W81XWH18R00250001_Amendment.docx

W81XWH-18-R-0025

SECTION SF 30 BLOCK 14 CONTINUATION PAGE

SUMMARY OF CHANGES

SECTION A - SOLICITATION/CONTRACT FORM

The following have been modified:

GENERAL INFORMATION

Project Title: PHARMACEUTICAL INTERVENTIONS FOR NOISE-INDUCED HEARING LOSS–ACUTE EXPOSURE TREATMENT (PINIHL-AET)

This is a Request for Proposal (RFP)/solicitation for a Research & Development (R&D) requirement.

The Government anticipates that any resulting award from the RFP/solicitation will be a Cost-Plus-Fixed-Fee (CPFF) contract.

The base period of performance (POP) will be sixty (60) months allocated as follows:

Base Task Period – Date of Award through 36 months of performance.

Optional Task 1 Period – Completion of base objectives through 12 months of performance.

Optional Task 2 Period – Completion of base or Optional Task 1 through 6 months of performance.

Optional Task 3 Period – Completion of Optional Task 2 through 6 months of performance.

North American Industry Classification System (NAICS) Code: 541715—Research and Development in the Physical, Engineering, and Life Sciences (except Nanotechnology and Biotechnology)

Product Service Code: AJ53—R&D-General Science/Technology: Life Sciences (Advanced Development)

Points of Contact (POCs): The primary point of contact (POC) for this solicitation is Toloria DuVall, Contract Specialist, toloria.s.duvall.civ@mail.mil. The alternate POC for this solicitation is Monica Ven Douern, Procurement Technician, monica.c.vendouern.civ@mail.mil. All inquiries regarding this requirement must be submitted via electronic mail (e-mail) to the Contract Specialist. Please carbon copy (cc) the Procurement Technician on all correspondence.

Solicitation Questions: Questions concerning this solicitation shall be submitted in writing to the primary POC (cc the alternate POC) via e-mail no later than 18 July 2018 at 3:00 PM Eastern Time. The e-mail must have a subject title of “W81XWH-18-R-0025 Solicitation Questions”. Any questions submitted after this date and time will not be accepted or answered. Answers to Contractor submitted questions will be provided to all Offerors through a solicitation amendment. Telephone inquiries will NOT be accepted at any time.

Proposal Submission: Proposals shall only be electronically submitted to the primary POC via e-mail. The e-mail must have a subject title of “W81XWH-18-R-0025 Proposal Submission”. The Offeror is responsible for verifying receipt by the POC. One electronic copy shall be submitted for each proposal volume. Each proposal volume should be a separate attachment.

Proposal Due Date: No later than 17 August 2018 at 3:00 PM Eastern Time. Any proposals received after this date and time may not be considered for evaluation. Offerors’ proposals shall remain open for a minimum of 150 days from the date of submission.

Alternate Proposals: Only one proposal from each Offeror will be evaluated by the Government.

The Government anticipates that this solicitation will result in up to (but not greater than) two (2) contract awards.

This invitation to submit a proposal does not assure that a contract will be awarded.

The Offeror’s proposal will be incorporated by reference into a resulting contract. The Offeror’s Statement of Work (SOW) will be incorporated in full text into any resulting contract.

(End of general information)

SECTION C - DESCRIPTIONS AND SPECIFICATIONS

STATEMENT OF OBJECTIVES (SOO)

Statement of Objectives (SOO)

Project Title: Pharmaceutical Interventions for Noise-Induced Hearing Loss–Acute Exposure Treatment (PINIHL-AET)

Requiring Activity/Agency Name: US Army Medical Research and Materiel Command / US Army Medical Materiel Development Activity

Program Name: Tissue Injury and Regenerative Medicine Project Management Office

1.0 PURPOSE/OBJECTIVE

The purpose of this SOO is to identify partner(s) with an ongoing product development strategy for pharmaceutical interventions for noise-induced hearing loss (PINIHL) that has successfully completed Phase 1 clinical studies, and who will obtain successful completion of a Phase 2 clinical study under a US Food and Drug Administration (FDA) Investigational New Drug (IND) application to support a Phase 3 clinical study. The goal is to develop an acute exposure treatment for Service Members to complement current hearing protection strategies with clinically meaningful endpoints for use in operational environments within seventy-two (72) hours after exposure to unanticipated noise hazards (e.g., blasts, forgotten ear plugs while on patrol), aimed at mediating the cellular and metabolic processes to prevent permanent noise-induced hearing loss (NIHL); excluding products designed to regenerate lost auditory neurons or hair cells.

