Attachment F - Sample Task Order Statement of Work.docx

Attachment #1 – Statement of Work Sample Task Order Project Title: Bioequivalence of generic oral products coadministration with acid-reducing agent in Healthy Volunteers

1. Description of Work/Statement of Work (SOW)

1.1. Background

For drug products containing active pharmaceutical ingredient (API) with pH-sensitive solubility, reference listed drug (RLD) may be designed to mitigate pH sensitivity (e.g., adding pH modifier in formulation). For those drug products, prescribing RLD labeling allows concomitant use of acid-reducing agents (ARA). For certain drug products, strong evidence was found in support of recommendation of assessing the risk of pH-dependent bio-inequivalence due to formulation differences between test and reference. For example, in May 2022, product-specific guidance (PSG) for Palbociclib tablets was revised to recommend a bioequivalence study with ARA under fasting conditions. RLD with weak bases specially formulated to reduce ARA interactions may require additional regulatory considerations to ensure generic products perform similarly under label conditions.

For RLDs formulated to withstand an ARA effect, their generic products may include pH modifiers in their formulation but with some variations in their formulation compared to the RLD. The current study intends to evaluate 2 formulations such as RLD and one generic product under fasting with ARA with fully replicated design. The bioequivalence assessment will follow current recommendation outlined in PSG. The SmartPill technology will be used to monitor the GI tract conditions.

This study will inform the Agency on the bioequivalence of the generic products available on the current market to the RLD under the conditions of ARA coadministration and will help the Agency plan the next step of investigations if needed. Additionally, the study results may help the Agency gain a better understanding of in vitro-in vivo correlation of drugs and establish regulatory standards of BE approaches for this category of generic oral products.

1.2. Objective

The goal of this study is to determine the extent to which a formulation strategy can reduce an ARA interaction compared to the same product with different formulation design strategy to reduce ARA effects. This study evaluates the PK performances of RLD and its approved generic drug product under coadministration with ARA. In addition, GI tract conditions are monitored during the in vivo study. Further, factors affecting PK performance (e.g., race, gender) are studied. The outcome of this study will assist the Agency’s regulatory decision making when applicants submit an abbreviated new drug application (ANDA) with differences in formulation compared to RLD.

1.3. Description of Work/Statement of Work

The following shall be conducted for the purpose of the Sample Task Order (TO):

1.3.1 In discussion with the FDA, develop a protocol considering the following clinical trial design: a randomized, active-controlled, 2-treatment, 2- sequence, 4-period, fully replicated crossover study in adult healthy volunteers under fasting conditions to compare the PK endpoints of the selected drug products. The study shall include the followings:

· The two study drug treatment arms using RLD and Generic A

· 50 Adult Healthy Volunteers completed all four periods; the primary endpoint data shall be available for completed subjects

· Fasting conditions with ARA co-administration for 5 days

· Recruiting adult healthy volunteers with various racial backgrounds

· All arms require an administration of SmartPill™

· Wash-out period: 7 days

· Collection of 22 PK samples per subject per period (up to 72 hours)

· PK sample analysis using a validated bioanalytical method

· Evaluation of bioequivalence using plasma levels of two analytes

· Primary study endpoints include the PK measures of Cmax, Tmax, AUClast, and AUCinf of RLD and approved generic drug product coadministration with ARA

· Appropriate statistical analysis

· Appropriate analysis of data (pH, pressure, temp and gastric emptying time) collected through SmartPill™

· Safety evaluation using adverse event reports, vital signs, and laboratory parameters (hematology, chemistry and urinalysis)

· COVID-19 preventive measures

1.3.2 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 Conditions, Blood Sampling Times and Volume, Sample Storage, Potential Risks to the Subjects, Protection Against and Mitigation of 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, Case Report Form, and Adverse Event Reporting Plan and Quality Control plan. The protocol developed by the Contractor shall comply with the requirements of the Contractor’s local IRB and/or FDA IRB (if needed – of note we intend to abide by the revised Common Rule and use a single IRB for clinical studies). The contractor shall submit to FDA a protocol that follows the FDA IRB guidelines for format and content if needed.

