19-223-SOL-00023_-_Final.pdf

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CODE 18a. PAYMENT WILL BE MADE BY

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OFFEROR

DAP

Beltsville MD 20705 4041 Powder Mill Road ATTN: Richard Robinson

DHHS/FDA/OAGS/DAP

WO66 CODE 16. ADMINISTERED BYCODE

X

X

X

541714

SIZE STANDARD:

100.00 % FOR:SET ASIDE:UNRESTRICTED ORDAP

RFPIFB

10. THIS ACQUISITION ISCODE

RFQ

14. METHOD OF SOLICITATION

13b. RATING

NAICS:

SMALL BUSINESS

05/16/2019 1400 ET

04/15/2019

301-796-6508RICHARD ROBINSON

(No collect calls)

INFORMATION CALL:

FOR SOLICITATION 8. OFFER DUE DATE/LOCAL TIMEb. TELEPHONE NUMBER a. NAME

4. ORDER NUMBER3. AWARD/ 6. SOLICITATION

19-223-SOL-00023

5. SOLICITATION NUMBER

SOLICITATION/CONTRACT/ORDER FOR COMMERCIAL ITEMS 1. REQUISITION NUMBER PAGE OF

1 62 1208631OFFEROR TO COMPLETE BLOCKS 12, 17, 23, 24, & 30

TELEPHONE NO.

17a. CONTRACTOR/

Silver Spring MD 20993 Building 66 10903 New Hampshire Avenue The US Food and Drug Administration

WHITE OAK CAMPUS, BUILDING 66

15. DELIVER TO

Beltsville MD 20705 4041 Powder Mill Road ATTN: RIchard Robinson

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VETERAN-OWNED

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8(A)

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WOMEN-OWNED SMALL BUSINESS

(WOSB) ELIGIBLE UNDER THE WOMEN-OWNED

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EDWOSB

24.

AMOUNT

23.

UNIT PRICE

22.

UNIT

21.

QUANTITY

20.

SCHEDULE OF SUPPLIES/SERVICES

19.

ITEM NO.

The U.S. Food and Drug Administration intends to award a Single Award Indefinite Delivery Indefinite Quantity contract for services to support the requirement entitled, "In Vitro and Non-Clinical Evaluation of Locally-Acting Topical Dermal and Ophthalmic Formulation Properties."

The contract will be awarded to the offeror representing the best value to the Government.

See attached pages for specific terms and conditions regarding this solicitation.

Delivery: 07/27/2024

(Use Reverse and/or Attach Additional Sheets as Necessary)

HEREIN, IS ACCEPTED AS TO ITEMS:

XX

DATED

RICHARD W. ROBINSON

. YOUR OFFER ON SOLICITATION (BLOCK 5),

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ALL ITEMS SET FORTH OR OTHERWISE IDENTIFIED ABOVE AND ON ANY ADDITIONAL

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OFFER

STANDARD FORM 1449 (REV. 2/2012)

Prescribed by GSA - FAR (48 CFR) 53.212

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ARE NOT ATTACHED.

AUTHORIZED FOR LOCAL REPRODUCTION

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ACCEPTED, AND CONFORMS TO THE CONTRACT, EXCEPT AS NOTED:

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41a. I CERTIFY THIS ACCOUNT IS CORRECT AND PROPER FOR PAYMENT

STANDARD FORM 1449 (REV. 2/2012) BACK

24.

AMOUNT

23.

UNIT PRICE

22.

UNIT

21.

QUANTITY

20.

SCHEDULE OF SUPPLIES/SERVICES

19.

ITEM NO.

Period of Performance: 07/28/2019 to 07/27/2024

1 Not-To-Exceed IDIQ Ceiling for Performance of In

Vitro and Non-Clinical Evaluation of

Locally-Acting Topical Dermal and Ophthalmic

Formulation Properties

32f. TELEPHONE NUMBER OF AUTHORIZED GOVERNMENT REPRESENTATIVE

32d. PRINTED NAME AND TITLE OF AUTHORIZED GOVERNMENT REPRESENTATIVE

62 2 of

19-223-SOL-00023 – In Vitro and Non-Clinical Evaluation of Locally-Acting Topical Dermal and Ophthalmic Formulation Properties

PART I

SECTION B - SUPPLIES OR SERVICES AND PRICES/COSTS

B.1 SOLICITATION DESCRIPTION

The Contractor shall furnish all necessary facilities, materials, and personnel, and shall perform all non-personal services and program support necessary in a requirement titled, “In Vitro and Non-Clinical Evaluation of Locally-Acting Topical Dermal and Ophthalmic Formulation Properties.”