In addition, if warranted, the US Government may support the following product development activities:

Noise trauma is one of the most common sources of injury among Service Members, and NIHL is a leading cause of service-related disability among Veterans despite current hearing conservation efforts. The long term goal of the Tissue Injury and Regenerative Medicine Project Management Office (TIRM PMO) is to make wounded warfighters whole by restoring form, function, and appearance. The outcome of this development will enable TIRM PMO to lead the development of products that will treat wounded warriors with NIHL in operational environments.

2.0 BACKGROUND

The inherently noise-hazardous environments common to military service make Service Members particularly vulnerable to the vast subset of sensorineural hearing loss known as noise-induced hearing loss. Hearing is a critical sense for Service Members. Hearing injuries can threaten safety and fitness for duty by impeding communication, reducing situational awareness, hindering threat detection, and ultimately degrading mission effectiveness. In some cases, hearing loss may preclude redeployment or result in less optimal job assignment, and may permanently reduce their quality of life.

For the past 70 years, the Department of Defense (DoD) has invested in hearing conservation efforts, and interventions such as hearing protection devices and noise reduction engineering have been widely implemented1. From the systems perspective of safety, primary interventions should include engineering and technological solutions to mitigate noise exposure, followed by personal protective equipment or hearing protection devices to attenuate remaining noise levels. Despite these efforts, hearing loss remains the second most prevalent disability among Veterans receiving compensation from the Veterans Benefits Administration for the past decade, according to the Department of Veterans Affairs, and prevalence continues to climb. Since 1999 the number of Veterans receiving compensation for hearing loss has steadily increased. In 2005, 15.7% of Veterans received service-connected disability compensation due to hearing loss. This number has increased to 24.9% (1.1 million) in 20162.

The rising incidence of service-related hearing loss indicates that current hearing conservation efforts are not sufficient to protect Service Members from acoustic injury, so additional measures are needed. Although no FDA approved pharmaceuticals for the treatment of NIHL are currently marketed, recent discoveries related to cellular and metabolic processes thought to underlie permanent NIHL have led to the development of products targeting 1) mechanical damage to the cochlea caused by physical vibratory trauma, which can lead to structural damage and loss of blood flow to hair cells and other cochlear supporting cells, and 2) excitation- and stress-triggered release of cellular messengers and toxins that activate an apoptotic (cell-death) pathway in hair cells and other vital supporting cells within the cochlea(3-11).

According to our market research, the developmental phases of these pharmacological interventions with potential to protect from or mitigate NIHL currently range from preclinical to start of Phase 2 clinical studies. Hence, the US Army Medical Research and Materiel Command (USAMRMC) is working to develop PINIHL for Service Members to complement current hearing protection strategies.

1. McIlwain DS, Gates K, Ciliax D. Heritage of Army Audiology and the Road Ahead: The Army Hearing Program. Am J Public Health. 2008;98(12):2167-2172. doi:10.2105/AJPH.2007.128504.

2. Veterans Benefits Administration Reports. U.S. Department of Veterans Affairs. https://www.benefits.va.gov/REPORTS/abr_archive.asp. Accessed August 30, 2017.

3.Puel J-L, Ruel J, d'Aldin CG, Pujol R. Excitotoxicity and repair of cochlear synapses after noise‐trauma induced hearing loss. NeuroReport. 1998;9(9):2109.

4.Murai N, Kirkegaard M, Järlebark L, Risling M, Suneson A, Ulfendahl M. Activation of JNK in the Inner Ear following Impulse Noise Exposure. J Neurotrauma. 2008;25(1):72-77. doi:10.1089/neu.2007.0346.

5.Coordes A, Gröschel M, Ernst A, Basta D. Apoptotic cascades in the central auditory pathway after noise exposure. J Neurotrauma. 2012;29(6):1249-1254. doi:10.1089/neu.2011.1769.

6. Maeda Y, Fukushima K, Omichi R, Kariya S, Nishizaki K. Time courses of changes in phospho- and total- MAP kinases in the cochlea after intense noise exposure. Sokolowski B, ed. PLoS ONE. 2013;8(3):e58775. doi:10.1371/journal.pone.0058775.

