inventory management as described in

SECTION C.5.

TBD TBD TBD

0004 FFP *Distribution and Shipping of products (VMI) in a declared emergency as described in SECTION C.6. (FOB Destination)

TBD TBD TBD

FFP Prepare product stored as VMI for pick up by the USG as described in SECTION C.7. (FOB Origin)

TBD TBD TBD

* For purposes of proposing shipping prices, the Offeror shall use a uniform cost assumption of shipping from its manufacturing/storage facility to a destination approximately 2400 miles away.

Optional

CLIN #

Cost Type

Description of Option Item(s) -or- Option Service(s)

Estimated Cost

Fixed Fee

Total Estimated Cost Plus Fixed Fee

CPFF

Advanced Development of an elected cytokine for studies leading to an FDA licensure for the indication of mitigation of neutropenia arising from exposure to ionizing radiation

TBD TBD TBD

B.3.1. Firm Fixed Price Options

B.3.1.1. Option to purchase additional product (CLIN 0002)

The USG may exercise this optional CLIN to purchase additional product.

The Offeror shall submit a plan and schedule for additional drug product manufacture and control at large-scale production and under cGMP compliance to provide access to up to 2.79 million doses.

The plan shall provide unit dose prices for additional doses so that the USG has the option of ordering additional doses in increments of 1000 doses. Offeror shall propose volume discounts of G or GM-CSF products as described in SECTION C in increments of 100,000 unit doses up to 2.79M unit doses. Additional product purchases shall be initiated by exercising an option for incremental purchase(s) of product at the price(s) negotiated at contract award.

B.3.1.2. Option to purchase additional VMI (CLIN 0003)

The USG may exercise this optional CLIN to purchase VMI for additional storage of product in monthly increments.

B.3.1.3. Option to purchase distribution and shipping of product upon a declared emergency

(CLIN 0004)

The USG may exercise this optional CLIN for a requested number of doses to be delivered to the location of the emergency as requested by the Contracting Officer in the Notification of Release of Product for each shipment (see SECTION C.5.3.).

B.3.1.4. Option to prepare product stored as VMI for pick up by the USG (CLIN 0005)

The USG may exercise this optional CLIN for a requested number of doses to be picked up by the USG from the VMI as requested by the Contracting Officer, or by an individual designated by the Contracting Officer, in the Notification of Release of Product for each shipment.

a. Unless the Government exercises its option pursuant to the option clause referenced in SECTION

I.3. Additional Contract Clauses, this contract consists only of the base award.

b. The Government may, by unilateral contract modification, require the Contractor to perform the Option(s) listed in the table below. Pursuant to FAR 52.217-7 Option for Increased Quantity – Separately Priced Line Item, if the Government exercises this/these option(s), notice will be given 30 days before exercising the Option. The fixed price of this contract will be increased as set forth in paragraph c., below.

c. Upon the delivery and acceptance of the [Option Item/Option Items/Option Service/Option

Services] identified in the schedule of charges below, the Government shall pay the Contractor the unit price(s) set forth below:

B.3.2. Cost Reimbursement Options

B.3.2.1. Option to fund advanced development (CLIN 0006)

The USG may fund the advanced development of an elected cytokine for studies leading to FDA licensure for the indication of mitigation of neutropenia arising from exposure to ionizing radiation.

The Offeror shall provide the USG, under an agreed upon level of funding (Cost Reimbursement) with a compendium of studies which may provide sufficient evidence of efficacy and safety to allow for the USG to place the product under consideration for potential use in a declared emergency under Emergency Use Authorization (EUA; see guidance documents at FDA web site).

The following will be included in the contract for any Cost Reimbursement options:

a. The estimated cost of the Optional CLIN of this contract is $ .

b. The fixed fee for the Optional CLIN of this contract is $ . [For completion contracts: The fixed fee shall be paid in installments based on the percentage of completion of work, as determined by the Contracting Officer. / For level of effort contracts: The fixed fee shall be paid in direct ratio to the level of effort expended; that is, the percent of fee paid shall be equal to the percent of total effort expended.] Payment shall be subject to the withholding provisions of the clauses ALLOWABLE COST AND PAYMENT and FIXED FEE referenced in the General Clause Listing in Part II, SECTION I.1. of this contract.

c. The total estimated amount of the contract, represented by the sum of the estimated cost plus the fixed fee for the Optional CLIN is $ .

d. If the Government exercises its option pursuant to the OPTION PROVISION in SECTION H of this contract, the Government's total estimated contract amount represented by the sum of the estimated cost plus the fixed fee will be increased as follows:

Estimated Cost ($) Fixed Fee ($) Estimated Cost

Plus Fixed Fee ($) Base Period Option (s):

Total [Base Period and Option(s)]

e. Payments will be made from the following Line Items as follows:

Line

Item No.

