Accelerating NAMs For A Human-Based Future In CGT Development

By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

When it comes to advancing new approach methodologies (NAMs) to transform preclinical research and drug development, the Complement Animals in Research Experiment (Complement-ARIE) Consortium is playing a leading role. The multi-pillar initiative, launched under the National Institutes of Health (NIH), is driving the development, validation, and regulatory adoption of NAMs with the goal of delivering more human-relevant models that can improve safety and efficacy assessments while reducing reliance on animal testing.

At the heart of this work is the Validation and Qualification Network (VQN), a public-private partnership managed by Foundation for the National Institutes of Health (FNIH) that focuses on moving mature NAMs through validation and qualification to ensure regulatory readiness. I sat down with Stacey Adam, Ph.D., Vice President of Science Partnerships at FNIH, to understand how the VQN and its fellow Complement-ARIE pillars are building the framework to integrate NAMs into critical pipelines such as CGT.

The Three Pillars of Complement-ARIE

Dr. Adam explained The Complement-ARIE Consortium is built around three distinct but interconnected pillars:

• Technology Development Centers (TDCs): Designated centers of excellence that drive NAM development in areas of greatest need. These centers focus on advancing biologically complex, high-throughput, and combinatorial approaches while ensuring robust data sharing.
• NAMs Data Hub and Coordinating Center (NDHCC): A central repository for NAMs data, designed to standardize data structures, improve FAIRness (Findability, Accessibility, Interoperability, and Reusability), and create a searchable, credible data ecosystem.
• Validation and Qualification Network (VQN): The arm responsible for moving NAMs through precompetitive validation, ensuring reproducibility and building the regulatory confidence necessary for broad adoption.

Each pillar plays a unique role in driving NAMs toward acceptance in regulatory submissions and across biopharma R&D. For CGT developers, this integrated approach could significantly change how early safety and efficacy testing is conducted.

NAMs Integration into CGT Pipelines

NAMs span a wide array of methodologies from advanced in vitro models, such as organ-on-a-chip to in silico modeling powered by AI and machine learning. For CGT development, the opportunities to deploy these approaches in the preclinical pipeline are substantial.

“We’re seeing promising 3D, high throughput multicell models that can accommodate the introduction of CGT products into specific cell types or biological niches,” Dr. Adam explained. “On the computational side, in silico approaches using large preclinical and clinical datasets can drive complex modeling and predict toxicity and efficacy outcomes with significant precision.”

The advantages for CGT developers mirror those for other therapeutic modalities. Preclinical studies using NAMs can often be completed in days or weeks rather than the weeks or months required by animal studies. The time savings could allow products to reach regulatory review faster, offering sponsors potentially more time under patent if clinical trials prove successful. Cost efficiencies also come into play; when deployed at scale, NAMs can be less expensive than traditional animal models, reducing overall R&D spend.

Working with Regulators on Data Acceptance

One of the most critical components of the VQN’s mission is to work closely with the FDA and other regulatory agencies to ensure that NAM-derived data is regulatory ready.

“The VQN includes representation from multiple FDA divisions, including CBER, which is critical for CGT-focused NAMs,” Dr. Adam said. “Regulatory partners are directly engaged in the design and execution of each precompetitive project, ensuring the resulting data will meet the standards required for product submissions and clinical trial advancement.”

By embedding regulatory experts early in the process, the VQN is paving a more predictable path for developers who want to rely on NAM-generated data for safety and efficacy packages.

Selecting the Right NAM Platforms

The VQN has not yet finalized its prioritized NAMs but has established a clear project concept selection framework. Submissions will be evaluated by the VQN Steering Committee based on readiness for further development and their potential to address key gaps in preclinical testing.

“We’ll be issuing a Request for Information (RFI) on August 1, 2025, to solicit project ideas from the broader NAMs community,” she said. “This is an opportunity for CGT stakeholders to submit proposals for NAMs that could address the unique complexities of their products.” NAM platforms capable of mimicking the intricate biological environments involved in CGT, such as immune cell interactions or gene delivery vectors, are likely to be top contenders.

Data Standards for a Diverse Field

The VQN has also formed a Data Standards and Integration Workstream, which will collaborate closely with the NDHCC and external groups such as the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Common Data Elements Workgroup.

“This workstream is focused on harmonizing common data elements across NAMs, including subspecialties like CGT,” Dr. Adam said. “We’re considering everything from alignment with existing industry systems like LIMS and ELNs to ensuring interoperability with commercial data pipelines.” For CGT developers, harmonized data standards could make collaboration and cross-comparison much easier, reducing redundancies, and accelerating development.

How CGT Stakeholders Can Get Involved

More than 40 organizations have already joined the VQN, but the network is still accepting new partners. According to Dr. Adam, CGT-focused biotechs, CDMOs, and other ecosystem players have multiple avenues to engage:

• Steering Committee Membership: Organizations that want a direct role in shaping the VQN’s long-term strategy can apply for a Steering Committee seat, which requires a financial contribution scaled to the size of the organization.
• Project Submissions: Any CGT stakeholder can submit project concepts through the upcoming RFI.
• Public Workshops: The VQN’s Community Engagement and Training Workstream will host workshops open to the broader NAMs community.
• Precompetitive Project Participation: Stakeholders may be invited to join specific projects if they align with their interests and capabilities.

“We already have Steering Committee members with a focus on CGT, and they would welcome additional colleagues from this space,” Dr. Adam emphasized. Interested parties can contact her directly at sadam@fnih.org.

The Opportunity for CGT

For cell and gene therapy developers, NAMs offer a powerful opportunity to tackle longstanding challenges in preclinical testing. Complex in vitro models could replicate immune system dynamics or tissue-specific delivery challenges in ways that animal models simply cannot. In silico approaches could leverage vast datasets to predict safety and efficacy issues before a single patient is treated. But these benefits will only be realized if the field works together. “The VQN is intentionally operating in the precompetitive space,” Dr. Adam said. “By building consensus frameworks and generating the robust, reproducible data regulators need, we can accelerate the adoption of NAMs and ultimately bring safer, more effective therapies to patients faster.”

With its multipillar structure and deep engagement with regulatory agencies, Complement-ARIE is positioned to be a catalyst for this transformation. For CGT developers navigating a rapidly evolving landscape, now is the time to get involved.