Impurities in viral-based therapeutics: mastering residual hcDNA: a harmonized approach for AAV gene therapies
AAV gene therapy products are produced in continuous cell lines which can leave host cell DNA (hcDNA) in the final product, posing potential risks to patient safety. Regulatory guidelines keep evolving to address these risks, recommending limits on hcDNA levels and fragment sizes. To better control hcDNA impurities manufacturers rely on risk assessments, characterisation and quantitation, and removal strategies.Based on survey insights, the BioPhorum workstream highlights differences in hcDNA reporting across the industry, proposes a standardized reporting approach by normalizing hcDNA levels to AAV genomes (vg), establishing a reference range for vg-normalized hcDNA level in AAV manufacturing processes. This supports risk assessment and better comparison across gene therapy products.Holistic manufacturing control strategies for hcDNA are outlined, including optimizing cell line selection, robust purification techniques, and nuclease treatments.By adopting these harmonized reporting and control strategies, the industry can master hcDNA impurities, ensuring safer gene therapy products for patients.
Authors
- Roland Pach
- Yong-Syu Lee
- R. Ashton Lavoie (ORCID: https://orcid.org/0000-0001-9842-8520)
- Marija Brgles (ORCID: https://orcid.org/0000-0002-6080-8808)
- Reshma Sundar (ORCID: https://orcid.org/0000-0001-8737-8302)
- Haiqing Yu
- Hunter Walker
- Beata Adamiak
- Parag Kumthekar
- Pepijn P. Burgers
- Qirong Wu (ORCID: https://orcid.org/0000-0001-8878-0918)
- Kate Groves (ORCID: https://orcid.org/0000-0001-9207-6392)
- Steven J. Henry (ORCID: https://orcid.org/0000-0003-2085-7733)
- Nic Preyat
- Ying Zhang (ORCID: https://orcid.org/0000-0002-3608-3798)
- Xue Mi (ORCID: https://orcid.org/0000-0001-7066-2526)
- Victor Chen (ORCID: https://orcid.org/0000-0003-2844-9347)
- Ishtiaq Khaliq
- Simon W. Walker
- Spyridon Gerontas
- Ane Quesada Ganuza
- Suna Lipp
- Denise Teber
- Ashoka Maddur
Institutions
- Fujifilm (Japan) (JP)
- AbbVie (United States) (US)
- Pharmaron (United Kingdom) (GB)
- Gene Bridges (Germany) (DE)
- BioPhorum (United Kingdom) (GB)
- Charles River Laboratories (Germany) (DE)
- Boehringer Ingelheim (Egypt) (EG)
- Johnson & Johnson (Israel) (IL)
- BridgeBio (United States) (US)
- Fujifilm (United Kingdom) (GB)
- Eurofins (Germany) (DE)
- Sarepta Therapeutics (United States) (US)
- Roche (Sweden) (SE)
- Bayer (France) (FR)
- AbbVie (Japan)
Publication Details
- Journal
- Cell and Gene Therapy Insights
- Published
- 2025-10-15
- DOI
- https://doi.org/10.18609/cgti.2025.127
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Sarepta Therapeutics