PWS_Broad_Panel_Sceening_Final_Revision_8_Sept_17).docx

Off-Target Broad Panel Screening of Novel Therapeutic Candidates

PERFORMANCE WORK STATEMENT (PWS)

1.0. INTRODUCTION

1.0.1. Since 1969, the U.S. Army Medical Research Institute of Infectious Disease (USAMRIID) has served as the Department of Defense's (DoD’s) lead laboratory for medical biological defense research. While its core mission is to protect the warfighter from biological threats, USAMRIID also investigates disease outbreaks and threats to public health. Research conducted at USAMRIID leads to medical solutions—therapeutics, vaccines, diagnostics, and information—that benefit both military personnel and civilians. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command at Fort Detrick, located in Frederick, MD.

1.0.2. Some of the most serious biothreat agents, such as alphaviruses, Burkholderia pseudo mallei, and Klebsiella pneumonia, there are still no Food and Drug Administration (FDA) approved therapeutic treatments available to the warfighter. Various programs at USAMRIID have focused on screening novel small molecule libraries in efforts to identify potential therapeutics to treat these biothreat agents. However, many compounds that are found to be active against biothreat agents in vitro do not selectively modulate a single pharmacological target at efficacious drug plasma levels in vivo. This ‘off-target pharmacology’ often either confounds the interpretation of in vivo results or leads to off-target toxicity, precluding if from further development. The most efficient way to asses a compound for off-target pharmacology is to test it for activity against a broad panel of receptors, channels and enzymes. The purpose of this requirement is to identify a source to conduct Broad Panel Screening to evaluate off-target pharmacology of compounds to support further evaluation of these molecules in vivo.

1.1. BACKGROUND: USAMRIID has an extensive program focused on the development of therapeutic medical countermeasures against high priority biothreat agents, including alphaviruses, Burkholderia pseudomallei, and emerging threat pathogens. This core team of individuals utilizes a pharmaceutical industry drug development model to design, screen and select those small molecules and multi-functional antibodies with the requisite properties to achieve regulatory approval from FDA. Key activities include the design of new chemical entities (NCEs), in vitro screening against a panel of biothreat agents and supporting activities, such as in vitro absorption, distribution, metabolism, and excretion (ADME), in vivo pharmacokinetics (pK), toxicology profiles, and proof-of-concept studies. In order to support these key activities, it will be necessary to evaluate potential off-target pharmacology of key compounds against a broad panel of receptors, channels, and enzymes; therefore, establishing a service requirement to conduct the broad panel screening is necessary.

1.2. SCOPE

Over a course of five years, USAMRIID is requiring Broad Panel Screening of up to 25 small molecule antibacterial and antiviral compounds. For compounds meeting in vitro pharmacology, in vitro ADME, in vivo pharmacokinetics and in vivo tolerability criteria, a ‘safety panel’ screen against 35~90 receptors, channels and enzymes with known safety liabilities is needed to down select preclinical candidates and inform toxicological experiments, particularly for pharmacological targets known to cause central nervous system (CNS) or cardio related side effects. In addition, compounds showing a proof of concept in animal models of infection may need to be tested in a broader screen of 90-140 receptors, channels and enzymes to determine pharmacological selectivity in support of Investigational New Drug (IND) submission and advanced development.

1.3. Organizational Conflict of Interest (OCI) (Deliverable 1, Exhibit 1). This contract will be used to procure U.S. Army Medical Research and Material Command (USAMRMC) OCI Category 3, Product Support that falls within the scope of the PWS. The contractor shall provide an OCI certification with their proposal. If there is an OCI, the contractor shall provide a draft OCI Mitigation Plan with their proposal.

1.4. Non-Disclosure Statement (NDS) (Deliverable 2, Exhibit 2). The contractor shall ensure that all contractor personnel are advised of nondisclosure policies as well as restrictions from communicating official business to media outlets. The contractor personnel may be required to sign specific non-disclosure statements as required by the contract. The contractor shall provide signed non-disclosure statements from each personnel assigned, prior to performing any services.

