FDA-SOL-1146520.7-28.pdf

FDA-SOL-1146520

PART 2

SERVICES AND PRICES/COSTS

2.1 DESCRIPTION OF SERVICES

The U.S. Department of Health and Human Services, Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), requires a contract to conduct in vivo studies of generic drug products in human subjects.

2.2 CONTRACT TYPE

The anticipated contract type is Indefinite Delivery Indefinite Quantity (IDIQ) with the issuance of Labor Hour and Fixed Price Task Orders.

2.3 CONTRACT PERIOD OF PERFORMANCE

The period of performance for this IDIQ will be for a base year with four (4) one year options beginning date of award.

Base Year: September 30, 2015 through September 29, 2016

The following option is anticipate:

Option Year 1: September 30, 2016 through September 29, 2017 Option Year 2: September 30, 2017 through September 29, 2018 Option Year 3: September 30, 2018 through September 29, 2019 Option Year 4: September 30, 2019 through September 29, 2020

2.4 CONTRACT CEILING

The IDIQ guaranteed minimum amount of $2,500.00 over five years (5). The contract maximum ceiling amount will be $20,000,000.00 over five (5) years.

2.5 PRICING

The pricing chart below outlines all of the labor categories and fixed hourly rates that shall be required throughout the life of the contract.

2.5.1 Pricing Chart:

CLIN Description of Services Estimated Hours

Full Loaded BurdenedRate Quantity

Amount

Base Year: Period of Performance 09/2015-09/2016 Labor Category - Base Contract

1 Principal Investigator 2000 1 $ 2 Research Assistant 4000 1 $ 3 Physician 2000 1 $ 4 Study Coordinator 4000 1 $ 5 Registered Nurse 4000 1 $ 6 Statistician 800 1 $ Total Estimated Hours Base Contract 16,800 Total Amount for the Base

Option Year 1: Period of Performance 9/2016-9/2017 7 Principal Investigator 4000 1 $ 8 Research Assistant 8000 1 $ 9 Physician 4000 1 $ 10 Study Coordinator 8000 1 $ 11 Registered Nurse 8000 1 $ 12 Statistician 1600 1 $ Total Estimated Hours – Option Year 1 33,600 Total Amount for the Option Year 1

Option Year 2: Period of Performance 2017-2018 13 Principal Investigator 6000 $ 14 Research Assistant 12000 $ 15 Physician 6000 $ 16 Study Coordinator 12000 $ 17 Registered Nurse 12000 $ 18 Statistician 2400 $ 50,400 Total Estimated Hours – Option Year 2 Total Amount for the Option Year 2

Option Year 3: Period of Performance 2018-2019 19 Principal Investigator 6000 $ 20 Research Assistant 12000 $ 21 Physician 6000 $ 22 Study Coordinator 12000 $ 23 Registered Nurse 12000 $ 24 Statistician 2400 $

Total Estimated Hours – Option Year 3 50,400 Total Amount for the Option Year 3

Option Year 4: Period of Performance 2019-2020 25 Principal Investigator 2000 $ 26 Research Assistant 4000 $ 27 Physician 2000 $ 28 Study Coordinator 4000 $ 29 Registered Nurse 4000 $ 30 Statistician 800 $

Total Estimated Hours – Option Year 4 16,800 Total Amount for the Option Year 4

Labor Category Descriptions:

Principle Investigator: It is preferred the Principal Investigator possess a Master’s Degree or a Ph.D. Degree in drug delivery, pharmacokinetics, pharmacodynamics, pharmacology AND have 5 years professional experience in developing study protocols, protecting subject’s rights, safety and welfare, supervising staff, clinical data management, and overseeing the conduct of in vivo human study of oral, parenteral, nasal, inhalation, or topical drug products.

Physician: It is preferred the Physician in the clinical team possess a Master’s Degree in any medical discipline AND have a 1 year professional experience in safety monitoring of clinical trials in related therapeutic areas.

Study Coordinator: It is preferred the study coordinator possess a Bachelor’s degree (in any discipline) AND have 3 years professional experience in coordinating clinical trials.

Nurse: It is preferred the Nurse possess an accredited Diploma or college degree in nursing AND, during the past three years, have 1 year professional experience in their nursing specialty.

Scientist (bioanalytical): It is preferred the Scientist possess a Bachelor’s degree (in analytical chemistry, biopharmaceutics, and related areas) AND a 8 years of professional experience in analytical chemistry, biopharmaceutics, and related areas. OR the possess a Master’s degree (in analytical chemistry, biopharmaceutics, and related areas ) AND 5 years of professional experience in analytical chemistry, biopharmaceutics, and related areas. OR possess a Ph.D. degree (in analytical chemistry, biopharmaceutics, and related areas ) AND 1 year professional experience in analytical chemistry, biopharmaceutics, and related areas.

The Scientist must demonstrate strong proficiencies in instrumental techniques, including but limited to HPLC and LC/MS/MS, for pharmacokinetics sample analysis.

