Making the Most of Your Viral Clearance Study

Six tips for optimizing your viral clearance study

Two years ago, the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) finalized the 2nd revision (R2) of the viral clearance guideline ICH Q5A with several significant updates. Since then, the guideline has been implemented by local authorities worldwide (for implementation status, check the ICH’s Quality Guidelines No. 5-2), which has provided clearer guidance on new industry standards and, most importantly, introduced several options to reduce the scope of viral clearance testing. These options include:

1.    Prior knowledge is now accepted. While the ICH Q5A (R2) itself does not specify the extent of data required, the official ICH Q5A (R2) training material provides further insight into this. In short, only confirmatory runs might be required, depending on the platform data provided to the authorities. Virus retentive filtration, for instance, definitely requires a confirmatory run.

2.    Skip the used resin runs of the Protein A chromatography. The ICH has acknowledged that over the last few decades, we have accumulated enough data showing that end-of-life aged Protein A resin has at least the same potential to remove virus compared to fresh Protein A resin or even higher. Thus, there is no need to test the used Protein A resin anymore!

3.    Reduce virus retentive filtration runs. The ICH has recognized that virus-retentive filtration operates primarily through size-based exclusion. Therefore, demonstrating the effective removal of a small model virus, such as parvovirus, is considered sufficient to support the clearance of larger viruses, without the need to test each one individually. And in case prior knowledge is claimed, one confirmatory run with the most challenging virus is sufficient.

4.    Continuous manufacturing - keep it simple. Identify the critical process parameters and, whenever possible, perform the viral clearance study in a batch process mode to avoid overcomplicating matters. Running at worst-case or setpoint conditions, if a worst-case scenario cannot be clearly defined, is recommended.

5.    Expanded scope. Genetically engineered viral vectors and viral vector-derived products are now covered. The guideline now provides specific recommendations for products such as baculovirus-expressed virus-like particles (VLPs) and adeno-associated virus (AAV) gene therapy vectors, and explicitly emphasizes the need to address helper viruses when using these products within viral clearance studies.

6.    Open to new testing approaches. Whereas the previous emphasis had been on infectivity-based assays, the ICH now permits the use of molecular analytical techniques and supports the inclusion of non-infectious retrovirus-like particle (RVLP) spikes as part of the viral clearance strategy

There is a lot to unpack with these ICH updates, but ultimately, the changes should benefit biological testing labs in multiple ways. Therefore, keeping these tips in mind should significantly reduce the scope of your viral clearance study and reduce costs. Do you have questions about your viral clearance studies? You can reach out to [email protected]

Anja joined Charles River, Germany in January 2015. She initially worked as a Study Director and Study Director Supervisor obtaining profound knowledge of setting-up, planning, and performing viral clearance studies.

Prior to joining Charles River, Anja worked as Research Director at Antitope, UK overseeing antibody humanization projects. Anja studied biochemistry at the Universities of Greifswald and Witten/Herdecke, both located in Germany. She performed her M.Sc. thesis working on Borna disease virus at the University of Marburg, Germany. Afterwards she worked in the field of innate immunity at the DKFZ, Heidelberg, Germany where she obtained a PhD from the University of Heidelberg in 2008.