RFP No. 75N95020R00036 - Final.pdf

National Institute on Drug Abuse Request for Proposal (RFP) No. 75N95020R00036

“Development & Manufacture of Pharmaceutical Products for the Treatment of Substance Abuse Disorders”

Issued by:

Tracy Cain, Contracting Officer NIDA Section, Contracts Management Branch Red Office of Acquisitions, NIDA National Institute on Drug Abuse, NIH c/o 3WFN MSC 6012 301 N Stonestreet Ave Bethesda, MD 20892 Point of Contact: Tracy Cain, Contracting Officer E-Mail: tracy.cain@nih.gov Phone: 301.443.6677

DATE ISSUED: Tuesday, March 2, 2020

PROPOSAL DUE DATE: Friday, April 16, 2020, 2:00 P.M. Eastern Time

The National Institute on Drug Abuse invites you to submit a proposal responding to the requirements of this RFP No. 75N95020R00036 titled “Development & Manufacture of Pharmaceutical Products for the Treatment of Substance Abuse Disorders”.

This RFP is prepared in accordance with the Uniform Contract Format (UCF) prescribed for Government wide application by the Federal Acquisition Regulation (FAR). The UCF is both an RFP and contract award document. The resulting contract will consist of Parts I, II, III of the Uniform Contract Format.

We expect to award an Indefinite Delivery Indefinite Quantity (Task Order) cost reimbursement level of effort-type contract for a period of 5 years. Please anticipate that the base performance period of the contract will be from September 18, 2021 to September 17, 2026. You must respond with technical and pricing proposals for the entire project and total period of performance.

General

Part IV of the RFP contains instructions, provisions, and evaluation factors for the submission and review of proposals. Attachment 2 is a "Proposal Intent Response Sheet." Please complete this form and return it to tracy.cain@nih.gov by March 30, 2021. The balance of Parts I, II, and III contain provisions, clauses, and special requirements which will be made a part of any resultant award. Please review these sections and consider their impact on performance, capability, technical, and cost factors as you develop your proposal. Do not fill in blanks or otherwise complete portions of Parts I, II, and III which appear to require additional information.

The Government will complete these items prior to contract award and, if negotiations are mailto:tracy.cain@nih.gov conducted, will tailor those items through final negotiations.

Furnish in writing (e-mail is acceptable) to the Contracting Officer any areas of uncertainty, which, in your opinion, require clarification or correction. You must submit your questions in sufficient time for receipt by the Contracting Officer on or before March 30, 2021. Mark the e-mail, "Offeror's Questions, RFP No. 75N95020R00036."

The Business Proposal

The Business Proposal must contain a detailed breakdown of costs by task, for each cost category/element, an explanation of the basis for all costs, and provide documentation to support these costs. Please utilize the Breakdown of Proposed Estimated Costs and Excel spreadsheet contained in Attachment 10.

A completed Form NIH-2043, “Proposal Summary and Data Record” must be included with the Business Proposal. Include the e-mail addresses of both the Principal Investigator and the responsible business representative on the form.

The Offeror must submit its Travel Policy, Total Compensation Plan and Annual Report with the initial Business Proposal.

See Section L.2.c. for additional detail.

The Technical Proposal

Offerors shall complete and attach the “Technical Proposal Cover Sheet” to their technical proposal. Be sure to list all professional personnel and organizations named in the proposal who have any role in the proposed work including staff, subcontractors, collaborating organizations, and consultants. Organizational affiliation(s) must be shown for each person named. If needed, additional sheets may be included using the same format. This information is vital to ensure that no conflicts of interest exist with the review committee members.

Format and content requirements for the Technical Proposal are detailed in Section L.2.b.

Submitting a Proposal

Proposals must be submitted via the electronic Contract Proposal Submission (eCPS) website (https://ecps.nih.gov) no later than Friday, April 16, 2021, 2:00 P.M. Eastern Time. Proposals submitted by facsimile, e-mail, or hard copy will not be accepted. An official authorized to bind your organization must sign the proposal.

