RFP.pdf

Contents

SOLICITATION INFORMATION

1. Solicitation Information

1.1 Notice of Combined Synopsis/Solicitation

1.2 Notice of FAC

2. Pricing and ordering services

2.1 Overview of Pricing Schedule

2.2 Pricing Terms

2.3 Contract Type

2.4 Minimum and Maximum Contract Value

2.5 Ordering

3. Description of Requirement/Statement of Work

3.1 BACKGROUND

3.2 OBJECTIVE

3.3 SCOPE OF WORK

3.4 REQUIREMENTS

3.5 PERSONNEL

3.6 DELIVERABLES AND REPORTING REQUIREMENTS

3.7 CONTRACTOR PROVIDED SPECIAL MATERIAL REQUIREMENTS

3.8 TRAVEL

3.9 OTHER CONSIDERATIONS

4.Deliverables

4.1 Criteria for Acceptance for Deliverables

5.0 Personnel

5.1 Key Personnel

5.2 Non-Personal Services and Inherently Government Functions

6.0 Period of Performance

7.0 Place of Performance

8.0 Other Direct Costs

9.0 GOVERNMENT-FURNISHED PROPERTY, MATERIAL, EQUIPMENT, OR

INFORMATION (GFP, GFM, GFE, OR GFI)

10.0 508 Standard Requirements

11.0 Contractor Conformance with Applicable Laws, Regulations, Policies and Standards

12.0 CONTRACTOR PERFORMANCE ASSESSMENT REPORT

13.0 GOVERNMENT POINTS OF CONTACT, AUTHORITY, AND DIRECTION

13.1 The contact information for the Contract Specialist (CS)

13.2 The contact information for the Contracting Officer (CO)

13.3 IDIQ Contracting Officer’s Representative

13.4 Task Order Contracting Officer’s Representatives

13.5 Technical Direction

14.0 Payment and Invoicing Procedures

15.0 Provisions and Clauses

15.1 Federal Acquisition Regulation (FAR) Provisions Incorporated by Reference

15.2 Federal Acquisition Regulation (FAR) Provisions Incorporated in Full Text

15.3 Federal Acquisition Regulation (FAR) Clauses Incorporated by Reference

15.4 Federal Acquisition Regulation (FAR) Clauses Incorporated in Full Text

15.5 Health and Human Services Acquisition Regulation (HHSAR) Provisions Incorporated by Reference

15.6 Health and Human Services Acquisition Regulation (HHSAR) Clauses Incorporated by Reference47

15.7 Health and Human Services Acquisition Regulation (HHSAR) Clauses Incorporated in Full Text ... 47

16. SECURITY LANGUAGE

17. OCCUPATIONAL SAFETY AND HEALTH TERMS AND CONDITIONS

18. Contractor Personnel Security Clearance Standards and Residency Requirements (October

2017)

19. Conflicts of Interest

20. INSTRUCTIONS TO OFFERORS

20.1. VOLUME I – TECHNICAL PROPOSAL INSTRUCTIONS

20.1.1 Technical Factor 1: Technical Understanding and Approach

20.1.2 Technical Factor 2: Staffing Plan and Key Personnel

20.1.3 Technical Factor 3: Equipment and Facilities

20.2. VOLUME II – BUSINESS/PRICE PROPOSAL INSTRUCTIONS

20.3. VOLUME III – PAST PERFORMANCE INSTRUCTIONS

21. BASIS OF AWARD AND EVALUATION CRITERIA

21.1 BASIS OF AWARD AND EVALUATION CRITERIA

21.1.1 Technical Factor 1: Technical Understanding and Approach

21.1.2 Technical Factor 2: Staffing Plan and Key Personnel

21.1.3 Technical Factor 3: Equipment and Facilities

21.2 PAST PERFORMANCE PROPOSAL EVALUATION CRITERIA

21.3 BUSINESS/PRICE PROPOSAL EVALUATION CRITERIA

23. Attachments

SOLICITATION INFORMATION

1. Solicitation Information

1.1 Notice of Combined Synopsis/Solicitation

This is a combined synopsis/solicitation for commercial services prepared in accordance with the Federal Acquisition Regulation (FAR) format in Subpart 12 and Subpart 15, as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and a written solicitation will not be issued. This synopsis is to notify contractors that the government intends to issue an Indefinite Delivery/Indefinite Quantity (IDIQ) contract.

This requirement is being solicited as a competitive 8(a) set-aside and is being processed under a Partnership Agreement (PA) between the Department of Health and Human Services (HHS) and the Small Business Administration (SBA), under which the SBA has delegated to HHS, authority to enter into 8(a) contracts directly with eligible 8(a) firms in accordance with Section 8(a) of the Small Business Act (15 U.S.C. 637(a)). Only those companies certified by the U.S.

Small Business Administration (SBA) as an 8(a) business that have not graduated from the program by the solicitation closing date are eligible for award. The associated North American Industry Classification System (NAICS) Code is 541715, Research and Development in the Physical, Engineering, and Life Sciences (except Nanotechnology and Biotechnology), with a small business size standard of 1,000 employees. Offerors must have an active registration in SAM.gov (www.sam.gov), with completed representations and certifications, by the close date of the solicitation. Proposals submitted by offerors without an active registration in SAM.gov will not be considered.

