A1(b)-Draft Statement of Work.docx

Statement of Work Title: Follow-up Qualification on Oncogenicity of 293F Cells Period of performance of this contract is: Septemer 25th, 2024 to September 24th, 2025

SECTION 1 – BACKGROUND

CDC Influenza’s Division is responsible for the development of Candidate Vaccine Viruses based on circulating and novel influenza strains. Candidate Vaccine Viruses (CVVs) are influenza viruses which are used as the starting materials for seasonal and pandemic vaccines. CDC and FDA require current Good Manufacturing Practices (cGMP) grade banks of cells to make products that can be used in pharmaceutical manufacturing and vaccine manufacturing, including influenza CVVs.

cGMP cell banks are inherently stored as two banks per cell line, one Master Cell Bank (MCB) and one Working Cell Bank (WCB). The MCB is used to make the WCB, and the WCB is used in actual production workflows. According to current FDA guidance, both banks require significant characterization before use. Finally, once the qualified cell banks are produced, they must be maintained under cGMP cryostorage.

The Virology Surveillance and Diagnostic Branch of the Influenza Division identified a new cell line, Expi293F™ cells, that significantly increases the success rate of CVV generation and enables egg- independent production of vaccines and influenza viruses. A contractor previously created a MCB and WCB of Expi293F™ cells under cGMP conditions.

Unfornately, the testing of tumor formation in nude mice (post injection of a suspension of Expi293F™ cells into the mice) showed tumor formation. This was found to be an inherent artifact of Expi293F™ cells and not an error in their production or other part of the cell suspension/test matrix.

This does not inherently disqualify the Expi293F™ cells from being used, however, it does require further and more costly oncogenic testing which otherwise can be skipped if no tumor formation was found in the nude mice.

SUBSECTION A – Definitions

1. Title 21 of the Code of Federal Regulations (21 CFR): 21 CFR is a part of the United States law that governs food and drugs. Specifically, 21 CFR Parts 210 and 211 outline the Current Good Manufacturing Practices (cGMP) and current Good Laboratory Practices (cGLP) that manufacturers must follow to ensure the quality of drug products.

a. Compliance with 21CFR shall be considered to be expanded to include the FDA’s published guidance, most notably for the current work, the FDA’s publications:

i. REF #1: “Guidance for Industry: Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications,” 2010.

ii. REF #2: “Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals,” 1993.

2. Current Good Manufacturing Practice (cGMP): cGMP refers to the regulations enforced by the US FDA to ensure that the design, monitoring, and control of manufacturing processes and facilities are up to standard. Following cGMP guidelines ensures the identity, strength, quality, and purity of drug products by requiring that manufacturers adequately control manufacturing operations. Certain reagents, such as the cells used for CVV production, must be made under cGMP conditions.

3. Master Cell Bank (MCB): This is a collection of uniform cells stored in multiple identical aliquots. The MCB is created to establish a stable, long-term supply of cells for manufacturing biological products, in this case CVV’s made by CDC.

4. Working Cell Bank (WCB): This is a collection of cells derived from the MCB and is used in routine production to increase the number of aliquots available for production.

5. Candidate Vaccine Virus (CVV): An engineered or wildtype virus used for the manufacturing or development of vaccines, created within regulated environments.

6. Expi293F™ cells: These are a specific line of human cells commonly used in research and pharmaceutical production. The Expi293F™ expression system is a derivative of the widely used HEK293 cell line that has been adapted for high-yield, suspension culture in Expi293 Expression Medium. The CDC has previously showed significant increases in both vaccine titer and protein yield using these cells, and a license was previously obtained for their use in CVV production.

7. Tumorigenicity: This refers to the ability of cells or substances to induce tumors, typically in an in vivo context. It's a crucial safety aspect that needs to be assessed, especially for cell lines that are used to produce vaccines or vaccine components.

8. Oncogenicity: Oncogenicity refers to the capacity of a cell, a virus, or a chemical (known as an oncogenic agent) to cause cancer. In terms of cell lines used for biological production, oncogenicity testing can involve evaluating the transformed cells for the ability to induce tumors in suitable animal models.

9. CDC (Center for Disease Control and Prevention): The Government entity in need of work proposed.

10. Offeror: entity that provides a proposal to CDC for listed work.

11. Contractor: entity, if any, awarded a contract to perform proposed work.

SECTION 2 – PURPOSE/OBJECTIVE

Overall objective is to test the Master Cell Bank (MCB) of Expi293F™ cells in further follow-up testing for tumorigenicity and oncogenicity.

The Vaccine Preparedness Team of the Virology, from the Virology Surveillance and Diagnosis Branch within the Influenza Division of the CDC shall be the principal scientific and technical party representing the Government’s needs, working with an indetermined Contractor from selected Offerors.

