The Fall 2025 CAACB Workshop will be conducted as a hybrid event, featuring discussions on:
Topic 1: Understanding and Mitigating the Risk of Endogenous Viruses in Cell Therapy Manufacturing
This session explores the risks from endogenous and endemic viruses in cell therapies, which are not well understood. Recent literature shows the potential for reactivation of latent HHV-6 and HHV-7 during CAR T-cell manufacturing, though detection remains a challenge. Theoretical risks from human endogenous retroviruses (HERV) also exist due to similarities with lentiviral vectors. Topics include:
- Consideration of risk differences between autologous and allogeneic products
- Case studies on reactivation of endemic viruses in cell therapies
- Risk assessments of endogenous viruses with supporting data
- Testing approaches for detecting these viruses in donor cells, including interpretation when replication is not evident
- Mitigation strategies companies are using or proposing
- New tools and methods for detecting endemic or endogenous viruses
Topic 2: Development and Validation of NGS as a GMP Viral Safety Assay
The workshop will address the use of next-generation sequencing (NGS) as a viral safety assay in light of ICH Q5A(R2), which recommends NGS over in vivo testing. Despite progress, questions remain about how to validate NGS and how regulators are responding to submitted approaches. Global regulatory perspectives vary, posing challenges for implementation strategies. Key areas of discussion include:
- Strategies for using NGS in regions outside FDA/EMA oversight
- Examples of NGS validation attempts and successes
- Needed standards, tools, or consensus positions for regulatory acceptance
- Case studies of NGS used in characterization, adventitious agent testing, raw material testing, or contamination investigations—especially for cell and gene therapies or novel cell lines
- Substitution of traditional tests with NGS and regulatory feedback
- Internal and external barriers to GMP implementation of NGS
- Collaborative NGS work and associated challenges
- Bioinformatics issues and how they were addressed
- Success stories and contributing factors