Attach_9_Addtl_Tech_Prop_Instructions_CGMP_10.22.18.pdf

Attachment 9 N01CN87006-18

Additional Technical Proposal Instructions

ADDITIONAL TECHNICAL PROPOSAL INSTRUCTIONS

PREVENT Cancer Preclinical Drug Development Program: cGMP Production of Vaccines &

Biologicals for Cancer Prevention

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), 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 how each aspect of the SOW is to be accomplished. The technical proposal should reflect a clear understanding of the nature of the work being undertaken and management of important events or tasks. The technical proposal must include information on how the project is to be organized, staffed, and managed. 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.

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, and is advantageous for effective implementation of this project.

The Offeror must adhere to a 120-page limit. Pages in excess of this limitation will be removed from the proposal and will not be provided to the reviewers to be read or evaluated. The 120-page limit excludes the cover sheet, resumes, and all appendices or attachments. The 120-page limit also excludes the proposals for the Initial Task Order and

Task Order #1- Contract Orientation and Kickoff Meeting.

Pages shall be of standard size (8.5x11) with a font size of 10 to 12 points, single spaced.

Proposal pages shall be numbered “Page 1 of 120”, “Page 2 of 120” and so on.

SECTION 1: COVER PAGES AND TABLE OF CONTENTS

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

B. PROJECT OBJECTIVES;

C. GOVERNMENT NOTICE FOR HANDLING PROPOSALS;

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

E. TABLE OF CONTENTS. Include a Table of Contents with indicated pages of proposal sections that at a minimum uses the underlined Headings and Subheadings that appear below.

Additional subheadings may be entered at the Offeror’s discretion.

SECTION 2: MANDATORY QUALIFICATION CRITERIA

Not Applicable.

SECTION 3: TECHNICAL DISCUSSIONS

The Technical Discussion included in the Technical Proposal should respond to the items set forth below.

General Requirements

a. Personnel, Organizational Capabilities, and Project Management a-i) The Technical Proposal should include all information relevant to document individual training, education, experience, qualifications and expertise necessary for the successful completion of all contract requirements. The Offeror shall provide an organizational chart that describes reporting structure of the organization.

The Offeror shall clearly identify in a list or table showing name, highest degree, organizational affiliation (employer), role on the project and percentage of effort to be committed to the project for all Personnel, including any Subcontractor Personnel.

Include for each named person an NIH Biosketch or a Curricula Vitae (CV), that is limited to five (5) pages and which provides selected references for publications relevant to the scope of the RFP, and include experience with projects of similar scope, size and complexity carried out by the Offeror and any proposed subcontractors over the past five

(5) years.

1. Principal Investigator: Describe the education, training, experience, expertise, qualifications, and percentage of effort of the proposed Principal Investigator to lead and direct the activities to be carried out under the Statement of Work. The qualifications and experience of the Principal Investigator should also be discussed in terms of how they are appropriate to the management of any planned subcontract(s) if applicable. Discuss how the technical and scientific planning and implementation of Task Orders will be managed by the Principal Investigator.

2. Project Manager(s): Describe the education, training, experience, expertise, qualifications, and percentage of effort of the proposed Project Manager(s) to oversee, coordinate, integrate and manage all tasks/activities proposed. The qualifications and experience of the Project Manager(s) should also be discussed in terms of how they are appropriate to the management of any planned subcontract(s) if applicable. Discuss how the planning and implementation of Task Orders will be managed by the Project

Manager(s).

3. Other Key Scientific and Technical Personnel: Describe the education, training, experience, expertise, qualifications, role in the project, and percentage of effort for all proposed scientific and technical personnel of the Offeror and all proposed subcontractors. At minimum, include the following personnel: lead scientific, technical, and regulatory personnel.

a-ii) The Offeror shall also provide information related to Project Management as specified in the SOW, specifically:

• Describe the Project Management approach, including but not limited to staffing, organization, responsibilities, leadership, and lines of authority;

• Describe the systems for tracking project activities and monitoring progress, timelines and budgets;

• Describe the communication approach between the PI and the Government, and between all performance sites and activities, including Subcontractors;

• Address how privity of contract issues will be handled, and explain how information will flow between the National Cancer Institute (NCI), the

Offeror, and any Subcontractors since the Prime Contractor’s presence is required for any discussions; and