Clinical Statistician: It is preferred the Clinical Statistician possess a Master’s Degree in statistics, biostatistics, mathematics, applied mathematics, or related fields AND 4 years professional experience in clinical study design, development of statistical analysis plan, data analysis, and statistical inferences OR possess a Ph.D. Degree in statistics, biostatistics, mathematics, applied mathematics, or related fields AND 1 year professional experience in clinical study design, development of statistical analysis plan, data analysis, and statistical inferences.

PART 3

STATEMENT OF WORK

3.1 Background

This contract is to conduct in vivo studies of generic drug products in human subjects to proactively address scientific questions in developing generic approval standards and to ensure post-market safety and efficacy of approved generic drug products. Below is an example demonstrating how CDER uses the contracted, in vivo human study mechanism to monitor post-market generic drug safety and efficacy.

Example: Bioequivalence of generic antiepileptic drugs in patients with epilepsy

Several patient advocacy groups express concerns that switching from a reference to a generic antiepileptic drugs and the switching between two generic antiepileptic drug products would result in increased seizure frequency and other types of therapeutic failure. There has been the advocacy for establishing bioequivalence (BE) in patient populations using a multiple-dose study design.1,2

In 2010 and 2011, FDA awarded two contracts to investigate the bioequivalence of immediate release lamotrigine tablets in patients with epilepsy. In these contracts, a total of three in vivo human studies were conducted:

1) A multiple-dose, 2-sequence, 4-period, crossover, fully replicated study to evaluate BE between a generic and the reference product;3

2) A multiple-dose, 2-sequence, 4-period, crossover, fully replicated study to evaluate BE between two generic products with most distinct features in terms of formulation, manufacturing, and PK parameters in generic drug applications;4

3) A single-dose, 3-sequence, 6-period, crossover, replicated study to evaluate BE between the reference and two generic products.5

Both contracts are close to completion. Results of these studies help address some physician concerns on whether single-dose BE studies in healthy subjects can ensure bioequivalence in patients.

FDA has identified other topics for which in vivo studies in human subjects would be necessary to address scientific questions or quality concerns of specific generic drug products. For instance, FDA is interested in whether formulation complexity warrants additional BE evaluation of generic modified release (MR) drug products.

ACRONYMS: Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), bioequivalence (BE), pharmacokinetic (PK), modified release (MR), area under the concentration-time curve (AUC), Institutional Review Board (IRB), Good Manufacturing Practices (GMP), Good Laboratory Practices (GLP), Good Clinical Practice (GCP), Institutional Review Board (IRB), Research Involving Human Subjects Committee (RIHSC), Statement of Work (SOW), Contracting Officer Representative (COR), Contracting Officer (CO) and Principal Investigator.

3.2. Objectives

The objective of this study is to conduct appropriate in vivo studies of generic drug products in healthy subjects or patients as determined by the question of interest. The in vivo human studies include but are not limited to pharmacokinetic study. The outcome of this study will help address scientific questions in developing generic approval standards and ensure post-market safety and efficacy of approved generic drug products.

Ultimately, the outcome of this study will help improve the generic review practice when applicable.

3.3. Description of Work/Statement of Work

Each year FDA may order a minimum of five (5) studies from the following table, depending on the need for such studies and available funds. Each type of study is subject to repeat with different drug products as a function of regulatory need.

Type of Studies Dosing Schedule Food Effect Study Population

Single dose Fasting In healthy subjects

In patients

Fed In healthy subjects In patients

Multiple dose Fasting/Fed In healthy subjects In patients

Other study design factors, including but not limited to 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), and the selection of bioequivalence metrics (e.g. AUC from Time 0 to infinity vs. partial AUCs) may be adjusted as determined by the study topic.

FDA will order multiple in vivo human studies in a single task order.

With each awarded task order, the Contractor shall:

3.3.1 Perform quality characterization on drug products including but not limited to potency, content uniformity, impurity, and in vitro dissolution. If necessary, stability testing of drug products will be performed.

3.3.2 For studies that require a blinding process, submit a proposal of the blinding process (e.g., over-encapsulation, double dummy) and ensure that the blinding process will not alter the physicochemical properties or the clinical performance of the study drugs, prior to beginning the study.

3.3.3 For studies that require manufacturing drug products or placebo product, follow applicable Good Manufacturing Practice (GMP) regulations.

3.3.4 Develop protocol for the planned in vivo human study. The protocol shall conform to all applicable Good Clinical Practice (GCP) regulations. The protocol shall include at a minimum: Informed Consent Form, Clinical and Analytical Site Identification, Key Personnel, Background Material, Demographics, Inclusion and Exclusion Criteria, Method of Subject Selection, Randomization Scheme, Study Design, Sample Size Determination, Fasting and Fed Conditions, Blood Sampling Times and Volume, Sample Storage, Potential Risks to the Subjects, Protection Against Risks, Potential Benefits to the Subjects and to Society, Risk/Benefit Assessment, Confidentiality of Subject Information, Data Safety Monitoring Plan, Subject Recruitment Oversight, Study Progress, and Adverse Event Reporting Plan. The protocol developed by the Contractor shall comply with the requirements of FDA’s IRB, the Research Involving Human Subjects Committee (RIHSC) in addition to the Contractor’s local IRB. The contractor shall submit to FDA a protocol that follows RIHSC guidelines for format and content.