1.2 Notice of FAC

This solicitation document incorporates provisions and clauses in effect through the Federal Acquisition Circular (FAC) Number 2023-05, Effective September 22, 2023. It is the contractor's responsibility to be familiar with the applicable clauses and provisions. The provisions and clauses may be accessed in full text at www.acquisition.gov/far.

2. Pricing and ordering services

2.1 Overview of Pricing Schedule

The Contractor’s pricing schedules for price categories shall contain fully burdened rates. The fully burdened rates for each price category shall include all wages, indirect costs, fringe benefits, overhead, general and administrative, and profit. All prices/rates will be incorporated into the contract in Attachment A.

http://www.acquisition.gov/far

By mutual agreement of the parties, additional price categories may be added to this IDIQ contract to support the tasks of this contract.

2.2 Pricing Terms

The Contractor shall comply with FAR Clause 52.212-4, Contract Terms and Conditions – Commercial Items (Oct 2018) regarding firm-fixed-prices for individual task orders. The total amount specified in Firm-Fixed Price (FFP) task orders shall be fixed for the task order period of performance and shall not be subject to adjustment; except, as a result of a direct action or inaction by the Government which delays the Contractor from completing the task order within the time specified in the order.

2.3 Contract Type

This competitive 8(a) requirement will be a single award Indefinite Delivery, Indefinite Quantity (IDIQ) type contract with a five (5) year ordering period, and is being processed under a Partnership Agreement (PA) between the Department of Health and Human Services (HHS) and the Small Business Administration (SBA), under which the SBA has delegated to HHS, authority to enter into 8(a) contracts directly with eligible 8(a) firms in accordance with Section 8(a) of the Small Business Act (15 U.S.C. 637(a)). The performance period end date of the last task order option cannot exceed twelve (12) months past the ordering period end date of the IDIQ contract.

2.4 Minimum and Maximum Contract Value

The guaranteed minimum amount for this contract is $2,000.00. This minimum shall be met by obligating funding in the amount of $2,000.00 on the contract at the time of award. The maximum contract amount, inclusive of the five (5) year ordering period under the contract is estimated not to exceed $20,000,000.00

See FAR Clause 52.216-19 (Oct 1995) for individual task order limitations.

2.5 Ordering

Any Contracting Officer of the Food and Drug Administration (FDA) is authorized and may place orders under this IDIQ contract. Each individual task order will describe the specific performance requirements. The process for issuing task orders is as follows:

1. The FDA CO will issue a Request for Task Order Proposal (RFTOP) via email. The RFTOP will include the following information:

a. SOW

b. Period of performance

c. Anticipated contract type (FFP only)

d. Reporting requirements and deliverables

e. Key Personnel (If applicable)

f. Any special terms and conditions specifically applicable to the task order

2. The Contractor will typically have a minimum of ten (10) business days, unless otherwise specified, to provide a proposal in response to the RFTOP. The proposal shall include:

a. Description of the technical approach to the task order requirements

b. Price buildup (including labor categories, hours for each labor category, extended pricing, total task order pricing, other direct costs, and concurrence with the anticipated contract type)

c. Resumes of any key personnel identified in the RFTOP

3. The FDA will evaluate the task order proposal for technical acceptability and price reasonableness. If the FDA has questions or concerns, the Contracting Officer will contact the Contractor and may request a revised proposal.

4. If the task order proposal is determined acceptable, the Contracting Officer will issue a task order. All task orders will, at a minimum, include the following:

a. Task Order number

b. Date of Task Order

c. Funding for the Task Order

d. Task order SOW and specific deliverables and due dates

e. Task order pricing

f. Period of performance of the task order

g. Any terms, conditions and instructions specific to the task order

Any work that the Contractor undertakes prior to receiving a fully executed task order that has been signed by the Contracting Officer (or the Contractor has received prior written authorization to proceed from the Contracting Officer) shall be at the Contractor’s risk.

Pricing of Orders

1. Proposals submitted in response to a RFTOP must be in accordance with the

Ordering Period rates in the base IDIQ contract Price Schedule based on the performance start date of the task order, and that rate must be used for the duration of the task order performance period; however, if a task order’s performance period is longer than 12 months, the Contractor may propose the applicable ordering period rate for that portion of the performance period after the 12 month period. The Contractor may propose lower rates in response to a RFTOP.

2. RFTOPs may include option periods in accordance with FAR Clause 52.217-9 (Mar 2000). However, option periods must utilize the Ordering Period rates listed in the IDIQ Price Schedule, based on the performance start date of the option period. The performance period end date of the last task order option cannot exceed twelve (12) months past the ordering period end date of the IDIQ contract.

3. Description of Requirement/Statement of Work

3.1 BACKGROUND

FDA has identified topics for which post-market Bioequivalence (BE) studies would be necessary to address scientific questions or quality concerns of specific generic drug products.

For instance, FDA is interested in whether formulation complexity or post-marketing reports of therapeutic inequivalence warrant additional BE evaluation of generic modified release drug products. In vivo BE studies with fully replicated design may be desirable to evaluate the effect of formulation differences on the pharmacokinetic (PK) behavior of these products.