Cost Type

Option/Increment Description Line Item Period of

Performance

Funded Amount

B.4. CONTRACT TYPE

The Government intends to award one or more indefinite-delivery, indefinite-quantity (IDIQ) contract(s). During the period of performance of the contract, the contracting officer assigned to the contract may order, and the Contractor shall provide, supplies and services at the unit price listed above. Delivery orders and task orders issued under this contract will be Firm-Fixed Price (FFP) or Cost Plus Fixed Fee (CPFF). See SECTION G.4. for Ordering Procedures.

B.5. ADVANCE UNDERSTANDINGS

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

B.5.1 Specific Cost Elements

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

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) Travel Costs;

e) Consultant Costs;

f) Subcontract Costs;

g) Patient Care Costs; and

h) Accountable Government Property

SECTION C – STATEMENT OF WORK (SOW)

C.1. INTRODUCTION

As outlined in the National Strategy to Combat Weapons of Mass Destruction (WMD) (December, 2002), the three pillars of the U.S. strategy are 1) counter-proliferation to combat WMD use, 2) strengthen non-proliferation to combat WMD proliferation, and, 3) consequence management to respond to WMD use. The intent of this RFP is, in part, to address pillar 3.

The Office of the Assistant Secretary for Preparedness and Response (ASPR) within the HHS plans to acquire (purchase) and arrange for USG access to a granulocyte or granulocyte-macrophage colony stimulating factor cytokine (i.e., G- or GM-CSF) for use as a medical countermeasure (MCM) that can specifically treat neutropenia arising as a pathology of bone marrow injury that may be a consequence of a mass casualty event. Neutropenia is a blood dyscrasia pathology that can follow acute exposure to certain chemical agents or following a generalized whole body exposure to high doses of ionizing radiation (IR). The condition needs to be addressed by normalizing blood counts, specifically neutrophils, within days of the exposure to prevent infection from opportunistic bacteria which can bloom under conditions of immunosuppression. Efficacy of the product will be determined only in terms of treating neutropenia or the ability to shorten or reduce time to neutrophil recovery under the respective licensed indications.

C.2. BACKGROUND

Weapons of Mass Destruction as listed by the Department of Homeland Security (DHS) provide a wide range of biologic effects. Neutropenia is an effect that may arise following exposure to ionizing radiation (i.e., gamma, beta, alpha, or x-rays) or radionuclides with sufficient energy, and range of their energy-releasing disintegrations, to induce cellular damage or exposure to and absorption of certain chemicals that can injure the hematopoietic system. While radiation industry accidents have been the prevailing source of human radiation injuries in the last half-century, the intentional use of a chemical weapon or radiological or nuclear device to cause injury has become an unfortunate possibility. DHS lists radiological/nuclear threats as risks for hematopoietic, pulmonary, cutaneous or gastrointestinal injury. The radiologic threats include: 1) an attack on nuclear power plants or spent fuel storage facilities; 2) a malevolent act exposing individuals to radiation sources placed in public locations (radiological exposure device, RED; example: Ir-192 gamma sources for industrial imaging, i.e., detection of cracks in bridge struts, etc.); 3) use of a radiological dispersal device (RDD), such as a “dirty bomb” (isotope dispersal), although other means of dispersion may be encountered; 4) contamination of food or water supplies; or 5) use of an improvised nuclear device (IND) or a military nuclear weapon. In each of these risk categories the predominant early onset injury is neutropenia.

