RFP_8919_06.20.14.pdf

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SOLICITATION

SECTION A - SOLICITATION/CONTRACT FORM

1. Requisition or other Purchase Authority: P.L. 102-321 as amended

2. Request for Proposal (RFP) Number:

N01DA-15-8919

3. Issue Date:

June 20, 2014

4. Set Aside:

[X] No

[ ] Yes See Part IV Section L

5. Title : In Vitro Metabolism and Metabolite Quantification

6. ISSUED BY:

NIDA R&D Contracts Management Branch Office of Acquisitions National Institute on Drug Abuse National Institutes of Health.

6001 Executive Blvd. Suite 4211 Bethesda, MD 20892-9559

* For FEDEx/UPS/Courier/Hand Delivery:

Rockville, MD 20852

7. SUBMIT OFFERS TO:

See Part III, Section J, "Packaging and Delivery of the Proposal," ATTACHMENT 1 of this Solicitation.

8. Proposals for furnishing the supplies and/or services in THE SCHEDULE will be received at the place specified in, and in the number of copies specified in Attachment 1, "Packaging and Delivery of the Proposal," until 3:00 pm local time on August 4, 2014. Offers will be valid for 120 days unless a different period is specified by the offeror on the Attachment entitled, "Proposal Summary and Data Record, NIH 2043.

9. This solicitation requires delivery of proposals as stated in ATTACHMENT 1, "PACKAGING AND DELIVERY OF THE PROPOSAL." If proposals are required to be delivered to two different locations, the OFFICIAL POINT OF RECEIPT for determining TIMELY DELIVERY is the address provided for the OFFICE OF ACQUISITIONS.

IF YOUR PROPOSAL IS NOT RECEIVED BY THE CONTRACTING OFFICER OR HIS DESIGNEE AT THE PLACE AND TIME SPECIFIED FOR THE OFFICE OF ACQUISITIONS, THEN IT WILL BE CONSIDERED LATE AND HANDLED IN ACCORDANCE WITH HHSAR Clause 352.215-70, "Late Proposals and Revisions"

LOCATED IN SECTION L.1. OF THIS SOLICITATION.

10. Offeror must be registered in the Central Contractor Registry (CCR) prior to award of a contract. Offerors must access the CCR through The System for Award Management (SAM) at http://www.sam.gov

11. FOR INFORMATION CALL: Lisa Bielen

PHONE: (301) 443-6677

e-MAIL: lisa.bielen@nih.gov

COLLECT CALLS WILL NOT BE ACCEPTED.

Brian H. O'Laughlin Contracting Officer

NIDA R&D CMB

Office of Acquisitions, NIDA http://www.sam.gov

RFP Number : N01DA-15-8919

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RFP TABLE OF CONTENTS

PART I - THE SCHEDULE

SECTION A - SOLICITATION/CONTRACT FORM

SECTION B - SUPPLIES OR SERVICES AND PRICES/COSTS

SECTION C - DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

SECTION D - PACKAGING, MARKING AND SHIPPING

SECTION E - INSPECTION AND ACCEPTANCE

SECTION F - DELIVERIES OR PERFORMANCE

SECTION G - CONTRACT ADMINISTRATION DATA

SECTION H - SPECIAL CONTRACT REQUIREMENTS

PART II - CONTRACT CLAUSES

PART III - LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACHMENTS

SECTION J - LIST OF ATTACHMENTS

SOLICITATION ATTACHMENTS

TECHNICAL PROPOSAL ATTACHMENTS

BUSINESS PROPOSAL ATTACHMENTS

INFORMATIONAL ATTACHMENTS

PART IV - REPRESENTATIONS AND INSTRUCTIONS

SECTION K - REPRESENTATIONS, CERTIFICATIONS AND OTHER STATEMENTS OF OFFERORS

SECTION L - INSTRUCTIONS, CONDITIONS, AND NOTICES TO OFFERORS

1. GENERAL INFORMATION

a. INSTRUCTIONS TO OFFERORS--COMPETITIVE ACQUISITION

b. NAICS CODE AND SIZE STANDARD

c. TYPE OF CONTRACT AND NUMBER OF AWARDS

d. TASK ORDERS UNDER SINGLE AWARD INDEFINITE DELIVERY CONTRACTS

e. ESTIMATE OF EFFORT

f. COMMITMENT OF PUBLIC FUNDS

g. PROMOTING EFFICIENT SPENDING

h. COMMUNICATIONS PRIOR TO CONTRACT AWARD

i. RELEASE OF INFORMATION

j. PREPARATION COSTS

k. SERVICE OF PROTEST

l. LATE PROPOSALS AND REVISIONS

2. INSTRUCTIONS TO OFFERORS

a. GENERAL INSTRUCTIONS

1. Contract Type and General Clauses

2. Authorized Official and Submission of Proposal

3. Proposal Summary and Data Record (NIH-2043)

4. Separation of Technical and Business Proposals

5. Alternate Proposals

6. Evaluation of Proposals

7. Potential Award Without Discussions

8. Use of the Metric System of Measurement

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9. Privacy Act - Treatment of Proposal Information