This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in Subpart 12.6, 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 solicitation is a Request for Proposals (RFP). The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular 2019-01. The applicable North American Industry Classification System (NAICS) code assigned to this procurement is 541714 – Research and Development in Biotechnology (Except Nanotechnology).

Its associated Small Business Size Standard is 1000 employees.

This requirement is 100% set aside to small businesses. Only businesses that qualify as small businesses under the above referenced NAICS code are permitted to submit a proposal as a result of this solicitation.

B.2 CONTRACT TYPE

In accordance with FAR 52.216-27, the government intends to make a single Indefinite-Delivery, Indefinite-Quantity (IDIQ) Contract award with the issuance of Firm-Fixed price task orders (though the Government reserves the right to issue Labor Hour/T&M task orders if that mechanism is determined to be more reasonable). The structure of the contract shall be a five (5) year base period.

B.3 CONTRACT CEILING

The IDIQ guaranteed minimum amount will be $5,000.00 over five (5) years. The contract maximum ceiling amount will be $3,500,000.00 over five (5) years.

B.4 PRICING

The pricing chart below outlines the labor categories that are anticipated throughout the life of the contract. Minimum requirements for these labor categories are described in greater detail in Section C.7. The Contractor shall provide services in accordance with the Statement of Work with fully loaded, fixed hourly rates.

Labor Category Est.

Annual Hours

Year 1 Rates

Year 2 Rates

Year 3 Rates

Year 4 Rates

Year 5 Rates

Principal Investigator* 32

Program Manager 64

Veterinarian/Veterinary Ophthalmologist* 76

Analytical Scientist* 80

Research Specialist 480

TOTAL 732

*denotes labor category defined as Key Personnel.

Expense QTY Unit Estimated Unit Price

Estimated Total

Non-Labor ODCs 1 LOT $450,000.00 $450,000.00 Travel 1 LOT $10,000.00 $10,000.00

SECTION C - DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

C.1 BACKGROUND

1.1 Background

This contract is to conduct in vitro release testing (IVRT), in vitro permeation testing (IVPT), and/or in vivo animal studies of locally-acting topical dermal and ophthalmic drug formulations.

Formulations composed of different inactive ingredients and made under different manufacturing conditions will be provided. These studies will facilitate patient access to safe, effective, and high-quality complex generic drug products by addressing scientific questions in the development of generic drug approval standards.

The localized and inherent complex nature of dermal and ocular site(s) of administration and action make formulating and assessing bioavailability of these drug products challenging. For example, ocular bioavailability is affected by the complex physicochemical structure of the eye and potential rapid elimination of drug via reflexive blinking, tear production, and nasolacrimal drainage. As a result, locally-acting topical drug substances are commonly formulated in complex dosage forms such as suspensions, emulsions, gels, ointments, creams, or lotions. The type and amount of ingredients used as well as the manufacturing process can affect the properties of these complex dosage forms, which may in turn effect the in vivo performance of the drug product.

Due in part to the challenges of measuring, and thus the limited data on, local tissue drug distribution there is still limited understanding of how the physicochemical properties and/or individual components of these complex formulations effect the overall bioavailability and therapeutic performance of the drug product. Thus, studies to build the fundamental understanding of how formulation properties, known as the critical quality attributes (CQAs), effect local and/or systemic pharmacokinetics (PK) and/or pharmacodynamics (PD) will help establish in vitro-in vivo correlation (IVIVC) or in vitro-in vivo relationship (IVIVR) models. In addition to these models, the development of IVRT and/or IVPT methods that are sensitive and discriminatory of CQA differences and/or correlate to in vivo PK/PD effects that will support the regulatory review and development of bioequivalence testing recommendations for these complex drug products.

C.2 OBJECTIVE

The objective of this contract is to develop and conduct appropriate IVRT, IVPT, in vivo animal model PK and drug distribution studies, and/or in vivo animal model PD studies of locally-acting topical dermal and ophthalmic drug product formulations. The outcome of these studies will support the regulatory science in developing and reviewing generic drug product approval standards that will ensure safe, effective, and high-quality generic drugs are available to the public.