• Describe plans for managing transitions as outlined in the Statement of Work.

a-iii) The Offeror shall provide documentation of abilities to interact with industrial collaborators and academic researchers and shall discuss the organization’s experience and ability to collaborate with other individuals and organizations. In addition, the

Offeror shall describe the organization’s experience in appropriate use of Subcontractors to supplement areas of expertise and shall discuss how the infrastructures composed of one or more collaborating institutions will be managed as applicable. The Offeror shall describe organizational experience in data collection and processing capabilities (IT systems), including quality management.

b. Quality Management

The Technical Proposal shall document a Quality Management Plan (QMP) that includes management responsibilities, resources, training programs, oversight of all subcontracted manufacturing operations (if applicable), and communication processes, including timelines. The QMP outlines the procedures the Contractor shall follow to ensure that products generated under this contract, as specified in the SOW, adhere to the Current

Good Manufacturing Practice (cGMP) quality standards.

The Offeror shall describe their Quality Control (QC)/Quality Assurance (QA) program required for compliance with all cGMP regulations and guidelines, and for implementation and completion of the Task Areas and other activities described in the

SOW. The description of the Quality Management System(s) shall include, but is not limited to, a description of the personnel, resources and lines of authority for a Quality

Assurance Unit (QAU); the model, governing policies and standard operating procedures of the QAU; a description of the Quality System including QA and QC responsibilities;

and a description of the process to ensure the commitment of senior management support for the Quality Management System(s). In addition, the Offeror shall also describe the management of Quality System activities at the proposed Subcontractor’s site, if proposed, that is appropriate for the phase of product development and within all applicable Regulatory regulations. Furthermore, the Offeror shall also describe any relevant organizational experience, problems or obstacles encountered with

Subcontractor performance and approaches implemented to identify, resolve, remediate or correct identified problems.

c. Facilities, Equipment and Other Resources

The Technical Proposal shall document and provide evidence that the Offeror has access to a fully cGMP-compliant facility by submitting a copy of a current Food and Drug

Administration (FDA) Establishment Inspection Report (EIR) obtained in the last 2 years with No Action Indicated (NAI) or Voluntary Action Indicated (VAI) classification, and/or detailed descriptions of facilities, equipment, space and other resources that are available for the Offeror to carry out each of the proposed Task Areas and other activities in a cGMP-compliant manner as outlined in the SOW. The Technical Proposal shall also document the capacity of the proposed cGMP-compliant facilities, equipment, and resources to perform the proposed tasks as described in the SOW in a timely and efficient manner.

In addition, the Offeror shall provide information on the following:

• Location, space, and features of facilities and a list of equipment and resources dedicated to the project for the Prime Contractor and any proposed

Subcontractors.

• Lease or ownership information for proposed facilities.

The Offeror shall also provide a copy of their Safety and Health Plan. Offerors shall describe procedures and controls to be employed to ensure that the work is conducted in a safe and healthful manner. All pertinent chemical and/or biological hazards shall be addressed, from receipt of agents to ultimate disposal. Details of appropriate administrative and emergency controls, personnel training, protective equipment and work practices shall be addressed. All work shall comply with applicable local, State and

Federal statutes relating to occupational safety and health, transportation and handling, and environmental protection. Discuss equipment and operating procedures established to protect personnel from hazards associated with this project and other factors deemed important to support the proposed approach. Discussion shall include, as appropriate, but not be limited to:

• Identification and description of all support resources, including information technology systems, which will be required to effectively complete the proposed Task Areas in the SOW;

• Information on facility and equipment validation;

• History and details of facility audits and/or inspections, and any relevant

Master File information;

• Experience, plans and procedures to be utilized for compliance with all safety regulations and guidelines in general, including but not limited to handling of potential biohazards, toxic chemicals, and radioisotopes as applicable, as well as training and monitoring of personnel for exposure to potentially infectious and other hazardous materials;

• Proposed plans and procedures for the receipt, storage, retrieval, packaging, labeling and shipping of products, materials and reagents from domestic and/or international locations; and

• Available data back-up systems.

B. Technical Approach

Offerors shall address each of the proposed Task Areas in the Statement of Work. Offerors should clearly specify their planned source for their planned technical capabilities (e.g. in-house, subcontract, etc.). If technical capabilities are to be obtained from a Subcontractor, identify the Subcontractor.