1.5. Contractor Requirements: Contractor shall:

1.5.1. Have Standard Operating Procedures (SOP’s) in place for performing screens for individual compounds against a broad panel of binding and functional assays.

1.5.2. Have a Quality Control Plan, including self-inspection plan, an internal staffing plan in place, including the inclusion of small molecule standards as controls for validating each assay.

1.5.3. Have a Chemical Hygiene Plan and all relevant safety SOP’s in place.

1.5.4. Have the proper facilities, infrastructure, instrumentation and equipment to carry out requested broad panel screening.

1.5.5. Have existing binding assays available in predefined panels or existing binding assays that can be selected for custom panel development. Contractor shall also have the capability to evaluate functional activity (e.g. agonist versus antagonist) for pharmacological targets within the broad panel screen.

1.5.6. Safety binding assay panels (35-90 assays) should include human targets where possible, and should appropriately span the following targets: adenosine, adrenergic, angiotensin, bradykinin, cannabinoid, chemokines, cholecystokinin, dopamine, endothelin, gamma-amino butyric acid (GABA), glutamate, histamine, leukotrienes, melanocortin, muscarinic, neurokinin, neuropeptide Y, opioid, platelet activating factor, serotonin, vasopressin, adenosine transporter, dopamine transporter, GABA transporter, norepinephrine transporter, serotonin transporter, GABA channels, glutamate channels, glycine channels, nicotinic channels, serotonin channels, calcium channels, sodium channels, non-steroid nuclear receptors, steroid nuclear receptors, protein tyrosine kinases, protein-serine/threonine kinases, cyclooxygenases, ATPase, monoamine and neurotransmitter enzymes, phosphodiesterases, proteases and acetylcholinesterase.

1.5.7. Broader Panel Screens (90-140 assays) shall include all of the targets within the ‘Safety Panel’, but with an expanded scope (e.g. inclusion of metalloproteases, bradykinin, NO synthases, and others) and include additional receptor subtypes.

1.5.8. Have a demonstrated ability to perform Broad Panel Screening of novel compounds in a timely manner (3-4 weeks turnaround of data from the receipt of compound).

1.5.9. Provide a team of experienced Pharmacologists and Biochemists with specialized experience in therapeutic drug development. At the bench, each with either a MS or PhD degree should have at least 2 years of experience. Contractor shall provide a Program Manager to oversee the other personnel, recommend either a PhD Pharmacologist or Biochemist with at least 8 years of experience with in vitro pharmacological assay development.

SECTION 2 GENERAL REQUIREMENT

2.0. Performance

2.0.1. Place of Performance. All services shall be performed at the contractor facility and location.

2.0.2. Period of Performance. This contract is for one (1) twelve (12) months Base Year and four (4) twelve (12) months option years. The periods of performance for this contract are as follows:

2.1. Non-Personal Services

This PWS identifies services that are strictly non-personal in nature, as defined by Federal Acquisition Regulation (FAR) Part 37, Service Contracting. To ensure there is no appearance of any personal services, the Government shall neither supervise contractor personnel nor control the method by which the contractor performs the required tasks. Under no circumstances shall the Government assign tasks or prepare work schedules for individual contractor personnel. It shall be the responsibility of the contractor to manage its personnel and to guard against any actions that give the perception of personal services. If the contractor believes that any actions constitute, or are perceived to constitute personal services, it shall be the contractor's responsibility to notify the Contractor Officer (KO) immediately.

2.2. Contract Management

2.2.1. Government Management. The Contracting Officer’s Representative (COR) and Alternate Contracting Officer’s Representative (ACOR) for this contract will be appointed by the Contracting Officer (KO). The COR will serve as the primary point of contact for all activities and issues that occur under this contract. In the event that the COR is not available, the ACOR will assume the COR’s responsibilities.

2.2.2. Contractor Management. The contractor shall designate a single Program Manager (PM) to be the contractor’s authorized point of contact (POC) with the COR. The PM will be responsible for formulating and enforcing performance standards, assigning contractor schedules, reviewing performance quality, communicating policies, purposes, and goals to subordinates. This will include coordination with the KO and the COR to resolve any issues that may arise, trends relating to the contract, or proposed changes or modifications to the contract. The PM shall demonstrate capability in the overall management of complex tasks, and strong team building skills.