1.3.3 Conduct the study in accordance with all applicable regulations/guidance/policies but not limited to 45 CFR 46, 21 CFR, and GCP.

1.3.12 Work with the OGD Contracting Officer’s Representative (COR), Project Officer (PO) and/or Quality Assurance (QA) team, accommodate visit requests, and make all study documents available for monitoring/inspection at all times.

NOTE: The study design including sample size is not final, and upon award, more details will be discussed. The number of subjects to be dosed to obtain the data for 50 completed subjects will depend on a site, therefore, it is not specified. Please include the number needed to be dosed to ensure the required data will be obtained and provide its justification. The proposal shall address all tasks described above and shall include plans for the recruitment, strategies to meet the requirements, per subject cost, bioanalytical method approach, risk management approach, proposed timeline, and time/cost control management plan. If any additional work that may enhance the project is proposed, please include it as an option. If a remote session is proposed as an option for any processes (e.g. consenting), please include a plan and processes/infrastructures that enable successful sessions. For this sample proposal purpose, please assume the procurement of SmartPill™ and its associated materials (recorder and software) and drugs (test and ARA) will be provided.

1.4. References

Not Applicable

1.5 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 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) 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 the local IRB and the FDA COR 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.

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 subject 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 (CO) determines, in consultation with FDA COR and/or local IRB, that the Contractor is not in compliance with any of the requirements and/or standards stated in Sections 1.6 and 1.7, the CO 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 CO. If the Contractor fails to complete the corrective action within the period of time designated in the CO's written notice of suspension, the CO may, in consultation with FDA COR or local IRB, terminate this contract in whole or in part, and the Contractor’s name may be removed from the list of those Contractors with approved HHS Human Subject Assurances.

All research under this task order must address the involvement of human subjects and protections from research risk related to their participation in the proposed research plan and comply with 32 CFR 219, 10 U.S.C. 980, and, as applicable, 21 CFR Parts 11, 50, 54, 56, 312) (45 CFR Part 46) and the ICH as well as other applicable federal and state regulations. HHS Policy also requires that women and members of minority groups and their subpopulations: children and the elderly (pediatric and geriatric) must be included in the study population of research involving human subjects, unless a clear and compelling rationale and justification is provided with respect to the health of the subjects or the purpose of the research. The HHS policy on studies that involved human subjects can be accessible through the HHS website:

http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html.

Research Projects involving humans and/or human specimens can only be initiated with written approval by the FDA Contracting Officer. The Food and Drug Administration Amendments Act of 2007 (FDAAA) contains provisions that expand the current database known as ClinicalTrials.gov to include additional requirements for individuals and entities who are involved in conducting clinical trials that involve products regulated by FDA or that are funded by the HHS, including FDA. These additional requirements include mandatory registration of certain types of clinical trials, as well as reporting of results for certain trials (“applicable trials”) for inclusion in the ClinicalTrials.gov database. More detailed information on the definition of "applicable clinical trial" and the registry and results reporting requirements can be found at https://clinicaltrials.gov/ct2/manage-recs/fdaaa.

FDAAA also added new requirements concerning clinical trials supported by grants and contracts from HHS, including FDA. Under these provisions, any contract or progress report forms required under a contract from any part of HHS, including FDA, must include a certification that the “responsible party" has submitted all required information to the ClinicalTrials.gov registry database. The responsible party is the term used in Title VIII of FDAAA (PL 110-85) to refer the entity or individual responsible for meeting FDAAA’s requirement. Under the contracts, the Contractor assumes the responsibility, and will register a clinical investigation and submit Clinical Trial Information to the Clinical Trial Registry Data Bank if determined to be an applicable clinical trial. In case where the existing policy at the contractor’s institution requires a registration at the Clinical Trial Registry, the contractor shall provide a letter that clearly states the policy and the extent of responsibility within 30 days of the Award/Contract. This letter should be signed by the contractor and cosigned by the institutional official, and sent to the COR and the CO. More detailed information on the definition of "applicable clinical trial" and the “responsible party” can be found at http://prsinfo.clinicaltrials.gov/ElaborationsOnDefinitions.pdf. There are also provisions regarding when agencies within HHS, including FDA, are required to verify compliance with the database requirements before releasing funding to contractors.