7. Fujioka M, Okano H, Ogawa K. Inflammatory and immune responses in the cochlea: potential therapeutic targets for sensorineural hearing loss. Front Pharmacol. 2014. doi:10.3389/fphar.2014.00287/full.

8. Zheng H-W, Chen J, Sha S-H. Receptor-interacting protein kinases modulate noise-induced sensory hair cell death. Cell Death Dis. 2014. doi:10.1038/cddis.2014.177+[doi].

9. Yamaguchi T, Nagashima R, Yoneyama M, Shiba T, Ogita K. Disruption of ion-trafficking system in the cochlear spiral ligament prior to permanent hearing loss induced by exposure to intense noise: possible involvement of 4-hydroxy-2-nonenal as a mediator of oxidative stress. PLoS ONE. 2014;9(7):e102133-e102133. doi:10.1371/journal.pone.0102133.

10. Kopke RD, Danielson RW. Antioxidants – Good for Your Health, Good For Your Hearing. Update, the newsletter of the Council for Accreditation in Occupational Hearing Conservation. www.caohc.org/updatearticles/spring03.pdf. Published 2003.

11. Dinh CT, Van De Water TR. Blocking pro-cell-death signal pathways to conserve hearing. Audiol Neurootol. 2009;14(6):383-392. doi:10.1159/000241895.

3.0 SCOPE OF EFFORT

The scope of this effort is to develop a pharmaceutical intervention for prevention of permanent NIHL for acute exposure treatment within 72 hours of exposure to unanticipated noise hazards common to military operations. The desired status at the end of this procurement action is completion of a Phase 2 clinical trial and an approved Phase 3 clinical study plan, both under an IND. The pharmaceutical intervention should have clinically meaningful endpoints, appropriate for use in military operational environments, and aim at mediating the cellular and metabolic processes thought to underlie permanent noise-induced hearing loss; excluding products designed to regenerate lost auditory neurons or hair cells. The US Government may make up to two (2) individual awards to Contractor(s) to successfully complete a Phase 2 clinical study.

The Contractor shall:

3.1 Ensure all proposed products to be considered have at minimum completed a Phase 1 clinical study with data available (e.g., final Clinical Study Report) to support the purpose and scope of this effort.

3.2 Include an interim analysis milestone into the Phase 2 clinical study design to evaluate study progress. At a minimum, the interim analysis should examine safety, efficacy, and futility of the drug to determine if the study needs to have an altered design or should be halted.

3.3 Provide the necessary qualified personnel, facilities, equipment, supplies, services, subcontractors and related administrative and information technology support to accomplish the objectives.

3.4 Serve as the FDA Sponsor and assume all responsibilities in accordance with applicable Federal, State, DoD, U.S. Army, and FDA regulations, and applicable International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E6 Good Clinical Practice (GCP), and Good Manufacturing Practice (GMP) guidelines.

3.5 Coordinate with the Department of Defense Hearing Center of Excellence, if clinical studies are to be conducted in the military population.

3.6 Allow the Government or its designee, to audit the Contractor and/or its subcontractor(s) for regulatory compliance and quality assurance purposes.

3.7 Allow access to records, files, and other data derived from this work for the purposes of audit by the FDA and/or other Government entities.

3.8 Maintain the Trial Master File according to Drug Information Association reference model in Electronic Common Technical Document format.

3.9 Maintain and allow Government access to clinical data management documents including, but not limited to, the following:

3.9.1 Approved data management plan and its supporting appendices, all versions.

3.9.2 Study database design specifications.

3.9.3 Approved electronic CRF (eCRF) annotation/specifications, all versions.

3.9.4 Approved edit check specifications, all versions.

3.9.5 Approved ad hoc data listing/report specifications.

3.9.6 Approved study database validation plan (DBVP) and the study database testing and validation supporting documentation.

3.9.7 Study database release for production approval documentation.

3.9.8 Approved CRF completion and data entry guidelines.

3.9.9 End user training completion records.

3.9.10 Approved data transfer validation plan and its supporting documentation.

3.9.11 Approved completion of Medical Dictionary for Regulatory Activities (MedDRA) and World Health Organization (WHO) pharmaceutical coded data or analogous standard.

