N01DA-16-8926_RPF.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-16-8926

3. Issue Date:

March 11, 2016

4. Set Aside:

[ ] No

[X] Yes See Part IV Section L

5. Title : Development and Manufacture of Pharmaceutical Products for Treatment of Substance Abuse Disorders

6. ISSUED BY:

NIDA R&D Contracts Management Branch Office of Acquisitions, NIDA National Institute on Drug Abuse National Institutes of Health 6001 Executive Blvd., Suite 4211, MSC 9559 Bethesda, MD 20892-9559* *Note: For Other Than USPS Delivery, use: 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 April 26, 2016. 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." The OFFICIAL POINT OF RECEIPT for determining TIMELY DELIVERY is the address provided for the OFFICE OF ACQUISITIONS. (Not the lobby of the building)

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 subparagraph (c)(3) of FAR Clause 52.215-1, Instructions to Offerors--Competitive Acquisition," 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: Tracy Cain

PHONE: 301.443.6677

e-MAIL: tracy.cain@nih.gov

COLLECT CALLS WILL NOT BE ACCEPTED.

Brian H. O'Laughlin Contracting Officer Office of Acquisitions

R&D CMB, NIH/NIDA

http://www.sam.gov

RFP Number : N01DA-16-8926

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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. NOTICE OF SMALL BUSINESS SET-ASIDE

c. NAICS CODE AND SIZE STANDARD

d. TYPE OF CONTRACT AND NUMBER OF AWARDS

e. TASK ORDERS UNDER MULTIPLE AWARD INDEFINITE DELIVERY CONTRACTS

f. ESTIMATE OF EFFORT

g. COMMITMENT OF PUBLIC FUNDS

h. PROMOTING EFFICIENT SPENDING

i. COMMUNICATIONS PRIOR TO CONTRACT AWARD

j. RELEASE OF INFORMATION

k. PREPARATION COSTS

l. SERVICE OF PROTEST

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. Certification of Filing and Payment of Taxes

13. Past Performance Information

14. Information and Physical Access Security

15. 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. Total Compensation Plan

7. Other Administrative Data

8. Qualifications of the Offeror

9. Subcontractors

10. Proposer's Annual Financial Report

11. Travel Costs/Travel Policy

SECTION M - EVALUATION FACTORS FOR AWARD

1. GENERAL

2. COST/PRICE EVALUATION

3. MANDATORY QUALIFICATION CRITERIA

4. EVALUATION OF DATA SHARING PLAN

5. TECHNICAL EVALUATION FACTORS

6. EVALUATION OF ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY- SECTION

7. PAST PERFORMANCE FACTOR

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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, IF NECESSARY, 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 purpose of this contract is to carry out the development and manufacture of pharmaceutical preparations to be used in the medications development program for addiction treatment at the National Institute on Drug Abuse (NIDA).

ARTICLE B.2. PRICES/COSTS - TASK ORDER

a. This is an Indefinite Delivery, 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 $10,000 (minimum) nor more than a total of $7,000,000 (maximum) for successful performance of this contract. The minimum amount is inclusive of all task orders issued under this contract. Total compensation will be based on the combined negotiated task orders (cost reimbursement or fixed price).

b. For cost reimbursement task orders, the fixed fee for individual task orders will be negotiated by task order. The fixed fee shall be paid in installments as negotiated (based on percentage of completion of work or the percent of total effort expended), as determined by the Contracting Officer, and shall be subject to the withholding provisions of the clauses ALLOWABLE COST AND PAYMENT and FIXED FEE referenced in the General Clause Listing in Part II, ARTICLE I.1. of this contract. Payment of fixed fee shall not be made in less than monthly increments.

c. The costs/prices set forth in this ARTICLE will cover the contract period September 18, 2016 through September 17, 2021.

d. The Government will issue fixed price or cost reimbursement Task Orders (severable and nonseverable) based on the work described in SECTION C of this contract.

e. Ordering procedures are described in the TASK ORDER PROCEDURE Article in SECTION G of this contract.