Offerors are solely responsible for submitting proposals in a timely manner. Please note that creating an account to submit may take up to three (3) business days. Please plan accordingly. Additional instructions on how to submit a proposal via eCPS can be found at https://ecps.nih.gov/home/howto and in Attachment 01.

All notices related to this solicitation will be posted on beta.Sam.gov (https://www.beta.sam.gov) http://rcb.cancer.gov/rcb-internet/forms/2043.pdf http://ocm.od.nih.gov/contracts/rfps/TechCov.htm https://ecps.nih.gov/ https://ecps.nih.gov/home/howto https://www.beta.sam.gov/ as well as the NIDA Contracts Home Page (https://www.drugabuse.gov/funding/funding-opportunities/nida-requests-contract-proposals-rfps). If you would like to receive e-mail notifications of updates to this solicitation, please register with Beta.SAM.gov.

In accordance with FAR 15.306(a)(3) and FAR 52.215-1, the Government intends to evaluate proposals and award a contract without discussions. Therefore, your initial proposal should contain the best terms from cost or price and technical standpoints. The Government does, however, reserve the right to conduct discussions if the Contracting Officer determines them to be necessary.

Disclaimers

This RFP does not commit the Government to pay the costs for the preparation and submission of a proposal. The Contracting Officer is the only individual who legally can commit the Government to the expenditure of public funds in connection with this acquisition.

Any contract award for this requirement is contingent on the availability of funds (see FAR 52.232-18, Availability of Funds – April 1984).

The National Institute on Drug Abuse appreciates your interest in this RFP and looks forward to receipt of your proposal. Requests for any information concerning this RFP should be directed to Tracy Cain, at the NIDA Section, Contracts Management Branch Red, who may be reached at (301) 443-6677; collect calls will not be accepted. Discussions with any other individual outside the NIDA Section, Contracts Management Branch Red should not occur.

Sincerely, Tracy Cain, Contracting Officer NIDA Section, Contracts Management Branch Red Office of Acquisitions, NIDA/NIH

Enclosure https://www.drugabuse.gov/funding/funding-opportunities/nida-requests-contract-proposals-rfps https://www.drugabuse.gov/funding/funding-opportunities/nida-requests-contract-proposals-rfps

SOLICITATION

SECTION A - SOLICITATION/CONTRACT FORM

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

2. Request for Proposal (RFP) Number:

75N95020R00036

3. Issue Date:

3/2/2021

4. Set Aside:

[X] No [ ] Yes See Part IV Section L

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

6. ISSUED BY:

NIDA Section, Contracts Management Branch Red Office of Acquisitions, National Institute on Drug Abuse, NIH c/o 3WFN MSC 6012 301 N Stonestreet Ave Bethesda, MD 20892

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 Proposals for Use with the NIH electronic Contract Proposal Submission (eCPS) Website," until 2:00 PM local time on April 16, 2021. 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 Proposals for Use with the NIH electronic Contract Proposal Submission (eCPS) Website." If proposals are required to be delivered to two different locations, the OFFICIAL POINT OF RECEIPT for determining TIMELY DELIVERY is the eCPS Website.

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 System for Award Management (SAM) 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, Contracting Officer

PHONE: (301) 443-6677

e-MAIL: tracy.cain@nih.gov

COLLECT CALLS WILL NOT BE ACCEPTED.