3.3.5 Begin the study within 15 calendar days from the date the Contractor obtains both RIHSC approval and local IRB approval.

3.3.6 Perform the bio-analytical study according to Good Laboratory Practice (GLP) regulations. Document and justify any deviations from these regulations. Bio-analytical method validation includes all the procedures that demonstrate that a particular method used for quantitative measurement of analysts in a given biological matrix such as blood, plasma, serum is reliable and reproducible for the intended use. The fundamental parameters for this validation include (a) accuracy, (b) precision, (c) selectivity, (d) sensitivity, (e) reproducibility and (f) stability. Incurred sample reanalysis should be performed.

3.3.7 Monitor and record any side effects or adverse reactions during the in vivo human study.

3.3.8 Conduct appropriate statistical analyses of study outcome. For bioequivalence studies, use appropriate statistical analysis software to determine the pharmacokinetic parameters and to evaluate bioequivalence between study products.

3.3.9 Generate study report on the evaluation of study products and on safety outcome of the study.

3.3.10 Be responsible for subject recruitment, supplies, equipment, data collection, and computational software.

3.3.11 Adhere to all relevant FDA guidance documents.

1.1. References

1. American Epilepsy Society. 2007. The substitution of different formulations of antiepileptic drugs for the treatment of epilepsy. (Accessed in Februry 2015, at https://www.aesnet.org/sites/default/files/file_attach/AboutAES/PositionStatements/p osition%20statement%20on%20substitution%20of%20generic%20formulations.pdf).

2. MD Privitera. 2008. Generic antiepileptic drugs: current controversies and future directions. Epilepsy Curr 8(5):113-117.

3. https://clinicaltrials.gov/ct2/show/NCT01995825

4. https://clinicaltrials.gov/ct2/show/NCT01713777?term=equigen&rank=2

5. https://clinicaltrials.gov/ct2/show/NCT01733394?term=equigen&rank=1

PART 4

PACKAGING AND MARKING

4.1 Marking Instructions for Reports

All deliverables required under this contract shall be packaged, marked, and shipped with the organizations name and contract and task order number. As appropriate, note on the face page of the report and when feasible on the binding: (1)”one volume only” or (2) “volume 1 of 2, volume 2 of 2” etc.

http://www.aesnet.org/77B16A48-E7FF-0F41-218E9CB3E54919D4) http://www.aesnet.org/77B16A48-E7FF-0F41-218E9CB3E54919D4) http://www.aesnet.org/77B16A48-E7FF-0F41-218E9CB3E54919D4) https://clinicaltrials.gov/ct2/show/NCT01995825 https://clinicaltrials.gov/ct2/show/NCT01713777?term=equigen&rank=2 https://clinicaltrials.gov/ct2/show/NCT01733394?term=equigen&rank=1

PART 5

INSPECTION AND ACCEPTANCE

5.1 The Contracting Officer or the duly authorized Contracting Officers Representative (COR) will perform inspection and acceptance of materials and services to be provided.

5.1.1 For the purpose of this SECTION, (The Contracting Officer’s Representative (COR) – to be named in separate correspondence is the authorized representative of the Contracting Officer and is responsible for inspection and acceptance of all items to be delivered under this contract.

5.1.2 Inspection and acceptance will be performed at 9200 Corporate Blvd., Rockville, MD 20850. Acceptance may be presumed unless otherwise indicated in writing by the Contracting Officer or the duly authorized COR within 30 days of receipt.

5.1.3 The contract incorporate the following clause by reference, with the same force and effect as if it were given in full text. FAR clauses are also available on the Internet at: http://farsite.hill.af.mil/. Upon request, the Contracting Officer will make its full text available.

5.1.4 FAR Clause 52.246-4, Inspection of Services-Fixed-Price (Aug 1996).

PART 6

DELIVERIES OR PERFORMANCE

The reporting requirements and deliverables apply to each task order award.

All deliverables shall be 508 compliant. All electronic and information technology (EIT) must met the applicable accessibility standards at 36 CFR 1194, unless an agency exception to this requirement exists. 36 CFR 1194 implements Section 508 of the Rehabilitation Act of 1973, as amended, and is viewable at:

http://www.access-board.gov/sec508/standards.htm.

Pursuant to the HHSAR clause 352.270-19, the Section 508 standards applicable to the prospective award are:

• § 1194.41 Information, documentation, and support

• § 1194.21 Software applications and operating systems

• § 1194.22 Web-based intranet and internet information and applications http://farsite.hill.af.mil/

DELIVERABLE / REPORT/

DOCUMENT DELIVERY DATE

Study protocol and implementation plan 30 calendar days after individual task order award.

Submission of RIHSC package 90 calendar days after individual task order award.