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)

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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 provided benefit NIDA and any other component of HHS.

[Remainder of Page Intentionally Left Blank]

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SECTION C - DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

ARTICLE C.1. DESCRIPTION-STATEMENT OF WORK

Background Statement/project history

The purpose of this contract is to carry out the development and manufacture of pharmaceutical preparations to be used in the medications development program of the National Institute on Drug Abuse (NIDA) for treating substance use disorders. Development of medications for the treatment of substance use disorders is a major mission of NIDA.

Some of the potential treatment drugs currently being investigated are new chemical entities (e.g., AZD 8529, etc.)

and previously approved drug substances. These drugs are acquired by the Government from private industry, Government contractors/grantees, or independent investigators. This contract is to provide the Government a resource for the development and manufacture of stable dosage forms for use in preclinical and clinical studies.

The Contractor shall be responsible for carrying out preformulation studies on drug substances, developing and manufacturing dosage forms, developing and validating analytical methods for dosage forms, carrying out stability studies, and packaging and delivering of the pharmaceutical products to NIDA designated sites. In addition, the Contractor shall provide adequate facilities for the storage of bulk drug substances, including controlled substances and their finished dosage forms. The Contractor shall have appropriate DEA Registrations for Schedules II-V Controlled Substances in order to use the controlled substances in research and manufacture of dosage forms under the Controlled Substance Act of 1970. The Contractor must either possess or demonstrate the ability to obtain DEA Registrations for Schedule I Controlled Substances should the research and manufacture of the Schedule I drugs be required under this IDIQ, task order contract.

The Contractor shall carry out the tasks in compliance with the Food and Drug Administration's (FDA) current Good Manufacturing Practice regulations (cGMP). The data and documentation prepared should be in a format acceptable to FDA for inclusion in Drug Master Files (DMF), Investigational New Drugs (IND), or New Drug Applications (NDA).

I. Objectives

The Contractor will to serve as a resource for developing and manufacturing dosage forms to be used in preclinical pharmacological/ toxicological evaluations and clinical trials. In brief, the objectives of this contract are: (1) preformulation studies on bulk drug substances; (2) formulation studies to select a formulation(s); (3) manufacture of active formulations and placebos; (4) analytical method development and validation; (5) preparation of drug product specifications; (6) packaging of the dosage forms; (7) determination of stability of finished dosage forms under accelerated and/or long-term storage; (8) maintenance of an adequate storage facility for drug substances and finished dosage forms including controlled substances; (9) shipment of drug substances and dosage forms to NIDA designated sites; and (10) generation of reports, data, and documentation to be used by NIDA in the preparation of Investigational New Drug (IND), New Drug Application (NDA), and/or Drug Master File (DMF).

II. Services to be Performed

A. General Requirements

1. Independently, and not as an agent of the Government, the Contractor shall furnish all necessary labor, facilities, materials (except experimental bulk drugs), supplies, equipment, and services (except as otherwise specified herein) and perform the work set forth below.

2. The Contractor shall provide adequate facilities for the storage of bulk drug substances, including controlled substances, and their finished dosage forms.

3. All work under this contract shall be monitored by the Government Contract Officer's Representative (COR), whose position is defined in this contract.

4. The Contractor may not inititate work until a Task Order has been issued.

B. Specific Requirements

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1. Specific Tasks to Be Performed Through Issued Task Orders:

The Contractor shall provide the COR with a delivery schedule for Tasks A through L in accordance with Section F.

Task A - Preformulation Study I: The Contractor shall perform physical and chemical characterization of drug substances to determine the properties as described below. The Preformulation Study I puts emphasis on obtaining preliminary information for early identification of problems with the drug substances under study. Task A emphasizes crude estimation of solubility and stability with less emphasis on analytical method development. The COR will provide the Contractor with any physical, chemical, and safety information on any analytical methods available concerning the drug substances. The Contractor is responsible for validating methods used.