Tracy Cain Contracting Officer Office of Acquisitions http://www.sam.gov/

RFP Number : 75N95020R00036

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

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. LEVEL OF EFFORT

e. COMMITMENT OF PUBLIC FUNDS

f. PROMOTING EFFICIENT SPENDING…………………………………………………………………………..48

g. COMMUNICATIONS PRIOR TO CONTRACT AWARD

h. RELEASE OF INFORMATION

i. PREPARATION COSTS

j. SERVICE OF PROTEST

k. LATE PROPOSALS AND REVISIONS

2. INSTRUCTIONS TO OFFERORS

a. GENERAL INSTRUCTIONS

b. TECHNICAL PROPOSAL INSTRUCTIONS

c. BUSINESS PROPOSAL INSTRUCTIONS

SECTION M - EVALUATION FACTORS FOR AWARD

1. GENERAL

2. COST/PRICE EVALUATION

3. MANDATORY QUALIFICATION CRITERIA

4. EVALUATION OF AUTHENTICATION OF KEY BIOLOGICAL AND/OR CHEMICAL RESOURCES………..73

5. EVALUATION OF DATA SHARING PLAN

6. TECHNICAL EVALUATION FACTORS

7. PAST PERFORMANCE FACTOR

8. SUBCOTRACTING PROGRAM EVALUATION CRITERIA

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 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, 2021 through September 17, 2026.

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) 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 in this contract benefit NIDA and other components of NIH.

To ensure that the Contractor is aware of the criticality of beginning contract close out process immediately following contract expiration, the Contractor shall include an Advance Understandings provision identifying the requirement to submit certain close out documents at the time of delivery of the final report under the contract, and is advised that quick close out procedures in accordance with FAR 42.7 shall be used by the Government to the maximum extent possible to expedite the administrative close of the contract or task order.

[Remainder of Page Intentionally Left Blank]

SECTION C - DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

ARTICLE C.1. STATEMENT OF WORK

I. Objectives

The National Institute on Drug Abuse (NIDA) is soliciting a Contractor providing services for developing and manufacturing dosage forms to be used for preclinical pharmacological/ toxicological evaluations and clinical trials in support of NIDA’s medication development programs. In brief, the objectives of this contract are: (1) pre-formulation studies on bulk drug substances and formulation studies to select a formulation(s); (2 ) manufacture and packaging of finished dosage forms and placebos; (3 ) analytical method development and validation for the dosage forms; (4) establishment of specifications for the dosage forms ;; (5) determination of stability of the finished dosage forms and the placebos under accelerated and/or long-term storage in compliance of the FDA guidance on stability of drug products; (6) maintenance of an adequate storage facility for drug substances and finished dosage forms including controlled substances; (7) shipment of drug substances and dosage forms to sites designated by the NIDA; and (8) generation of reports, data, and documents 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

a. 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.

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

c. All work under this contract shall be monitored by the Government Contract Officer’s Representative (COR), whose position is defined in Section G of this contract.

B. Specific Requirements

a. Specific Tasks to Be Performed:

The Contractor shall provide the COR with a delivery schedule for Tasks A through K in accordance with Section G. The COR will notify the contractor of approval or modifications to the delivery schedule within 10 business days after receiving the schedule. The Contractor may not initiate work until a Task Order has been issued.

Task A – Pre-formulation Study: The Contractor shall perform physicochemical characterization of drug substances and physicochemical stability of drug- excipients mixtures either in solid or solution state under accelerated and/or long-term conditions. The COR will provide physicochemical properties or analytical method of drug substances to the Contractor if they are available at the time of task order assignment.

The work elements for Task A are as follows depending on dosage forms assigned:

● Hygroscopicity, polymorphism, particle size distribution, pKa, partition coefficient, pH-dependent aqueous solubility, solubility in solvents, mixed solvents or cyclodextrins, solution stability under long-term, accelerated and light conditions, bulk density, flow properties, compressibility, compatibility of drug-excipients in either solid or solution state, dissolution rates of drug- excipients mixtures at pHs 1 and 7.4, and development of analytical method to be used to evaluate the stability of the solution of drug substances in solubilizing medium or the drug-excipients mixtures in either solid or solution state, etc.

Task B – 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 physicochemical stability of candidate formulations including solid, liquid, or semi-solid under accelerated and/or long-term storage conditions, manufacturing procedures, and product specifications.

The work elements for the Task B are as follows:

● Preparation of prototype formulations for Phases I and II based on the pre-formulation data or other data available, physicochemical stability studies of the prototype formulations under accelerated and/or long-term storage conditions, selection of container/closure system, stability studies on the optimized/selected formulations, establishment of a final formulation and matching placebo based on a stability data, establishment of manufacturing procedures for a batch size of up to 30,000 units for active and placebo drugs, establishment of analytical methods for active and placebo drug products, and establishment of tentative product specifications for active and placebo.