As part of 21st Century Cures, HHS is required to consult with relevant Federal agencies, including FDA, and other stakeholders within 90 days of enactment to receive recommendations with respect to enhancements to the ClinicalTrials.gov databank. These recommendations are to address the usability, functionality, and search capability of the databank. NIH has confirmed that it is the lead agency for this provision and has indicated that the recommendations should be focused on the outward facing aspects of ClinicalTrials.gov, as opposed to items related to entering information or new data elements to be collected.

FDA’s Office of Good Clinical Practice (OGCP) is requesting input to help NIH address this 21st Century Cures requirement. Because many different groups at FDA (e.g., review divisions, compliance offices) use ClinicalTrials.gov for a variety of purposes, we ask that you share this request broadly within your organization. Please focus on suggestions related to enhancements of the usability and search functions of ClinicalTrials.gov which may improve or augment work at FDA. Suggestions may include, but are not limited to, items such as the ease of use of the main ClinicalTrials.gov webpage, improved search capabilities, or data output formats. Recommendations related to enhancements which may be useful for FDA stakeholders, such as patients searching for clinical trials, are also being requested.

1.6 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 the IRB. 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 IRB review.

c. All consent forms shall comply with HHS and FDA regulations at 5 CFR 46.116, 21 CFR 50.25 and 45 CFR 46 subpart A regarding the required elements of informed consent.

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

e. 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.

f. 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 the FDA COR and then the IRB, prior to implementation.

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

h. The Contractor must provide an internal monitoring plan that describes the procedures and documentation that shall be used for quality management purpose.

i. More details on Human Subject Research Terms and Conditions can be found in the base contract.

The proposed research study protocol shall comply with ICH E6 (R2) 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).

1.7 FDA Review

Upon contract award, the Government will arrange a kickoff meeting with the Contractor to discuss requirements of the FDA as appropriate and if necessary and the roles and responsibilities of Government personnel throughout the FDA 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), survey questions, phone scripts, 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.

In consultation with OGD HSP Liaison, the Contractor and the PO will prepare the documents for Non-Engagement (NE) Determination or for IRB Authorization Agreement (IAA). Following the review and sign off by the OGD HSP Liaison, the submission package shall be submitted to the FDA IRB and/or Office of Chief Scientist (OCS) for their review and approval/determination.

If necessary, the FDA IRB and/or OCS will review the research study documents to assure that the rights and welfare of human subjects involved are adequately protected. The FDA will also determine whether the proposed research is exempt under 45 CFR 46.104(b). The FDA COR will provide the Contractor with a copy of FDA IRB’s and/or OCS’ letter of approval/IAA approval/NE determination where applicable. Upon the study initiation, the contractor shall submit the CDER study update form either monthly or bi-weekly.

If the Contractor has already received local IRB approval for the final study documents prior to submission to FDA IRB (when deemed necessary), a copy of the approval letter from the local IRB must be included in the submission package to the FDA COR if applicable. The IRB approval letter must state that the proposed research study documents adequately protect the rights and welfare of human subjects. The Contractor is required to submit the approval letter from the local IRB to the FDA COR upon receipt of the letter if applicable. 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.

If appropriate, the Contractor shall seek FDA COR’s approval 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 study protocol, consent form(s), recruitment materials, any planned deviations and the addition or deletion of key personnel/investigators. The Contractor shall submit modified/amended study documents to the FDA PO for FDA review and approval. The Contractor shall also submit a copy of the local IRB approval of modifications/amendments to the FDA COR upon receipt if applicable.

Questions regarding FDA review shall be directed to ORSHSR@fda.hhs.gov.