The following properties will be determined:

a. Organoleptic.

b. Microscopic: Morphology, birefringency, and particle size.

c. Physical: Hygroscopicity, melting point, thermal analysis, and polymorphism.

d. Solution: pKa, partition coefficient, and solubility in various solvent systems, such as water and buffers (pH 1 and pH 7.4). If necessary, surfactant solutions, cyclodextrin solutions, non-aqueous solvents, and mixed solvents may be used for solubility.

e. Stability: Solid and solution stability, including photostability under accelerated and/or long-term storage conditions, such as room temperature and refrigeration conditions using thermal analysis, spectroscopy techniques, and/or other methods available.

Task B - Preformulation Study II: The Contractor shall perform Preformulation Study II on drug substances designated by the COR. Preformulation Study II puts emphasis on physical and chemical stability of drug-excipients mixtures either in solid or solution state under accelerated and/or long-term storage conditions without too much emphasis on method validation. The work elements for Task B are as follows:

a. Physical characteristics of bulk drugs: Density, surface area, static charge, flow properties, compressibility, dissolution rates at pHs 1 and 7.4, and pH-solubility profiles.

b. Drug-excipients compatibility in solid state: Physical mixtures of drug and commonly used excipients for tablets and capsules will be evaluated for physical and chemical stability under accelerated and/or long-term storage conditions. Dissolution rates of the drug-excipients mixtures will be measured at pHs 1 and 7.4.

c. Drug-excipients compatibility in solution state: Physical and chemical stability of drug solutions in aqueous vehicles containing commonly used excipients, such as antioxidants, buffers, antimicrobial agents, non-aqueous solvents, or solubilizing agents, will be evaluated under accelerated and/or long-term storage conditions.

d. Analytical methods development: Analytical methods development to evaluate the stability of the drug-excipients mixtures in solid and solution states for screening purposes.

Task C - Formulation Study: The Contractor shall perform Formulation Studies for drug substances designated by the COR. Formulation Studies should put emphasis on dosage form development for Phase I and II clinical trials, evaluation of physical and chemical stability of candidate formulations including solid, liquid (solution, emulsion, and suspension), and semi-solid under accelerated and/or long-term storage conditions, manufacturing procedures, and product specifications. The work elements for the Task C are as follows:

a. Preparation of prototype formulations for Phases I and II based on the preformulation data or other data available.

b. Physical and chemical stability studies of the prototype formulations under accelerated and/or long-term storage conditions.

c. Optimization of the prototype formulations, if needed.

d. Selection of packaging/closure system based on the stability study for moisture-sensitive dosage forms and on the compatibility study especially for liquid dosage forms.

e. Stability studies on the optimized/selected formulations, if needed.

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f. Establishment of a final formulation based on the stability data.

g. Establishment of a placebo formulation.

h. Establishment of manufacturing procedures for a batch size of up to 30,000 units for active and placebo drugs.

i. Establishment of test methods for active and placebo in accordance with United States Pharmacopeia (USP) and FDA/International Conference on Harmonization (ICH) guidelines.

j. Establishment of tentative product specifications for active and placebo in accordance with USP and FDA/ICH guidelines.

Task D - Development and Validation of Stability-Indicating Methods for Drug Products: The Contractor shall develop and validate stability-indicating methods for release of the products and stability testing in accordance with FDA regulations/ICH guidelines. Parameters for validation include accuracy, detection limit, quantitation limit, linearity, precision, range, recovery, robustness, sample solution stability, specificity/selectivity, and system suitability specifications/tests.