10. Selection of Offerors

11. Institutional Responsibility Regarding Investigator Conflicts of Interest

12. Past Performance Information

13. Information and Physical Access Security

14. Solicitation Provisions Incorporated by Reference

b. TECHNICAL PROPOSAL INSTRUCTIONS

1. Technical Discussions

2. Other Considerations

3. Technical Evaluation

4. Obtaining and Disseminating Biomedical Research Resources

5. Electronic and Information Technology Accessibility, HHSAR 352.239-73(a)

c. BUSINESS PROPOSAL INSTRUCTIONS

1. Basic Cost/Price Information

2. Proposal Cover Sheet

3. Information Other than Cost or Pricing Data

4. Requirements for Cost or Pricing Data or Information Other than Cost and Pricing Data

5. Salary Rate Limitation

6. Small Business Subcontracting Plan

7. HUBZone Small Business Concerns

8. Extent of Small Disadvantaged Business Participation

9. Total Compensation Plan

10. Other Administrative Data

11. Qualifications of the Offeror

12. Subcontractors

13. Proposer's Annual Financial Report

14. Travel Costs/Travel Policy

SECTION M - EVALUATION FACTORS FOR AWARD

1. GENERAL

2. MANDATORY QUALIFICATION CRITERIA

3. TECHNICAL EVALUATION FACTORS

4. EVALUATION OF ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY- SECTION

5. PAST PERFORMANCE FACTOR

6. EXTENT OF SMALL DISADVANTAGED BUSINESS PARTICIPATION

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PART I - THE SCHEDULE

THE INFORMATION SET FORTH IN SECTION A - SOLICITATION/CONTRACT FORM, HEREIN 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, HEREIN, 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 PERTINENT TO THE OFFEROR (i.e., those relating to the organizational structure [e.g., Non-Profit, Commercial] and specific cost authorizations unique to the Offeror's proposal and requiring Contracting Officer Prior Approval) WILL BE DISCUSSED IN THE NEGOTIATION PROCESS AND WILL BE INCLUDED IN THE RESULTANT CONTRACT. THE ENCLOSED CONTRACT SCHEDULE IS

INTENDED TO PROVIDE THE OFFEROR WITH THE NECESSARY INFORMATION TO UNDERSTAND THE

TERMS AND CONDITIONS OF THE RESULTANT CONTRACT.

SECTION B - SUPPLIES OR SERVICES AND PRICES/COSTS

ARTICLE B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES

The in vitro metabolism studies for this contract include metabolite profiling for interspecies comparison using hepatocytes and microsomes, CYP 450 phenotyping reaction, CYP 450 inhibition, and CYP 450 induction for potential medications. It may also include evaluation of in vitro metabolism by other systems such as hepaticcytosol, hepatic mitochondrial fraction, or Phase II reactions (glucuronidation, sulfation, acetylation, methylation, conjugation with glutathione, conjugation with amino acids). This contract should also provide structure identification of major metabolites by mass spectrometry or nuclear magnetic resonance (NMR). Additional in vitro studies include determination of intestinal and or blood-brain barrier permeability of new compounds.

ARTICLE B.2. PRICES

a. This is an Indefinite Quantity contract as contemplated by FAR 16.504. The Contractor shall be reimbursed by the Government in an amount not less than a total of $1,000 (minimum) nor more than a total of $1,200,000 (maximum) for successful performance of this contract.

b. The prices set forth in this ARTICLE will cover the contract period December 29, 2014 through December 30, 2019.

c. The Government will issue Task 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 Order, the Government shall pay to the Contractor the unit price(s) set forth below:

SCHEDULE OF CHARGES FOR THE BASIC AWARD PERIOD

Description of Item Unit Price

Task 1 - Interespecies Comparison of In Vitro Metabolism

Task 2 - Metabolic Pathway Identification (Reaction Phenotyping)

Task 3 - CYP 450 Inhibition

Task 4 - Induction of CYP 450 Enzymes

Task 5 - Metabolite Identification

Task 6 - Metabolic Stability

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Description of Item Unit Price

Task 7 - In Vitro Permeability Studies

Task 8 - Archival Maintenance of Records

Task 9 - Administrative Support

ARTICLE B.3. PROVISIONS APPLICABLE TO DIRECT COSTS

This article will prohibit or restrict the use of contract funds, unless otherwise approved by the Contracting Officer. The following is a list of items that may be included in the resultant contract as applicable. 1) Conferences & Meetings, 2) Food for Meals, Light Refreshments & Beverages, 3) Promotional Items, 4) Acquisition, by purchase or lease, of any interest in real property; 5) Special rearrangement or alteration of facilities; 6) Purchase or lease of any item of general purpose office furniture or office equipment regardless of dollar value; 7) Travel Costs including Foreign Travel; 8) Consultant Costs; 9) Subcontract Costs; 10) Patient Care Costs; 11) Accountable Government Property; 12) Printing costs; and 13) Research Funding.

ARTICLE B.4. ADVANCE UNDERSTANDINGS

Specific elements of cost, which normally require prior written approval of the Contracting Officer before incurrence of the cost (e.g., foreign travel, consultant fees, subcontracts) will be included in this Article if the Contracting Officer has granted his/her approval prior to contract award.NIDA reserves the right to have the contracted services benefit NIDA and any other component of NIH.

The Contractor shall correct all mistakes, errors, and typographical errors at no additional cost to the Government as deemed necessary by the Contracting Officer's Representative (COR). If the COR determines that the deliverables need to be redone to correct errors it shall be done at the Contractor's expense.

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SECTION C - DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

ARTICLE C.1. STATEMENT OF WORK

a. I. Background Information and Objectives

The National Institute on Drug Abuse (NIDA) supports research and development of new medications for the treatment of addiction. The medications development program of NIDA involves in vitro evaluations, preclinical pharmacology and toxicology studies, pharmaceutical development, and clinical evaluations for potential new medications for treating addiction. The body generally eliminates drugs either by excretion or by metabolism to one or more active or inactive metabolites. Metabolic pathways, individual differences in metabolic rates, and genetic polymorphism in enzymes can significantly affect safety and efficacy of the drug. It is important to understand these metabolic pathways and potential interactions at an early stage of drug development. One can characterize drug metabolism using simple, rapid, and low cost in vitro methods to provide predictions of toxicity and efficacy which may significantly affect the design (or initiation) of clinical evaluations.