2.2.2.1. The contractor shall establish clear organizational lines of authority and responsibility to ensure effective management of the resources assigned to the requirement. The contractor shall ensure that all contractor personnel are advised of their chain of command and who they should contact if they have questions.

2.2.2.2. The contractor shall provide a draft Quality Control Plan (QCP) (Deliverable 3) with their proposal and a final QCP no later than 15 days after contract award. The contractor shall prepare and adhere to a QCP describing how the contractor intends to manage the contract to achieve the established standards set forth in the Performance Standards Summary Matrix and the contractor’s QCP.

2.2.3. Subcontract Management. The subcontractor shall be:

2.2.3.1. Responsible for any subcontract management necessary to integrate services performed on this contract.

2.2.3.2. Responsible and accountable for subcontractor performance on this contract.

2.2.3.3. Responsible to manage task distribution to ensure there are no OCI considerations.

2.2.3.4. Contractors may add subcontractors to their team after notification and approval from the PCO and COR. Cross teaming shall be permitted.

2.3. Reports

2.3.1. Reports and documents delivered by the contractor in the performance of this contract shall be considered Technical Data as defined in the applicable FAR clause 52.227-14, Rights in Data. All documentation shall reflect the latest version of the work product or activity, unless specifically directed otherwise by the Government. All documentation shall be prepared in accordance with (IAW) standard industry practices, ensuring electronically produced documents which reflect logical flow of material, tables of contents indexes and page numbering. Where applicable, the contractor’s attention is called to the availability of commercial, industry, federal, and military guides, instructions, and standards for many of the topics addressed in this PWS and under this contract.

2.3.2. Monthly Financial Tracking Report (Deliverable 4). The contractor shall provide a spreadsheet with detail of real time expenditure levels of every contract line item number (CLIN). The initial report is due 45 days after contract award and monthly thereafter.

2.3.3. Contract Manpower Reporting (Deliverable 5). This is a mandatory requirement IAW Army Federal Acquisition Regulation Supplement (AFARS) 5137.91, Accounting for Contract Services.

The contractor shall report ALL contractor labor hours (including subcontractor labor hours) required for performance of services provided under this contract for the USAMRIID via a secure data collection site. Reporting inputs will be for the labor executed during the period of performance during each Government fiscal year (FY), which runs October 1 through September 30. While inputs may be reported any time during the FY, all data shall be reported no later than October 31 of each calendar year, beginning with 2013. The contractor is required to completely fill in all required data fields using the following web address: http://www.ecmra.mil.

The four service specific CMRA systems have been merged into one combined application. All user accounts and system data were transferred to the new consolidated Enterprise Contractor Manpower Reporting Application (ECMRA) at:

http://www.ecmra.mil.

Contractors may direct questions to the new ECMRA Support Desk at dod.ecmra.support.desk@mail.mil or obtain detailed instructions from the CMR User Guide available on the new ECMRA website www.ecmra.mil.

2.4. Training Requirements

2.4.1. Contractor Attendance at Government Training Opportunities. The Government may require contractor attendance at Government provided or Government sponsored training offered by the Research, Development and Acquisition Support Office, or as outlined in the current version of USAMRMC Command Policy Memorandums “US Army Medical Research and Materiel Command (USAMRMC) Decision Gate (DG) Training Requirements” and “Requirement for Training of Personnel Involved in Food and Drug Administration (FDA)-Regulated Activities”. These training opportunities will be provided via web-based offerings, at on-site classroom settings or at local venues that will not otherwise incur travel expenses by the attendee. The Government determination for contractor attendance at one or more of the aforementioned training opportunities will be based on the applicability of the specific training opportunity to tasks being performed in this PWS and the above referenced USAMRMC Command Policy Memorandums. The COR will document all government training determinations made for each contractor employee performing under this contract as well as training opportunity attendance/completion.

