BTF 2020 SOW for Combined Sample Tasks.pdf

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SAMPLE TASKS FOR BIOLOGICAL TESTING FACILITY REQUEST FOR PROPOSALS

Introduction to Sample Task Order Proposals

The Medicinal Chemistry Facility has identified 10 novel steroidal small molecules as male contraceptive agents. It is hoped that these New Chemical Entities (NCEs) have both androgenic and progestational activities to act as a single male contraceptive drug. These steroidal NCEs are ester analogs of the active free alcohol. The 10 steroidal NCEs have been shipped to the Offeror’s facility to carry out the tasks described in Sample Task 2, Sample Task 3 and Sample Task 4.

Sample Task 2

Following the SOW as described in the Base SOW, propose a general strategy and specific approach in detail, including the experiments, studies, processes, evaluation and steps, that the Offeror would carry out to identify the best male contraceptive candidates from this mix. The resulting outcome of this task is identification of two lead candidates, Compound X and Compound Y.

Sample Task 3 in detail, including the experiments, studies, processes, evaluation and steps, that the Offeror would carry out to identify the better of the two (Compound X or Compound Y) as a male contraceptive drug candidate. The resulting outcome of this task is the identification of a Lead Candidate as the best potential drug to test in a phase I clinical trial for male contraception.

Sample Task 4 in detail, including the experiments, studies, processes, evaluation and steps, that the Offeror would carry out in order for the Lead Candidate to be released for administration in a phase I clinical trial for male contraception.

1. STATEMENT OF WORK – SAMPLE TASK 2 – Efficacy Evaluation

A. BACKGROUND AND OVERALL OBJECTIVE:

Biological Testing Facility is designed to permit rapid evaluation of new compositions of matter, NCEs, potential drug products, drug formulations, delivery systems and devices for contraceptive and endocrine activity. NICHD has supported research to develop compounds that can disrupt normal ovulation, sperm production or sperm function so that safe, effective and inexpensive contraceptives can be developed for men or women. The Biological Testing Facility provides overall project management and the capabilities to support all phases of preclinical development of contraceptives, including process and product development, formulation, clinical lot production, , preclinical enabling studies and associated tasks leading to the filing of investigational new drug (IND) applications. The objective of this task is to explore safety, efficacy, range of activity and other relevant properties of NCEs that can be used for contraception. The agents may be administered orally, intramuscularly, transdermally or other routes of administration acceptable for clinical materials.

B. SCOPE

The task will support services designed to demonstrate safety, efficacy, range of activity and other relevant properties of NCEs that will be suitable for use as a contraceptive product. The agents may be administered orally, intramuscularly, transdermally or other routes of

2 12/20/2019 administration that are acceptable for clinical materials. The products shall be characterized for in vitro and in vivo safety, activity and effectiveness in all cells, receptors and species that would be appropriate for the proposed route of administration and duration of activity pursuant to filing an IND that would support testing of the agents in a phase I clinical trial.

C. TECHNICAL REQUIREMENTS

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment, and facilities, not otherwise provided by the Government, as needed to perform safety, efficacy, range of activity and other relevant properties for compounds of interest to NICHD. The services must be designed to characterize NCEs in appropriate vehicles, at appropriate concentrations and for an appropriate duration of activity that will be suitable for use as a contraceptive product. The agents may be administered orally, intramuscularly, transdermally or other routes of administration acceptable for clinical materials. The products will be characterized for in vitro and in vivo safety, activity and effectiveness in all cells, receptors and species that would be appropriate for the proposed route of administration and duration of activity.

Technical approach

• Perform all appropriate assays to characterize receptor activity, cell specificity, effectiveness and other tests relevant to characterizing and comparing a group of compounds.

• Prepare and assess vehicle and compound formulations at concentrations suitable for in vitro and in vivo evaluation for oral, intramuscular, transdermal or other route of administration as requested by the Project Officer.

• Develop analytical methods and support for assessing cytoplasmic and serum levels in appropriate cells and species.

• Prepare documents that meet regulatory standards to support submission of an IND application for a New Chemical Entity.

