Attach 16 Addit Tech Proposal Instrucs.pdf

Attachment 16 - Additional Technical Proposal Instructions dated 11/20/2020

ADDITIONAL TECHINCAL PROPOSAL INSTRUCTIONS

It is strongly recommended that Offerors use the following template as the Table of Contents for the Technical Proposal. All information presented in the Technical Proposal should be presented in the order specified below.

These additional Technical Proposal instructions reflect the requirements of the RFP and provide specific instructions and formatting for the Technical Proposal. While Section L.2.b. of the RFP provides a generic set of Technical Proposal instructions applicable to all NIH Research & Development (R&D) solicitations, these additional Technical Proposal instructions are tailored to the specific requirements of the RFP. The information requested in these instructions should be used, along with Section L. to format and prepare the Technical Proposal, and should be used as a Table of Contents for your Technical Proposal.

Offerors are advised to give careful consideration to the Statement of Work (SOW) and attachments, Mandatory Qualification Criteria and Technical Evaluation Criteria in Section M, and the RFP as a whole in the development of their Technical Proposals.

Offerors should submit a proposal that addresses the Mandatory Qualification Criteria and the Task Areas in the Statement of Work. If the proposed approach will involve a subcontracting arrangement, then the Offeror shall include a letter of commitment from the subcontractor(s), plus documentation of subcontractor's expertise, qualifications and prior performance, as well as a narrative describing how the Offeror will manage the subcontractor.

A detailed work plan should be submitted indicating how each aspect of the Statement of Work is to be accomplished. Your technical proposal should be in as much detail as you consider necessary to explain fully your proposed methods and rationale for their selection and should reflect a clear understanding of the nature of the work being undertaken. The technical proposal must also include information on how the project is to be organized, staffed, and managed.

Information should be provided which will demonstrate your understanding of management of timeframes for planning and accomplishing the work to be performed. Information should be provided which will demonstrate your understanding and management of tasks related to bioanalytical methods development and utilization, pharmacokinetic studies and data analysis.

Record and discuss specific factors not included elsewhere which support your proposal. Using specifically, titled subparagraphs, items may include: Unique arrangements, equipment, etc., which none or very few organizations are likely to have which is advantageous for effective implementation of this project.

The total page count of the Technical proposal shall not exceed 150 pages. Proposal pages shall be numbered "Page 1 of 150, "Page 2 of 150" etc. The page Limits for the Technical Proposals excludes any sample task order proposals and the proposal for Task Order # 1 Kick-Off meeting. The total page count for Technical proposals for the Task Order and each Sample Task Orders shall not exceed 10 pages (per task order/sample task order). Pages in excess of this limitation will be removed form the proposal and will not be provided to the reviewers to read or evaluate.

Pages shall be of standard size (8.5x11) with a font size of 10 points or larger. Proposal pages shall be numbered "Page 1 of 150", "Page 2 of 150" and so on.

TECHNICAL PROPOSAL-TABLE OF CONTENTS

General Instructions:

SECTION 1

A. PROPOSAL TITLE PAGE. Include RFP title and number, name of organization, DUNS number, proposal part, and identify if the proposal is an original or a copy.

B. PROJECT OBJECTIVES (NIH FORM 1688-1)

C. GOVERNMENT NOTICE FOR HANDLING PROPOSALS

D. PROPOSAL SUMMARY AND DATA RECORD (NIH-2043)

E. TABLE OF CONTENTS

SECTION 2: MANDATORY QUALIFICATION CRITERIA

Mandatory qualification criteria (MQC) related to animal care and use are regulatory requirements for conducting in vivo pharmacokinetic and other pharmacology studies. Some or all of the studies expected to be assigned under contract(s) resulting from this solicitation will require use of vertebrate animals.

Offerors should include all information which documents and/or supports the mandatory qualification criteria in one clearly marked section of their technical proposal:

The Offeror shall establish and provide resources for an animal care and use program that is managed in compliance with applicable federal, state, and local laws and regulations, such as:

• Animal Welfare Regulations (9 CFR, 1985/1989) https://www.nal.usda.gov/awic/final-rules-animal-welfare-9-cfr-parts-1-2-and-3

• Guide for the Care and Use of Laboratory Animals 8th ed., National Research

Council, 2011 http://www.ncbi.nlm.nih.gov/books/NBK54050/

• Public Health Service Policy on Humane Care and Use of Laboratory Animals, revised 2015.

https://grants.nih.gov/grants/olaw/references/phspol.htm.