In drug discovery, with compounds that are developed for the treatment of central nervous system diseases, it is important to determine compound's bioavailability. A compound administered orally must be absorbed from the gastro-intestinal tract and must reach its target organ for its pharmacological action. Barriers such as permeability through intestinal wall and blood-brain barrier for penetration into brain needs to be overcome for the compound to reach the target organ.

It is important for new compounds under early drug development consideration to be evaluated for intestinal permeability and penetration into brain through blood-brain barrier.

In vitro metabolism studies can predict biotransformation (rate and route) using hepatocytes (fresh and cryopreserved), microsomes, and tissue slices from different species (e.g., rat, rabbit, dog, monkey and human).

Interspecies comparison of in vitro metabolism studies can be extremely useful in identifying the most relevant species for preclinical evaluation (e.g. toxicological and pharmacokinetic studies) of a potential medication.

Identification of specific enzymes that are involved in the metabolism of a new medication is necessary for predication of potential drug-drug interactions. In vitro metabolism studies also predict inhibition of CYP 450, which may result in accumulation of drugs in the body - a common cause of drug toxicity.

A careful evaluation of the pharmacokinetics of a drug and its active metabolites is critical for the understanding of its pharmacological effects. It is therefore important to identify the metabolites. It is important for new compounds under early drug development consideration to be evaluated for intestinal permeability and penetration into brain through blood-brain barrier.

The objective of this contract is to carryout in vitro metabolism studies (including metabolite identification), and permeability studies to support the medications development program of the National Institute on Drug Abuse (NIDA). NIDA and NIDA sponsored investigators will use the data obtained for submissions to the Food and Drug Administration (FDA) in support of INDs (Investigational New Drugs) and NDAs (New Drug Applications).

II. Contractor Performed Services

A. General Requirements

1. Independently, and not as an agent of the Government, the Contractor must furnish all necessary labor, materials (except new medications the Contractor will study) supplies, equipment, services, and facilities, as necessary to perform the work set forth below. NIDA will provide new potential medications to the Contractor to study.

2. The Contractor will provide in vitro metabolism and permeability studies for the medications development program of the National Institute on Drug Abuse (NIDA). The Contractor must follow pertinent FDA guidance and regulations.

New compounds from NIDA contractors, grantees or pharmaceutical industry sources, which show promise in initial pharmacological screening, will be the subject of studies detailed in this contract. The in vitro metabolism

- 7 -services for this contract include metabolite profiling for interspecies comparison using hepatocytes and microsomes, CYP 450 phenotyping reaction, CYP 450 inhibition, CYP 450 induction, and metabolic stability of new compounds. It may also include evaluation of in vitro metabolism by other systems such as hepatic cytosol, hepatic mitochondrial fraction, or Phase II reactions (glucuronidation, sulfation, acetylation, methylation, conjugation with glutathione, conjugation with amino acids).

This contract will provide structure identification of major metabolites by mass spectrometry or nuclear magnetic resonance (NMR). In addition, the in vitro studies include determination of intestinal and blood-brain barrier permeability of new compounds under development. The Contractor shall evaluate the permeabilities in the presence and absence of specific inhibitors of drug-transport systems.

The Contracting Officer's Representative (COR) must approve all reports and protocols, in content and format.

NIDA and NIDA sponsored investigators will use the obtained data for submissions to the FDA. The reports shall be adequate in format and substance for submission to the FDA in support of IND and NDA applications. The contractor shall also establish electronic data files and keep all reports, protocols, raw data, and assay results in secure storage.

For proposal purposes: the in vitro studies provided for this contract include Tasks 1 through 9 as listed under Specific Requirement.

For proposal purposes: approximately once a year and under an issued task order, the contactor may be required to participate in a meeting or to meet with the COR at NIDA or at a scientific meeting.

3. The Government COR, whose position is defined in this contract, will monitor all work under this contract.

B. Specific Requirements

1. Through issued task orders the Contractor shall perform the following tasks:

Task 1. Interspecies Comparison of In Vitro Metabolism:

• Study in vitro metabolism of a new compounds under development typically by using hepatic microsomes or hepatocytes from a variety of species for interspecies metabolism comparison.

• Evaluate in vitro metabolism by other systems such as hepatic cytosol, hepatic mitochondrial fraction or phase II reaction.

Task 2. Metabolic Pathway Identification (Reaction Phenotying):

• Perform in vitro metabolism studies to identify the CYP 450 enzyme(s) involved in the metabolism of a new medication.

Task 3. CYP 450 Inhibition:

• Perform studies to evaluate new compounds for their potential to inhibit hepatic CYP 450 enzymes.

• Perform studies to determine if there are interactions between new compounds with drugs commonly abused by the target population, such as methamphetamine. The study involves determination of Ki (inhibitory constant) and IC50 (the concentration at 50% inhibition of enzyme activity) values for new compounds.

Task 4. Induction of CYP 450 Enzymes:

• Perform studies to evaluate new compounds for their potential to induce human CYP 450 enzymes.

Task 5. Metabolite Identification:

• Identify the structure of major metabolite(s) produced either by in vitro system or in vivo system (from biological samples obtained in other NIDA sponsored studies) by mass spectrometry. For proposal purposes, NIDA may not be able to provide reference standards of metabolites.