D. PERIOD OF PERFORMANCE AND DELIVERABLES

Period of Performance: 24 months

Deliverables: Clinical study reports and all documentation for compounds of interest that can be used to support an IND application to qualify products for use in a clinical trial will be delivered to NICHD or its designated recipient.

Milestones:

• Milestones are dependent on the experimental design.

• Quarterly progress reports are required and weekly teleconferences will be scheduled to provide real-time updates with a summary of status and any problems that may have arisen.

• Complete study reports will be prepared for each study that would need to be included in an IND application pursuant to a clinical trial.

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• A final report will summarize the work in its entirety prior to the last day of the active task.

2. STATEMENT OF WORK – SAMPLE TASK 3 – Safety and Toxicology Assessment new chemical entities, potential drug products, drug formulations, delivery systems and devices for contraceptive and endocrine activity. NICHD has supported research to develop compounds that can disrupt normal ovulation, sperm production or sperm function so that safe, effective and inexpensive contraceptives can be developed for men or women. The Biological Testing Facility provides overall project management and the capabilities to support all phases of preclinical development of contraceptives, including process and product development, formulation, clinical lot production, , preclinical enabling studies and associated tasks leading to the filing of investigational new drug (IND) applications. The objective of this task is to explore safety and toxicological profile of NCEs that can be used for contraception. The agents may be administered orally, intramuscularly, transdermally or other routes of administration acceptable for clinical materials.

The task will support services designed to demonstrate safety of NCEs in appropriate vehicles and appropriate concentrations that will be suitable for use as a contraceptive product. The agents may be administered orally, intramuscularly, transdermally or other routes of administration that are acceptable for clinical materials. The formulated products shall be characterized for in vivo safety and toxicology in all areas and species that would be appropriate to the route of administration and duration of activity pursuant to filing an IND that would support testing in a phase I clinical trial.

C. TECHNICAL REQUIREMENTS

provided by the Government, as needed to perform safety and toxicological profile for compounds of interest to NICHD. The services must be designed to characterize NCEs in appropriate vehicles, at appropriate concentrations and for an appropriate duration of activity that will be suitable for use as a contraceptive product. The agents may be administered orally, intramuscularly, transdermally or other routes of administration acceptable for clinical materials.

The products will be characterized by all assessments of safety that would be required for submission of an IND for a clinical trial.

• Dose formulation development.

• Preparation of vehicle and compound formulations at concentrations suitable for toxicological evaluation for oral, intramuscular, transdermal or other route of administration as requested by the Project Officer.

• Analytical method development and support for assessing serum levels and ADME profiles.

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• Purchase of excipients, materials, supplies, and animals needed to conduct either in house or via subcontract all safety studies needed to submit an IND that will support a clinical trial on the NCEs.

D. PERIOD OF PERFORMANCE AND DELIVERABLES

Period of Performance: 24 months

Deliverables: Clinical study reports and all documentation for compounds of interest that can be used to submit an IND for use in a clinical trial will be delivered to NICHD or its designated recipient.

• Quarterly progress reports are required and weekly teleconferences will be scheduled to provide real-time updates with a summary of status and any problems that may have arisen.

• Complete study reports will be prepared for each study that would need to be included in an IND application pursuant to a clinical trial.

• A final report will summarize the work in its entirety prior to the last day of the active task.

3. STATEMENT OF WORK – SAMPLE TASK 4 – Formulation and Batch Release

NCEs, potential drug products, drug formulations, delivery systems and devices for contraceptive and endocrine activity. NICHD has supported research to develop compounds that can disrupt normal ovulation, sperm production or sperm function so that safe, effective and inexpensive contraceptives can be developed for men or women. The Biological Testing Facility provides overall project management and the capabilities to support all phases of preclinical development of contraceptives, including process and product development, formulation, clinical lot production, , preclinical enabling studies and associated tasks leading to the filing of investigational new drug (IND) applications. The objective of this task is to explore formulations of NCEs that can be used for contraception. The agents may be administered orally, intramuscularly, transdermally or other routes of administration acceptable for clinical materials.