To demonstrate compliance with the above policies and guidance, Offerors shall submit: 1) a copy of their organization’s most recent letter from NIH’s Office of Laboratory Animal Welfare (OLAW) documenting approval of a valid Animal Welfare Assurance, 2) a copy of your organization’s most recent USDA Animal Welfare Act registration certificate.

SECTION 3: TECHNICAL DISCUSSIONS

The technical discussions included in the technical proposal should respond to the items set forth below:

A. Personnel https://www.nal.usda.gov/awic/final-rules-animal-welfare-9-cfr-parts-1-2-and-3 https://grants.nih.gov/grants/olaw/references/phspol.htm

OFFERORS SHOULD ASSURE THAT THE PROJECT DIRECTOR/PROJECT

MANAGER AND ALL OTHER PERSONNEL PROPOSED SHALL NOT BE

COMMITTED ON FEDERAL GRANTS AND CONTRACTS FOR MORE THAN A

TOTAL OF 100 PERCENT OF THEIR TIME. IF THE SITUATION ARISES WHERE

IT IS DETERMINED THAT A PROPOSED EMPLOYEE IS COMMITTED FOR

MORE THAN 100 PERCENT OF HIS OR HER TIME, THE GOVERNMENT WILL

REQUIRE ACTION ON THE PART OF THE OFFEROR TO CORRECT THE TIME

COMMITMENT.

(1) Principal Investigator

A Principal Investigator responsible for overseeing the project should be named.

This individual shall demonstrate leadership experience in pharmacologic and pharmacokinetic investigation of therapeutic agents (particularly antitumor agents) and have demonstrated an ability to lead a multi-disciplinary team of scientists, which shall include individuals with analytical methods and pharmacokinetic expertise. He or she shall have attained doctorate level (or equivalent) educational status in pharmacology, pharmaceutical sciences, or a closely related discipline. A resume for the proposed Project Director/Project Manager shall demonstrate his/her education, background, recent experience, and specific scientific accomplishments. A comprehensive bibliographic listing of published or accepted papers as well as any unpublished technical study reports should also be provided (proprietary compound names may be censored). Study reports that have been submitted to the FDA as part of an IND or NDA is considered of equal importance with peer-reviewed publications in demonstrating experience.

(2) Other Professional Personnel

All other professional personnel should be named, indicating their present responsibilities and availabilities to the project. Current resumes of all proposed personnel, which indicate education, scientific background, recent experience, and specific scientific or technical accomplishments, should be provided.

Unrelated information or resumes of individuals not assigned to, or involved with, the proposed project is neither necessary nor desired, and will be considered as detracting from the proposal. A bibliography that lists publications (including any study reports) relevant to this project should be included for each individual proposed.

Particular emphasis should be placed on the senior professional staff who will oversee and manage the specific technical tasks described in the SOW [e.g., bioanalytical mass spectrometry, animal dosing and sample collection, pharmacokinetic data analyses, metabolite identification, drug metabolism, etc.].

Documented participation of an American College of Laboratory Animal Medicine (ACLAM), or equivalent, certified veterinarian on staff is highly desirable.

Alternatively, the ACLAM, or equivalent, veterinarian may also have an established relationship as a contracted on-call consultant.

Experience of proposed personnel with one or more of the following techniques is considered desirable, but will not be an absolute requirement for award: (1) the ability to perform pharmacokinetic studies in large animals such as dogs and non-human primates; (2) expertise with specialized animal procedures (e.g., serial blood collection techniques in mice, bile duct cannulation, surgical techniques to perform site specific absorption or hepatic clearance experiments);

(3) the identification and quantitation of biological therapeutic agents (e.g., immunotoxins, antibodies, oligonucleotides) using techniques such as ELISA, PCR, immunoblots, and mass spectroscopy.

(3) Additional Personnel

List names, titles, level of effort, and proposed duties of all additional personnel, including technical and support staff, proposed on the contract. Current resumes of the proposed personnel, which indicate education, training, and recent experience and accomplishments relevant to their proposed activities, should be provided as appropriate.

Since technical expertise will be an important consideration in the work to be performed, particular emphasis should be placed on the overall technical capabilities of the group, identifying those individuals who will be responsible for specific technical tasks, (e.g., bioanalytical mass spectrometry, animal dosing and sample collection, animal care, pharmacokinetic analyses, metabolite identification, etc.).