1.8 Reporting

Annual Submission Requirements: Contractor shall provide an approval letter from their local IRB, at least annually; stating that the research protocol performed under this contract has been reviewed and approved to continue for another year. This shall be submitted to the FDA COR for inclusion in the contract file.

1.9 Quality Assurance and Monitoring

The Government will perform quality assurance monitoring (remotely and/or via on-site visits) to ensure human subject protections throughout the conduct of the study and document compliance with the regulations and the FDA requirements that govern the conduct of research involving human subjects. The OGD QA team, the FDA COR will provide the Contractor with a report of all identified deviations and/or violations related to human subject protections. If significant deviations are found, the Contractor shall provide responses to the corrective actions listed in the report to the OGD QA team and the FDA COR within 2 weeks of receipt of the report/violation notice. If the Contractor has established a Steering Committee (SC) and/or a Data Safety Monitoring Board (DSMB) for this contract, the Contractor shall submit the responses to the corrective actions of violations to the SC and/or DSMB as established.

The Contractor must provide documentation of acknowledgement of the significant deviations either by the local IRB and/or SC/DSMB to the OGD QA team and the FDA COR. This documentation will be forwarded to OGD Human Subject Protection (HSP) Liaison for review and any required actions will be provided to the Contractor where applicable.

2. Contractor Key Personnel In accordance with HHSAR 352.242-70:

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

Principal Investigator Bioanalytical Scientist Study Coordinator

3. Meetings

3.1. Kick-Off Meeting

The Contractor shall participate in an initial meeting with the COR and PO; within 2 weeks of a receipt of a task order award. The Contractor is responsible for preparing meeting notes and providing a copy of those notes to the COR 5 days after the meeting. This discussion shall include the following:

· The objectives for the Performance Work Statement,

· A high-level overview and discussion of the execution plan,

· Introduction of the Federal CO, COR and PO, as well as the key members of the Contractor’s team,

· A high-level overview and discussion of the transition plans,

· Questions and answers regarding the engagement.

Meeting notes shall detail the discussion held at the initial meeting, capture pertinent clarifications to the scope of work, and reflect any areas of disagreement or misunderstanding on the part of either the FDA or the Contractor.

3.2. Site Visit

During the performance period or upon agreement with the PI, the COR shall perform site visits. The purpose of the site visit is to inspect the facilities and study volunteer safety arrangements at the clinical site. The site visit schedule shall be mutually agreed upon by both parties. If the site visit is cancelled, the cancelling party shall give the other party at least 48 hours’ notice prior to the site visit date. If possible, the site visit shall be rescheduled for an alternate day during that work week.

3.3. Monthly Progress Meeting

One (1) meeting shall be held every four to eight weeks between the Contractor’s Program (Contract) Manager and the COR at the discretion of the COR, and possibly CO via conference call or at the FDA, White Oak Campus – New Hampshire Avenue, Silver Spring, MD. The meetings shall be held to discuss general contract progress; current issues/resolutions; and any other topics as deemed necessary by any party.

The Contractor shall schedule the meetings and provide the meeting agenda to the COR one week prior to the meeting date. The Contractor shall provide the meeting minutes five business days after the meeting has been held.

The following are representative of the meeting types that the Contractor can be expected to perform:

Location(s) Estimated Occurrences

Facility or remote The site visit schedule shall be mutually agreed upon by both parties.

Program (Contract) Manager

4. Reporting Requirements and Deliverable Items

Table below shows rough descriptions of deliverable/dates and will change depending on the study design and agreement. All dates listed are in calendar days.

Annual Report: 30 days following the close of every 12 months from the contract award date Annual Presentation: within 60 days following the close of every 12 months from the contract award date

Final Presentation: prior to the contract expiration date

Reports (i.e., quarterly progress reports, annual reports and final report), containing the description of experiments and data analysis, will be provided to the FDA in both paper and electronic format. In addition, all of the raw data from the studies must be provided to the FDA in both paper and 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 Technical 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. The contractor and the Government will mutually agree on the authorship of any scientific paper(s) resulting from this contract.

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 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.