3.9.12 Data quality assessment completion record(s).

3.9.13 Study database lock approval(s).

3.9.14 Copy of clinical database, clinical study data conforming to Clinical Data Acquisition Standards Harmonization (CDASH) standards.

3.9.15 All documentation related to change control.

3.10 Provide the Government with advanced notification of all meetings with the FDA to enable the Government to participate as observers.

3.11 Provide the Government copies of all communications with the FDA, pertaining to the performance of the clinical trial including, but not limited to, annual and periodic reports, IND submissions, pre-meeting packages, other correspondence including those initiated by the FDA, and official minutes of each FDA meeting to the Government in accordance with the deliverables schedule.

3.12 Participate in appropriate Quality Assurance audits, provide responses to audit findings to the Government, and provide support during U.S. Army Quality oversight visits.

3.13 Provide a Summary report, in accordance with the deliverables schedule, of events that will cause more than a thirty (30) calendar day delay in schedule or an increase in Cost Estimate at Completion.

3.14 Ensure all controlling and/or applicable rules, regulations, and statutes as they relate to pharmaceutical development are enforced. The Government requires that clinical trials are carried out in compliance with all applicable Federal, State, DoD, US Army, and FDA regulations and Good Clinical Practice Guidelines.

3.15 Ensure local Institutional Review Board (IRB) approval, continuing review (in the intervals specified by the local IRB, but at a minimum, annually), and approval by the U.S. Army Human Research Protections Office (HRPO) prior to the start of any clinical study.

4.0 PLACE AND PERIOD OF PERFORMANCE

The estimated period of performance for this contract is up to sixty (60) months allocated as follows (actual dates will be specified in the contract at time of award):

Base Task Period – Date of Award through 36 months of performance.

Optional Task 1 Period – Completion of base objectives through 12 months of performance.

Optional Task 2 Period – Completion of base or Optional Task 1 through 6 months of performance.

Optional Task 3 Period – Completion of Optional Task 2 through 6 months of performance.

The Contractor is to determine the place of performance (i.e., in the U.S. and/or outside of the U.S.) in its Technical proposal.

(End of Statement of Objectives)

SECTION F - DELIVERIES OR PERFORMANCE

DELIVERABLES

1.0. General Deliverable Information

Delivery Address: All deliverables shall be submitted to the COR designated in the COR appointment letter.

Method of Delivery: Electronic copies shall be delivered using Microsoft Office suite of tools (for example, MS WORD, MS EXCEL, MS POWERPOINT, MS PROJECT, or MS ACCESS format) or in Adobe PDF format, unless otherwise specified by the COR. Electronic submission shall be made via email, unless otherwise agreed to by the COR. This method of delivery also applies to Contract Data Requirement List (CDRL) deliveries.

Shipping: The Contractor shall use appropriate, cGMP-compliant refrigerated shipping carriers for pharmaceutical product shipments (FedEx, World Courier, or similar, as agreed to by the COR), and appropriate shipping methods for all other materials, equipment, and hard copy documents. In the United States, the contractor shall use the US Postal Service standard delivery for delivery of all such shipments.

Government Acceptance Period: The COR will have ten (10) business days to review draft deliverables and make comments. The Contractor shall have five (5) business days to make corrections. Upon receipt of the final deliverables, the COR will have ten (10) business days for final review prior to acceptance or providing documented reasons for non-acceptance. Should the Government fail to complete the review within the review period the deliverable will become acceptable by default, unless prior to the expiration of the ten (10) business days the Government notifies the Contractor in writing to the contrary. The final submission should be deemed approved if the Government has not rejected it in thirty (30) calendar days.

The COR will have the right to reject or require correction of any deficiencies found in the deliverables that are contrary to the information contained in the Contractor’s accepted proposal. In the event of a rejected deliverable, the Contractor will be notified in writing by the COR of the specific reasons for rejection. The Contractor shall have five (5) business days to correct the rejected deliverable and return it per delivery instructions.

The period of performance (POP) shall be up to sixty (60) months from the POP start date.

2.0. Deliverable/Delivery Schedule:

NOTE: For this requirement “deliver” means that the USAMMDA COR is in possession of the deliverable.

A summary of deliverables follows. Copies are to be provided to the Government officials in electronic file unless otherwise stated. Contract Data Requirements List (CDRL) will be incorporated into the contract in CDRL (DD1423) format. If a deliverable due date falls on Saturday or Sunday, the Contractor shall submit the deliverable on the next business day.

