The whitepaper, a collaboration between the Alliance for Regenerative Medicine (ARM) and the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), summarizes a Scientific Exchange held on November 1, 2023. This event brought together CGT developers, FDA staff, and industry stakeholders to discuss development and regulatory challenges in the CGT field and identify reusable "building blocks" that could streamline processes and improve efficiency.
The meeting aimed to explore how building blocks could enhance CGT development, particularly for rare and ultra-rare diseases. Participants discussed the FDA’s Platform Technology designation as a potential mechanism to facilitate the reuse of specific technologies across multiple products, thereby accelerating development timelines and regulatory approvals.
Participants submitted and reviewed proposals across three main areas: Lipid Nanoparticles (LNP), induced Pluripotent Stem Cells (iPSCs), and Adeno-Associated Virus (AAV) platforms. Each area was evaluated for its potential impact, feasibility, and the regulatory considerations necessary for implementation.
Cellistic founder and CTO Stefan Braam, along with other leading experts in the iPSC field, contributed proposals and evaluations of incoming suggestions. These iPSC proposals included creating unedited and gene-edited master cell banks, developing AI/machine-learning assays for cell characterization, and using ddPCR assays to ensure the absence of residual pluripotent cells, thereby enhancing safety and potentially reducing the need for extensive in vivo studies.
The potential for building blocks to transform CGT development was highlighted, with nonclinical testing (e.g., toxicology and biodistribution) being identified as a promising area for standardization. Participants emphasized the importance of balancing proprietary technology with the benefits of shared, validated building blocks.
Regulatory acceptance requires the ability to demonstrate control and validation of building blocks. The use of cross-referenced Drug Master Files (DMFs) or Investigational New Drug (IND) applications was discussed as a strategy to incorporate building blocks early in development, requiring comprehensive details for Biologics License Applications (BLAs).
The Scientific Exchange marked a pivotal step in recognizing and advancing the concept of building blocks within the CGT industry. While promising, the implementation of these reusable elements will require further development, collaboration, and clarity to realize their full potential in accelerating the availability of CGT therapies.
The whitepaper underscores the importance of innovative, standardized approaches to streamline CGT development, aiming to make therapies more accessible and efficient to produce, ultimately benefiting patients with rare and ultra-rare diseases.