Task C – Development and Validation of Stability-Indicating Analytical Methods for Drug Products: The Contractor shall develop and validate stability- indicating analytical methods for release of the products and stability testing in accordance with FDA regulations/ International Conference on Harmonization (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 D – Manufacture of Drug Products for Phase I and II Clinical Trials (tablets, sublingual tablets, hard gelatin capsules, soft gelatin capsules, etc. except parenteral dosage forms): 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 D are as follows:

a. Manufacturing a batch of active drug product and matching placebo under cGMP. In-process controls for blend uniformity, 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 stored securely in accordance with DEA regulations.

e. Shipping the drug product to clinical study sites or a location designated by the

COR.

Task E – Stability Study I: The Contractor shall initiate stability studies for the drug products manufactured under the Task D. The Contractor shall set up a 5-year stability study protocol to monitor the stability of the products 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 in compliance with FDA regulations and ICH guidance on stability studies on drug products.

The work elements for Task E are as follows:

a. Prepare stability study protocols in compliance with the Stability Guidance by the FDA and ICH. The storage conditions and sampling schedules will be depending on the stability of the drug products.

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

b. Store the drug product under appropriate conditions for stability and stability product samples containing controlled substances should be stored securely in accordance with DEA regulations.

Task F – Stability Study II: This task is for continuing stability studies that were previously initiated. The Contractor shall follow the established stability protocols to conduct the stability testings.

The work elements for the Task F are as follows:

a. Continue the stability study following the stability study protocols established under the Task E for long-term (usually 60 months), accelerated (6 months), intermediate (12 months), and photostability conditions.

b. Store the drug products according to the stability study protocols and stability product samples containing controlled substances should be stored securely in accordance with DEA regulations.

Task G – 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 G are as follows:

a. Manufacturing a batch of active or placebo product under cGMP.

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 the sites designated by the COR.

Task H – Manufacture of Parenteral Dosage Form: The Contractor shall manufacture a batch of single or multiple dose vials at an appropriate manufacturing facility under cGMP 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 parenteral dosage forms 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 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 H are as follows:

a. Clarity of the solution, pH, potency, integrity of aseptic filter, fill volume, and particulates, aseptic environment, packaging components in terms of sterility and bacterial endotoxins/pyrogens contamination, and/or the lyophilization process should be controlled in the manufacture of the parenteral 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.

Task I – Purchase of Drug Substances and/or Drug Products for Manufacture of Drug Products for Phase I-III Clinical Trials: The Contractor shall purchase drug substances and/or drug products from vendors on the open market for the manufacture of clinical supplies for Phase I-III clinical trials.

Task J – 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 J, 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 cGMP audit, which may be required by the FDA in connection with a DMF, 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 K – 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. Additional activity shall include adoption of the received stability-indicating methods for all stability samples.

Most of the drug substances, drug products, and data require storage and handling specified under cGMP 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 sample Task Order encompasses Tasks A, B, C, D, E, and F. 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 (Pre-formulation Study): Three drug substances, new chemical entities or previously approved drug substances, to be studied.

b. Task B (Formulation Study): Formulation studies for two drug substances.

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

d. Task D (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.

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

f. Task F (Stability Study II): Perform continuing stability studies for 7 batches of active drug products and 7 batches of matching placebos that have been under study about a year or longer.

2. Sample Task Order 2:

The Contractor shall perform Task A (Pre-formulation Study ) for two additional drug substances.

3. Sample Task Order 3:

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

4. Sample Task Order 4:

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

5. Sample Task Order 5:

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.

6. Sample Task Order 6:

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

7. Sample Task Order 7:

The Contractor shall perform Task F (Stability Study II) for 4 batches of active drug products and matching placebos that have been under stability study about a year or longer.