Task 6. Metabolic Stability:

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• Perform in vitro metabolism of new compounds by hepatic microsomes or hepatocytes from a variety of species for metabolic stability and intrinsic clearance estimate.

Task 7. In Vitro Permeability Studies:

• Determine the intestinal permeability of new compounds in order to assess its oral absorption using Caco-2 cells or other appropriate systems.

• Use appropriate cell-line used in the industry to assess blood-brain barrier permeability.

• Evaluate the permeabilities in the presence and absence of specific inhibitors of drug-transport systems.

• Determine the solubility if such information is not available.

Task 8. Archival Maintenance of Records

• Place all data, including laboratory notebooks, hard copies of raw data, and databases of assay results on disk or tape in secure storage for 5 years. During this period, the contractor will be responsible for the integrity and organization of the material and its confidentiality. At the end of this period, all reference material, data files, etc.

will be disposed of per instructions of the COR.

Task 9. Administrative Support:

• Perform additional support services related to contract administration. The support services may include, but are not limited to, preparing deliverables as required by the contract (for example monthly/annual progress reports), meeting contract requirements, invoicing, monthly/annual progress reports, preparing monthly invoices, and general contract meetings. A list of possible example deliverables follows:

i. Annual Progress Reports;

ii. Final Contract Report w/ Summary of Salient Results;

iii. All data, etc. as directed by the COR;

iv. Annual Utilization Reports;

v. Final Invention Statement (if applicable);

vi. Reporting of Financial Conflict of Interest (FCOI);

vii. Small Business Subcontracting Reports (if applicable);

viii. Roster of Employees Requiring Suitability Investigations;

ix. IT Security Plan;

xii. IT Security Certification and Accreditation (if applicable);

xiii. Reports of New and Departing Employees; and

xiv. Non-Disclosure Agreements.

C. Sample Task Orders

For purposes of proposal preparation , offerors are to provide a separate technical proposal (including timelines) and cost estimates for the 9 sample tasks listed below.

Sample Task Order 1- Interspecies Comparison of In Vitro Metabolism:

• Study in vitro metabolism of a new compounds under development typically by using hepatic microsomes or hepatocytes from a variety of species for interspecies metabolism comparison.

• Evaluate in vitro metabolism by other systems such as hepatic cytosol, hepatic mitochondrial fraction or phase II reaction.

Sample Task Order 2 - Metabolic Pathway Identification (Reaction Phenotying):

• Perform in vitro metabolism studies to identify the CYP 450 enzyme(s) involved in the metabolism of a new medication.

Sample Task Order 3 - CYP 450 Inhibition:

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• Perform studies to evaluate new compounds for their potential to inhibit hepatic CYP 450 enzymes.

• Perform studies to determine if there are interactions between new compounds with drugs commonly abused by the target population, such as methamphetamine. The study involves determination of Ki (inhibitory constant) and IC50 (the concentration at 50% inhibition of enzyme activity) values for new compounds.

Sample Task Order 4 - Induction of CYP 450 Enzymes:

• Perform studies to evaluate new compounds for their potential to induce human CYP 450 enzymes

Sample Task Order 5 - Metabolite Identification:

• Identify the structure of major metabolite(s) produced either by in vitro system or in vivo system (from biological samples obtained in other NIDA sponsored studies) by mass spectrometry. For proposal purposes, NIDA may not be able to provide reference standards of metabolites.

Sample Task Order 6 - Metabolic Stability:

• Perform in vitro metabolism of new compounds by hepatic microsomes or hepatocytes from a variety of species for metabolic stability and intrinsic clearance estimate.

Sample Task Order 7- In Vitro Permeability Studies:

• Determine the intestinal permeability of new compounds in order to assess its oral absorption using Caco-2 cells or other appropriate systems.

• Use appropriate cell-line used in the industry to assess blood-brain barrier permeability.

• Evaluate the permeabilities in the presence and absence of specific inhibitors of drug-transport systems.

• Determine the solubility if such information is not available.

Sample Task Order 8 - Archival Maintenance of Records

• Place all data, including laboratory notebooks, hard copies of raw data, and databases of assay results on disk or tape in secure storage for 5 years. During this period, the contractor will be responsible for the integrity and organization of the material and its confidentiality. At the end of this period, all reference material, data files, etc.

will be disposed of per instructions of the COR.

Sample Task Order 9 - Other support services - This study involves work described in Task 9. A related Task Order is expected to be issued with the contract award. Offerors are to submit a budget estimate for this Task. The scope of this task is for severable services to provide general support for set up and administration of the basic contract. This does not include the administrative activities that will be performed under each awarded task order.

a. The Contractor shall prepare and submit contract deliverables such as:

i. Individual Task Reports (i.e., Methods Development and Validation Reports, Analytical Study Reports);

ii. Monthly Progress Reports;

iii. Annual Progress Reports;

iv. Final Contract Report w/ Summary of Salient Results;

v. All data, etc. in accordance with Task G;

vi. Annual Utilization Reports;

vii. Final Invention Statement;

viii. Reporting of Financial Conflict of Interest (FCOI);

ix. Small Business Subcontracting Reports;

x. Roster of Employees Requiring Suitability Investigations;

xiii. FIPS 199 Assessment;

xiv. IT Security Certification and Accreditation;

xv. Reports of New and Departing Employees; and

xvi. Non-Disclosure Agreements.

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* This list is not exclusive of other deliverables.

b. The Contractor shall provide services for the general administration of the contract.

ARTICLE C.2. REPORTING REQUIREMENTS

All reports required herein shall be submitted in electronic format. In addition, hardcopies of each report shall be submitted in accordance with Section F.