Multiple studies may be necessary to cover a range of products including those containing controlled drug substances. Studies may not be limited to pos-market BE evaluation and may include pharmacodynamic endpoint assessments.

To this end, this contract is to conduct BE studies of generic drug products to proactively address controversial scientific questions in developing generic approval standards and to reactively address public concerns regarding the quality of specific generic drug products.

3.2 OBJECTIVE

The objective of this project is to conduct appropriate Human Subject Research (HSR) studies of generic drug products in healthy subjects or patients as determined by the question of interest. The outcome of this project will help address scientific questions in developing generic approval standards and help address public concerns regarding the quality of specific generic drug. Additionally, this project will help improve the review practice of generic drug products and develop -associated guidance when applicable.

3.3 SCOPE OF WORK

Each task order may have its own scope of work. We present two examples to demonstrate how the Center of Drug Evaluation and Research (CDER) Office of Generic Drugs (OGD) uses the contracted, post-market BE and/or PK study mechanism to address these concerns.

Example 1. BE of generic hypertensive drug in healthy volunteers

In 2016, FDA awarded a contract to investigate the BE of Extended-Release (ER) nifedipine tablets with or without proton pump inhibitor (PPI) in healthy volunteers. In this contract, a single-dose, open-label, 4-way crossover, 4-period, 4-sequence, randomized study to evaluate BE between a generic and the reference listed drug (RLD). The objective of this study was to investigate the dependence of in vivo PK on the formulation design of generic oral ER products in comparison with that of their RLD when co-administered with PPIs/antacids.

A question that arises with generic oral ER products is related to pH-dependent dissolution kinetics in comparison with that of their RLD. For example, poorly water-soluble drugs with the presence of pKa in the gastrointestinal (GI) pH range have pH-dependent solubility and dissolution behaviors during in vivo drug release. In this case, the generic product which utilizes a different release mechanism could amplify or reduce such a pH dependence (e.g. osmotic pump RLD vs. matrix generic counterparts). This may render these generic ER products more or less dependent on gastric pH modification, commonly occurred in patients taking concomitant over-the-counter (OTC) PPIs for the treatment of gastric acid-related disorders. It has been noted that PPIs (e.g. lansoprazole, omeprazole, esomeprazole) and PPIs with antacids (e.g.

omeprazole/sodium bicarbonate) can drastically elevate the gastric pH, thus potentially triggering a drug-drug interaction.1

Nifedipine is a calcium channel blocker, indicated for the long-term treatment of hypertension and angina, was selected as a study drug. The drug substance is a weak acid and practically insoluble in water. One internally conducted in vitro study with nifedipine indicated an impact of pH on drug release mechanism attributable to a formulation difference (published in 2019).2 Due to complicated release mechanisms, quality attribute profiles and in vivo PK behaviors of ER products, FDA assessed the need of a drug-drug interaction study between PPIs/antacids (e.g. omeprazole/sodium bicarbonate) and generic nifedipine ER products based on a formulation design which is different from that of its RLD. For this study, one RLD of oral ER nifedipine tablets based on an osmotic pump design and a generic counterpart of ER nifedipine tablets employing a matrix formulation design were studied with or without PPI/antacid. To this end, a SmartPillTM technology was utilized to monitor physiological pH changes.

The outcome of this study helped the Agency advance further understanding about product PK performance in potential patient population with abnormal gastric pH. Additionally, the study results helped the Agency gain a better understanding of drug-drug interaction between oral modified-release products and PPIs/antacids and establish regulatory standards of BE approaches for this category of generic oral ER products. This study has been completed and the manuscript is underway. Brief results are available at the clinicaltrials.gov.3

Example 2. BE of warfarin sodium products

Warfarin is an anti-coagulant that is generally considered a narrow therapeutic index drug.

Warfarin sodium is a racemic mixture of the R- and S-enantiomers and exists as a crystalline clathrate form with a potential conversion to an amorphous form. The clathrate form consists principally of warfarin sodium and isopropyl alcohol (IPA), in a 2:1 molecular ratio. Clathrates are unstable and may lose IPA during storage and drug product manufacturing in a temperature dependent manner.4 Stress storage studies conducted by FDA demonstrate that at 70% RH (relative humidity), the clathrate converts to amorphous form within 14 hours which have different dissolution profiles under various dissolution conditions. Thus, variation in IPA content may significantly affect bioavailability of warfarin.

Variations in IPA may come from different manufacturing and storage conditions. In 2014, FDA awarded a contract to determine BE between warfarin sodium tablet products from different suppliers and under different storage conditions (i.e., fresh lots or stored under stress conditions). The contractor is expected to determine IPA content in these products and conduct a single-dose, 4-treatment, 4-period, crossover, fasting BE study in healthy volunteers. Results of this study helped address public concern of the quality and switchability of generic warfarin sodium tablet product.

Combined with modeling and simulation approach, the outcome of this study was published.5

3.4 REQUIREMENTS

FDA may order a total of up to 5 studies using one type of approach of studies described in the following table, depending on the need for such studies and available funds. Each type may need to be repeated with different drug products as a function of regulatory need.