1. Task Area A, cGMP Manufacture, Related Activities and Documentation (Parent

Contract SOW section 4.3:

a. Describe the approach to synthesis or procurement of peptides for use in the vaccine.

b. Describe any acquisition processes, procedures and anticipated timelines for obtaining any of the technical capabilities required to fulfill the SOW requirements.

c. Describe proposed plans, timelines, process, and procedures for fill-finish and labeling activities.

d. Describe plans to characterize, release and store cGMP-grade Final Drug Product for use in clinical studies.

e. Describe plans for the implementation and oversight of suitable product stability programs as required for the successful performance of contract activities.

f. Describe plans, processes and procedures for completing, directing and ensuring the successful delivery to the Government of all products as specified in the individual Task Orders (e.g. bulk product substance, intermediate and final products), all data obtained from in-process and release tests, stability programs and accurate and updated information regarding design, development and production of the biopharmaceutical product, including pertinent Contractor activities, computerized data files, original data and any related information such as Chemistry, Manufacturing and Controls (CMC).

2. Task Area B, Analytical Assay Development and Product Characterization (Parent

Contract SOW section 4.1): Describe the demonstrated performance, usage, or implementation of described technical capabilities, processes and procedures to implement and perform the scope of activities described in Task Area B as follows:

a. Describe technical capabilities, processes and procedures for designing, developing, qualifying and validating assays as needed for the characterization of the vaccine.

b. Describe technical capabilities, processes and procedures for designing and developing stability-indicating assays as needed for a biopharmaceutical product as required for the successful performance of contract activities.

c. Describe proposed plans, processes and procedures for completing, directing and ensuring the successful technology transfer of all materials, assays, methods and procedures as required for the successful performance of contract activities.

3. Task Area C, Process Development and Related Activities (Parent Contract SOW section 4.2): Describe the demonstrated performance, usage, or implementation of described technical capabilities, processes and procedures to implement and perform the scope of activities described in Task Area C as follows:

a. Describe any acquisition processes, procedures and anticipated timelines for obtaining any of the technical capabilities required to fulfill the SOW requirements for the following biopharmaceutical products including, but not limited to, recombinant proteins, peptides, nucleic acid based materials (such as

RNAs and plasmids), vaccine adjuvant and delivery systems, and other biotechnology or cell-derived products.

b. Describe technical capabilities, processes and procedures for the development and performance of scalable production processes and suitable for use in subsequent

CGMP operations for the listed biopharmaceutical product classes, including establishment of master and working cell/viral banks.

c. Describe technical capabilities to produce biopharmaceutical products and diagnostic reagents suitable for IND-enabling safety and activity testing, and performance of the necessary characterization tests required for product release.

d. Describe technical capabilities, processes and procedures for the development and performance of formulation studies.

e. Describe technical capabilities, processes and procedures for the performance and/or support of stability indicating assays.

C. Relevant Experience

The Offeror shall discuss prior experience with similar tasks proposed, and provide documentation of completed studies. For example:

• A list of cGMP manufacturing and related activities from the past five (5) years, including information on the type of agent, production platform, and other pertinent information, but devoid of any proprietary information;

• Relevant organizational experience with cGMP compliance and interactions with

Regulatory Agencies;

• Experience with and plans for completion of in-process and release tests for clinical grade materials suitable for clinical studies;

• Experience with the implementation, oversight and execution of appropriate stability testing programs;

• Successful planning and implementation of procedures utilized to ensure compliance with all cGMP regulations and guidelines, including personnel training and monitoring program.

D. Initial Task Order

Provide a response to the Initial Task Order Statement of Work in accordance with these

Additional Technical Proposal Instructions, addressing ALL Technical Tasks.

The response to the Initial Task Order shall be included as a separate section

(appropriately marked) in the Technical Proposal. The page limit for the Initial Task

Order proposal is 12 pages. The Initial Task Order 12-page limit excludes the cover sheet, resumes, and all appendices or attachments. The Initial Task Order response does not count towards the technical proposal 120-page limit. The Offeror’s response to the

Initial Task Order shall include discussion of technical approach, including quality management; personnel, organizational capabilities and project management; facilities, equipment, and other resources; and relevant experience. The response to the Initial Task

Order shall include a proposed work breakdown structure (WBS) and Gantt charts.

See Section J- Attachments for the Initial Task Order Statement of Work.