(4) Subcontractors and Consultants

List names, titles, level of effort, and proposed duties of any personnel who are proposed on a subcontract or consultant basis. The technical areas, character, and extent of subcontract or consultant activity should be indicated, and the anticipated sources should be specified and described. For all proposed personnel who are not currently members of the offeror's staff, a letter of commitment or other evidence of availability is required. A resume or Curriculum Vitae (CV) for each proposed subcontractor employee or consultant should be provided, but this does not meet the requirement for evidence of availability.

Commitment letters for use of consultants must include:

• The specific items or expertise they will provide.

• Their availability to the project and the amount of time anticipated.

• Willingness to act as a consultant.

• How rights to publications and patents will be handled.

B. Technical Approach and Awareness of the Problem

Offerors shall submit a proposal that addresses the task areas in the Statement of Work. If the proposed approach will involve a subcontracting arrangement, then the offeror shall include a letter(s) of commitment from the subcontractor(s), plus documentation of subcontractor's expertise, qualifications and prior performance, as well as a narrative describing how the Offeror will manage the subcontractor.

Describe in detail how the group will be organized, both scientifically and administratively. The proposal should include a detailed description of at least one recent example from the group's own experience with the implementation of a method for the analysis of a drug in biological fluids such as plasma or urine. Also include a description of a pharmacokinetic study in the mouse, rat, dog or other species recently performed by the proposed group of personnel and the approach used to model the data. Discuss in detail previous work experiences and approaches that will be used in conducting the proposed pharmacological studies, encompassing the items listed in the SOW. This discussion should detail the breadth of experience of the proposed project team with analyses of diverse chemical structures and the conduct of in vivo and in vitro pharmacokinetic studies.

Additional discussions should show your awareness and use of analytical method standard operating procedures (SOPs) suitable for early discovery-stage evaluations studies as well as approaches to be used for later-stage non-clinical and clinical sample analyses; available techniques for collecting single or multiple blood samples from individual rodents; the ability to conduct pharmacokinetic-pharmacodynamic-efficacy studies in tumor-bearing animals, and the procedures to be used for small animal necropsy, including collection, processing, analysis, shipping, and storage of selected tissue samples.

Successful contractors shall be expected to apply state-of-the-art instrumental analysis techniques to the design, implementation, and validation of quantitative assays for test compounds in plasma, urine, tissues, and/or other biological fluids.

The core technique expected to be available is liquid chromatography tandem mass spectrometry (LC-MS/MS). Additional desirable techniques may include (but are not limited to) gas chromatography, capillary electrophoresis, and immunoassays.

The ability to receive, process, analyze, and properly dispose of specimens (plasma, urine, tumor) from human clinical trials is highly desirable. Evidence of Institutional Review Board oversight should be provided.

Discuss in detail the procedures for carrying out the work indicated in each of the sample Task Orders/protocols appended to this RFP. Where applicable, discuss suitable analytical methods implementation, numbers of animals for study, implanting and staging xenograft studies, procedures for collection of blood or tissue samples, criteria for moribund sacrifice, and data collection and analysis. See below for additional information related to the Sample Task Orders/Protocols.

C. Facilities and Equipment

The work to be conducted will NOT require compliance with FDA Good Laboratory Practice (GLP) regulations.

Describe in detail the laboratory space and equipment available for the performance of the work proposed. A floor plan to scale, indicating relevant dimensions should be provided for all laboratory space available to this project, identifying the areas where different facets of the work are conducted. In situations where more than one building or institution is involved, a clear description should be given of the locations of all sites, the distances and travel time between them, and (if proposed) the procedures for transport of animals and/or biological samples from one site to the other.

A complete description of animal facilities to be used on the project should be provided, along with relevant floor plans to scale. Accreditation of the facility by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International) is highly desirable. A copy of the latest review, if applicable, should be included. Offerors should have appropriate facilities and equipment to perform pharmacokinetic studies in rodents (and optionally in larger species) using various routes of administration (e.g., intravenous, oral, subcutaneous, and intraperitoneal injections and/or infusions).

A description of all major equipment available for the work should be provided and its location noted. Particular attention should be given to the analytical instrumentation available for this project. The availability and capacity of mass spectrometric instrumentation in conjunction with liquid chromatography for routine quantitative analysis of samples from pharmacokinetic studies should be stated. If this equipment is NOT under the direct control of the Principal Investigator, procedures for assuring suitable access for this project should be described and documented. Availability of appropriate mass spectrometric instrumentation for elucidation of chemical structures is also required.

Information should be provided on institutional procedures for equipment maintenance, calibration, and validation. When equipment is only available on a shared basis, some evidence should be provided as to who is responsible for controlling access and how the determination of priority of usage will be made (letter of commitment from Department Head, etc).