C.3 SCOPE OF WORK

The Contractor shall conduct and furnish all of the necessary personnel, materials, services, facilities, (except as otherwise provided), and otherwise do all things necessary for or incidental to the performance of the functional areas set forth below:

• In vitro release testing (IVRT)

• In vitro permeating testing (IVPT)

• In Vivo Animal Model Pharmacokinetic (PK) and Drug Distribution Studies of Locally-

Acting Dermal and Ophthalmic

• In Vivo Animal Model Pharmacodynamic (PD) Studies of Locally-Acting Dermal and

Ophthalmic

The size, scope, type, timeline, and other details of each functional area may vary and will be specified within each task order.

C.3.1 FUNCTIONAL AREAS

Tasks may require the contractor to perform the following functional areas and require all deliverables to be submitted electronically, as approved by the FDA Contracting Officer Representative (COR).

C.3.1.1 – Functional Area 1: In vitro release testing (IVRT)

An in vitro release rate can reflect the combined effect of several physical and chemical parameters of a formulation. An appropriately developed IVRT method should be able to discriminate the effect of differences in formulation composition and process variability in the manufacture of the product. In general, this is demonstrated by comparing the release rate of drug products manufactured with meaningful variations, such as particle size, drug loading, types and/or amounts of excipients. In general, the FDA will provide and/or direct the Contractor to purchase formulations for testing.

For this contract the Contractor shall develop and validate appropriate IVRT methods to measure common complex dermal and ophthalmic formulations. This can include, but is not limited to, suspensions, emulsions, gels, ointments, creams, and lotion dosage forms. The Contractor shall select and/or develop a suitable IVRT apparatus and experimental conditions relative to the dosage form being tested. Information shall be provided to support the selection of the IVRT apparatus, product dose amount, sampling times, stirring/agitation rate, and other parameters of the test method. This can include, but is not limited to, use of USP Apparatus (i.e 1, 2, or 4), vertical diffusion cell, immersion cell, rotating bottle, and/or a flow through cell. In addition, the Contractor shall demonstrate that the experimental conditions used, including membrane, receiving medium, and sampling schedule are appropriate to meet the expectations of a validated IVRT method. This includes the general considerations and expectations outlined in USP General Chapter <1724> and FDA’s product specific Guidance on Acyclovir cream.

C.3.1.2 – Functional Area 2: In vitro permeation testing (IVPT)

The contractor shall develop and validate IVPT testing methods to measure complex dispersion and/or semi-solid formulations including, but not limited to, suspensions, emulsions, gels, ointments, creams, and lotion dosage forms. An appropriate IVPT apparatus, relative to the dosage form being tested, should be selected and/or developed. Appropriate animal and/or human dermal and/or ocular tissues samples representative of the local biological environment at site of administration and/or action should be chosen for IVPT measurements. This can include, but is not limited to, fresh or frozen skin, cornea, and conjunctiva tissue samples. The preparation, size, thickness, and validity of tissue sections used in the study shall be measured to evaluate the integrity of the tissue sample barrier.

The IVPT apparatus, methodologies and study conditions shall be appropriately validated, qualified, verified and/or justified. In general, suitable apparatus for IVPT studies can include, but are not limited to, vertical diffusion cells and flow through diffusion cells. The composition and pH of the receptor solution shall be qualified in relation to its compatibility with the selected tissue sample (e.g. skin or cornea) as well as the solubility and stability of drug substance. The minimum solubility of drug substance in the receptor solution shall be empirically determined in triplicate to a concentration exceeding the highest sample concentration in the IVPT study. The study duration shall be sufficient to characterize the PK profile of drug being tested, including a sufficiently complete flux profile to identify the maximum (peak) flux and a decline in the flux thereafter across multiple subsequent time points.

The Contractor shall demonstrate that the experimental conditions used, including apparatus, tissues, receiving medium, and sampling schedule are appropriate to meet the expectations of a validated and biologically relevant IVPT method. This includes the general considerations and expectations outlined above as well as those in USP General Chapter <1724> and FDA’s product specific Guidance on Acyclovir cream.

C.3.1.3 – Functional Area 3: In Vivo Animal Model Pharmacokinetic (PK) and Drug Distribution Studies of Locally-Acting Dermal and Ophthalmic

In general, systemic PK measurements are considered the most sensitive, accurate, and robust method to compare drug product formulations. Although, not typically considered feasible and/or relevant for comparing locally-acting dermal and ophthalmic product formulations, systemic PK measurements may provide a deeper understanding during product development how formulation properties may affect the in vivo drug delivery and clearance characteristics. A more representative measure of formulation effects of locally-acting drug products is a measure of drug distribution and/or PK in the local tissue of administration and/or more preferably at the site of action. For ophthalmic products, this can include, but is not limited to, measuring drug concentration and calculating the PK parameters in plasma, tear fluid, cornea, conjunctiva, and aqueous humor.