Approval from local IRB 180 calendar days after individual task order award.

Quarterly Progress Report 30 days following the close of every 3rd month from individual task order award.

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 individual task order award.

Annual Report (written document)

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

Final Report (Draft)

45 days prior to the individual task order expiration date for comments. Comments will be provided to contractor within 25 days of receipt and addressed in the final report.

Final Report No later than the individual task order expiration date.

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

*Additional deliverables will be identified on task orders

Reports (i.e., quarterly progress reports, and final report), containing the description of experiments and data analysis, will be provided to the FDA using FDA recommended format in both paper and electronic format. In addition, all of the raw data from the experiments will be provided to the FDA in electronic format, along with these reports.

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 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. At study initiation, each study group 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 likely that a Contractor employee will 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 2-x 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 will likely 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.

6.1 Research Involving Human Subjects

All research conducted, supported, or regulated by any U.S. Government Agency is subject to certain uniform requirements of the Federal Policy for the Protection of Human Subjects including Institutional Review Board (IRB) membership, IRB review and approval criteria, IRB operations and record keeping, and informed consent. The Contractor agrees that the rights and welfare of human subjects involved in research under this contract shall be protected in accordance with 45 CFR Part 46 and with the Contractor’s current Assurance of Compliance on file with the Office for Human Research Protections (OHRP), Department of Health and Human Services.

The Institutional Review Board (IRB) specified in the Contractor’s Assurance of Compliance, hereafter referred to as "the local IRB," shall review the proposed research protocol. A letter from the local IRB stating that the proposed research protocol adequately protects the rights and welfare of human subjects involved, or a letter stating that the proposed research is exempt under 45 CFR 46.101(b) and shall be submitted to the FDA Contracting Officer’s Representative (COR).

The Contractor further agrees that research involving human subjects and funded by the FDA shall receive approval from FDA’s Research Involving Human Subjects Committee (RIHSC) prior to enrolling human subjects. The Contractor shall submit its proposed research protocol and all related documents (including but not limited to the informed consent form, recruitment material, telephone script, questionnaire, and Investigator’s brochure or package insert of study drug(s) as appropriate) through the FDA COR to the FDA’s Research Involving Human Subjects Committee (RIHSC).

The Contractor shall understand and comply with ethical principles and regulatory requirements involving human subjects research as specified in the Federal regulations for the Protection of Human Subjects, 45 CFR 46. The Contractor shall remain in compliance with the Health and Human Services (HHS) policies and procedures that concern the conduct of human subjects research.

The Contractor shall bear full responsibility for the performance of all work and services involving the use of human subjects under this contract in a proper manner and as safely as is feasible. Nothing in this contract shall be deemed to constitute the Contractor or any sub-Contractor, agent or employee of the Contractor, or any other person, organization, institution, or group of any kind whatsoever, as the agent or employee of FDA. The Contractor agrees that it has entered into this contract and will discharge its obligations, duties, and undertakings and the work pursuant thereto, whether requiring professional judgment or otherwise, as an independent Contractor without imputing liability on the part of FDA for acts of the Contractor or its employees.

If at any time during performance of this contract, the Contracting Officer determines, in consultation with FDA’s RIHSC, that the Contractor is not in compliance with any of the requirements and/or standards stated in Section 3.5, the Contracting Officer may immediately suspend, in whole or in part, work and further payments under this contract until the Contractor corrects the noncompliance. Notice of the suspension may be communicated by telephone and confirmed in writing by the Contracting Officer. If the Contractor fails to complete the corrective action within the period of time designated in the Contracting Officer's written notice of suspension, the Contracting Officer may, in consultation with FDA’s RIHSC, terminate this contract in whole or in part, and the Contractor’s name may be removed from the list of those Contractors with approved Department of Health and Human Services Human Subject Assurances.

6.2 Compliance

The Contractor shall ensure compliance with the following requirements:

a. No FDA funds shall be expended to implement any part of the proposed research protocol funded in whole or part under this contract until approval is received from both the local IRB and RIHSC. Activities requiring approval include recruitment, enrollment, screening, records review or any other activity related to protocol implementation.

b. Should a portion of the FDA funds be applied to protocol development or other support activities conducted prior to protocol implementation, the Contractor shall provide an accounting of the use of these funds at the time of RIHSC review.

c. All consent forms shall comply with HHS and FDA regulations at 5 CFR 46.116 and 21 CFR 50.25 regarding the required elements of informed consent.

d. The FDA COR will serve as the responsible party for a trial which is determined to be an applicable clinical trial under Title VIII of FDAAA. The FDA COR or their delegate shall register and submit the results of the research study to ClinicalTrials.gov. https://clinicaltrials.gov/. For trials which do not meet the definition of an applicable clinical trial under Title VIII of FDAAA, the contractor may register and submit the results of the study with prior approval by the FDA COR.