All electronic reports submitted shall be compliant with Section 508 of the Rehabilitation Act of 1973. Additional information about testing documents for Section 508 compliance, including guidance and specific checklists, by application, can be found at: http://www.hhs.gov/web/508/index.html under "Making Files Accessible."

All paper/hardcopy documents/reports submitted under this contract shall be printed or copied, double-sided, on at least 30 percent post consumer fiber paper, whenever practicable, in accordance with FAR 4.302(b).

a. Technical Progress Reports

1. In addition to the required reports set forth elsewhere in this Schedule, the preparation and submission of regularly recurring Technical Progress Reports will be required in any contract resulting from this solicitation. These reports will require descriptive information about the activities undertaken during the reporting period and will require information about planned activities for future reporting periods. The frequency and specific content of these reports will be determined prior to contract award. Note: The Contractor shall include the applicable PubMed Central or NIH Manuscript Submission reference number when citing publications that arise from its NIH funded research.

* If there are no active task orders during a specific reporting period then the contractor does not need to submit a report.

Deliverables and Reporting Requirements

The Contractor shall prepare and submit the following reports using the format below:

Front cover to contain: Date, title, study report name, chemical compound/formulation identification, agency (NIDA), division (DPMCDA) and NIDA COR name/address/phone number, contract number, Contractor name and investigator names.

Main body to contain: Narrative summaries of the work accomplished, raw data and interpreted results, and tables and graphs as necessary.

The Contractor shall ensure that all Reports are free from spelling, typographical, or grammatical errors. Study Reports containing such errors shall be deemed unacceptable and returned to the Contractor for correction.

Appendices to contain: All approved (with signatures) methods of analyses and specifications.

a. Individual Study/Task Reports (i.e., Interspecies comparison in vitro metabolism studies, CYP 450 inhibition studies, CYP 450 induction, drug-drug interaction, permeability studies, etc.): Within 15 business days after completion of a study or a task, the Contractor shall submit two copies of a comprehensive draft report detailing the work completed, results, and conclusions to the NIDA COR.

Within 5-10 business days after receiving comments from the COR; the contractor shall submit four hard copies and electronic copy (PDF and Word files) of a final study/task report to the NIDA COR.

The study reports must be in a format suitable for submission to the FDA.

b. Monthly Progress Reports: Within the first 5 business days after each calendar month, the Contractor shall provide the COR two hard copies and electronic copy (Word file) of a report on http://www.hhs.gov/web/508/index.html

- 11 -activities during the preceding month. In the monthly report, the Contractor shall briefly (in one or two paragraphs) describe work accomplished (data generated), planned, any changes in staff, and actual or projected problems and proposed solutions. In addition, the Contractor shall include a list of final study/task reports sent to the NIDA COR during the month under report.

c. Annual Reports: Not later than 15 business days after the end of each year of contract work, the Contractor shall provide an executive summary and a comprehensive report on activities during the year. The executive summary shall provide a list of all studies performed during the year and status of studies. This comprehensive report shall contain detailed summary of all tasks/studies performed during the year including description of procedures/methods, results, and tentative conclusions. Four hard copies and electronic copy (PDF and Word files) of an executive summary and a report are to be sent to the NIDA COR. One hard copy of an executive summary is to be sent to the Contracting Officer. The annual report for the last year of the contact shall be incorporated into the Final Report.

d. Final report: On or before the expiration date of the contract, the Contractor shall provide an executive summary and a comprehensive summary of work conducted for each task. The report shall also include copies of publications and manuscripts, which the contractor may intend to submit for publication. This report shall incorporate the final annual report. Four hard copies and electronic copy (PDF and Word files) of an executive summary and a report are to be sent to the NIDA COR. One hard copy of an executive summary is to be sent to the Contracting Officer. The annual report for the last year of the contact shall be incorporated into the Final Report.

2. Summary of Salient Results

The Contractor will be required to prepare and submit, with the final report, a summary (not to exceed 200 words) of salient results achieved during the performance of the contract. This report will be required on or before the expiration date of the contract.

b. Other Reports/Deliverables

1. Reporting of Financial Conflict of Interest (FCOI)

All reports and documentation required by 45 CFR Part 94, Responsible Prospective Contractors including, but not limited to, the New FCOI Report, Annual FCOI Report, Revised FCOI Report, and the Mitigation Report, shall be submitted to the Contracting Officer in Electronic format. Thereafter, reports shall be due in accordance with the regulatory compliance requirements in 45 CFR Part 94.

45 CFR Part 94 is available at: http://www.ecfr.gov/cgi-bin/text-idx?

c=ecfr&SID=0af84ca649a74846f102aaf664da1623&rgn=div5&view=text&node=45:1.0.1.1.51&idno=45.

See Part 94.5, Management and reporting of financial conflicts of interest for complete information on reporting requirements.

(Reference subparagraph g. of the INSTITUTIONAL RESPONSIBILITY REGARDING INVESTIGATOR FINANCIAL CONFLICTS OF INTEREST Article in SECTION H of this contract.)