Table 1. List of Deliverables

COR (Subsequent)

COR (Subsequent)

COR (Subsequent)

Deliverable 8 (Exhibit A, CDRL A001)

COR (Subsequent)

Deliverable 9 (Exhibit B, CDRL A002)

Deliverable 10 (Exhibit C, CDRL A003)

NLT thirty (30) calendar days after POP start date.

FDA Interactions:

Draft copies of all submissions NLT ten (10) business days prior to FDA submission.

Copies of all meeting documents, communications, inspections and enforcements, and registration and listing concurrently or NLT two (2) business days after occurrence.

Final copies of all submissions concurrently with submission to the FDA.

Follow-up documentation as necessary and within two (2) business days.

FDA Communication Plan:

Updated annually on the 15th calendar day of the contract award month through the end of the POP or within fifteen (15) calendar days of COR request.

FDA Interactions:

Draft copies of all submissions NLT ten (10) business days prior to FDA submission.

Copies of all meeting documents, communications, inspections and enforcements, and registration and listing concurrently or NLT two (2) business days after occurrence.

Final copies of all submissions concurrently with submission to the FDA.

Follow-up documentation as necessary and within two (2) business days.

Must include Government in all FDA communication, both formal and informal.

The Government will review FDA submissions and provide recommendations on these documents within five (5) business days of receiving them.

COR (Subsequent)

Deliverable 12 (Exhibit D, CDRL A004)

COR (Subsequent)

COR (Subsequent)

Deliverable 14 (Exhibit E, CDRL A005)

Deliverable 16 (Exhibit F, CDRL A006)

COR (Subsequent)

3.0 Deliverable Descriptions

Deliverable 1: Kick-Off Meeting Material. The Contractor shall schedule and conduct a Kick-Off meeting in coordination with the Government within ten (10) business days after the start of the contract period of performance. The Contractor and the Government will reach agreement regarding the meeting location after contract award. The meeting may be held at Fort Detrick, MD or the Contractor’s site. The Contractor shall meet with the Government to present an overview of their approach and establish schedules, procedures, and points of contact necessary to conduct the tasks outlined herein. This meeting should not exceed two (2) hours in length. The primary outcome of this meeting is to come to an agreement on the cost, schedule, and performance baselines. The Contractor shall provide the Government with a Kick-Off meeting agenda NLT three (3) business days prior to the meeting. The Contractor shall provide the Government with Kick-Off meeting minutes NLT three (3) business days after the meeting.

Deliverable 2: Project Management Plan (PMP). The PMP shall document how the Contractor will meet and comply with the requirements to control, coordinate, and direct performance, as well as organize and manage resources that will achieve the technical/scientific requirements established in their SOW. The Contractor shall prepare a PMP that includes, but is not limited to, an organization chart, Integrated Management Schedule (IMS), Work Breakdown Structure (WBS), Gantt charts, and security plan that encompasses the entire scope of the contract based on the Government provided Statement of Objectives (SOO). The PMP should consist of control policies and procedures in accordance with standard industry practices for project administration, execution and tracking. The PMP should represent how the Contractor plans to accomplish the entire work scope of this contract and additionally should include, but is not limited to, the following:

1. IMS with identification of milestones where Government information/activity is required and timeline dependencies for subsequent Contractor activities;

1. Description of the Contractor’s overall management approaches, policies, and procedures including suggested project metrics; and,

1. A Staffing Plan that details its approach to selecting, directing, and managing staff and subcontractors to include its approach to overseeing execution of tasks.

The plan shall be used to manage, track and evaluate the Contractor’s performance along with the Government-provided Quality Assurance Surveillance Plan (QASP). The contractor shall provide a revised PMP as a deliverable to the Government if any changes occur to the PMP that was submitted with the proposal.

Deliverable 3: Quality Control Plan (QCP). The QCP shall document how the Contractor will meet and comply with the quality standards established in their proposal. The QCP should include, but is not limited to a self-inspection plan, internal staffing plan, and outline the procedures that the Contractor will use to maintain quality, timeliness, responsiveness, customer satisfaction, and any other requirements set forth in the SOO. The contractor shall provide a revised QCP as a deliverable to the Government if any changes occur to the QCP that was submitted with the proposal.