In such a case, the contractor is responsible for all matters relating to the ClinicalTrials.gov databank. The information on the registry can be found at the link above.

e. If FDA is providing partial funding for the research study, details of the expenses paid for with FDA funds shall be tracked separately.

f. Should funds support any salaries, information on what activities are being performed by each individual for that salary support must be tracked and reported to the FDA.

g. Any changes to the protocol, informed consent form, recruitment materials or any other documents related to the protocol implementation shall be reviewed and approved by RIHSC as well as the local IRB, prior to implementation.

h. Research approved by the local IRB and RIHSC may not continue beyond one year from the approval date unless a continuing review is conducted by both the local IRB and RIHSC and approved.

The RIHSC shall review the research protocol to assure that the rights and welfare of human subjects involved are adequately protected. The RIHSC shall also determine whether the proposed research is exempt under 45 CFR 46.l01 (b).

Research involving human subjects may commence immediately upon the Contractor’s receipt of RIHSC approval provided by the FDA COR and the local IRB approval.

If the Contractor fails to obtain RIHSC approval of its proposed research during RIHSC's initial review, the Contractor shall have the opportunity to correct the deficiencies identified during the RIHSC review and resubmit the proposed research protocol to RIHSC for a second review. The Contractor is to solicit the RIHSC's input during the resubmission process.

The Contractor must provide a risk-based monitoring plan in the protocol that describes the procedures and documentation that shall be used to monitor the clinical study. This includes resources available to the Contractor for oversight and quality assurance monitoring of the study (e.g. Quality Assurance Program, Human Subject Research Compliance Program).

The proposed research study protocol shall comply with ICHE6 Good Clinical Practice Consolidated Guidance which sets an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. All human subject research regulated by FDA may also be subject to FDA's regulations regarding the protection of human subjects (21 CFR parts 50 and 56).

6.3 Research Involving Human Subject Committee

Upon contract award, the Government will arrange a kickoff meeting with the Contractor to discuss requirements of the Research Involving Human Subjects Committee (RIHSC), the FDA’s Institutional Review Board (IRB) and the roles and responsibilities of Government personnel throughout the RIHSC review process.

Following the kickoff meeting, the Contractor shall submit the proposed study documents including the research protocol, informed consent form(s), participant information sheet (if applicable), and recruitment advertisements to the FDA COR. The FDA COR shall review the submission package to ensure completeness and will provide comments/suggestions. All final research documents shall be submitted to the FDA COR for review including CVs or resumes and appropriate training records of key personnel, a medical license of medically accountable officer, Investigator’s brochure or package insert of study drug(s) as appropriate, a federal wide assurance number of local IRB, and FDA form 1572. Following the review and sign off by the Center’s RIHSC Liaison, the submission package shall be submitted electronically to the RIHSC. The Contractor and the FDA COR copied on the email submission to the RIHSC.

If the Contractor has already received local IRB approval for the final study documents prior to submission to RIHSC, a copy of the approval letter from the local IRB must be included in the submission package to the FDA COR. The IRB approval letter must state that the proposed research study documents adequately protect the rights and welfare of human subjects. The Contractor may submit the research study documents to their IRB at the same time the Contractor submits its package to the FDA COR for RIHSC review.

The Contractor is required to submit the approval letter from the local IRB to the FDA COR upon receipt of the letter. This requirement would include proposed research that is exempt from IRB approval.

Please note: Certification of local IRB review and 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, and appropriate signatures. The IRB must ensure that any corresponding protocol(s) are consistent with the specific application.

The RIHSC will review the research study documents to assure that the rights and welfare of human subjects involved are adequately protected. The RIHSC will also determine whether the proposed research is exempt under 45 CFR 46.101(b). The FDA COR will provide the Contractor with a copy of RIHSC’s letter of approval/approval with stipulations/disapproval. If RIHSC renders a decision other than approval of the proposed research study documents, the FDA COR will assist the Contractor in revising the research study documents for re-submission to RIHSC for review and approval.

The Contractor shall seek RIHSC approval and 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 study protocol, consent form(s), recruitment materials, and the addition or deletion of key personnel/investigators. The Contractor shall submit modified/amended study documents to the FDA COR for RIHSC review and approval. The FDA COR will provide the Contractor with a copy of RIHSC’s letter of approval/approval with stipulations/disapproval. The Contractor shall also submit a copy of the local IRB approval of modifications/amendments to the FDA COR upon receipt.

Questions regarding FDA RIHSC shall be directed to CDER’s Extramural Clinical Studies Coordinator

6.4 Reporting

a) Changes/amendments to the protocol/informed consent document must promptly report to the RIHSC all proposed changes in the research activity including any modifications to the Study Protocol, and Informed Consent document.

b) Non-compliance: the Contractor must report any alleged breaches of the protocol, such as breakdowns in the informed consent process, violations of confidentiality of data or privacy of a research subject, complaints by participants or their representatives, and any serious or continuing noncompliance with federal regulations by the investigators or research staff via FDA Sponsor.

c) Adverse event reporting: the Contractor must report to the FDA Sponsor, any unanticipated problems involving risk to human subjects or others and anticipated adverse events may reported to the RIHSC in the annual report for continuing review.

