Independent Verification and Validation of Engineered Cell Lines

1. BACKGROUND

The Advanced Research Projects Agency for Health (ARPA-H) Resilient Systems Office seeks to support the procurement of independent verification and validation (IV&V) of the engineered cell lines utilized in the Resilient Extended Automatic Cell Therapies (REACT) program.

The REACT program is developing wireless implantable medical devices for the surveillance and treatment of chronic diseases. These devices will interface with patients through a software platform, allowing for confirmation of therapy delivery or current disease status. The “Living Pharmacy” device will deliver tunable therapeutic molecules on demand, while the “Living Sentinel” device will track disease biomarker status. Both devices have similar components including engineered cells (to deliver therapies or track biomarkers) and electronic control with patient interface through a simple software platform.  

Cellular engineering for human-implantable devices requires standardization and reproducibility. To this end, a key component of the REACT effort is developing a manufacturing process for the routine engineering of cells to form standardized cell lines that can either deliver therapies or detect biomarkers. Independent verification and validation (IV&V) is essential for developing Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs) during preclinical assessment and scale up for manufacturing. This includes benchmarking therapeutic production, limits of detection, differentiation processes, and establishing purity.

1. PURPOSE OF THE REQUEST FOR INFORMATION

1. 1. Seeking Capabilities Statements: The Government is considering a FAR based acquisition to meet the needs described in Section 3 below. The Government seeks feedback from industry on this approach, including information regarding alternate solutions that may be capable of meeting the Government’s full range of requirements.

1. 1.  Engagement and Insights Gathering: We encourage industry partners to provide constructive feedback on the information provided via the RFI under section 3. The Government also seeks information regarding the Rough Order of Magnitude (ROM) of effort required to fulfill its requirements.

1. INFORMATION SOUGHT

ARPA-H seeks innovative insights and capabilities that can address the challenges associated with producing engineered cells at commercial scales with an emphasis on CQA and CPP development necessary for FDA approval to improve patient health. Specific capability areas are below. Responses are welcome from all capable sources.

3.1 Facilitate performer navigation of the FDA processes.

• What in-house expertise and experience does your team have with FDA regulatory processes, particularly as they relate to implantable devices, cell-based product biomanufacturing, and cell-based therapies?
• Outline experience, and understanding of, standardization methods for characterization of living therapeutic products and how these can assist in meeting regulatory requirements and expectations.

3.2 Determine critical quality attributes (CQAs) and critical process parameters (CPPs) for mammalian cells

• Describe previous experience in establishing manufacturing CQAs and in-process controls for biological products? What analytical methods did you implement?
• What expertise or past experience do you have ensuring CQAs and cell-based therapeutics are in line with FDA requirements and regulations?
• What facilities, protocols, staff, and equipment are available which could be combined for purposes of establishing critical quality attributes (CQAs) and in-process controls to support the regulatory process?
• What facilities, protocols, staff, equipment, and methodology pipelines are available which could be combined for purposes of evaluating CQAs for determining CPPs?

3.3 Independent Verification & Validation (IV&V) for mammalian cells

• What facilities, protocols, staff, and equipment are available that have been used in the past for scalable expansion of autologous and allogeneic cells in closed, automated cell culture platforms?
• Describe IV&V infrastructure that currently exists to test and evaluate manufacture of cell-line based therapeutics at scale. What kind of available capacity do you have to support new work?
• Describe current infrastructure for IV&V that exists to test and evaluate scalable expansion and differentiation of cell-based therapeutics from induced pluripotent stem cells (iPSCs) at scale. Describe platforms for automated differentiation of cells at scale. What kind of available capacity do you have to support new work?
• Describe current infrastructure for IV&V that exists to test and evaluate cellular transduction of biomarker sensing for the “Living Sentinel”. What kind of available capacity do you have to support new work?

3.4 Conflicts of Interest – IV&V activities require the exchange of proprietary information. IV&V teams must therefore be free of conflicts of interest or the appearance of conflicts.

• • What relationships do you have that could present potential conflicts of interest?
  • Describe an organizational structure that could allow you to avoid real or perceived conflicts.

• • Due to the potential for conflicts, we are looking for existing teams composed of all functions, not newly formed teams. What experience does your team have in supporting similar efforts.

NOTE: The vendor will not retain any IP or be reimbursed for any eventual product that results from the IV&V work. All current and future IP will be retained by the original institution that provided the cells or the U.S. Government.  

1. SUBMISSION REQUIREMENTS (IN THIS ORDER)

1. Complete Business Name, including UEI Number, Tax ID, CAGE Code, and GSA contract number (if applicable).
2. Contact Information (Respondent’s name and title, address, telephone, e-mail).
3. Business Size and Classification (small, small-disadvantaged, SBA Certified 8(a), HUBZone, service-disabled veteran-owned, women-owned, other than small, etc.).
4. Capability statement that proves technical competencies and management/personnel experience relative to the parameters identified above.
5. Responses to the requested information proposed in Section 3.
6. Confirmation of your entities intent to propose if there is a subsequent solicitation.
7. Description of the anticipated structure of the proposer’s team – do you anticipate being the prime vendor or a subcontractor? Do you anticipate being able to meet the requirements on your own or as part of a team? What would that potential team look like in terms of participants and their associated functions?
8. All responses shall be no more than 10 pages total.

Vendors are requested to submit their response to the RFI no later than 4:00 pm EST 16 May 2025. Send responses to Acquisitions@arpa-h.gov.

Please note that the RFI is for informational purposes only and does not constitute a contract, commitment, or invitation to bid. Costs incurred for the preparation of a response by the submitter to this notice will not be reimbursed by the Government. The information provided by vendors will be used solely for ARPA-H’s internal evaluation and planning purposes.

Thank you for your interest in partnering with ARPA-H. We look forward to your valuable insights and recommendations.