Although not directly representative of human PK, appropriate animal PK studies can provide better understanding of how a formulation and/or CQA change may alter the relative bioavailability and/or in vivo behavior of a drug product. The Contractor shall select and justify a small and/or large animal appropriate for measuring the systemic and local dermal/ophthalmic tissue PK profiles of common topical dermal and ophthalmic drug products and dosage forms.

The developed bioanalytical analysis for each dosage form and biological matrix studied should be separately validated, or partially validated when appropriate, as per the recommendations outlined in the FDA’s Bioanalytical Method Validation guidance for industry.

C.3.1.4 – Functional Area 4: In Vivo Animal Model Pharmacodynamic (PD) Studies of Locally-Acting Dermal and Ophthalmic

In general, clinical and/or PD endpoints are more often used to compare locally-acting dermal and ophthalmic drug product formulations due to the inherent challenges and limitations of measuring the local PK. Although not as sensitive or reproducible as a PK study due to the results being confounded by the disease state, PD studies are often correlated well to the in vivo performance of the drug product.

The Contractor, in conjunction with the FDA COR, shall select and justify a small and/or large animal disease model appropriate for measuring the PD of common topical dermal and ophthalmic drug products. For ophthalmics this can include, but is not limited to, dry eye, inflammation, and glaucoma animal models and corresponding equipment and expertise to measure tear film break up time, anterior chamber cell count, and intraocular pressure.

C.4 DESCRIPTION OF WORK/STATEMENT OF WORK

Each year FDA may order a total of up to 10 studies from the following table, depending on the need for such studies and available funds. Each type of study may need to be repeated with different drug products as a function of regulatory need. The scope of activities to be performed includes:

Type of Study Description In Vitro Release Testing (IVRT) Membrane In Vitro Permeation Testing (IVPT) Animal and/or human tissue from tissue bank Pharmacokinetic (PK) Small / large animal model Pharmacodynamic (PD) Small / large animal model

FDA may order multiple studies in a single task order.

Specific Tasks will be defined at the individual Task Order level. However, each task order will include some or all of the following general tasks/conditions:

C.4.1 In discussion with the FDA, develop a protocol for the planned study. The protocol shall conform to all applicable regulations and FDA guidance. The protocol shall include at a minimum, and where applicable: Key Personnel, Background Material, Study Aims, Study Design, Sample Size Determination, Instrumentation and Analytical Sampling Procedure(s), Inclusion and Exclusion Criteria, Method of Subject Selection, Randomization Scheme, Sampling Times and Volume, Sample Storage, Animal Husbandry Conditions, Potential Risks to the Subjects, Protection Against Risks, Study Progress, and Adverse Event Reporting Plan.

C.4.2 For all in vivo animal studies, the Contractor shall ensure that the protocol meets and is approved by an Institutional Animal Care and Use Committee (IACUC). Contractor shall submit IACUC approval documentation and the proposed study protocol to the Government Contracting Officer’s Representative (COR) for approval prior to beginning the study, in accordance with HHSAR 370.270-5a and HHSAR 370.270-5b.

C.4.3 Perform IVRT and/or IVPT studies according to Good Laboratory Practice (GLP) regulations and the general considerations outlined in the FDA’s product specific Guidance on Acyclovir cream for method development and validation. This includes, but is not limited to, membrane qualification, receptor solution qualification, method precision, reproducibility, and robustness.

C.4.4 Perform bioanalytical studies according to GLP regulations and the validation criteria outlined in the FDA guidance for industry Bioanalytical Method Validation. Document and justify any deviations from these regulations. Bioanalytical method validation includes all the procedures that demonstrate that a particular method used for quantitative measurement of analytes in a given matrix such as blood, plasma, serum, or media 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.

C.4.5 Begin study within 15 calendar days from the date the Contractor obtains approval for the protocol from the COR.

C.4.6 Conduct a pilot study to verify study design and bioanalytical methodology prior to conducting the full protocol study.