6.5 Quality Assurance and Monitoring

The Government will perform quality assurance monitoring (either remotely or via on-site visits) to ensure human subject protections throughout the conduct of the study and document compliance with the regulations and the RIHSC requirements that govern the conduct of research involving human subjects. The CDER’s Extramural Clinical Studies

Coordinator and/or the FDA COR will provide the Contractor with a report of all identified deviations and/or violations related to human subject protections. If violations are found, the Contractor shall provide responses to the corrective actions listed in the report to the CDER’s Extramural Clinical Studies Coordinator and the FDA COR within 2 weeks of receipt of the report/violation notice. If the Contractor has established a Steering Committee and/or a Monitoring Board (for monitoring quality assurance) for this contract, the Contractor shall submit the responses to the corrective actions of violations to the Steering Committee and/or Monitoring Board as established.

The Contractor shall provide documentation of acknowledgement of the violations either by the local IRB and/or Steering Committee/Monitoring Board to the CDER’s Extramural Clinical Studies Coordinator and the FDA COR. This documentation will be forwarded to RIHSC for review and documentation of the review and any required actions will be provided to the Contractor.

PART 7 - CONTRACT ADMINISTRATION DATA

7.1 CONTRACTING OFFICER’S REPRESENTATIVE (COR)

The following COR will represent the Government for the purpose of this contract:

7.1.1. 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.

COR contact information shall be provided at time of award.

7.2 CONTRACT ADMINISTRATION

7.2.1 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 RFQ; (2) modify or extend the period of performance; (3) change the delivery schedule; (4) authorize reimbursement to the Contractor any costs incurred during the performance of this contract; or (5) otherwise change any terms and conditions of this contract.

Linda Troutman Contract Specialist Linda.Troutman@fda.hhs.gov 404-253-1258 mailto:Linda.Troutman@fda.hhs.gov

7.2.3 PAYMENT TERMS

A. Progress payment will be made on a monthly basis with the receipt of a proper invoice/voucher, and a description of the studies delivered during the invoice period.

B. After completion of the work, and prior to final payment, the Contractor shall furnish to the Contracting Officer a release of claims against the United States arising out of the Contractor, other than claims with exceptions from the operation of the release.

7.2.4 INVOICING SUBMISSION

In accordance with clause 52.232-33 all payments made under this contract shall be made using electronic funds transfer through the Automated Clearing House (ACH). The Contractor shall provide the following information to the Food and Drug Administration no later than 14 days prior to submission of the first invoice:

A. The contractor shall submit all invoices to all addresses in the manner specified below:

(I) One original to the Contracting Officer:

U.S. Food and Drug Administration Office of Acquisitions and Grants Services ATTN: Linda Troutman, Contracting Officer 60 8th street, NE Room 116 Atlanta, GA 30309 E-mail: Linda.Troutman@fda.hhs.gov

*** Acceptable methods of delivery include: mail, hand delivery and email***

(II) One copy to the contracting officer representative (COR), clearly marked “Courtesy Copy Only”:

U.S. Food and Drug Administration

ATTN: , COR

Email:

*** Acceptable methods of delivery include: mail, hand delivery and email***

B. Invoices submitted under this contract must comply with the requirements set forth in FAR Clauses 52.232-25 (Prompt payment) AND 52.232-33 (Payment by electronic funds transfer – Central Contractor Registration) and/or other applicable FAR clauses specified herein. To constitute a proper invoice, the invoice must be submitted on company letterhead and include each of the following:

1. Name and address of the Contractor

2. Invoice date and invoice number

3. IDIQ Contract number/Task Order Number

4. Description, Quantity, Unit of Measure, Unit Price, and Extended Price of supplies delivered

5. Shipping number and date of shipment, including the bill of lading number and weight of shipment if shipped on Government bill of lading

6. Terms of any discount for prompt payment offered

7. Name and address of official to whom payment is to be sent (Must be the same as that in the purchase order or in a proper notice of assignment)

8. Name, title, and phone number of person to notify in event of defective invoice

9. Taxpayer identification number

10. Electronic Funds Transfer (EFT) banking information

11. Name and telephone number of the FDA COR referenced on the purchase order

12. Any other information or documentation required by the purchase order

An electronic invoice is acceptable if submitted in adobe acrobat (PDF) format. All items listed in 1-12 of this clause must be included in the electronic invoice. Electronic invoices must be on company letterhead and must contain no ink changes and be legible for printing.

Questions regarding invoice payments should be directed to the FDA Payment Office at:

FDA Payment Services ATTN: Vendor payment, OFS FDA 10903 New Hampshire Avenue Bldg. 32, Rm 2162, Mail Hub 2145 Silver Spring, MD 20993-0002

301.827.3742 OR 866.807.3742

OFS/paymentservices@fda.hhs.gov

7.2.4.1 Final payments will occur upon verification by the FDA COR, noting acceptance of the work.

7.2.4.2 Payment will be made after acceptance and receipt of a proper invoice.

PART 8 - SPECIAL CONTRACT REQUIREMENTS

8.1 Security and Privacy

Contractor personnel performing work under this contract shall satisfy all requirements for appropriate security eligibility in dealing with access to sensitive information and information systems.

mailto:OFS/paymentservices@fda.hhs.gov

The contractor agrees that contractor personnel will not divulge or release data or information developed or obtained in connection with the performance of the resulting contract, unless made public by FDA or upon written approval from the Government.