If dosage is given orally, the formulation is likely to be a powder or a solution in oil that can be sufficiently concentrated to be able to fit in a capsule suitable for daily dosing. If the product is determined to be more effective as an injection or a transdermal gel, the concentration will need to be small enough for injection (maximum of 2 ml) or application to the skin (maximum of 5 ml). Smaller volumes are more desirable.

The task will support formulation services designed to develop NCEs in appropriate vehicles and appropriate concentrations that will be suitable for use as a contraceptive product. The agents

5 12/20/2019 may be administered orally, intramuscularly, transdermally or other routes of administration acceptable for clinical materials. The formulated products will be characterized with respect to pharmacokinetics, in vivo activity, safety, stability and other preclinical evaluations pursuant to filing an IND that would support batch release and testing in a phase I clinical trial.

C. Technical Requirements provided by the Government, as needed to perform pre-formulation and formulation development for compounds of interest to NICHD. The formulation services must be designed to develop NCEs in appropriate vehicles and appropriate concentrations that will be suitable for use as a contraceptive product. The agents may be administered orally, intramuscularly, transdermally or other routes of administration acceptable for clinical materials. The formulated products will be characterized with respect to pharmacokinetics, in vivo activity, safety and other preclinical evaluations pursuant to filing an IND that would support testing in a phase I clinical trial.

• Initial solubility and dose formulation development.

• Preparation of vehicle and compound formulations suitable for oral, intramuscular, transdermal or other route of administration as requested by the Project Officer.

• Analytical method development and support for assessing concentration, homogeneity, and stability.

• Characterization of formulated products with respect to pharmacokinetics and pharmacodynamics.

• Preparation and release of a clinical batch under GMP.

D. PERIOD OF PERFORMANCE AND DELIVERABLES

Period of Performance: 24 months

Deliverables: Suitable clinical batch and vehicle formulations for compounds of interest with appropriate documentation for IND submission and use in a clinical trial will be delivered to NICHD or its designated recipient.

• Quarterly progress reports are required and weekly teleconferences will be scheduled to provide real-time updates with a summary of status and any problems that may have arisen.

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• Complete study reports will be prepared for each study that would need to be included in an IND application pursuant to a clinical trial.

• A final report will summarize the work in its entirety prior to the last day of the active task.

EVALUATION FACTORS FOR SAMPLE TASKS

A. GENERAL

Selection of an Offeror for contract award will be based on an evaluation of proposals. A portion of the evaluation for the award of the base contract is based on response proposals for three sample tasks.

The intention is to describe the process of evaluating a new chemical entity to determine if it is a suitable drug candidate, perform appropriate safety and toxicology assessments to qualify the drug for clinical trials, and develop the best formulation as well as prepare and released a batch for a clinical trial. Redundancy of information should be avoided, if possible.

a. Sample Task 2 (Total of 20 Points) – Efficacy Evaluation

b. Sample Task 3 (Total of 20 Points) – Safety and Toxicology Assessment

c. Sample Task 4 (Total of 20 Points) – Formulation and Batch Release

B. TECHNICAL EVALUATION CRITERIA

The evaluation criteria are used by the technical evaluation committee when reviewing technical proposals. The criteria listed below are identical for each sample task and are listed below with weights assigned for evaluation purposes.

Technical Approach on Sample Tasks:

a. Experience of the proposed investigative team to provide preclinical development services and resources appropriate for proposed sample tasks described below. (5 Points)

b. Soundness and feasibility of the technical approach to the proposed sample task

i. Demonstration of Offeror’s understanding of the task and adequacy of the proposed approach with a description of milestones and approaches to tracking progress. (5 points)

ii. Demonstration of the requirements, if needed, for following Good Laboratory Practice guidelines or Good Manufacturing Practice guidelines as defined under the U.S. Code of Federal Regulations with anticipation of problems that may arise with suggestions for solutions to address the problems. (5 points)

iii. Demonstration of the resources and facilities appropriate to the sample task, including appropriate quality assurance/quality controls. (5 points)