2. Information Security and Physical Access Reporting Requirements

The Contractor shall submit the following reports as required by the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract. Note: Each report listed below includes a reference to the appropriate subparagraph of this article.

a. Roster of Employees Requiring Suitability Investigations http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&SID=0af84ca649a74846f102aaf664da1623&rgn=div5&view=text&node=45:1.0.1.1.51&idno=45 http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&SID=0af84ca649a74846f102aaf664da1623&rgn=div5&view=text&node=45:1.0.1.1.51&idno=45

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The Contractor shall submit a roster, by name, position, e-mail address, phone number and responsibility, of all staff (including subcontractor staff) working under the contract who will develop, have the ability to access, or host and/or maintain a Federal information system(s). The roster shall be submitted to the Contracting Officer's Representative (COR), with a copy to the Contracting Officer, within 14 calendar days of the effective date of the contract. (Reference subparagraph A.d. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

b. IT Security Plan (IT-SP)

In accordance with HHSAR Clause 352.239-72, Security Requirements For Federal Information Technology Resources, the contractor shall submit the IT-SP within thirty

(30) days after contract award. The IT-SP shall be consistent with, and further detail the approach to, IT security contained in the Contractor's bid or proposal that resulted in the award of this contract. The IT-SP shall describe the processes and procedures that the Contractor will follow to ensure appropriate security of IT resources that are developed, processed, or used under this contract. If the IT-SP only applies to a portion of the contract, the Contractor shall specify those parts of the contract to which the IT-SP applies.

The Contractor shall review and update the IT-SP in accordance with NIST SP 800-53A, Guide for Assessing the Security Controls in Federal Information Systems and Organizations, on an annual basis.

(Reference subparagraph D.c.1. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

c. IT Security Certification and Accreditation (IT-SC&A)

In accordance with HHSAR Clause 352.239-72, Security Requirements For Federal Information Technology Resources, the Contractor shall submit written proof to the Contracting Officer that an IT-SC&A was performed within three (3) months after contract award.

The Contractor shall perform an annual security control assessment and provide to the Contracting Officer verification that the IT-SC&A remains valid.

(Reference subparagraph D.c.4. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

d. Reporting of New and Departing Employees

The Contractor shall notify the Contracting Officer's Representative (COR) and Contracting Officer within five working days of staffing changes for positions that require suitability determinations as follows:

a. New Employees who have or will have access to HHS Information systems or data: Provide the name, position title, e-mail address, and phone number of the new employee. Provide the name, position title and suitability level held by the former incumbent. If the employee is filling a new position, provide a description of the position and the Government will determine the appropriate security level.

b. Departing Employees: 1) Provide the name, position title, and security clearance level held by or pending for the individual; and 2) Perform and document the

- 13 -actions identified in the "Employee Separation Checklist", attached in Section J, ATTACHMENTS of this contract, when a Contractor/Subcontractor employee terminates work under this contract. All documentation shall be made available to the COR and/or Contracting Officer upon request.

(Reference subparagraph E.3.a-c. of the INFORMATION AND PHYSICAL ACCESS

e. Contractor - Employee Non-Disclosure Agreement(s) The contractor shall complete and submit a signed and witnessed "Commitment to Protect Non-Public Information

- Contractor Agreement" form for each contractor and subcontractor employee who may have access to non-public Department information under this contract. This form is located at: https://ocio.nih.gov/aboutus/publicinfosecurity/acquisition/Documents/ Nondisclosure.pdf.

(Reference subparagraph E.3.d. of the INFORMATION AND PHYSICAL ACCESS

3. Section 508 Annual Report

The contractor shall submit an annual Section 508 report in accordance with the schedule set forth in the ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY Article in SECTION H of this contract. The Section 508 Report Template and Instructions for completing the report are available at: http://www.hhs.gov/web/508/contracting/technology/vendors.html under "Vendor Information and Documents."

ARTICLE C.3. INVENTION REPORTING REQUIREMENT

All reports and documentation required by FAR Clause 52.227-11, Patent Rights-Ownership by the Contractor including, but not limited to, the invention disclosure report, the confirmatory license, and the Government support certification, shall be directed to the Division of Extramural Inventions and Technology Resources (DEITR), OPERA, OER, NIH, 6705 Rockledge Drive, Suite 310, MSC 7980, Bethesda, Maryland 20892-7980 (Telephone: 301-435-1986). In addition, one copy of an annual utilization report, and a copy of the final invention statement, shall be submitted to the Contracting Officer. The final invention statement (see FAR 27.303(b)(2)(ii)) shall be submitted to the Contracting Officer on the expiration date of the contract.

The annual utilization report shall be submitted in accordance with the DELIVERIES Article in SECTION F of this contract.The final invention statement (see FAR 27.303(b)(2)(ii)) shall be submitted on the expiration date of the task order. All reports shall be sent to the following address:

Contracting Officer NIDA R&D Contracts Management Branch Office of Acquisition National Institute on Drug Abuse National Institutes of Health 6001 Executive Boulevard, Suite 4211, MSC 9559 Bethesda, Maryland 20892

* If using Fed-Ex, UPS, other courier, or hand-delivery, please use Rockville, MD 20852.

If no invention is disclosed or no activity has occurred on a previously disclosed invention during the applicable reporting period, a negative report shall be submitted to the Contracting Officer at the address listed above.

http://www.hhs.gov/web/508/contracting/technology/vendors.html

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To assist contractors in complying with invention reporting requirements of the clause, the NIH has developed "Interagency Edison," an electronic invention reporting system. Use of Interagency Edison is encouraged as it streamlines the reporting process and greatly reduces paperwork. Access to the system is through a secure interactive Web site to ensure that all information submitted is protected. Interagency Edison and information relating to the capabilities of the system can be obtained from the Web ( http://www.iedison.gov), or by contacting the Extramural Inventions and Technology Resources Branch, OPERA, NIH.

[Remainder of page intentionally left blank] http://www.iedison.gov

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SECTION D - PACKAGING, MARKING AND SHIPPING

All deliverables required under this contract shall be packaged, marked and shipped in accordance with Government specifications. At a minimum, all deliverables shall be marked with the contract number and Contractor name. The Contractor shall guarantee that all required materials shall be delivered in immediate usable and acceptable condition.