ASPR, working through the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) and the Biomedical Advanced Research and Development Authority (BARDA), has established a drug and biologics development program with a portfolio of products that are under aggressive and rigorous advanced development programs to meet the requirements established for HHS to serve as medical countermeasures for the DHS threat assessments. Upon demonstration of required efficacy and safety, HHS can subsequently procure products for the SNS, thereby establishing initial stockpiles of drugs, biologics, medical supplies, etc., needed for federal emergency preparedness.

Consistent with the PHEMCE Strategic Plan for medical countermeasure (MCM) preparedness, the USG seeks to acquire and arrange access to a specific class of MCMs that will be clinically useful in the recovery of blood cell (specifically neutrophil) counts and function, following a civilian public health medical emergency where bone marrow injury is a consequence, such as in a radiation or nuclear event. This Request for Proposals (RFP) is intended to solicit proposals either from companies that are marketing, in the United States, G- or GM-CSF (or PEGylated forms of the same) for the treatment of neutropenia, or to shorten or reduce time to neutrophil recovery; or from distributors with contractual relationships with CSF manufacturing companies. G- or GM-CSF cytokine therapy, as a clinical treatment for neutropenia, is well established and is recognized as a preferred treatment for adults, as well as children. The G- and GM-CSFs are unique to our needs and concepts of operation, as no other alternative drugs or biologics are currently approved to shorten or reduce the time to neutrophil recovery. This contract is required to support the agency’s response to National emergencies. This contract establishes the Vendor-Managed Inventory (VMI) requirements under which the Contractor shall maintain and provide availability of the products and quantities cited herein 24 hours a day, 7 days a week (24/7). If any, or all, of the specified product under this contract is released at the request of the Government in support of a national emergency, the Government will issue a Notification of Release of Product in accordance with the contract.

C.3. SCOPE AND REQUIREMENTS

Independently and not as an agent of the Government, the Contractor(s) shall be required to furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government, to meet the requirements of the contract.

C.3.1. Scope

1) CLIN 0001and CLIN 0002: Acquire and provide USG access to an FDA licensed G- and/or GM-CSF product for use in a mass casualty event where neutropenia or neutrophil loss is a major concern. The product selected will be procured in stages, e.g. initial purchase of “X” adult daily doses (unit doses1) plus additional deliveries all over a 5-year period to procure a total of up to 2.79 million unit doses; and/or

2) CLIN 0003: For the Contractor(s) to provide, as part of the contract, a VMI program for the specified products in which the Contractor shall monitor and maintain specified inventory levels and product shelf life. Provide the availability of shipments 24 hours a day, 7 days a week, 365 days a year and shall be able to deploy as requested. An inventory management plan shall be provided by the Contractor(s) and shall also include a plan to provide the USG with an accurate inventory of product as well as location(s) should the USG have an immediate need for product in an emergency situation. The Contractor shall participate in simulated deployment exercises. The Contractor's plan to provide access to the product as needed by the USG and the Quality Agreement with the CDC/SNS (see Attachment 10) shall be negotiated to align with the USG’s specific product use during a mass casualty event. In order to meet the above objectives, the Contractor shall have evidence that the labeling, storage, distribution and transport programs are secure and controlled.

1 A unit dose for the purpose of this solicitation is an adult daily dose and not a multi-dose vial. A product that requires less than daily dosing, i.e. a PEGylated cytokine, shall be termed an equivalent to seven daily doses.

Contract Options (CLIN 0006) are available for the advanced development of an elected cytokine for studies leading to an FDA licensure for the indication of mitigation of neutropenia arising from exposure to ionizing radiation. The Contractor shall provide the USG, under an agreed upon level of funding, with a compendium of studies which may provide sufficient evidence of efficacy and safety to allow for the USG to place the product under consideration for potential use in a declared emergency under Emergency Use Authorization (EUA; see guidance documents at FDA web site).

C.4. PRODUCT REQUIREMENTS (CLINs 0001 & 0002)

The material deliverable under this RFP is a G- or GM-CSF formulated cytokine product. This product shall be held in Vendor Managed Inventory (VMI) or other managed inventory systems, until such time it is requested by the USG for emergency use and transfer to USG custody. All line item inventory levels shall be maintained at 100% availability of the USG acquisition. In the event of a shortfall below 100%, the Contractor shall notify the CO, COR and/or other officials as designated by the CO, within 2 business days and provide a plan that ensures 100% inventory availability level within 5 calendar days. If replenishment will require more time, the Contractor shall notify the Contracting Officer (CO), Contracting Officer’s Representative (COR) or other officials as designated by the CO, of required time.