Except as may otherwise be permitted by a data owner, the contractor personnel agrees not to use, disclose or reproduce proprietary data, other than as required in performance of the contact; provided, however, that nothing herein shall be construed as precluding the use of any data independently acquired by the contractor without such limitation.

The contractor shall submit a roster, by name, position and responsibility, of all staff (including subcontractor staff) working under the contract that will develop, have the ability to access, or host and/or maintain a Federal information system(s). The roster shall be submitted to the COR, with a copy to the Contracting Officer, within 14 calendar days of the effective date of the contract. Any revisions to the roster as a result of staffing changes shall be submitted within 15 calendar days of the change.

Each contractor/subcontractor employee who may have access to non-public Department information and/or sensitive information under this contract may be required to sign a Confidentiality form and/or a FDA Form 3398: Contractor’s Commitment to Protect Non-Public Information (NPI) Agreement available upon request from the FDA Intranet site. A copy of each signed and witnessed Non-Disclosure agreement shall be submitted to the COR or designee prior to performing any work under the contract. The COR or designee will inform the contractor of the forms and training that are required. However, it is the responsibility of the Contractor to assure that such forms have been signed.

8.2 FDA 1338 Individual Conflict of Interest

As a regulatory agency charged with protection of public health, the Food and Drug Administration (FDA) must maintain public confidence in the integrity of its decisions.

The FDA has policies and procedures that safeguard against actual and apparent conflict of interest on the part of its employees. In contacting for review and evaluation of scientific data and information submitted to the agency, it is critical that the FDA be assured that there is no actual or apparent conflict of interest on the part of the individual contractor. Offers performing work under this contract must assure the protection of information and data they receive under this contract from unauthorized use or disclosure, and must avoid actions that would cause a reasonable person to question the impartiality of the contractor.

8.3 Conflict of Interest Screening

An individual offeror/contractor submitting a proposal in response to this solicitation must submit the following information (if no relevant information exists, please provide a statement to that effect, limited to only those projects or financial holdings where the contractor believes there is or may be a potential for conflict).

1. Any contracts, grants, or cooperative research and development assignments that you are working on or have under negotiation;

2. Any other relevant information concerning any past, present, or planned interest that may have a bearing on the responsibilities described in the Statement of Work

The Contracting Officer’s Representative shall conduct a review of the information submitted and determine if a conflict of interest exist prior to forwarding any documents to the contractor. Prior to submitting new work assignment, the Contracting Officer’s Representative will follow-up with the contractor to determine if any changes to his/her financial interest have occurred.

8.4 Conflict of Interest Agreement

In executing this contract, the individual contractor agrees:

1. To report to the proper authority within the FDA (the Contracting Officer), any situation or event that may constitute a conflict of interest, whether actual or potential.

2. To act impartially and not give preferential treatment to any individual or organization which has submitted applications, information, and or data.

3. Not to solicit any gift or other item, nor accept any gift or other item, of monetary value exceeding $20.00 from any person or entity seeking official action from, doing business with or conducting activities related to the evaluations and work performed under this contract. Aggregate market value of individual gifts should not exceed $50.00 in a calendar year.

4. Not to participate in any matter involving specific parties who are likely to or can directly affect the financial interest of a member of his household or a relative with whom they have a close personal relationship; and

5. To disqualify himself from participating in particular matters involving former employees or their representatives, with whom they have worked within the past (3) years and who might represent a conflict of interest.

8. 5 Organizational Conflict of Interest

(a) Purpose. The purpose of this clause is to ensure that the contractor and its subcontractors:

(1) Are not biased because of their financial, contractual, organizational, or other interests which relate to the work under this contract, and

(2) Do not obtain any unfair competitive advantage over other parties by virtue of their performance of this contract.

(b) Scope. This clause applies to performance or participation by the contractor, its parents, affiliates, divisions and subsidiaries, and successors in interest (hereinafter collectively referred to as “contractor”) in the performance of this contract as a prime contractor, subcontractor, co-sponsor, joint venture, consultant, or in any similar capacity.

(c) Warrant and Disclosure. The warrant and disclosure requirements apply to both the contractor and all subcontractors. The contractor warrants that, to the best of the contractor's knowledge and belief, there are no relevant facts or circumstances which would give rise to an organizational conflict of interest, as defined in FAR Subpart 9.5, and that the contractor has disclosed all relevant information regarding any actual or potential conflict. The contractor agrees it shall make an immediate and full disclosure, in writing, to the Contracting Officer of any potential or actual organizational conflict of interest or the existence of any facts that may cause a reasonably prudent person to question the contractor's impartiality because of the appearance or existence of bias or an unfair competitive advantage. Such disclosure shall include a description of the actions the contractor has taken or proposes to take in order to avoid, neutralize, or mitigate any resulting conflict of interest.