Type of BE Studies Dosing Schedule Food Effect Study Population

Single dose Fasting

In healthy subjects In patients

Fed In healthy subjects In patients

Multiple dose

Fasting In healthy subjects In patients

Fed In healthy subjects In patients

Other study design factors, including the replicate level (e.g., 2-sequence, 2-period vs.2-sequence, 4- period), the use of specific study populations (e.g., patients with concomitant medication vs. patients without concomitant medication), the selection of BE/PK metrics (e.g., AUC0-t vs. partial AUCs), and the use of pharmacodynamic assessments may be adjusted as determined by the study topic.

FDA may order multiple BE/PK studies in a single task order. With each awarded task order, the contractor shall:

1) In discussion with FDA, perform quality characterization on drug products including but not limited to dissolution and assay of drug substance and related substances in accordance with the United States Pharmacopeia standards if needed.

2) Design the study and develop protocol in discussion with FDA for the planned studies.

It may not be limited to BE/PK studies. The Contractor shall perform statistical analysis to modify the number of subjects in order to achieve sufficient study power if appropriate.

3) Submit protocol, informed consent form and any related documents needed for in vivo BE/PK studies to a local Institutional/Independent Review Board (IRB) for review and obtain approval before conducting any clinical studies.

4) Draft, revise and finalize all study documents and/or template including protocol, informed consent, plans, reports, essential documents, and source documents in English. Report and complete all study documents effectively in English.

5) Develop an appropriate bioanalytical method, submit a validation report, and perform sample analysis including Incurred Sample Reanalysis. Depending on a study, multiple analytes including, but not limited to a metabolite may be needed. FDA’s guidance on “Bioanalytical Method Validation: Guidance for Industry” (May 2018) should be followed for reporting on bioanalytical method parameters.

6) Procure study drugs as needed. Most BE/PK studies require the procurement of multiple bottles of the same lot.

7) Conduct clinical studies and monitor and record adverse events through the study in accordance with all applicable regulations/guidance/policies including, but not limited to 45 CFR 46, 21 CFR, and Good Clinical Practice.

8) Consult OGD Project Officer (PO) for any proposed changes to the study documents or the procedures prior to implement any changes.

9) Establish and maintain all essential documents. It may include a regulatory submission including, but not limited to Investigational New Drug and Investigational Device Exemption. Ensure all records that are generated during the project are maintained and retained in accordance with all applicable regulations, policies, and guidelines.

10) In discussion with FDA, act as an IND and/or IDE holder and assume responsibilities as needed.

11) Generate preliminary data in a timely manner and subsequently submit clinical study report on the BE/PK evaluation of study product and on safety outcome of the BE/PK study.

12) Be responsible for subject recruitment, supplies, equipment, and computational software. May need to recruit a patient population.

13) Recruit diverse racial and/or ethnic populations representative of the general population in the United States as needed. A large database including active participants with various demographics is preferred.

14) Deliver the required data as outlined in each task order. The primary, secondary and exploratory (if applicable) endpoint data shall be available for completed subjects.

15) In discussion with FDA, work to resolve any foreseeable and/or unforeseeable issues.

This may include a delay in planning and/or an implementation of preventive measures.

16) Acquire clinical trial liability insurance against all liabilities, damages, losses, injuries, complaints and/or claims arising from the trial including, but not limited to, claims that arise from malpractice and/or negligence. Account for the costs of this insurance in the budget and will be responsible for maintaining an insurance certificate that satisfies any relevant regulations/guidance/policies including local requirements.

17) Provide the project management oversight for each task order.

18) Be responsible for replacement or corrections to the deliverables to meet the requirements identified in the task order.

19) Work with the OGD COR, PO and/or Quality Assurance (QA) team, accommodate visit requests, and always make all study documents available for monitoring/inspection.

20) Manage subcontractor(s) and assume all responsibilities if subcontract(s) becomes necessary.

21) Remote site access, direct data entry/capture and/or remote monitoring platform/capability are preferred.

22) Assume the responsibility and manage all Clinical Data Management (CDM) activities required for the project.

References

1. Ogawa, R. et al. Clinically Significant Drug Interactions with Antacids. Drugs 71: 1839-1864 (2011)

2. Gao, Z. et al. Effects of Dissolution Medium pH and Simulated Gastrointestinal Contraction on Drug Release From Nifedipine Extended-Release Tablets. J Pharm Sci 108, 1189-94 (2019).

3. https://clinicaltrials.gov/ct2/show/NCT03100838

4. Gao, D. et al. Physical chemical stability of warfarin sodium. AAPS PharmSci 3(1):E3 (2001).

5. Zhang, X. et al. Integrating In Vitro, Modeling, and In Vivo approaches to Investigate Warfarin

BE. CPT Pharmacometrics Syst Pharmacol 6(8): 523-531 (2017).

3.5 PERSONNEL

The Contractor shall ensure that all personnel have the expertise, knowledge, training, and possess credentials for appropriate to their labor categories to meet the IDIQ contract and all awarded task orders. The Contractor shall ensure qualified high-level support required by this contract prior to being assigned to the awarded Task Order. The Contractor shall ensure the ability to understand and effectively service the scientific and information technology community with knowledgeable, professional, and capable personnel.

