CASE STUDY
Enhancing In-Process Control Testing in Adenoviral Production Using Multi-Angle Dynamic Light Scattering
Abstract:
In-process control (IPC) testing plays a vital role in ensuring consistent product quality throughout viral vector manufacturing, particularly as timelines tighten approaching GMP readiness. Delayed analytical feedback at critical process points can lead to particle aggregation, increased polydispersity, and ultimately a loss of vector functionality.
These quality risks are closely linked: aggregation broadens particle size distribution and elevates the polydispersity index (PDI). Detecting these shifts early is key to mitigating downstream challenges and ensuring batch-to-batch consistency.
For viral vectors such as Adenovirus and AAV, the most widely used titer methods include:
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- OD260: fast but limited in both specificity and sensitivity
- HPLC: moderate resolution and sensitivity, though more time- and reagent-intensive
- ddPCR: considered the gold standard for titer accuracy and sensitivity, albeit with longer turnaround and higher cost
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While these techniques are invaluable for definitive quantification, they often lack the responsiveness required for real-time IPC applications. At Exothera, we have implemented a complementary, in-house method using Multi-Angle Dynamic Light Scattering (MADLS) to enable rapid, reproducible, and cost-effective IPC monitoring. This case study outlines how MADLS has improved titer determination efficiency in adenoviral production, building on its established use for polydispersity and aggregation monitoring.