If the need for product release/deployment arises, the authorization procedures in Notification of Release of Product shall be followed.

In the event the Government requires deployment of all or any portion of the required inventory level, the Government shall then provide the Contractor with a Contracting Officer or designee’s Notification of Release of Product reflecting the procurement of the quantity and product(s) released/deployed.

A minimum of 6 months remaining on product shelf life at time of product release/deployment is required.

Descriptions of material transfer will be specified in a Quality Agreement between HHS [Centers for Disease Control and Prevention, Strategic National Stockpile (CDC/SNS)] and the Contractor.

Sample items in a Quality Agreement are provided as Attachment 10 in SECTION J.

C.4.1. The USG is seeking to purchase up to 2,790,000 doses of a G- or GM-CSF (Colony

Stimulating Factor) for the treatment of individuals who are suspected of having an absorbed dose exceeding 2 Gy for adults and 1.5 Gy for children (<18 yrs). The cytokine shall be acquired by HHS under a vendor-managed inventory (VMI), or other acceptable structured plan, within the anticipated period of performance of the base contract (5 years). At the Government’s sole discretion, the base period may be extended, during performance, pursuant to the additional time parameters set forth in the Project BioShield Act of 2004.

Contractors however shall base their technical proposals on the five-year base contract period of performance contained in this solicitation. Offeror(s) shall propose a delivery schedule that may be subject to negotiation. The schedule for delivery of product will be incorporated into the final contract.

C.4.2. The USG seeks offers for FDA-approved anti-neutropenia cytokine. The finished drug product (FDP) shall be packaged in single unit dose syringes or vials or other approved packaging, and potentially as full treatment course packaging, 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.

C.4.3. The G- or GM-CSF cytokine shall indicate the dosing schedule per the approved indication.

This may be a maximum treatment course of one unit dose per day administered for up to 14 days, or, as a PEGylated product which is, for purposes here, equivalent to seven adult doses of the standard product.

C.4.4. Since no G- or GM-CSF is approved for radiation-induced neutropenia, the initial approved label indication shall be for treatment of neutropenia in symptomatic adults (18-64 years general population) and children (<18 years with dosage adjustment based upon the Contractor’s product’s Package Insert and medical practice for the cytokine in children afflicted with neutropenia).

C.5. VMI REQUIREMENTS (CLIN 0003)

C.5.1. General VMI Requirements

a. Within 15 days of the signing of this contract, the Contractor shall provide a listing of the names, titles and telephone numbers (non-emergency and emergency) of its key personnel who should be contacted for USG visits, inventory status, and access to and/or deployment of product, and a simulated deployment of the product(s), during normal and after business hours. The Contractor shall notify by telephone and provide the CO and COR in writing any future updates or changes to the listing within 24 hours of making the update or change.

b. Within 30 days of the signing of this contract, the CO will identify to the Contractor those representatives authorized by the Government as requiring access to the Contractor’s VMI facility(s) for inspection of VMI product availability. The CO shall then notify the Contractor via telephone and in writing of any updates or changes to that list within 24 hours of any such updates/changes.

c. The Contractor shall allow announced and unannounced visits to its VMI facility(s) by Government personnel for the purpose of inspection and the review of the required product inventory levels. Quality assessments of Contractor’s facility and quality systems shall undergo an initial qualification audit. The CO will provide the Contractor with a minimum of a 24-hour advance notice of any announced visits. A Quality Assessment agenda shall be provided prior to the assessment date. Upon completion of the assessment, the Government shall provide to the Contractor a written Quality Assessment Report summarizing all findings and recommendations. The Contractor shall provide a written response addressing each finding/recommendation within 30 calendar days from the date report is received by the Contractor. The Contractor shall provide additional information and/or clarification regarding the assessment findings as requested by the Government. Government will limit visits to no more than 2 per year, per facility, provided that each visit is uneventful. All visits, announced and unannounced, will be limited to normal business hours.