Task E - Manufacture of Drug Products for Phase I and II Clinical Trials (tablets, sublingual tablets, hard gelatin capsules, soft gelatin capsules, etc. except injectables): The Contractor shall manufacture under cGMP a batch of active drug product and matching placebo for each of two strengths based on the formulation and manufacturing procedures developed under formulation studies or based on the data provided by the COR in case the product had been manufactured elsewhere and the information on formulation, manufacturing procedures, test methods, and product specifications are available. The typical batch size falls within 30,000 tablets/capsules. The batches may be manufactured manually or using automatic or semi-automatic production equipment. Production for oral dosage forms shall be completed within 8 weeks of assignment, and quality control for batch release, labeling, and packaging shall be completed within the following 4 weeks. The work elements for Task E are as follows:

a. Manufacturing a batch of active drug product and matching placebo under cGMP for each of two strengths. In-process control on blend uniformity, tablets or capsules weight variation, and content uniformity should be closely monitored for solid dosage forms.

b. Packaging and labeling in accordance with Federal Regulations for Investigational New Drugs.

c. Testing for release of the product based on release specifications.

d. Storing the drug product under appropriate conditions for stability. Products containing controlled substances should be handled for security in accordance with DEA regulations.

e. Shipping the drug product to clinical study sites or a location designated by the COR for distribution to preclinical/clinical investigators.

Task F - Stability Study I: This task is for a stability study to be initiated for new drug product. The Contractor shall set up a 5-year stability study protocol to ensure the product stability during the preclinical/ clinical studies. The stability study will be conducted under long-term (usually 60 months), accelerated (6 months), intermediate (12 months), and photostability conditions. FDA regulations and International Conference on Harmonization (ICH) guidances on stability studies on drug products should be consulted.

The work elements for Task F are as follows:

a. Prepare a stability study protocol for long-term (usually 60 months), accelerated (6 months), intermediate (12 months), and photostability conditions in accordance with FDA and ICH guidelines on stability.

b. Store the drug product under appropriate conditions for stability. Products containing controlled substances should be handled for security in accordance with DEA regulations.

c. The recommended sampling schedules are as follows:

Long-term study: 0, 3, 6, 9, 12, 24, 36, 48, 60 months Accelerated study: 1, 2, 3, 6 months Intermediate study: 2, 4, 6, 9, 12 months

d. The storage conditions and sampling schedules will vary depending on the stability of drug and the dosage form under study.

Task G - Stability Study II: This task is for continuing a stability study that was previously initiated.

The Contractor shall follow the stability protocol to conduct the stability testings. FDA regulations and

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International Conference on Harmonization (ICH) guidances on stability studies on drug products should be consulted. The work elements for the Task G are as follows:

a. Continue the stability study following the already established stability study protocol for long-term (usually 60 months), accelerated (6 months), intermediate (12 months), and photostability conditions in accordance with FDA and ICH guidelines on stability.

b. Store the drug product under appropriate conditions for stability. Products containing controlled substances should be handled for security in accordance with DEA regulations.

c. The recommended sampling schedules are as follows:

Long-term study: 0, 3, 6, 9, 12, 24, 36, 48, 60 months Accelerated study: 1, 2, 3, 6 months Intermediate study: 2, 4, 6, 9, 12 months

d. The storage conditions and sampling schedules will vary depending on the stability of drug and the dosage form under study.

Task H - Manufacture of Drug Products for Phase III Clinical Trials (mainly Tablets or Capsules):

The Contractor shall manufacture under cGMP a batch of active drug product and matching placebo based on the formulation and manufacturing procedures developed under formulation studies or based on the data provided by the COR in case the product had been manufactured elsewhere and the information on formulation, manufacturing procedures, test methods, and product specifications are available. It may be necessary to modify the formulation or manufacturing procedures to scale up to the larger batch sizes.

The typical batch size is 400,000 tablets or capsules. Production shall be completed within 12 weeks of assignment, and quality control, labeling, and packaging shall be completed within the following 4 weeks.