(d) Remedies. The Contracting Officer may terminate this contract for convenience, in whole or in part, if the Contracting Officer deems such termination necessary to avoid, neutralize or mitigate an actual or apparent organizational conflict of interest. If the contractor fails to disclose facts pertaining to the existence of a potential or actual organizational conflict of interest or misrepresents relevant information to the Contracting Officer, the Government may terminate the contract for default, suspend or debar the contractor from Government contracting, or pursue such other remedies as may be permitted by law or this contract.

(e) Subcontracts. The contractor shall include a clause substantially similar to this clause, including paragraphs (f) and (g), in any subcontract or consultant agreement.

(f) Prime Contractor Responsibilities.–1, and shall determine in writing whether the interests disclosed present an actual, or significant potential for, an organizational conflict of interest. The contractor shall identify and avoid, neutralize, or mitigate any subcontractor organizational conflict prior to award of the contract to the satisfaction of the Contracting Officer. If the subcontractor's organizational conflict cannot be avoided, neutralized, or mitigated, the contractor must obtain the written approval of the Contracting Officer prior to entering into the subcontract. If the contractor becomes aware of a subcontractor's potential or actual organizational conflict of interest after contract award, the contractor agrees that the Contractor may be required to eliminate the subcontractor from its team, at the contractor's own risk. The contractor shall obtain from its subcontractors or consultants the disclosure required in FAR Part 9.507

(g) Waiver. The contractor may seek a waiver from the Head of the Contracting Activity by submitting such waiver request to the Contracting Officer, including a full written description of the requested

8.6 Personnel Security Clearance Requirements

FDA 1335 Personnel Security Clearance Requirements (12/2010)

1. BACKGROUND

The office of the Assistant Secretary of Management and Budget of Health and Human Services (DHHS), requires that DHHS employees and contractor employees (including subcontractors) who will be working in DHHS-owned or leased space and/or who will have access to DHHS equipment, and non-public privileged, proprietary, or trade secret information undergo a background investigation or some type.

Contractor employee who will be in DHHS-owned or lease space for less than thirty

(30) days, are exempted from the background investigation requirement. The contractor employees must be escorted at all time while in DHHS-owned or leased space.

PART 9

CONTRACT CLAUSES

52.252-2 FAR Clauses Incorporated by Reference (FEB 1998) This contract incorporates one or more clauses by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. Also, the full text of a clause may be accessed electronically at:

https://acquisition.gov/far/

(a) The Contractor shall comply with the following Federal Acquisition Regulation (FAR) clauses, which is incorporated in this contract by reference, to implement provisions of law or Executive orders applicable to acquisitions of commercial items:

Clause Date Clause Title

52.202-1 Nov 2013 Definition (Over the Simplified Acquisition Threshold) 52.203-3 Apr 1984 Gratuities (Over the Simplified Acquisition Threshold) 52-203-5 May 2014 Covenant Against Contingent Fees (Over the Simplified Threshold

52.203.6 Sep 2006 Restrictions on Subcontractor Sales to the Government (Over the

Simplified Acquisition Threshold) 52.203-7 May 2014 Anti-Kickback Procedures (Over the Simplified Acquisition

Threshold) 52.203-8 May 2014 Cancellation, Rescission, and Recovery of Funds for Illegal or

Improper Activity (Over the Simplified Acquisition Threshold) 52.203-10 May 2014 Price of Fee Adjustment for illegal or Improper Activity (Over the

Simplified Acquisition Threshold) 52.203-12 Oct 2010 Limitation on Payments of Influence Certain Federal Transactions

(Over $150,000) 52.204-4 May 2011 Printed or Copied Double-Sided on Postconsumer Fiber Content

Paper (Over the Simplified Acquisition Threshold) https://acquisition.gov/far/

52.204-10 Jul 2013 Reporting Executive Compensation and First-Tier Subcontract Award

52.204-13 Jul 2013 Central Contractor Registration Maintenance 52.209-6 Aug 2013 Protecting the Government’s Interest When Subcontracting With

Contractor Debarred, Suspended, or Proposed for Debarment (Over $30,000)

52.211-5 Aug 2000 Material Requirements 52.212-1 Apr 2014 Instructions to Offerors-Commercial Items 52.212-4 May 2015 Contract Terms and Conditions - Commercial Items 52.215-2 Oct 2010 Audit and Records - Negotiation [Note: Applies to ALL contacts funded in whole or in part with Recovery Act Funds, regardless of dollar value, AND contracts over the Simplified Acquisition Threshold funded exclusively with non-Recovery Act funds.]

52.215-8 Oct 1997 Order of Precedence – Uniform Contract Format 52.215-14 Oct 2010 Integrity of unit Prices (Over the Simplified Acquisition Threshold) 52.215-15 Oct 2010…