2.5. Contractor Hours

2.5.1. Duty Hours.

2.5.1.1. Contractor personnel shall perform services during regular duty hours.

2.6. Travel/Temporary Duty (TDY)

2.6.1. Travel Process.

2.6.1.1. The Government is not authorizing travel for this effort. Contractor shall be able to meet by other means of communication, such as telephonic, audiovisual, or other electronic communication system.

SECTION 3 PERFORMANCE REQUIREMENTS

3.0. The contractor shall provide all necessary personnel required to perform ADME Evaluation of Novel Therapeutic Candidates Services at USAMRIID. The following section specifies the Performance Objectives and Elements for this requirement.

3.1. TECHNICAL / PERFORMANCE REQUIREMENTS

3.1.1. BASE YEAR (1 October 2017 – 30 September 2018) (12 months)

3.1.1.1. Objective: Contractor shall evaluate up to 3-4 novel small molecules against 35-90 targets with known safety liabilities, and 1-2 compounds against an expanded set of 90-140 targets capable of defining a compound’s off-target pharmacology profile. The number of compounds to be evaluated may be increased by USAMRIID in the Base Year.

3.1.2. OPTION YEARS (Years 1, 2, 3, and 4, (12 months each)

3.1.2.1.Objective: Contractor shall continue to provide support for evaluation of small molecules against broad panel screens. The number of compounds to be evaluated may be increased by USAMRIID in the option years, but will not exceed 25 compounds tested in 5 years.

3.2. USAMRIID will use the broad panel screen results to:

3.2.1. Evaluate potential off-target activity that presents a safety concern at concentrations within 10 fold of the EC90.

3.2.2. Guide experiments to define a compound’s mechanism of action.

3.2.3. Select compounds to test in animal models of infection to evaluate their in vivo efficacy and protection against Burkholderia pseudo mallei (Bp), Klebsiella pneumonia (Kp), and various viral targets including Alphaviruses.

3.2.4. Select compounds for preclinical development.

3.3. Performance Requirement Summary Matrix:

3.4. DELIVERABLES

3.4.1. The Contactor evaluate up to 5 small molecule compounds in the Base Year, as described in Technical/Performance Requirements, paragraph 3.1 above; and up to 25 novel small molecules within 5 years.

3.4.2. The Contractor shall meet the objectives of this requirement as stated in the Technical/Performance Requirements, paragraph 3.1 above for the Base Year and option years.

3.4.3. Data: Contractor shall electronically provide a report of all completed analyses to USAMRIID within 4 weeks of receiving compound. (Deliverable 6)

3.4.4. The COR will submit to the Contract Specialist and Contracting Officer a monthly report concerning performance of services rendered under this contract based on paragraph 3.5 below: Quality Assurance Surveillance Plan, as described in Attachment A. (Deliverable 5)

3.4.5. The Contractor shall report contract‐related information in accordance with the Contractor Manpower Reporting (CMR) clause by 31 October of each year to the CMR website at: https://cmra.army.mil.

3.5. QUALITY ASSURANCE SURVEILLANCE PLAN (QASP)

3.5.1. Every DoD contract awarded for services in excess of $2,500.00 shall contain a Quality Assurance Surveillance Plan (QASP) as discussed in the FAR 46, Government Contract Quality Assurance. A QASP is a plan that specify the particular services the COR will inspect and the method(s) used to complete that surveillance. Each offeror shall digest the PWS in this RFP and offer a QASP associated therewith. The QASP shall be submitted as part of the offeror’s technical proposal. It will not be subjectively evaluated and rated. However, it may be discussed during the pre-award period for finalization prior to its inclusion in the awarded contract.

3.5.2. The QASP is a tool used by the Government (i.e. COR) as a way to assess contractor performance. The following performance based service acquisition items will be monitored under this QASP and shall be uploaded to the Virtual Contractor Enterprise (VCE) at https://cor.army.mil on a monthly basis by the COR:

SECTION 4 SPECIAL REQUIREMENTS

4.0. Government Furnished Property

4.0.1. USAMRIID will make available to the contractor the required amount of compound material necessary to evaluate target panels.