The work elements for the Task H are as follows:

a. Manufacturing a batch of active or placebo product under cGMP. In-process control on blend uniformity, tablets or capsules weight variation, and content uniformity should be closely monitored.

b. Packaging and labeling in accordance with Federal Regulations for Investigational New Drugs.

c. Testing for release of the product based on release specifications.

d. Storing the drug product under appropriate conditions for stability. Products containing controlled substances should be handled in accordance with DEA regulations.

e. Shipping the drug product to a place designated by the COR for distribution to clinical investigators.

Task I - Manufacture of Injectables: The Contractor shall manufacture at an appropriate manufacturing facility under cGMP a batch of single or multiple dose vials based on the formulation and manufacturing procedures developed under formulation studies or based on the data provided by the COR in case the product had been manufactured elsewhere and the information on formulation, manufacturing procedures, test methods, and product specifications are available. The injectables to be manufactured include cocaine, methamphetamine, and other drugs as designated by the COR. The typical batch size is 5,000 multiple dose vials of 5 mL/vial or its equivalent number of vials in case of using single dose vials. Production for injectables shall be completed within 6 months of assignment, and quality control for batch release, labeling, and packaging shall be completed within the following 2 months. The work elements for Task I are as follows:

a. Manufacturing of Injectables with in-process control and monitoring on clarity of the solution, pH, potency, integrity of aseptic filter, fill volume, and particulates, control of aseptic environment, control of packaging components in terms of sterility and bacterial endotoxins/pyrogens contamination, and/or monitoring of the lyophilization process.

b. Packaging and labeling in accordance with Federal Regulations for Investigational New Drugs.

c. Testing for release of the product based on release specifications.

d. Storing the drug product under appropriate conditions for stability. Products containing controlled substances should be handled for security in accordance with DEA regulations.

e. Shipping the drug product to clinical study sites or a location designated by the COR for distribution to preclinical/clinical investigators.

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Task J - Purchase of Drug Substances, Drug Products, and/or Other Items for Manufacture of Drug Products for Phase I-III Clinical Trials: The Contractor shall use Task J to purchase drug substances, drug products, and other necessary items (e.g., packaging) from vendors on the open market for the manufacture of clinical supplies for Phase I-III clinical trials.

Task K - End of Contract Transition Activities and Archival Maintenance of Records: At the end of the Contract, all drug substances and drug products shall be delivered to a NIDA Contractor for storage and/or stability testing as designated by the COR. At the end of the Contract, if the Government opts to issue a Task Order for Task K, all data including laboratory notebooks, hard copies of raw data, and databases of assay results on disk shall be placed in secure storage for a period of 5 years after the Contract ends for a GMP audit, which may be required by FDA in connection with an IND or NDA submission. During this period, the contractor shall be responsible for the integrity and organization of the material and its confidentiality. At any time during this task, all reference material, data files, etc. will be disposed of per instructions of the COR.

Task L - Phase-In Transition Activities: At the beginning of the Contract, if a Contractor other than the incumbent receives the follow-on award, the Contractor shall receive from the incumbent all inventory of drug substances and drug products under storage and stability studies and all data including laboratory notebooks, hard copies of raw data, and databases of assay results on disk. Most of the drug substances, drug products, and data require storage and handling specified under GMP regulations. Some of the drug substances and drug products require storage and handling specified under DEA regulations.

C. Sample Task Orders

FOR TECHNICAL PROPOSAL EVALUATION: For purposes of technical proposal preparation, offerors are to provide a technical proposal including timelines for each of the tasks listed above, the number of hours the offeror would spend on each task, and the way the offeror would accomplish each task.

FOR COST PROPOSAL EVALUATION: For purposes of cost proposal preparation, offerors are to provide a cost proposal including timelines and cost or price estimates, as applicable, for each of the tasks listed below. At contract award, NIDA expects to award one or more of the following sample task orders.

1. Sample Task Order 1:

An example of Sample Task Order 1 is included in the Attachments. This task order is anticipated to be ordered annually.