3.6 DELIVERABLES AND REPORTING REQUIREMENTS

The reporting requirements and deliverables apply to each task order award. This table shows a typical requirement.

DELIVERABLE /

REPORT/ DOCUMENT

DE

LIVERY DATE

ACCEPTANCE STANDARD

Schedule a kick-off meeting

15 calendar days after task order award.

In discussion with FDA Contracting Officer’s Representative (COR) and Project Officer (PO) if different from COR, contractor to discuss a tentative study design at a kick-off meeting and propose a tentative timeline.

Schedule Monthly Progress Meetings

Every month In discussion with FDA Contracting Officer’s Representative (COR) and Project Officer (PO) if different from COR, schedule monthly progress meetings. At least two days prior to the meeting, an agenda and slide set should be sent to the COR, PO, and Project Manager. Contractor to take minutes and send it within 7 calendar days. Ad-hoc meetings may be needed, and the same requirements apply.

Study draft protocol and implementation plan

45 calendar days after task order award.

Contractor to submit Protocol and Implementation Plan with the timeline for Government review. Protocol and Implementation plan shall conform to all applicable GCP regulations.

Contractor shall clearly identify and explain any deviation from the proposed protocol and implementation plan submitted with the Contractor’s original proposal. Multiple review cycles may be required before finalizing the study documents.

Submission of IRB package

150 calendar days after task order

Contractor to submit finalized Protocol and other associated documents for local IRB review

Approval from local

IRB

180 calendar days after task order award.

Contractor to obtain an approval from local IRB

Monthly or bi-weekly study update form

Monthly or bi-weekly while the study is active

Contractor to submit the CDER study update form monthly or bi-weekly once the enrollment starts until the last subject’s last visit. Frequency will be determined in discussion with FDA.

Quarterly Progress Report

30 days following the close of every 3rd month from task order award date.

The report shall be determined acceptable if it adequately addresses the following content and is submitted in the following format:

Cover page containing contract # and title, contractor’s name and address, Author(s), and date.

Section I: An introduction covering purpose and scope of effort expended that quarter. A description of the overall progress on the project + a separate description of each task or milestone on which effort was expended during the report period. The description shall include pertinent data, graphs, tables to explain any significant results achieved.

Section II: A description of any problems which may impede performance along with proposed corrective action.

Section III: A “living milestone plan” that matches the one contained in the Contractor’s original Study Protocol and Implementation Plan. The living milestone plan shows the actual dates the milestones are hit in comparison to the original dates in the plan. The monthly progress report shall explain any difference in actual progress and planned progress, what corrective steps are planned if project schedule slips.

Shall also include projected accomplishment for the next period, and any pertinent information on any pending issues.

Annual Presentation at

FDA

To be determined by FDA in consultation with the contractor, no later than 60 days following the close of every 12th month from the task order award date.

Prior to the actual presentation taking place, the Contractor shall provide narrative/slides of the presentation for Government COR and/or its designee review and approval. At a minimum, the presentation shall address accomplishments to date, results from the research study, hypotheses, issues and concerns, next steps.

Annual Report (written document)

30 days following the anniversary of the task order award date. The annual report makes each fourth quarter report of each contract year unnecessary.

The report shall be determined acceptable when it addresses the following in sufficient detail (as determined by the COR and/or its designee):

Provide overall report on progress, year to date on the objectives, including a summary of data and figures provided in each monthly report as well as a plan for the coming year.

Final Report (Draft)

60 days prior to the task order expiration date for comments.

Contractor to submit a draft final report (clinical study report) and HSR final report. Comments will be provided to contractor within 21 days of receipt and addressed in the final report.

Final Report

No later than the task order expiration date.

The report shall be determined acceptable when it addresses the following in sufficient scientific detail (as determined by the COR): The final report shall include, at a minimum: study design, detailed description on study procedure, results, conclusions, and future research suggestions. Raw data from the experiments shall be considered acceptable when all final data has been submitted in Statistical Analysis System (SAS) XPORT Transport Format files or other appropriate format.

Final Presentation at

FDA

To be determined by FDA, in consultation with the Contractor, no later than the task order expiration date.

The deliverable will be determined acceptable after the Contractor has provided the Government with narrative/slides for the presentation and then has performed the presentation at FDA facilities or remotely. The presentation shall address study design, detailed description on study procedure, results, conclusions, and future research suggestions.

Reports (i.e., quarterly progress reports, and final report), containing the description of study, will be provided to FDA using FDA recommended format in electronic format. In addition, all the raw data from the research will be provided to FDA in electronic format, along with these reports. FDA will neither obtain nor analyze any identifiable, private data and/or biospecimens or have access to the code key that re-identified the data.

No information furnished to or generated by the contractor in the performance of this contract will be released to the public until it has been reviewed by the Government Contracting Officer’s Representative (COR) for accuracy of factual data and interpretation.

The Government will have sixty (60) calendar days after receipt of the manuscript or other written draft of the material to be released, to review, comment, and return to the contractor.