Representative batch sampling of the MCB lot will be sent to the Contractor for regulated testing.

SECTION 3 – SCOPE OF WORK

The Contractor shall provide the following tests on the Expi293F™ MCB:

(a) Provide 21CFR and cGLP compliant in vivo oncogenicity testing via newborn nude mice per FDA guidance. The expected turnaround time (TAT) shall be 24 weeks.

SECTION 4 – TASKS TO BE PERFORMED

Task 1: 21CFR and cGLP or cGMP compliant Expi293F™ cell growth and sample preparation:

1. Must follow guidelines provided by FDA in REF #1-2.

2. The minimum requirement is that this be handled at cGLP regulatory standards, but it is acceptable for this to be conducted at cGMP regulatory standards as they exceed cGLP standards. Higher regulatory controls are preferred.

3. Test sample shall be the minimum volume required per Offeror’s validated assay, of the Expi293F™ MCB.

Task 2: 21CFR and cGLP or cGMP compliant murine DNA preparation:

1. The minimum requirement is that this be handled at cGLP regulatory standards, but it is acceptable for this to be conducted at cGMP regulatory standards as they exceed cGLP standards. Higher regulatory controls are preferred.

2. This is a required control, and if Offeror’s oncogenicity testing does not include murine DNA per standard, it will need to be shown as validated independently or as an optional addition.

Task 3: 21CFR and cGLP or cGMP compliant Expi293F™ cells DNA preparation:

1. The minimum requirement is that this be handled at cGLP regulatory standards, but it is acceptable for this to be conducted at cGMP regulatory standards as they exceed cGLP standards. Higher regulatory controls are preferred.

2. This is required for the validation of the test article and element.

Task 4: 21CFR and cGLP or cGMP compliant in vivo oncogenicity testing via newborn nude mice:

1. Must follow guidelines provided by FDA in REF #1-2.

2. Test should target fifteen (15) surviving nude mice in both test and control groups.

SECTION 5 – GOVERNMENT FURNISHED PROPERTY

The Government (CDC) will furnish aliquots of the Expi293F™ MCB as needed for testing.

SECTION 6 – PLACE OF PERFORMANCE AND CONTRACT SUPPORT HOURS

SUBSECTION A – PLACE OF PERFORMANCE

Work will be conducted entirely at the Contractor’s facility.

SECTION 7 – TRAVEL

No travel is anticipated for this award.

SECTION 8 – DELIVERABLES/REPORTING SCHEDULE

Deliverables will be presented to a Subject Matter Expert (SME) from the Influenza Division in an electric format (PDF).

preparation

preparation

3: Regulated Expi293F™ DNA Preparation Sample to be retained and used in 4, report on sample preparation

4: Regulated Oncogenicity in Newborn Nude Mice 21CFR cGLP Compliant Test

SECTION 9 – REFERENCE MATERIALS

None.

SECTION 10 – MINIMUM VENDOR QUALIFICATIONS

1. Proven capacity of 21CFR and GLP Compliant in vitro and in vivo testing.

2. Previously validated testing protocols, which should be referenced in any proposal, for required tests.

3. Previous FDA audit of facility showing compliance.

SECTION 11 – ADDITIONAL REQUIREMENTS

Information Security and Privacy The Contractor (and/or any subcontractor) shall not have access to, or host, and/or maintain any Government information system(s) in relation to the proposed work. All data will be provided via secured web portal or service (e.g., Amazon Web Services or FileShare). No sensitive data, patient information, or personally identifiable information will be provided to the Contractor on the basis of the proposed work.

Section 508 Compliance Electronic and Information Technology Accessibility Notice

(a) Section 508 of the Rehabilitation Act of 1973 (29 U.S.C. 794d), as amended by the Workforce Investment Act of 1998 and the Architectural and Transportation Barriers Compliance Board Electronic and Information (EIT) Accessibility Standards (36 CFR part 1194), require that when Federal agencies develop, procure, maintain, or use electronic and information technology, Federal employees with disabilities have access to and use of information and data that is comparable to the access and use by Federal employees who are not individuals with disabilities, unless an undue burden would be imposed on the agency. Section 508 also requires that individuals with disabilities, who are members of the public seeking information or services from a Federal agency, have access to and use of information and data that is comparable to that provided to the public who are not individuals with disabilities, unless an undue burden would be imposed on the agency.

(b) Accordingly, any offeror responding to this solicitation must comply with established HHS EIT accessibility standards. Information about Section 508 is available at http://www.hhs.gov/web/508. The complete text of the Section 508 Final Provisions can be accessed at http://www.access- board.gov/sec508/standards.htm.