This sample Task Order encompasses Tasks A, B, C, D, E, F, and G. FOR PROPOSAL PURPOSES, the number of drug substances and drug products to be studied, etc. is given under each task as described below and also summarized in Table 1:

a) Task A (Preformulation Study I): Six drug substances, new chemical entities or previously approved drug substances, to be studied.

b) Task B (Preformulation Study II): Two drug substances, new chemical entities or previously approved drug substances, to be studied.

c) Task C (Formulation Study): Formulation studies for two drug substances.

d) Task D (Development and Validation of Stability Indicating Methods for Drug Products): Develop and validate methods for the formulations (active and matching placebo) developed under Task C for two drug substances.

e) Task E (Manufacture of Drug Products for Phases I and II Clinical Trials, such as tablets, sublingual tablets, hard gelatin capsules, soft gelatin capsules, etc.): Manufacture up to 30,000 dosing units of active and 30,000 dosing units of matching placebo for two strengths or batches for each of two drug substances.

f) Task F (Stability Study I): Perform stability studies for four batches of active drug products and up to two strengths or batches of matching placebos manufactured under Task E.

g) Task G (Stability Study II): Perform continuing stability studies for 10 batches of active drug products and 10 batches of matching placebos that have been under study about a year or longer.

2. Sample Task Order 2:

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The Contractor shall perform Task A (Preformulation Study I) for three additional drug substances.

3. Sample Task Order 3:

The Contractor shall perform Task B (Preformulation Study II) for an additional drug substance.

4. Sample Task Order 4:

The Contractor shall perform Task C (Formulation Study) for an additional drug substance.

5. Sample Task Order 5:

The Contractor shall perform Task D (Development and Validation of Stability Indicating Methods for Drug Products) for an additional drug product and placebo.

6. Sample Task Order 6:

The Contractor shall perform Task E (Manufacture of Drug Products for Phase I and II Clinical Trials) for an additional drug substance to manufacture two batches of an active drug product and matching placebo.

7. Sample Task Order 7:

The Contractor shall perform Task F (Stability Study I) for two batches of an active drug product and matching placebo.

8. Sample Task Order 8:

The Contractor shall perform Task G (Stability Study II) for 10 batches of active drug products and matching placebos that have been under stability study about a year or longer.

9. Sample Task Order 9:

The Contractor shall perform Task H (Manufacture of Drug Products for Phase III Clinical Trials) to manufacture two batches of active and matching placebo drug products.

10. Sample Task Order 10:

The Contractor shall perform Task I (Manufacture of Injectables) to manufacture an injectable dosage form.

11. Sample Task Order 11:

The Contractor shall perform Task J (Purchase of Drug Substances, Drug Products, and/or Other Items) for the manufacture of clinical supplies.

12. Sample Task Order 12:

The Contractor shall perform Task K (End of Contract Transition Activities).

13. Sample Task Order 13:

The Contractor shall perform Task L (Phase-In Transition Activities).

ARTICLE C.2. REPORTING REQUIREMENTS

All reports required herein shall be submitted in electronic format. In addition, hardcopies of reports shall be submitted to the Contracting Officer, in accordance with Section F.

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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.

For proposal preparation purposes only, it is estimated that in addition to the required electronic version(s) hard copies of these reports will be required as follows:

a. Monthly Progress Reports: Within the first 5 working days after each calendar month, the Contractor shall provide the COR two hard copies and one electronic copy of a report on 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.

b. Task Reports submitted after the completion of a task for a drug substance and/or a drug product should present a detailed description of procedures, methods, results, discussions, and conclusions. Additionally, a report at the completion of all tasks required for a drug substance and/or a drug product is to be prepared and delivered. The Contractor shall submit one hard copy and an electronic version of the Study Report, mailed to the NIDA COR, and shall prepare Chemistry, Manufacturing and Control (CMC) section of IND, DMF or NDA documents and deliver to NIDA when there is a need.