d. The Contractor shall be responsible to notify the CO and COR immediately of any notice of inspection and unscheduled inspections or actions by regulatory agencies, other enforcement agencies (e.g., FDA, DEA, OSHA), and third party Contractors that may involve and/or impact Government-owned products. The Government shall be permitted to delegate at least two persons to observe the inspection. The notifications should be sent electronically to the CO, COR or other officials as designated by the CO.

e. The Contractor shall make all directed mutually agreed upon changes as soon as possible, but no later than 15 days from the Government’s identification of problems regarding storage, inventory management, or other discrepancies identified through scheduled or non-scheduled storage sites visits, or by other means of acknowledgment.

f. Should the Government’s requirements decrease or increase, the Government will inform and instruct the Contractor to adjust the amount of product held so as to achieve the new requirement level. Upon any decrease or increase to the required inventory levels that results in the total inventory value being changed, the resultant VMI fees shall be adjusted accordingly.

g. Should the Government’s requirement for certain National Drug Codes (NDC) change, the Government reserves the right to submit a request, in writing to add or delete NDCs. All changes of this nature shall be mutually agreed upon via a written modification of this contract. Product additions shall be subject to a 60 day implementation period to achieve full required inventory availability level.

h. If a product covered under this contract is discontinued or the regulatory status of a product changes (e.g. from “prescription” to “over-the counter” or other change in approval status), or if Contractor no longer markets, co-markets or sells a product, the Contractor must notify the CO, COR and/or other officials as designated by the CO in writing, and request that the product be deleted from this contract.

i. Contractor shall be a participant in simulated exercises with the USG. The USG anticipates not more than one such exercise during a 12-month period which would involve the Contractor to participate in a teleconference and provide information pertaining to the product stored in the VMI and its deployment during an emergency.

j. In the event of a drug recall, Contractor shall notify the CO, COR and/or other officials as designated by the CO, in writing within 24 hours.

C.5.2. Additional VMI Services

The VMI program shall include storage, holding, inventory management, quality control, stock rotation, secure safe keeping and possible deployment of the product(s).

C.5.2. 1. The Contractor shall establish and maintain inventory, maintain shelf life criteria, and provide quality control of product as necessary in accordance with cGMP federal regulations to ensure that the Government is provided 24/7 availability of the product(s) as necessary to support emergency situations. Storage of the product at the Contractor’s facility(s) shall be in a secured and properly temperature controlled area. Any stored product must maintain minimum shelf life expectancy as agreed upon and described within this contract. It is expected that any stored product shall be rotated with the Contractor’s commercial stock in order to maintain the minimum shelf life expectancy agreed upon and described within this contract.

Inventory shall be located in any or all of the manufacturing plants or warehouses. All inventories at those locations will be shipped on a “First In, First Out” basis, ensuring the most recent dating of inventory for VMI target inventory.

C.5.2. 2. The Contractor's product must be approved for clinical indications, and a plan and operational consideration shall be in place that ensure the product will be stored and shipped in compliance with cGMP. A summary describing validated storage conditions as they relate to storage in a Vendor-Managed Inventory (VMI) shall be provided in the Offeror’s proposal.

C.5.2. 3. The Contractor shall provide their FDA approved quality control/quality assurance monitoring plan that shall ensure appropriate storage conditions of the product while being held for the USG and this shall include the assurance of monitoring in the VMI holdings and in accordance with the Quality Agreement with the USG. In addition, this Quality Agreement shall outline the responsibilities of both the Contractor and the USG (i.e., CDC/SNS–Quality Control and ASPR) for event-driven product custody by the USG. These documents shall be drafted and signed by all parties prior to the transport and custody of the product under the VMI or the USG.

C.5.2. 4. The Contractor shall develop an inventory plan that meets the objectives of this contract. The Offeror shall propose a product inventory schedule that front loads the level of product available to the USG. As an example, the Offeror may propose a first year holding of 700,000 unit doses and four subsequent years adding 700,000, 600,000, 500,000 and 290,000 unit doses, respectively. The Offeror may propose an alternate schedule. The Contractor shall store FDP at an appropriate cGMP compliant facility.

C.5.2. 5. At the discretion of the USG and independent of quality testing conducted by the Contractor, the USG reserves the right to conduct inspections and collect samples of product held by the Contractor at the manufacturing facility(s), satellite sites, or under the VMI.

