- Case Study -
Predicting Viral Clearance Early with MockV
Enhancing Viral Clearance Prediction and Process Optimization with MockV Technology
The Challenge
In biopharmaceutical development, ensuring product safety is paramount. A critical aspect of this safety is the rigorous demonstration of viral reduction, proving that the manufacturing process effectively reduces the risk associated with potential viral contaminants. Traditionally, this has been achieved through viral clearance studies, where process samples are spiked with infectious viruses and then analyzed to determine the level of viral reduction.
While essential, the traditional method of performing these studies presents challenges. The viral clearance studies are typically conducted late in the development process, often in collaboration with external virus CROs, and after the manufacturing process has been scaled up, limiting opportunities for further process optimization based on the viral clearance data. Additionally, traditional studies often focus on a limited set of process parameters, restricting the ability to explore the impact of potential variations on viral safety.
Finally, conducting viral clearance studies at external CROs is an additional cost for any developer. But, if you can have some additional preliminary data, it enables selection of specific downstream steps and process parameters to test and can reduce the overall cost of the typical studies performed at this stage.
The AGC Biologics Solution
Improve viral safety, refine and optimize processes, and cut costs on extra external testing.
To address these challenges and enhance viral safety assessment, our process development teams implemented MockV technology. This innovative approach utilizes non-infectious retrovirus-like particles (RVLPs). These MockV particles can be introduced into process samples, mimicking viral contamination, and their removal can be tracked throughout the downstream process.
The key advantage of MockV technology lies in its ability to predict viral clearance capacity early in the downstream process development (DPD) phase, without using infectious viruses, thus permitting testing in our in-house development facilities. This allows for proactive risk mitigation and process optimization, ensuring robust viral safety even before GMP manufacturing begins, and can potentially reduce costs for our developer partners by eliminating additional third-party testing.
During our initial proof of concept studies, a Protein A chromatography step, typically used for antibody purification, was evaluated using both the traditional external CRO infectious XMuLV and the internal non-infectious Mock-XMuLV (MockV). The results demonstrated that the MockV particles behaved similarly to the infectious virus, with comparable log reduction levels observed, confirming the ability of MockV to predict viral clearance capacity.
| Study setup | Log10 reduction |
| XMuLV (Infectious) | 1.35 ± 0.04 |
| 1.27 ± 0.08 | |
| Mock-XMuLV (Non-infectious) | 0.88 ± 0.08 |
| 1.26 ± 0.23 |
Clarified harvest was spiked with either infectious (XMuLV) or non-infectious (MockV) virus stock and loaded on a Protein A chromatography resin (i.e. MabSelect PrismA). The flow through and the eluate fractions were collected, and viral particles were quantified by qPCR.
Log10 reduction was calculated as log10(N0/N), where N0 is the viral count in the load and N is the viral count in the eluate. Generally a log10 reduction of ≥ 4 is considered efficient at reducing viral particles.
MockV technology can detect steps that are inefficient at virus reduction, potentially saving resources and materials.
The Results
Enhancing Viral Clearance for a Strong and Dependable Drug Manufacturing Process
AGC Biologics' adoption of MockV technology represents a significant advancement. By enabling early prediction and optimization of viral clearance, MockV empowers our downsteram development teams to reduce development timelines, improve process understanding, enhance process robustness, and mitigate risks, from a viral reduction perspective. This commitment to innovation and cutting-edge technologies ensures we deliver safe and effective biopharmaceuticals to patients worldwide.
Our MockV technology provides us with a range of benefits. It allows for early identification of process steps with high viral reduction potential, enabling informed decision-making about which steps to include in the final viral clearance studies with infectious viruses. This can lead to significant cost savings for our developer partners by avoiding unnecessary testing and streamlining the overall development process of their drug product. Additionally, MockV facilitates the investigation of a wider range of process parameters, providing a more comprehensive understanding of their impact on viral clearance. This enables the identification of optimal conditions for viral clearance, ensuring a robust and reliable process.