4.0.2. USAMRIID will make available to the contractor the structures of novel small molecules.

4.0.3. All structural, synthetic and biological information and data that is either shared or generated through this contract remains the sole property of the US Government and must not be shared with a third party.

4.2. Security and Safeguard Methods

4.2.1. The contractor shall establish appropriate administrative, technical, and physical safeguards to protect any and all Government data. The contractor shall ensure the confidentiality, integrity, and availability of Government data is in compliance with all applicable laws and regulations, including data breach reporting and response requirements, in accordance with Defense Federal Acquisition Regulation Supplemental (DFARS) Subpart 224.1, Protection of Individual Privacy, which incorporates by reference Department of Defense (DoD) 5400.11, DoD Privacy Program, May 8, 2007; and DoD 5400.11-R, DoD Privacy Program, May 14, 2007. The contractor shall also comply with federal laws relating to freedom of information and records management.

4.2.2. Contractors That Do Not Require CAC, But Require Access to a DoD Facility or Installation. Contractor and all associated sub-contractors employees shall comply with adjudication standards and procedures using the National Crime Information Center Interstate Identification Index (NCIC-III) and Terrorist Screening Database (TSDB) (Army Directive 2014-05/AR 190-13), applicable installation, facility and area commander installation/facility access and local security policies and procedures (provided by government representative), or, at OCONUS locations, IAW status of forces agreements and other theater regulations.

4.2.3. Visitor Group Security Agreement. The contractor shall sign a Contractor Visitor Group Security Agreement to protect Government information involved in performance under this contract. The agreement shall outline responsibilities in the following areas: contractor security supervision; standard practice procedures; access, accountability, storage, and transmission of and other responsibilities, as required.

4.3. Special Security Requirements

4.3.1. Contractor Personnel Who Require Access to Government Information Systems. All contractor personnel with access to a government information system shall be registered in the ATCTS (Army Training Certification Tracking System) at commencement of services and shall successfully complete the DoD Information Assurance Awareness training prior to access to the information system and then annually thereafter.

4.3.2. Prior to commencement of services, the contractor shall provide the COR, within seven (7) calendar days in advance of the event, full names, date of birth, place of birth and Social Security numbers (or equivalent identification numbers for non-U.S. citizens) of all personnel who will be entering Army-controlled installation and facilities.

4.3.3. The contractor shall ensure that its personnel entering Army-controlled installations or facilities have obtained access badges and passes IAW facility regulations and that these badges and passes are obtained in advance so as not to delay the accomplishment of contracted services. The contractor shall contact COR or designated Government Trusted Associate Sponsorship System (TASS) Trusted Agent who is responsible to facilitate and sponsoring contractor’s Army Knowledge Online (AKO) registration and TASS in-processing and out-processing, to include approval, rejection and re-verification.

4.3.4. The contractor shall return all issued U.S. Government Common Access Cards, installation badges, access badges to the COR when the contract is completed or when a contractor personnel no longer requires access to the installation and facility.

4.3.5. Force Protection Condition (FPCON) impact on work levels. The contractor workforce shall comply with all personal identity verification requirements as directed by DoD, Headquarters Department of the Army (HQDA), and local policy. In addition to the changes otherwise authorized by the changes clauses of this contract, should the FPCON at any individual facility or installation change, the Government may require changes in contractor security matters or process. IAW Department of Defense Instructions (DoDI) 2000.16, DoD AT Standards, the FPCON is defined as follows:

4.3.5.1. FPCON ALPHA. This condition applies when there is a general threat of possible terrorist activity against personnel and facilities, the nature and extent of which are unpredictable, and circumstances do not justify full implementation of FPCON BRAVO measures. However, it may be necessary to implement certain measures from higher the Terrorist Threat Conditions (THREATCONS) resulting from intelligence received or as a deterrent. The measures in this THREATCON must be capable of being maintained indefinitely.

4.3.5.2. FPCON BRAVO. This condition applies when an increased and more predictable threat of terrorist activity exists. The measures in this THREATCON must be capable of being maintained for weeks without causing undue hardship, affecting operational capability, and aggravating relations with local authorities.