C.5.2. 6. A specific place of performance is not necessary for the accomplishment of this contract, other than that the site(s) must be within the continental United States. It will be necessary for the Contractor to store the product in one or more locations that allow it to be shipped to the site(s) of an emergency within hours.

C.5.2. 7. Upon expiration or termination (including partial termination) of this contract, the USG may effect final distribution of any inventory on this contract, and remaining in storage at the Contractor’s facility by any one or combination of the following methods:

a. The USG may elect to direct the Contractor to ship to a consignee(s) designated by the USG, all products remaining in storage at the Contractor’s facility.

b. The USG may offer the drug to be repurchased by the Contractor at the original purchase price.

c. The USG may request disposal of unshipped products stored at the Contractor’s facility.

C.5.3. Notification of Release of Product

Notification to release product(s) under this contract shall be submitted in writing to the Contractor by the Contracting Officer, or as designated by the Contracting Officer.

a. The Government will periodically provide the Contractor with a current list or memo identifying the personnel authorized to release product.

b. The USG representative(s) named in the list are authorized to request a release/deployment of product(s). No other person shall be entitled to authorize a release/deployment of product(s) unless the Contractor has been advised in advance, in writing by one of the approved USG representatives as to the addition/change in authorized representatives. All authorizations for release of product for deployment will be confirmed by an authorized USG representative. In addition to the issuance and the standard requirements of the USG’s requisition form, a valid request for the release of product shall be established after the contract is awarded.

c. The Contractor shall acknowledge the Government’s request for deployment within 30 minutes of notification by the Contracting Officer (CO) or CO authorized USG personnel who have contacted the Contractor.

d. The Contractor shall be responsible for the packing, palletizing and preparation of the product for shipping and deployment including any necessary shrink wrapping and loading of the product into the transportation vehicles that have been arranged for and paid for by the Government.

e. The Contractor shall provide, at USG request, sufficient climate controlled and non-climate control trucking capability for routine movement of USG assets, 24 hours per day 365 days per year, throughout the continental United States.

f. The Contractor shall provide the USG transportation reports (such as order confirmation, pick-up notification, proof of delivery) and monthly completion reports (showing all data such as run number, pick up date and time, and final costs) to the CO and COR via email or approved courier services.

C.6. DISTRIBUTION AND SHIPPING SERVICES (CLIN 0004)

The USG may exercise optional CLIN 0004 for a requested number of doses to be delivered to the location of the emergency as requested by the CO or designee in the Notification of Release of Product for each shipment.

The Contractor shall perform the following activities for distribution. Following the completion of packaging the product into cartons and master cartons, the master cartons shall be palletized in a pattern suitable for storage and eventual shipment. The pallet pattern shall be standardized for each product type such that the quantity shall be uniform across all full pallets in a lot. The master cartons on the full pallets and partial pallets, if one exists, shall be securely stretch wrapped to the pallet itself in order to prevent damage in transit.

At the time of shipping, a temperature recorder (preferably a TempTale) shall be placed on each pallet. The temperature recorder shall have alarm limits set based on the established temperature parameters and they shall be activated when the pallets are placed on the trucks that have been pre-cooled to their target temperature prior to loading. After loading, numbered seals shall be affixed to the cargo doors and the numbers entered on the bill of lading.

The Contractor shall be responsible for delivering Government-owned product in a condition fit for its intended use to shorten time to neutrophil recovery and reduce the incidence of severe and life-threatening infections and infections resulting in death.

C.7. PACKAGE PRODUCT FOR PICKUP BY THE USG (CLIN 0005)

The Contracting Officer may request the Contractor to transfer product to the USG for pick up at the Contractor’s VMI facility(s). The Contractor shall perform the following activities to prepare the product for pickup by the USG. Following the completion of packaging the product into cartons and master cartons, the master cartons shall be palletized in a pattern suitable for storage and eventual shipment. The pallet pattern shall be standardized for each product type such that the quantity shall be uniform across all full pallets in a lot. The master cartons on the full pallets and partial pallets, if one exists, shall be securely stretch wrapped to the pallet itself in order to prevent damage in transit.

The product shall be inspected and accepted by the USG at the VMI facility(s) prior to being transferred to the USG. USG will formally transfer possession, title and custody transfer of the product at the Contractor’s VMI facility; the USG will be responsible for all shipping costs and handling all shipping/logistics.