8. Sample Task Order 8:

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

9. Sample Task Order 9:

The Contractor shall perform Task H (Manufacture of Parenteral Dosage Form) to manufacture an injectable dosage form.

10. Sample Task Order 10:

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

11. Sample Task Order 11:

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

12. Sample Task Order 12:

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

TABLE 1: Anticipated Volume per Year for All Sample Tasks (for proposal purposes):

Task 1 Task 2 Task 3 Task 4 Task 5 Task 6 Task 7 Task 8 Task 9 Task 10 Task 11 Task 12 Task A (Pre-formulation)

3 DS 2 DS

Task B (Formulation)

2 DS 1 DS

Task C (Method development & validation)

2DP +

2PL

1 DP +

1 PL

Task D (Manufacture of dosage forms for Phases I and II)

2 DP (2

batches)

+ 2 PL

1 DP (2

batches)

+ 1 PL

Task E (Stability Study I)

2 DP (2

batches)

+ 2 PL

1 DP (2

batches)

+ 1 PL

Task F (Stability Study

II)

7 DP + 7

PL

4 DP +

4 PL

Task G (Manufacture of dosage forms for Phase III)

1 DP (1

batch)

+1 PL

Task H (Manufacture of parenteral dosage forms)

1 Inj.

dosage form

Task I (Purchase of Drugs)

DS/DP

Task J (End of contract requirement)

X

Task K (Phase-In Requirement)

X

DS: Drug substance, DP: Drug product, Inj.: Injection dosage form, PL: Placebo. Detail of Tsk A through Task K are shown under II.B.1. Specific Tasks to be performed. Batch is used here interchangeably with strength of a drug product.

ARTICLE C.2. REPORTING REQUIREMENTS

All reports required herein shall be submitted in electronic format as specified in Section F of the RFP..

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."

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. 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 reports will be required as follows:

1. Reporting Format/Procedures

The Contractor shall prepare and submit the following reports in electronic copies in Microsoft Windows compatible personal computer files using Microsoft Word for text and numerical data following the formats described below:

Front cover to contain: Date, title, study report name, drug substance/formulation identification, agency (NIDA), division (DPMC) and NIDA COR name/address/ phone number, period of performance, contract number, NIDA Reference number (N01DA-xx-xxxx), Contractor name and investigator names.

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

The Contractor shall ensure that all Reports are free from spelling 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, product specifications, and protocols for testing, sampling, and stability study. All appropriate references and batch records.

2. Specific Reports Required

Task Reports: Within ten working days after completion of a study, the Contractor shall submit one electronic copy of the Study Report to the NIDA COR. In the task order reports, the Contractor shall provide 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 also prepare Chemistry, Manufacturing and Control (CMC) section of IND, DMF or NDA documents and deliver to NIDA when there is a need.

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

Monthly Progress Reports: Within the first five working days after each calendar month of contract work, the Contractor shall submit one electronic copy of a report on activities during the preceding month to the NIDA COR. In the monthly report, the Contractor shall briefly describe work accomplished, any change in staff, any problems encountered and their solutions while performing any tasks. In addition, the Contractor shall include a list of final study/task reports sent to the NIDA COR during the month under report. The monthly report for the last month of a contract year shall be incorporated into the Annual Report.

Annual Progress Reports: Not later than fifteen working days after the end of each year of contract work, the Contractor shall submit 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. One electronic copy is to be sent to the NIDA COR and one electronic copy to the Contracting Officer. The annual report for the last Contract Year shall be incorporated into the Final Report.

Final Contract Report: On or before the expiration date of the contract, the Contractor shall provide an executive summary and comprehensive summary of work conducted during the entire contract period. 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. One electronic copy is to be sent to the NIDA COR and one electronic copy to the Contracting Officer.

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.)