A description of computer hardware and software available for the project should be provided. Particular emphasis should be given to the pharmacokinetic modeling software to be used. A description of available electronic information and/or library resources should be provided; if not completely in-house, a description should be given of outside facilities within easy traveling distance of the institution that are available for use.

D. Organizational Experience and Support

Organizational experience is defined as the past accomplishment of work which is comparable or related to the effort required by this RFP. This includes overall offeror or corporate experience, not necessarily the experience and/or past performance of individuals who are offered as personnel in your proposal.

The established existence of an organizational environment that fosters pharmacological investigations of therapeutic agents should be demonstrated, especially for the recent past. Examples of institutional accomplishments in these areas should be provided. An organizational chart(s) that shows lines of authority within the organization and the project team should be included. Assurance should be provided that the organization is capable and willing to provide appropriate personnel and resources to accomplish the stated work over the period of performance of any contract awarded.

E. Safety and Security

Each test agent will be considered potentially hazardous. Therefore, all necessary precautions must be taken to protect personnel and the environment against possible exposure to the agents being tested. The Contractor shall perform all work associated with this contract in accordance with all applicable Federal, State and local regulations for Occupational exposure to hazardous chemicals in laboratories.

(e.g. 29 CFR 1910.1450) and follow regulations governing transportation and disposal of hazardous waste.

Describe fully the proposing organization’s policy on safety and security. Describe laboratory safety controls and procedures for handling and disposing of carcinogens and toxic waste materials proposed to be used for this project. Describe procedures for the prevention of contamination during laboratory operations. Indicate your awareness of OSHA regulations, etc., and provide documentation of any recent OSHA inspections and compliance. Please supply one copy of the organization’s current Health and Safety Manual. Describe current security procedures for protection of animal and other facilities.

F. Additional Technical Proposal Information

(1) In assessing proposals relative to the proper care and use of laboratory animals, guidance from the following references will be utilized:

a. Guide for the Care and Use of Laboratory Animals 8th ed., National Research Council, 2011 http://www.ncbi.nlm.nih.gov/books/NBK54050/

b. Public Health Service Policy on Humane Care and Use of

Laboratory Animals, revised 2015.

https://grants.nih.gov/grants/olaw/references/phspol.htm.

G. OTHER CONSIDERATIONS: Please also address understanding of the requirements outlined in the RFP regarding the protection and use of information such as:

Confidentiality of Information; Intellectual Property Option to Collaborator and other related clauses; Information Security & Non-Disclosure Agreements; Data rights & required language on reports/deliverables; and understanding that the Government requires that all data generated under the projected contracts be immediately available for its review and provisions be made to maintain confidentiality of all data. Authority to release data may be granted only by the Contracting Officer together with the COR and must be in writing.

H. SAMPLE TASK ORDERS

The following sample Task Order Requests are typical of the work that may be requested and are appended to this solicitation:

1. Kick- Off Meeting with NCI Staff.

https://grants.nih.gov/grants/olaw/references/phspol.htm

2. Pharmacokinetic-Pharmacodynamic-Efficacy Study of Anticancer Compounds in Tumor-Bearing Mice.

3. Analytical Support for animal Pharmacology Studies with Selected Anticancer Agents

4. Determination of [NSC #] in Plasma and Urine Samples from an NCI-supported Human Phase I Clinical Trial.

5. Pharmacokinetic and Bioavailability Studies of Anticancer Compounds in Mice.

Offerors must respond to ALL Task Orders and Sample Task Orders.

The responses to the Sample Task Orders should be included as a separate section (appropriately marked) in the Technical Proposal. The page limit for each Sample Task Order proposal is 15 pages. The Sample Task Order 15-page limit excludes the cover sheet, resumes, and all appendices or attachments. The responses to the Sample Task Orders do not count towards the technical proposal 150-page limit. The Offeror's responses to the Sample Task Orders should include discussion of technical approach, personnel proposed, facilities and equipment.

In addition to the Technical response, Business responses to each Sample Task Order must also be provided in your proposal, according to the specific instructions included in each sample Task Order. Budgets for the base period and any options should be provided separately. Detailed itemizations need not be repeated for any options which are identically priced. Note that Task Orders 1-4 are for informational and evaluation purposes only – no actual awards will be made. For Task Order 5, it is anticipated that a Task for participation in a kick-off meeting with the NCI will be made at the time of award of all contracts resulting from this solicitation.

See Section J- Attachments for Sample Task Order Statements of Work