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

FDA considers the sharing of research resources developed through FDA-sponsored research an important means to enhance the value and further the advancement of research. When research resources have been developed with FDA funds and the associated research findings published, those findings must be made readily available to the scientific community.

Upon acceptance for publication, scientific researchers must submit the author’s final manuscript of the peer-reviewed scientific publication resulting from research supported in whole or in part with FDA funds to the NIH National Library of Medicine's (NLM) PubMed Central (PMC). FDA defines the author's final manuscript as the final version accepted for journal publication, which includes all modifications from the publishing peer review process. The PMC archive is the designated repository for these manuscripts for use by the public, health care providers, educators, scientists, and FDA. Please see the FDA Public Access Policy.

4.1 Study protocol and implementation plan

The Contractor shall provide a study protocol and implementation plan to the COR 2 months from the award date. A protocol format will be determined at the kick-off meeting. At a minimum the plan shall include:

· Specific Aims

· Significance

· Research Design and Methods

· Expertise

· Facilities and Other Resources

· Curriculum vitae of PI and key personnel, and if any, Co-PI(s) and collaborator(s)

· Letters of support from collaborators, if any

· Study timelines and diagrammatic representation of the proposed workflow

4.2 Bioanalytical method validation

In discussion with FDA, the calibration curve range will be determined. The Contractor shall provide a method validation report to the COR within 5 months from the award date. The stability study may be ongoing at the time of validation report submission. If referencing the existing Standard Operating Procedures (SOPs), those SOPs shall be submitted to the COR at the time of protocol submission. The Contractor shall provide the raw and/or final data including quality control results to the COR upon request. In addition to the requirement described in 1.3.4, at a minimum the validation report shall include:

· Specific Aims

· Significance

· Research Design and Methods

· Materials, Instrumentations and Equipment

· Procedures

· Acceptance criteria

· Certificate of analysis

4.3 Submission of IRB package

The Contractor shall submit the IRB package to the PO within 8 months from the award date. In discussion with FDA, the contractor shall submit the required documents for FDA IRB submission – see Section 1.7 FDA Review. The PO will provide instructions for submission. The submission date may differ from the planned date upon agreement of the COR.

4.4 Regulatory submission

If applicable, the Contractor shall prepare and submit the required regulatory application in discussion with FDA. The contractor shall assume the responsibility of the sponsor-investigator if needed. The timing of submission may differ from the planned upon agreement of the COR.

4.5 IRB Approval and study start-up

The Contractor shall submit the approval from IRB to the COR within 10 months from the award date. The PO will provide a determination and/or approval from FDA IRB to the Contractor when applicable. Prior to IRB submission, the Contract shall start preparation for the clinical study. The preparation includes, but not limited to essential documents establishment and maintenance, source documents, case report forms, associated study documents and plans and training of site personnel. The study drug shipment arrangement may be necessary as a part of start-up. The Contractor shall submit all requested document to the COR within 7 months from the Contract award date. The timing of approval and/or start-up may differ from the planned upon agreement of the COR.

4.6 Clinical study

The Contractor shall start recruitment upon the PO’s and/or COR’s agreement and the site initiation activity. The completion of Deliverables #7 and 8 may require a monitor’s report. The Contractor shall conduct the clinical study in accordance with all applicable regulations/guidance/policies. The timing of clinical study activities may differ from the plan upon agreement of the COR.

4.7 Bioanalytical study Report

The Contractor shall submit the bioanalytical study draft report to the COR within 20 months from the award date. The timing of draft report submission may differ from the planned upon agreement of the COR.

4.8 Clinical study report and data

The Contractor shall submit the clinical study draft report and its associated data to the COR within 24 months from the contract award date. The timing of draft report submission may differ from the planned upon agreement of the COR.

