The AMP BGTC recognized the need for a comprehensive playbook that would serve as a guiding framework for the development and regulatory submission of AAV gene therapies for rare diseases. Building out this playbook to support the key processes up to a Sponsor’s first-in-human (FIH) trial required a collaborative and modular approach. Version 1.0 of the playbook is designed to serve as a one-stop-shop guide and roadmap to IND submission for these innovative gene therapies.
To ensure the playbook’s credibility and integrity, the BGTC embarked on an ambitious journey to consolidate external information with its own internal expertise. The goal was to generate an operational playbook that would serve AAV drug developers of all backgrounds, but primarily those who could benefit from simplified language, guidelines, and templates for this complex process (e.g., family groups, non-profits, patient foundations, academic research labs, small biotechs, but not necessarily large pharmaceutical companies).
The process for developing this playbook started with collating source documents, such as FDA regulatory guidances, publications, and other publicly available resources. These foundational guidelines were supplemented with the BGTC’s extensive expertise and experience in gene therapy regulatory processes. The initial playbook structure was framed around key milestones common to a sponsor’s typical regulatory journey, from research and development (R&D), to pre-clinical, through clinical development. The BGTC plans to enhance the playbook in future versions by incorporating learnings from standardized outputs, leveraging BGTC subject matter experts (SMEs), defining efficiencies, platform strategies, and accrued knowledge from FDA interactions. These invaluable insights formed the bedrock of the playbook, ensuring that it would encapsulate the latest advancements and emerging best practices.
As the playbook took shape, it became evident that this collaborative endeavor had the potential to revolutionize the field of gene therapy, particularly through its continued evolution, capturing learnings from the BGTC projects and advances across healthcare and drug development. Not only would it provide researchers and developers a unified resource to navigate the intricate regulatory landscape of AAV gene therapies, but it would also facilitate harmonization and streamlining among various stakeholders, including researchers, regulatory bodies, clinicians, and ultimately, benefiting patients with these rare diseases.
The BGTC Regulatory Playbook is a collective effort of the BGTC SMEs, setting the stage for a paradigm shift in rare disease gene therapy development. With the BGTC leading the charge and drawing upon the collective experience, expertise, and passion of the scientific community, this playbook aims to serve as a guiding light, enabling researchers and developers to bring safe, effective, and transformative gene therapies to patients in need.
Acknowledgements
We would like to thank all BGTC consortium members for their valuable review and contributions to the playbook.
BGTC Regulatory Playbook contact
For questions, email Kira Gillett, Program Manager, Translational Science Cell and Gene Therapies, at kgillett@fnih.org.