Scientific manuscripts/publications resulting from work conducted by the Contractor and Government site investigators will be prepared and published according to guidelines agreed upon at study initiation by the investigator team for that study. During the study, the project team shall determine the first and senior author positions. While the order of listing authors on each publication shall be determined on a case-by-case basis by mutual decision of all collaborative parties and shall reflect appropriately each author’s contribution to the project, it is possible that a Contractor employee may be offered the first author position for the primary manuscript arising from the study. However, the senior author position may be offered to any member of the study team who is willing to provide substantial input into study design, implementation, and manuscript preparation and oversight of all study procedures. Study Site Principal Investigator (PI) and Principal Investigators from the other sites, including FDA, will be listed as authors on the manuscripts, with ordering in these positions determined by consensus based on the amount of input into the actual production of the manuscript. All authors shall provide final approval of the manuscript as written. Even though the Contractor may be the first author on resulting publications, it is the Government’s discretion as to when the articles should be published. The Contractor shall not unduly delay publication or unilaterally decide that the data should not be published. This right is retained by the Government only.

Receipts for appropriate expenditures should be submitted and will be reimbursed at each three (3) month reporting period.

Human Subjects Research (HSR) Terms and Conditions of Award

The Contractor/PI must adhere to the following processes for Contracts and Grants involving Human Subject research from FDA.

1. The Contractor is required to have a current Federal-wide Assurance (FWA) for the Protection of Human Subjects for its institution on file with the Office for Human Research Protections (OHRP), 1101 Wootton Parkway, Suite 200, Rockville, MD 20852, before conducting research that involves human subjects. Questions about FWAs should be directed to OHRP. A copy of the current FWA shall be included in the Contractor/PI's proposal. All study sites conducting HSR shall obtain FWA and submit it to the OGD COR prior to a study initiation.

2. The Contractor shall be responsible for any, and all liabilities, damages, losses, claims, and expenses, including court costs and reasonable attorneys’ fees resulting from or arising out of any third-party claims, actions or proceedings caused by negligence or willful misconduct, whether by act or omission, of the Contractor or any of its personnel.

3. Upon award, the OGD COR or its designee will arrange a kick-off meeting with the Contractor/PI to discuss requirements of FDA, including the roles and responsibilities of FDA Contracting Officer (CO), OGD COR, OGD PO (if different from OGD COR) and OGD Human Subject Protection (HSP) Liaison.

4. Following the kick-off meeting, the Contractor/PI shall submit the proposed study documents including but not limited to: the research protocol, informed consent and recruitment advertisements to the OGD COR and PO for review. The Contractor/PI also shall submit the finalized study documents to the OGD COR and PO. The FDA study team and HSP Liaison shall review the submitted study documents to ensure completeness of the submission package. The protocol shall be developed specifically for this contract, and it needs to stand alone.

5. Following the review and sign-off by the HSP Liaison (signatory authority), the OGD PO shall submit the required documents to the FDA IRB and/or Office of Chief Scientists (OCS). FDA will determine if FDA is considered engaged in the research for purposes of 45CFR part 46 or if an IRB Authorization Agreement (IAA) is needed. The outcome will be communicated to the Contractor so that appropriate documents may be prepared for submission.

6. For research studies under IAA where FDA IRB is the relying institution, the Contractor/PI shall make required reports to the local IRB (for reviews, approval, and oversight considerations), including proposed changes in the research and unanticipated problems involving risks to subjects or others (i.e., unanticipated problems), any serious or continuing noncompliance.

7. For research studies under IAA where FDA IRB is the relying institution or non-engagement is determined, the Contractor/PI shall submit to the OGD PO: a copy of the reviewing IRB approval of the research, including amendment and continuing review approval letters, as applicable; a copy of any documents reported to the reviewing IRB (as described above); a copy of any findings from the local IRB, for example, any decisions made by the local IRB related to unanticipated problems, any serious or continuing noncompliance, and any suspension or termination of IRB approval; any communications between the Contractor/PI and the local IRB; and notification of study closure. As needed, the OGD PO will update the memo with these communications between the local IRB and the Contractor/PI for tracking purpose and reference (and to inform the Chief Scientist).

8. If the Contractor/PI has already received local IRB approval or exemption for the final study documents prior to the submission to the FDA IRB and/or OCS, then a copy of the IRB approval/acknowledgement letter must be included in the submission package sent to the OGD PO, COR and HSP Liaison. The OGD PO and/or HSP Liaison may request modifications to the approved documents. If that occurs, the Contractor/PM shall submit all study documents to their local IRB for review and shall provide the approval letter to the OGD PO.

9. The Contractor shall submit all local IRB documents to the OGD COR and PO.

Certification of IRB review, exemption or approval must include the following: the PHS/HHS application number, title of the project, name of the program director/principal investigator, date of IRB approval or exemption, IRB Organization (IORG) number/its expiration date and appropriate signatures. The PI must ensure that any protocol(s) are consistent with the research plan in the corresponding application.

10. The FDA IRB and/or OCS may review the research study documents, to assure that the rights and welfare of human subjects involved are adequately protected and for compliance with all relevant regulations. OCS may also determine whether the proposed research is exempt under 45 CFR 46.104(b) and whether an IND/ANDA/IDE application is required (see 21 CFR Part 312/314/812).