[Remainder of page intentionally left blank]

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SECTION E - INSPECTION AND ACCEPTANCE

a. The Contracting Officer or the duly authorized representative will perform inspection and acceptance of materials and services to be provided.

b. For the purpose of this SECTION, TBD is the authorized representative of the Contracting Officer.

c. Inspection and acceptance will be performed at:

National Institute on Drug Abuse National Institutes of Health 6001 Executive Boulevard Bethesda, MD 20892

Acceptance may be presumed unless otherwise indicated in writing by the Contracting Officer or the duly authorized representative within 30 days of receipt.

d. This contract incorporates the following clause by reference, with the same force and effect as if it were given in full text. Upon request, the Contracting Officer will make its full text available.

FAR Clause 52.246-7, Inspection of Research and Development - Fixed Price (August 1996).

FAR Clause 52.246-16, Responsibility for Supplies (April 1984).

[Remainder of the page intentionally left blank]

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SECTION F - DELIVERIES OR PERFORMANCE

ARTICLE F.1. PERIOD OF PERFORMANCE

The period of performance of this contract shall be from December 29, 2014 through December 30, 2019.

ARTICLE F.2. DELIVERIES

Through awarded Task Orders satisfactory performance of the final contract shall be deemed to occur upon performance of the work described in the Description Article in SECTION C of this contract and upon delivery and acceptance by the Contracting Officer, or the duly authorized representative, of the following items in accordance with the stated delivery schedule:

a. The items specified below as described in the REPORTING REQUIREMENTS Article in SECTION C of this contract will be required to be delivered F.o.b. Destination as set forth in FAR 52.247-35, F.o.b. DESTINATION, WITHIN CONSIGNEES PREMISES (APRIL 1984), and in accordance with and by the date(s) specified below:

Item Description Quantity Delivery Schedule Place of Delivery

(1) Draft Study/Task

Report* 1 Within 15 business days of study completion

1 to COR

(2) Individual Study/ Task Reports*

2 Within 5-10 business days after receiving comments from COR

2 to COR

(3) Monthly Progress Report*

1 Within 5 calendar days of end of each calendar month

1 to COR

(4) Annual Progress Reports*

2 Within 15 business days of end of contract year

1 to COR 1 to CO

(5) Final Contract Report*

2 On or before end of contract

1 to COR 1 to CO

(6) All data, etc. in accordance with Task 9 and the "End of Contract" special requirements

3 On or before contract expiration

To be designated by

COR

(7) Annual Invention Report

1 Within 15 business days of end of contract year

1 to COR 1 to CO

(8) Summary of Salient Results

2 On or before contract expiration.

1 to COR 1 to CO

(9) IT Security Plan 3 Within 30 calendar days of contract effective date; and annually from contract effective date.

2 hardcopy to CO; 1 hardcopy to COR

(10) IT Security Certification and Accreditation

2 each Within 90 calendar days of contract effective date; and annually from contract

1 to CO; 1 to COR

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Item Description Quantity Delivery Schedule Place of Delivery effective date .

(11) Report of New and Departing Employees

2 Within 5 business days of staff changes for positions that require suitability determinations per Section C.

1 hardcopy to to CO;

1 hardcopy to COR

(12) Reporting of Financial Conflicts of Interest

2 See Article C.2(b)(1) for details

2 to CO

(13) Non-Disclosure Agreements

1 Prior to performance of any work under this contract.

1 to CO

* One electronic copy of the report shall also be provided to the COR. The electronic files in the form of a Microsoft Word document and a PDF format preferably on a CD.

b. The above items shall be addressed and delivered to:

c.

Addressee Deliverable Item No

Contracting Officer, 6001 Executive Blvd Suite 4211

MSC 9559

Bethesda, Maryland 20892-9559*

4-5, 7-13

Contracting Officer Representative, 6001 Executive Blvd Bethesda, Maryland 20892-9551*

1-11

* If using Fed-Ex, UPS, other courier, or hand-delivery, please use Rockville, MD 20852.

ARTICLE F.3. CLAUSES INCORPORATED BY REFERENCE, FAR 52.252-2 (FEBRUARY

1998)

This contract incorporates the following clause(s) by reference, with the same force and effect as if it were given in full text. Upon request, the Contracting Officer will make its full text available. Also, the full text of a clause may be accessed electronically at this address: http://www.acquisition.gov/far .

FEDERAL ACQUISITION REGULATION (48 CFR CHAPTER 1) CLAUSE:

52.242-15, Stop Work Order (August 1989)

Alternate I (April 1984) is not applicable to this contract.

52.242-17, Government Delay of Work (April 1984).

http://www.acquisition.gov/far

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SECTION G - CONTRACT ADMINISTRATION DATA

ARTICLE G.1. CONTRACTING OFFICER'S REPRESENTATIVE (COR)

The following Contracting Officer's Representative (COR) will represent the Government for the purpose of this contract:

TBD

The COR is responsible for: (1) monitoring the Contractor's technical progress, including the surveillance and assessment of performance and recommending to the Contracting Officer changes in requirements; (2) interpreting the statement of work and any other technical performance requirements; (3) performing technical evaluation as required; (4) performing technical inspections and acceptances required by this contract; and (5) assisting in the resolution of technical problems encountered during performance.

The alternate COR is responsible for carrying out the duties of the COR only in the event that the COR can no longer perform his/her duties as assigned.