C.4.7 Conduct basic analyses and plotting of study outcomes including, but not limited to, drug concentration, flux rates, and pharmacokinetic parameters to facilitate project progress reporting.

The Contractor is not required to perform statistical analysis of the results.

C.4.8 Provide study progress updates via monthly teleconference and/or in person meetings.

Contractor shall provide a summary of the study results, details of the analytical procedures, plotted data for discussion, and tables of all raw data collected. Contractor shall also prepare and submit meeting minutes to the COR no later than 5 days after the progress update meeting.

C.4.9 Generate a final study report within 30 days of completing the study protocol for FDA review. Obtain COR approval of the final study report within 120 of completing the study protocol. At a minimum the study report should contain: Summary, Study Aims, Background Material, Materials and Methods, Procedures, Sources of Error, Results, Protocol Deviations, Adverse Events and Concomitant Treatments, Experimental Raw Data, Amendments, and Addendums.

C.5 CONTRACT DELIVERABLES AND REPORTING

Deliverables will be defined at the Task Order Level. However, each Task Order will include some or all of the deliverables provided below: The Contractor shall provide the following, as a result of specific tasking in performance of the activities in Section C.4 above:

Activity Delivery Date

Submission of Study Protocol and Implementation Plan approved by COR and IACUC (when applicable)

As per individual task order.

Submission of COR approved Bioanalytical Method Validation Report As per individual task order.

Completion of Pilot Study As per individual task order.

Completion of Full Study As per individual task order.

Submission of Biannual Reports (number depending on study duration) As per individual task order.

Submission of Final Report approved by COR As per individual task order.

Reports (i.e., biannual progress reports and final report), containing the description of experiments and data analysis, shall 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 shall 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 shall be released to the public until it has been reviewed by the COR for accuracy of factual data and interpretation.

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.

C.5.1 Study protocol and implementation plan

• The Study Protocol and Implementation 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 work flow

C.5.2 Bioanalytical Method Validation Report

The Bioanalytical Method Validation Report shall include:

• Experimental Method

• Deviations

• Results

• Chromatograms

• SOPs

• Storage

The FDA’s guidance on “Bioanalytical Method Validation: Guidance for Industry” (May 2018) should be followed for reporting on bioanalytical method parameters.

C.5.3 Pilot Study

The Pilot Study shall include:

• Synopsis

• Study Objectives

• Research Design and Methods

• Results

• Tables and Figures

• Individual Subject Data (if applicable)

• Conclusion

C.5.4 Full Study

The Full Study shall include:

• Synopsis

• Study Objectives

• Research Design and Methods

• Results

• Tables and Figures

• Individual Subject Data (if applicable)

• Conclusion

C.5.5 Bi-Annual Report

Bi-annual reports may be needed depending on the study duration. At a minimum the bi-annual and 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 institutional review board (IRB) letter and RIHSC approval letter for the study.

• Any presentation or publication material during this period

• Study Coordinator Contact Information

C.5.6 Final Report

At a minimum the Final 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

C.6 MEETINGS

C.6.1 Kick-Off Meeting

The Contractor shall participate in an initial meeting with the COR; within 1 week of a receipt of the Base IDIQ Award. The Contractor is responsible for preparing meeting notes and providing a copy of those notes to the COR 3 days after the meeting. This discussion shall include the following:

• The objectives for the Base Award Contract.

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

• Introduction of the Federal Contracting Officer (CO) and Contracting Officer’s

Representative (COR), 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.

C.6.2 Task Order Meetings

Meeting requirements will be defined at the Task Order Level. However, each Task Order will include some or all of the meetings provided below:

C.6.3 Task Order Kick-off Meetings

Individual Kickoff Meetings will be held after the issuance of individual Task Orders as well.

C.6.4 Annual Presentation at FDA

To be determined by COR in consultation with the contractor, no later than 60 days following the close of every 12th month from kick-off meeting. 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

C.6.5 Final Presentation at FDA

To be determined by FDA, in consultation with the Contractor, no later than the contract expiration date. At a minimum the final presentation at FDA shall include:

• Objective of the study

• Significance of the study

• Protocol Amendments and Deviation

• Final results of the study

• Conclusion

• Strengths of Study

• Limitations of Study

• Recommendations and Implications for Generic Drug Developments

C.7 STAFFING/KEY PERSONNEL MINIMUM REQUIREMENTS

The Contractor shall ensure that all Contractor support personnel are adequately trained, possess the requisite experience, and are otherwise fully qualified to provide the high level of support required by this SOW prior to being assigned to this contract. The contractor shall ensure that all staff are onboard and ready to begin work no later than four weeks after the start date of the Contract Period of Performance.