(c) The Section 508 accessibility standards applicable to this contract are:

1) Reports are to be provided as PDF’s that are 508 compliant.

In order to facilitate the Government's determination whether proposed EIT supplies meet applicable Section 508 accessibility standards, offerors must submit an HHS Section 508 Product Assessment Template, in accordance with its completion instructions. The purpose of the template is to assist HHS acquisition and program officials in determining whether proposed EIT supplies conform to applicable Section 508 accessibility standards. The template allows offerors or developers to self-evaluate their supplies and documentation detail - whether they conform to a specific Section 508 accessibility standard, and any underway remediation efforts addressing conformance issues. Instructions for preparing the HHS Section 508 Evaluation Template are available under Section 508 policy on the HHS Web site http://hhs.gov/web/508.

(d) Respondents to this solicitation must identify any exception to Section 508 requirements. If an offeror claims its supplies or services meet applicable Section 508 accessibility standards, and it is later determined by the Government, i.e., after award of a contract or order, that supplies or services delivered do not conform to the accessibility standards, remediation of the supplies or services to the level of conformance specified in the contract will be the responsibility of the Contractor at its expense.

(e) Electronic content must be accessible to HHS acceptance criteria. Checklist for various formats is available at http://508.hhs.gov/, or from the Section 508 Coordinator listed at https://www.hhs.gov/web/section-508/additional-resources/section-508-contacts/index.html. Materials that are final items for delivery should be accompanied by the appropriate checklist, except upon approval of the Contracting Officer or Representative.

OTHER CONSIDERATIONS AND ADDITIONAL INFORMATION FOR OFFICE OF ACQUISITION SERVICES

SECTION 1 – PROPOSED CONTRACT TYPE

Firm-fixed-price

SECTION 2 – OPTIONAL SPECIAL CONSIDERATIONS SUBSECTION A – PAYMENT CLAUSES

Standard payments through the Invoice Processing Platform (IPP).

SUBSECTION B – DATA RIGHTS CLAUSES

Data rights shall follow FAR 52.227-17

SECTION 3 – EVALUATION FACTORS

The work proposed here is technically complex, highly regulated, and moderately available.

SUBSECTION A – TECHNICAL

Technical Evaluation Criteria:

1. Methodology and Approach (Maximum: 50 points)

The proposal shall describe the offeror’s approach to successfully accomplish the technical performance and delivery requirements of this contract.

The proposal shall address known complexities of performance and demonstrate the soundness, practicality and feasibility of the offeror’s approach to successfully accomplish the technical performance and delivery requirements of this contract. Several key areas of concern are to be evaluated:

A. Regulatory Compliance:

a. The proposal demonstrates that all protocols to be utilized meet current Good Manufacturing Practices (cGMP).

b. The offeror has a history and experience in working in cGMP conditions for the production and qualification of cell lines used in pharmaceutical processes (e.g. has created cell banks that were used to make products resulting in FDA Masterfile submissions).

B. Validation, Quality Control, and Quality Assurance:

a. The offeror has an existing, in place, material management and control system that allows for in-process checks and post cell banking certifications on quality.

b. All equipment and processes in the proposal undergo regular validations and are on validated maintenance or review plans.

C. Capacity:

a. Must be able to begin of project within sixty (60) days of PO/contract issuance.

b. Proposal shall demonstrate the likelihood of production being interrupted by outside forces (notably the SARS-CoV-2 Pandemic) or orders/contracts placed by the offeror’s other customers. The Government seeks to reduce the likelihood of production being interrupted, and proposals that demonstrate capacity and preparedness for outside disruptions (e.g. staff redundancy) will be evaluated more favorably.

D. Turnaround Time (TAT):

a. Speed is inherently important in all work by the Influenza Division. Proposals shall included estimated turnaround times (TATs) for each milestone (see Scope of Work), with preference given to shorter TATs that are demonstrated to be feasible.

2. Facilities and Equipment (Maximum: 30 points)

The proposal shall demonstrate the current availability of offeror’s facilities and equipment required to successfully accomplish the technical performance and delivery requirements of this contract. To aid in regulatory compliance with both the FDA and CDC, preference is given to offerors that will qualify and maintain the cell banks within the United States, further preventing the need to continually import the products to be created.

3. Staff Qualifications and Management Commitment of Resources (Maximum: 20 points)

The proposal shall demonstrate the availability, qualifications, experience, education, competence and management commitment of professional, technical and other proposed personnel (as evidenced by resumes, endorsements, and explanations of previous efforts), to successfully accomplish the technical performance and delivery requirements of this contract. Expertise in regulatory qualification of cell banks is required.