The Contracting Officer is the only person with authority to act as agent of the Government under this contract. Only the Contracting Officer has authority to: (1) direct or negotiate any changes in the statement of work; (2) modify or extend the period of performance; (3) change the delivery schedule; (4) authorize reimbursement to the Contractor for any costs incurred during the performance of this contract; (5) otherwise change any terms and conditions of this contract; or (6) sign written licensing agreements. Any signed agreement shall be incorporated by reference in Section K of the contract

The Government may unilaterally change its COR designation.

ARTICLE G.2. KEY PERSONNEL, HHSAR 352.242-70 (January 2006)

The key personnel specified in this contract are considered to be essential to work performance. At least 30 days prior to diverting any of the specified individuals to other programs or contracts (or as soon as possible, if an individual must be replaced, for example, as a result of leaving the employ of the Contractor), the Contractor shall notify the Contracting Officer and shall submit comprehensive justification for the diversion or replacement request (including proposed substitutions for key personnel) to permit evaluation by the Government of the impact on performance under this contract. The Contractor shall not divert or otherwise replace any key personnel without the written consent of the Contracting Officer. The Government may modify the contract to add or delete key personnel at the request of the Contractor or Government.

(End of Clause)

The following individual(s) is/are considered to be essential to the work being performed hereunder:

Name Title

ARTICLE G.3. TASK ORDER PROCEDURE

This contract provides for the issuance of Task Orders on a negotiated basis as follows:

a. General

Only the Contracting Officer may issue Task Orders to the Contractor, providing specific authorization or direction to perform work within the scope of the contract and as specified in the Statement of Work. Unless specifically authorized by the Contracting Officer, the Contractor shall not commence work until a fully executed

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Task Order has been awarded. The Contractor may incur costs under this contract in performance of task orders and task order modifications issued in accordance with this ARTICLE.

No other costs are authorized unless otherwise specified in the contract or expressly authorized by the Contracting Officer.

b. Requesting Task Order Proposals.

The Contracting Officer or a designated individual may solicit responses to requirements from the Contractor. A Task Order Request for Proposals (TORFP) will be prepared and issued for each task order requirement.

Generally, the Task Order Request for Proposal (TORFP) will include but is not limited to the following:

1. Statement of Work;

2. Reporting Requirements and Deliverables;

3. Proposal Due Date and Location to Deliver Proposals;

4. Period of Performance of Task Order;

5. Anticipated type of Task Order;

6. Technical Proposal Instructions;

7. Business proposal Instructions

8. Evaluation Factors for Award

All contract clauses contained in this contract shall be incorporated in the TORFP and the resultant task order. If conflicts exist between the contract clauses and the information outlined in the task order, the contract language takes precedence over the information in the task order.

c. Ordering Process.

1. The Contractor will receive e-mail or letter notification advising of the availability of each proposed task order requirement. All proposed task orders will incorporate all terms of this contract unless otherwise specified in the proposed task order.

2. The Contractor will be provided an adequate time to prepare and submit responses based on the Contracting Officer's consideration of the estimated dollar value and complexity of proposed task order.

Responses will not be considered a proposal as defined in FAR Part 15. However, the Contractor shall provide information sufficient for consideration in accordance with FAR Part 16. Each TORFP will indicate the criteria for the evaluation of proposals. The responses shall demonstrate capability for each criterion to be evaluated. Generally, the Contractor will be asked to demonstrate the following as appropriate:

• Understanding of the requirements;

• Experience and capability on similar tasks;

• Technical approach, methods and procedures for satisfying the requirements with a discussion of potential problems to be encountered and proposed solutions and/or risk mitigation strategies.

• Procedures for assuring quality of work, products, and deliverables;

• Plan for managing the task order, including meeting requirements and schedules, and performance measures (if applicable);

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• Staffing plan with skill levels and level of effort for each individual proposed. Generally, resumes will be required for proposed personnel (if not previously submitted); and

• Cost/Price to perform the task order.

d. Evaluation and Award of Task Order Proposals

The Government will evaluate the Task Order proposal against the requirements of the TORFP. Specifically, the technical evaluation factors, price, and any other factor specifically identified in the TORFP will be used for evaluation of each proposal.

Upon completion of the evaluation, the Contracting Officer will issue a task order.

ARTICLE G.4. INVOICE SUBMISSION

a. Invoice Instructions for NIH Fixed-Price Type Contracts, NIH(RC)-2, are attached and made part of this contract.

The Contractor shall follow the attached instructions and submission procedures specified below to meet the requirements of a "proper invoice" pursuant to FAR Subpart 32.9, Prompt Payment.

1. Payment requests shall be submitted to the offices identified below. Do not submit supporting documentation (e.g., receipts, time sheets, vendor invoices, etc.) with your payment request unless specified elsewhere in the contract or requested by the Contracting Officer.

a. The original invoice shall be submitted to the following designated billing office:

National Institutes of Health Office of Financial Management Commercial Accounts 2115 East Jefferson Street, Room 4B-432, MSC 8500 Bethesda, MD 20892-8500

b. Two copies of the invoice shall be submitted to the following approval official:

Contracting Officer NIDA R&D Contracts Managment Branch Office of Acquisitions, NIDA National Institutes of Health 6001 Executive Boulevard Suite 4211 MSC 9559 Bethesda, MD 20892-9559

* If using Fed-Ex, UPS, other courier, or hand-delivery, please use Rockville, MD 20852.

2. In addition to the requirements specified in FAR 32.905 for a proper invoice, the Contractor shall include the following information on the face page of all payment requests:

a. Name of the Office of Acquisitions. The Office of Acquisitions for this contract is NIDA R&D Contracts Management Branch, Office of Acquisitions, NIDA .

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b. Federal Taxpayer…