The following Labor Categories are considered Key Personnel:

Principal Investigator Veterinarian/Veterinary Ophthalmologist Analytical Scientist

Specific information regarding the labor category minimum qualifications are set forth below:

The Principal Investigator should:

1. Have either a MS or a PhD in drug delivery, pharmacokinetics, pharmacodynamics, pharmacology, biopharmaceutics, analytical chemistry, pharmaceutical sciences, or other relevant degree in science or medicine.

2. Have 5 years of professional experience in developing study protocols, managing projects, supervising staff, and overseeing the conduct of in vitro and animal studies for topical drug products.

3. Have expertise in either topical dermal or ophthalmic drug delivery.

The Veterinarian / Veterinary Ophthalmologist must:

1. Have a DVM and/or a DACVO.

2. Have a minimum of 3 years veterinarian work experience with a minimum of 1 year research experience on small and/or large animals.

3. Working knowledge of IACUC guidelines, Federal regulations, medical terminology, animal welfare, and veterinary pharmacology research.

4. Have the demonstrated ability to comply with regulatory reporting requirements and methods.

The Analytical Scientist must:

1. Have a MS or a PhD in chemistry, pharmaceutical sciences, engineering, or other relevant degree in science.

2. Have a minimum of 3 years’ experience with gas chromatography (GC), high-pressure liquid chromatography (LC), and/or combined GC and LC mass spectrometric (MS) procedures, such as LC-MS, LC-MS-MS, GC-MS, and GC-MS-MS along with demonstrated ability of analytical method development and validation.

3. Working knowledge of FDA and other relevant guidance on bioanalytical method development and validation.

All labor categories under this contract are considered non-personal services. The Government shall neither supervise contractor employees nor control the method by which the Contractor performs the required tasks. Under no circumstances shall the Government assign tasks to, or prepare work schedules for individual contractor employees. It shall be the responsibility of the contractor to manage its employees and to guard against any actions that are of the nature of personal services, or give the perception of personal services. If the Contractor believes that any actions constitute, or are perceived to constitute personal services, it shall be the contractor's responsibility to notify the Contracting Officer (CO) immediately.

Additional requirements regarding Key Personnel are subject to the terms pursuant to the following clause:

352.237-75 – Key Personnel (DEC 2015)

The key personnel specified in this contract are considered to be essential to work performance.

At least 30 days prior to the contractor voluntarily diverting any of the specified individuals to other programs or contracts the Contractor shall notify the Contracting Officer and shall submit a justification for the diversion or replacement and a request to replace the individual. The request shall 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). If the employee of the contractor is terminated for cause or separates from the contractor voluntarily with less than 30 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.

SECTION D - PACKAGING AND MARKING

All deliverables required under this contract shall be packaged, marked and shipped/submitted in accordance with the Government specifications below. At a minimum, all deliverables shall be marked with the contract number and contractor name.

1. The Contractor shall guarantee that all required materials shall be delivered in immediate usable and acceptable condition.

2. The Contractor shall scan all deliverables for viruses before submitting to the FDA.

3. Deliverables under this contract shall be prepared and packaged for shipment using standard shipping practices to ensure safe and timely delivery.

Electronic delivery is the preferred method of delivery and all deliverables shall assume to be submitted electronically, unless otherwise specified by the COR.

SECTION E - INSPECTION AND ACCEPTANCE

The Contracting Officer’s Representative (COR) will, in accordance with FAR 52.212-4, perform inspection and acceptance of all the services. The Government shall review all reporting requirement deliverables in accordance with specifications and standards identified in the statement of work or any directives issued by the COR. Contract Deliverables and Reporting shall be submitted to the COR or government designee in accordance with the delivery schedule. The acceptance of deliverables and satisfactory work performance shall be based upon the timeliness and accuracy/quality of the deliverables.

Acceptance may be presumed unless, otherwise indicated in writing by the Contracting Officer, COR, or the duly authorized representative within 10 business days of receipt.

The Contractor shall implement necessary changes within 10 business days, or a mutually agreed upon period of time from the day of change notification.