HHS SECURITY AND PRIVACY LANGUAGE FOR INFORMATION AND IT PROCUREMENTS

INFORMATION AND/OR PHYSICAL SECURITY

2. See ARTICLE H.10. for a description of required Information Security deliverables.

3. Section 508 Annual Report

The contractor shall submit an annual Section 508 report in accordance with the schedule set forth http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&SID=0af84ca649a74846f102aaf664da1623&rgn=div5&view=text&node=45%3A1.0.1.1.51&idno=45 http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&SID=0af84ca649a74846f102aaf664da1623&rgn=div5&view=text&node=45%3A1.0.1.1.51&idno=45 http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&SID=0af84ca649a74846f102aaf664da1623&rgn=div5&view=text&node=45%3A1.0.1.1.51&idno=45 by the Contracting Officer (CO)/Contracting Officer's Representative (COR). 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 contract. All reports shall be sent to the following address:

NIDA Section, Contracts Management Branch Red Office of Acquisitions, NIDA National Institute on Drug Abuse, NIH c/o 3WFN MSC 6012 301 N Stonestreet Ave Bethesda, Maryland 20892

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

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.

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 (COR), whose position is described in 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 c/o 3WFN MSC 6012 301 N Stonestreet Ave 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 52.246-8, Inspection of Research and Development - Cost-Reimbursement (May 2001).

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

SECTION F - DELIVERIES OR PERFORMANCE

ARTICLE F.1. PERIOD OF PERFORMANCE

The period of performance of this contract shall be from September 18, 2021 through September 17, 2026.

ARTICLE F.2. DELIVERIES

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:

In accordance with FAR 4.804, following contract expiration/completion, the Contractor shall be responsible for providing the following items: Indirect cost rate proposals for all years (in which a proposal was not previously submitted); final property inventory (excluding intellectual property); standard forms 1428 and 1429 (if applicable); settling all subcontract costs and any issues thereunder; subcontracting compliance reports for all years to the eSRS; final patent and royalty reports; Contractor's release of claims, i.e. Contractor's closing statement; the Contractor's Assignment of Refunds, Rebates and Credits; and a final invoice or completion voucher (marked final).

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

Addressee Deliverable Item No Quantity Contracting Officer 3-4, 7-12 1 electronic

Item Description Quantity Delivery Schedule

(1) Task Report 1 electronic Within 10 Business Days of Task Completion

(2) Monthly Progress Report 1 electronic Within 5 Business Days following the end of each month

(3) Annual Progress Report 2 electronic Within 15 Business Days of the contract anniversary date

(4) Final Contract Report with Summary of Salient Results

2 electronic On or before contract expiration

(5) Archived Data, Tapes, Materials, etc.

(Task K)

All As required by Task Order

(6) All Drug Substances/ Products All As required by Task Order

(7) Annual Utilization Report 1 electronic See Article C.3

(8) Final Invention Report 1 electronic See Article C.3

(9) System Security Plan (SSP) with System Architecture Diagram/ Details

1 electronic See Article H.10

(10) Non-Disclosure Agreement(s) 1 electronic Prior to performance of any work under the contract

(11) Encryption Validation 1 electronic Within 15 days of validation.

Verification validated under the Cryptographic with FIPS 140-2

(12) Reporting of Financial Conflict of Interest

(FCOI)

1 electronic See Article C.2(b)(1)

Addressee Deliverable Item No Quantity Contracting Officer’s Representative

1-6 1 electronic

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: https://www.acquisition.gov/?q=browsefar.

FEDERAL ACQUISITION REGULATION (48 CFR CHAPTER 1) CLAUSE:

52.242-15, Stop Work Order (August 1989)

Alternate I (April 1984) is applicable to this contract.

https://www.acquisition.gov/?q=browsefar

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:

[To be specified prior to award]

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 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 352.237-75 (December 2015)

The key personnel specified in this contract are considered to be essential to work performance. At least 30 days prior to the contractor voluntarily diverting any of the specified individuals to other programs or contracts the Contractor shall notify the Contracting Officer and shall submit a justification for the diversion or replacement and a request to replace the individual. The request must identify the proposed replacement and provide an explanation of how the replacement's skills, experience, and credentials meet or exceed the requirements of the contract (including, when applicable, Human Subjects Testing requirements).