C.8. OPTIONAL ADVANCED DEVELOPMENT (CLIN 0006)

It is the requirement of this contract to obtain licensed products which have the indication of treatment of neutropenia (regardless of cause). No product currently holds a US license for the indication of neutropenia arising from exposure to ionizing radiation alone. Thus, the USG intends to fund the advanced development of G- and GM-CSF products for this new indication. Prior to the submission of the proposal, the Contractor must request regulatory consult with FDA on the appropriate path for approval of their respective therapeutic for use in the treatment of neutropenia arising from exposure to ionizing radiation. It is the requirement of BARDA to acquire one or more Colony Stimulating Factors (G- or GM-CSF) for mitigation of neutropenia arising from exposure to ionizing radiation.

The Contractor shall provide the USG with a compendium of already executed studies that may provide sufficient evidence of efficacy and safety (a CDC and FDA agreement) to use of the product in a declared emergency, and aid in taking the product to license or approval. The Contractor shall conduct additional animal and clinical studies which may be anticipated to be necessary for CDER/CBER to support approval/ licensure.

C.8.1. Regulatory, Non-Clinical, and Clinical Objectives

Contractor shall be responsible to maintain comprehensive Quality System programs which shall comply with all, applicable federal, state, and local regulations.

The Contractor shall submit evidence of an effective Quality Management System (QMS). The Contractor shall ensure that the details in the submitted proposal incorporate the QMS in all aspects of the proposal to fulfill the project objectives.

The Contractor shall develop, submit, and execute non-clinical and clinical study protocols, as determined by FDA, to support the potential use of the product in adults during a declared emergency. http://www.fda.gov/RegulatoryInformation/Guidances/ucm125127.htm

The Contractor shall inform BARDA of all communications with the FDA and provide all written communication from the FDA. The Contractor shall include the BARDA Contracting Officer’s Representative (COR) and subject matter experts as observers, in all scheduled phone calls or face-to-face meetings with the FDA

For the optional advanced development CLIN 0006, sufficient non-clinical and clinical study data shall be presented to support the use of the product per its intended label indication and in accordance with FDA guidance. The Contractor shall carry out an assessment of bioavailability in animals and humans.

http://www.fda.gov/RegulatoryInformation/Guidances/ucm125127.htm

The Contractor shall follow the advice and guidance from the FDA in the identification of parameters for validation of critical assays to support product development and subsequent approval of the product.

Contractor should identify studies that may be required to fulfill FDA requirements. The contractor will evaluate product efficacy in any additional NHP model that will provide further information in support of approval from the FDA.

The Contractor shall develop, submit, and execute non-clinical plans to demonstrate efficacy under the Animal Efficacy Rule and human safety and pharmacokinetic studies adequate to support FDA approval. The FDA has published "Approval of Biological Products when Human Efficacy Studies are not Ethical or Feasible" [21 CFR 601 Subpart H, as well as 21 CFR 314 Subpart I for New Drugs]. This rule, known simply as the "Animal Rule," was designed to permit approval or licensing of drugs and biologics that are intended to reduce or prevent serious or life-threatening conditions caused by exposure to biological, chemical, radiological, or nuclear substances. This rule amends the new drug and biological product regulations to identify the information needed to provide substantial evidence of the efficacy of new drug and biological products when human efficacy studies are not ethical and field trials are not feasible. The new rule does not address the need for human safety and pharmacokinetic data, which still must be established. When the Contractor develops plans for studies under the Animal Rule, the plans and studies shall be designed in consultation with appropriate USG agencies, and the data from these studies should support FDA approval of the product, as well as the potential use of the product in adults during a declared emergency. Further, these plans shall include studies to demonstrate safety and efficacy of an optimized dosing regimen, based on supporting data to justify such usage.

In addition, as promulgated under the Animal Rule, the Contractor shall develop a Phase 4 post-marketing plan/protocol when deemed appropriate by FDA to begin such a task for the collection of data to evaluate the safety and efficacy of the drug during its actual use. This “post-marketing plan/protocol” shall describe, in general terms, the method of collection of human safety and efficacy data when the product is used in the event of a declared emergency.