SECTION F - DELIVERIES OR PERFORMANCE

F.1 ANTICIPATED DELIVERABLES

To be Defined at the individual Task Order level (See also Section C.5)

F.2 ORDERING PERIOD

Task Orders may be issued up to the final day of this contract, and the contract shall remain in force to allow for the completion of all task orders issued (See FAR 52.216-22 for more information). However, the Government shall not issue, and the Contractor shall not accept any new task orders issued subsequent to the performance period of this contract.

F.3 PERIOD OF PERFORMANCE

The period of performance for the base period of the contract shall be five (5) years from the effective date of the contract.

F.4 PLACE OF PERFORMANCE

The place of performance will be specified at the Task Order level, though it is anticipated that all performance will be at the Contractor’s site.

SECTION G - CONTRACT ADMINISTRATION DATA

G.1 ORDERING PROCEDURES

Ordering services under this contract shall be accomplished by the issuance of written task orders specifying the requirements to be performed. All task orders issued under this contract shall conform to the provisions of the contract clauses in Part II, Section I entitled “Contract Clauses” (See FAR 52.216-18 and 52.216-19). The only office authorized to process task orders through the Office of Acquisitions & Grants Services is the Food and Drug Administration (FDA) Contracting Officer.

TASK ORDER PROCESSING

All task orders issued hereunder are subject to the terms and conditions of this contract.

This contract shall control in the event of conflict with any task order. A task orders shall be “issued” for purposes of this contract upon the effective date of the order.

The general process for individual task orders is as follows:

a) The FDA will prepare a statement of work. The SOW will include, at a minimum, the following elements:

1. Description of work in terms of the purpose or objectives of the work and location to be performed.

2. Description of how the work performance is assessed relative to objectives, goals, and outcomes.

3. Period and place of performance

4. Reporting requirements and deliverables

5. Whether the order will be fixed price, labor hour, time and material or a hybrid type task order.

b) Requests for Task Order Proposals (RTOPs) shall only be issued by the Contracting Officer.

c) The Contractor shall prepare and submit a task proposal addressing all areas of the requirement. The Contractor shall submit the task proposal within the time period specified in the RTOP and adhere to the ceiling rates established in the contract. No separate payment will be made to the contractor for the cost to prepare, submit and/or negotiate a task order proposal.

The Government shall evaluate task order proposals for technical acceptability and price reasonableness.

G.2 CONTRACTING OFFICERS REPRESENTATIVE (COR)

The following COR will be assigned to this contract: (To Be Determined Upon Contract Award)

The COR is responsible for: (1) monitoring the Contractor's technical progress, including the surveillance and assessment of performance and recommending to the Contracting Officer changes in requirements; (2) interpreting the Statement of Work and any other technical performance requirements; (3) performing technical evaluation as required; (4) performing technical inspections and acceptances required by this contract; and (5) assisting in the resolution of technical problems encountered during performance.

G.3 CONTRACTING OFFICER (CO)

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 a task order; (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.

The contact information for the Contracting Officer is:

Richard Robinson Email: Richard.robinson@fda.hhs.gov Tel: (301) 796-6508

G.4 INVOICE SUBMISSION

A. The contractor shall submit all invoices to:

U.S. FOOD AND DRUG ADMINISTRATION

Attn: Vendor Payments Office of Financial Services 10903 New Hampshire Ave WO32 - Second Floor

MAIL HUB 2145

Silver Spring, MD 20993-0002 301-827-3742 FDAVendorPaymentsTeam@fda.hhs.gov

*** Acceptable methods of delivery include: E-mail (preferred) and Standard Mail.

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 - System for Award Management) 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:

(i) Name and address of the contractor;

(ii) Invoice date and invoice number;

(iii) Contract/Order number (including a reference to any base award for Indefinite- Delivery/Indefinite-Quantity Contracts or Blanket Purchase Agreements);

(iv) Description, quantity, unit of measure, unit price, and extended price supplies delivered or services performed, including:

(a) period of performance for which costs are claimed;

(b) itemized travel costs, including origin and destination;

(c) any other supporting information necessary to clarify questionable expenditures;

(d) the contractor shall include the Contract Line Item/Funding line item for each description, quantity, unit of measure, unit price, and extended price supplies delivered or services performed;

(v) Shipping number and date of shipment, including the bill of lading number and weight of shipment if shipped on government bill of lading;

(vi) Terms of any discount for prompt payment offered (Prompt Payment terms other than

NET 30);

(vii) Name and address of contractor official to whom payment is to be sent (must be the same as that in the contract or in a proper notice of assignment);