4.9 Quarterly Progress Reporting

The Contractor shall provide an original and/or electronic copy of the quarterly progress report to the COR within 15 days following the close of every third month from the contract award date. FDA may provide a progress report template. At a minimum the report shall include the following:

· Study timeline and justifications for any delays

· Accomplishments/Milestones reached for each specific deliverable and/or activity for the reporting period of the contract

· General Progress on activities relating to the specific project plan from the contract submission

· Projected Timeline for uncompleted deliverable and/or activities based on Project Aim

· General Progress on Recruitment Activities

· Information on any additional studies completed during the reporting period

· Information on any pending issues/concerns that are impeding completion of contract deliverables and/or activities.

· Key Personnel Report

· Any Protocol Amendments and Deviation the study protocol

· The most recent IRB letter and/or FDA IRB approval letter for the study

· Any presentation or publication material during this period

· Study Coordinator Contact Information

4.10 Annual Presentation

To be determined by COR in consultation with the contractor, no later than 60 days following the close of every 12th month from the contract award date. At a minimum the annual presentation at FDA shall include:

· Objective of the study

· Significance of the study

· General Progress on activities relating to the specific project

· General Progress on Recruitment Activities

· Protocol Amendments and Deviation

· Preliminary results if available

· Study timeline and future planning

4.11 Annual Report (written document)

The Contractor shall provide an original and/or electronic copy of the annual report to the COR within 15 days following the anniversary of the contract award date. The annual report makes each fourth quarter report of each contract year unnecessary. FDA may provide an annual report template. At a minimum the annual report shall include:

· Study timeline and justifications for any delays

· Accomplishments/Milestones reached for each specific deliverable and/or activity for the reporting period of the contract

· General Progress on activities relating to the specific project plan from the contract submission

· Projected Timeline for uncompleted deliverable and/or activities based on Project Aim

· General Progress on Recruitment Activities

· Information on any additional studies completed during the reporting period

· Information on any pending issues/concerns that are impeding completion of contract deliverables and/or activities.

· Key Personnel Report

· Any Protocol Amendments and Deviation the study protocol.

· The most recent IRB letter and FDA IRB approval letter for the study.

· Any presentation or publication material during this period

· Study Coordinator Contact Information

4.12 Final Report

By the expiration date of the contract, the Contractor shall submit a 508 compliant Final Report that shall detail, document, and summarize the results of the entire contract work. The report shall explain comprehensively the results achieved. Included in the final report shall be an executive summary (in plain language) within the report to summarize the results of the contract and include outcomes with possible impacts on FDA mission. The final report must have a table of contents and page numbers. All raw data shall be submitted at the time of a draft submission. The Contractor shall provide an electronic draft of the final report as well as the raw data to the COR within 45 days prior to the expiration of the contract. The COR shall provide the Contractor comments within 30 days from receipt. The final report is due 60 days after the task order expiration date. The COR shall provide the Contractor comments within 15 days from receipt of the final report. The Contractor shall incorporate any comments in the final report and submit to the COR within 15 days from receipt. FDA may provide a final report template. At a minimum the annual report shall include:

Cover Page

· Contract Number and Project Title

· Project period Being Reported

· Contract Organization Name

· Author(s)

· Date of Submission

Final Report Content

· Background

· Study Aims

· Study Methods

· Study Results

· Interpretation of Study Results

· Conclusion

· Strengths of Study

· Limitations of Study

· Recommendations and Implications for Generic Drug Developments

· References

· List of Publications Posters and oral presentations (title and slides)

· Publications (reference list and articles)

· Appendices as appropriate

4.13 Final Presentation

To be determined by FDA, in consultation with the Contractor, no later than the contract expiration date. The final presentation may be given remotely or on-site at the FDA campus. At a minimum the final presentation at FDA shall include:

· Objective of the study

· Significance of the study

· Protocol Amendments and Deviations

· Final results of the study

· Conclusion

· Strengths of Study

· Limitations of Study

· Recommendations and Implications for Generic Drug Development

5. Period of Performance/Hours of Performance/Place of Performance:

The period of performance for this contract is Thirty-six (36) months from date of Task Order award. NOTE: The Government assumes the first six to seven months will be for start-up activities (i.e. Protocol development, IRB approval, etc.).

6. Travel All travel costs shall be included in the Contractor’s firm-fixed-price.