11. Upon approval/IAA approval/Non-Engagement Determination by the FDA IRB and/or OCS, the OGD PO and/or HSP Liaison will provide a copy of the FDA IRB’s and/or OCS’ letter stating that it has reviewed and approved/IAA-approved the proposed research study or determined that FDA is not engaged in the research to the OGD COR and the Contractor/PI. If FDA IRB and/or OCS renders a decision other than approval of the proposed research study documents (i.e., contingent approval or disapproval), the HSP Liaison will provide a copy of the FDA IRB’s or OCS’ letter to the Contractor/PI and will assist the Contractor/PI in revising the research study documents for re-submission to the FDA IRB and/or OCS for review and approval.

12. The Contractor shall not advertise for, recruit, or enroll human subjects, or otherwise commence any research involving human subjects until the FDA IRB and/or OCS has reviewed and approved/IAA- approved the proposed research study or determined that FDA is not engaged in the research. The Contractor may begin other limited aspects of contract performance prior to receiving the FDA IRB and/or OCS approval of the proposed research study (such as training, and development of protocol training documents, planning, communications, travel, etc.). Research involving human subjects may commence upon the Contractor/PI receipt of the FDA IRB’s and/or OCS’ letter and local IRB approval documentations.

13. The Contractor/PI shall seek the OGD PO review, and then local IRB review and approval whenever modifications, amendments or other changes are made to the research study documents. Modifications and amendments include, but are not limited, to changes to the protocol, consent forms, recruitment materials, and the addition or deletion of investigators. Changes may be instituted after the Contractor has received the local IRB approval, unless the changes are necessary to eliminate apparent immediate hazards to the subject.

14. Where possible, the QA monitoring will be performed (either remotely and/or via on-site visits) by the OGD COR, PO, HSP Liaison, and/or its designee to help ensure human subject protection throughout the conduct of the study and assess compliance with all applicable regulations/guidance/policies and the OHRP requirements that govern the conduct of research.

15. The QA team or its designee will provide the Contractor/PI, OGD PO and COR with a report of all identified concerns related to human subject protections, along with suggested corrective actions if appropriate. If concerns are identified, the Contractor/PI is responsible for providing responses to the corrective actions listed in the report to the OGD PO and COR, within two weeks of receipt. If a Steering Committee (SC) or Data Safety Monitoring Board (DSMB) is established by the Contractor/PI, in collaboration with the OGD PO and HSP Liaison, responses to the report must be routed through the SC or the DSMB. Non-compliance with federal regulations and OHRP requirements may be reported to OHRP or CDER’s Office of Compliance. As warranted, the HSP Liaison will notify OHRP or CDER’s Office of Compliance of any regulatory concerns.

16. The Contractor/PI must provide documentation that the monitoring reports and revised study documents (if appropriate) have been submitted to the local IRB. The documentation should reflect that the IRB is aware and indicate whether any further action is required. Copies of this documentation must also be provided to the SC, DSMB, HSP Liaison and the OGD PO.

17. The Contractor shall establish its own internal Quality Management process (such as internal monitoring) prior to the study initiation and submit its plan for review by the OGD PO, COR and HSP Liaison.

18. Where applicable, the Contractor/PI will provide an IRB approval letter, at least annually, stating that the IRB has reviewed and approved the continuation of the research performed under this contract. This letter shall be submitted to the OGD PO and the COR.

19. Within 30 days of the award, the PI must provide a letter that includes the names of the key personnel, and the title of the human subjects’ protection education program completed by each of the key personnel. This letter should be signed by the PI and cosigned by the institutional signing official and sent to OGD COR whose names appears on the contract.

20. The Contractor/PI is responsible for ensuring that all key personnel receive appropriate training in their human subject protection responsibilities in addition to a study-specific training. Key personnel include all principal investigators, co-investigators, main study coordinators and all individuals deemed Key Personnel by the PI. All personnel listed in the FDA form 1572 (Statement of Investigator) are deemed key personnel. HHS, FDA, and OGD do not require or endorse any specific education programs, but a brief description of HSP training may be requested.

21. If it is determined that the proposed research study is not subject to 45 CFR Part 46, then the contract and programmatic file will be documented accordingly.

Questions on FDA requirements can be directed to OGD HSR ORSHSR@FDA.HHS.GOV.

Certificates of Confidentiality – 42 U.S.C. 241(d)

Contractors are responsible for complying with all requirements to protect the confidentiality of identifiable, sensitive information that is collected or used in biomedical, behavioral, clinical, or other research (including research on mental health and research on the use and effect of alcohol and other psychoactive drugs) funded wholly or in part by the Federal Government.

See 42 U.S.C. 241(d). All research funded by FDA, in whole or in part, that is within the scope of these requirements is deemed to be issued a “Certificate of Confidentiality” through these Terms and Conditions. Certificates issued in this manner will not be issued as a separate document.

Contractors are expected to ensure that any investigator or institution not funded by FDA who receives a copy of identifiable, sensitive information protected by these requirements, understand they are also subject to the requirements of 42 U.S.C. 241(d). Awardees are also responsible for ensuring that any subrecipient that receives funds to carry out part of the FDA award involving a copy of identifiable, sensitive information protected by these requirements understand they are also subject to subsection 42 U.S.C. 241(d).

mailto:ORSHSR@FDA.HHS.GOV.