(viii) Name, title, and phone number of person to notify in event of defective invoice;

(ix) Taxpayer Identification Number (TIN);

mailto:Richard.robinson@fda.hhs.gov mailto:FDAVendorPaymentsTeam@fda.hhs.gov

(x) Electronic funds transfer (EFT) banking information, including routing transit number of the financial institution receiving payment;

(xi) Name and telephone number of the FDA Approving Official (i.e., Contracting Officer (CO) or Contract Specialist (CS), as referenced in the award document);

(xii) Name and telephone number of the FDA Contracting Officer Representative (COR) or other program center/office point of contact, as referenced in the award document;

(xiii) Contractor is required to attach an invoice log addendum to each invoice which shall include, at a minimum, the following information for contract administration and reconciliation purposes:

(a) list of all invoices submitted to date under the subject award, including the following:

(1) invoice number, amount, & date submitted

(2) corresponding payment amount & date received

(b) total amount of all payments received to date under the subject contract or order

(c) and, for definitized contracts or orders only, total estimated amounts yet to be invoiced for the current, active period of performance;

(xiv) Any other information or documentation required by the contract/order award.

C. An electronic invoice is acceptable if submitted in Adobe Acrobat (PDF) format. All items listed in (i) through (xii) 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.

D. Questions regarding invoice payments should be directed to the FDA Payment Office at the e-mail address or phone number provided above in Section A.

SECTION H. – SPECIAL CONTRACT REQUIREMENTS

H.1 CONTRACTOR PERFORMANCE EVALUATION(S)

In accordance with Federal Acquisition Regulation (FAR) 42.15, FDA will complete annual and final contractor performance evaluations. Annual evaluations will be prepared to coincide with the anniversary date of the contract. Additional interim performance evaluations may be prepared at Contracting Officer discretion, as necessary. Final performance evaluations will be completed upon contract expiration.

FDA will utilize the Contractor Performance Assessment Reporting System (CPARS) in order to execute annual and final contractor performance evaluations. CPARS is a secure Internet website located at http://www.cpars.csd.disa.mil/cparsmain.htm. FDA will register the contractor in CPARS upon receipt of the name and email address of two (2) individuals who will be responsible for serving as the Contractor’s primary and alternate CPARS contacts. Once FDA registers the contractor in CPARS, the Contractor will receive an automated CPARS email message which contains User IDs and instructions for creating a password.

Once a performance evaluation is issued, the Contractor’s primary and alternate CPARS contact will receive an email instructing them to logon to CPARS in order to review the performance http://www.cpars.csd.disa.mil/cparsmain.htm evaluation. The Contractor has 14 days from the date of performance evaluation issuance in which to review the evaluation. If the Contractor is in agreement with the performance evaluation outcome, the evaluation becomes final. Should the Contractor be in disagreement with the performance evaluation outcome, rebuttal comments must be submitted via the CPARS within 14 days from date the evaluation was issued by FDA. Any disagreement between the Contracting Officer and the Contractor will be referred to a contracting official one level above the Contracting Officer, whose decision will be final.

Copies of each performance evaluation and contractor responses, if any, will be retained as part of the official contract file and will be used to support future award decisions. Evaluations will also be stored for a 3-year period in the Past Performance Information Retrieval System (PPIRS) at www.ppirs.gov.

Contractors may obtain CPARS training material and register for on-line training at http://www.cpars.gov/allapps/cpcbtdlf.htm. There is no fee for registration or use of the CPARS.

H.2 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 contracting 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.

(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. The restrictions described herein shall apply 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 activities covered by this clause as a prime contractor, subcontractor, co-sponsor, joint venturer, consultant, or in any similar capacity. For the purpose of this clause, affiliation occurs when a business concern is controlled by or has the power to control another or when a third party has the power to control both.

(c)Warrant and Disclosure. The warrant and disclosure requirements of this paragraph apply with full force 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 http://www.ppirs.gov/ http://www.cpars.gov/allapps/cpcbtdlf.htm 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 at any tier expected to exceed the simplified acquisition threshold. The terms “contract,” “contractor,” and “Contracting Officer” shall be appropriately modified to preserve the Government's rights.

(f)Prime Contractor Responsibilities. The contractor shall obtain from its subcontractors or consultants the disclosure required in FAR Part 9.507-1, and shall determine in writing whether the interests disclosed present an actual, or significant potential for, an organizational conflict of interest.