4.3.5.3. FPCON CHARLIE. This condition applies when an incident occurs or intelligence received indicating some form of terrorist action against personnel and facilities is imminent. Implementation of measures in this THREATCON for more than a short period probably will create hardship and affect the peacetime activities of the unit and its personnel.

4.3.5.4. FPCON DELTA. This condition applies in the immediate area where a terrorist attack has occurred or when intelligence has been received that terrorist action against a specific location or person is likely. Normally, this THREATCON is declared as a localized condition. See also anti-terrorism

4.3.5.5. During FPCONs Charlie and Delta, non-essential services are discontinued. Designated essential service will resume when the FPCON level is reduced to level Bravo or lower.

4.3.5.6. When contractor personnel are considered mission essential, all contractor personnel are required to report for duty and remain on duty during declared emergencies or elevated FPCON levels unless otherwise directed by the contracting officer via the appropriate COR.

4.3.5.7. Generation, handling and storage of classified material. The contractor shall not generate, handle or store classified material for this contract.

SECTION 5 DELIVERABLES

5.1. Deliverables. The contractor shall provide the following deliverable as listed.

SECTION 6 APPLICABLE DIRECTIVES, REGULATIONS, AND POLICIES

6.1. Environmental Requirements

6.1.1. Mandatory Compliance. Occupational Safety and Health Act and AR 200-1 Environmental Protection and Enhancement.

6.1.2. Non Mandatory Documents. Additional DoD and Army environmental program and regulations are available on-line at http://aec.army.mil.

6.2. Applicable Directives. None applicable to this contract.

6.3. Mandatory Compliance. None applicable to this contract.

SECTION 7 DEFINITIONS AND ACRONYMS

7.1. Definitions

7.1.1. CONTRACTOR. A supplier or vendor awarded a contract to provide specific supplies or service to the government. The term used in this contract refers to the prime.

7.1.2. CONTRACTING OFFICER. A person with authority to enter into, administer, and/or terminate contracts, and make related determinations and findings on behalf of the government. The Contracting Officer is the only individual who can legally bind the government.

7.1.3. CONTRACTING OFFICER'S REPRESENTATIVE (COR). An employee of the U.S. Government appointed by the contracting officer to administer the contract. Such appointment shall be in writing and shall state the scope of authority and limitations. This individual has authority to provide technical direction to the contractor as long as that direction is within the scope of the contract, does not constitute a change, and has no funding implications. This individual does NOT have authority to change the terms and conditions of the contract.

7.1.4. DEFECTIVE SERVICE. A service output that does not meet the standard of performance associated with the Performance Work Statement.

7.1.5. DELIVERABLE. Anything that can be physically delivered, but may include non-manufactured things such as meeting minutes or reports.

7.1.6. KEY PERSONNEL. Contractor personnel that are evaluated in a source selection process and that may be required to be used in the performance of a contract by the Key Personnel listed in the PWS. When key personnel are used as an evaluation factor in best value procurement, an offer can be rejected if it does not have a firm commitment from the persons that are listed in the proposal.

7.1.7. PHYSICAL SECURITY. Actions that prevent the loss or damage of Government property.

7.1.8. QUALITY ASSURANCE. The government procedures to verify that services being performed by the contractor are performed according to acceptable standards.

7.1.9. QUALITY ASSURANCE SURVEILLANCE PLAN (QASP). An organized written document specifying the surveillance methodology to be used for surveillance of contractor performance.

7.1.10. QUALITY CONTROL. All necessary measures taken by the contractor to assure that the quality of an end product or service shall meet contract requirements.

7.1.11. SUBCONTRACTOR. One that enters into a contract with a prime contractor. The Government does not have privity of contract with the subcontractor.

7.1.12. WORK DAY. The number of hours per day the contractor provides services IAW the contract.

7.1.13. WORK WEEK. Monday through Friday, unless specified otherwise.

7.2. Acronyms. None applicable to this requirement.

7.3. Related Documents (List of attachments)