Deliverable 4: Monthly Progress Report and Meeting Minutes. The contractor shall submit the report for this requirement to the COR with a transmittal letter not to exceed one page. The Report shall highlight major events in the reporting period. The report shall include, but is not limited to details outlining the expenditures and billings to date, projected expenditures and billings, progress, status, any problems/issues encountered, reaching milestones, and completing deliverables as appropriate for the reporting period. The contractor shall require and incorporate input from subcontractors where there are critical or significant tasks. Critical or significant tasks shall be defined by mutual agreement between the Government and contractor. The format for the report shall be agreed upon by the Government and Contractor. The report shall include an updated IMS. Monthly meetings shall be held within seven (7) calendar days after the reports are submitted and /or as requested by the COR with minutes due NLT five (5) business days after the meeting.

Deliverable 5: Spend Plan. The Contractor shall provide a Spend Plan which details how they expect to incur and invoice for costs against the contract. The Spend Plan shall detail costs to be incurred monthly by fiscal year (1 October – 30 September) through the entire POP, starting with proposal submission and, subsequently, monthly with the Monthly Progress Report if there are changes. The Spend Plan total shall match with the total costs proposed for the entire contract in the Cost/Pricing Sheet. The Spend Plan shall be updated as necessary. The Contractor shall report actual progress against the Spend Plan in the Monthly Progress Report.

Deliverable 6: Verification of Contractor Manpower Reporting (CMR) Submission. The contractor shall provide verification of CMR submission to the COR and the Contract Specialist via e-mail. The contractor shall report ALL contractor labor hours (including subcontractor labor hours) required for the development of pharmaceutical interventions for noise-induced hearing loss (PINIHL) via a secure data collection site. The contractor is required to completely fill in all required data fields using the following web address: www.ecmra.mil. 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 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 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 Contractor Manpower Reporting User Guide available on the new eCMRA website www.ecmra.mil.

The Order Data tab on the CMRA Contractor Data Entry website will ask for the “Requiring Activity Unit Identification Code” (UIC). The Unit Identification Code (UIC) of the Requiring Activity that would be performing the mission if not for the contractor. This is not necessarily the Contracting Office, Contracting Administrative Office, or Funding Source. The UIC is not the same as the Department of Defense Activity Address Code (DODAAC).

The UIC of the Requiring Activity for this contract is W4QFAA - W4QF USAMMDA.

Deliverable 7: Annual Product Review. The Contractor shall participate in an Annual Product Review in-person meeting with US Government personnel either at Fort Detrick, MD or at the Contractor site to review progress and discuss technical issues. The Contractor and the Government will reach agreement regarding the location for each Annual Product Review after contract award. Each review shall provide insight into expenditures, staffing, progress, risks, and status of any Government property, including Contractor-acquired property (if any). The Contractor shall provide project briefings addressing cost/price, schedule, performance, and status of each key element of this contract, noting any problems or risks and alternative and recommended solutions. The Contractor shall provide the Government with a meeting agenda and related materials NLT ten (10) business days prior to the Annual Product Review. The Contractor shall provide the Government with meeting minutes NLT five (5) business days after the Annual Product Review.

Deliverable 8: Clinical Development Plan (CDP). The Contractor shall provide the CDP as defined in Data Item Description (DID) DI-TCSP-82040, section 2.a.(4) in its entirety and in the format outlined in section 1 (Exhibit A, CDRL A001).

Deliverable 9: Regulatory Development Plan (RDP). The Contractor shall provide the RDP as defined in DID DI-TCSP-82040, section 2.a.(2) in its entirety and in the format outlined in section 1 (Exhibit B, CDRL A002).

Deliverable 10: FDA Interactions. The Contractor shall provide documentation related to FDA Interactions as defined in DI-TCSP-82040, section 2.b. in its entirety and in the format outlined in section 1 (Exhibit C, CDRL A003).

Deliverable 11: Commercial Transition Plan (CTP). The Contactor shall provide a CTP that includes, but is not limited to, the commercial marketing analysis, strategy, and plan to demonstrate commercial uses and viability of the product under development, and estimated cost to manufacture and unit price based on projected manufacturing quantities (e.g., 10,000, 100,000, 1,000,000, 10,000,000 units, etc.).