c. Annual Reports: Not later than 15 working 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 one electronic copy 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 one electronic copy 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.

http://www.hhs.gov/web/508/index.html

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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 Hard Copy 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. Final Status Report on Data, Products and Materials

Final Status Report on Data, Products and Materials: 30 days prior to contract expiration, the Contractor shall submit a Final Status Report on all Deliverables covered by items 4, 5, & 7 under Article F.2, including but not limited to: all archived data, tapes, materials, drugs substances/products, data sets, files, supplies and records generated under the contract. The Report shall be submitted to the Contracting Officer (CO) electronically.

3. 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

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 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

- 14 -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 Risk Assessment (IT-RA)

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

(30) days after contract award. The IT-RA shall be consistent, in form and content, with NIST SP 800-30, Risk Management Guide for Information Technology Systems, and any additions or augmentations described in the HHS-OCIO Information Systems Security and Privacy Policy.

The Contractor shall update the IT-RA on an annual basis.

(Reference subparagraph D.c.2. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

d. FIPS 199 Assessment

In accordance with HHSAR Clause 352.239-72, Security Requirements For Federal Information Technology Resources, the Contractor shall submit a FIPS 199 Assessment within thirty (30) days after contract award. The FIPS 199 Assessment shall be consistent with the cited NIST standard.

(Reference subparagraph D.c.3. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECITON H of this contract.

e. 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.)

f. 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:

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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 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

g. 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

h. Vulnerability Scanning Reports

The Contractor shall report the results of the required monthly special vulnerability scans no later than 10 days following the end of each reporting period. If required monthly, this report may be included as part of the Technical Progress Report. Otherwise, this report shall be submitted under separate cover on a monthly basis.

(Reference subparagraph E.5. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

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

- 16 -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 contract. All reports shall be sent to the following address:

Contracting Officer NIDA R&D Contracts Management Branch National Institute on Drug Abuse 6001 Executive Blvd.

Room 4211, MSC 9559 Bethesda, Maryland 20892- 9559

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.

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 required 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.

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.

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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, The Contracting Officer's Representative (see Section G) 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 Blvd 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.

The Government may reject any deliverable deemed to be of unacceptable quality by the Government using a standard that would be acceptable to a reasonable person of the proper scientific and mathematical knowledge.

Quality, as used in this clause, refers to thoroughness and attention to detail rather than disagreements as to the scope of the specific assignment. Deliverables rejected under this clause will be raised to acceptable quality, whether through revision or complete reproduction, at cost to Contractor not to be reimbursed by the Government. The Government reserves all other rights to rejection elsewhere in this contract.

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 52.246-8, Inspection of Research and Development - Cost-Reimbursement (May 2001).

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

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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 September 18, 2016 through September 17, 2021.

ARTICLE F.2. DELIVERIES

Satisfactory performance of the final contract shall be deemed to occur upon performance of the work described in the Statement of Work 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 and any specifications stated in SECTION D, PACKAGING, MARKING AND SHIPPING, of this contract:

b.

Item Description Quantity Delivery Schedule Place of Delivery

(1) Monthly Progress Reports with Vulnerability Scanning Requirements

1 Within 5 days of end of calender month

1 to Contracting Officer's Representative

(COR)

(2) Task Reports 1 Within 5 days of task completion

1 to COR

(3) Annual Progress Reports

2 Within 15 days of end of contract year

1 to COR, 1 to Contracting Officer

(CO)

(4) Final Contract Report 2 On or before contract expiration

1 to COR, 1 to CO

(5) Archived data, tapes, materials, etc. (Task K)

All On or before contract expiration

Per instruction of disposal

(6) All drugs substances/ products

All On or before contract expiration

Per instruction of disposal

(7) Summary of Salient Results

2 With Final Report 1 to COR, 1…