3.7 CONTRACTOR PROVIDED SPECIAL MATERIAL REQUIREMENTS

Each task order will identify whether any special materials are required by the Contractor.

3.8 TRAVEL

The Government does not intend travel costs (local and non-local) to be incurred during the term of this contract. If deemed necessary and appropriate, the Contractor shall identify and forecast travel requests per each individual task order. If local or non-local travel is deemed necessary, it must be approved in writing by the CO and COR in advance (at least ten (10) calendar days). The travel to be reimbursed shall not exceed the travel ceilings specified in the Federal Travel Regulations and award.

All travel charges for this order will be in accordance with the Federal Travel Regulation:

www.gsa.gov/travelpolicy

3.9 OTHER CONSIDERATIONS

To be determined within each task order.

4.Deliverables All deliverables will be specified and detailed by the FDA in specific task orders. All deliverables required under this contract shall be packaged, marked and shipped in accordance with FDA 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.

Be advised that FDA does not accept documents which contain the use of macros. When submitting documents via email, DO NOT include .exe, .mso, or any other executable file types that could potentially trigger email security protections (i.e. email blocks, quarantine). Document submissions required throughout the award period(s) shall not have macro enabled functionality and any document delivered having that functionality will be deemed delinquent, if not corrected prior to the due date. The Contractor shall scan all electronic deliverables for viruses before submitting to the FDA.

4.1 Criteria for Acceptance for Deliverables

The FDA COR will inspect and make acceptance decision for all documents and services provided under this contract. The COR shall monitor the Contractor’s performance, evaluate the quality of services, and perform the final inspection and acceptance of all deliverables.

Deliverables aligned with the task areas and service levels will be specified in each individual Task Order. The Contractor shall provide the COR with an electronic copy, in a file format specified by the COR, of each deliverable via physical media or via electronic mail (as specified by the COR) according to established deliverable schedule. The COR will review and provide comments back on deliverables within fifteen (15) working days of receipt or as designated in the Task Order. The Contractor will have ten (10) working days to review and incorporate the COR’s comments and resubmit to the COR. This review cycle will repeat until Government’s https://www.gsa.gov/node/79894 acceptance of a deliverable, and depending on a timeline, it may be adjusted upon agreement of all parties. These deliverables shall become the property of the Government.

Each individual task order will provide for the frequency of reporting and/or meeting requirements.

This contract incorporates the following clause(s) by reference:

• FAR 52.242-15 – Stop-Work Order (Aug 1989)

• FAR 52.242-17 – Government Delay of Work (Apr 1984)

• 52.246-4 - Inspection of Services - Fixed-Price (AUG 1996)

5.0 Personnel

5.1 Key Personnel

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). A resume shall be submitted for the proposed new key personnel, as well as the resume submitted with your initial proposal for comparison. If the employee of the contractor is terminated for cause or separates from the contractor voluntarily with less than thirty days’ notice, the Contractor shall provide the maximum notice practicable under the circumstances. The Contractor shall not divert, replace, or announce any such change to key personnel without the written consent of the Contracting Officer. The contract will be modified to add or delete key personnel as necessary to reflect the agreement of the parties. The contractor shall submit the resume/CV of a proposed replacement and shall be notified of approval of key personnel within 10 business days.

The Government reserves the right to evaluate the technical skill and competence of any Contractor staff members, to require removal and replacement, upon written notice, of any individuals whose qualifications or performance are judged deficient at any time. The following personnel are considered key personnel by the government:

Contract Level Key Personnel: See Attachment F - Labor Categories & Minimum Qualifications

Project Manager

Contract Manager

Task order key personnel to be identified on each individual task order.

5.2 Non-Personal Services and Inherently Government Functions Pursuant to FAR 37.1, no personal services shall be performed under this contract. Work requirements shall flow only from the Contracting Officer or the COR to the Contractor's Project Manager. No Contractor employee will be directly supervised by the Government. All employee assignments, and daily work direction, shall be given by the applicable Contractor supervisor. If the Contractor believes any Government action or communication has been given that would create a personal services relationship between the Government and any Contractor employee, the Contractor shall promptly notify the Contracting Officer of this communication or action.

Pursuant to FAR 7.5, the Contractor shall not perform any inherently governmental actions under this contract. No Contractor employee shall hold him or herself out to be a Government employee, agent, or representative. No Contractor employee shall state orally or in writing at any time that he or she is acting on behalf of the Government. In all communications in connection with this contract, Contractor employees shall identify themselves as Contractor employees and specify the name of the company for which they work. In all communications with other Government Contractors in connection with this contract, the Contractor employee shall state that they have no authority to in any way change this contract and that if the other Contractor believes this communication to be a direction to change their contract, they shall notify the Contracting Officer for that contract and not carry out the direction until a clarification has been issued by the Contracting Officer.

The Contractor shall insure that all of its employees working on this contract are informed of the substance of this article. Nothing in this article shall limit the Government’s rights in any way under the other provisions of this contract, including those related to the Government’s right to inspect and accept the services…