Deliverable 12: Quality Assurance (QA). The Contractor shall provide a plan for Quality Assurance (QA) as defined in DID DI-TCSP-82040, section 2.f. in its entirety and in the format outlined in section 1 (Exhibit D, CDRL A004).

Deliverable 13: Risk Management Plan (RMP). The Contractor shall develop and maintain a Risk Management Plan that highlights potential risks that may arise during the life of the contract, their impact on cost, schedule and performance, and appropriate mitigation plan. This plan should reference relevant Statement of Objectives or Statement of Work elements where appropriate.

Deliverable 14: Clinical Study Protocol. The Contractor shall provide a Clinical Study Protocol as defined in DID DI-TCSP-82040, section 2.d.(1) and in the format outlined in section 1 (Exhibit E, CDRL A005).

Deliverable 15: Interim Analysis Report. The Contractor shall provide an interim analysis report for the Phase 2 clinical study that includes, but is not limited to information on the clinical study progress, results, analysis, and preliminary conclusions. At a minimum, the interim analysis should examine safety, efficacy, and futility of the drug to determine if the study needs to have an altered design or should be halted. The interim analysis period should be designed in the Phase 2 clinical study protocol.

Deliverable 16: Manufacturing Development Plan (MDP). The Contractor shall provide a MDP as defined in DID DI-TCSP-82040, section 2.a.(5) and in the format outlined in section 1 (Exhibit F, CDRL A006).

Deliverable 17: Biostatistics Deliverables. The Contractor shall provide Biostatistics Deliverables as defined in DID DI-TCSP-82040, section 2.d.(5) and in the format outlined in section 1 (Exhibit G, CDRL A007).

Deliverable 18: Trial Master File (TMF) Structure. The Contractor shall provide a TMF structure in International Conference on Harmonisation (ICH) Electronic Common Technical Document (eCTD) format.

Deliverable 19: Clinical Study Report. The contractor shall provide a clinical study report that includes, but is not limited to the clinical study design, results, statistical analysis, discussions, and conclusions. The contractor shall submit the report in ICH eCTD format as required.

Deliverable 20: Contractor Recommended Surveillance. The contractor shall provide its recommended methods of quality surveillance for this requirement in the following format. This information may be utilized by the Government to create a Quality Assurance Surveillance Plan.

*Add or delete rows as necessary.

Deliverable 21: Non-Disclosure/Non-Use Agreement. The Contractor shall sign and submit a Non-Disclosure Statement (Solicitation Attachment 1) on behalf of the company, and shall also ensure that all staff assigned to, including all subcontractors and consultants, or performing on the contract execute and adhere to the terms of the non-disclosure statement, protecting the procurement sensitive information of the Government and the proprietary information of other contractors. Assignment of staff who has not executed this statement or failure to adhere to this statement may constitute default on the part of the Contractor.

Deliverable 22: Issue Summary Report (ISR). The Contactor shall report any significant positive or negative deviation to the schedule or scope of a task immediately to the Government, and the deviation shall be explained within three (3) business days of issue being identified and documented by the Contractor in its Monthly Progress Report.

4.0 Contract Data Requirements List

Table 2. Contract Data Requirements List (CDRL) Contract Line Item Number (CLIN) Contract Data Requirements List

(CDRL)

Description (DID) DID Number & Reference

5.0 Deliverables Schedules Abbreviations

The following abbreviations are used in the deliverable schedules.

Table 3. Contracting Term Abbreviations

(End of deliverables)

SECTION J - LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACHMENTS

The Table of Contents has changed from:

Exhibit/Attachment Table of Contents

to:

Exhibit/Attachment Table of Contents

SECTION L - INSTRUCTIONS, CONDITIONS AND NOTICES TO BIDDERS

PROPOSAL SUBMISSION

L.1. INTRODUCTION

This section provides general guidance for preparation of proposals as well as specific instructions on the format and content of the proposal. The Offeror’s proposal must include all data and information requested and must be submitted in accordance with these instructions. The proposal shall also be compliant with all requirements as stated in the SOO.

The use of contractor teaming arrangements (as defined in FAR 9.601(1)) and subcontractor relationships are acceptable. Any subcontracting/teaming arrangements contemplated by the Offeror must be presented in detail. The details should disclose those portions of the task which will be subcontracted and the anticipated organizations with which subcontracting or teaming arrangements are planned. Since there is a direct relationship from the Cost/Price proposal to the Management Approach, teaming and functional capabilities, and Past Performance proposal, the Offeror shall cross-reference enough information on subcontracting/teaming arrangements to allow for a thorough proposal review from a technical and management perspective. The Offeror shall include evidence (e.g., statement of intent to enter into a teaming agreement) of subcontractor relationships.

The Offeror shall submit documentation illustrating its approach for satisfying the requirements of this solicitation. Proposals must be clear, coherent, and prepared in sufficient detail for effective evaluation of the Offeror’s proposal against the evaluation criteria. This documentation shall cover all aspects of this solicitation and include the Offeror’s approach for integration and program management activities. Proposals must clearly demonstrate how the Offeror intends to accomplish the project and must include convincing rationale and substantiation of all claims. Unnecessarily elaborate brochures or other presentations beyond those sufficient to present a complete effective response to the solicitation are not desired.

The Offeror shall describe its proposal through the use of graphs, charts, diagrams and narrative in sufficient detail for the Government to understand and evaluate the nature of the approach. In its evaluation and confidence assessment, the Government will consider the degree of substantiation of the proposed approaches in all proposal volumes.

The Offeror’s proposal shall be submitted in electronic format as set forth below.

Offerors’ proposals must include a statement that the proposal shall remain open for a minimum of 150 days from the date of submission.

The Government intends to award without discussions. Therefore, the Offeror’s proposal is presumed to represent the Offeror’s best effort in response to the Solicitation. If discussions are required they will be conducted with Offerors in the competitive range to the extent deemed necessary by the Contracting Officer, in accordance with FAR 15.306. Discussions will be conducted on the content of the proposal and, if discussions have been conducted, a Final Revised Proposal (FRP) will be solicited from those Offerors within the competitive range. A common cut-off date will be established for receipt of all FRPs.

Offerors are prohibited from modifying any documents, printed or electronic, associated with this solicitation and any amendments in any way, shape or form, unless specifically authorized to do so. The electronic solicitation documents posted on http://www.fbo.gov shall be the official documents for this solicitation.

Offers submitted in response to this solicitation shall be in the English language. Offers received in any language other than English shall be determined non-responsive.

If proprietary information in included in a proposal submitted by a contractor, the Contractor shall mark its proposal accordingly (see Section L.2.3).

All proposal information is subject to verification by the Government. Falsification of any proposal submission documents or statements may subject the Offeror to civil or criminal prosecution under Section 1001 of Title 18 of the United States Code.

All Offerors must comply with FAR Clause 52.204-7 System for Award Management (SAM). In complying with this clause, the Offeror must ensure that ALL representations and certifications contained in Solicitation Section K are completed and uploaded to its SAM record at http://www.sam.gov by the date specified for receipt of proposals. Any Offeror that does not have an active SAM record or has a record that does not include all representations and certifications required in Section K may be found non-responsive and may not be considered for award. The NAICS for this requirement is 541715—Research and Development in the Physical, Engineering, and Life Sciences (except Nanotechnology and Biotechnology). Offeror must be registered in SAM under NAICS 541715 in order to be eligible for award. Registration of a new entity in SAM has changed as of 22 March 2018; the registrant must provide an original, signed notarized letter stating that you are the authorized Entity Administrator before your registration will be activated. Registration updates and renewals of existing entities in SAM has also changed as of 27 April. Please visit http://www.sam.gov and https://www.gsa.gov/about-us/organization/federal-acquisition-service/office-of-systems-management/integrated-award-environment-iae/sam-update to learn more about these process changes. Please note that international entities must follow a different process. It is recommended that Offerors allow sufficient time to complete the SAM registration process. An entity can be registered in SAM under multiple NAICS if they are applicable to the entity’s business.

Any data previously submitted in response to another solicitation to USAMRAA or another agency shall be assumed to be unavailable during this proposal evaluation and source selection process. Proposal data shall not be incorporated into this proposal by referring to another proposal or other source.

The Government will not reimburse any Offerors for costs incurred as a result of preparation and submission of a proposal in response to this solicitation.

L.2. PROPOSAL FORMAT

L.2.1. Proposal Format

The Offeror shall provide their proposal in electronic format as noted below. It shall include the Technical Approach, Regulatory Approach, Management Approach, Experience, Past Performance information, Section K Representations and…